KR20200111120A - Novel naphthofuran derivatives and use thereof - Google Patents

Abstract

The present invention relates to a novel naphthofuran derivative and a use thereof. A compound of chemical formula 2 according to the present invention can be usefully used in fluorescent dyes, particularly fluorescent dyes for bio-imaging. In the compound of the formula 2, A represents a hydrocarbon ring selected from benzene or naphthalene.

Description

Novel naphthofuran derivatives and use thereof

The present invention relates to novel naphthofuran derivatives and uses thereof.

Polycyclic heteroaromatic compounds are an important group of aromatic organic functional materials exhibiting a variety of biological, electrochemical and photochemical properties. Among the various applications of heteroaromatic scaffolds, the development of new fluorescent probes is of great importance in biomedical research, especially in the field of bioimaging. The required characteristics of a fluorescent probe for bio-imaging are better light stability and high contrast of fluorescence. The aggregation-caused quenching (ACQ) effect of conventional phosphors such as pyrene, perylene and naphthalene diimide (NDI) presents difficulties in practical applications of bio-imaging, optoelectronic materials and sensors. . Aggregation-induced emission (AIE) or aggregation-induced emission enhancement (AIE) molecules show great potential in a new way because they are not identified at high concentrations. The non-radioactive inactivation pathway observed in solution was inhibited by limited intramolecular rotation (RIR) in a highly concentrated solution or solid state, showing better contrast in fluorescence imaging. To date, a variety of AIE light-emitting materials with nearly 100% quantum efficiency (QY) have been developed, but solubility problems still remain in most bio-imaging systems, requiring a nanoparticle manufacturing process that improves cellular uptake.

New phosphors having high fluorescence in the solid state as well as in solution are highly required for bio-imaging and biosensors, but such probes are still limited. In particular, blue fluorescent materials that work in solution and solid state are still rare, and there is high demand for high-performance blue OLEDs. Additionally, dual state emission (DSE) molecules that are radioactive in all types of solvents are very rare.

An object of the present invention is to provide a novel compound, a method for preparing the same, and a use thereof to overcome the practical limitations of the existing phosphor.

The present inventors have completed the present invention as a result of trying various methods to synthesize a new polycyclic heteroaromatic scaffold.

The present invention provides a compound of the following formula (2).

[Formula 2]

A represents a hydrocarbon ring selected from benzene or naphthalene,

R ₁ is C _1-6 alkyl; C _1-6 alkoxy; Aldehyde; It is a substituent selected from the group consisting of halogen, haloalkyl, hydroxy and phenyl,

m is an integer from 0 to 4,

When m is 2 or more, R ₁ may each be a different substituent,

R ₃ may be aryl or heteroaryl unsubstituted or substituted with one or more substituents.

In this specification,

A "substituted" group is one in which one or more hydrogen atoms have been replaced with one or more non-hydrogen atoms, provided that the valence requirements are satisfied and a chemically stable compound arises from the substitution. In this specification, all substituents are to be construed as capable of being substituted or unsubstituted unless explicitly stated as "unsubstituted". Each of the substituents of R ₁ to R ₄ on the compound according to the present invention may be again substituted with one or more of the above-defined substituents.

"Halogen" or "halo" represents fluoro, chloro, bromo and iodo.

"Hydroxy" represents -OH.

"Alkyl" generally means a straight chain and branched saturated hydrocarbon group having the specified number of carbon atoms (eg, 1 to 12 carbon atoms). Examples of the alkyl group include, without limitation, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, t-butyl, pent-1-yl, pent-2-yl, pent-3- Yl, 3-methylbut-1-yl, 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2,2-trimethyleth-1-yl, n-hexyl, n-heptyl and n-octyl and the like. Alkyl can be attached to a parent group or substrate at any ring atom provided the attachment does not violate the atom requirement. Likewise, an alkyl group may contain one or more non-hydrogen substituents provided the attachment does not violate the valence requirements. For example, "haloalkyl" refers to -CH ₂ (halo) _, -CH (halo) ₂ or C (halo) ₃ , and, for example, refers to a methyl group in which at least one of the hydrogens of the methyl group is replaced by halogen. . Examples of “haloalkyl” groups include, without limitation, trifluoromethyl, trichloromethyl, tribromomethyl and triiodomethyl, and the like.

"Alkoxy" refers to alkyl-O-, wherein alkyl is defined above. Examples of alkoxy groups include, without limitation, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, s-pentoxy, and the like. do. Alkoxy can be attached to a parent group or substrate at any ring atom provided the attachment does not violate the atom requirement. Likewise, an alkoxy group may contain one or more non-hydrogen substituents provided the attachment does not violate the valency requirements. For example, "haloalkoxy" is -O-CH ₂ (halo), It refers to -O-CH (halo) ₂ or -OC (halo) _3, and refers to a methyl group in which at least one of the hydrogens of the methyl group is replaced by halogen. Examples of “haloalkoxy” groups include, without limitation, trifluoromethoxy, trichloromethoxy, tribromomethoxy and triiodomethoxy, and the like.

"Aryl" may mean an aromatic ring in which one hydrogen has been removed from an aromatic hydrocarbon ring, and may be a single ring or multiple rings. "Aryl of 3 to 12 atoms" may mean an aryl containing 3 to 12 atoms forming a ring, as an example, phenyl, naphthyl, anthracenyl, phenanthryl, biphenyl, terphenyl, etc. It may include, but is not limited thereto. The "aryl" may be attached to a parent group or substrate at any ring atom provided the attachment does not violate the valence requirements. Likewise, "aryl" may contain one or more non-hydrogen substituents provided the substitution does not violate the valence requirements.

"Heteroaryl" may mean an aromatic ring containing at least one hetero atom among N, O, and S as an atom forming the ring, and may be a single ring or a multi-ring. In addition, "3 to 12-membered heteroaryl" may mean a heteroaryl containing 3 to 12 atoms forming a ring, wherein, for example, 1 to 4 independently selected from nitrogen, oxygen and sulfur Four heteroatoms replace carbon atoms. As an example, "heteroaryl" is thienyl, thiophene, furyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isothiazolyl, oxadiazolyl, triazolyl, pyridinyl, bipyridyl , Pyrimidyl, triazinyl, triazolyl, acridyl group, pyridazinyl group, pyrazinyl, quinolinyl, quinazoline, quinoxalinyl, phenoxazyl, phthalazinyl, pyrimidinyl, pyrido pyrimidinyl , Pyrido pyrazinyl, pyrazino pyrazinyl, isoquinoline, indole, carbazole, imidazopyridazinyl, imidazopyridinyl, imidazopyrimidinyl, pyrazolopyrimidinyl, imidazopyrazinyl or pyrazolo Pyridinyl, N-arylcarbazole, N-heteroarylcarbazole, N-alkylcarbazole group, benzoxazole, benzoimidazole, benzothiazole, benzocarbazole, benzothiophene, dibenzothiophenyl, thieno Thiophene, benzofuranyl, phenanthroline, isoxazolyl, oxadiazolyl, thiadiazolyl, benzothiazolyl, tetrazolyl, phenothiazinyl, dibenzosilol or dibenzofuranyl, etc. may be included. It is not limited. The "heteroaryl" may be attached to a parent group or substrate at any ring atom provided the attachment does not violate the valence requirement. Likewise, "heteroaryl" may contain one or more non-hydrogen substituents provided the substitution does not violate the valence requirements.

In one embodiment, the aryl or heteroaryl may be phenyl, naphthyl, anthracenyl, phenanthryl, biphenyl, terphenyl or thiophene.

In one example, the aryl or heteroaryl is C _1-6 alkyl; C _1-6 alkoxy; Aldehyde; It may be unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, haloalkyl, and hydroxy.

In one embodiment,

A represents a hydrocarbon ring selected from benzene or naphthalene,

R ₁ is C _1-6 alkyl; C _1-6 alkoxy; And a substituent selected from the group consisting of an aldehyde group,

n is an integer from 0 to 4,

When n is 2 or more, R ₁ may be each different substituent,

R ₃ is C _1-6 alkyl; Or C _1-6 alkyl; C _1-6 alkoxy; It may be phenyl, naphthyl, phenanthryl, biphenyl, or thiophene unsubstituted or substituted with one or more substituents selected from halogen and haloalkyl.

In a preferred embodiment, the compound of Formula 2 may be any one of the following compounds.

The present invention also provides a method for preparing the compound of Formula 2.

Specifically, the present invention provides a method for preparing a compound of Formula 2, comprising reacting a compound of Formula 1 with a compound of Formula 3 to obtain a compound of Formula 4 and obtaining a compound of Formula 2 from the compound of Formula 4.

[Formula 1]

[Formula 2]

[Formula 3]

[Formula 4]

In the above formula,

A represents a hydrocarbon ring selected from benzene or naphthalene,

R ₁ is C _1-6 alkyl; C _1-6 alkoxy; Aldehyde; It is a substituent selected from the group consisting of halogen, haloalkyl, hydroxy and phenyl,

m is an integer from 0 to 4,

When m is 2 or more, R ₁ may each be a different substituent,

R ₂ is halogen,

R ₃ may be aryl or heteroaryl unsubstituted or substituted with one or more substituents.

It is not limited thereto, and the compound of Formula 1 is not limited thereto, but may be the following compound used in the following examples.

Although not limited thereto, the compound of Formula 3 may be the following compound used in the following examples.

For the reaction of the compound of formula 1 with the compound of formula 3, a suitable catalyst, for example, Et ₃ N, (Ph ₃ P) ₂ PdCl ₂ and CuI may be used. This reaction corresponds to the so-called Sonogashira coupling reaction, which is well known in the art. A suitable reaction temperature may be 60 to 100°C, for example 70 to 90°C. The reaction to obtain the compound of formula 2 of formula 4 is carried out through exposure to appropriate temperature conditions in the presence of TFA/1,2-dichloroethane (DCE).

For example, in the following examples, 2 {1, 1} compounds were synthesized under the following conditions.

The present invention also provides a fluorescent dye comprising the compound of Formula 2.

As can be seen in the following examples, the compound of Formula 2 was identified as a fluorescent compound capable of emitting light in a dual state with high blue emission in a solid state and most solvents. Therefore, in one embodiment of the present invention, the compound may be one that exhibits fluorescence in a solid state and/or a solvent. In addition, the fluorescent dye may exhibit blue fluorescence. Although not limited thereto, the blue fluorescence may be a fluorescent dye exhibiting a maximum emission wavelength of 400 to 500 nm.

The fluorescent dye may be used as a fluorescent dye for coloring organic and inorganic materials such as plastics, paints, printing inks, inorganic-organic composites, and oxide layer systems, but may not be limited thereto. In addition, the fluorescent dye may be used as an electron emission source of an electroluminescent device and a chemiluminescent device, but may not be limited thereto. In addition, the fluorescent dye may be used as an active component for fluorescence conversion, a fluorescent solar collector, a bioluminescent array, and solar power generation, or as a laser dye, but may not be limited thereto.

According to the following examples, it was confirmed that the compound of Formula 2 has high cell permeability and low phototoxicity, so that it can be usefully utilized in live cell imaging. Therefore, the fluorescent dye according to the present invention can be particularly advantageously utilized for bioimaging.

Advantages and features of the present invention, and a method of achieving them will become apparent with reference to embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in a variety of different forms. It is provided to completely inform the scope of the invention to those who have it, and the invention is only defined by the scope of the claims.

The compound of Formula 2 according to the present invention can be usefully used as a fluorescent dye, particularly a fluorescent dye for bioimaging.

1 shows absorption spectra (a) and emission spectra (b) of 6NP-14, 6NP-2, 6NP-7, 6NP-8, 6NP-11, 6NP-12 and 6NP-13 measured with DMSO.
Figure 2 shows the fluorescence spectra of 0.5 μM of 6NP-14 (a) , 6NP-1 (b) , 6NP-9 (c) , 6NP-6 (d) , and 6NP-13 (e) in various solvents. .
3 shows fluorescence spectra of the compounds according to Examples 20 to 28 at 0.5 μM in various solvents.
4 shows the results of live cell imaging of HeLa cells. (a) Fluorescent and bright field live cell images of HeLa cells stained for 1 h with 10 μM and 20 μM of 6-substituted naphtho[2,1- b ]benzofuran. Enlarged image: 20 μM 6NP-12 (b) , 6NP-13 (c) , and 6NP-10 (d) . Scale bar represents 100 μm.
5 shows the results of confocal live cell imaging of HeLa cells. In HeLa cells, live-cell confocal images for 20 minutes, 150 nM of MitoTracker Red (a) and 30 minutes and then incubated for 1 hour in 6NP-13 of lead 10 μm was treated with 75 nM LysoTracker Red (b). The blue channel (Ex: 405 nm, Em: 410-560 nm) comes from 6NP-13 fluorescence, and the red channel from LysoTracker Red fluorescence or MitoTracker Red fluorescence (Ex: 561 nm, Em:> 566 nm). Scale bar is 10 μm. Intensity profile of the region of interest (ROI) with yellow lines on HeLa cells.
6 shows the results of a cytotoxicity test of the compound of Formula 2. 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d)
7 shows the DSE properties of the compound of Formula 2. Of 10 μM 6NP-8 (a) , 6NP-7 (b) , and 6NP-12 (c) in a THF/water mixture (0-99%) in natural light (top) and ultraviolet (bottom, λex = 312 nm) Photo. 10 μM of 6NP-8 (d) , 6NP-7 (e ) in a THF/water mixture (0-99%) excited at 308 nm (d) , 332 nm (e), 342 nm (f) ) , and the fluorescence spectrum of 6NP-12 (f) ; Insertion: Fluorescence intensity graph of 6NP-8 (d) at 396 nm, 6NP-7 (e) at 388 nm, and 6NP-12 (f) at 405 nm.
8 shows the fluorescence spectrum of the compound of Formula 2 in EtOH and solid state. Fluorescence spectra of 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d) in EtOH (0.5 μM, dotted line) and solid state (solid line); Insertion: 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d) in the solid state under natural light (left) and ultraviolet (right, λ _ex = 365 nm ) Photo.
9 shows the result of particle size analysis of the compound of Formula 2. It can be seen from the particle size distribution in the THF/water mixture (5/95: v/v) that it exists as nanoparticles of about 200 nm. 10 μM of 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d) ; Upper left: intensity distribution, upper right: volume distribution, lower left: numeric distribution, lower right: LN(G2(τ)-1) vs τ.
10 shows the fluorescence spectra of 6NP-7 in various dispersion solvents.
11 shows the results of crystal structure analysis of 6NP-7. (a) CH in the molecule indicated by the yellow line... Crystal structure of 6NP-7 with O interaction (2.249Å). (b) Slip-stacked 6NP-7 molecule viewed from the side. (c) Intermolecular S… shown by the red line. Packing structure of 6NP-7 through S bond (3.769 Å). (d) packing structure of 6NP-7 through intermolecular interactions; Red: Intermolecular S… S bond (3.769 Å); Green: Intermolecular CH… S bond (3.156 Å); Orange: Intermolecular CH… O bond (2.524 Å).

Hereinafter, the present invention will be described in detail through examples. The following examples are merely illustrative of the present invention, and the scope of the present invention is not limited to the following examples.

[Example]

General method

Unless specified, all reagents and starting materials were purchased from commercial sources and used without purification. "Concentration" refers to the removal of volatile solvents through distillation using a rotary evaporator. "Dried" refers to filtering after pouring or passing anhydrous magnesium sulfate. Flash chromatography was performed using silica gel (230-400 mesh) using hexane, ethyl acetate, and dichloromethane as eluents. All reactions were monitored by thin layer chromatography on 0.25 mm silica plates (F-254) visualized by UV light. The melting point was measured using a capillary melting point device. ^{The 1} H and ¹³ C NMR spectra were recorded on a 400 MHz NMR spectrometer, and the chemical shift, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet), the coupling constant of Hertz (Hz), And the number of protons. HRMS was measured by electrospray ionization (ESI) and Q-TOF mass spectrometry.

Synthesis of starting materials and intermediates

1-(2-iodophenyl)-2-phenoxyethanone

In a solution of 2-bromo-1-(2-iodophenyl)ethanone (400 mg, 1.23 mmol) in acetone (10 mL) stirred at room temperature, K ₂ CO ₃ (255 mg, 1.85 mmol) and phenol (139 mg, 1.47 mmol). After refluxing for 12 hours, the reaction mixture was cooled to room temperature, filtered using a Celite pad, washed with EtOAc, and concentrated under reduced pressure to obtain a crude product. The product was purified by flash chromatography on silica gel (hexanes:EtOAc, 49:1) to obtain 1-(2-iodophenyl)-2-phenoxyethanone as a yellow oil (262 mg, 63%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.94 (d, J = 7.6 Hz, 1H), 7.41-7.46 (m, 2H), 7.27-7.31 (m, 2H), 7.15-7.19 (m, 1H), 6.99 (t, J = 7.2 Hz, 1H), 6.92 (d, J = 8.8 Hz, 2H), 5.10 (s, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 199.9, 157.8, 141.6, 140.8, 132.5, 129.7, 128.7, 128.1, 121.9, 114.9, 91.7, 71.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₄ H ₁₂ IO ₂ 338.9876, found 338.9880.

2-(4-( tert -Butyl)phenoxy)-1-(2-iodophenyl)ethanone

This compound contains 2-bromo-1-(2-iodophenyl)ethanone (400 mg, 1.23 mmol), K ₂ CO ₃ (255 mg, 1.85 mmol), and 4- tert -butylphenol (222 mg, 1.47 mmol) was synthesized in the same manner as 1-(2-iodophenyl)-2-phenoxyethanone. Clear oil, (310 mg, 64%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.94 (d, J = 8.0 Hz, 1H), 7.42-7.44 (m, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.15-7.19 (m, 1H), 6.86 (d, J = 8.8 Hz, 2H), 5.08 (s, 2H), 1.29 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 200.1, 155.6, 144.7, 141.8, 140.8, 132.4, 128.7, 128.1, 126.5, 114.5, 91.7, 71.9, 34.3, 31.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₈ H ₂₀ IO ₂ 395.0502, found 395.0505.

2-(3,4-dimethoxyphenoxy)-1-(2-iodophenyl)ethanone

This compound contains 2-bromo-1-(2-iodophenyl)ethanone (400 mg, 1.23 mmol), K ₂ CO ₃ (255 mg, 1.85 mmol), and 3,4-dimethoxyphenol (227.5 mg, 1.47 mmol) was synthesized in the same manner as 1-(2-iodophenyl)-2-phenoxyethanone. Yellow oil, (332 mg, 68%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.93 (d, J = 8.0 Hz, 1H), 7.42-7.43 (m, 2H), 7.15-7.19 (m, 1H), 6.75 (d, J = 8.4 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.39 (dd, J = 2.4, 8.8 Hz, 1H), 5.05 (s, 2H), 3.83 (s, 3H), 3.82 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 200.2, 152.4, 150.0, 144.4, 141.7, 140.8, 132.4, 128.7, 128.1, 111.6, 104.3, 101.4, 91.7, 72.4, 56.5, 56.0; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₆ H ₁₆ IO ₄ 399.0088, found 399.0091.

2-(3,5-dimethoxyphenoxy)-1-(2-iodophenyl)ethanone

This compound contains 2-bromo-1-(2-iodophenyl)ethanone (400 mg, 1.23 mmol), K ₂ CO ₃ (255 mg, 1.85 mmol), and 3,5-dimethoxyphenol (222 mg, 1.47 mmol) was synthesized in the same manner as 1-(2-iodophenyl)-2-phenoxyethanone. Yellow oil (406 mg, 83%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.93 (d, J = 8.0 Hz, 1H), 7.41-7.45 (m, 2H), 7.17 (br s, 1H), 6.08-6.16 (m, 3H), 5.06 (s, 2H), 3.75 (s, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 199.5, 161.6, 159.6, 141.5, 140.8, 132.5, 128.7, 128.1, 94.2, 93.8, 91.7, 71.6, 55.5; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₁₆ H ₁₅ NaIO ₄ 420.9907, found 420.9906.

1-(2-iodophenyl)-2-(naphthalen-1-yloxy)ethan-1-one

In a solution of 2-bromo-1-(2-iodophenyl)ethanone (200 mg, 0.62 mmol) in acetonitrile (10 mL) stirred at room temperature, K ₂ CO ₃ (144 mg, 1.24 mmol) and 1 -Naphthol (75 mg, 0.52 mmol) was added. After stirring at room temperature for 6 hours, the reaction mixture was concentrated under reduced pressure, diluted with water (10 mL), and extracted with CH ₂ Cl ₂ (10 mL × 2). The combined organic layers were washed with brine, dried over MgSO ₄ and then concentrated under reduced pressure to give the crude product. Purification by flash chromatography (hexane:EtOAc:dichloromethane, 50:1:2) on silica gel to obtain 1-(2-iodophenyl)-2-(naphthalen-1-yloxy)ethan-1-one as a yellow oil. Obtained (146.9 mg, 76.3%).

¹ H NMR (400 MHz, CDCl ₃ ) δ8.11 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.51- 7.40 (m, 5H), 7.35 (t, J = 8.0 Hz, 1H), 7.16 (td, J = 7.8, 1.6 Hz, 1H), 6.79 (d, J = 7.6 Hz, 1H), 5.25 (s, 2H ); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 200.2, 153.4, 141.8, 140.5, 134.5, 132.3, 128.7, 127.9, 127.4, 126.6, 125.5, 125.5, 122.0, 121.4, 105.2, 91.6, 71.6; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₁₈ H ₁₃ INaO ₂ 410.9852, found 410.9857.

1-(2-iodophenyl)-2-(naphthalen-2-yloxy)ethan-1-one

In a solution of 2-bromo-1-(2-iodophenyl)ethanone (270 mg, 0.83 mmol) in acetonitrile (10 mL) stirred at room temperature, K ₂ CO ₃ (192 mg, 1.39 mmol) and 2 -Naphthol (100 mg, 0.69 mmol) was added. After stirring at room temperature for 6 hours, the reaction mixture was concentrated under reduced pressure, diluted with water (10 mL), and extracted with CH ₂ Cl ₂ (10 mL × 2). The combined organic layers were washed with brine, dried over MgSO ₄ and then concentrated under reduced pressure to give the crude product. The product was purified by flash chromatography on silica gel (hexane:EtOAc:dichloromethane, 50:1:2), and as a yellow oil, 1-(2-iodophenyl)-2-(naphthalen-2-yloxy)ethane-1- On was obtained (157.8 mg, 61.4%).

¹ H NMR (400 MHz, CDCl ₃ ) δ7.93 (d, J = 7.6 Hz, 1H), 7.78-7.73 (m, 3H), 7.47-7.36 (m, 4H), 7.20-7.14 (m, 3H) , 5.21 (s, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 199.8, 155.6, 141.4, 140.7, 132.4,132.4, 129.8, 129.4, 128.6, 127.9, 127.7, 126.9, 126.6, 124.1, 118.6, 107.4, 91.7, 71.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₈ H ₁₄ IO ₂ 389.0033, found 389.0030.

2-([1,1'-biphenyl]-3-yloxy)-1-(2-iodophenyl)ethan-1-one.

In a solution of 2-bromo-1-(2-iodophenyl)ethanone (210 mg, 0.65 mmol) in acetonitrile (10 mL) stirred at room temperature, K ₂ CO ₃ (163 mg, 1.18 mmol) and 3 -Phenylphenol (100 mg, 0.59 mmol) was added. After stirring at room temperature for 6 hours, the reaction mixture was concentrated under reduced pressure, diluted with water (10 mL), and extracted with CH ₂ Cl ₂ (10 mL × 2). The combined organic layers were washed with brine, dried over MgSO ₄ and then concentrated under reduced pressure to give the crude product. Purified by flash chromatography on silica gel (hexane:EtOAc:dichloromethane, 50:1:2) as a transparent oil 2-([1,1'-biphenyl]-3-yloxy)-1-(2-iodo Phenyl)ethan-1-one was obtained (180 mg, 73.8%).

¹ H NMR (400 MHz, acetone-d ₆ ) δ7.99 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.52 (t, J = 7.6 Hz, 1H), 7.42 (t, J = 7.4 Hz, 2H), 7.36-7.34 (m, 2H), 7.25-7.24 (m, 3H), 6.98 (d, J = 8.0 Hz) , 1H), 5.34 (s, 2H); ¹³ C NMR (100 MHz, acetone-d ₆ ) δ 198.9, 158.6, 142.5, 141.5, 140.7, 140.6, 132.5, 129.9, 128.8, 128.8, 128.2, 127.5, 126.9, 120.0, 113.8, 113.3, 91.3, 71.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₀ H ₁₆ IO ₂ 415.0819, found 415.0816

Synthesis of the compound of formula 1

Synthesis of 3-(2-iodophenyl)benzofuran (1 { 2 } )

To a stirred solution of 1-(2-iodophenyl)-2-phenoxyethanone (150 mg, 0.44 mmol) in CH ₂ Cl ₂ (4 mL) was added methanesulfonic acid (0.286 mL, 4.4 mmol) . After stirring at 55° C. for 40 hours, the reaction mixture was extracted with diethyl ether (10 mL × 2) and washed with brine (10 mL). The combined organic layers were dried over anhydrous MgSO ₄ and concentrated under reduced pressure to give the crude product. Purification by flash chromatography on silica gel (hexanes:EtOAc:CH ₂ Cl ₂ , 50:1:2) gave 1 { 2 } as a colorless oil (86.4 mg, 61%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02-8.05 (m, 1H), 7.79-7.81 (m, 1H), 7.57-7.61 (m, 1H), 7.49-7.52 (m, 1H), 7.44-7.46 (m, 2H), 7.35-7.40 (m, 1H), 7.27-7.32 (m, 1H), 7.09-7.14 (m, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 155.0, 143.0, 140.1, 136.9, 131.2, 129.5, 128.3, 127.2, 124.7, 124.3, 122.9, 122.9, 121.0, 111.8, 99.9, 99.8; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₄ H ₁₀ IO 320.9771, found 320.9776.

.

5-( tert -butyl)-3-(2-iodophenyl)benzofuran (1 { 3 } )

The compound is 2- (4- (tert - butyl) phenoxy) -1- (2-iodo-phenyl) -ethanone (200 mg, 0.51 mmol) and methanesulfonic acid using (0.33 mL, 5.1 mmol) 1 It was synthesized in the same way as { 2 } Colorless gum, (94 mg, 49%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 8.0 Hz, 1H), 7.74 (s, 1H), 7.41-7.50 (m, 5H), 7.11 (t, J = 7.6 Hz, 1H) , 1.37 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 153.3, 146.1, 143.3, 140.2, 137.2, 131.3, 129.4, 128.3, 126.6, 124.4, 122.6, 117.3, 111.0, 99.8, 34.9, 32.0; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₈ H ₁₈ IO 377.0397, found 377.0401.

3-(2-iodophenyl)-5,6-dimethoxybenzofuran (1 { 4 } )

BCl in a solution of 2-(3,4-dimethoxyphenoxy)-1-(2-iodophenyl)ethanone (200 mg, 0.50 mmol) in CH ₂ Cl ₂ (20 mL) stirred at -78°C ₃ (1M solution in CH ₂ Cl ₂ , 0.75 mL, 0.75 mmol) was added. After stirring for 1 hour under a nitrogen atmosphere, water (2 ml) was added to the reaction mixture at -78 °C and heated to room temperature. The reaction mixture was diluted with water (10 mL) and extracted with CH ₂ Cl ₂ (10 mL × 2). The combined organic layers were washed with brine, dried over MgSO ₄ and then concentrated under reduced pressure to give the crude product. Purified by flash chromatography (hexane:EtOAc, 49:1) on silica gel to obtain 1 { 4 } as a colorless gum (161 mg, 84%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 7.6 Hz, 1H), 7.65 (s, 1H), 7.40-7.46 (m, 2H), 7.08-7.12 (m, 2H), 6.86 ( s, 1H), 3.95 (s, 3H), 3.88 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 149.7, 148.4, 146.8, 141.9, 140.1, 137.3, 131.2, 129.5, 128.4, 124.6, 119.0, 102.2, 99.9, 95.6, 56.6, 56.4; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₆ H ₁₄ IO ₃ 380.9982, found 380.9986.

3-(2-iodophenyl)-4,6-dimethoxybenzofuran (1 { 5 } )

This compound contains 2-(3,5-dimethoxyphenoxy)-1-(2-iodophenyl)ethanone (200 mg, 0.50 mmol) and BCl ₃ (1M solution in CH ₂ Cl ₂ , 0.75 mL, 0.75 mmol) was synthesized in the same manner as 1 { 4 }. White solid, (158 mg, 83%), mp: 120.4-122.4 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.94 (d, J = 8.0 Hz, 1H), 7.43 (s, 1H), 7.34-7.38 (m, 2H), 7.05 (t, J = 8.0 Hz, 1H) , 6.70 (s, 1H), 6.33 (s, 1H), 3.87 (s, 3H), 3.69 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.4, 156.9, 154.6, 140.5, 138.9, 137.9, 131.2, 129.0, 127.5, 124.3, 110.8, 101.3, 94.7, 88.4, 55.9, 55.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₆ H ₁₄ IO ₃ 380.9982, found 380.9983.

Synthesis of 3-(2-iodophenyl)-4,6-dimethoxybenzofuran-7-carbaldehyde (1 { 6 } )

POCl ₃ (0.49 mL, 0.52 mmol) was added to a solution of 1 { 5 } (100 mg, 0.26 mmol) in DMF (2 mL) being stirred. After stirring at 100° C. for 12 hours, the reaction mixture was cooled to room temperature and quenched with an aqueous Na ₂ CO ₃ solution. The aqueous layer was extracted with EtOAc (10 mL × 3), washed with water (10 mL × 2) and brine (10 mL), dried over anhydrous MgSO ₄ , and concentrated under reduced pressure to obtain a crude product. Purification was performed on silica gel by flash chromatography (hexane:EtOAc, 7:3) to obtain 1 { 6 } as a yellow solid. (67 mg, 62%). mp: 202.4-204.7 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.47 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.55 (s, 1H), 7.34-7.37 (m, 2H), 7.05 (t, J = 7.2 Hz, 1H), 6.30 (s, 1H), 3.99 (s, 3H), 3.81 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.5, 163.6, 159.9, 155.2, 142.1, 138.9, 137.2, 131.1, 129.3, 127.6, 123.7, 111.7, 106.4, 101.1, 89.8, 56.8, 55.9; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₁₇ H ₁₃ NaIO ₄ 430.9751, found 430.9751.

3-(2-iodophenyl)naphtho[1,2-b]furan

To a solution of 1-(2-iodophenyl)-2-(naphthalen-1-yloxy)ethan-1-one (80 mg, 0.22 mmol) in CH ₂ Cl ₂ (20 mL) stirred at -78° C. ₃ (1M solution in CH ₂ Cl ₂ , 0.26 mL, 0.26 mmol) was added. After stirring for 1 hour under a nitrogen atmosphere, water (2 mL) was added to the reaction mixture at -78 °C, and the temperature was raised to room temperature. The reaction mixture was diluted with water (10 mL) and extracted with CH ₂ Cl ₂ (10 mL × 2). The combined organic layers were washed with brine, dried over MgSO ₄ and then concentrated under reduced pressure to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc:dichloromethane, 50:1:2) gave 3-(2-iodophenyl)naphtho[1,2- b ]furan as a yellow oil (79.8 mg, 100 %).

¹ H NMR (400 MHz, CDCl ₃ ) δ8.39 (d, J = 7.6 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.92 ( s, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.64 (t, J = 7.4 Hz, 1H), 7.55-7.52 (m, 2H), 7.48 (s, 2H), 7.13 (t, J = 5.8 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 150.5, 141.9, 139.9, 136.9, 131.6, 131.2, 129.4, 128.3, 128.2, 126.5, 125.4, 125.4, 123.4, 122.7, 121.6, 120.1, 119.3, 99.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₈ H ₁₃ IO ₂ 370.9927, found 370.9916.

1-(2-iodophenyl)naphtho[2,1-b]furan

BCl in a solution of 1-(2-iodophenyl)-2-(naphthalen-2-yloxy)ethan-1-one (130 mg, 0.33 mmol) in CH ₂ Cl ₂ (20 mL) stirred at -78 °C ₃ (1M solution in CH ₂ Cl ₂ , 0.40 mL, 0.40 mmol) was added. After stirring for 1 hour under a nitrogen atmosphere, water (2 mL) was added to the reaction mixture at -78 °C, and the temperature was raised to room temperature. The reaction mixture was diluted with water (10 mL) and extracted with CH ₂ Cl ₂ (10 mL × 2). The combined organic layers were washed with brine, dried over MgSO ₄ and then concentrated under reduced pressure to give the crude product. Purified by flash chromatography on silica gel (hexane:EtOAc:dichloromethane, 50:1:2) to give 1-(2-iodophenyl)naphtho[1,2- b ]furan as a yellow solid (122 mg, 100 %).

Yellow solid, mp: 120.8-121.4° C.; ¹ H NMR (400 MHz, CDCl ₃ ) δ8.08 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.75 ( s, 1H), 7.72 (d, J = 5.6 Hz, 1H), 7.54-7.49 (m, 3H), 7.45 (t, J = 7.6 Hz, 1H), 7.36 (t, J = 7.4 Hz, 1H), 7.23-7.19 (m, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 152.7, 141.9, 139.3, 138.4, 131.5, 130.6, 129.8, 128.7, 128.3, 128.2, 126.3, 126.3, 126.0, 124.5, 123.1, 120.9, 112.6, 101.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₁₈ H ₁₃ IO ₂ 370.9927, found 370.9923.

3-(2-iodophenyl)-6-phenylbenzofuran.

2-([1,1'-biphenyl]-3-yloxy)-1-(2-iodophenyl)ethan-1-one (180) in CH ₂ Cl ₂ (20 mL) stirred at -78°C mg, 0.43 mmol) BCl ₃ (1M solution in CH ₂ Cl ₂ , 0.52 mL, 0.52 mmol) was added. After stirring for 1 hour under a nitrogen atmosphere, water (2 mL) was added to the reaction mixture at -78 °C, and the temperature was raised to room temperature. The reaction mixture was diluted with water (10 mL) and extracted with CH ₂ Cl ₂ (10 mL × 2). The combined organic layers were washed with brine, dried over MgSO ₄ and then concentrated under reduced pressure to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc:dichloromethane, 50:1:2) to obtain 3-(2-iodophenyl)-6-phenylbenzofuran as a transparent oil (130 mg, 75.6%).

¹ H NMR (400 MHz, acetone-d ₆ ) δ8.07 (d, J = 8.0 Hz, 1H), 8.00 (s, 1H), 7.87 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H ), 7.60 (d, J = 8.0 Hz, 1H), 7.55-7.46 (m, 5H), 7.37 (t, J = 7.0 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, acetone-d ₆ ) δ 155.6, 143.9, 140.8, 139.9, 138.2, 136.6, 131.3, 129.8, 128.9, 128.5, 127.3, 127.2, 126.3, 124.3, 122.3, 121.0, 109.8, 99.2; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₀ H ₁₄ IO 397.0084, found 397.0074.

Synthesis of compound of formula 4

Synthesis of 6-methoxy-3-(2-(phenylethynyl)phenyl)benzofuran (4 { 1,1 } )

To a vial filled with 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol) in Et ₃ N (2 mL), phenylacetylene (3 { 1 } ) ( 17 μL, 0.154 mmol), (Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to obtain a crude product.

Purification was performed on silica gel by flash chromatography (hexane:EtOAc, 49:1) to obtain 4 { 1,1 } as a yellow gum (40.6 mg, 88%). ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.99 (s, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.61-7.64 (m, 2H), 7.44 (t, J = 7.6 Hz, 1H) , 7.36 (t, J = 7.2 Hz, 1H), 7.29 (s, 5H), 7.11 (s, 1H), 6.94 (dd, J = 2.0, 8.8 Hz, 1H), 3.89 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.2, 156.3, 142.8, 134.0, 133.4, 131.5, 129.4, 128.7, 128.4, 128.4, 127.3, 123.3, 122.2, 121.3, 120.5, 120.4, 112.1, 96.2, 93.1, 89.4 , 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₃ H ₁₇ O ₂ 325.1223, found 325.1225.

6-methoxy-3-(2-((4-methoxyphenyl)ethynyl)phenyl)benzofuran (4 { 1,2 } )

This compound was prepared in advance of 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol), 1-ethynyl-4-methoxybenzene (20 μL, 0.154 mmol), (Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were synthesized in the same manner as 4 { 1,1 }. Yellow gum, (43 mg, 85%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.98 (s, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.59-7.64 (m, 2H), 7.41 (t, J = 7.2 Hz, 1H) , 7.34 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 2.0 Hz, 1H), 6.92 (dd, J = 2.0, 8.8 Hz, 1H) , 6.81 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.80 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ; 159.7, 158.2, 156.3, 142.7, 133.7, 133.1, 132.9, 129.4, 128.3, 127.3, 122.6, 121.4, 120.6, 120.5, 115.5, 114.1, 112.0, 96.2, 93.2, 88.1, 55.9, 55.4; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₃ 355.1329, found 355.1326.

6-methoxy-3-(2-((3-methoxyphenyl)ethynyl)phenyl)benzofuran (4 { 1,3 } )

This compound is 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol) 1-ethynyl-3-methoxybenzene (19.5 μL, 0.154 mmol), (Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were used to synthesize 4 { 1,1 } in the same manner. Yellow gum, (42 mg, 83%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.93 (s, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.58-7.63 (m, 2H), 7.43 (t, J = 7.6 Hz, 1H) , 7.36 (t, J = 7.6 Hz, 1H), 7.19 (t, J = 8.0 Hz, 1H), 7.09 (d, J = 2.0 Hz, 1H), 6.88-6.94 (m, 2H), 6.84 (dd, J = 2.4, 8.4 Hz, 1H), 6.70 (s, 1H), 3.88 (s, 3H), 3.74 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.4, 158.2, 156.4, 142.6, 134.1, 133.3, 129.5, 129.5, 128.7, 127.4, 124.3, 124.0, 122.3, 121.5, 120.6, 120.6, 115.9, 115.3, 112.0, 96.1 , 93.1, 89.2, 55.9, 55.4; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₃ 355.1329, found 355.1325.

6-methoxy-3-(2-( p -tolylethynyl)phenyl)benzofuran (4 { 1,4 } )

This compound is 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol) 1-ethynyl-4-methylbenzene (19.5 μL, 0.154 mmol), ( Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were synthesized in the same manner as 4 { 1,1 }. Yellow solid, (43.5 mg, 90%); mp: 74.5-76.2 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.99 (s, 1H), 7.69 (d, J = 6.8 Hz, 1H), 7.60-7.64 (m, 2H), 7.42 (t, J = 7.2 Hz, 1H) , 7.35 (t, J = 6.8 Hz, 1H), 7.19 (d, J = 7.6 Hz, 2H), 7.08-7.10 (m, 3H), 6.93 (dd, J = 2.0, 8.8 Hz, 1H), 3.89 ( s, 3H), 2.34 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.2, 156.3, 142.8, 138.6, 133.9, 133.3, 131.4, 129.4, 129.2, 128.5, 127.3, 122.4, 121.3, 120.6, 120.4, 120.2, 112.0, 96.2, 93.3, 88.7 , 55.9, 21.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₂ 339.1380, found 339.1377.

6-methoxy-3-(2-( m -tolylethynyl)phenyl)benzofuran (4 { 1,5 } )

This compound is 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol) 1-ethynyl-3-methylbenzene (20 μL, 0.154 mmol), ( Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were synthesized in the same manner as 4 { 1,1 }. Yellow gum, (44 mg, 91%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.97 (s, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.60-7.63 (m, 2H), 7.43 (t, J = 7.2 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H ), 7.17 (t, J = 7.2 Hz, 1H), 7.09-7.11 (m, 3H), 7.04 (s, 1H), 6.93 (d, J = 8.4 Hz, 1H), 3.89 (s, 3H), 2.29 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.2, 156.3, 142.7, 138.1, 134.0, 133.3, 132.1, 129.4, 129.3, 128.6, 128.5, 128.3, 127.3, 123.1, 122.4, 121.4, 120.6, 120.5, 112.0, 96.2 , 93.4, 89.0, 55.9, 21.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₂ 339.1380, found 339.1382.

6-methoxy-3-(2-((6-methoxynaphthalen-2-yl)ethynyl)phenyl)benzofuran (4 { 1,6 } )

This compound is 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol) 2-ethynyl-6-methoxynaphthalene (28 mg, 0.154 mmol), (Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were used to synthesize 4 { 1,1 } in the same manner. Gray solid (45 mg, 78%); mp: 92.2-94.4 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (s, 1H), 7.72 (d, J = 7.2 Hz, 1H), 7.61-7.66 (m, 5H), 7.44 (t, J = 7.6 Hz, 1H) , 7.37 (t, J = 7.6 Hz, 1H), 7.26-7.29 (m, 1H), 7.12-7.15 (m, 2H), 7.08 (d, J = 2.0 Hz, 1H), 6.93 (dd, J = 2.0 , 8.8 Hz, 1H), 3.92 (s, 3H), 3.90 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.4, 158.2, 156.4, 142.8, 134.2, 133.9, 133.2, 131.3, 129.5, 128.8, 128.5, 128.5, 127.4, 126.9, 122.5, 121.4, 120.6, 120.6, 119.5, 118.2 , 112.0, 105.9, 96.2, 93.8, 89.1, 55.9, 55.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₈ H ₂₁ O ₃ 405.1485, found 405.1488.

3-(2-((4-chlorophenyl)ethynyl)phenyl)-6-methoxybenzofuran (4 { 1,7 } )

This compound contains 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol), 2- 1-chloro-4-ethynylbenzene (21 mg, 0.154 mmol). ), (Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were synthesized in the same manner as 4 { 1,1 }. Yellow gum, (41 mg, 80%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.92 (s, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.45 (t, J = 7.6 Hz , 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.24 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 2.0 Hz, 1H ), 6.92 (dd, J = 2.0, 8.8 Hz, 1H), 3.89 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.2, 156.4, 142.6, 134.4, 134.1, 133.3, 132.7, 129.6, 128.9, 128.8, 127.4, 122.0, 121.8, 121.3, 120.5, 120.5, 112.1, 96.2, 92.0, 90.3 , 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₃ H ₁₆ ClO ₂ 359.0833, found 359.0838.

6-methoxy-3-(2-(thiophen-3-ylethynyl)phenyl)benzofuran (4 { 1,8 } )

This compound contains 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol), 2-3-ethynylthiophene (15 μL, 0.154 mmol), ( Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) was synthesized in the same manner as 4 { 1,1 }. Yellow gum, (39.2 mg, 83%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.94 (s, 1H), 7.67 (d, J = 7.6 Hz, 1H), 7.59-7.63 (m, 2H), 7.43 (t, J = 7.6 Hz, 1H) , 7.35 (t, J = 7.6 Hz, 1H), 7.22-7.28 (m, 2H), 7.10 (d, J = 2.0 Hz, 1H), 6.91-6.96 (m, 2H), 3.89 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.2, 156.3, 142.7, 134.0, 133.2, 129.7, 129.5, 128.6, 128.6, 127.4, 125.4, 122.4, 122.2, 121.4, 112.0, 96.2, 88.8, 88.4, 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₁ H ₁₅ O ₂ S 331.0787, found 331.0783.

3-(2-(hex-1-yn-1-yl)phenyl)-6-methoxybenzofuran (4 { 1,9 } )

This compound is 3-(2-iodophenyl)-6-methoxybenzofuran (1 { 1 } ) (50 mg, 0.14 mmol) 1-hexyne (17.7 μL, 0.154 mmol), (Ph ₃ P) ₂ PdCl ₂ (9.8 mg, 0.014 mmol), and CuI (2.7 mg, 0.014 mmol) were used to synthesize 4 { 1,1 } in the same manner. Yellow gum, (42.5 mg, 98%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.91 (s, 1H), 7.53-7.57 (m, 3H), 7.36 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H) , 7.07 (d, J = 2.0 Hz, 1H), 6.91 (dd, J = 2.0, 8.8 Hz, 1H), 3.88 (s, 3H), 2.30 (t, J = 6.8 Hz, 2H), 1.38-1.45 ( m, 2H), 1.24-1.34 (m, 2H), 0.85 (t, J = 7.2 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.1, 156.2, 142.5, 133.7, 133.4, 129.3, 127.8, 127.2, 123.1, 121.4, 120.6, 120.5, 111.8, 96.0, 94.5, 80.3, 55.9, 30.6, 22.0, 19.4 , 13.7; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₁ H ₂₁ O ₂ 305.1536, found 305.1536.

3-(2-(phenylethynyl)phenyl)benzofuran (4 { 2,1 } )

This compound contains 3-(2-iodophenyl)benzofuran (1 { 2 } ) (50 mg, 0.16 mmol), phenylacetylene (19.3 μL, 0.18 mmol), (Ph ₃ P) ₂ PdCl ₂ (11.2 mg, 0.016 mmol), and CuI (3 mg, 0.016 mmol) were synthesized in the same manner as 4 { 1,1 }. Colorless gum, (42.5 mg, 92%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.06 (s, 1H), 7.74 (d, J = 7.6 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.63 (d, J = 7.6 Hz , 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.34-7.39 (m, 2H), 7.25-7.31 (m, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 155.4, 143.7, 133.9, 133.3, 131.5, 129.5, 128.7, 128.4, 127.5, 127.2, 124.5, 123.2, 122.9, 122.4, 121.2, 120.6, 111.8, 93.2, 89.3. HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₂ H ₁₅ O 295.1117, found 295.1113.

3-(2-((4-chlorophenyl)ethynyl)phenyl)benzofuran (4 { 2,7 } )

This compound is 3-(2-iodophenyl)benzofuran (1 { 2 } ) (50 mg, 0.16 mmol), 1-chloro-4-ethynylbenzene (24.5 mg, 0.18 mmol), (Ph ₃ P) ₂ PdCl ₂ (11.2 mg, 0.016 mmol), and CuI (3 mg, 0.016 mmol) were used to synthesize 4 { 1,1 } in the same manner. Gray solid, (34 mg, 66%); mp 72.4-74.6 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.00 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.58-7.63 (m, 2H) , 7.46 (t, J = 7.6 Hz, 1H), 7.35-7.40 (m, 2H), 7.29 (d, J = 7.6 Hz, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 155.4, 143.5, 134.4, 134.0, 133.2, 132.7, 129.7, 128.9, 128.7, 127.6, 127.1, 124.5, 122.9, 122.2, 121.7, 121.2, 120.7, 111.8, 92.0, 90.3 ; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₂ H ₁₄ ClO 329.0728, found 329.0725.

5-( tert -butyl)-3-(2-((3,5-dimethoxyphenyl)ethynyl)phenyl)benzofuran (4 { 3,10 } )

This compound contains 5-( tert -butyl)-3-(2-iodophenyl)benzofuran (1 { 3 } ) (50 mg, 0.13 mmol), 1-ethynyl-3,5-dimethoxybenzene ( 23 mg, 0.14 mmol), (Ph ₃ P) ₂ PdCl ₂ (9 mg, 0.013 mmol), and CuI (2.5 mg, 0.013 mmol) were synthesized in the same manner as 4 { 1,1 }. Colorless gum (33.9 mg, 62%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.94 (s, 1H), 7.69-7.72 (m, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.49 (t, J = 8.8 Hz, 2H) , 7.37-7.41 (m, 2H), 6.36-6.38 (m, 1H), 6.25 (d, J = 1.2 Hz, 2H), 3.70 (s, 6H), 1.30 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 160.5, 153.6, 145.9, 143.6, 134.5, 133.1, 129.7, 128.8, 127.5, 126.7, 124.5, 122.4, 121.1, 117.5, 110.9, 109.1, 102.1, 93.3, 88.9, 55.5 , 34.9, 31.9; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₂₈ H ₂₆ NaO ₃ 433.1774, found 433.1775.

5-( tert -butyl)-3-(2-( p -tolylethynyl)phenyl)benzofuran (4 { 3,4 } )

This compound contains 5-( tert -butyl)-3-(2-iodophenyl)benzofuran (1 { 3 } ) (50 mg, 0.13 mmol), 1-ethynyl-4-methylbenzene (18 μL, 0.14 mmol), (Ph ₃ P) ₂ PdCl ₂ (9 mg, 0.013 mmol), and CuI (2.5 mg, 0.013 mmol) were synthesized in the same manner as 4 { 1,1 }. Colorless gum, (38.4 mg, 79%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.97 (s, 1H), 7.70-7.73 (m, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H) , 7.36-7.47 (m, 3H), 7.05 (s, 4H), 2.32 (s, 3H), 1.32 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 153.6, 145.9, 143.7, 138.5, 134.2, 133.1, 131.4, 129.6, 129.1, 128.5, 127.4, 126.7, 122.8, 122.5, 121.0, 120.2, 117.4, 111.0, 93.5, 88.7 , 34.9, 32.0, 21.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₇ H ₂₅ O 365.1900, found 365.1898.

5,6-dimethoxy-3-(2-((3-methoxyphenyl)ethynyl)phenyl)benzofuran (4 { 4,3 } )

This compound contains 3-(2-iodophenyl)-5,6-dimethoxybenzofuran (1 { 4 } ) (50 mg, 0.13 mmol), 1-ethynyl-3-methoxybenzene (18 μL, 0.14 mmol), (Ph ₃ P) ₂ PdCl ₂ (9 mg, 0.013 mmol), and CuI (2.5 mg, 0.013 mmol) were synthesized in the same manner as 4 { 1,1 }. Yellow gum, (40.9 mg, 81%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.87 (s, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.44 (t, J = 7.2 Hz , 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.12-7.19 (m, 3H), 6.82-6.87 (m, 2H), 6.65 (s, 1H), 3.96 (s, 3H), 3.83 ( s, 3H), 3.72 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.4, 150.0, 148.1, 146.6, 142.4, 134.4, 133.3, 129.6, 129.5, 128.8, 127.5, 124.2, 123.9, 122.4, 121.2, 119.1, 115.7, 115.4, 102.8, 95.5 , 93.3, 89.2, 56.5, 56.4, 55.2; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₅ H ₂₁ O ₄ 385.1434, found 385.1438.

4,6-dimethoxy-3-(2-(naphthalen-1-ylethynyl)phenyl)benzofuran (4 { 4,11 } )

This compound contains 3-(2-iodophenyl)-5,6-dimethoxybenzofuran (1 { 4 } ) (50 mg, 0.13 mmol), 1-ethynylnaphthalene (20 μL, 0.14 mmol), ( Ph ₃ P) ₂ PdCl ₂ (9 mg, 0.013 mmol), and CuI (2.5 mg, 0.013 mmol) was synthesized in the same manner as 4 { 1,1 }. Yellow gum, (49.5 mg, 93%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.93 (s, 1H), 7.83-7.89 (m, 2H), 7.79 (t, J = 8.0 Hz, 2H), 7.59-7.61 (m, 1H), 7.44- 7.50 (m, 4H), 7.36-7.39 (m, 2H), 7.17 (s, 1H), 7.16 (s, 1H), 3.97 (s, 3H), 3.78 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 150.1, 148.3, 146.8, 142.5, 134.2, 133.5, 133.2, 133.2, 130.4, 129.8, 128.9, 128.8, 128.3, 127.6, 126.7, 126.5, 126.1, 125.3, 122.9, 121.2 , 120.9, 119.3, 102.5, 95.6, 94.0, 91.5, 56.5, 56.5; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₂₈ H ₂₀ NaO ₃ 427.1305, found 427.1301.

5,6-dimethoxy-3-(2-((4-(trifluoromethyl)phenyl)ethynyl)phenyl)benzofuran (4 { 4,12 } )

This compound is 3-(2-iodophenyl)-5,6-dimethoxybenzofuran (1 { 4 } ) (50 mg, 0.13 mmol), 1-ethynyl-4- (trifluoromethyl) benzene (20 μL, 0.14 mmol), (Ph ₃ P) ₂ PdCl ₂ (9 mg, 0.013 mmol), and CuI (2.5 mg, 0.013 mmol) were synthesized in the same manner as 4 { 1,1 }. Yellow solid, (45 mg, 81%); mp 121.6-122.8 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.86 (s, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.46-7.52 (m, 3H) , 7.40 (t, J = 7.2 Hz, 1H), 7.30 (d, J = 8 Hz, 2H), 7.15 (s, 1H), 7.14 (s, 1H), 3.97 (s, 3H), 3.83 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 150.1, 148.3, 146.7, 142.5, 134.6, 133.5, 131.6, 129.7, 129.3, 127.6,, 125.4 (q, J = 3.6 Hz), 121.7, 120.9, 118.9, 102.5, 95.6, 91.7, 56.6, 56.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₅ H ₁₈ F ₃ O ₃ 423.1203, found 423.1202.

4,6-dimethoxy-3-(2-(phenylethynyl)phenyl)benzofuran (4 { 5,1 } )

This compound contains 3-(2-iodophenyl)-4,6-dimethoxybenzofuran (1 { 5 } ) (50 mg, 0.13 mmol), phenylacetylene (15.4 μL, 0.14 mmol), (Ph ₃ P ) ₂ PdCl ₂ (9 mg, 0.013 mmol), and CuI (2.5 mg, 0.013 mmol) were synthesized in the same manner as 4 { 1,1 }. Yellow gum, (44 mg, 94%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.68 (s, 1H), 7.63 (dd, J = 1.6, 7.6 Hz, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.31-7.39 (m, 2H), 7.23-7.25 (m, 3H), 7.16-7.18 (m, 2H), 6.73 (d, J = 1.6 Hz, 1H), 6.35 (d, J = 1.6 Hz, 1H), 3.88 (s, 3H ) 3.72 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.2, 157.3, 154.9, 141.5, 134.7, 132.1, 131.5, 130.9, 128.3, 128.1, 127.7, 127.1, 123.6, 123.3, 120.4, 110.9, 94.8, 92.0, 89.6, 88.4 , 55.9, 55.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₃ 355.1329, found 355.1328.

Synthesis of 3-(2-((3-fluorophenyl)ethynyl)phenyl)-4,6-dimethoxybenzofuran (4 { 5,13 } )

1 { 5 } in DMF (1 mL) (50 mg, 0.13 mmol) 1-ethynyl-3-fluorobenzene (16.5 μL, 0.14 mmol), (Ph ₃ P) ₂ PdCl ₂ (9 mg, 0.013 mmol), CuI (2.5 mg , 0.013 mmol), and DIPEA (0.5 mL) were added. After stirring at 80° C. for 12 hours, the reaction mixture was diluted with water and extracted with EtOAc (10 mL×3). The combined organic layer was washed with water (10 mL × 2) and brine (10 mL), dried under anhydrous MgSO ₄ , and then concentrated under reduced pressure to obtain a crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 49:1) to give 4 { 5,13 } as a yellow gum (34 mg, 69%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.60-7.63 (m, 2H), 7.53 (d, J = 7.2 Hz, 1H), 7.32-7.40 (m, 2H), 7.15-7.21 (m, 1H), 6.91-6.96 (m, 2H), 6.77 (d, J = 9.6 Hz, 1H), 6.73 (s, 1H), 6.34 (s, 1H), 3.88 (s, 3H), 3.71 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 162.4 (d, J = 244.7 Hz), 159.3, 157.3, 154.9, 141.3, 135.0, 132.1, 130.8, 129.8 (d, J = 8.8 Hz), 128.1, 127.2 (d , J = 3.1 Hz), 127.2, 125.4 (d, J = 9.8 Hz), 122.9, 120.4, 118.2 (d, J = 22.3 Hz), 115.4 (d, J = 21.2 Hz), 110.9, 94.9, 90.8, 90.5 , 88.5, 55.9, 55.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₈ F0 ₃ 373.1234, found 373.1237.

4,6-dimethoxy-3-(2-(phenylethynyl)phenyl)benzofuran-7-carbaldehyde (4 { 6,1 } )

This compound is 3-(2-iodophenyl)-4,6-dimethoxybenzofuran-7-carbaldehyde (1 { 6 } ) (50 mg, 0.12 mmol), phenylacetylene (14.3 μL, 0.13 mmol) , (Ph ₃ P) ₂ PdCl ₂ (8.4 mg, 0.012 mmol), and CuI (2.3 mg, 0.012 mmol) were synthesized in the same manner as 4 { 5,13 }. Yellow solid, (29.3 mg, 62%), mp: 175.4-177.8 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.51 (s, 1H), 7.77 (s, 1H), 7.60-7.65 (m, 1H), 7.44-7.48 (m, 1H), 7.32-7.38 (m, 2H) ), 7.20-7.24 (m, 3H), 7.10-7.14 (m, 2H), 6.29 (s, 1H), 3.98 (s, 3H), 3.81 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.5, 163.3, 160.4, 155.6, 142.8, 133.9, 132.2, 131.4, 130.7, 128.3, 128.2, 127.8, 127.5, 123.6, 123.3, 119.9, 111.9, 106.4, 92.3, 89.9 , 89.1, 56.9, 55.9; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₂₅ H ₁₈ NaO ₄ 405.1097, found 405.1096.

4,6-dimethoxy-3-(2-((4-methoxyphenyl)ethynyl)phenyl)benzofuran-7-carbaldehyde (4 { 6,2 } )

This compound is 3-(2-iodophenyl)-4,6-dimethoxybenzofuran-7-carbaldehyde (1 { 6 } ) (50 mg, 0.12 mmol), 1-ethynyl-4-methoxy Benzene (17 μL, 0.13 mmol), (Ph ₃ P) ₂ PdCl ₂ (8.4 mg, 0.012 mmol), and CuI (2.3 mg, 0.012 mmol) were synthesized in the same manner as 4 { 5,13 }. Gray solid, (32.8 mg, 65%), mp: 185.2 {186.9 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.51 (s, 1H), 7.77 (s, 1H), 7.59 (s, 1H), 7.44 (s, 1H), 7.34 (s, 2H), 7.06 (d, J = 8.2 Hz, 2H), 6.75 (d, J = 8.2 Hz, 2H), 6.30 (s, 1H), 3.99 (s, 3H), 3.82 (s, 3H), 3.78 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.4, 163.2, 160.3, 159.4, 142.7, 133.4, 132.7, 131.7, 130.5, 127.34, 127.28, 123.8, 119.8, 115.3, 113.8, 111.9, 106.2, 95.5, 92.2, 89.8 , 87.6, 56.7, 55.7, 55.2; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₂₆ H ₂₀ NaO ₅ 435.1203, found 435.1201.

3-(2-(thiophen-3-ylethynyl)phenyl)naphtho[1,2-b]furan.

To a vial filled with 3-(2-iodophenyl)naphtho[1,2- b ]furan (50 mg, 0.14 mmol) in Et ₃ N (2 mL), 3-ethynylthiopine (27 μL, 0.27 mmol) ), (Ph ₃ P) ₂ PdCl ₂ (9.5 mg, 0.014 mmol), and CuI (2.6 mg, 0.014 mmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 100:1) was performed to obtain 3-(2-(thiophen-3-ylethynyl)phenyl)naphtho[1,2-b]furan as a transparent oil ( 43 mg, 91%).

¹ H NMR (400 MHz, acetone-d ₆ ) δ8.35-8.33 (m, 2H), 8.05 (d, J = 8.4 Hz, 1H), 7.85-7.79 (m, 2H), 7.72 (t, J = 7.0 Hz, 2H), 7.69-7.65 (m, 1H), 7.58-7.53 (m, 2H), 7.48 (d, J = 7.6 Hz, 1H), 7.45-7.44 (m, 1H), 7.41-7.39 (m) , 1H), 6.91 (d, J = 4.8 Hz, 1H); ¹³ C NMR (100 MHz, acetone-d ₆ ) δ 158.6, 156.4, 142.5, 133.9, 133.2, 131.8, 131.1, 130.6, 130.2, 129.9, 129.9, 129.0, 128.5, 127.8, 127.8, 127.2, 127.2, 127.1, 126.5 , 122.9, 122.7, 122.5, 121.1, 120.9, 120.4, 119.4, 112.2, 95.9, 93.4, 91.1, 55.2; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₅ OS 351.0838, found 351.0839.

1-(2-(thiophen-3-ylethynyl)phenyl)naphtho[2,1- b ]Furan.

To a vial filled with 1-(2-iodophenyl)naphtho[1,2- b ]furan (20 mg, 0.05 mmol) in Et ₃ N (2 mL), 3-ethynylthiopine (9 μL, 0.08 mmol) ), (Ph ₃ P) ₂ PdCl ₂ (3.8 mg, 5.4 μmol), and CuI (1.0 mg, 5.4 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 100:1) was performed to obtain 1-(2-(thiophen-3-ylethynyl)phenyl)naphtho[1,2-b]furan as a transparent oil ( 18 mg, 100%).

Brown oil; ¹ H NMR (400 MHz, CDCl ₃ ) δ7.95 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.81-7.79 (m, 2H), 7.75-7.72 (m) , 2H), 7.61-7.59 (m, 1H), 7.51-7.47 (m, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.02-7.00 ( m, 1H), 6.65-6.64 (m, 1H), 6.37-6.35 (m, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 152.9, 142.4, 135.5, 132.0, 130.7, 129.2, 128.6, 128.5, 128.3, 128.2, 128.0, 125.9, 125.7, 124.8, 124.4, 124.3, 123.9, 122.7, 121.8, 121.4, 1126, 88.6, 88.1; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₅ OS 351.0838, found 351.0839.

1-(2-((6-methoxynaphthalen-2-yl)ethynyl)phenyl)naphtho[2,1- b ]Furan.

To a vial filled with 1-(2-iodophenyl)naphtho[1,2- b ]furan (14 mg, 0.04 mmol) in Et ₃ N (2 mL), 2-ethynyl-6-methoxynaphthalene (16 mg, 0.09 mmol), (Ph ₃ P) ₂ PdCl ₂ (5.3 mg, 7.6 μmol), and CuI (1.5 mg, 7.6 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to obtain a crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 100:1) as a brown oil 1-(2-((6-methoxynaphthalen-2-yl)ethynyl)phenyl)naphtho[2,1- b ]Furan was obtained (15 mg, 93%).

Brown oil; ¹ H NMR (400 MHz, acetone-d ₆ ) δ8.03-8.02 (m, 2H), 7.94 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.83 (d , J = 8.4 Hz, 1H), 7.78-7.76 (m, 1H), 7.67-7.65 (m, 1H), 7.60-7.57 (m, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.42 ( t, J = 7.2 Hz, 1H), 7.36 (d, J = 7.2 Hz, 1H), 7.12 (s, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.85 (s, 1H), 6.63 ( d, J = 9.2 Hz, 1H), 3.83 (s, 3H); ¹³ C NMR (100 MHz, acetone-d ₆ ) δ 142.8, 142.5, 134.1, 131.8, 131.5, 130.7, 130.5, 130.4, 129.0, 128.7, 128.6, 128.4, 128.1, 127.8, 127.5, 126.6, 126.3, 125.9, 125.6, 124.5, 123.6, 123.3, 119.3, 118.9, 112.5, 112.2, 105.7, 105.4, 54.7; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₁ H ₂₁ O ₂ 425.1536, found 425.1538.

6-phenyl-3-(2-(thiophen-3-ylethynyl)phenyl)benzofuran.

To a vial filled with 3-(2-iodophenyl)-6-phenylbenzofuran (30 mg, 0.08 mmol) in Et ₃ N (2 mL), 3-ethynylthiopine (9 μL, 0.09 mmol), (Ph ₃ P) ₂ PdCl ₂ (5.3 mg, 7.6 μmol), and CuI (1.5 mg, 7.6 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 100:1) gave 6-phenyl-3-(2-(thiophen-3-ylethynyl)phenyl)benzofuran as a yellow oil (28 mg, 100 %).

Brown oil; ¹ H NMR (400 MHz, CDCl ₃ ) δ8.07(s, 1H), 7.83-7.81 (m, 2H), 7.72-7.68 (m, 3H), 7.65 (d, J = 7.6 Hz, 1H), 7.58 -7.55 (m, 1H), 7.51-7.46 (m, 3H), 7.41-7.37 (m, 2H), 7.27-7.27 (m, 1H), 7.23-7.21 (m, 1H), 6.95-6.94 (m, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 155.9, 143.9, 141.2, 138.1, 133.6, 132.9, 129.5, 129.4, 128.9, 128.5, 128.5, 127.4, 127.4, 127.2, 126.2, 125.3, 122.4, 122.2, 122.2, 121.2, 120.5, 110.1, 88.7, 88.4; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₆ H ₁₇ OS 377.0995, found 377.0996.

6-methoxy-3-(2-(phenanthrene-9-ylethynyl)phenyl)benzofuran.

In a vial filled with 3-(2-iodophenyl)-6-methoxybenzofuran (30 mg, 0.08 mmol) in Et ₃ N (2 mL), 9-ethynylphenanthrin (17.6 mg, 0.09 mmol), ( Ph ₃ P) ₂ PdCl ₂ (5.3 mg, 7.6 μmol), and CuI (1.5 mg, 7.6 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 100:1) to give 6-methoxy-3-(2-phenanthrene-9-ylethynyl)phenyl)benzofuran as a yellow oil (12 mg, 35 %).

Brown oil; ¹ H NMR (400 MHz, acetone-d ₆ ) δ8.77 (t, J = 8.0 Hz, 2H), 8.15 (s, 1H), 7.94-7.87 (m, 3H), 7.83 (s, 1H), 7.71 -7.66 (m, 3H), 7.63 (d, J = 4.4 Hz, 1H), 7.60 (s, 1H), 7.57-7.49 (m, 3H), 7.29 (s, 1H), 6.92 (d, J = 8.8 Hz, 1H), 3.88 (s, 3H); ¹³ C NMR (100 MHz, acetone-d ₆ ) δ 150.6, 142.9, 133.6, 132.9, 131.6, 129.9, 129.3, 128.8, 128.8, 128.4, 127.6, 126.6, 125.9, 125.5, 123.4, 122.6, 122.3, 121.9, 121.9 , 121.4, 119.6, 119.5, 88.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₁ H ₂₁ O ₂ 425.1536, found 425.1535.

6-methoxy-3-(2-((4-methoxy-2-methylphenyl)ethynyl)phenyl)benzofuran.

To a vial filled with 3-(2-iodophenyl)-6-methoxybenzofuran (30 mg, 0.08 mmol) in Et ₃ N (2 mL) 1-ethynyl-4-methoxy-2-methylbenzene ( 13 mg, 0.09 mmol), (Ph ₃ P) ₂ PdCl ₂ (5.3 mg, 7.6 μmol), and CuI (1.5 mg, 7.6 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to obtain 6-methoxy-3-(2-((4-methoxy-2-methylphenyl)ethynyl)phenyl)benzofuran as a yellow oil. (12 mg, 41%).

¹ H NMR (400 MHz, CDCl ₃ ) δ7.95 (s, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.41 (t, J = 7.4 Hz, 1H), 7.35 (t, J = 5.6 Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H), 7.09 (d, J = 1.6 Hz, 1H), 6.92-6.89 (m, 1H), 6.69 (s, 1H), 6.66-6.63 (m, 1H), 3.88 (s, 3H), 3.78 (s, 3H), 2.20 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.5, 158.0, 156.1, 142.4, 141.9, 133.3, 133.2, 133.0, 129.4, 128.0, 127.2, 122.9, 121.1, 120.6, 120.4, 115.2, 114.9, 111.8, 111.2, 95.9 , 92.0, 91.5, 55.8, 55.2, 20.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₅ H ₂₁ O ₃ 369.1485, found 369.1480.

3-(2-([1,1'-biphenyl]-4-ylethynyl)phenyl)-6-methoxybenzofuran.

4-ethynyl-1,1'-biphenyl (21 mg) to a vial filled with 3-(2-iodophenyl)-6-methoxybenzofuran (30 mg, 0.08 mmol) in Et ₃ N (2 mL) , 0.12 mmol), (Ph ₃ P) ₂ PdCl ₂ (5.3 mg, 7.6 μmol), and CuI (1.5 mg, 7.6 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 100:1) as a yellow oil 3-(2-([1,1'-biphenyl]-4-ylethynyl)phenyl)-6-methoxybenzo Furan was obtained (21 mg, 58%).

¹ H NMR (400 MHz, CDCl ₃ ) δ7.99 (s, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.63 (t, J = 7.6 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H), 7.44 (t, J = 7.4 Hz, 3H), 7.39 (m, 4H), 7.12 (d, J = 2.0 Hz, 1H), 6.95- 6.93 (m, 1H), 3.89 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.0, 156.2, 142.6, 140.9, 140.3, 133.9, 133.2, 131.8, 129.3, 128.8, 128.5, 127.6, 127.2, 126.9, 126.9, 122.1, 122.0, 121.2, 120.4, 120.3 , 111.9, 96.0, 92.9,` 89.9, 55.8; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₉ H ₂₁ O ₂ 401.1536, found 401.1531.

3-(2-([1,1'-biphenyl]-4-ylethynyl)phenyl)-5,6-dimethoxybenzofuran.

4-ethynyl-1,1'-biphenyl to a vial filled with 3-(2-iodophenyl)-5,6-dimethoxybenzofuran (30 mg, 0.08 mmol) in Et ₃ N (2 mL) (21 mg, 0.12 mmol), (Ph ₃ P) ₂ PdCl ₂ (5.3 mg, 7.6 μmol), and CuI (1.5 mg, 7.6 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) and as a transparent oil, 3-(2-([1,1'-biphenyl]-4-ylethynyl)phenyl)-5,6-di Methoxybenzofuran was obtained (22 mg, 65%).

¹ H NMR (400 MHz, CDCl ₃ ) δ7.93 (s, 1H), 7.73 (d, J = 7.2 Hz, 1H), 7.58-7.56 (m, 4H), 7.51 (d, J = 7.6 Hz, 2H ), 7.45 (d, J = 7.2 Hz, 2H), 7.37 (t, J = 7.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.20 (s, 1H), 7.15 (s, 1H ), 3.98 (s, 3H), 3.85 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 149.9, 148.0, 146.5, 142.4, 140.9, 140.2, 134.1, 133.2, 132.9, 131.7, 129.4, 128.8, 128.6, 127.6, 127.3, 126.9, 122.2, 121.9, 120.8, 118.9 , 102.5, 95.4, 93.0, 89.9, 56.4, 56.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₀ H ₂₃ O ₃ 431.1642, found 431.1649.

5,6-dimethoxy-3-(2-(phenanthrene-9-ylethynyl)phenyl)benzofuran.

To a vial filled with 3-(2-iodophenyl)-5,6-dimethoxybenzofuran (30 mg, 0.08 mmol) in Et ₃ N (2 mL), 9-ethynylphenanthrin (24 mg, 0.12 mmol) ), (Ph ₃ P) ₂ PdCl ₂ (5.3 mg, 7.6 μmol), and CuI (1.5 mg, 7.6 μmol) were added. After stirring at 80° C. for 12 hours, the reaction mixture was concentrated in vacuo to give the crude product. Purification by flash chromatography on silica gel (hexane:EtOAc, 100:1) to give 5,6-dimethoxy-3-(2-(phenanthrene-9-ylethynyl)phenyl)benzofuran as a yellow oil ( 23 mg, 66%).

Bright oil, ¹ H NMR (400 MHz, CDCl ₃ ) δ8.62 (s, 2H), 7.98-7.96 (m, 2H), 7.88 (s, 1H), 7.78 (s, 2H), 7.65-7.60 (m , 4H), 7.53-7.47 (m, 3H), 7.22-7.18 (m, 2H), 3.98 (s, 3H), 3.79 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 149.9, 148.2, 146.7, 142.3, 134.1, 133.3, 131.8, 131.1, 130.8, 130.2, 129.9, 129.7, 128.7, 128.5, 127.5, 127.4, 126.9, 126.9, 126.7, 122.6 , 122.5, 121.1, 119.5, 119.2, 102.5, 95.5, 93.5, 91.6, 56.4, 56.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₂ H ₂₃ O ₃ 455.1642, found 455.1643.

Synthesis of the compound of formula 2

The compound of Formula 1 and the compound of Formula 3 were reacted to obtain the compound of Formula 4, and the compound of Formula 2 was obtained from the compound of Formula 4 again.

[Scheme 1]

Table 1 summarizes the synthesis examples of various 6-substituted naphtho[2,1-b]benzofuran obtained through the process of Scheme 1.

Synthesis of various 6-substituted naphtho[2,1-b]benzofuran Example One Alkaine 4 2 rescue Abbreviation
(yield) One 1 { 1 } 3 { 1 } 4 { 1,1 }
(85)

6NP-1
2 { 1,1 }
(93) 2 1 { 1 } 3 { 2 } 4 { 1,2 }
(85)

6NP-2
2 { 1,2 } (88) 3 1 { 1 } 3 { 3 } 4 { 1,3 }
(83)

6NP-3
2 { 1,3 } (90) 4 1 { 1 } 3 { 4 } 4 { 1,4 }
(90)

6NP-4
2 { 1,4 } (78) 5 1 { 1 } 3 { 5 } 4 { 1,5 }
(91)

6NP-5
2 { 1,5 } (86) 6 1 { 1 } 3 { 6 } 4 { 1,6 }
(78)

6NP-8
2{1,6} (76) 7 1 { 1 } 3 { 7 } 4 { 1,7 } (80)

6NP-6
2 { 1,7 } (74) 8 1 { 1 } 3 { 8 } 4 { 1,8 } (83)

6NP-7
2 { 1,8 } (63) - 1 { 1 } 3 { 9 } 4 { 1,9 } (98) trace 2 { 1,9 } 9 1 { 2 } 3 { 1 } 4 { 2,1 } (92)

6NP-14
2 { 2,1 } (77) 10 1 { 2 } 3 { 7 } 4 { 2,7 } (66)

6NP-15
2 { 2,7 } (89) 11 1 { 3 } 3 { 10 } 4 { 3,10 } (62)

6NP-16
2 { 3,10 } (95) 12 1 { 3 } 3 { 4 } 4 { 3,4 } (79)

6NP-17
2 { 3,4 } (88) 13 1 { 4 } 3 { 3 } 4 { 4,3 } (81)

6NP-12
2 { 4,3 } (92) 14 1 { 4 } 3 { 11 } 4 { 4,11 } (93)

6NP-11
2 { 4,11 } (78) 15 1 { 4 } 3 { 12 } 4 { 4,12 } (81)

6NP-13
2 { 4,12 } (86) 16 1 { 5 } 3 { 1 } 4 { 5,1 } (94)

6NP-9
2 { 5,1 } (84) 17 1 { 5 } 3 { 13 } 4 { 5,13 } (69)

6NP-10
2 { 5,13 } (65) 18 1 { 6 } 3 { 1 } 4 { 6,1 } (62)

6NP-18
2 { 6,1 } (77) 19 1 { 6 } 3 { 2 } 4 { 6,2 } (65)

6NP-19
2 { 6,2 } (76)

Hereinafter, specific synthesis information of the compounds of Formula 2 listed in Table 1 will be described.

Synthesis of 9-methoxy-6-phenylnaphtho[2,1- b ]benzofuran (2 { 1,1 } )

A solution of 4 { 1,1 } (25 mg, 0.08 mmol) in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial was stirred at 80 °C for 30 min. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexanes:EtOAc, 49:1) to obtain 2 { 1,1 } as a yellow solid, ( 23.2 mg, 93%); mp: 93.7-95.2 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.58 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.99 (d , J = 8.0 Hz, 2H), 7.95 (s, 1H), 7.69 (t, J = 6.8 Hz, 1H), 7.53-7.61 (m, 3H), 7.48 (t, J = 7.6 Hz, 1H), 7.25 (d, J = 2.0 Hz, 1H), 7.10 (dd, J = 2.0, 8.8 Hz, 1H), 3.93 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.2, 157.4, 152.1, 136.7, 131.0, 129.4, 129.2, 128.8, 128.2, 128.1, 126.9, 126.9, 126.2, 124.8, 123.4, 122.4, 118.4, 118.4, 112.0, 96.8 , 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₃ H ₁₇ O ₂ 325.1223, found 325.1226.

9-methoxy-6-(4-methoxyphenyl)naphtho[2,1- b ]benzofuran (2 { 1,2 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 1,2 } (25 mg, 0.07 mmol). Gray solid, (22 mg, 88%); mp: 148.2 {150.4 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.57 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.94 (d , J = 8.8 Hz, 2H), 7.90 (s, 1H), 7.67 (t, J = 6.8 Hz, 1H), 7.54 (t, J = 7.2 Hz, 1H), 7.24 (d, J = 1.6 Hz, 1H ), 7.08-7.13 (m, 3H), 3.92 (s, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.7, 159.1, 157.3, 152.2, 131.1, 130.3, 129.2, 129.1, 127.9, 126.6, 126.5, 125.6, 124.8, 123.4, 122.3, 118.4, 118.3, 114.3, 111.9, 96.8 , 55.9, 55.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₃ 355.1329, found 355.1329.

9-methoxy-6-(3-methoxyphenyl)naphtho[2,1- b ]benzofuran (2 { 1,3 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 1,3 } (25 mg, 0.07 mmol). Yellow gum, (22.3 mg, 90%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.58 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.96 (s , 1H), 7.69 (t, J = 7.2 Hz, 1H), 7.48-7.58 (m, 4H), 7.25 (d, J = 1.6 Hz, 1H), 7.09 (dd, J = 1.6, 8.8 Hz, 1H) , 7.03 (d, J = 7.2 Hz, 1H), 3.95 (s, 3H), 3.93 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.9, 159.2, 157.4, 152.0, 138.0, 130.9, 129.8, 129.4, 128.2, 126.9, 126.7, 126.2, 124.8, 123.4, 122.3, 121.7, 118.5, 118.3, 115.0, 113.5 , 112.0, 96.8, 55.9, 55.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₃ 355.1329, found 355.1327.

9-methoxy-6-( p -tolyl)naphtho[2,1- b ]benzofuran (2 { 1,4 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 1,4 } (25 mg, 0.07 mmol). Off-white solid, (19.5 mg, 78%); mp: 155.2 {157.4°C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.58 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.93 ( s, 1H), 7.88 (d, J = 8.0 Hz, 2H), 7.68 (t, J = 6.8 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 2H), 7.23-7.25 (m, 1H), 7.10 (d, J = 8.8 Hz, 1H), 3.93 (s, 3H), 2.48 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.2, 157.4, 152.2, 138.0, 133.7, 131.0, 129.6, 129.3, 129.1, 128.0, 126.9, 126.8, 125.9, 124.8, 123.4, 122.3, 118.4, 118.4, 111.9, 96.8, 55.9, 21.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₂ 339.1380, found 339.1378.

9-methoxy-6-( m -tolyl)naphtho[2,1- b ]benzofuran (2 { 1,5 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 1,5 } (25 mg, 0.07 mmol). Yellow solid (21.4 mg, 86%); mp: 133.3-134.8 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.58 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.94 (s , 1H), 7.78-7.80 (m, 2H), 7.69 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.25-7.26 (m, 1H), 7.10 (dd, J = 2.4, 8.8 Hz, 1H), 3.93 (s, 3H), 2.53 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.2, 157.4, 152.2, 138.4, 136.6, 130.9, 129.8, 129.3, 128.9, 128.7, 128.1, 127.1, 126.8, 126.4, 126.2, 124.8, 123.4, 122.3, 118.4, 111.9 , 96.8, 55.9, 21.8; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₂ 339.1380, found 339.1381.

9-methoxy-6-(6-methoxynaphthalen-2-yl)naphtho[2,1- b ]benzofuran (2 { 1,6 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 1,6 } (25 mg, 0.06 mmol). White solid, (19 mg, 76%); mp: 224.4-226.2 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.60 (d, J = 8.0 Hz, 1H), 8.40 (s, 1H), 8.31 (d, J = 8.8 Hz, 1H), 8.05-8.08 (m, 3H) , 7.92 (t, J = 8.8 Hz, 2H), 7.70 (t, J = 7.6 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.22-7.28 (m, 3H), 7.11 (dd, J = 2.0, 8.8 Hz, 1H), 3.99 (s, 3H), 3.94 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.2, 158.2, 157.4, 152.3, 134.4, 131.9, 131.1, 130.1, 129.3, 129.2, 128.1, 128.1, 127.6, 127.2, 126.9, 126.8, 126.3, 124.8, 123.4, 122.4 , 119.3, 118.5, 118.4, 112.0, 105.8, 96.8, 55.9, 55.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₈ H ₂₁ O ₃ 405.1485, found 405.1490.

6-(4-chlorophenyl)-9-methoxynaphtho[2,1- b ]benzofuran (2 { 1,7 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 1,7 } (25 mg, 0.07 mmol). White solid, (18.6 mg, 74%); mp: 193.2 {195.4° C.; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.56 (d, J = 8.0 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.90-7.93 (m, 3H), 7.70 (t, J = 7.6 Hz, 1H), 7.52-7.56 (m, 3H), 7.22 (d, J = 2.0 Hz, 1H), 7.09 (dd, J = 2.0, 8.8 Hz, 1H), 3.93 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.3, 157.3, 151.8, 135.1, 134.1, 130.9, 130.4, 129.4, 129.0, 128.2, 127.1, 126.0, 125.6, 124.9, 123.4, 122.4, 118.6, 118.2, 112.1, 96.8 , 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₃ H ₁₆ ClO ₂ 359.0833, found 359.0835

9-methoxy-6-(thiophen-3-yl)naphtho[2,1- b ]benzofuran (2 { 1,8 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 1,8 } (25 mg, 0.08 mmol). White solid, (15.8 mg, 63%); mp: 177.4-178.6 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.55 (d, J = 8.0 Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H), 8.19-8.20 (m, 1H), 8.06 (s, 1H) , 8.03 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 5.2 Hz, 1H), 7.67 (t, J = 7.2 Hz, 1H), 7.51-7.56 (m, 2H), 7.28 (d, J = 2.0 Hz, 1H), 7.10 (dd, J = 2.0, 8.4 Hz, 1H), 3.95 (s, 3H). ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.2, 157.3, 151.8, 136.8, 130.9, 129.3, 127.9, 127.5, 126.8, 125.8, 124.9, 124.7, 124.1, 123.4, 122.4, 121.4, 118.5, 118.3, 112.1, 96.8 , 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₁ H ₁₅ O ₂ S 331.0787, found 331.0791.

6-phenylnaphtho[2,1- b ]benzofuran (2 { 2,1 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 2,1 } (25 mg, 0.08 mmol). Orange solid, (19.3 mg, 77%); mp: 130.2 {132.4°C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.66 (d, J = 8.4 Hz, 1H), 8.44-8.46 (m, 1H), 8.07 (d, J = 8.0 Hz, 1H), 8.00-8.04 (m, 3H), 7.71-7.75 (m, 2H), 7.56-7.62 (m, 3H), 7.48-7.54 (m, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 155.9, 152.3, 136.5, 130.9, 129.5, 129.2, 128.9, 128.6, 128.2, 127.7, 127.2, 127.0, 126.1, 125.1, 124.9, 123.4, 123.4, 122.1, 118.2, 112.2 ; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₂ H ₁₅ O 295.1117, found 295.1119.

6-(4-chlorophenyl)naphtho[2,1- b ]benzofuran (2 { 2,7 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 2,7 } (25 mg, 0.08 mmol). Orange solid, (22.3 mg, 89%); mp: 177.4-178.8 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.65 (d, J = 8.4 Hz, 1H), 8.44-8.46 (m, 1H), 8.06 (d, J = 8.4 Hz, 1H), 8.00 (s, 1H) , 7.94 (d, J = 8.4 Hz, 2H), 7.71-7.76 (m, 2H), 7.48-7.60 (m, 5H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 155.9, 134.9, 134.2, 131.4, 130.9, 130.4, 129.5, 129.1, 128.7, 127.5, 127.4, 126.3, 125.8, 125.1, 125.0, 123.5, 123.4, 122.2, 118.3, 112.2 ; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₂ H ₁₄ ClO 329.0728, found 329.0732.

10-( tert -butyl)-6-(3,5-dimethoxyphenyl)naphtho[2,1- b ]benzofuran (2 { 3,10 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 3,10 } (25 mg, 0.06 mmol). Yellow gum, (23.7 mg, 95%); ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.68 (d, J = 8.4 Hz, 1H), 8.44 (s, 1H), 8.07 (d, J = 8.0 Hz, 1H), 8.01 (s, 1H), 7.75 (t, J = 8.0 Hz, 1H), 7.64-7.66 (m, 1H), 7.56-7.59 (m, 2H), 7.11-7.15 (m, 2H), 6.60 (s, 1H), 3.90 (s, 6H) ), 1.53 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 161.1, 154.2, 152.5, 146.4, 138.6, 130.8, 129.5, 128.7, 127.4, 127.2, 126.9, 124.8, 124.8, 124.1, 123.4, 118.3, 111.5, 107.5, 100.3, 55.7 , 35.2, 32.2; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₂₈ H ₂₆ NaO ₃ 433.1774, found 433.1780.

10-( tert -butyl)-6-( p -tolyl)naphtho[2,1- b ]benzofuran (2 { 3.4 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 3,4 } (25 mg, 0.07 mmol). Yellow solid, (22 mg, 88%); mp: 142.0-144.8 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.68 (d, J = 8.4 Hz, 1H), 8.45 (d, J = 1.6 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.00 (s , 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.74 (t, J = 7.2 Hz, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.55-7.59 (m, 2H), 7.40 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H), 1.54 (s, 9H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 154.2, 152.7, 146.4, 138.0, 133.7, 130.9, 129.6, 129.4, 129.1, 128.6, 127.1, 126.9, 124.8, 124.7, 123.9, 123.4, 118.3, 118.3, 111.5, 35.1 , 32.2, 21.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₇ H ₂₅ O 365.1900, found 365.1898.

9,10-dimethoxy-6-(3-methoxyphenyl)naphtho[2,1- b ]benzofuran (2 { 4,3 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 4,3 } (25 mg, 0.07 mmol). Gray solid, (23 mg, 92%); mp: 148.4-149.6 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.54 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.94 (s, 1H), 7.82 (s, 1H), 7.70 (t, J = 7.2 Hz, 1H), 7.54-7.57 (m, 3H), 7.49 (t, J = 8.0 Hz, 1H), 7.28 (s, 1H), 7.02 (dd, J = 2.0, 8.0 Hz, 1H), 4.12 (s, 3H), 4.00 (s, 3H), 3.94 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.9, 152.0, 151.1, 149.3, 146.7, 138.0, 130.9, 129.8, 129.4, 128.2, 126.8, 126.8, 125.9, 124.7, 123.1, 121.7, 118.8, 116.7, 115.1, 113.5 , 103.8, 96.1, 56.9, 56.4, 55.6; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₅ H ₂₁ O ₄ 385.1434, found 385.1432

9,10-dimethoxy-6-(naphthalen-1-yl)naphtho[2,1- b ]benzofuran (2 { 4,11 } )

This compound is 4 { 4,11 } (25 mg, 0.06 mmol) was synthesized in the same manner as 2 { 1,1 }. Gray solid, (19.5 mg, 78%); mp: 172.5-174.8 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.64 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 8.0 (t, J = 8.8 Hz, 2H), 7.91 (s , 1H), 7.87 (s, 1H), 7.77 (t, J = 6.8 Hz, 1H), 7.70-7.72 (m, 2H), 7.58-7.67 (m, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.11 (s, 1H), 4.13 (s, 3H), 3.91 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 152.9, 151.2, 149.3, 146.7, 134.8, 133.9, 132.3, 130.7, 129.4, 128.7, 128.5, 128.4, 128.1, 126.9, 126.4, 126.3, 126.1, 125.6, 124.8, 123.3 , 118.2, 116.8, 103.9, 96.2, 56.9, 56.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₈ H ₂₁ O ₃ 405.1485, found 405.1486.

9,10-dimethoxy-6-(4-(trifluoromethyl)phenyl)naphtho[2,1- b ]benzofuran (2 { 4,12 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 4,12 } (25 mg, 0.06 mmol). Off-white solid, (21.5 mg, 86%); mp: 184.4-186.2 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.54 (d, J = 8.4 Hz, 1H), 8.04-8.10 (m, 3H), 7.93 (s, 1H), 7.81-7.83 (m, 3H), 7.73 (t, J = 7.2 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.26 (s, 1H), 4.12 (s, 3H), 4.00 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 151.6, 151.1, 149.5, 146.8, 140.3, 130.8, 129.6, 129.4, 128.5, 127.3, 126.1, 125.7 (q, J = 3.9 Hz) 125.4, 124.9, 123.2, 119.0 , 116.5, 103.8, 95.9, 56.9, 56.4; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₅ H ₁₈ F ₃ O ₃ 423.1203, found 423.1208.

9,11-dimethoxy-6-phenylnaphtho[2,1- b ]benzofuran (2 { 5,1 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 5,1 } (25 mg, 0.07 mmol). Gray solid, (21 mg, 84%); mp: 179.2 {181.2° C.; ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.48 (d, J = 8.8 Hz, 1H), 7.94-8.00 (m, 3H), 7.92 (s, 1H), 7.45-7.65 (m, 5H), 6.85 ( s, 1H), 6.54 (s, 1H), 4.14 (s, 3H), 3.91 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 160.3, 158.4, 154.8, 151.1, 136.9, 131.4, 129.3, 128.9, 128.7, 128.0, 127.9, 127.5, 126.4, 126.3, 126.1, 124.6, 119.6, 108.9, 94.8, 88.9 , 55.9, 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₉ O ₃ 355.1329, found 355.1330.

6-(3-fluorophenyl)-9,11-dimethoxynaphtho[2,1- b ]benzofuran (2 { 5,13 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 5,13 } (25 mg, 0.07 mmol). Pale yellow solid (16.3 mg, 65%); mp: 143.5-145.6 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.55 (d, J = 8.0 Hz, 1H), 8.05-8.10 (m, 3H), 7.93 (s, 1H), 7.81-7.83 (m, 3H), 7.73 ( t, J = 7.6 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.25-7.26 (m, 1H), 4.12 (s, 3H), 4.01 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.0 (d, J = 243.7 Hz) 160.5, 158.5, 154.9, 131.3, 130.2 (d, J = 8.3 Hz), 129.1, 128.2, 127.5, 126.4 (d, J = 9.1 Hz), 124.9 (d, J = 2.8 Hz), 124.8, 116.3 (d, J = 22.1 Hz), 114.8 (d, J = 20.7 Hz), 108.8, 108.5, 94.9, 88.9, 55.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₈ F0 ₃ 373.1234, found 373.1236.

9,11-dimethoxy-6-phenylnaphtho[2,1- b ]benzofuran-8-carbaldehyde (2 { 6,1 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 6,1 } (25 mg, 0.07 mmol). Orange solid, (19.2 mg, 77%), mp: 226.2-228.3 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.47 (s, 1H), 9.12 (d, J = 8.0 Hz, 1H), 8.10-8.12 (m, 2H), 7.92-7.96 (m, 2H), 7.59- 7.62 (m, 2H), 7.45-7.55 (m, 3H), 6.25 (s, 1H), 4.04 (s, 3H), 3.92 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.6, 162.6, 159.3, 157.5, 151.5, 135.9, 131.5, 129.09, 129.08, 128.8, 128.2, 127.5, 127.0, 126.7, 126.2, 125.7, 124.7, 118.1, 109.1, 105.6 , 89.6, 56.4, 55.9; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₂₅ H ₁₈ NaO ₄ 405.1097, found 405.1097.

9,11-dimethoxy-6-(4-methoxyphenyl)naphtho[2,1- b ]benzofuran-8-carbaldehyde (2 { 6,2 } )

This compound was synthesized in the same manner as 2 { 1,1 } using 4 { 6,2 } (25 mg, 0.06 mmol). Gray solid, (19 mg, 76%), mp: 217.2-218.8 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.56 (s, 1H), 9.23 (d, J = 8.5 Hz, 1H), 8.09 (d, J = 8.6 Hz, 2H), 7.97 (s, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.14 (d, J = 8.6 Hz, 2H), 6.40 (s, 1H), 4.18 (s, 3H), 4.02 (s, 3H), 3.92 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.9, 162.8, 159.8, 159.6, 157.7, 151.8, 131.8, 130.3, 129.1, 128.4, 127.3, 127.0, 126.2, 126.1, 125.7, 124.8, 118.1, 114.4, 105.9, 89.8 , 56.6, 56.1, 55.6; HRMS (ESI-QTOF) m/z [M+Na] ⁺ calcd for C ₂₆ H ₂₀ NaO ₅ 435.1203, found 435.1205.

Compounds of Examples 20 to 28, which belong to the compound of Formula 2, were further synthesized in a similar manner to the above.

Example rescue Abbreviation 20

6NP-21 21

6NP-22 22

6NP-23 23

6NP-24 24

6NP-25 25

6NP-26 26

6NP-27 27

6NP-28 28

6NP-29

6-(thiophen-3-yl)dynaptho[1,2- b :1',2'- d ]Furan.

A solution of 3-(2-(thiophen-3-ylethynyl)naphtho[1,2- b ]furan (43 mg, 0.12 mmol) in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial The mixture was stirred for 30 minutes at 80° C. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) as a white solid. 6-(thiophen-3-yl) dynaptho [1,2- b :1',2'- d ]furan (6NP-21) was obtained (37 mg, 86%).

White solid, mp: 189.4-190.1 °C; ¹ H NMR (400 MHz, acetone-d ₆ ) δ8.86 (d, J = 8.4 Hz, 1H), 8.69 (d, J = 8.8 Hz, 1H), 8.66-8.64 (m, 2H), 8.44 (s , 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 4.8 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H ), 7.80-7.76 (m, 3H), 7.69-7.62 (m, 2H); ¹³ C NMR (100 MHz, acetone-d ₆ ) δ 136.3, 132.4, 131.3, 129.3, 128.4, 127.9, 127.2, 127.1, 126.9, 126.3, 126.1, 125.2, 125.1, 124.5, 24.3, 123.3, 121.3, 121.2, 120.6 , 119.9; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₅ OS 351.0838, found 351.0833.

6-(thiophen-3-yl)dynaptho[2,1- b :1',2'- d ]Furan.

A solution of 1-(2-(thiophen-3-ylethynyl)naphtho[1,2- b ]furan (18 mg, 0.05 mmol) in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial The mixture was stirred for 30 minutes at 80° C. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) as a white solid. 6-(thiophen-3-yl) dynaptho [2,1- b :1',2'- d ]furan (6NP-22) was obtained (18 mg, 100%).

White solid, mp: 156.0-156.6 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.12 (t, J = 9.6 Hz, 2H), 8.21 (s, 1H), 8.13 (s, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.97-7.95 (m, 1H), 7.87-7.85 (m, 2H), 7.75-7.69 (m, 2H), 7.60-7.53 (m, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 154.2, 151.8, 136.4, 131.4, 131.2, 129.5, 129.4, 128.5, 128.4, 127.6, 127.5, 126.2, 125.9, 125.6, 125.4, 124.7, 124.4, 124.1, 121.2, 120.2, 112.7; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₄ H ₁₅ OS 351.0838, found 351.0837.

1-(2-((6-methoxynaphthalen-2-yl)ethynyl)phenyl)naphtho[2,1- b ]Furan.

1-(2-((6-methoxynaphthalen-2-yl)ethynyl)phenyl)naphtho[2,1- b ]furan (15 in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial mg, 0.04 mmol) was stirred at 80° C. for 30 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo to give a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to obtain a white solid as 1-(2-((6-me). Toxinaphthalen- 2-yl)ethynyl)phenyl)naphtho[2,1- b ]furan (6NP-3) was obtained (15 mg, 100%).

White solid, mp: 198.7-199.4 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.19 (t, J = 7.6 Hz, 2H), 8.41 (s, 1H), 8.13-8.09 (m, 5H), 7.98-7.93 (m, 3H), 7.88 (t, J = 9.0 Hz, 2H), 7.79-7.74 (m, 2H), 3.99 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.1, 154.4, 134.2, 131.6, 131.2, 129.9, 129.5, 129.1, 128.6, 128.4, 128.1, 127.8, 127.6, 127.4, 127.0, 126.8, 126.2, 125.9, 125.6, 125.4, 124.7, 124.4, 119.2, 112.9, 105.7, 55.4; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₁ H ₂₁ O ₂ 425.1536, found 425.1533.

9-phenyl-6-(thiophen-3-yl)naphtho[2,1- b ]Benzofuran.

A solution of 6-phenyl-3-(2-(thiophen-3-ylethynyl)phenyl)benzofuran (28 mg, 0.07 mmol) in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial was added to 80 It was stirred at °C for 30 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to form 9-phenyl-6-(thiophene- ) as a white solid. 3-yl)naphtho[2,1- b ]benzofuran (6NP-24) was obtained (21 mg, 100%).

White solid, mp: 168.5-169 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ8.59 (d, J = 8.4 Hz, 1H), 8.41 (d, J = 8.4 Hz, 1H), 8.23-8.22 (m, 1H), 8.11 (s, 1H) ), 8.03 (d, J = 8.0 Hz, 1H), 7.96 (s, 1H), 7.84 (d, J = 4.8 Hz, 1H), 7.73 (t, J = 7.4 Hz, 3H), 7.68 (d, J = 8.0 Hz, 1H), 7.57-7.50 (m, 4H), 7.41 (t, J = 7.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 156.4, 152.3, 140.9, 139.5, 136.4, 130.7, 129.2, 128.9, 128.1, 127.5, 127.4, 127.2, 126.9, 125.9, 125.7, 124.8, 124.1, 123.9, 123.3, 122.7, 122.0, 121.3, 117.9, 110.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for calcd for C ₂₆ H ₁₇ OS 377.0995, found 377.0996.

9-methoxy-6-(phenanthrene-9-yl)naphtho[2,1- b ]Benzofuran.

A solution of 6-methoxy-3-(2-phenanthrene-9-ylethynyl)phenyl)benzofuran (12 mg, 0.03 mmol) in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial was added to 80 It was stirred at °C for 30 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to form 9-methoxy-6-(phenanthrene ) as a white solid. -9-yl)naphtho[2,1- b ]benzofuran (6NP-25) was obtained (12 mg, 100%).

White solid, mp: 205.8-206.1 °C; ¹ H NMR (400 MHz, acetone-d ₆ ) δ9.00 (d, J = 8.4 Hz, 1H), 8.96 (d, J = 8.0 Hz, 1H), 8.51 (d, J = 8.0 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 8.09-8.05 (m, 3H), 7.85-7.64 (m, 6H), 7.53 (t, J = 7.6 Hz, 1H), 7.15-7.13 (m, 2H) , 3.86 (s, 3H); ¹³ C NMR (100 MHz, acetone-d ₆ ) δ 159.6, 157.3, 152.7, 133.4, 131.6, 131.2, 130.9, 130.5, 130.4, 129.3, 128.9, 128.7, 128.2, 128.0, 127.3, 127.2, 127.1, 126.8, 126.8 , 125.8, 124.9, 123.5, 123.1, 122.7, 122.4, 117.7, 117.6, 112.3, 96.4, 55.2; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₁ H ₂₁ O ₂ 425.1536, found 425.1533.

9-methoxy-6-(4-methoxy-2-methylphenyl)naphtho[2,1- b ]Benzofuran.

6-methoxy-3-(2-((4-methoxy-2-methylphenyl)ethynyl)phenyl)benzofuran (12 mg, 0.03 mmol) in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial ) Was stirred at 80° C. for 30 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to form 9-methoxy-6-(4- Methoxy-2-methylphenyl)naphtho[2,1- b ]benzofuran (6NP-26) was obtained (12 mg, 100%).

White solid, mp: 80.4-81.2 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ8.61 (d, J = 8.4 Hz, 1H), 8.29 (d, J = 8.8 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.73 ( s, 1H), 7.69 (d, J = 7.2 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 2.0 Hz, 1H), 7.11-7.08 (m, 1H), 6.96 (d, J = 2.0 Hz, 1H), 6.93-6.90 (m, 1H), 3.91 (s, 6H), 2.26 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.5, 158.9, 157.2, 152.7, 138.5, 131.5, 130.6, 129.0, 128.9, 127.9, 127.4, 126.9, 126.6, 124.5, 123.3, 122.2, 118.4, 117.5, 115.7, 111.7 , 111.2, 96.7, 55.7. 55.3. 20.5; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₅ H ₂₁ O ₃ 369.1485, found 369.1489.

6-([1,1'-biphenyl]-4-yl)-9-methoxynaphtho[2,1- b ]Benzofuran.

3-(2-([1,1'-biphenyl]-4-ylethynyl)phenyl)-6-methoxybenzofuran (21 mg in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial , 0.05 mmol) was stirred at 80° C. for 30 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to obtain 6-([1,1'-by ) as a white solid. Phenyl]-4-yl)-9-methoxynaphtho[2,1- b ]benzofuran (6NP-27) was obtained (18 mg, 86%).

White solid, mp: 167.9-168.5 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.59 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.07 (t, J = 7.0 Hz, 3H), 8.00 ( s, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.73-7.68 (m, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.51 (t, J = 7.0 Hz, 3H), 7.41 (t, J = 7.0 Hz, 1H), 7.27 (d, J = 5.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 1H), 3.94 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.1, 157.2, 151.9, 140.8, 135.4, 130.9, 129.5, 129.4, 129.2, 128.8, 128.0, 127.4, 127.4, 127.1, 126.8, 126.2, 125.9, 124.7, 123.6, 122.2 , 118.2, 111.9, 96.7, 55.7; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₂₉ H ₂₁ O ₂ 401.1536, found 401.1537.

6-([1,1'-biphenyl]-4-yl)-9,10-dimethoxynaphtho[2,1- b ]Benzofuran.

3-(2-([1,1'-biphenyl]-4-ylethynyl)phenyl)-5,6-dimethoxybenzofuran in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial A solution of (22 mg, 0.05 mmol) was stirred at 80 °C for 30 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to obtain 6-([1,1'-by ) as a white solid. Phenyl]-4-yl)-9,10-dimethoxynaphtho[2,1- b ]benzofuran (6NP-28) was obtained (18 mg, 82%).

White solid, mp: 207.4-208.2 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.55 (d, J = 7.6 Hz, 1H), 8.10-8.05 (m, 3H), 7.98 (s, 1H), 7.82-7.80 (m, 3H), 7.71 -7.69 (m, 3H), 7.57 (t, J = 7.4 Hz, 1H), 7.51-7.49 (m, 2H), 7.41 (d, J = 6.8 Hz, 1H), 7.30 (s, 1H), 4.12 ( s, 3H), 4.01 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 150.9, 149.1, 146.5, 140.8, 135.5, 130.8, 129.4, 129.3, 128.8, 127.9, 127.4, 127.4, 127.1, 126.7, 126.3, 125.6, 124.6, 122.9, 118.6, 116.5 , 103.7, 95.9, 56.8, 56.3; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₀ H ₂₃ O ₃ 431.1642, found 431.1641.

9,10-dimethoxy-6-(phenanthrene-9-yl)naphtho[2,1- b ]Benzofuran.

5,6-dimethoxy-3-(2-(phenanthrene-9-ylethynyl)phenyl)benzofuran (23 mg, 0.05 mmol) in a mixture of DCE (2.0 mL) and TFA (1.0 mL) in a vial The solution of was stirred at 80° C. for 30 minutes. After cooling to room temperature, the reaction mixture was concentrated in vacuo to obtain a crude product, which was purified by flash chromatography on silica gel (hexane:EtOAc, 100:1) to form 9,10-dimethoxy-6- (Phenanthren-9-yl)naphtho[2,1- b ]benzofuran (6NP-29) was obtained (18 mg, 78%).

Bright brown solid, mp: 137.7-138.4 °C; ¹ H NMR (400 MHz, CDCl ₃ ) δ8.84 (d, J = 8.4 Hz, 1H), 8.80 (d, J = 8.4 Hz, 1H), 8.65 (d, J = 8.0 Hz, 1H), 8.08 ( d, J = 8.0 Hz, 1H), 7.97 (s, 2H), 7.88 (s, 1H), 7.88 (s, 1H), 7.77 (t, J = 8.0 Hz, 1H), 7.75-7.71 (m, 2H) ), 7.67 (t, J = 7.6 Hz, 2H), 7.61 (t, J = 7.6 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.07 (s, 1H), 4.14 (s, 3H ), 3.89 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 152.9, 151.1, 149.1, 146.5, 133.4, 131.5, 130.7, 130.5, 129.3, 128.9, 128.8, 127.8, 127.1, 126.9, 126.9, 126.8, 126.6, 124.7, 123.1, 122.9 , 122.7, 118.1, 116.6, 103.7, 96.0, 56.8, 56.1; HRMS (ESI-QTOF) m/z [M+H] ⁺ calcd for C ₃₂ H ₂₃ O ₃ 455.1642, found 455.1646.

[Experimental Example]

Experimental Example 1: Analysis of optical properties of the compound of Formula 2

The UV-Vis absorption spectrum of the synthesized compound was measured at room temperature using a Lambda25 UV/Vis spectrometer (PerkinElmer, Waltham, MA, USA). Fluorescence spectrum was measured using a FP-6500 spectrofluorometer (JASCO, Tokyo, Japan), which is a slit width specification of 3 nm excitation and 5 nm emission. The solid-state fluorescence spectrum was measured at room temperature using a fluoromax-4 spectrofluorometer (Horiba Jobin Yvon, Kyoto, Japan), which is a slit width specification of 0.5 nm for excitation and emission. The fluorescence quantum yield of the compound in the solution was measured using anthracene (Φ = 0.27 in EtOH) as a standard, and the absolute fluorescence quantum yield of the solid was measured using a Horiba FluoroMax-4 spectrophotometer with an integrating sphere assembly. Particle size distribution was analyzed using dynamic light scattering with ELSZ-2000 (Otsuka, Chiyoda, Japan).

The quantum yield and absorption and emission maximum values of the compounds according to Examples 1 to 19 are summarized in Table 3.

Optical properties of the compounds according to Examples 1 to 19 Example λ _abs (nm) λ _em (nm) ε _max (M ^-One cm ^-One ) Φ _F (Solution) DW EtOH DMSO Example 1
2 { 1,1 } 329 420.5 389.5 400.5 18600 0.60 Example 22 { 1,2 } 331 412.5 384.5 393.5 23200 0.74 Example 32 { 1,3 } 328 413.5 390.5 401.5 18600 0.67 Example 42 { 1,4 } 328 431.5 388 397.5 18800 0.62 Example 52 { 1,5 } 329 411.5 389 399.5 18800 0.57 Example 62 { 1,6 } 308 425.5 393.5 406 32800 0.78 Example 72 { 1,7 } 328 430.5 393.5 408.5 17900 0.63 Example 82 { 1,8 } 332 412.5 385.5 394 20100 0.63 Example 92 { 2,1 } 321 380 379.5 384.5 19300 0.38 Example 102 { 2,7 } 322 386 383.5 388.5 21700 0.45 Example 112 { 3,10 } 325 392 382.5 387 14400 0.39 Example 122 { 3,4 } 324 406 379.5 383.5 21800 0.51 Example 132 { 4,3 } 342 435.5 404.5 425 22800 0.66 Example 142 { 4,11 } 350 426.5 402 423 20700 0.70 Example 152 { 4,12 } 355 447.5 424.5 449 18400 0.72 Example 162 { 5,1 } 322 444.5 398.5 412 15900 0.52 Example 172 { 5,13 } 322 452 405.5 423 14900 0.58 Example 182 { 6,1 } 354 - 478 - 15400 0.06 Example 192 { 6,2 } 311 473.5 487 424.5 22100 0.03

Optical properties of the compounds according to Examples 20 to 28 were measured in a similar manner, and these are summarized in Table 4.

λ _abs (nm) DW
λ _em (nm) Tris (pH 7.5)
λ _em (nm) EtOH
λ _em (nm) DMSO
λ _em (nm) CHCl ₃
λ _em (nm) ε _max (M ^-One cm ^-One ) Example 20
6NP-21 354 - - 378.5 382.5 369.5 27200 Example 21
6NP-22 362 422.5 425.0 387.5 392.5 392.0 30000 Example 22
6NP-23 362 448.0 447.5 392.0 403.5 392.5 29900 Example 23
6NP-24 338 - - 368.5 390.0 372.0 33000 Example 24
6NP-25 345 426.0 429.0 389.5 405.5 388.5 18400 Example 25
6NP-26 345 393.5 416.0 375.5 384.0 379.5 20500 Example 26
6NP-27 298 414.0 408.5 399.0 412.5 498.0 36700 Example 27
6NP-28 338 439.5 435.0 414.0 437.5 406.5 23800 Example 28
6NP-29 350 425.0 420.5 406.0 426.5 398.0 22400

1 shows absorption spectra (a) and emission spectra (b) of 6NP-14, 6NP-2, 6NP-7, 6NP-8, 6NP-11, 6NP-12 and 6NP-13 measured with DMSO. The maximum absorption of the compound was observed at about 300-350 nm, whereas the maximum emission was observed at about 380-450 nm in DMSO. The observed huge Stokes shift shifts to 100 nm, avoiding reabsorption of the emitted photons, is an important variable for bioimaging applications. Structure-property relationship analysis based on optical properties shows that the electron-donating group (EDG) (-OCH ₃ ) attached to the A ring increases the red shift of the emission spectrum, and the electron withdrawal group (EWG) (-Cl and -CF ₃ ) resulted in a red shift of the maximum emission value (FIG. 2 ). Figure 2 shows the fluorescence spectra of 0.5 μM of 6NP-14 (a) , 6NP-1 (b) , 6NP-9 (c) , 6NP-6 (d) , and 6NP-13 (e) in various solvents. .

3 shows fluorescence spectra of the compounds according to Examples 20 to 28 at 0.5 μM in various solvents.

Experimental Example 2: Image-based cell screening

HeLa (human cervical cancer cell line) cells were inoculated on a Cellcarrier-96 black plate (PerkinElmer, Waltham, MA, USA) for 20,000 cells/well and cultured at 37° C. and 5% CO ₂ for 24 hours. For imaging of living cells, cells were treated with a compound for 1 hour, and cell screening images were collected at 410-480 nm through an Operetta High-Content imagine system (PerkinElmer, Waltham, MA, USA), with a 20x objective lens. Blue fluorescence was emitted upon excitation at 360-400 nm. Harmony software (PerkinElmer, Waltham, MA, USA) was used for image analysis.

For imaging of living cells, HeLa cells were laid on a confocal dish and incubated at 37° C. and 5% CO ₂ for 24 hours. The same sample was incubated with 10 μM NP compound for 1 hour at 37° C. under 5% CO ₂ , and then 150nM MitoTracker Red (Molecular probes, Eugene, OR, USA) or 75nM LysoTracker Red (Molecular probes, Eugene, OR) for 20 minutes. , USA) for 30 minutes. After treatment, the sample was washed twice with Dulbecco's phosphate-buffered saline (DPBS), and then live cell imaging was performed using a TCS-SP8 confocal laser scanning microscope (Leica, Wetzlar, Germany). Images of NP-treated cells were obtained at 410-560 nm with blue fluorescence upon excitation at 405 nm, whereas LysoTracker Red and MitoTracker Red were excited at 561 nm and detected at >566 nm with red fluorescence.

4 shows the results of live cell imaging of HeLa cells. (a) Fluorescent and bright field live cell images of HeLa cells stained for 1 h with 10 μM and 20 μM of 6-substituted naphtho[2,1- b ]benzofuran. Enlarged image: 20 μM 6NP-12 (b) , 6NP-13 (c) , and 6NP-10 (d) . Scale bar represents 100 μm.

5 shows the results of confocal live cell imaging of HeLa cells. Confocal live cell images of HeLa cells were incubated with 10 μm of 6NP-13 for 1 hour and then treated with 150 nM of MitoTracker Red (a) for 20 minutes and 75 nM of LysoTracker Red (b) for 30 minutes. The blue channel (e.g. 405 nm, Em: 410-560 nm) comes from 6NP-13 fluorescence, and the red channel from LysoTracker Red fluorescence or MitoTracker Red fluorescence (Ex: 561 nm, Em:> 566 nm). Scale bar is 10 μm. Intensity profile of the region of interest (ROI) with yellow lines on HeLa cells.

As a result of the experiment, synthetic compounds for live cell imaging of HeLa cells were selected, and it was found that the 6NP-12, 6NP-13, and 6NP-10 compounds have the highest cell permeability where they are located in the cytoplasm of HeLa cells (FIGS. 4 and 5 ).

Experimental Example 3: Cytotoxicity test

The phototoxicity of the compounds was evaluated using MTT assay. MCF7 (human breast cancer cell line) cells were inoculated on 96-well cell culture plates (SPL Life Science Co., Gyeonggi-do) at a density of 10,000 cells/well. After culturing for 24 hours, the cells were treated with various concentrations of compounds (0.5, 1, 2, 5 and 10 μM) in a cell culture medium at 37° C. for 1 hour. The cell medium was replaced with fresh medium and the cells were irradiated for 0, 5 and 10 minutes with blue LED light (800 lm/m ² ). After irradiation, the cells were cultured for 24 hours in a dark environment at 37° C. and 5% CO ₂ . After medium replacement, 20 μM 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (5 mg/mL) was added to each well and incubated for 3 hours. Finally, the medium was removed and the formazan product was dissolved in DMSO (100 μl/well). Cell viability was evaluated by measuring the absorbance at 570 nm using a Mithras ² plate reader (Berthold Technologies, Bad Wildbad, Germany).

6 shows the results of a cytotoxicity test of the compound of Formula 2. 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d)

6NP-8 and 6NP-7 exhibited high fluorescence through aggregation-induced emission characteristics. The phototoxicity of these compounds turned out to be negligible (Figure 6).

Experimental Example 4: DSE properties

7 shows the DSE properties of the compound of Formula 2. Of 10 μM 6NP-8 (a) , 6NP-7 (b) , and 6NP-12 (c) in a THF/water mixture (0-99%) in natural light (top) and ultraviolet (bottom, λex = 312 nm) Photo. 10 μM 6NP-8 (d) , 6NP-7 (e) in excited THF/water mixture (0-99%) at 308 nm (d) , 332 nm (e), 342 nm (f ) , And the fluorescence spectrum of 6NP-12 (f) ; Insertion: Fluorescence intensity graph of 6NP-8 (d) at 396 nm, 6NP-7 (e) at 388 nm, and 6NP-12 (f) at 405 nm.

Up to 70% of the moisture content in THF resulted in fluorescence enhancement, but a decrease in fluorescence was observed above 70%.

8 shows the fluorescence spectrum of the compound of Formula 2 in EtOH and solid state. Fluorescence spectra of 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d) in EtOH (0.5 μM, dotted line) and solid state (solid line); Insertion: 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d) in the solid state under natural light (left) and ultraviolet (right, λ _ex = 365 nm ) Photo.

These compounds showed high QY when dissolved in ethanol and in a solid state (Fig. 8 and Table 5).

Optical properties of 6NP-8, 6NP-7, 6NP-12 and 6NP-13 when dissolved in ethanol and in a solid state. compound EtOH solid λ _abs (nm) λ _em (nm) Φ _F (Solution) λ _abs (nm) λ _em (nm) Φ _F (Solid, %) 6NP-8
2 { 1,6 } 308 393.5 0.78 367 408 19.67 6NP-7
2 { 1,8 } 332 385.5 0.63 372 422 22.15 6NP-12
2 { 4,3 } 342 404.5 0.66 370 434 16.33 6NP-13
2 { 4,12 } 355 424.5 0.72 373 437 1.54

9 shows the result of particle size analysis of the compound of Formula 2. Particle size distribution in THF/water mixture (5/95: v/v). 10 μM of 6NP-8 (a) , 6NP-7 (b) , 6NP-12 (c) , and 6NP-13 (d) ; Upper left: intensity distribution, upper right: volume distribution, lower left: numeric distribution, lower right: LN(G2(τ)-1) vs τ. According to DLS analysis, 6NP-8, 6NP-7, 6NP-12 and 6NP The particle sizes of -13 are 211 nm, 208 nm, 167 nm and 200 nm, respectively (Fig. 9).

10 shows the fluorescence spectra of 6NP-7 in various dispersion solvents. Most of the solvents except for water exhibited high fluorescence (FIG. 10).

Experimental Example 5: Single crystal X-ray diffraction study

In order to understand the interactions that contributed to solid state release, the intermolecular interaction of 6NP-7 was analyzed by analyzing the geometry and packing arrangement in the crystal state.

Single crystals of 6NP-7 with a size of 0.427 × 0.22 × 0.104 mm ³ were grown by the vapor diffusion method using CH ₂ Cl ₂ and cyclopentane. Suitable crystals were mounted on SuperNova, Dual, Cu at home/near and AtlasS2 diffractometers (Agilent, Santa Clara, CA, USA). Data collection of 6NP-7 used a SuperNova dual source diffractometer operating with Cu-Kα radiation (λ = 1.542 mm ^-1 ) at 294.4 K. With Olex2, The structure was solved by the direct method using ShelXT software and refined by the least squares minimization method using ShelXL software. Additional crystallographic data for 6NP-7 is available at www.ccdc.cam.ac.uk/data_request/cif . It can be obtained from the Cambridge Crystallography Data Center. The deposition number of 6NP-7 is CCDC 1884862. Copies of all data can be downloaded upon request from CCDC, 12 Union Road, Cambridge CB2 1EZ, UK.

11 shows the results of crystal structure analysis of 6NP-7. (a) CH in the molecule indicated by the yellow line... Crystal structure of 6NP-7 with O interaction (2.249Å). (b) Slip-stacked 6NP-7 molecule viewed from the side. (c) Intermolecular S… shown by the red line. Packing structure of 6NP-7 through S bond (3.769 Å). (d) packing structure of 6NP-7 through intermolecular interactions; Red: Intermolecular S… S bond (3.769 Å); Green: Intermolecular CH… S bond (3.156 Å); Orange: Intermolecular CH… O bond (2.524 Å).

One of the characteristic interactions of 6NP-7 packing is slip-stacks with a pitch angle of 5.729 Å with a pitch angle of 54.711° between the 6-arylnaphtho[2,1- b ]benzofuran rings at each center. It deviates greatly from the conventional π-π stacking interaction that reduces Through slip-stacks, each 6NP-7 compound has a short distance between the S atoms of the thienyl group. Intermolecular S… with atypical hydrogen bonds (CH…O bonds: 2.524 Å, CH…S bonds: 3.156 Å) The S interaction (3.769Å) constitutes an intermolecular network that enhances the molecular packing of 6NP-7 as depicted in Figure 11. In addition to the well-ordered O and S atoms, these intermolecular hydrogen bonds have a significant influence on the molecular packing mode, resulting in high emission in the solid state. These non-bonding interactions have been found to expand electron interactions leading to radiation pathways.

In conclusion, the inventors have developed a modular synthesis method for a wide range of naphthofuran derivatives through Sonogashira cross-coupling and 6-endo-dig electrophilic cyclization. The optical and imaging properties of the synthesized compound were tested, and 6NP-12, 6NP-13 and 6NP-10 were used using a high-definition imaging system. The compound was found to be the most cellular permeable. 6NP-8 and 6NP-7 showed high fluorescence through aggregation-induced emission properties. Interestingly, 6NP-8, 6NP-7, and 6NP-12 have solid state emissivity and high fluorescence in most solvents in solution, resulting in a very important dual state emission (DSE) property for a wide range of applications, including biological imaging. Show. The compounds developed in this study will serve as new fluorescent scaffolds for a variety of biomedical and optoelectronic applications.

Claims (11)

Compounds of Formula 2:
[Formula 2]

A represents a hydrocarbon ring selected from benzene or naphthalene,
R ₁ is C _1-6 alkyl; C _1-6 alkoxy; Aldehyde; It is a substituent selected from the group consisting of halogen, haloalkyl, hydroxy and phenyl,
m is an integer from 0 to 4,
When m is 2 or more, R ₁ may each be a different substituent,
R ₃ may be aryl or heteroaryl unsubstituted or substituted with one or more substituents. The method of claim 1,
The aryl or heteroaryl is phenyl, naphthyl, anthracenyl, phenanthryl, biphenyl, terphenyl, or thiophene. The method of claim 1,
The aryl or heteroaryl is C _1-6 alkyl; C _1-6 alkoxy; Aldehyde; A compound unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, haloalkyl, and hydroxy. The method of claim 1,
A represents a hydrocarbon ring selected from benzene or naphthalene,
R ₁ is C _1-6 alkyl; C _1-6 alkoxy; And a substituent selected from the group consisting of aldehyde,
n is an integer from 0 to 4,
When n is 2 or more, R ₁ may be each different substituent,
R ₃ is C _1-6 alkyl; Or C _1-6 alkyl; C _1-6 alkoxy; A compound which is phenyl, naphthyl, phenanthryl, biphenyl or thiophene unsubstituted or substituted with one or more substituents selected from halogen and haloalkyl. The method of claim 1,
The compound of Formula 1 is any one of the following compounds.

Reaction of the compound of Formula 1 with the compound of Formula 3 to obtain a compound of Formula 4,
A method for preparing a compound of Formula 2 comprising obtaining a compound of Formula 2 from the compound of Formula 4:
[Formula 1]

[Formula 2]

[Formula 3]

[Formula 4]

In the above formula,
A represents a hydrocarbon ring selected from benzene or naphthalene,
R ₁ is C _1-6 alkyl; C _1-6 alkoxy; Aldehyde; It is a substituent selected from the group consisting of halogen, haloalkyl, hydroxy and phenyl,
m is an integer from 0 to 4,
When m is 2 or more, R ₁ may each be a different substituent,
R ₂ is halogen,
R ₃ may be aryl or heteroaryl unsubstituted or substituted with one or more substituents. A fluorescent dye comprising the compound according to any one of claims 1 to 4. The fluorescent dye according to claim 7, wherein the compound exhibits fluorescence in a solid state and/or in a solvent. The fluorescent dye according to claim 7, which exhibits blue fluorescence. The fluorescent dye according to claim 8, wherein the blue fluorescence exhibits a maximum emission wavelength of 400 to 500 nm. The fluorescent dye according to claim 8, which is for bioimaging.

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