KR20210050300A - Indolizine core skeleton-Based Emissive Fluorescent Compounds and Use thereof - Google Patents

Abstract

The present invention relates to indolizine skeleton-based radioactive fluorescent compounds and a use thereof, and more particularly, to indolizine skeleton-based radioactive fluorescent compounds, a manufacturing method thereof, a composition for detecting volatile organic compounds (VOC) containing the same, and a method for detecting a sensor and volatile organic compounds. In the present invention, as a result of detecting 35 different VOC substances using a fluorescent sensor array coated with a fluorescent compound and image analysis technology, the indolizine-based fluorescent sensor array shows different change patterns in response to 35 types of VOCs. As a result of learning the image pattern using statistical analysis and machine learning algorithms, the learned algorithm, which was able to detect volatile organic compounds with a high accuracy of 97%, has confirmed. The fluorescent compunds are represented by a chemical formula 1.

Description

Indolizine core skeleton-Based Emissive Fluorescent Compounds and Use thereof

The present invention relates to an indolizine skeleton-based radioactive fluorescent compound and its use, and more particularly, to an indolizine skeleton-based radioactive fluorescent compound, a method for preparing the same, and volatile organic compounds (VOC) detection including the same. It relates to a composition, a sensor, and a method for detecting volatile organic compounds.

In the 21st century, environmental pollution is occurring due to the artificial influence of the rapid increase in population and industrial growth. At the same time, humanity is aware that the environment is being polluted, and at the same time, interest in health due to environmental factors increases. Environmental pollution is occurring due to the artificial influence of the rapid increase and industrial growth. At the same time, humanity is aware that the environment is being polluted, and at the same time, interest in health due to environmental factors is increasing. Diseases are largely induced by environmental pollution such as water quality, soil, air, and food, and these pollutants are detected by ion chromatography, high performance liquid chromatography, liquid chromatography-mass spectrometry, etc. The pretreatment process is different depending on the material to be measured, expensive laboratory equipment is used for precise analysis, and because an expert is required for analysis, it is difficult to obtain data directly in the field.

In particular, volatile organic compounds (VOC), one of the elements of environmental toxic substances, are a generic term for liquid or gaseous organic compounds that are easily evaporated into the atmosphere due to their low boiling point. It is known to be mainly discharged from the surroundings of life such as plastic drying process and sick house syndrome. The effects of volatile organic compounds on the human body include respiratory irritation, carcinogenicity, causing abnormalities in the heart and liver, gastrointestinal nervous system, and central nervous system. When exposed to volatile organic compounds, fatigue, headache, drowsiness, dizziness, It has been reported to cause cardiac arrhythmias.

On the other hand, the fluorescence phenomenon is simple to use, the signal-to-noise ratio is high due to the characteristics of the excitation wavelength and the emission wavelength, and the sensitivity is very high enough to analyze a single molecule.Therefore, the sensor using the fluorescence phenomenon has high sensitivity and fast response time. It has an advantage. In general, in a fluorescence sensor, when an ion or a substance to be analyzed is combined with a recognition part of the sensor, a change in fluorescence is observed in a part representing a signal, and the presence or concentration of the substance is detected by using this change. Recently, research has been conducted to detect environmentally important ions and neutral organic molecules using such a fluorescent chemical sensor. Fluorescent chemical sensors are applied to intracellular imaging, environmental toxic substances detection, neurotoxic gas detection, enzyme reaction rate measurement, and molecular calculation, but conventional systems generally develop fluorescent chemical sensors with high selectivity and sensitivity for a single analyte. As the focus is on, it is limited to analyze various target substances with a single detection method.

In contrast, in the fluorescence array system, since each of the fluorescent materials constituting the system can interact with one or more analytes, the sum of the changes in the fluorescence properties of each of the fluorescent materials observed in the fluorescent chemical sensor array is a specific target. For the material, the array as a whole forms a specific pattern in terms of it. Therefore, the array system is relatively easy to construct because each fluorescent substance does not have to react selectively to the analyte, and once constructed, it can be applied even in the absence of a specific marker in disease diagnosis, allowing diagnosis of a wide range of diseases. There is an advantage that it is possible. In addition, artificial intelligence technologies such as deep learning and machine learning, which are rapidly developing in recent years, can find patterns that are easy to analyze from signals generated by the interaction between arrays and target materials.

Accordingly, the present inventors discovered a new design of a novel fluorescent core skeleton based on an indolizine central skeleton for constructing such a fluorescent array, and in order to confirm the possibility of such an array technology, the present invention relates to the detection of volatile organic compounds. I tried to apply. Development of a sensor array for detecting volatile organic compounds using fluorescent materials is of high interest in various research fields, but development of a sensor array using a new fluorescent material skeleton is insufficient. In the present invention, real-time monitoring of volatile organic compounds is performed. As a result of diligent efforts to develop a novel fluorescent material for this, a radioactive fluorescent compound based on an indolizine skeleton was developed, and a sensor array coated with a total of 75 fluorescent materials was fabricated. As a result of detecting volatile organic compounds using the sensor array of the present invention, and learning image patterns using statistical analysis and machine learning algorithms, the learned algorithm was able to detect volatile organic compounds with a high accuracy of 97%. Confirmed and completed the present invention.

An object of the present invention is to provide a radioactive fluorescent compound based on an indolizine skeleton and a method for preparing the same.

Another object of the present invention is to provide a composition for detecting volatile organic compounds (VOC) including the fluorescent compound.

Another object of the present invention is to provide a sensor array for detecting volatile organic compounds in which the fluorescent compounds are fixed, and a method for detecting volatile organic compounds using the same.

To achieve the above object,

The present invention provides a fluorescent compound represented by the following formula (1).

[Formula 1]

In Formula 1,

R ₁ is hydrogen; Nitrile group; halogen; Nitro group; C1-C6 alkoxy group; C6-C20 aryl group; C5-C20 cycloheterocyclic group; Boron group; Azide group; NR ₄ R ₅ (wherein R ₄ and R ₅ are each independently hydrogen, C1-C10 alkyl group, C6-C20 aryl group or C4-C20 heteroaryl group), nitrile, C1-C6 alkoxy, halogen , A boron group, a hydroxy group, or CH ₂ NR ₄ R ₅ (wherein R ₄ and R ₅ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group) A C6-C20 aryl group substituted with; C1-C8 linear or branched alkyl group; C2-C8 alkenyl group; C2-C8 alkynyl group; C3-C8 cycloalkyl group; Or a C4-C20 heteroaryl group,

R ₂ is hydrogen; C1-C8 linear or branched alkyl group; C2-C8 alkenyl group; C2-C8 alkynyl group; C3-C8 cycloalkyl group; Hydroxy group; C1-C6 alkoxy group; Polyethylene glycol group; Nitrile group; Nitro group; Carboxyl group; Sulfonyl group; Azide group; Methanesulfonyl group; Maleimide group; Alcohols protected by tertiary-butyldimethylsilyl group (TBS); Or NR ₆ R ₇ (wherein R ₆ and R ₇ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group or a C4-C20 heteroaryl group),

R ₃ is hydrogen; halogen; Nitrile group; Boron group; Hydroxy group; COY (wherein Y is hydrogen, a C1-C8 linear or branched alkyl group, a C2-C8 alkenyl group, a C2-C8 alkynyl group, a C3-C8 cycloalkyl group, or NR ₈ R ₉ (herein, R ₈ and Each R ₉ is independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group]); C1-C6 alkoxy group; C6-C20 aryl group; Or NR ₁₀ R ₁₁ (Wherein, R ₁₀ and R ₁₁ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group), a C6-C20 aryl group substituted with nitrile or halogen. .

In a preferred embodiment of the present invention, R ₁ is hydrogen; Trifluoromethyl group; Acetyl group; Methoxy group; Or a dimethylamine group, and R ₂ is methyl; Trifluoromethylphenyl group; Phenyl group; Methoxyphenyl group; Or a diethylaminephenyl group, and R ₃ is hydrogen; Trifluoromethyl group; Or it may be an acetyl group.

In another preferred embodiment of the present invention, Formula 1 may be represented by one or more selected from the group consisting of the following Formulas 1-1 to 1-75.

[Formula 1-1]

[Formula 1-2]

[Formula 1-3]

[Formula 1-4]

[Formula 1-5]

[Formula 1-6]

[Formula 1-7]

[Formula 1-8]

[Formula 1-9]

[Formula 1-10]

[Formula 1-11]

[Formula 1-12]

[Formula 1-13]

[Formula 1-14]

[Formula 1-15]

[Formula 1-16]

[Formula 1-17]

[Formula 1-18]

[Formula 1-19]

[Formula 1-20]

[Formula 1-21]

[Formula 1-22]

[Formula 1-23]

[Formula 1-24]

[Formula 1-25]

[Formula 1-26]

[Formula 1-27]

[Formula 1-28]

[Formula 1-29]

[Formula 1-30]

[Formula 1-31]

[Formula 1-32]

[Formula 1-33]

[Formula 1-34]

[Formula 1-35]

[Formula 1-36]

[Formula 1-37]

[Formula 1-38]

[Formula 1-39]

[Formula 1-40]

[Formula 1-41]

[Formula 1-42]

[Formula 1-43]

[Formula 1-44]

[Formula 1-45]

[Formula 1-46]

[Formula 1-47]

[Formula 1-48]

[Formula 1-49]

[Formula 1-50]

[Chemical Formula 1-51]

[Formula 1-52]

[Formula 1-53]

[Formula 1-54]

[Formula 1-55]

[Formula 1-56]

[Formula 1-57]

[Formula 1-58]

[Formula 1-59]

[Formula 1-60]

[Formula 1-61]

[Formula 1-62]

[Formula 1-63]

[Formula 1-64]

[Formula 1-65]

[Formula 1-66]

[Formula 1-67]

[Formula 1-68]

[Formula 1-69]

[Formula 1-70]

[Formula 1-71]

[Formula 1-72]

[Chemical Formula 1-73]

[Formula 1-74]

[Formula 1-75]

In the present invention, the emission wavelength of the fluorescent compound is 400 nm to 620 nm, and may exhibit liquid or solid state fluorescence.

In addition, the present invention comprises the steps of (a) reacting a compound of formula A and a compound of formula B to prepare a compound of formula C;

(b) reacting the compound of Formula C with ethyl acrylate, sodium acetate, and copper acetic acid monohydrate to prepare a compound of Formula D;

(c) preparing a compound of Formula E by reacting the compound of Formula D and NBS (N-Bromosuccinimide); And

(d) reacting the compound of Formula E and the compound of Formula F to prepare a compound of Formula 1, and provides a method for preparing a fluorescent compound of Formula 1 represented by the following Scheme 1:

[Scheme 1]

R ₁ is hydrogen; Trifluoromethyl group; Acetyl group; Methoxy group; Or a dimethylamine group, and R ₂ is methyl; Trifluoromethylphenyl group; Phenyl group; Methoxyphenyl group; Or a diethylaminephenyl group, and R ₃ is hydrogen; Trifluoromethyl group; Or an acetyl group.

In order to achieve another object, the present invention provides a composition for detecting volatile organic compounds (VOC) including the fluorescent compound.

In order to achieve another object, the present invention provides a sensor array for detecting volatile organic compounds including the fluorescent compound.

In a preferred embodiment of the present invention, the volatile organic compound is not particularly limited, but preferably ethanol (Ethanol), 1-butanol (1-Butanol), 1- (pentanol (1-Pentanol), 1- Hexanol (1-Hexanol), 3-hexanol (3-Hexanol), phenol (Phenol), 1-heptanol (1-Heptanol), 1-decanol (1-Decanol), 2-decanol (2- Decanol), 3-Decanol, 1-Dodecanol, Cyclopentanol, Cyclohexanol, Cycloheptanol, Benzene, Acetone (Acetone), 2-Octanone, 2-Picoline, 3-Picoline, 3-Acetylpyridine, 4-acetylpyridine (4) -Acetylpyridine), 2-Heptylamine, Di-n-propylamine, 2-Phenylethylamine, Cyclooctylamine, Propionic acid ), 3-Bromopropionic acid, 2-Methylbutyric acid, Formic acid, Valeric acid, Trifluoroacetic acid, Bromoacetic acid ( Bromoacetic acid), acetic acid, trichloroacetic acid, and 2-chloropropionic acid may be one or more substances selected from the group consisting of.

In addition, the present invention provides a method for detecting a volatile organic compound using the fluorescent compound.

In a preferred embodiment of the present invention, the method comprises the steps of: (a) exposing a volatile material to a sensor array for detecting a volatile organic compound to which a fluorescent compound is fixed, and then measuring a change in a fluorescence pattern; And

(b) learning the pattern change through a machine learning algorithm.

In another preferred embodiment of the present invention, in step (b), the RGB distance, hue value, or CIEDE2000 information of the pattern may be learned through a machine learning algorithm.

In the present invention, as a result of detecting 35 different VOC substances using a fluorescent sensor array coated with a fluorescent compound and an image analysis technology, the indolizine-based fluorescent sensor array reacts to 35 types of VOCs and shows each change pattern. As a result of learning the image pattern using statistical analysis and machine learning algorithm, it was confirmed that the learned algorithm can detect volatile organic compounds with a high accuracy of 97%.

1 is a diagram showing the molecular orbital calculation result of an indolizine structure.
FIG. 2 is a schematic diagram showing the chemical structure and shapes of HOMO and LUMO of the novel fluorescent compound of the present invention.
3 is a schematic diagram showing a method for preparing a novel fluorescent compound of the present invention.
4 is a diagram showing the structures (GxF 1 to 25) of newly synthesized fluorescent compounds.
5 is a diagram showing the structures (GxF 26 to 50) of newly synthesized fluorescent compounds.
6 is a diagram showing the structures (GxF 51 to 75) of newly synthesized fluorescent compounds.
7 is a diagram showing the characteristics of a fluorescent compound showing an emission wavelength over the entire visible light region.
8 is a diagram showing a change in fluorescence properties according to the shape of a molecular orbital of a GxF 63 material among fluorescent compounds and the dielectric constant of a solvent.
9 is a diagram illustrating solid fluorescence of GxF materials in the entire visible light region.
10 is a diagram illustrating a change in fluorescence in a solid phase of a GxF material according to different VOC exposures.
11 is a diagram showing an embodiment of a fluorescence sensor array in which a GxF material, which is a novel fluorescent compound of the present invention, is fixed in a solid phase and the degree of fluorescence of the sensor array under UV conditions.
12 is a view showing a sealed container for exposing VOCs to a fluorescent sensor array in which a GxF material is fixed in a solid phase. It is a sensor array in which (a) GxF 1 ~ 25, (b) GxF 26 ~ 50, and (c) GxF 51 ~ 75 are fixed respectively.
13 is a diagram showing an embodiment of a device for monitoring a fluorescent sensor array using 3D printing.
14 is a diagram showing a process of analyzing color information before and after VOC exposure through development of its own color information algorithm.
FIG. 15 is a diagram illustrating the degree of fluorescence after exposure of various VOCs to the fluorescence sensor array, and an experiment was repeated 5 times for each VOC.
16 is a diagram showing a fluorescence sensor array showing different patterns of change for each VOC.
17 is a view showing the result of analyzing the change of the fluorescence sensor array pattern according to the type of VOC by the principal component analysis method.
18 is a diagram showing VOC prediction results analyzed using a machine learning algorithm.

Hereinafter, the present invention will be described in detail.

In a single point of view, the present invention relates to a fluorescent compound represented by the following formula (1).

[Formula 1]

In Formula 1 above

R ₁ is hydrogen; Nitrile group; halogen; Nitro group; C1-C6 alkoxy group; C6-C20 aryl group; C5-C20 cycloheterocyclic group; Boron group; Azide group; NR ₄ R ₅ (wherein R ₄ and R ₅ are each independently hydrogen, C1-C10 alkyl group, C6-C20 aryl group or C4-C20 heteroaryl group), nitrile, C1-C6 alkoxy, halogen , A boron group, a hydroxy group, or CH ₂ NR ₄ R ₅ (wherein R ₄ and R ₅ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group) A C6-C20 aryl group substituted with; C1-C8 linear or branched alkyl group; C2-C8 alkenyl group; C2-C8 alkynyl group; C3-C8 cycloalkyl group; Or a C4-C20 heteroaryl group,

R ₂ is hydrogen; C1-C8 linear or branched alkyl group; C2-C8 alkenyl group; C2-C8 alkynyl group; C3-C8 cycloalkyl group; Hydroxy group; C1-C6 alkoxy group; Polyethylene glycol group; Nitrile group; Nitro group; Carboxyl group; Sulfonyl group; Azide group; Methanesulfonyl group; Maleimide group; Alcohols protected by tertiary-butyldimethylsilyl group (TBS); Or NR ₆ R ₇ (wherein R ₆ and R ₇ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group or a C4-C20 heteroaryl group),

R ₃ is hydrogen; halogen; Nitrile group; Boron group; Hydroxy group; COY (wherein Y is hydrogen, a C1-C8 linear or branched alkyl group, a C2-C8 alkenyl group, a C2-C8 alkynyl group, a C3-C8 cycloalkyl group, or NR ₈ R ₉ (herein, R ₈ and Each R ₉ is independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group]); C1-C6 alkoxy group; C6-C20 aryl group; Or NR ₁₀ R ₁₁ (Wherein, R ₁₀ and R ₁₁ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group), a C6-C20 aryl group substituted with nitrile or halogen. .

In the present invention, R ₁ is hydrogen; Trifluoromethyl group; Acetyl group; Methoxy group; Or a dimethylamine group, and R ₂ is methyl; Trifluoromethylphenyl group; Phenyl group; Methoxyphenyl group; Or a diethylaminephenyl group, and R ₃ is hydrogen; Trifluoromethyl group; Or it may be an acetyl group.

Preferably, Formula 1 may be represented by one or more selected from the group consisting of the following Formulas 1-1 to 1-75.

[Formula 1-1]

[Formula 1-2]

[Formula 1-3]

[Formula 1-4]

[Formula 1-5]

[Formula 1-6]

[Formula 1-7]

[Formula 1-8]

[Formula 1-9]

[Formula 1-10]

[Formula 1-11]

[Formula 1-12]

[Formula 1-13]

[Formula 1-14]

[Formula 1-15]

[Formula 1-16]

[Formula 1-17]

[Formula 1-18]

[Formula 1-19]

[Formula 1-20]

[Formula 1-21]

[Formula 1-22]

[Formula 1-23]

[Formula 1-24]

[Formula 1-25]

[Formula 1-26]

[Formula 1-27]

[Formula 1-28]

[Formula 1-29]

[Formula 1-30]

[Formula 1-31]

[Formula 1-32]

[Formula 1-33]

[Formula 1-34]

[Formula 1-35]

[Formula 1-36]

[Formula 1-37]

[Formula 1-38]

[Formula 1-39]

[Formula 1-40]

[Formula 1-41]

[Formula 1-42]

[Formula 1-43]

[Formula 1-44]

[Formula 1-45]

[Formula 1-46]

[Formula 1-47]

[Formula 1-48]

[Formula 1-49]

[Formula 1-50]

[Chemical Formula 1-51]

[Formula 1-52]

[Formula 1-53]

[Formula 1-54]

[Formula 1-55]

[Formula 1-56]

[Formula 1-57]

[Formula 1-58]

[Formula 1-59]

[Formula 1-60]

[Formula 1-61]

[Formula 1-62]

[Formula 1-63]

[Formula 1-64]

[Formula 1-65]

[Formula 1-66]

[Formula 1-67]

[Formula 1-68]

[Formula 1-69]

[Formula 1-70]

[Formula 1-71]

[Formula 1-72]

[Chemical Formula 1-73]

[Formula 1-74]

[Formula 1-75]

In the present invention, the fluorescent compound has an emission wavelength of 400 nm to 620 nm, and exhibits liquid or solid state fluorescence.

In the present invention, in order to monitor volatile organic compounds in real time, a novel fluorescent material based on an indolizine skeleton was synthesized. First, molecular orbital calculations were performed using the TD-DFT calculation method to construct an indolizine-based library.As a result, as shown in FIG. 1, the HOMO and LUMO lobes at positions C1, C3, and C6 of the indolizine structure The difference turned out to be large.

Based on this, a structure like the one below was finally set up for the construction of a fluorescent material library, and it was named as Galaxy Floor (GalaxyFluor; GxF, hereinafter referred to as "GxF" or "GxF material"), and as a result of quantum calculation, GxF material In the case of, it was verified that the compartmentalization of the HOMO and LUMO lobe is clearly occurring, and it was verified that intramolecular charge transfer (ICT) shape can be induced (FIG. 2).

In another aspect, the present invention comprises the steps of: (a) reacting a compound of formula A and a compound of formula B to prepare a compound of formula C;

(b) reacting the compound of Formula C with ethyl acrylate, sodium acetate, and copper acetic acid monohydrate to prepare a compound of Formula D;

(c) preparing a compound of Formula E by reacting the compound of Formula D and NBS (N-Bromosuccinimide); And

(d) reacting the compound of Formula E and the compound of Formula F to prepare a compound of Formula 1, and relates to a method for preparing a fluorescent compound of Formula 1 represented by the following Scheme 1.

[Scheme 1]

In Scheme 1, R ₁ is hydrogen; Trifluoromethyl group; Acetyl group; Methoxy group; Or a dimethylamine group, and R ₂ is methyl; Trifluoromethylphenyl group; Phenyl group; Methoxyphenyl group; Or a diethylaminephenyl group, and R ₃ is hydrogen; Trifluoromethyl group; Or it may be an acetyl group.

Specifically, the GxF material, which is the fluorescent compound of the present invention, can be synthesized by the method shown in FIG. 3, and more specifically, the method of preparing the fluorescent compound according to the present invention will be described step by step in detail.

a) step: acylation of the pyridine material

In this step, compound B is acylated using an alkyl halide.

The acylation may be performed without limitation using a conventional method known in the art. Preferably, as the alkyl halide, compound B is ₂ -bromo-1-[4-(tri Fluoromethyl)phenyl]ethane-1-one (2-bromo-1-[4-(trifluoromethyl)-phenyl]ethane-1-one), chloroacetone, 2-bromoacetophenone ), 2-bromo-4-methoxyacetophenone, 2-bromo-4'-(diethylamino_aceto-phenone (2-Bromo-4'-(diethylamino)aceto) -Phenone), etc. containing an electrophilic moiety is used, and _{a pyridine having an R 3} substituent is used.

Specifically, a solution of an organic mixture of alkyl halide and pyridine is stirred at an appropriate temperature (20°C to 100°C) for 1 to 24 hours to obtain a pyridine salt compound. At this time, the organic solvent used to send the reaction may be a conventional organic solvent, and can be appropriately determined by a person skilled in the art according to specific types of alkyl halide and pyridine compounds.

b) Step: 1,3-dipolar cyclization reaction

The acylated compound represented by formula c obtained in step a) is reacted with ethyl acrylate, sodium acetate, and copper acetic acid monohydrate. This is the step of obtaining a compound.

Specifically, the acylated compound organic mixture solution obtained in step a) is stirred at an appropriate temperature (50° C. to 120° C.) for 1 to 24 hours, and then the usual extraction, drying, filtration, concentration, and purification processes are performed. Through the process, a compound represented by Formula D is obtained. At this time, the organic solvent used to send the reaction may be a conventional organic solvent, and can be appropriately determined by a person skilled in the art according to the specific type of the compound.

c) step: Br substituent introduction step

This is a step of obtaining a compound represented by Formula E through saponification and bromination reactions of the compound represented by Formula D.

The above reaction can be carried out without limitation using a conventional method known in the art. Preferably, the compound represented by Formula D is first dissolved in an organic solvent, and then lithium hydroxide and potassium hydroxide. ), a strong base such as sodium hydroxide is added, and the resulting organic mixture solution is stirred at an appropriate temperature (50°C to 120°C) for 1 to 24 hours, followed by normal extraction, drying, filtration, concentration and purification Through the process, an intermediate material is obtained. After dissolving the intermediate material in an appropriate organic solvent, after treatment with NBS (N-Bromosuccinimide), the resulting organic mixture solution was stirred at an appropriate temperature (50℃ to 120℃) for 1 to 24 hours, followed by normal extraction and drying. , Filtration, concentration and purification to yield the compound represented by the formula (E). At this time, the organic solvent used to send the reaction may be a conventional organic solvent, and can be appropriately determined by a person skilled in the art according to the specific type of the compound.

d) Step: Suzuki coupling step

This is a step to obtain a fluorescent compound of the present invention by reacting a compound represented by Formula E with a compound represented by Formula F using a Pd catalyst.

The above reaction may be carried out without limitation using a conventional method known in the art. First, the compound represented by Formula F including the R1 substituent is not particularly limited, and preferably, trifluorophenyl boronic acid (triflulorophenyl boronic acid), 4-acetylphenyl boronic acid, phenyl boronic acid, 4-methoxyphenyl boronic acid, 4-(dimethylamino ) Phenyl boronic acid (4- (dimethylamino) phenyl boronic acid) can be used. The above reaction is performed _{by mixing a compound represented by Formula F having an R 1} substituent and a compound represented by Formula E obtained in step c) with Pd(PPh ₃ ) ₄ and Sodium carbonate in a common organic solvent, The organic mixture solution is stirred at an appropriate temperature (50° C. to 120° C.) for 1 to 24 hours, and then subjected to conventional extraction, drying, filtration, concentration, and purification processes to obtain the fluorescent compound of the present invention. At this time, the organic solvent used to send the reaction may be a conventional organic solvent, and can be appropriately determined by a person skilled in the art according to the specific type of the compound.

In a specific embodiment of the present invention, a combinatorial chemical synthesis method was developed to synthesize a total of 75 novel fluorescent substances represented by Chemical Formulas 2 to 76, and were named GxF 1 to GxF 75, respectively.

The photophysical properties of the GxF materials synthesized by the method of the present invention were observed and shown in Table 1. It was confirmed that the GxF materials cover the entire visible light range from 416 nm to 620 nm, and in particular, as shown in FIG. 7, it was confirmed that they can exhibit solid state fluorescence.

As initially expected, it was confirmed that these materials responded to the surrounding environment through the ICT phenomenon, and the fluorescent properties changed. As shown in FIG. 8, in the case of the GxF 63 material, fluorescence according to the change of the dielectric constant of the solvent in the solution phase. It was confirmed that it was affected by the brightness.

In addition, as a result of confirming whether the GxF material exhibits solid state fluorescence, four different GxF materials (GxF 1, GxF 3, GxF 5, GxF 11) have an emission wavelength covering the entire visible light region even in a solid state. Was confirmed.

Based on the above results, in the present invention, in order to confirm whether the fluorescence change occurs in the solid state in response to VOCs of GxF materials, GxF 15, GxF 40, and GxF 65 materials are applied as a film on the glass, and then three different VOCs Changes in fluorescence were observed by exposure to vapor (Ethyl acetate, acetic acid, ethylamine). As a result, as shown in FIG. 10, it was confirmed that the three substances were exposed to three different VOCs to induce a change in each of the fluorescence phenomena.

In another aspect, the present invention relates to a composition for detecting volatile organic compounds (VOC) including the fluorescent compound.

In another aspect, the present invention relates to a sensor array for detecting a volatile organic compound to which the fluorescent compound is fixed.

In the present invention, the volatile organic compound is not particularly limited, but preferably ethanol (Ethanol), 1-butanol (1-Butanol), 1- (pentanol (1-Pentanol), 1-hexanol (1- Hexanol), 3-hexanol (3-Hexanol), phenol (Phenol), 1-heptanol (1-Heptanol), 1-decanol (1-Decanol), 2-decanol (2-Decanol), 3- Decanol, 1-Dodecanol, Cyclopentanol, Cyclohexanol, Cycloheptanol, Benzene, Acetone, 2 -Octanone, 2-Picoline, 3-Picoline, 3-acetylpyridine, 4-Acetylpyridine, 2 -Heptylamine (2-Heptylamine), di-en-propylamine (Di-n-propylamine), 2-phenylethylamine (2-Phenylethylamine), cyclooctylamine (Cyclooctylaime), propionic acid (Propionic acid), 3-bromine Propionic acid (3-Bromopropionic acid), 2-Methylbutyric acid, Formic acid (Formic acid), Valeric acid (Valeric acid), Trifluoroacetic acid (Trifluoroacetic acid), Bromoacetic acid (Bromoacetic acid), acetic acid It may be one or more substances selected from the group consisting of (Acetic acid), trichloroacetic acid, and 2-Chloropropionic acid.

In the present invention, the sensor array may be fixed by patterning the compounds represented by Chemical Formulas 2 to 76 on a substrate. In the present invention, filter paper is preferably used as the substrate, but the present invention is not limited thereto, and a material capable of fixing the fluorescent material may be used without limitation.

In a specific embodiment of the present invention, an array frame was manufactured using wax printing on a filter paper for uniform application of fluorescent materials, and 75 GxF materials were spotted on an array coated with wax. . As shown in FIG. 11, a sensor array containing 25 new phosphors per fluorescent sensor array having a size of 2.5 cm X 2.5 cm was prepared, and the degree of luminescence of the fluorescent material was observed under UV.

In another aspect, the present invention relates to a method for detecting a volatile organic compound using the fluorescent compound.

In the present invention, the method comprises the steps of: (a) exposing a volatile material to a sensor array for detecting a volatile organic compound to which a fluorescent compound is immobilized, and then measuring a change in a fluorescence pattern; And

(b) learning the pattern change through a machine learning algorithm.

In the present invention, step (b) is characterized in that the RGB distance, hue value, and CIEDE2000 information of the pattern are learned through a machine learning algorithm.

In one specific embodiment of the present invention, in order to check whether the fluorescent sensor array can react with VOC to form a specific fluorescent pattern, three fluorescent sensor arrays each coated with 75 kinds of GxF materials are illustrated. It was intended to be exposed to VOC by introducing it into a closed container such as 12

In addition, for a study on the pattern formation of a fluorescent array, it was necessary to optimize a system that can see changes in color and brightness according to VOC exposure of the exposed sensor array. A system capable of implementing an ideal light composition was devised by adjusting the location of the light source and the location of the smartphone camera, which is shown in FIG. 13. A machine learning algorithm capable of automatically analyzing the color change information of the fluorescence sensor array obtained through this was developed, and change information in the color space of RGB, HSV, and CIELAB was analyzed as shown in FIG. 14.

As a result of monitoring each change of the fluorescent sensors after 5 repeated exposures to 35 different VOC materials, as shown in FIG. 16, the indolizine-based fluorescent sensor array reacts to 35 types of VOCs to determine each change pattern. I confirmed that it shows.

In particular, in the case of these change patterns, it was confirmed that each VOC can be classified through principle component analysis, and PCA (Principle Component Analysis) analysis was performed using the Hue value (color information value) before/after exposure. As a result, it was confirmed that it was identified as carboxylic acid (Carboxylic acid, 58.1%), alcohol (Alcohol, 57.6%), aliphatic amine (Aliphatic amine, 61.9%) and aromatic amine (Aromatic amine, 53.4%) (FIG. 17).

Based on the above results, RGB, Hue value, and CIEDE2000 (difference between color brightness and color) among the pattern change information of the fluorescence sensor array are used in a machine learning algorithm ( machine learning algorithm) and confirmed the degree of VOC discrimination. As a result, as shown in FIG. 18, it was confirmed that the learned algorithm can accurately predict VOC through analysis of changes in the fluorescence sensor image pattern with a high accuracy of 97%.

That is, in the present invention, it was confirmed that the new fluorescent central skeleton based on indolizine can produce fluorescent materials that can cover the entire visible light region, and in particular, the novel indolizine fluorescent material can exhibit a fluorescence phenomenon in the solid phase. And it was confirmed that changes in fluorescence properties may occur in response to the surrounding environment.

In addition, a fluorescence sensor array for VOC detection was constructed by utilizing the characteristics of a novel fluorescent material, and the constructed sensor array not only forms a specific fluorescence pattern in response to a specific VOC. As a result of learning the pattern formed in this way into a machine learning algorithm using image analysis technology and machine learning algorithm, it was confirmed that VOC can be detected with high accuracy.

Hereinafter, the present invention will be described in more detail through examples.

These examples are for illustrative purposes only, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not construed as being limited by these examples.

Synthesis of new fluorescent materials based on indolizine

In the present invention, a novel fluorescent material based on an indolizine skeleton was synthesized to monitor volatile organic compounds in real time.

Specifically, a novel fluorescent material, Galaxy Fluor (GxF), was synthesized by the method shown in Scheme 1 and FIG. 3, and the fluorescent compounds of Formula 1 were each combined to have the following substituents, resulting in a final 75 kinds of new GxFs. The material was synthesized:

R _1: hydrogen (-H), trifluoromethyl group (Trifluoromethyl; -CF _3), acetyl group (-COCH _3), a methoxy group (-OCH _3), dimethyl amine is (Dimethylamine; DMA; -N (CH ₃ ) ₂ )

R ₂ : methyl (-CH ₃ ), trifluoromethylphenyl group (Trifluoromethylphenyl; -CF ₃ Ph), phenyl group (-Ph), methoxyphenyl group (OCH ₃ Ph), diethylaminephenyl group (Diethylaminephenyl; -N(C ₂ H ₅ ) ₂ Ph)

R ₃ : hydrogen (-H), trifluoromethyl (-CF ₃ ), acetyl group (-COCH ₃ ).

^{The 1} H and ¹³ C NMR spectra were recorded using JEOL ECZ-600R (JEOL Ltd, Japan), and the chemical shift measured the downfield range of ppm of the internal tetramethylsilane standard.

The multiplicity was expressed as follows: s (singlet); d(doublet); t(triplet); q(quartet); m (multiplet); dd (doublet of doublet); ddd (doublet of doublet of doublet); dt (doublet of triplet); td (triplet of doublet); brs (broad singlet).

Coupling constants were reported in Hz. Routine mass analyses are an LC/MS system equipped with a reversed-phase column (C-18, 50 Х 2.1 mm, 5 μm) and a photodiode analysis detector using electron spray ionization (ESI) or atmospheric pressure chemical ionization (APCI). Performed on.

The molecular weight analysis of the compound was confirmed by high-resolution mass spectrometry (LRMS). LRMS analysis was performed using LCMS-2020 (Shimadzu, Japan).

The synthesized 75 kinds of GxF materials are shown in FIGS. 4 to 6, and the synthesis method of each of the materials is as follows:

<GxF 1 ~ 5>

IA-E : Synthesized as in Scheme 2 below, specifically, 4 (trifluoromethyl) pyridine (4- (trifluoromethyl) pyridine, 637 μL, 5.50 mmol) and 2-bromo-1-[4- (4 (trifluoro Dimethylformamide (dimethylformamide; DMF, containing romethyl)-phenyl]ethane-1-one (2-bromo-1-[4-(trifluoromethyl)-phenyl]ethane-1-one, 1.54 g, 5.70 mmol) 10.0 mL) was stirred at 100° C. overnight, and then ethyl acrylate (293 μL, 2.75 mmol), copper (II) acetate monohydrate, 1.64 g, 8.25 mmol) and sodium Acetate (sodium acetate, 1.35 g, 16.5 mmol) was added and stirred for 16 hours at 100° C. After completion of the reaction, it was monitored by TLC, and then copper acetate was removed by filtration through a pad of Celite. , The resulting filtrate was concentrated in vacuo The resulting crude product was washed with water and the organic material was extracted 3 times with DCM The extracted organic material was combined, dried over anhydrous Na ₂ SO _{4 and} then concentrated. The organic phase was purified by silica-gel flash column chromatography (1-15% hexane containing EtOAc) to obtain a yellow solid compound IA-E (518 mg, 1.20 mmol, 43.8% yield). I did.

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.0 (d, J = 7.2 Hz, 1H), 8.70 (s, 1H), 7.91 (d, J = 7.6 Hz 2H), 7.82 (s, 1H), 7.79 ( d, J = 8.0 Hz, 2H), 7.23 (d, J = 7.2 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.2 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 184.0, 162.8, 141.9, 137.7, 133.3, 132.6, 129.3, 128.9, 125.3, 124.7, 124.0, 122.6, 122.0, 121.2, 117.1, 110.9, 108.9, 60.6, 14.4.

IA-B : KOH (5386 mg, 96.00 mmol) was added to methanol (10 mL) containing IA-E (517.9 mg, 1.206 mmol), followed by stirring at room temperature overnight. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a brown solid compound IA-A.

The obtained compound IA-A was used in the next step without further purification, sodium bicarbonate (302.4 mg, 3.600 mmol) was added to DMF (10.0 mL) containing IA-A, and NBS (320.3 mg) , 1.800 mmol) was added in portions at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IA-B (434.1 mg, 0.99 mmol, 82.9% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 95.5 (d, J = 7.2 Hz, 1H), 7.90 (s, 2H), 7.87 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.40 (s, 1H), 7.13 (d, J = 7.2 Hz, 1H); ¹³ C NMR (100 MHz, NNN) δ 183.1, 142.4, 135.0, 133.1, 129.2, 127.6, 126.6, 125.6, 125.5, 124.4, 123.0, 121.7, 115.4, 110.4, 93.0; LRMS (ESI) m/z calcd for C ₁₇ H ₈ BrF ₆ NO [M+Na] ⁺ : 435.0, found: 436.3.

[Scheme 2]

Compound GxF 1 :

4-triflulorophenyl boronic acid, 88.0 mg, 0.46 mmol), tetrakis in a solution containing IA-B (50.4 mg, 0.11 mmol) and a mixture of DMF and water 2: 1 After (triphenyl phosphine) palladium (Tetrakis (triphenyl phosphine) palladium, 231 mg, 20.0 mol%) and sodium carbonate (Sodium carbonate, 49.0 mg, 0.46 mmol) were added, the mixture was stirred at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 1 (50.0 mg, 0.09 mmol, 86.7) represented by the following formula 1-1. % Yield) was obtained.

[Formula 1-1]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.6 (d, J = 7.6 Hz, 1H), 8.11 (s, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.8 Hz , 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.66 (s, 1H), 7.64 (s, 1H), 7.52 (s, 1H), 7.18 (d, J = 7.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.9, 142.9, 137.1, 134.4, 133.4, 133.1, 129.5, 129.2, 128.3, 127.3, 127.0, 126.2, 126.0, 125.6, 125.1, 124.5, 123.2, 122.8, 122.4, 121.8 , 119.2, 115.3, 110.4; LRMS (ESI) m/z calcd for C ₂₄ H ₁₂ F ₉ NO [M+Na] ⁺ : 501.1, found: 502.1.

Compound GxF 2 :

4-acetylphenyl boronic acid (4-acetylphenyl boronic acid, 75.0 mg, 0.46 mmol), tetrakis (tri Phenyl phosphine) palladium (231 mg, 20.0 mol%) and sodium carbonate (49.0 mg, 0.46 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 2 (48.4 mg, 0.10 mmol, 88.5) represented by the following Formula 1-2. % Yield) was obtained.

[Formula 1-2]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.0 (d, J = 7.6 Hz, 1H), 8.15 (s, 1H), 8.07 (d, J = 6.8 Hz, 2H), 7.95 (d, J = 8.4 Hz , 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 6.8 Hz, 2H), 7.54 (s, 1H), 7.18 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.2, 183.9, 142.9, 138.2, 135.8, 134.4, 133.0, 129.5, 129.3, 129.2, 128.0, 127.3, 126.9, 125.9, 125.6, 124.5, 123.3, 122.4, 121.8, 119.4 , 115.5, 115.4, 110.4, 26.9; LRMS (ESI) m/z calcd for C ₂₅ H ₁₅ F ₆ NO ₂ [M+Na] ⁺ : 475.1, found: 476.2.

Compound GxF 3 :

Phenyl boronic acid (57.0 mg, 0.46 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IA-B (51.2 mg, 0.11 mmol) and a mixture of DMF and water 2: 1 (231 mg, 20.0 mol%) and sodium carbonate (49.0 mg, 0.46 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 3 (48.7 mg, 0.11 mmol, 96.0) represented by the following Chemical Formula 1-3 (48.7 mg, 0.11 mmol, 96.0). % Yield) was obtained.

[Formula 1-3]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.04 (d, J = 8.4 Hz, 1H), 8.14 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz , 2H), 7.55 (s, 1H), 7.53 (d, J = 3.6 Hz, 2H), 7.49 (d, J = 3.2 Hz, 2H), 7.39 (d, J = 7.2 Hz, 1H) 7.13 (dd, J = 7.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.7, 143.1, 134.4, 133.3, 133.2, 132.9, 129.3, 129.2, 128.1, 127.5, 126.6, 125.8, 125.5, 125.4, 125.1, 124.7, 122.9, 122.0, 120.9, 115.7 , 110.1.

Compound GxF 4 :

In a solution containing IA-B (51.0 mg, 0.11 mmol) and a mixture of DMF and water 2: 1, 4-methoxyphenyl boronic acid (71.0 mg, 0.46 mmol), tetrakis ( After adding triphenyl phosphine) palladium (Tetrakis (triphenyl phosphine) palladium, 231 mg, 20.0 mol%) and sodium carbonate (Sodium carbonate, 49.0 mg, 0.46 mmol), the mixture was stirred at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 4 (51.4 mg, 0.11 mmol, 94.8) represented by the following formula 1-4. % Yield) was obtained.

[Formula 1-4]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.02 (d, J = 6.8 Hz, 1H), 8.08 (s, 1H), 7.94 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 8.0 Hz , 2H), 7.46 (s, 1H), 7.42 (d, J = 5.0 Hz, 2H), 7.10 (d, J = 7.4 Hz, 1H), 7.02 (d, J = 4.6 Hz, 2H), 3.86 (s , 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.5, 159.0, 143.1, 134.4, 133.0, 132.7, 129.2, 127.6, 126.3, 125.9, 125.6, 125.5, 125.4, 125.4, 125.1, 125.6, 122.7, 122.4, 121.9, 120.7 , 115.7, 114.6, 114.1, 109.9; LRMS (ESI) m/z calcd C ₂₄ H ₁₅ F ₆ NO ₂ for [M+Na] ⁺ : 463.1, found: 464.1.

Compound GxF 5 :

4-(dimethylamino)phenyl boronic acid, 78.0 mg, 0.47 in a solution containing IA-B (51.4 mg, 0.11 mmol) and a mixture of DMF and water 2: 1 mmol), tetrakis (triphenyl phosphine) palladium (Tetrakis (triphenyl phosphine) palladium, 231 mg, 20.0 mol%) and sodium carbonate (Sodium carbonate, 50 mg, 0.47 mmol) were added, and then at 100° C. for 12 hours Stirred. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and the orange solid compound GxF 5 (51.5 mg, 0.10 mmol, 91.6) represented by the following formula 1-5 % Yield) was obtained.

[Formula 1-5]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.01 (d, J = 7.6 Hz, 1H), 8.12 (s, 1H), 7.94 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz , 2H), 7.41 (d, J = 5.0 Hz, 2H), 7.40 (s, 1H), 7.09 (d, J = 7.6 Hz, 1H), 6.84 (d, J = 7.6 Hz, 2H), 3.02 (d , J = 6.4 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.4, 149.8, 143.3, 134.3, 132.9, 132.6, 129.2, 129.1, 128.8, 125.9, 125.7, 125.5, 125.1, 124.7, 122.6, 122.4, 122.0, 121.5, 121.4, 121.0 , 116.0, 115.9, 112.9, 109.7, 40.6; LRMS (ESI) m/z calcd for C ₂₅ H ₁₈ F ₆ N ₂ O[M+Na] ⁺ : 476.1, found: 476.2.

<GxF 6 ~ 10>

IB-E : Synthesized as in Scheme 3 below, and specifically, DMF (10.0 mL) containing 4 (trifluoromethyl) pyridine (695 μL, 6.00 mmol) and chloroacetone (chloroacetone, 501 μL, 6.30 mmol) was prepared at 100° C. After stirring overnight at, ethyl acrylate (320 μL, 3 mmol), copper (II) acetate monohydrate (1.79 g, 9.00 mmol) and sodium acetate (1476.5 mg, 18 mmol) were added thereto at 100° C. for 16 hours. While stirring. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IB-E (659.5 mg, 2.2 mmol, 73.4% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.96 (d, J = 7.2 Hz, 1H), 8.66 (t, J = 1.2Hz, 1H), 8.06 (s, 1H), 7.15 (dd, J = 2 Hz, 1H), 4.43 (q, J = 7.2 Hz, 2H), 2.63 (s, 3H), 1.45 (t, J = 7.0 Hz, 3H); ¹³ C NMR (400 MHz, CDCl ₃ ) δ 188.0, 163.1, 136.7, 129.1, 128.3, 128.0, 127.6, 127.3, 126.9, 126.0, 124.2, 123.4, 121.5, 118.8, 116.9, 116.8, 110.5, 110.4, 108.1, 60.6 , 27.5, 14.5; LRMS (ESI) m/z calcd for C ₁₄ H ₁₂ F ₃ NO ₃ [M+Na] ⁺ : 299.1, found: 300.1.

IB-B : KOH (5386 mg, 96.00 mmol) was added to methanol (10 mL) containing IB-E (0.66 g, 2.20 mmol), followed by stirring at room temperature for 4 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a brown solid compound IB-A.

The obtained compound IB-A was used in the next step without further purification, sodium bicarbonate (554 mg, 6.60 mmol) was added to DMF (10.0 mL) containing IB-A, and NBS (587 mg, 3.30 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IB-B (588 mg, 1.92 mmol, 100% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.88 (d, J = 7.2 Hz, 1H), 7.85 (s, 1H), 7.60 (s, 1H), 7.02 (d, J = 7.6 Hz, 1H), 2.59 (s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 204.4, 186.9, 133.6, 128.7, 124.9, 123.5, 121.7, 115.2, 109.7, 92.0, 27.5.

[Scheme 3]

Compound GxF 6 :

4-trifluorophenyl boronic acid (103 mg, 0.97 mmol), tetrakis (triphenyl phosphine) in a solution containing IB-B (74.6 mg, 0.24 mmol) and a mixture of DMF and water 2: 1 ) Palladium (231 mg, 20.0 mol%) and sodium carbonate (49.0 mg, 0.46 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to obtain a yellow solid compound GxF 6 (75.9 mg, 0.2 mmol, 85) represented by the following formula 1-6. % Yield) was obtained.

[Formula 1-6]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.95 (d, J = 8.0 Hz, 1H), 8.03 (s, 1H), 7.75 (d, J = 8.8 Hz, 2H), 7.71 (s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.03 (dd, J = 7.6 Hz, 1H), 2.65 (s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 187.6, 137.4, 133.0, 129.2, 129.0, 128.1, 126.1, 125.7, 125.5, 124.6, 123.8, 123.1, 122.8, 121.9, 118.2, 115.1, 109.7, 27.8; LRMS (ESI) m/z calcd for C ₁₈ H ₁₁ F ₆ NO [M+Na] ⁺ : 371.1, found: 372.1.

Compound GxF 7 :

In a solution containing IB-B (52.4 mg, 0.22 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (144 mg, 0.88 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (93.0 mg, 0.88 mmol) were added, followed by stirring at 100° C. for 17 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound GxF 7 (56.4 mg, 0.16 mmol, 74.2) represented by the following formula 1-7. % Yield) was obtained.

[Formula 1-7]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.91 (d, J = 7.2 Hz, 1H), 8.06 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.0 Hz, 1H), 7.72 (s , 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.01 (d, J = 7.2 Hz, 1H), 2.63 (s, 3H), 2.61 (s , 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.4, 187.9, 144.4, 138.8, 136.7, 135.8, 133.3, 129.5, 128.0, 127.6, 124.9, 124.1, 123.4, 122.1, 118.7, 115.5, 109.9, 28.1, 27.1; LRMS (ESI) m/z calcd for C ₁₉ H ₁₄ F ₃ NO ₂ [M+Na] ⁺ : 345.1, found: 346.1.

Compound GxF 8 :

Phenyl boronic acid (117 mg, 0.96 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, in a solution containing IB-B (73.8 mg, 0.24 mmol) and a mixture of DMF and water 2: 1) 20.0 mol%) and sodium carbonate (102 mg, 0.96 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 8 (79.8 mg, 0.26 mmol, 100) represented by the following formula 1-8. % Yield) was obtained.

[Formula 1-8]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.94 (d, J = 7.6 Hz, 1H), 8.07 (s, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 8.4 Hz , 2H), 7.66 (d, J = 8.0 Hz, 1H), 7.57 (s, 1H), 7.07 (dd, J = 7.2 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H), 3.90 (s , 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.2, 162.6, 137.5, 133.3, 132.1, 131.2, 129.2, 128.1, 126.1, 126.0, 125.8, 125.1, 123.7, 118.2, 113.7, 109.5, 55.6.

Compound GxF 9 :

4-methoxyphenyl boronic acid (133 mg, 0.87 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IB-B (52.1 mg, 0.22 mmol) and a mixture of DMF and water 2:1 (231 mg, 20.0 mol%) and sodium carbonate ((92.7 mg, 0.87 mmol) were added, and then stirred for 8 hours at 100° C. After completion of the reaction, the reaction was monitored by TLC, washed with water, and the organic material was DCM. The extracted organic substances were combined, dried over anhydrous Na ₂ SO ₄ and concentrated, the concentrated organic phase was subjected to silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%). Purified with GxF 9 (547.2 mg, 0.14 mmol, 64% yield) as a yellow solid represented by the following Chemical Formula 1-9.

[Formula 1-9]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.89 (d, J = 7.2 Hz, 1H), 7.99 (s, 1H), 7.60 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 7.2 Hz, 1H), 3.87 (s, 3H), 2.62 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 187.4, 158.8, 132.8, 129.1, 128.8, 126.0, 125.0, 124.8, 124.6, 123.3, 122.7, 122.1, 119.8, 115.5, 114.5, 109.2, 55.5, 27.7; LRMS (ESI) m/z calcd for C ₁₈ H ₁₄ F ₃ NO ₂ [M+Na] ⁺ : 333.11, found: 334.2.

Compound GxF 10 :

In a solution containing IB-B (77.8 mg, 0.25 mmol) and a mixture of DMF and water 2: 1, 4-(dimethylamino) phenyl boronic acid (167 mg, 1.01 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (108 mg, 1.01 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 10 (85.3 mg, 0.25 mmol, 100) represented by the following formula 1-10 (85.3 mg, 0.25 mmol, 100). % Yield) was obtained.

[Formula 1-10]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.88 (d, J = 8.0 Hz, 1H), 8.03 (s, 1H), 7.57 (s, 1H), 7.41 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 7.6 Hz, 1H), 6.83 (d, J = 8.8 Hz, 2H), 3.01 (s, 6H), 2.62 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.9, 149.3, 132.4, 128.3, 124.5, 124.1, 123.8, 122.9, 121.9, 121.8, 121.1, 121.0, 120.1, 115.4, 112.5, 108.6, 40.2, 27.3; LRMS (ESI) m/z calcd for C ₁₉ H ₁₇ F ₃ N ₂ O [M+Na] ⁺ : 346.1, found: 347.2.

<GxF 11 ~ 15>

IC-E : It was synthesized as shown in Scheme 4 below, and specifically, DMF containing 4 (trifluoromethyl) pyridine (348 μL, 3.00 mmol) and 2-bromoacetophenone (627 mg, 3.15 mmol) ( 7.0 mL) was stirred at 100° C. overnight, and then ethyl acrylate (160 μL, 0.50 mmol), copper (II) acetate monohydrate (898 mg, 1.50 mmol) and sodium acetate (738 mg, 9.00 mmol) were added. Then, the mixture was stirred at 100° C. for 16 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IC-E (481.9 mg, 1.3 mmol, 88.9% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.88 (d, J = 7.6 Hz, 1H), 8.59 (s, 1H), 7.78 (s, 1H), 7.74 (d, J = 6.8 Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.44 (d, J = 7.6 Hz, 2H), 7.10 (dd, J = 7.4 Hz, 1H), 4.35 (q, J = 7.1 Hz, 2H), 1.37 (t , J = 7.0 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.3, 163.0, 138.8, 137.2, 131.7, 129.2, 128.8, 128.5, 128.3, 128.2, 128.0, 124.2, 123.2, 121.5, 117.0, 110.4, 108.5, 60.5, 14.5; LRMS (ESI) m/z calcd for C ₁₉ H ₁₄ F ₃ NO [M+Na] ⁺ : 361.1, found: 362.1.

IC-B : After adding KOH (519mg, 10.0 mmol) to methanol (10 mL) containing IC-E (481.9 mg, 1.3 mmol), the mixture was stirred at room temperature for 4 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a white solid compound IC-A.

The obtained compound IC-A was used in the next step without further purification, sodium bicarbonate (162.4 mg, 1.9 mmol) was added to DMF (10.0 mL) containing IC-A, and NBS (172.0 mg, 0.9 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IC-B (219.2 mg, 0.595 mmol, 99.2% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.96 (d, J = 7.6 Hz, 1H), 7.90 (s, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.59 (t, J = 7.4 Hz , 1H), 7.51 (t, J = 7.4 Hz, 1H), 7.46 (s, 1H), 7.09 (d, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.4, 139.1, 134.2, 131.7, 128.9, 128.8, 128.3, 127.4, 126.1, 125.7, 124.4, 123.2, 121.7, 115.1, 109.8, 92.3; LRMS (ESI) m/z calcd for C ₁₆ H ₉ BrF ₃ NO [M+Na] ⁺ : 367.0, found: 368.0.

[Scheme 4]

Compound GxF 11 :

In a solution containing IC-B (51.2 mg, 0.14 mmol) and a mixture of DMF and water 2: 1, 4-trifluorophenyl boronic acid (106 mg, 0.55 mmol), tetrakis (triphenyl phosphine) After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (59.0 mg, 0.55 mmol), the mixture was stirred at 100° C. for 5 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to obtain a yellow solid compound GxF 11 (54.0 mg, 0.12 mmol, 89.0) represented by the following formula 1-11. % Yield) was obtained.

[Formula 1-11]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.05 (d, J = 7.6 Hz, 1H), 8.09 (s, 1H), 7.85 (dd, J = 8.2 Hz, 2H), 7.74 (d, J = 8.0 Hz , 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.60 (t, J = 6.8 Hz, 1H), 7.57 (s, 1H), 7.54 (d, J = 7.6 Hz, 2H), 7.14 (d , J = 7.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.5, 139.8, 137.5, 133.9, 131.8, 129.5, 129.1, 128.6, 128.3, 126.4, 126.2, 126.2, 126.0, 125.8, 123.8, 118.7, 115.3, 110.0, 110.0, 47.1 , 34.7; LRMS (ESI) m/z calcd for C ₂₃ H ₁₃ F ₆ NO [M+Na] ⁺ : 433.1, found: 434.3.

Compound GxF 12 :

In a solution containing IC-B (36.9 mg, 0.1 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (65.6 mg, 0.4 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (42.4 mg, 0.4 mmol) were added, followed by stirring at 100° C. for 6 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 12 (38.1 mg, 0.09 mmol, 93.5) represented by the following formula 1-12. % Yield) was obtained.

[Formula 1-12]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.03 (d, J = 7.2 Hz, 1H), 8.13 (s,1H), 8.06 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz , 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.59 (s, 1H), 7.52 (d, J = 7.4 Hz, 3H), 7.12 (dd, J = 7.2 Hz, 1H), 2.65 (s , 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.5, 185.6, 139.9, 138.8, 135.8, 134.1, 132.0, 129.7, 129.5, 129.3, 128.7, 128.1, 126.8, 126.5, 126.1, 124.9, 123.9, 122.2, 119.1, 115.6 , 115.6, 110.1, 110.2, 27.1; LRMS (ESI) m/z calcd for C ₂₄ H ₁₆ F ₃ NO ₂ [M+Na] ⁺ : 407.1, found: 408.1.

Compound GxF 13 :

In a solution containing IC-B (40.5 mg, 0.11 mmol) and a mixture of DMF and water 2: 1, phenyl boronic acid (53.7 mg, 0.44 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, 20.0 mol%) and sodium carbonate (46.6 mg, 0.44 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 13 (79.8 mg, 0.10 mmol, 94.5) represented by the following formula 1-13. % Yield) was obtained.

[Formula 1-13]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.04 (d, J = 7.2 Hz, 1H), 8.12 (s, 1H), 7.86 (d, J = 7.2 Hz, 2H), 7.58 (d, J = 6.0 Hz , 1H), 7.52 (m, 7H), 7.38 (d, J = 7.6 Hz, 1H), 7.10 (dd, J = 7.6 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.3, 140.0, 133.8, 133.7, 131.5, 129.2, 129.1, 129.1, 128.4, 128.1, 127.3, 126.0, 125.8, 125.7, 123.4, 122.1, 120.4, 115.7, 115.6, 109.6 , 47.0, 34.6; LRMS (ESI) m/z calcd for C ₂₂ H ₁₄ F ₃ NO [M+Na] ⁺ : 365.1, found: 366.1.

Compound GxF 14 :

4-methoxyphenyl boronic acid (79.0 mg, 0.52 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IC-B (47.9 mg, 0.13 mmol) and a mixture of DMF and water 2:1 (231 mg, 20.0 mol%) and sodium carbonate (55.1 mg, 0.52 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 14 (57.6 mg, 0.14 mmol, 100) represented by the following formula 1-14. % Yield) was obtained.

[Formula 1-14]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.02 (d, J = 7.6 Hz, 1H), 8.07 (s, 1H), 7.85 (d, J = 6.8 Hz, 2H), 7.58 (d, J = 7.2 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.48 (s, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.07 (dd, J = 7.2 Hz, 1H), 7.02 ( d, J = 8.8 Hz, 2H), 3.86 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.1, 158.8, 139.9, 133,6, 131.4, 129.2, 129.0(2), 128.3, 125.9, 125.6, 125.5, 125.4, 125.2, 123.1, 120.1, 115.6, 115.5, 114.5, 109.4, 109.3, 55.5; LRMS (ESI) m/z calcd for C ₂₃ H ₁₆ F ₃ NO ₂ [M+Na] ⁺ : 395.1, found: 396.1.

Compound GxF 15 :

In a solution containing IC-B (39.5 mg, 0.10 mmol) and a mixture of DMF and water 2: 1, 4- (dimethylamino) phenyl boronic acid (45.5 mg, 0.43 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (108 mg, 1.01 mmol) were added, followed by stirring at 100° C. for 19 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 15 (43.5 mg, 0.10 mmol, 99.7) represented by the following formula 1-15. % Yield) was obtained.

[Formula 1-15]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 10.02 (d, J = 7.2 Hz, 1H), 8.11 (s, 1H), 7.87 (d, J = 7.2 Hz, 2H), 7.57 (d, J = 7.2 Hz , 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.48 (s, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.05 (dd, J = 7.4 Hz, 1H), 6.87 (d , J = 8.0 Hz, 2H), 3.02 (s, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 185.2, 166.7, 149.8, 140.3, 133.8, 131.5, 129.2, 129.0, 128.4, 127.3, 125.8, 125.4, 125.1, 125.0, 123.2, 122.3, 121.0, 116.1, 116.0, 113.2 , 109.4, 47.1, 41.0, 34.7; LRMS (ESI) m/z calcd for C ₂₄ H ₁₉ F ₃ N ₂ O [M+Na] ⁺ : 408.1, found: 409.2.

<GxF 16 ~ 20>

ID-E : Synthesized as in Scheme 5 below, specifically, 4 (trifluoromethyl) pyridine (695 μL, 6.00 mmol) and 2-bromo-4-methoxyacetophenone (2-bromo-4-methoxyacetophenone, 1.44 g) , 6.30 mmol) containing DMF (10.0 mL) was stirred at 100° C. overnight, followed by ethyl acrylate (320 μL, 3.00 mmol), copper (II) acetate monohydrate (1.79 g, 9.00 mmol) and sodium acetate. (1.47 g, 18.0 mmol) was added and stirred at 100° C. for 16 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound ID-E (1.02 g, 2.63 mmol, 87.6% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.93 (d, J = 7.2 Hz, 1H), 8.69 (s, 1H), 7.89 (s, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 7.4 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 4.41 (d, J = 7.2 Hz, 2H), 3.92 (s, 3H), 1.42 (d, J = 6.6 Hz , 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.1, 163.2, 162.7, 137.0, 131.3, 131.1, 129.2, 127.9, 127.8, 127.6, 124.3, 123.3, 121.6, 121.3, 116.9, 113.6, 110.1, 108.2, 60.5, 55.4 , 14.5; LRMS (ESI) m/z calcd for C ₂₀ H ₁₆ F ₃ NO ₄ [M+Na] ⁺ : 391.1, found: 392.2.

ID-B : After adding KOH (5.91 g, 105 mmol) to methanol (18 mL) containing ID-E (1.02 g, 2.62 mmol), the mixture was stirred at room temperature for 4 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water, and dried in a drying oven to obtain a white solid compound ID-A.

The obtained compound ID-A was used in the next step without further purification, sodium bicarbonate (660 mg, 7.86 mmol) was added to DMF (10.0 mL) containing ID-A, and NBS (699 mg, 3.93 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound ID-B (0.93 g, 2.36 mmol, 90.0% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.88 (d, J = 8.0 Hz, 1H), 7.88 (s, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.46 (s, 1H), 7.05 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.3, 162.5, 133.8, 131.5, 131.1, 128.8, 126.7, 125.6, 125.3. 124.4, 123.3, 121.7, 121.3, 115.1, 109.4, 62.0, 55.5.

[Scheme 5]

Compound GxF 16 :

In a solution containing ID-B (1.05 g, 0.26 mmol) and a mixture of DMF and water 2: 1, 4-trifluorophenyl boronic acid (202 mg, 1.06 mmol), tetrakis (triphenyl phosphine) After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (112 mg, 1.06 mmol), the mixture was stirred at 100° C. for 5 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 16 (90.2 mg, 0.19 mmol, 73.4) represented by the following formula 1-16. % Yield) was obtained.

[Formula 1-16]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.91 (d, J = 7.2 Hz, 1H), 8.05 (s, 1H), 7.65 (s, 1H), 7.51 (m, 6H), 7.37 (t, J = 7.2 Hz, 1H), 2.63 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 187.4, 133.6, 132.8, 129.0, 128.8, 127.9, 127.1, 125.2, 124.9, 124.7, 123.4, 122.9, 122.0, 119.9, 115.4, 115.4, 109.3, 109.2, 27.7.

Compound GxF 17 :

In a solution containing ID-B (94.3 mg, 0.23 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (155 mg, 0.94 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (100 mg, 0.94 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 17 (118 mg, 0.27 mmol, 100) represented by the following formula 1-17. % Yield) was obtained.

[Formula 1-17]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.96 (d, J = 7.6 Hz, 1H), 8.12 (s, 1H), 8.07 (t, J = 8.2 Hz, 3H), 7.88 (d, J = 9.2 Hz , 2H), 7.72 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.60 (s, 1H), 7.09 (dd, J = 7.4 Hz, 1H), 7.03 (d , J = 8.8 Hz, 1H), 3.91 (s, 3H), 2.66 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.0, 183.8, 162.4, 143.8, 138.4, 136.2, 135.2, 133.0, 131.8, 131.1, 129.0, 128.7, 127.5, 127.1, 125.4, 124.9, 124.5, 123.6, 121.8, 118.3 , 115.1, 113.5, 109.2, 55.4, 26.6; LRMS (ESI) m/z calcd for C ₂₅ H ₁₈ F ₃ NO ₃ [M+Na] ⁺ : 437.1, found: 438.2.

Compound GxF 18 :

In a solution containing ID-B (94.0 mg, 0.23 mmol) and a mixture of DMF and water 2: 1, phenyl boronic acid (115 mg, 0.94 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, 20.0 mol%) and sodium carbonate (100 mg, 0.94 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 18 (97.6 mg, 0.24 mmol, 100) represented by the following formula 1-18. % Yield) was obtained.

[Formula 1-18]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.95 (d, J = 7.6 Hz, 1H), 8.11 (s,1H), 7.88 (d, J = 8.8 Hz, 2H), 7.56 (m, 3H), 7.49 (t, J = 7.8 Hz, 2H), 7.38 (q, J = 7.6 Hz, 1H), 7.06 (dd, J = 7.8 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H), 3.91 (s , 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.5, 162.7, 134.1, 133.6, 132.7, 131.6, 129.4, 129.3, 128.4, 127.5, 125.8, 125.5, 125.4, 125.1, 123.7, 122.4, 120.3, 115.9, 115.8, 114.0 , 109.6, 109.5, 55.9; LRMS (ESI) m/z calcd for C ₂₃ H ₁₆ F ₃ NO ₂ [M+Na] ⁺ : 395.1, found: 396.1.

Compound GxF 19 :

4-methoxyphenyl boronic acid (182 mg, 1.20 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing ID-B (120 mg, 0.30 mmol) and a mixture of DMF and water 2: 1 (231 mg, 20.0 mol%) and sodium carbonate (127 mg, 1.20 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 19 (125.6 mg, 0.29 mmol, 98.4) represented by the following Formula 1-19 (125.6 mg, 0.29 mmol, 98.4). % Yield) was obtained.

[Formula 1-19]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.93 (d, J = 7.6 Hz, 1H), 8.05 (s, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.49 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 6.4 Hz, 3H), 7.01 (d, J = 6.4 Hz, 2H), 3.90 (s, 3H), 3.87 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.8, 162.2, 158.7, 133.0, 132.2, 131.1, 129.0, 128.8, 126.0, 124.9, 124.8, 124.7, 124.6, 123.1, 122.1, 119.7, 115.4, 115.4, 114.4, 113.5 , 108.8, 108.9, 55.4, 55.3; LRMS (ESI) m/z calcd for C ₂₄ H ₁₈ F ₃ NO ₃ [M+Na] ⁺ : 425.1, found: 426.2.

Compound GxF 20 :

In a solution containing ID-B (1.32 mg, 0.33 mmol) and a mixture of DMF and water 2: 1, 4- (dimethylamino) phenyl boronic acid (220 mg, 1.33 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (141 mg, 1.33 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 20 (151 mg, 0.34 mmol, 100) represented by the following formula 1-20. % Yield) was obtained.

[Formula 1-20]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.92 (d, J = 7.6 Hz, 1H), 8.08 (s,1H), 7.87 (d, J = 7.6 Hz, 2H), 7.48 (s, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 3H), 6.85 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H), 3.01 (s, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.8, 162.1, 149.5, 133.0, 132.4, 131.1, 128.7, 128.6, 127.5, 124.8, 124.5, 124.4, 124.2, 123.8, 123.0, 122.1, 121.4, 120.5, 119.4, 115.7 , 113.4, 112.7, 108.7, 55.4, 40.5; LRMS (ESI) m/z calcd for C ₂₅ H ₂₁ F ₃ N ₂ O ₂ [M+Na] ⁺ : 438.2, found: 439.2.

<GxF 21 ~ 25>

IE-E : Synthesized as in Scheme 6 below, specifically, 4 (trifluoromethyl) pyridine (695 μL, 6.00 mmol) and 2-bromo-4'- (diethylamino) acetophenone (2-Bromo-4' DMF (6.0 mL) containing -(diethylamino)aceto-phenone, 1.70 mL, 6.30 mmol) was stirred overnight at 100°C, and then ethylacrylate (320 μL, 3.00 mmol), copper (II) acetate monohydrate (1.79 g, 9.00 mmol) and sodium acetate (1.47 g, 18.0 mmol) were added, followed by stirring at 100°C for 16 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IE-E (1.12 g, 2.60 mmol, 86.9% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.83 (d, J = 8.0 Hz, 1H), 8.66 (s, 1H), 7.91 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 7.4 Hz, 1H), 6.72 (d, J = 5.4 Hz, 2H), 4.41 (q, J = 6.9, 2H), 3.46 (q, J = 6.6 Hz, 4H), 1.43 (t, J = 5.2, 3H), 1.25 (d, J = 5.5 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 182.8, 163.1, 150.4, 136.1, 131.4, 128.9, 126.7, 126.4, 126.1, 124.6, 124.3, 123.6, 121.6, 116.5(2), 109.8, 109.1, 109.2, 107.4, 60.0, 44.2, 14.3, 12.3; LRMS (ESI) m/z calcd for C ₂₃ H ₂₃ F ₃ N ₂ O ₃ [M+Na] ⁺ : 432.2, found: 433.2.

IE-B : After adding KOH (5.85 g, 104 mmol) to methanol (10 mL) containing IE-E (1.12 g, 2.60 mmol), the mixture was stirred at room temperature for 4 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water, and dried in a drying oven to obtain a white solid compound IE-A.

The obtained compound IE-A was used in the next step without further purification, sodium bicarbonate (655 mg, 7.80 mmol) was added to DMF (10.0 mL) containing IE-A, and NBS (694 mg, 3.90 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IE-B (829 mg, 1.88 mmol, 72.6% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.83 (d, J = 8.0 Hz, 1H), 8.66 (s, 1H), 7.91 (s, 1H), 7.84 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 7.4 Hz, 1H), 6.72 (d, J = 5.4 Hz, 2H), 4.41 (q, J = 6.9, 2H), 3.46 (q, J = 6.6 Hz, 4H), 1.43 (t , J = 5.2, 3H), 1.25 (d, J = 5.5 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 182.0, 152.9, 135.2, 134.2, 133.9, 129.0, 128.8, 126.9, 126.0, 125.7, 124.6, 123.2, 122.3, 121.9, 120.1, 115.3, 92.5, 46.5, 12.8, 12.7 .

[Scheme 6]

Compound GxF 21 :

4-trifluorophenyl boronic acid (94.4 mg, 0.49 mmol), tetrakis (triphenyl phosphine) in a solution containing IE-B (54.0 mg, 0.12 mmol) and a 2:1 mixture of DMF and water After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (52.7 mg, 0.49 mmol), the mixture was stirred at 100° C. for 5 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 21 (43.1 mg, 0.08 mmol, 68.8) represented by the following formula 1-21 % Yield) was obtained.

[Formula 1-21]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.95 (d, J = 7.6 Hz, 1H), 8.07 (s, 1H), 7.83 (dd, J = 8.6 Hz, 1H), 7.76 (s, 1H), 7.74 (d, J = 5.6 Hz, 1H), 7.67 (m, 5H), 7.64 (s, 1H), 7.15 (d, J = 8.4 Hz, 1H), 7.09 (dd, J = 6.6 Hz, 1H), 3.00 (q, J = 6.9 Hz, 4H), 0.98 (t, J = 7.0 Hz, 6H); ¹³ C NMR δ 184.3, 152.6, 145.1, 137.7, 133.6, 133.5, 133.2, 132.5, 130.1, 129.4, 129.3, 129.0(2), 128.3, 126.3, 126.2(2), 125.7, 125.6, 125.5, 125.1, 124.0, 120.0, 118.4, 46.0, 12.4; LRMS (ESI) m/z calcd for C ₂₇ H ₂₂ F ₆ N ₂ O[M+Na] ⁺ : 504.2, found 505.2.

Compound GxF 22 :

In a solution containing IE-B (49.7 mg, 0.11 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (74.2 mg, 0.45 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (48.0 mg, 0.45 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%), and a yellow solid compound GxF 22 (9.70 mg, 0.02 mmol, 18) represented by the following formula 1-22 % Yield) was obtained.

[Formula 1-22]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.95 (d, J = 7.6 Hz, 1H), 8.12 (s, 1H), 8.08 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 2.0 Hz, 1H), 7.30 (m, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.63 (s, 1H), 7.00 (m, 2H), 3.29 (q, J = 7.0 Hz, 4H), 2.66 (s, 3H), 1.14 (t, J = 7.2 Hz, 6H); ¹³ C NMR δ 197.2, 183.1, 151.4, 138.6, 135.6, 133.6, 133.3, 132.1, 129.2, 128.7, 128.2, 127.9, 125.2, 121.5, 118.8, 46.1, 29.9, 26.9, 12.7; LRMS (ESI) m/z calcd for C ₂₈ H ₂₅ F ₃ N ₂ O ₂ [M+Na] ⁺ : 478.2, found 479.3.

Compound GxF 23 :

In a solution containing IE-B (50.0 mg, 0.11 mmol) and a mixture of DMF and water 2: 1, phenyl boronic acid (55.0 mg, 0.45 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, 20.0 mol%) and sodium carbonate (49.0 mg, 0.45 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 23 (39.9 mg, 0.09 mmol, 80.1) represented by the following formula 1-23 % Yield) was obtained.

[Formula 1-23]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.96 (d, J = 7.2 Hz, 1H), 8.11 (s,1H), 7.81 (s, 1H), 7.66 (s, 1H), 7.59 (t, J = 7.6 Hz, 3H), 7.50 (t, J = 6.8 Hz, 1H), 7.40 (m, 2H), 7.32 (d, J = 6.6 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 7.2 Hz, 1H), 3.03 (q, J = 6.5 Hz, 4H), 1.01 (t, J = 6.6 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.7, 152.6, 141.7, 135.1, 134.2, 133.6, 133.5, 132.5, 129.7, 129.4, 129.3, 128.8, 128.7, 128.4, 127.4, 127.1, 125.3, 125.2, 124.0, 120.2 , 119.8, 115.9, 109.4, 46.1, 12.6; LRMS (ESI) m/z calcd for C ₂₆ H ₂₃ F ₃ N ₂ O[M+Na] ⁺ : 436.2, found 437.2.

Compound GxF 24 :

4-methoxyphenyl boronic acid (74.0 mg, 0.48 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IE-B (53.7 mg, 0.12 mmol) and a mixture of DMF and water 2:1 (231 mg, 20.0 mol%) and sodium carbonate (52.0 mg, 0.48 mmol) were added, followed by stirring at 100° C. for 10 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 24 (44.8 mg, 0.09 mmol, 78.7) represented by the following Formula 1-24. % Yield) was obtained.

[Formula 1-24]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.84 (d, J = 7.6 Hz, 1H), 8.02 (s, 1H), 7.86 (d, J = 9.2 Hz, 2H), 7.54 (s, 1H), 7.48 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.96 (dd, J = 7.6 Hz, 1H), 6.71 (d, J = 9.2 Hz, 2H), 3.87 ( s, 3H), 3.45 (q, J = 6.9 Hz, 4H), 1.23 (t, J = 7.2 Hz, 6H).; ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.0, 152.0, 141.0, 134.4, 133.6, 133.0, 132.8, 131.9, 129.0, 128.7, 128.2, 128.1, 127.8, 126.8, 126.5, 124.9, 124.7, 124.5, 123.3, 121.8 , 119.6, 119.1, 115.2, 108.8, 45.4, 29.6, 12.0.

Compound GxF 25 :

In a solution containing IE-B (57.5 mg, 0.13 mmol) and a mixture of DMF and water 2: 1, 4- (dimethylamino) phenyl boronic acid (88.0 mg, 0.52 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (55.5 mg, 0.52 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 25 (43.1 mg, 0.08 mmol, 72.4) represented by the following formula 1-25. % Yield) was obtained.

[Formula 1-25]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.95 (d, J = 7.2 Hz, 1H), 8.10 (s, 1H), 7.81 (d, J = 2.4 Hz, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.61 (s, 1H), 7.52 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 8.8 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 7.00 ( dd, J = 7.4 Hz, 1H), 6.87 (d, J = 8.8 Hz, 1H), 6.79 (d, J = 8.8 Hz, 1H), 3.07 (q, J = 7.1 Hz, 4H), 3.03 (s, 3H), 3.00 (s, 3H), 1.01 (d, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.2, 151.8, 149.3, 149.0, 134.6, 132.7, 132.2, 129.0, 128.8, 128.6, 128.5, 128.1, 124.6, 124.2, 124.1, 123.8, 123.2, 121.9, 121.5, 120.1 , 119.2, 115.5, 112.6, 112.1, 108.4, 45.1, 40.4, 11.9; LRMS (ESI) m/z calcd for C ₂₈ H ₂₈ F ₃ N ₃ O [M+Na] ⁺ : 479.2, found 480.4.

<GxF 26 ~ 30>

IF-E : Synthesized as in Scheme 7 below, specifically, 4-acetylpyridine (4-Acetylpyridine, 394.6 μL, 3.567 mmol) and 2-bromo-4'-(trifluoromethyl)acetophenone (2-Bromo-4 DMF (12.0 mL) containing'-(trifluoromethyl)acetophenone, 1.0 g, 3.8 mmol) was stirred at 80°C for 4 hours, and then ethyl acrylate (193.6 μl, 1.79 mmol), copper (II) acetate monohydrate (2.14 g, 10.7 mmol) and sodium acetate (1.17 g, 14.3 mmol) were added, followed by stirring at 100° C. for 16 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IF-E (556.5 mg, 77.3% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.87 (dd, J = 7.2, 1.2 Hz, 1H), 8.96 (s, 1H), 7.92 (d, J = 8.0 Hz, 2H), 7.79 (m, 3H ), 7.61 (dd, J = 7.4, 2.4 Hz, 1H), 4.40 (q, J = 7.2 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) 195.6, 184.4, 163.5, 142.5, 138.8, 134.8,133.7, 133.3, 129.4, 129.1, 128.9, 125.8, 125.7 (2), 125.2, 123.4, 122.5, 121.6, 121.1, 113.1 , 109.9 60.9, 26.6, 14.9; LRMS (ESI) m/z calcd for C ₂₁ H ₁₆ F ₃ NO ₄ [M+Na] ⁺ : 403.1, found: 404.2.

IF-B : KOH (2.21 g, 55.2 mmol) was added to methanol (5 mL) containing IF-E (556.5 mg, 1.379 mmol), followed by stirring at room temperature overnight. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a brown solid compound IF-A.

The obtained compound IF-A was used in the next step without further purification, sodium bicarbonate (350.3 mg, 4.170 mmol) was added to DMF (10.0 mL) containing IF-A, and NBS (259.6 mg, 1.459 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IF-B (358.6 mg, 63.4% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.87 (d, J = 7.4 Hz, 1H), 8.18 (s, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.53 (dd, J = 7.4, 2 Hz, 1H), 7.39 (s, 1H), 2.72 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) 195.2, 183.3, 142.7, 135.8, 133.5, 133.2, 132.8, 129.3, 128.5, 127.6, 125.7(2), 125.2, 123.5, 122.5, 119.2, 112.5, 94.5, 26.7; LRMS (ESI) m/z calcd for C ₁₈ H ₁₁ BrF ₃ NO ₂ [M+Na] ⁺ : 409.0, found: 410.0.

[Scheme 7]

Compound GxF 26 :

4-trifluorophenyl boronic acid (35.9 mg, 0.189 mmol), tetrakis (triphenyl phosphine) in a solution containing IF-B (30.0 mg, 0.063 mmol) and a 10:1 mixture of DMF and water After adding palladium (15.0 mg, 0.013 mmol) and sodium carbonate (33.6 mg, 0.315 mmol), the mixture was stirred at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 26 (28.6 mg, 95.4% yield) represented by the following formula 1-26 Was obtained.

[Formula 1-26]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.97 (d, J = 7.4 Hz, 1H), 8.42 (s, 1H), 7.95 (d, J = 8 Hz, 2H), 7.78 (dd, J = 19 Hz, 4H), 7.95 (d, J = 8 Hz, 2H), 7.55 (dd, J = 7.2 Hz, 1H), 7.49 (s, 1H), 2.67 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.3, 184.0,143.1,137.4, 135.3, 133.5, 133.1, 129.7, 129.4, 129.3, 128.7, 128.5, 126.3, 126.3, 125.8, 125.7, 125.7, 125.2, 123.7, 122.9, 122.5, 120.5, 119.1, 112.6, 26.8; LRMS (ESI) m/z calcd for C ₂₅ H ₁₅ F ₆ NO ₂ [M+Na] ⁺ : 375.1, found: 376.1.

Compound GxF 27 :

In a solution containing IF-B (30.0 mg, 0.063 mmol) and a mixture of DMF and water 10:1, 4-acetylphenyl boronic acid (31.0 mg, 0.189 mmol), tetrakis (triphenyl phosphine) palladium ( 15.0 mg, 0.013 mmol) and sodium carbonate (33.6 mg, 0.315 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 27 (27.3 mg, 96.3% yield) represented by the following formula 1-27 Was obtained.

[Formula 1-27]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.97 (d, J = 7.2 Hz, 1H), 8.46 (s, 1H), 8.08 (d, J = 8.4 Hz, 2H), 7.96 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 6.6 Hz, 2H), 7.55 (dd, J = 7.4 Hz, 2 Hz, 1H), 7.51 (s, 1H), 6.90 (d, J = 8.4 Hz, 1H), 2.68 (s, 3H), 2.66 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 197.4, 195.4, 185.5, 140.0, 138.9, 135.7, 134.8, 132.6, 131.8, 129.4,129.2, 128.6, 128.1, 125.8, 124.3, 120.4,119.3, 112.2, 27.0, 26.7.; LRMS (ESI) m/z calcd for C ₂₆ H ₁₈ F ₃ NO ₃ [M+Na] ⁺ : 449.1, found: 450.0.

Compound GxF 28 :

In a solution containing IF-B (30.0 mg, 0.063 mmol) and a mixture of DMF and water 10:1, 4-acetylphenyl boronic acid (23.0 mg, 0.189 mmol), tetrakis (triphenyl phosphine) palladium ( 15.0 mg, 0.013 mmol) and sodium carbonate (33.6 mg, 0.315 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 28 (23.6 mg, 91.9% yield) represented by Formula 1-28 below. Was obtained.

[Formula 1-28]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃₎ , δ 9.94 (d, J = 8 Hz, 1H), 8.41 (s, 1H), 7.86 (d, J = 6.8 Hz, 2H), 7.72 (dd, J = 23 Hz, 8 Hz, 4H), 7.62 (t, J = 5.2, 2 Hz, 1H), 7.54 (m, 4H), 2.67 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), 195.4, 185.5, 140.0, 137.8, 134.7, 132.6, 131.8, 129.5, 129.2, 128.6, 128.4, 126.3, 126.2, 125.8, 124.2, 120.1, 119.1, 112.2, 26.7; LRMS (ESI) LRMS (ESI) m/z calcd for C ₂₄ H ₁₆ F ₃ NO ₂ [M+Na] ⁺ : 407.1, found: 408.2.

Compound GxF 29 :

4-methoxyphenyl boronic acid (28.7 mg, 0.189 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IF-B (30.0 mg, 0.063 mmol) and a 10:1 mixture of DMF and water (15.0 mg, 0.013 mmol) and sodium carbonate (33.6 mg, 0.315 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 29 (25.4 mg, 92.2% yield) represented by the following formula 1-29. Was obtained.

[Formula 1-29]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃₎ , δ 9.92 (d, J = 7.4 Hz, 1H), 8.39 (s, 1H), 7.94 (d, J = 8 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.49 (m, 3H), 7.38 (s, 1H), 7.04 (d, J = 8.8 Hz, 1H), 3.88 (s, 3H), 2.66 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.5, 183.7, 159.2, 143.4, 135.2, 133.2, 132.9, 132.4, 129.5, 129.4, 128.5, 126.1, 125.6, 125.5, 125.4, 125.3, 123.3, 122.6, 122.3, 119.8, 116.2, 115.0, 114.8, 112.2, 56.1, 55.7, 30.1, 26.7; LRMS (ESI) m/z calcd for C ₂₅ H ₁₈ F ₃ NO ₃ [M+Na] ⁺ : 437.1, found: 438.2.

Compound GxF 30 :

In a solution containing IF-B (30.0 mg, 0.063 mmol), DMF and water 10:1, 4-(dimethylamino)phenylboronic acid (31.2 mg, 0.189 mmol), tetrakis (triphenylphos) Fin) palladium (15.0 mg, 0.013 mmol) and sodium carbonate (33.6 mg, 0.315 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%), and the orange solid compound GxF 30 (26.5 mg, 93.5% yield) represented by the following formula 1-30 (26.5 mg, 93.5% yield) Was obtained.

[Formula 1-30]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.91 (d, J = 7.6 Hz, 1H), 8.43 (s, 1H), 7.95 (d, J = 8 Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.46 (m, 3H), 7.36 (s, 1H), 6.85 (d, J = 8 Hz, 2H), 3.03 (s, 6H), 2.65 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.5, 183.6, 150.0, 143.6, 135.2, 133.1, 132.8, 132.1, 129.4, 129.1, 128.4, 125.5, 125.5, 125.3, 125.0, 123.3, 123.1, 122.6, 121.5, 120.2, 113.1, 112.0, 40.9, 30.1, 26.6; LRMS (ESI) m/z calcd for C ₂₆ H ₂₁ N ₂ O ₂ [M+Na]+: 450.2, found: 451.2.

<GxF 31 ~ 35>

IG-E : Synthesized as in Scheme 8 below, specifically, DMF (12.0 mL) containing 4-acetylpyridine (158.1 μL, 1.431 mmol) and 2-chloroacetone (2-chloroacetone, 120.7 μL, 1.5 mmol) at 80° C. After stirring at for 4 hours, ethyl acrylate (77.5 μl, 0.715 mmol), copper (II) acetate monohydrate (856.5 mg, 4.29 mmol) and sodium acetate (469.2 mg, 5.72 mmol) were added thereto at 100° C. for 5 Stir for hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IG-E (166.7 mg, 85.3% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.85 (d, J = 6.8 Hz, 1H), 8.80(s, 1H), 7.44(d, J = 7.4 Hz, 1H), 4.39(q, J = 14.2 Hz, 2H), 2.62(s, 3H), 2.58(s, 3H) , 1.43 (t, J = 7.6 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 185.4, 159.1, 140.2, 134.6, 131.8, 131.6, 129.5, 129.2, 128.5, 128.3, 126.4, 125.4, 123.8, 121.8, 121.6, 119.9, 114.8, 111.7, 55.7, 26.7 ^; LRMS (ESI) m/z calcd for C ₁₅ H ₁₅ NO ₄ [M+Na] ⁺ : 273.3, found: 274.1.

IG-B : KOH (1.37 g, 24.4 mmol) was added to methanol (5 mL) containing IG-E (166.7 mg, 0.610 mmol), followed by stirring at room temperature overnight. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a brown solid compound IG-A.

The obtained compound IG-A was used in the next step without further purification, sodium bicarbonate (51.2 mg, 1.83 mmol) was added to DMF (10.0 mL) containing IG-A, and NBS (108.5 mg, 0.64 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IG-B (135.5 mg, 79.3% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.65 ( d, J = 7.4 Hz, 1H), 8.00 (s, 1H), 7.49 (s, 1H), 7.32 (d, 7.4 Hz), 2.63 (s, 3H), 2.53 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.2, 187.1, 134.4, 131.7, 128.0, 124.8, 124.1, 119.1, 111.8, 93.6, 27.9, 26.6; LRMS (ESI) m/z calcd for C ₁₂ H ₁₀ BrNO ₂ [M+Na] ⁺ : 280.1, found: 280.0.

[Scheme 8]

Compound GxF 31 :

4-trifluorophenyl boronic acid (50.71 mg, 0.27 mmol), tetrakis (triphenyl phosphine) in a solution containing IG-B (25.0 mg, 0.089 mmol) and a 10:1 mixture of DMF and water After adding palladium (20.58 mg, 0.018 mmol) and sodium carbonate (47.13 mg, 0.45 mmol), the mixture was stirred at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 31 (29.9 mg, 97.2% yield) represented by the following Formula 1-31. Was obtained.

[Formula 1-31]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃₎ , δ 9.86 (d, J = 7.6 Hz, 1H), 8.36 (s, 1H), 7.74 (dd, J = 8.4, 24.6 Hz, 5H), 7.43 (d, J = 8 Hz, 1H), 2.66 (s, 3H), 2.64 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.5, 187.9, 156.9, 137.8, 134.0, 132.1, 129.5, 129.1, 128.4, 126.3, 126.3, 125.7, 124.4, 123.1, 123.0, 119.8, 119.1, 112.1, 28.1, 26.7; LRMS (ESI) m/z calcd for C ₁₉ H ₁₄ F ₃ NO ₂ [M+Na] ⁺ : 345.3, found: 346.1.

Compound GxF 32 :

4-acetylphenyl boronic acid (43.78 mg, 0.27 mmol), tetrakis (triphenyl phosphine) palladium ( 20.58 mg, 0.018 mmol) and sodium carbonate (47.13 mg, 0.45 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 32 (27.6 mg, 97.2% yield) represented by the following Chemical Formula 1-32. Was obtained.

[Formula 1-32]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃₎ , δ 9.86 (d, J = 7.4 Hz, 1H), 8.39 (s, 1H), 8.10 (d, J = 6.6 Hz, 2H), 7.70 (d, J = 5.2 Hz, 2H), 7.69 (s, 1H), 7.42 (dd, J = 2 Hz, 7.2 Hz, 1H), 2.67 (s, 3H), 2.66 (s, 3H), 2.64 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 197.5, 195.5, 187.9, 139.0, 135.7, 134.1, 132.1, 129.4, 128.5, 128.1, 124.4, 123.1, 120.1, 119.3,112.1, 28.1, 27.1, 26.7; LRMS (ESI) m/z calcd for C ₂₀ H ₁₇ NO ₃ [M+Na]+: 319.4, found: 320.1.

Compound GxF 33 :

Phenyl boronic acid (32.56 mg, 0.27 mmol), tetrakis (triphenyl phosphine) palladium (20.58 mg,) in a solution containing IG-B (25.0 mg, 0.089 mmol) and a 10:1 mixture of DMF and water 0.018 mmol) and sodium carbonate (47.13 mg, 0.45 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 33 (23.5 mg, 95.4% yield) represented by the following Chemical Formula 1-33. Was obtained.

[Formula 1-33]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.81 (d, J = 7.4 Hz, 1H), 8.37 (s, 1H), 7.64 (s, 1H), 7.59 (d, J = 7.4 Hz, 2H), 7.51 (t, J = 7.2 Hz, 2H), 7.40 (t, J = 7.2 Hz, 2H), 2.64 (s, 3H), 2.61 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.6, 187.8, 134.1, 133.9, 131.6, 129.3, 128.3, 128.2, 127.4, 124.1, 122.9, 121.7, 119.8, 111.7, 28.1, 26.7; LRMS (ESI) m/z calcd for C ₁₈ H ₁₅ NO ₂ [M+Na] ⁺ : 277.3, found: 278.3.

Compound GxF 34 :

4-methoxyphenyl boronic acid (40.57 mg, 0.27 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IG-B (25.0 mg, 0.089 mmol) and a 10:1 mixture of DMF and water (20.58 mg, 0.018 mmol) and sodium carbonate (47.13 mg, 0.45 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 34 (26.5 mg, 96.9% yield) represented by the following Formula 1-34. Was obtained.

[Formula 1-34]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.78 (d, J = 7.4 Hz, 1H), 8.31 (s, 1H), 7.57 (s, 1H), 7.49 (d, J = 6.6 Hz, 2H), 7.35 (dd, J = 2H, 7.4 Hz, 1H), 7.05 (s, 1H), 7.03 (s, 1H), 3.88 (s, 3H), 2.62 (s, 3H), 2.60 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.6, 187.7, 159.1, 133.8, 131.3, 129.4, 128.1, 126.5, 124.0, 122.6, 121.6, 119.9, 114.8, 111.5, 55.7, 28.0, 26.6; LRMS (ESI) m/z calcd for C ₁₉ H ₁₇ NO ₃ [M+Na] ⁺ : 307.4, found: 308.1.

Compound GxF 35 :

4-(dimethylamino)phenyl boronic acid (44.06 mg, 0.27 mmol), tetrakis (triphenyl phosphonic acid) in a solution containing IG-B (25.0 mg, 0.089 mmol) and a 10:1 mixture of DMF and water Fin) palladium (20.58 mg, 0.018 mmol) and sodium carbonate (47.13 mg, 0.45 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 35 (26.9 mg, 94.8% yield) represented by the following Formula 1-35. Was obtained.

[Formula 1-35]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.78 (d, J = 6.8 Hz), 8.36 (s, 1H), 7.56 (s, 1H), 7.47 (dd, J = 2.4, 9.2 Hz, 2H), 7.36 (dd, J = 2, 2 Hz, 1H), 6.87 (d, J = 8.8 Hz), 3.03 (s, 6H), 2.63 (s, 3H), 2.60 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.7, 187.7, 149.9, 33.8, 131.0, 129.1, 128.0, 124.0, 122.4, 122.3, 122.0, 121.6(2), 120.3, 113.2, 111.4, 111.2, 40.9, 28.1 , 26.6; LRMS (ESI) m/z calcd for C ₂₀ H ₁₇ NO ₃ [M+Na] ⁺ : 320.2, found: 321.2.

<GxF 36 ~ 40>

IH-E : It was synthesized as in Scheme 9 below, and specifically, DMF (4.0 mL) containing 4-acetylpyridine (105.9 μL, 0.957 mmol) and 2-bromoacetophenone (2-bromoacetophenone, 200.0 mg, 1.01 mmol) After stirring at 80° C. for 5 hours, ethyl acrylate (51.8 μl, 0.479 mmol), copper(II) acetate monohydrate (573.2 mg, 2.87 mmol) and sodium acetate (314.0 mg, 3.83 mmol) were added to 100° C. Stir for 5 hours at. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IH-E (556.5 mg, 77.3% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.83 (dd, J = 7.2, 0.8 Hz, 1H), 8.90 (s, 1H), 7.80 (m, 3H), 7.54 (m, 4H) 4.38 (q, 2H) ), 2.69 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) 195.7, 163.7, 139.4, 138.3, 134.3, 132.1, 129.2, 128.9, 128.9, 128.9,121.1, 60.8, 26.6, 14.9; LRMS (ESI) m/z calcd for C ₂₀ H ₁₇ NO ₄ [M+Na] ⁺ : 335.1 ,found: 336.2.

IH-B : KOH (336.8 mg, 6.0 mmol) was added to methanol (4 mL) containing IH-E (200.0 mg, 0.60 mmol), followed by stirring at room temperature overnight. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a brown solid compound IH-A.

The obtained compound IH-A was used in the next step without further purification, sodium bicarbonate (131.1 mg, 1.56 mmol) was added to DMF (2.0 mL) containing IH-A, and NBS (97.9 mg, 0.55 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IH-B (135.2 mg, 76.3% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.85 (d, J = 7.4 Hz, 1H), 8.17 (s, 1H), 7.8 (d, J = 7.6 Hz, 2H), 7.52 (m,5H), 2.71 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.3, 184.8, 139.5, 135.2, 132.2, 131.9, 129.1, 128.6, 128.3, 127.5, 123.9, 119.2, 112.0, 94.1, 26.7; LRMS (ESI) m/z calcd for C ₁₇ H ₁₂ BrNO ₂ [M+Na] ⁺ : 341.0, found: x.

[Scheme 9]

Compound GxF 36 :

4-trifluorophenyl boronic acid (49.95 mg, 0.26 mmol), tetrakis (triphenyl phosphine) in a solution containing IG-B (30.0 mg, 0.088 mmol) and a 10:1 mixture of DMF and water After adding palladium (20.28 mg, 0.018 mmol) and sodium carbonate (46.4 mg, 0.44 mmol), the mixture was stirred at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 40%) to form a yellow solid compound GxF 36 (33.8 mg, 94.3% yield) represented by the following formula 1-36. Was obtained.

[Formula 1-36]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.92 (d, J = 7.6 Hz, 1H), 8.09 (s, 1H), 7.85 (dd, J = 8.2 Hz, 2H), 7.74 (d, J = 8.0 Hz , 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.60 (t, J = 6.8 Hz, 1H), 7.57 (s, 1H), 7.54 (d, J = 7.6 Hz, 2H), 7.14 (d , J = 7.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) 185.5, 139.9, 137.5, 133.1, 131.8, 129.5, 129.8, 128.2, 128.3, 126.4, 126.7, 126.2, 126.1, 125.4, 123.8, 118., 115.7, 110.0, 110.0, 47.1 , 34.4; LRMS (ESI) m/z calcd for C ₂₄ H ₁₆ F ₃ NO ₂ [M+Na] ⁺ : 407.1, found: 408.1.

Compound GxF 37 :

4-acetylphenyl boronic acid (343.12 mg, 0.26 mmol), tetrakis (triphenyl phosphine) palladium ( 20.28 mg, 0.018 mmol) and sodium carbonate (46.4 mg, 0.44 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 37 (32.1 mg, 95.6% yield) represented by Formula 1-37 below. Was obtained.

[Formula 1-37]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.92 (d, J = 8 Hz, 1H), 8.44 (s, 1H), 8.07 (d, J = 7.2 Hz, 2H), 7.85 (d, J = 7.6 Hz, 2H), 7.54 (m, 5H), 2.66 (s, 3H), 2.65 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 197.4, 195.4, 185.5, 140.0, 138.9, 135.7, 134.8, 132.6, 131.8, 129.4,129.2, 128.6, 128.1, 125.8, 124.3, 120.4,119.3, 112.2, 27.0, 26.7.; LRMS (ESI) m/z calcd for C ₂₅ H ₁₉ NO ₃ [M+Na] ⁺ : 381.1, found: 382.2.

Compound GxF 38 :

Methyl boronic acid (32.07 mg, 0.26 mmol), tetrakis (triphenyl phosphine) palladium (20.28 mg,) in a solution containing IG-B (30.0 mg, 0.088 mmol) and a 10:1 mixture of DMF and water 0.018 mmol) and sodium carbonate (46.4 mg, 0.44 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 38 (28.5 mg, 95.4% yield) represented by the following formula 1-38. Was obtained.

[Formula 1-38]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.92 (d, J = 7.6 Hz, 1H), 8.43 (s, 1H), 7.86 (d, J = 6.4 Hz, 2H), 7.58 (m, 3H), 7.50 (m, J = 30.4 Hz, 7H), 7.38 (t, J = 7.2 Hz, 1H), 2.65 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.6, 185.5, 140.2, 134.7, 134.1, 132.1, 131.7, 129.3, 129.2, 128.5, 128.3, 125.7, 119.8, 111.8; LRMS (ESI) m/z calcd for C ₂₃ H ₁₇ NO ₂ [M+Na]+: 339.1, found: 340.2.

Compound GxF 39 :

In a solution containing IG-B (30.0 mg, 0.088 mmol) and a mixture of DMF and water 10:1, 4-methoxyphenyl boronic acid (39.97 mg, 0.26 mmol), tetrakis ( Triphenyl phosphine) palladium (20.28 mg, 0.018 mmol) and sodium carbonate (46.4 mg, 0.44 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 39 (30.1 mg, 92.7% yield) represented by the following formula 1-39. Was obtained.

[Formula 1-39]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) 9.89 (d,e J = 8 Hz, 1H), 8.36 (s, 1H), 7.84 (d, 8.2 Hz, 2H), 7.51 (m,7H), 7.03 (d , 7 Hz, 2H), 3.87 (s, 3H), 2.65 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) 195.6, 185.4, 159.1, 140.2, 134.6, 131.8, 131.6, 129.5, 129.2, 128.5, 128.3, 126.4, 125.4, 123.8, 121.8, 121.6, 119.9, 114.8, 111.7, 55.7, 26.7; LRMS (ESI) m/z calcd for C ₂₄ H ₁₉ NO ₃ [M+Na]+ :369.1, found: 370.2.

Compound GxF 40 :

Phenyl (dimethylamino) phenylboronic acid, 43.40 mg, 0.26 mmol) in a solution containing IG-B (30.0 mg, 0.088 mmol) and a mixture of DMF and water 10:1, After tetrakis (triphenyl phosphine) palladium (20.28 mg, 0.018 mmol) and sodium carbonate (46.4 mg, 0.44 mmol) were added, the mixture was stirred at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form an orange solid compound GxF 40 (32.9 mg, 94.9% yield) represented by Formula 1-40 below. Was obtained.

[Formula 1-40]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.89 (d, J = 7.4 Hz, 1H), 8.41 (s, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.51 (m, 8H), 6.85 (d, J = 7.8 Hz, 2H), 3.02 (s, 6H), 2.65 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.6, 185.3, 149.9, 140.4, 134.5, 131.5, 131.5, 129.3, 129.1, 128.5, 128.2, 125.0, 123.8, 122.6, 121.9, 120.3, 113.1, 111.5, 53.8, 40.9, 26.6; LRMS (ESI) m/z calcd for C ₂₅ H ₂₂ N ₂ O ₂ [M+Na]+: 382.2, found: 383.2.

<GxF 41 ~ 45>

II-E : Synthesized as in Reaction Scheme 10 below, and specifically, DMF (17.6 mL) containing 4-acetylpyridine (585.2 μL, 5.29 mmol) and 2-bromoacetophenone (1.5 g, 5.6 mmol) was 5 at 80°C. After stirring for an hour, ethyl acrylate (286.6 μl, 2.65 mmol), copper (II) acetate monohydrate (3.17 g, 15.87 mmol) and sodium acetate (1.74 g, 21.16 mmol) were added thereto at 100° C. for 5 hours. Stirred. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain Compound II-E (709.8 mg, 73.3% yield) as a yellow solid.

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) 9.62 (dd J = 7.4, 0.4 Hz, 1H), 8.76 (s, 1H), 7.74 (dd, J = 6.6, 2 Hz, 2 H), 7.69 (s, 1H ), 7.39 (dd, J = 7.4, 2 Hz, 1H), 6.92 (dd, J = 6.8, 2 Hz, 2H), 4.33 (q, J = 7.2 Hz, 2H), 3.82 (s,3H), 2.61 (s, 3H), 1.362 (t, J = 7.2 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) 195.6, 184.3, 163.4, 162.8, 137.6, 133.7, 131.9, 131.4, 128.4, 127.5, 123.2, 120.9, 113. 8, 112.5, 109.1, 60.6, 55.6, 26.4, 14.8; LRMS (ESI) m/z calcd for C ₂₁ H ₁₉ NO ₄ [M+Na]+: 365.1 ,found :366.2.

II-B : KOH (3.1 g, 77.6 mmol) was added to methanol (19 mL) containing II-E (709.8 mg, 1.94 mmol), followed by stirring at room temperature overnight. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a brown solid compound II-A.

The obtained compound II-A was used in the next step without further purification, sodium bicarbonate (478.9 mg, 5.7 mmol) was added to DMF (10.0 mL) containing II-A, and NBS (354.9 mg, 2.0 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain Compound II-B (462.0 mg, 72.1% yield) as a yellow solid.

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) 9.73 (d, J = 7.2 Hz, 1 H), 8.12 (s, 1H), 7.81 (d, J = 8.8 Hz, 2H), 7.42 (m, 1H), 6.99 (d, 2H), 3.88 (s, 3H), 2.68 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) 195.3, 183.7, 162.8, 134.8, 132.0, 131.9, 131.4, 128.1, 126.9, 124.0, 119.3, 113.9, 111.7, 93.9, 55.8, 26.6; LRMS (ESI) m/z calcd for C ₁₈ H ₁₄ NO ₄ [M+Na]+: 372. 2 ,found: 372.1.

[Scheme 10]

Compound GxF 41 :

In a solution (1.1 mL) containing II-B (30.0 mg, 0.081 mmol) and a 10:1 mixture of DMF and water, 4-trifluorophenyl boronic acid (46.2 mg, 0.243 mmol), tetrakis (tri Phenyl phosphine) palladium (18.7 mg, 0.016 mmol) and sodium carbonate (42.9 mg, 0.405 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 40%) to form a yellow solid compound GxF 41 (34.4 mg, 97.2% yield) represented by the following formula 1-41. Was obtained.

[Formula 1-41]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ) 9.84 (d, J = 7.4 Hz, 1H), 8.39 (s, 1H), 7.88 (d, J = 6.8 Hz, 2H), 7.72 (q, J = 1.2 Hz, 4H), 7.54 (s, 1H), 7.45 (dd, J = 7.2, 2 Hz, 2H), 3.90 (s, 3H), 2.66 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) 195.6, 184.5, 162.8, 137.9, 134.3, 132.8, 132.4, 132.2, 131.5, 129.4, 129.0, 128.4, 126.3, 126.2, 125.7, 125.3, 124.3, 123.0, 122.5, 119.9, 119.3, 115.8, 114.0, 111.9; LRMS (ESI) m/z calcd for C ₂₅ H ₁₈ F ₃ NO ₃ [M+Na]+ :437.1, found: 438.2.

Compound GxF 42 :

4-acetylphenyl boronic acid (39.8 mg, 0.243 mmol), tetrakis (triphenyl phosphonic acid) in a solution (1.1 mL) containing II-B (30.0 mg, 0.081 mmol) and a mixture of DMF and water 10:1 Fin) palladium (18.7 mg, 0.016 mmol) and sodium carbonate (42.9 mg, 0.405 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 42 (32.5 mg, 97.5% yield) represented by the following formula 1-42. Was obtained.

[Formula 1-42]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.84 (d, J = 7.2 Hz, 1H), 8.4 (s, 1H), 8.07 (d, J = 8 Hz, 2H), 7.88 (dd, J = 7 , 2Hz, 2H), 7.68(d, J = 8.4 Hz, 2H), 7.56(s, 1H) 7.45 (dd, J = 7.4, 2 Hz), 3.90(s, 3H), 2.65(s, 3H) ; ¹³ C NMR (100 MHz, CDCl ₃ ), δ 197.4, 195.5, 184.5, 162.8, 139.1, 135.6, 134.3, 132.4, 132.3, 131.5, 129.4, 128.4, 128.1, 125.2, 124.4, 120.1, 119.4, 114.0, 111.9, 55.8, 30.1, 27.0, 26.7; LRMS (ESI) m/z calcd for C ₂₆ H ₂₁ NO ₄ [M+Na]+ :411.5, found: 412.2.

Compound GxF 43 :

Benzene boronic acid (29.6 mg, 0.243 mmol), tetrakis (triphenyl) in a solution (1.1 mL) containing II-B (30.0 mg, 0.081 mmol) and a 10:1 mixture of DMF and water Phosphine) palladium (18.7 mg, 0.016 mmol) and sodium carbonate (42.9 mg, 0.405 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 43 (28.9 mg, 96.6% yield) represented by the following formula 1-43. Was obtained.

[Formula 1-43]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.84 (d, J = 7.2, 0.8 Hz, 1 H), 8.42 (s, 1H), 7.89 (dd, J = 7.6, 2 Hz, 2H), 7.58 (d , J = 1.2 Hz, 2H), 7.51 (m, 3H), 7.43 (dd, J = 7.6, 2 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.13 (s, 2H), 7.01 (d, J = 6.8 Hz, 2H), 3.9 (s, 3H), 2.64 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.63, 184.4, 162.6, 134.2(2),132.7, 131.8, 131.5, 129.3, 129.3, 128.2, 127.4, 125.1, 124.1,121.7,121.6,113.9, 111.5, 55.8 , 30.1, 26.7; LRMS (ESI) m/z calcd for C ₂₆ H ₂₁ NO ₄ [M+Na]+ :369.1, found: 370.2.

Compound GxF 44 :

4-methoxyphenyl boronic acid (36.9 mg, 0.243 mmol), tetrakis (triphenyl) in a solution (1.1 mL) containing II-B (30.0 mg, 0.081 mmol) and a 10:1 mixture of DMF and water Phosphine) palladium (18.7 mg, 0.016 mmol) and sodium carbonate (42.9 mg, 0.405 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 44 (30.4 mg, 94.0% yield) represented by the following formula 1-44. Was obtained.

[Formula 1-44]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.80 (d, J = 7.2 Hz, 1H), 8.36 (s, 1H), 7.87 (d, J = 7 Hz, 2H), 7.49 (d, J = 6.6 Hz, 2H), 7.45(s, 1H), 7.40(dd, J = 7.2, 2 Hz, 1H), 7.02(m, 4H), 3.90(s, 3H), 3.87(s, 3H), 2.63( s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.6, 184.4, 162.6, 159.0, 134.2, 132.7, 131.5, 129.5, 128.1, 126.6, 124.8, 124.0, 121.6, 119.9, 114.8, 113.8, 111.4, 55.8, 55.7, 26.6 LRMS (ESI) m/z calcd for C ₂₅ H ₂₁ NO ₄ [M+Na]+ :399.2, found: 400.2.

Compound GxF 45 :

In a solution (1.1 mL) containing II-B (30.0 mg, 0.081 mmol) and a 10:1 mixture of DMF and water, 4-dimethylaminophenyl boronic acid (40.0 mg, 0.24 mmol), tetrakis (tri Phenyl phosphine) palladium (18.7 mg, 0.016 mmol) and sodium carbonate (42.9 mg, 0.405 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 45 (31.2 mg, 93.3% yield) represented by the following formula 1-45. Was obtained.

[Formula 1-45]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.80 (d, J = 7.2 Hz, 1H), 8.40 (s, 1H), 7.88 (d, J = 2.8 Hz, 2H), 7.46 (m, 3H), 7.40 (dd, J = 7.4, 2 Hz, 1H), 7.00 (d, J = 6.6 Hz, 2H), 6.86 (d, J = 6.8 Hz, 2H), 3.90 (s, 3H), 3.02 (s, 6H) ), 2.63 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.7, 184.4, 162.5, 149.9, 134.1, 132.9, 131.5, 131.2, 129.1, 128.0, 124.5, 124.0, 122.4, 122.1, 120.4, 113.8, 113.2, 111.2, 55.8, 40.9, 26; LRMS (ESI) m/z calcd for C ₂₆ H ₂₄ N ₂ O ₃ [M+Na]+ :412.2, found: 413.2.

<GxF 46 ~ 50>

IJ-E : Synthesized as in Scheme 11 below, specifically, 4-acetylpyridine (194.9 μL, 1.76 mm) and 2-bromo-4'-diethylaminoacetophenone (500 mg, 1.85 mmol) containing DMF (6.0 mL) was stirred at 80° C. for 5 hours, and then ethyl acrylate (88.1 μl, 0.88 mmol), copper (II) acetate monohydrate (1.05 g, 5.28 mmol) and sodium acetate (577.5 mg, 7.04 mmol) were added. And stirred at 100° C. for 5 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IJ-E (295.6 mg, 82.7% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.66 (d, J = 7.6 Hz, 1H), 8.89 (s, 1H), 7.8 (m, 3H), 7.46 (dd, J = 7.6Hz, 2Hz, 1H ), 6.69 (d, J = 7 Hz, 2H), 4.39 (q, J = 7.2 Hz, 2H), 3.43 (q, J = 7.2 Hz, 4H), 2.68 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H), 1.21 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.9, 183.9, 164.1, 151.0, 137.5, 133.3, 132.3, 132.2, 128.5, 127.1, 125.4, 124.7, 121.6, 121.3, 111.7, 110.5, 108.8, 60.6, 44.9, 26.5, 14.9, 13.0; LRMS (ESI) m/z calcd for C ₂₄ H ₂₆ N ₂ O ₄ [M+Na]+: 406.2, found: 407.2.

IJ-B : KOH (1.63 g, 29.2 mmol) was added to methanol (16 mL) containing IJ-E (295.6 mg, 0.73 mmol), followed by stirring at room temperature overnight. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a brown solid compound IJ-A.

The obtained compound IJ-A was used in the next step without further purification, sodium bicarbonate (306.6 mg, 3.65 mmol) was added to DMF (10.0 mL) containing IJ-A, and NBS (136.4 mg, 0.77 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound IJ-B (241.0 mg, 80.1% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.61 (d, J = 7.2 Hz, 1H), 8.06 (s, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.32 (dd, J = 2 Hz, 7.4 Hz), 6.66 (d, J = 8.8 Hz, 2H), 3.42 (q, 7.2 Hz, 4H), 2.64 (s, 3H), 1.21 (t, J = 7.2 Hz , 6H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.4, 183.1, 150.9, 133.9, 132.1, 131.0, 127.8, 125.9, 125.6, 124.6, 119.4, 111.0, 110.5, 93.4, 77.7, 77.4, 77.1, 44.9, 26.6, 13.0; LRMS (ESI) m/z calcd for C21H21BrN2O2 [M+Na]+: 412.08 ,found: x.

[Scheme 11]

Compound GxF 46 :

In a solution (1.1 mL) containing IJ-B (20.0 mg, 0.048 mmol) and a 10:1 mixture of DMF and water, 4-trifluorophenyl boronic acid (27.3 mg, 0.14 mmol), tetrakis (tri Phenyl phosphine) palladium (11.1 mg, 0.01 mmol) and sodium carbonate (25.4 mg, 0.24 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 40%) to form a yellow solid compound GxF 46 (22.2 mg, 96.6% yield) represented by the following formula 1-46. Was obtained.

[Formula 1-46]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.75 (d, J = 7.7 Hz, 1H), 8.39 (s, 1H), 7.88 (d, 7.2 Hz, 2H), 7.73 (q, J = 8.8 Hz, 5.2 Hz, 4H), 7.59 (s, 1H), 7.40 (dd, J = 1.6 Hz, 7.6 Hz, 1H), 6.72 (d, J = 9.2 Hz, 2H), 3.46 (q, J = 7.2 Hz, 4H ), 2.65 (s, 3H), 1.24 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.6, 183.9, 150.9, 138.3, 133.5, 132.2, 131.5, 128.3, 128.2, 126.2, 126.0, 125.0, 124.3, 119.5, 119.4, 111.3, 110.5, 44.9, 26.7, 13.0; LRMS (ESI) m/z calcd for C ₂₈ H ₂₅ F ₃ N ₂ O ₂ [M+Na]+: 478.2, found: x.

Compound GxF 47 :

4-acetylphenyl boronic acid (323.6 mg, 0.14 mmol), tetrakis (triphenyl phosphonic acid) in a solution (1.1 mL) containing IJ-B (20.0 mg, 0.048 mmol) and a 10:1 mixture of DMF and water Fin) palladium (11.1 mg, 0.01 mmol) and sodium carbonate (25.4 mg, 0.24 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 47 (20.5 mg, 94.5% yield) represented by the following formula 1-47. Was obtained.

[Formula 1-47]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.74 (d, J = 7.4 Hz, 1H), 8.43 (s, 1H), 8.08 (d, J = 6.4 Hz, 2H), 7.87 (d, J = 7.2 Hz, 2H), 7.70 (d, J = 6.8 Hz, 2H), 7.61 (s, 1H), 7.39 (dd, J = 7.8 Hz, 1H), 6.72 (d, J = 7.2 Hz, 2H), 3.46 ( q, J = 7.2 Hz, 4H), 2.67 (s, 3H), 2.65 (s, 3H), 1.24 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 197.5, 195.6, 183.9, 150.9, 139.5, 135.4, 133.6, 132.2, 131.5, 129.4, 128.2, 128.0, 126.0, 125.1, 124.3, 119.7, 119.6, 111.3, 110.6, 44.9, 27.0, 26.7, 13.0; LRMS (ESI) m/z calcd for C ₂₉ H ₂₈ N ₂ O ₃ [M+Na] ⁺ : 452.1, found: x.

Compound GxF 48 :

4-benzene boronic acid (23.8 mg, 0.14 mmol), tetrakis (triphenylphosphine) in a solution (1.1 mL) containing IJ-B (20.0 mg, 0.048 mmol) and a 10:1 mixture of DMF and water ) Palladium (11.1 mg, 0.01 mmol) and sodium carbonate (17.6 mg, 0.24 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 48 (18.2 mg, 92.2% yield) represented by Formula 1-48 below. Was obtained.

[Formula 1-48]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.73 (d, J = 7.4 Hz, 1H), 8.41 (s, 1H), 7.88 (d, J = 8Hz, 2H), 7.60 (d, J = 8.2 Hz , 2H), 7.57(s, 1H), 7.52(t, J = 7.2Hz, 2H), 7.37(m, 2H), 6.71(d, J = 9.2Hz, 2H), 3.45(q, J = 6.8Hz , 4H), 2.63 (s, 3H), 1.24 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.7, 184.0, 150.8, 134.6, 133.4, 132.1, 131.0 129.2, 128.3, 128.0, 127.1, 126.3, 124.7, 1242.3, 121.3, 120.0, 110.9, 110.5, 44.9, 26.6 , 13.0; LRMS (ESI) m/z calcd for C ₂₇ H ₂₆ N ₂ O ₂ [M+Na]+: 410.2, found: x.

Compound GxF 49 :

4-methoxyphenyl boronic acid (21.9 mg, 0.14 mmol), tetrakis (triphenyl) in a solution (1.1 mL) containing IJ-B (20.0 mg, 0.048 mmol) and a 10:1 mixture of DMF and water Phosphine) palladium (11.1 mg, 0.01 mmol) and sodium carbonate (25.4 mg, 0.24 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 49 (19.7 mg, 93.4% yield) represented by the following formula 1-49. Was obtained.

[Formula 1-49]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.72 (d, J = 7.8 Hz, 1H), 8.36 (s, 1H), 7.87 (d, J = 7.2 Hz, 2H), 7.52 (d, J = 6.6 Hz, 3H), 7.35 (dd, J = 1.6 Hz, 7.6 Hz, 1H), 7.04 (d, J = 6.6 Hz, 2H), 6.71 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H) , 3.45 (q, J = 8 Hz, 4H), 2.63 (s, 3H), 1.23 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.7, 183.9, 158.9, 150.7, 133.3, 132.1, 130.7, 129.5, 127.9, 127.0, 126.4, 124.6, 124.0, 121.2, 120.1, 114.7, 110.8, 110.5, 55.7, 44.9, 26.6, 13.0; LRMS (ESI) m/z calcd for C ₂₈ H ₂₈ N ₂ O ₃ [M+Na]+: 440.2, found: x.

Compound GxF 50 :

4-dimethylaminophenyl boronic acid (23.8 mg, 0.14 mmol), tetrakis (tri Phenyl phosphine) palladium (11.1 mg, 0.01 mmol) and sodium carbonate (25.4 mg, 0.24 mmol) were added, followed by stirring at 100° C. for 8 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to form a yellow solid compound GxF 50 (20.2 mg, 93.0% yield) represented by Formula 1-50 below. Was obtained.

[Formula 1-50]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.70 (d, J = 7.2 Hz, 1H), 8.39 (s, 1H), 7.87 (d, J = 9.2 Hz, 2H), 7.49 (d, J = 8.6 Hz, 3H), 7.34(dd, 2.0Hz, 7.6Hz, 1H), 6.87(d, J = 8.8Hz, 2H), 6.70(d, J = 8.8 Hz, 2H), 3.45(q, J = 7.6Hz , 4H), 3.03 (s, 6H), 2.62 (s, 3H), 1.24 (t, J = 6.8 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ), δ 195.8, 183.0, 150.7, 149.8, 133.3, 132.2, 130.4, 129.1, 127.8, 126.4, 124.6, 123.8, 122.5, 122.0, 120.6, 113.2, 110.6, 110.5, 44.9, 41.0, 26.5, 13.0; LRMS (ESI) m/z calcd for C ₂₉ H ₃₁ N ₃ O ₂ [M+Na]+: 453.2, found: x.

<GxF 51 ~ 55>

IK-E : Synthesized as in Reaction Scheme 12, specifically, pyridine (pyridine, 564 μL, 7 mmol) and 2-bromo-1-[4-(4(trifluoromethyl)-phenyl]ethan-1-one ( DMF (15.0 mL) containing 1.96 mL, 7.35 mmol) was stirred at 100° C. overnight, and then ethyl acrylate (372 μL, 3.50 mmol), copper (II) acetate monohydrate (2.09 g, 10.5 mmol) and Sodium acetate (1.72 g, 21.0 mmol) was added and stirred for 16 hours at 100° C. After completion of the reaction, it was monitored by TLC, and then copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was removed. The resulting crude product was washed with water and the organics were extracted 3 times with DCM The extracted organics were combined, dried over anhydrous Na ₂ SO ₄ and concentrated, The concentrated organic phase was silica-gel flash Purified by column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IK-E (906 mg, 2.50 mmol, 71.6% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.98 (d, J = 6.8 Hz, 1H), 8.42 (d, J = 9.2 Hz, 1H), 7.91 (d, J = 8.0 Hz, 2H), 7.78 ( d, J = 8.4 Hz, 2H), 7.76 (s, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.14 (d, J = 6.2 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.6, 163.6, 142.9, 140.0, 132.9, 132.6, 129.1, 129.9, 128.9, 128.1, 125.3(3), 125.0, 122.3, 121.9, 121.4, 119.5, 115.6, 106.8, 60.3, 14.7; LRMS (ESI) m/z calcd for C ₁₉ H ₁₄ F ₃ NO ₃ [M+Na] ⁺ : 361.1, found: 362.1.

IK-B : KOH (8.44 g, 150 mmol) was added to methanol (20 mL) containing IK-E (632 mg, 2.50 mmol), followed by stirring at room temperature for 4 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water, and dried in a drying oven to obtain a white solid compound IK-A.

The obtained compound IK-A was used in the next step without further purification, sodium bicarbonate (630 mg, 7.50 mmol) was added to DMF (10.0 mL) containing IK-A, and NBS (667 mg, 3.75 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IK-B (664 mg, 1.80 mmol, 72.1% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.96 (d, J = 7.2 Hz, 1H), 7.87 (d, J = 7.6 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.64 ( d, J = 9.2 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 7.32 (s, 1H), 7.05 (t, J = 7.0 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 181.4, 142.9, 136.6, 132.4, 128.8, 128.3, 126.5, 125.4, 125.0, 124.9, 122.2, 121.3, 116.7, 114.6, 89.9; LRMS (ESI) m/z calcd for C ₁₆ H ₉ BrF ₃ NO[M+Na] ⁺ : 367.0, found: 368.0.

[Scheme 12]

Compound GxF 51 :

4-trifluorophenyl boronic acid (122 mg, 0.64 mmol), tetrakis (triphenyl phosphine) in a solution containing IK-B (59.0 mg, 0.16 mmol) and a mixture of DMF and water 2: 1 After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (68.0 mg, 0.64 mmol), the mixture was stirred at 100° C. for 1 hour. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 51 (62.1 mg, 0.14 mmol, 89.5) represented by the following formula 1-51. % Yield) was obtained.

[Chemical Formula 1-51]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.05 (d, J = 6.8 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.78 ( d, J = 8.4 Hz, 2H), 7.68 (q, J = 8.0 Hz, 5H), 7.43 (s, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.08 (t, J = 6.2 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 182.8, 143.6, 138.0, 136.7, 132.7, 132.4, 129.2, 129.0, 128.7, 128.4, 127.8, 126.2, 125.8, 125.8, 125.5, 125.4, 125.3(2), 122.1, 117.3, 116.4, 114.9.

Compound GxF 52 :

In a solution containing IK-B (58.6 mg, 0.16 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (104 mg, 0.64 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (67.5 mg, 0.64 mmol) were added, followed by stirring at 100° C. for 7 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound GxF 52 (58.4 mg, 0.14 mmol, 89.5) represented by the following formula 1-52. % Yield) was obtained.

[Formula 1-52]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.03 (d, J = 7.2 Hz, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 9.2 Hz, 1H), 7.77 ( d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.27 (t, J = 7.4 Hz, 1H), 7.00 (d, J = 8.8 Hz, 3H), 3.86 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 182.3, 158.5, 144.0, 136.8, 132.4, 132.0, 129.0(2), 126.6, 125.3, 125.2(2), 125.1(2), 124.9, 122.5, 121.5, 118.0, 117.6, 114.5, 114.3, 55.4.

Compound GxF 53 :

Phenyl boronic acid (71.2 mg, 0.57 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, in a solution containing IK-B (53.0 mg, 0.14 mmol) and a mixture of DMF and water 2: 1) 20.0 mol%) and sodium carbonate (61.0 mg, 0.57 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 53 (53.1 mg, 0.14 mmol, 100) represented by the following formula 1-53 (53.1 mg, 0.14 mmol, 100). % Yield) was obtained.

[Formula 1-53]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.04 (d, J = 6.8 Hz, 1H), 7.92 (t, J = 8.0 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.55 ( d, J = 7.6 Hz, 2H), 7.45 (t, J = 7.8 Hz, 2H), 7.39 (s, 1H), 7.32 (m, 3H), 6.97 (t, J = 6.6 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 182.5, 143.9, 136.8, 134.2, 132.5, 132.1, 129.1, 129.0, 128.9, 127.8, 126.7, 125.6, 125.3, 125.2, 122.5, 121.7, 118.2, 117.6, 114.6; LRMS (ESI) m/z calcd for C ₂₂ H ₁₄ F ₃ NO[M+Na] ⁺ : 365.1, found: 366.1.

Compound GxF 54 :

4-methoxyphenyl boronic acid (92.8 mg, 0.61 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IK-B (56.2 mg, 0.15 mmol) and a mixture of DMF and water 2: 1 (231 mg, 20.0 mol%) and sodium carbonate (64.7 mg, 0.61 mmol) were added, followed by stirring at 100° C. for 10 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 54 (65.9 mg, 0.16 mmol, 100) represented by the following formula 1-54. % Yield) was obtained.

[Formula 1-54]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.99 (d, J = 7.2 Hz, 1H), 7.99 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), 7.73 ( d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.42 (s,1H), 7.32 (t, J = 8.0 Hz, 1H), 7.01 (t, J = 6.8 Hz, 1H), 2.60 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.1, 182.6, 144.0, 143.5, 139.1, 136.7, 136.3, 135.0, 132.6, 132.2, 129.1, 128.9, 128.8, 127.4, 127.2, 126.2, 125.2, 122.4, 122.1, 117.4 , 116.6, 114.9, 26.7; LRMS (ESI) m/z calcd for [M+Na] ⁺ : 395.1, found: 396.4.

Compound GxF 55 :

In a solution containing IK-B (60.6 mg, 0.16 mmol) and a mixture of DMF and water 2: 1, 4-(dimethylamino) phenyl boronic acid (108.6 mg, 0.66 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (69.7 mg, 0.66 mmol) were added, followed by stirring at 100° C. for 11 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to obtain a yellow solid compound GxF 55 (59.5 mg, 0.14 mmol, 91) represented by the following formula 1-55. % Yield) was obtained.

[Formula 1-55]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.03 (d, J = 6.8 Hz, 1H), 7.92 (d, J = 8.0 Hz, 2H), 7.87 (d, J = 8.4 Hz, 1H), 7.75 ( d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.8 Hz, 2H), 7.31 (s, 1H), 7.27 (t, J = 7.2 Hz, 1H), 6.95 (t, J = 6.9 Hz, 1H), 6.82 (d, J = 8.8 Hz, 2H), 2.98 (s, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 181.7, 149.1,143.8, 136.5, 131.9, 131.6, 128.8, 128.6, 128.3, 124.9, 124.8, 124.7, 124.3, 122.2, 121.8, 121.1, 118.4, 117.5, 114.1, 112.5 , 40.3; LRMS (ESI) m/z calcd for C ₂₄ H ₁₉ F ₃ N ₂ O [M+Na] ⁺ : 408.1, found: 409.2.

<GxF 56 ~ 60>

IL-E : Synthesized as in Scheme 13 below, specifically, DMF (15.0 mL) containing pyridine (564 μL, 7.00 mmol) and chloroacetone (chloroacetone, 585 μL, 7.35 mmol) was stirred at 100° C. overnight, Ethyl acrylate (373 μL, 3.50 mmol), copper (II) acetate monohydrate (2.09 g, 10.5 mmol) and sodium acetate (1.72 g, 21.0 mmol) were added, followed by stirring at 100° C. for 16 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IL-E (633 mg, 2.73 mmol, 85.0% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.88 (d, J = 6.4 Hz, 1H), 8.34 (d, J = 5.0 Hz, 1H), 7.99 (s, 1H), 7.38 (q, J = 9.3 Hz, 1H), 6.95 (t, J = 7.0 Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 2.60 (s, 3H), 1.43 (t, J = 7.2 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 187.6, 164.0, 139.2, 129.1, 127.2, 126.2, 122.7, 119.4, 115.2, 105.8, 60.3, 27.6, 14.9; LRMS (ESI) m/z calcd for C ₁₃ H ₁₃ NO ₃ [M+Na] ⁺ : 231.1, found: 232.1.

IL-B : After adding KOH (6.14 g, 109 mmol) to methanol (20 mL) containing IL-E (633 mg, 2.73 mmol), the mixture was stirred at room temperature for 4 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a white solid compound IL-A.

The obtained compound IL-A was used in the next step without further purification, sodium bicarbonate (688 mg, 8.19 mmol) was added to DMF (10.0 mL) containing IL-A, and NBS (2.18 g, 12.3 mmol) was added, and NBS (2.18 g, 12.3 mmol) was added. ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IL-B (477 mg, 2.0 mmol, 73.4% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.83 (d, J = 6.8 Hz, 1H), 7.56 (d, J = 9.2 Hz, 1H), 7.51 (s, 1H), 7.22 (q, J = 7.8 Hz, 1H), 6.91 (t, J = 6.4 Hz, 1H), 2.54 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) [ delta] 185.5, 135.4, 127.9, 124.0, 123.8, 121.9, 116.5, 113.9, 88.5, 27.1; LRMS (ESI) m/z calcd for C ₁₀ H ₈ BrNO[M+Na] ⁺ : 237.0, found: 238.0.

[Scheme 13]

Compound GxF 56 :

In a solution containing IL-B (21.7 mg, 0.09 mmol) and a mixture of DMF and water 2: 1, 4-trifluorophenyl boronic acid (69.0 mg, 0.36 mmol), tetrakis (triphenyl phosphine) After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (39.0 mg, 0.36 mmol), the mixture was stirred at 100° C. for 10 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to obtain a yellow solid compound GxF 56 (24.4 mg, 0.08 mmol, 89.3) represented by the following formula 1-56. % Yield) was obtained.

[Formula 1-56]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.93 (d, J = 7.6 Hz, 1H), 7.82 (d, J = 9.2 Hz, 2H), 7.69 (d, J = 4.4 Hz, 2H), 7.65 ( s, 1H), 7.49 (d, J = 8.6 Hz, 1H), 7.24 (dd, J = 10.0 Hz, 1H), 6.95 (t, J = 7.0 Hz, 1H), 2.62 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.8, 138.4, 135.7, 129.0, 128.1, 127.8, 125.8, 125.8, 125.6, 125.1, 122.8, 122.6, 117.1, 115.5(2), 114.4, 27.5; LRMS (ESI) m/z calcd for C ₁₇ H ₁₂ F ₃ NO [M+Na] ⁺ : 303.1, found: 304.1.

Compound GxF 57 :

In a solution containing IL-B (25.8 mg, 0.10 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (71.0 mg, 0.43 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (46.0 mg, 0.43 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound GxF 57 (19.0 mg, 0.06 mmol, 63.4) represented by the following formula 1-57. % Yield) was obtained.

[Formula 1-57]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.91 (d, J = 6.8 Hz, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.85 (d, J = 8.8 Hz, 1H), 7.68 ( s, 1H), 7.66 (d, J = 3.6 Hz, 2H), 7.23 (dd, J = 7.8 Hz, 1H), 6.93 (t, J = 6.9 Hz, 1H), 2.63 (s, 3H), 2.61 ( s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.5, 186.9, 139.9, 135.7, 134.9, 129.1, 127.6, 127.5, 125.3, 122.9, 122.8, 117.5, 115.7, 114.5, 27.7, 27.0; LRMS (ESI) m/z calcd for C ₁₈ H ₁₅ NO ₂ [M+Na] ⁺ : 277. 1, found: 278.1.

Compound GxF 58 :

In a solution containing IL-B (54.4 mg, 0.23 mmol) and a mixture of DMF and water 2: 1, phenyl boronic acid (111 mg, 0.91 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, 20.0 mol%) and sodium carbonate (97.0 mg, 0.91 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 58 (66.8 mg, 0.28 mmol, 100) represented by the following formula 1-58. % Yield) was obtained.

[Formula 1-58]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.91 (d, J = 7.2 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.61 (s, 1H), 7.58 (d, J = 7.2 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.32 (t, J = 7.4 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 6.90 (t, J = 6.8 Hz, 1H), 2.60 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.2, 135.2, 134.4, 128.5, 128.4, 127.6, 126.2, 124.0, 122.2, 122.0, 117.2, 116.7, 113.7, 27.2; LRMS (ESI) m/z calcd for C ₁₆ H ₁₃ NO [M+Na] ⁺ : 235.1, found: 236.1.

Compound GxF 59 :

4-methoxyphenyl boronic acid (52.0 mg, 0.34 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IL-B (20.3 mg, 0.08 mmol) and a mixture of DMF and water 2: 1 (231 mg, 20.0 mol%) and sodium carbonate (36.0 mg, 0.34 mmol) were added, followed by stirring at 100° C. for 13 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 59 (13.3 mg, 0.05 mmol, 62.6) represented by the following formula 1-59 % Yield) was obtained.

[Formula 1-59]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.90 (d, J = 6.8 Hz, 1H), 7.77 (d, J = 6.8 Hz, 1H), 7.55 (s, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.16 (t, J = 7.7 Hz, 1H), 7.01 (t, J = 6.8 Hz, 2H), 6.88 (t, J = 6.8 Hz, 1H), 3.87 (s, 3H), 2.60 ( s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.4, 158.3, 135.5, 129.0, 128.7, 127.2, 124.0, 122.2, 117.5, 116.8, 114.3, 113.9, 55.5, 27.5; LRMS (ESI) m/z calcd for C ₁₇ H ₁₅ NO ₂ [M+Na] ⁺ : 265.1, found: 266.1.

Compound GxF 60 :

In a solution containing IL-B (27.5 mg, 0.11 mmol) and a mixture of DMF and water 2: 1, 4- (dimethylamino) phenyl boronic acid (76.0 mg, 0.46 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (49.0 mg, 0.46 mmol) were added, followed by stirring at 100° C. for 11 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 60 (12.5 mg, 0.04 mmol, 40.8) represented by the following formula 1-60 (12.5 mg, 0.04 mmol, 40.8) % Yield) was obtained.

[Formula 1-60]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.89 (d, J = 6.4 Hz, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.53 (s, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.13 (t, J = 7.8 Hz, 1H), 6.84 (d, J = 6.8 Hz, 3H), 3.00 (s, 6H), 2.59 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.2, 149.3, 135.5, 128.7, 123.7, 122.8, 122.0, 121.9, 117.7, 117.5, 113.8, 113.0, 40.8, 27.5; LRMS (ESI) m/z calcd for C ₁₈ H ₁₈ N ₂ O [M+Na] ⁺ : 278.1, found: 279.2.

<GxF 61 ~ 65>

IM-E : Synthesized as in Scheme 14 below, specifically, DMF (15.0 mL) containing pyridine (564 μL, 7.00 mmol) and bromoacetophenone (1.46 g, 7.35 mmol) was stirred at 100° C. overnight, Ethyl acrylate (373 μL, 3.50 mmol), copper (II) acetate monohydrate (2.09 g, 10.5 mmol) and sodium acetate (1.72 g, 21.0 mmol) were added, followed by stirring at 100° C. for 16 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IM-E (616 mg, 2.10 mmol, 60% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.83 (d, J = 7.2 Hz, 1H), 8.25 (d, J = 9.0 Hz, 1H), 7.73 (d, J = 7.2 Hz, 2H), 7.71 ( s, 1H), 7.46 (d, J = 7.2 Hz, 1H), 7.40 (t, J = 7.2 Hz, 2H), 7.29 (t, J = 8.0 Hz, 1H), 6.93 (t, J = 7.0 Hz, 1H), 4.29 (q, J = 7.0 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.8, 163.4, 139.5, 139.3, 131.1, 128.7, 128.6, 128.4, 128.0, 127.2, 122.1, 121.2, 119.0, 114.9, 105.9, 59.9, 14.5; LRMS (ESI) m/z calcd for C ₁₈ H ₁₅ NO ₃ [M+Na] ⁺ : 293.1, found: 294.2.

IM-B : After adding KOH (7.06 g, 126 mmol) to methanol (20 mL) containing IM-E (616 mg, 2.10 mmol), the mixture was stirred at room temperature for 4 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a white solid compound IM-A.

The obtained compound IM-A was used in the next step without further purification, sodium bicarbonate (529 mg, 6.30 mmol) was added to DMF (10.0 mL) containing IM-A, and NBS (561 mg, 3.15 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IM-B (590 mg, 1.96 mmol, 93.6% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.04 (d, J = 6.8 Hz, 1H), 7.78 (d, J = 6.4 Hz, 2H), 7.61 (d, J = 8.8 Hz, 1H), 7.54 ( d, J = 7.6 Hz, 1H), 7.50 (d, J =7.6 Hz, 2H), 7.37 (s, 1H), 7.30 (m, 1H), 6.98 (t, J = 7.0 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.0, 140.3, 136.9, 131.3, 129.0, 128.8, 128.5, 127.2, 125.4, 122.3, 117.3, 114.8, 89.9, 47.1, 34.8; LRMS (ESI) m/z calcd for C ₁₅ H ₁₀ BrNO [M+Na] ⁺ : 299.0, found: 300.0.

[Scheme 14]

Compound GxF 61 :

4-trifluorophenyl boronic acid (150 mg, 0.79 mmol), tetrakis (triphenyl phosphine) in a solution containing IM-B (59.4 mg, 0.19 mmol) and a mixture of DMF and water 2: 1 After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (84.0 mg, 0.79 mmol), the mixture was stirred at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 61 (33.9 mg, 0.09 mmol, 46.8) represented by the following formula 1-61 % Yield) was obtained.

[Formula 1-61]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.04 (d, J = 6.8 Hz, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.84 (m, J = 6.8 Hz, 2H), 7.67 ( m, J = 2.4 Hz,4H), 7.56 (d, J = 7.2 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 7.49 (s, 1H), 7.31 (m, J = 7.9 Hz, 1H), 6.96 (m, J = 6.9 Hz, 1H); ¹³ C NMR (400 MHz, CDCl ₃ ) δ 184.5, 140.4, 138.3, 136.1, 131.0, 129.0, 128.8, 128.7, 128.4, 128.2, 128.0, 127.7, 125.7, 125.7, 125.7, 125.6, 125.4, 122.9, 122.4, 117.1 , 115.8, 114.4; LRMS (ESI) m/z calcd for C ₂₂ H ₁₄ F ₃ NO [M+Na] ⁺ : 365.1, found: 366.1.

Compound GxF 62 :

In a solution containing IM-B (55.5 mg, 0.18 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (121 mg, 0.74 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (78.7 mg, 0.74 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%), and a yellow solid compound GxF 62 (50.0 mg, 0.14 mmol, 79.2) represented by the following formula 1-62 % Yield) was obtained.

[Formula 1-62]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.02 (d, J = 6.8 Hz, 1H), 8.02 (d, J = 7.2 Hz, 2H), 7.89 (d, J = 8.8 Hz, 1H), 7.84 ( d, J = 6.8 Hz, 2H), 7.69 (d, J = 7.6 Hz, 1H), 7.63 (d, J = 7.6 Hz, 2H), 7.56 (d, J = 7.2 Hz, 1H), 7.53 (s, 1H), 7.51 (s, 1H), 7.29 (t, J = 7.0 Hz, 1H), 7.00 (t, J = 6.6 Hz, 1H), 2.63 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.0, 184.3, 143.9, 140.3, 139.4, 136.2, 136.1, 134.6, 130.9, 128.9, 128.8, 128.7, 128.1, 127.2, 127.1, 125.6, 125.3, 122.4, 117.2, 115.9 , 114.4, 26.7, 26.6; LRMS (ESI) m/z calcd for C ₂₃ H ₁₇ NO ₂ [M+Na] ⁺ : 339.1, found: 340.2.

Compound GxF 63 :

In a solution containing IM-B (61.5 mg, 0.21 mmol) and a mixture of DMF and water 2: 1, phenyl boronic acid (100 mg, 0.82 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, 20.0 mol%) and sodium carbonate (87.0 mg, 0.82 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 63 (56.2 mg, 0.18 mmol, 89.9) represented by the following formula 1-63. % Yield) was obtained.

[Formula 1-63]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.04 (d, J = 6.8 Hz, 1H), 7.89 (d, J = 9.2 Hz, 1H), 7.84 (d, J = 6.8 Hz, 2H), 7.19 ( m, 7H), 7.31 (t, J = 7.4 Hz, 1H), 7.27 (dd, J = 6.6 Hz, 1H), 7.25 (dd, J = 6.6 Hz, 1H), 6.94 (t, J = 6.6 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.9, 140.3, 135.9, 134.2, 130.4, 128.5, 128.4, 127.8, 127.5, 126.1, 125.0, 124.6, 121.8, 117.2, 117.1, 113.8; LRMS (ESI) m/z calcd for C ₂₁ H ₁₅ NO [M+Na] ⁺ : 297.1, found: 298.1.

Compound GxF 64 :

4-methoxyphenyl boronic acid (129 mg, 0.83 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IM-B (62.0 mg, 0.21 mmol) and a mixture of DMF and water 2: 1 (231 mg, 20.0 mol%) and sodium carbonate (88.0 mg, 0.83 mmol) were added, followed by stirring at 100° C. for 9 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and the yellow solid compound GxF 64 (51.4 mg, 0.15 mmol, 74.7) represented by the following formula 1-64 % Yield) was obtained.

[Formula 1-64]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.03 (d, J = 6.8 Hz, 1H), 7.84 (s, 1H), 7.82 (m, 2H), 7.53 (d, J = 6.8 Hz, 1H), 7.50 (s, 1H), 7.48 (m, 4H), 7.40 (s, 1H), 7.23 (m, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.1, 158.3, 140.7, 136.2, 130.7, 128.9, 128.8, 128.8, 128.1, 127.0, 125.0, 124.7, 121.9, 121.3, 117.5, 117.4, 114.2, 114.0, 55.4; LRMS (ESI) m/z calcd for C ₂₂ H ₁₇ NO ₂ [M+Na] ⁺ : 327.1, found: 328.1.

Compound GxF 65 :

In a solution containing IM-B (27.5 mg, 0.11 mmol) and a mixture of DMF and water 2: 1, 4- (dimethylamino) phenyl boronic acid (149 mg, 0.90 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (95.7 mg, 0.90 mmol) were added, followed by stirring at 100° C. for 11 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 65 (67.0 mg, 0.19 mmol, 87) represented by the following formula 1-65. % Yield) was obtained.

[Formula 1-65]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 10.02 (d, J = 7.6 Hz, 1H), 7.87 (s, 1H), 7.84 (d, J = 6.4 Hz, 2H), 7.53 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H), 7.39 (s, 1H), 7.21 (m, 1H), 6.92 (t, J = 7.0 Hz, 1H), 6.82 (d, J = 8.8 Hz, 2H), 2.99 (s, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.9, 149.3, 140.9, 136.2, 130.6, 128.8, 128.7, 128.6, 128.0, 124.7, 124.3, 122.5, 121.8, 121.3, 118.1, 117.7, 113.9, 112.8, 40.7; LRMS (ESI) m/z calcd for C ₂₃ H ₂₀ N ₂ O [M+Na] ⁺ : 340.2, found: 341.2.

<GxF 66 ~ 70>

IN-E : Synthesized as in Scheme 15 below, and specifically, DMF (10.0 mL) containing pyridine (483 μL, 6.00 mmol) and 2-bromo-4-methoxyacetophenone (1.44 g, 6.30 mmol) was prepared at 100° C. After stirring overnight at, ethyl acrylate (320 μL, 3.00 mmol), copper (II) acetate monohydrate (1.79 g, 9.00 mmol) and sodium acetate (1.47 g, 18.0 mmol) were added thereto at 100° C. for 16 hours. While stirring. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IN-E (467 mg, 1.44 mmol, 48.2% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.90 (d, J = 6.8 Hz, 1H), 8.38 (d, J = 8.8 Hz, 1H), 7.85 (s, 1H), 7.83 (d, J = 3.2 Hz, 2H), 7.42 (q, J = 9.0 Hz, 1H), 6.97 (t, J = 7.0 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 4.38 (q, J = 7.1 Hz, 2H), 3.90 (s, 3H), 1.40 (t, J = 7.0 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.6, 163.6, 162.2, 139.2, 132.1, 131.0, 128.7, 127.6, 127.0, 122.3, 121.6, 119.0, 114.7, 113.5, 105.7, 60.0, 55.4, 14.7; LRMS (ESI) m/z calcd for C ₁₉ H ₁₇ NO ₄ [M+Na] ⁺ : 323.1, found: 324.2.

IN-B : After adding KOH (4.84 g, 86.4 mmol) to methanol (10 mL) containing IN-E (467 mg, 1.44 mmol), the mixture was stirred at room temperature for 14 hours. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a white solid compound IN-A.

The obtained compound IN-A was used in the next step without further purification, sodium bicarbonate (363 mg, 4.32 mmol) was added to DMF (5.0 mL) containing IN-A, and NBS (384 mg, 2.16 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IN-B (350 mg, 1.06 mmol, 73.6% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.83 (d, J = 6.8 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 8.8 Hz, 1H), 7.34 ( s, 1H), 7.18 (q, J = 8.8 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 6.89 (t, J = 6.8 Hz, 1H), 3.84 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 184.0, 164.1, 162.2, 139.3, 132.0, 130.9, 128.7, 127.9, 127.1, 122.3, 119.1, 114.8, 113.4, 105.3, 55.4, 51.2.

[Scheme 15]

Compound GxF 66 :

In a solution containing IN-B (50.2 mg, 0.15 mmol) and a mixture of DMF and water 2: 1, 4-trifluorophenyl boronic acid (115 mg, 0.60 mmol), tetrakis (triphenyl phosphine) After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (64.4 mg, 0.60 mmol), the mixture was stirred at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 66 (48.2 mg, 0.12 mmol, 80.2) represented by the following formula 1-66. % Yield) was obtained.

[Formula 1-66]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.96 (d, J = 6.8 Hz, 1H), 7.85 (d, J = 8.8 Hz, 3H), 7.68 (s, 3H), 7.51 (s, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 8.8 Hz, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.8, 162.1, 138.4, 136.1, 132.8, 131.1, 129.0, 128.4, 128.1, 127.8, 126.9, 125.8(2), 125.6, 125.4, 125.1, 122.6, 117.2, 115.7, 115.6, 114.4, 113.6, 55.6; LRMS (ESI) m/z calcd for C ₂₃ H ₁₆ F ₃ NO ₂ [M+Na] ⁺ : 395.1, found: 396.1.

Compound GxF 67 :

In a solution containing IN-B (21 mg, 0.06 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (42 mg, 0.25 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (27 mg, 0.25 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%) to obtain a yellow solid compound GxF 67 (22.6 mg, 0.06 mmol, 97.1) represented by the following formula 1-67. % Yield) was obtained.

[Formula 1-67]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.96 (d, J = 7.2 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.90 (d, J = 9.2 Hz, 2H), 7.86 ( d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.54 (s, 1H), 7.28 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 8.4 Hz, 2H), 3.90 (s, 3H), 2.64 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.1, 183.4, 161.8, 139.4, 135.7, 134.4, 132.5, 130.7, 128.7, 127.1, 125.1, 124.7, 122.4, 177.0, 115.5, 114.0, 113.3, 55.3, 26.4; LRMS (ESI) m/z calcd for C ₂₄ H ₁₉ NO ₃ [M+Na] ⁺ : 369.1, found: 370.2.

Compound GxF 68 :

In a solution containing IN-B (20.0 mg, 0.06 mmol) and a mixture of DMF and water 2: 1, phenyl boronic acid (29.0 mg, 0.24 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, 20.0 mol%) and sodium carbonate (26.0 mg, 0.24 mmol) were added, followed by stirring at 100° C. for 13 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 68 (21.8 mg, 0.06 mmol, 100) represented by the following formula 1-68 % Yield) was obtained.

[Formula 1-68]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.97 (d, J = 6.8 Hz, 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.49 ( s, 1 H), 7.44 ( d, J = 7.6 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.0 (d, J = 8.4 Hz , 2H), 6.92 (t, J = 6.9 Hz, 1H), 6.89 (t, J = 6.8 Hz, 1H), 3.89 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.5, 161.9, 136.0, 134.7, 133.2, 131.0, 128.8, 127.9, 126.4, 126.6, 124.9, 124.6, 123.9, 122.2, 118.6, 117.5, 117.3, 115.4, 114.0, 113.5 , 102.3, 55.6; LRMS (ESI) m/z calcd for C ₂₂ H ₁₇ NO ₂ [M+Na] ⁺ : 327.1, found: 328.2.

Compound GxF 69 :

4-methoxyphenyl boronic acid (38.0 mg, 0.25 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IN-B (20.8 mg, 0.06 mmol) and a mixture of DMF and water 2: 1 (231 mg, 20.0 mol%) and sodium carbonate (26.7 mg, 0.25 mmol) were added, followed by stirring at 100° C. for 13 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to obtain a yellow solid compound GxF 69 (22.6 mg, 0.06 mmol, 100) represented by the following formula 1-69. % Yield) was obtained.

[Formula 1-69]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.96 (d, J = 7.2 Hz, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 7.6 Hz, 1H), 7.48 ( d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.19 (m, J = 8.2 Hz, 1H), 6.99 (dd, J = 8.8 Hz, 4H), 6.93 (t, J = 6.8 Hz, 1H), 3.89 (s, 3H), 3.85 (s, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.7, 162.1, 158.6, 136.2, 133.6, 131.3, 129.3, 129.1, 127.5, 124.9, 124.7, 122.4, 117.8, 117.4, 114.6, 114.2, 113.8, 55.9, 55.8; LRMS (ESI) m/z calcd for C ₂₃ H ₁₉ NO ₃ [M+Na] ⁺ : 357.14, found: 358.1.

Compound GxF 70 :

In a solution containing IN-B (20.0 mg, 0.06 mmol) and a mixture of DMF and water 2: 1, 4- (dimethylamino) phenyl boronic acid (40.0 mg, 0.24 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (26.0 mg, 0.24 mmol) were added, followed by stirring at 100° C. for 13 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 70 (23.8 mg, 0.06 mmol, 100) represented by the following formula 1-70. % Yield) was obtained.

[Formula 1-70]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.96 (d, J = 7.2 Hz, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.83 (s,1H), 7.44 (d, J = 6.8 Hz, 2H), 7.41 (s, 1H), 7.17 (dd, J = 8.8 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 6.90 (t, J = 6.9 Hz, 1H), 6.83 ( d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.99 (s, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.3, 161.8, 149.3, 136.0, 133.5, 131.1, 128.7(2), 124.4, 124.0, 122.9, 117.8, 113.8, 113.5, 113.0, 55.6, 40.9; LRMS (ESI) m/z calcd for C ₂₄ H ₂₂ N ₂ O ₂ [M+Na] ⁺ : 370.2, found: 371.2.

<GxF 71 ~ 75>

IO-E : Synthesized as in Scheme 16 below, specifically, DMF (10.0 mL) containing pyridine (695 μL, 6.00 mmol) and 2-bromo-4'- (diethylamino) acetophenone (1.70 mL, 6.3 mmol) ) Was stirred at 100° C. overnight, and then ethyl acrylate (320 μL, 3.00 mmol), copper (II) acetate monohydrate (1.79 g, 9.00 mmol) and sodium acetate (1.47 g, 18.0 mmol) were added to 100°C. Stirred at °C for 16 hours. After completion of the reaction, after monitoring by TLC, copper acetate was removed by filtration through a pad of Celite, and the resulting filtrate was concentrated under vacuum. The resulting crude product was washed with water and the organic material was extracted 3 times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (hexane 1-15% containing EtOAc) to obtain a yellow solid compound IO-E (273 mg, 0.75 mmol, 25.0% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.94 (d, J = 8.0 Hz, 1H), 8.35 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 6.0 Hz, 1H), 7.86 ( s,2H), 7.34 (m, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.72 (d, J = 9.2 Hz, 2H), 4.41 (q, J = 7.2 Hz, 2H), 3.43 ( q, J = 7.1 Hz, 4H), 1.43 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.2 Hz, 6H).; ¹³ C NMR (100 MHz, CDCl ₃ ) δ 186.8, 156.2, 136.0, 134.4, 129.4, 128.8, 127.8, 126.5, 124.8, 124.4, 124.1, 123.0, 122.1, 120.0, 118.5, 117.5, 117.4, 115.4, 114.3, 113.9 , 102.5, 27.1, 27.9; LRMS (ESI) m/z calcd for C ₂₂ H ₂₄ N ₂ O ₃ [M+Na] ⁺ : 364.2, found: 365.2.

IO-B : KOH (4.20 g, 74.9 mmol) was added to methanol (10 mL) containing IO-E (273 mg, 0.74 mmol), followed by stirring at room temperature overnight. After acidification by adding 6N HCl to the reaction mixture, the resulting solid was obtained through filtration, washed with water and dried in a drying oven to obtain a white solid compound IO-A.

The obtained compound IO-A was used in the next step without further purification, sodium bicarbonate (189 mg, 2.24 mmol) was added to DMF (5.0 mL) containing IO-A, and NBS (200 mg, 1.12 mmol) ) Was added partially at 0°C. After the reaction mixture was stirred at room temperature for 12 hours, the resulting crude product was washed with water and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:8-ethyl acetate 12%) to obtain a yellow solid compound IO-B (187 mg, 0.50 mmol, 67.3% yield).

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.88 (d, J = 7.2 Hz, 1H), 8.03 (s, 1H), 7.83 (s, 1H), 7.69 (dd, J = 8.2 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.41 (s, 1H), 7.28 (m, 1H), 7.12 (d, J = 8.4 Hz, 1H), 6.98 (t, J = 7.0 Hz, 1H), 3.25 (q, J = 6.9 Hz, 4H), 1.10 (t, J = 7.0 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 181.4, 152.2, 136.6, 135.2, 134.9, 128.6, 126.5, 125.1, 122.6, 122.0, 121.9, 120.5, 117.2, 114.6, 89.7, 46.6, 46.43, 12.8, 12.7.

[Scheme 16]

Compound GxF 71 :

4-trifluorophenyl boronic acid (49.0 mg, 0.25 mmol), tetrakis (triphenyl phosphine) in a solution containing IO-B (24 mg, 0.06 mmol) and a mixture of DMF and water 2: 1 After adding palladium (231 mg, 20.0 mol%) and sodium carbonate (27.0 mg, 0.25 mmol), the mixture was stirred at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to form a yellow solid compound GxF 71 (19.0 mg, 0.04 mmol, 72.5) represented by the following formula 1-71. % Yield) was obtained.

[Formula 1-71]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.97 (d, J = 7.2 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.70 ( m, 6H), 7.58 (s, 1H), 7.26 (m, 1H), 7.15 (d, J = 8.4 Hz, 1H), 6.98 (m, 1H), 2.99 (q, J = 7.0 Hz, 4H), 0.98 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.9, 152.2, 136.3, 134.0, 133.7, 133.1, 130.1, 129.3(2), 129.2, 128.2(2), 126.1(2), 125.7,125.6(2), 123.0 , 120.3, 117.5, 115.9, 114.6, 46.2, 30.2, 12.5; LRMS (ESI) m/z calcd for C ₂₆ H ₂₃ F ₃ N ₂ O [M+Na] ⁺ : 436.2, found: 437.2.

Compound GxF 72 :

In a solution containing IO-B (30.0 mg, 0.08 mmol) and a mixture of DMF and water 2: 1, 4-acetylphenyl boronic acid (53.0 mg, 0.32 mmol), tetrakis (triphenyl phosphine) palladium ( 231 mg, 20.0 mol%) and sodium carbonate (34.0 mg, 0.32 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:5-ethyl acetate 40%), and a yellow solid compound GxF 72 (18.9 mg, 0.04 mmol, 57.5) represented by the following formula 1-72 % Yield) was obtained.

[Formula 1-72]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.95 (d, J = 6.8 Hz, 1H), 8.05 (d, J = 7.2 Hz, 3H), 7.90 (s, 1H), 7.71 (d, J = 8.4 Hz, 3H), 7.67 (d, J = 8.4 Hz, 1H), 7.56 (s, 1H), 7.30 (m, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.00 (m, 1H), 3.27 (q, J = 7.0 Hz, 4H), 2.65 (s, 3H), 1.13 (t, J = 7.0 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.1, 182.1, 150.4, 143.9, 139.3, 136.1, 135.9, 134.5, 134.1, 131.5, 128.7, 128.6, 128.4, 127.7, 127.1, 125.3, 124.6, 122.1, 121.4, 117.1 , 115.7, 114.1, 45.8, 29.6, 26.6, 12.3; LRMS (ESI) m/z calcd for C ₂₇ H ₂₆ N ₂ O ₂ [M+Na] ⁺ : 410.2, found: 411.2.

Compound GxF 73 :

Phenyl boronic acid (39.4 mg, 0.32 mmol), tetrakis (triphenyl phosphine) palladium (231 mg, in a solution containing IO-B (30.0 mg, 0.08 mmol) and a mixture of DMF and water 2: 1) 20.0 mol%) and sodium carbonate (34.0 mg, 0.32 mmol) were added, followed by stirring at 100° C. for 13 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and the yellow solid compound GxF 73 (22.2 mg, 0.06 mmol, 75.3) represented by the following formula 1-73 % Yield) was obtained.

[Chemical Formula 1-73]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.98 (d, J = 7.2 Hz, 1H), 7.87 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.59 ( m, 3H), 7.46 (m, 2H), 7.38 (m, 2H), 7.30 (d, J = 7.6 Hz, 1H), 7.20 (m, 1H), 7.12 (dd, J = 8.2 Hz, 1H), 6.94 (d, J = 7.0 Hz, 1H), 3.01 (q, J = 4.4 Hz, 4H), 0.97 (t, J = 7.0 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 183.5, 151.4, 141.1, 135.6, 134.6, 133.0, 132.7, 128.8, 128.5, 128.3, 128.0, 127.6, 126.4, 126.1, 124.5, 124.1, 122.1, 121.1, 119.3, 117.2 , 116.8, 113.6, 45.9, 45.5, 12.0; LRMS (ESI) m/z calcd for C ₂₅ H ₂₄ N ₂ O [M+Na] ⁺ : 368.2, found: 369.2.

Compound GxF 74 :

4-methoxyphenyl boronic acid (65.0 mg, 0.42 mmol), tetrakis (triphenyl phosphine) palladium in a solution containing IO-B (39.5 mg, 0.10 mmol) and a mixture of DMF and water 2: 1 (231 mg, 20.0 mol%) and sodium carbonate (45.0 mg, 0.42 mmol) were added, followed by stirring at 100° C. for 13 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%) to obtain a yellow solid compound GxF 74 (42.5 mg, 0.10 mmol, 100) represented by the following formula 1-74. % Yield) was obtained.

[Formula 1-74]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.95 (d, J = 6.8 Hz, 1H), 7.89 (s, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.70 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.44 (s, 1H), 7.22 (m, 1H), 7.11 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 6.8 Hz, 2H), 6.96 (t, J = 7.2 Hz, 2H), 3.86 (s, 3H), 3.26 (q, J = 7.1 Hz, 4H), 0.96 (t, J = 7.2 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 182.2, 158.4, 150.4, 136.3, 135.0, 131.8, 129.7, 129.1, 128.9, 128.0, 127.1, 124.7, 124.6, 121.8(2), 117.6, 117.4, 114.4, 114.1, 113.7, 55.5, 46.7, 45.7, 29.9, 12.6; LRMS (ESI) m/z calcd for C ₂₆ H ₂₆ N ₂ O ₂ [M+Na] ⁺ : 398.2, found: 399.4.

Compound GxF 75 :

In a solution containing IO-B (73.0 mg, 0.16 mmol) and a mixture of DMF and water 2: 1, 4-(dimethylamino) phenyl boronic acid (109 mg, 0.66 mmol), tetrakis (triphenyl phosphine) Fin) palladium (231 mg, 20.0 mol%) and sodium carbonate (70.0 mg, 0.66 mmol) were added, followed by stirring at 100° C. for 12 hours. After completion of the reaction, it was monitored by TLC, washed with water, and the organic material was extracted three times with DCM. The extracted organic materials were combined, dried over anhydrous Na ₂ SO ₄ and concentrated. The concentrated organic phase was purified by silica-gel flash column chromatography (EA: Hexane = 1:4-ethyl acetate 25%), and a yellow solid compound GxF 75 (257.8 mg, 0.14 mmol, 84.6) represented by the following formula 1-75 % Yield) was obtained.

[Formula 1-75]

The NMR analysis results are as follows.

¹ H NMR (400 MHz, CDCl ₃ ), δ 9.95 (d, J = 6.8 Hz, 1H), 7.89 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.70 (dd, J = 8.4 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.43 (s, 1H), 7.20 (m, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.94 (t, J = 6.8 Hz, 1H), 6.84 (d, J = 6.8 Hz, 2H), 3.26 (q, J = 7.1 Hz, 4H), 3.00 (s, 6H), 1.12 ( t, J = 7.0 Hz, 6H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 197.5, 197.2, 183.5, 151.8, 146.4, 139.7, 135.9, 135.4, 134.7, 133.6, 133.1, 132.7, 129.7, 129.0, 128.9, 128.7, 128.5, 127.4, 125.3, 124.7 , 122.7, 119.8, 117.3, 115.7, 114.2, 45.8, 26.8, 12.2; LRMS (ESI) m/z calcd for C ₂₇ H ₂₉ N ₃ O [M+Na] ⁺ : 411.2, found: 412.3.

Confirmation of photophysical properties of 75 kinds of GxF materials

In the present invention, 75 kinds of synthesized in Example 1 The photophysical properties of the GxF materials were observed.

UV absorption of the final fluorescent compound was measured using a UV-VISIBLE spectrophotometer (JASCO V-670, JASCO, INC. Japan), and the excitation fluorescent emission wavelength is a JASCO fluorescence spectrophotometer (JASCO FP-8200, JASCO, INC. Japan). Quantum yield (absolute quantum yield) was measured by the Absolute PL quantum yield measurement system (QE-2000, Otsuka Electronics, Japan).

(T: Trifluoromethyl, A: Acetyl, H: Hydrogen, T _P :4-trifluoromethylphenyl, C: Methyl, M _P : 4-methoxyphenyl, DE _P : 4-Diethylaminophenyl, M: Methoxy, DM: dimethylamino, L: solution state , S: solid state, λ _A : Absorption maxima, λ _E : Emission maxima, ε: extinction coefficient (x10 ⁴ ) in solution state, Φ: quantum yield (%) in solution state, H: HOMO energy level (ev), L: LUMO energy level (ev), gap: energy gap between LUMO and HOMO ( ev))

As shown in Table 1, it was confirmed that the GxF materials cover the entire visible light range from 416 nm to 620 nm, and in particular, as shown in FIG. 7, the GxF materials can exhibit solid state fluorescence. Confirmed.

As shown in FIG. 8, in the case of the GxF 63 material, it was confirmed that the fluorescence brightness was affected by the change in the dielectric constant of the solvent in the solution.

In addition, as a result of confirming whether the GxF material exhibits solid state fluorescence, as shown in FIG. 9, four different GxF materials (GxF 1, GxF 3, GxF 5, GxF 11) are in the entire visible light region even in the solid state. It was confirmed that it has an emission wavelength that encompasses.

Observation of fluorescence changes in the solid phase of GxF substances according to different VOC exposures

In the present invention, in order to check whether the fluorescence change occurs in the solid state in response to the GxF substances in response to VOC, substances GxF 15, GxF 40, and GxF 65 are applied as a film on the glass, and then three different VOC vapors (ethyl acetate, acetic acid) are applied. acid, ethylamine) was exposed to observe the change in fluorescence.

_{Specifically, each substance is dissolved in chloroform (CHCl 3} ) at a concentration of 20 mg/mL, and then the slide glass is washed in deionized water, acetone, and isopropanol for 10 minutes with an ultrasonic generator, and then for about 20 minutes. Disinfect by exposure to UV. The mother liquor was spin-coated on a slide glass at 1500 rpm for 1 minute to obtain a coated film, and then 3 different VOC vapors (Ethyl acetate, acetic acid, ethylamine) were added to each of 5 mL in a glass container and saturated It was sealed and the applied film was attached to the inside of the glass container lid and exposed to a glass container saturated with VOC vapor for 1 minute. After 1 minute of exposure time, each film was subjected to absorption and emission spectrum data using a JASCO V-670 spectrophotometer and a JASCO FP-8200 spectrofluorimeter.

As a result, as shown in FIG. 10, it was confirmed that the three substances were exposed to three different VOCs to induce changes in the fluorescence phenomena of each.

Fluorescence sensor array fabrication for volatile organic compound detection

In the present invention, a sensor array in which the compounds represented by Chemical Formulas 2 to 76 are patterned and fixed was fabricated.

For uniform application of fluorescent materials, an array frame was manufactured using wax printing on filter paper. After designing the array frame using Hancom Office Hangul 2010 program, xerox ColorQube on HYUNDAI MICRO Qualitative Filter Paper (No. 22) The print was done with wax using 8870. The wax-coated qualitative filter paper as an array frame was heated for 5 minutes at a temperature of about 150°C. The line thickness before heating is 0.7 mm, and the line thickness after heating is 1.0 mm as the wax melts by heat. Then, after cooling the prepared array frame sufficiently for 1 hour, spotting on the array coated with a wax stock solution of 75 GxF materials made with 10 mM DMSO (Dimethyl Sulfoxide) solvent. ) After that, dry the array coated with the GxF materials in a dry oven for 10 minutes.

As shown in FIG. 11, a sensor array containing 25 new phosphors per fluorescent sensor array having a size of 2.5 cm X 2.5 cm was prepared, and the degree of luminescence of the fluorescent material was observed under UV.

Observation of changes in fluorescence pattern according to VOC exposure

In the present invention, in order to check whether the fluorescent sensor array can react with VOC to form a specific fluorescent pattern, three fluorescent sensor arrays, each of which 25 kinds of 75 kinds of GxF materials are applied, are placed in a sealed container as shown in FIG. 12. Introduced and exposed to VOC. In the present invention, for this purpose, a system capable of implementing an ideal light composition by adjusting the position of the ultraviolet light source and the position of the smartphone camera using 3D printing technology was devised, and is shown in FIG. 13.

Specifically, in order to analyze the color change of the array, the fluorescence sensor array before VOC exposure and the fluorescence sensor array after VOC exposure are photographed with a smartphone camera, and then the colors of 75 phosphors in the fluorescence sensor before exposure and the fluorescence sensor after exposure in the two pictures. After extracting the colors of 75 phosphors, the colors were expressed in RGB, HSV, and CIELAB color spaces. In order to find the difference between the two colors, a method according to the characteristics of each color space was used, in the case of the RGB color space, the RGB Euclidean distance (expression (3) in Fig. 14) was used, and in the case of the HSV color space, the Hue difference ( Figure 14 (4)) was used, and CIEDE2000 (an industry standard for calculating color differences) was used in the CIELAB color space.

A machine learning algorithm capable of automatically analyzing the color change information of the fluorescence sensor array obtained through this was developed, and change information in the color space of RGB, HSV, and CIELAB was analyzed as shown in FIG. 14.

Ethanol, 1-Butanol, 1-(Pentanol), 1-Hexanol, 3-Hexanol, and 35 volatile organic compounds ), Phenol, 1-Heptanol, 1-Decanol, 2-Decanol, 3-Decanol, 1-Dode Canol (1-Dodecanol), Cyclopentanol, Cyclohexanol, Cycloheptanol, Benzene, Acetone, 2-Octanone, 2- Picoline (2-Picoline), 3-Picoline (3-Picoline), 3-acetylpyridine (3-Acetylpyridine), 4-acetylpyridine (4-Acetylpyridine), 2-heptylamine (2-Heptylamine), di- Di-n-propylamine, 2-Phenylethylamine, Cyclooctylamine, Propionic acid, 3-Bromopropionic acid, 2-methyl 2-Methylbutyric acid, Formic acid, Valeric acid, Trifluoroacetic acid, Bromoacetic acid, Acetic acid, Trichloroacetic acid ) And 2-Chloropropionic acid were exposed to the sensor array prepared in Example 5 five times, and then, as a result of monitoring each change of the fluorescent sensors, as shown in FIG. 16, indolizine-based fluorescence It was confirmed that the sensor array showed different patterns of change in response to 35 types of VOCs.

In order to confirm the pattern change of the fluorescent substances according to the VOC exposure, a principal component analysis method (Principa Component Analysis) was performed. Through the principal component analysis method, two significant principal components, which can represent the most complete data, were extracted out of 75 patterns of color change of fluorescent substances. 17 is a graph showing two main components on a two-dimensional plane. As a result of PCA using Hue value (color information value) before/after exposure, it was confirmed that each VOC can be visually distinguished on the graph, carboxylic acid (Carboxylic acid, 58.1%), alcohol (Alcohol, 57.6%), It was confirmed that it was identified as an aliphatic amine (Aliphatic amine, 61.9%) and an aromatic amine (Aromatic amine, 53.4%) (FIG. 17).

VOC determination through machine learning analysis

In the present invention, based on the above results, RGB, Hue value, and CIEDE2000 (difference between color brightness and color) are machined from among pattern change information of a fluorescent sensor array in order to check whether the VOC type can be further distinguished using artificial intelligence. The degree of VOC discrimination was confirmed by learning with a machine learning algorithm.

For the five representative VOC substances (Acetic acid, Acetone, Ethylendiamine, Phenol, Toluene), 100 repeated experiments were conducted, and 100 data samples for each VOC substance were randomly divided into training data and test data in a ratio of 7:3. . Each data sample consists of 75 fluorophore color change patterns. Using the results, 75 color change patterns of fluorescent substances were learned from the training data using machine learning algorithms such as K-Means and Random forest, which are statistical classification methods. At this time, three VOC classification models were created for each algorithm by learning with three different color change features such as RGB distance, Hue difference, and CIEDE2000.

As a result, as shown in FIG. 18, it was confirmed that the learned algorithm can accurately predict the VOC through analysis of the change in the fluorescence sensor image pattern with a high accuracy of 97% of the inspection data. Also, among the three color change features, RGB distance and CIEDE2000 information showed the best performance.

Claims (10)

Fluorescent compound represented by the following formula (1):
[Formula 1]

In Formula 1 above
R ₁ is hydrogen; Nitrile group; halogen; Nitro group; C1-C6 alkoxy group; C6-C20 aryl group; C5-C20 cycloheterocyclic group; Boron group; Azide group; NR ₄ R ₅ (wherein R ₄ and R ₅ are each independently hydrogen, C1-C10 alkyl group, C6-C20 aryl group or C4-C20 heteroaryl group), nitrile, C1-C6 alkoxy, halogen , A boron group, a hydroxy group, or CH ₂ NR ₄ R ₅ (wherein R ₄ and R ₅ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group) A C6-C20 aryl group substituted with; C1-C8 linear or branched alkyl group; C2-C8 alkenyl group; C2-C8 alkynyl group; C3-C8 cycloalkyl group; Or a C4-C20 heteroaryl group,
R ₂ is hydrogen; C1-C8 linear or branched alkyl group; C2-C8 alkenyl group; C2-C8 alkynyl group; C3-C8 cycloalkyl group; Hydroxy group; C1-C6 alkoxy group; Polyethylene glycol group; Nitrile group; Nitro group; Carboxyl group; Sulfonyl group; Azide group; Methanesulfonyl group; Maleimide group; Alcohols protected by tertiary-butyldimethylsilyl group (TBS); Or NR ₆ R ₇ (wherein R ₆ and R ₇ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group or a C4-C20 heteroaryl group),
R ₃ is hydrogen; halogen; Nitrile group; Boron group; Hydroxy group; COY (wherein Y is hydrogen, a C1-C8 linear or branched alkyl group, a C2-C8 alkenyl group, a C2-C8 alkynyl group, a C3-C8 cycloalkyl group, or NR ₈ R ₉ (herein, R ₈ and Each R ₉ is independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group]); C1-C6 alkoxy group; C6-C20 aryl group; Or NR ₁₀ R ₁₁ (Wherein, R ₁₀ and R ₁₁ are each independently hydrogen, a C1-C10 alkyl group, a C6-C20 aryl group, or a C4-C20 heteroaryl group), a C6-C20 aryl group substituted with nitrile or halogen. .
The method of claim 1, wherein R ₁ is hydrogen; Trifluoromethyl group; Acetyl group; Methoxy group; Or a dimethylamine group,
R ₂ is methyl; Trifluoromethylphenyl group; Phenyl group; Methoxyphenyl group; Or a diethylamine phenyl group,
R ₃ is hydrogen; Trifluoromethyl group; Or a fluorescent compound, characterized in that the acetyl group.
The fluorescent compound according to claim 1, wherein the fluorescent compound has an emission wavelength of 400 nm to 620 nm, and exhibits liquid or solid state fluorescence.
(a) reacting a compound of formula A and a compound of formula B to prepare a compound of formula C;
(b) reacting the compound of Formula C with ethyl acrylate, sodium acetate, and copper acetic acid monohydrate to prepare a compound of Formula D;
(c) preparing a compound of Formula E by reacting the compound of Formula D and NBS (N-Bromosuccinimide); And
(d) reacting the compound of Formula E and the compound of Formula F to prepare a compound of Formula 1, and a method for preparing a fluorescent compound of Formula 1 represented by the following Scheme 1:
[Scheme 1]

R ₁ is hydrogen; Trifluoromethyl group; Acetyl group; Methoxy group; Or a dimethylamine group, and R ₂ is methyl; Trifluoromethylphenyl group; Phenyl group; Methoxyphenyl group; Or a diethylaminephenyl group, and R ₃ is hydrogen; Trifluoromethyl group; Or an acetyl group.
A composition for detecting volatile organic compounds (VOC) comprising the fluorescent compound of any one of claims 1 to 3.
A sensor array for detecting volatile organic compounds comprising the fluorescent compound of claim 1.
The method of claim 6, wherein the volatile organic compound is ethanol (Ethanol), 1-butanol (1-Butanol), 1- (pentanol (1-Pentanol), 1-hexanol (1-Hexanol), 3-hexane 3-Hexanol, Phenol, 1-Heptanol, 1-Decanol, 2-Decanol, 3-Decanol ), 1-Dodecanol, Cyclopentanol, Cyclohexanol, Cycloheptanol, Benzene, Acetone, 2-octanone (2- Octanone), 2-picoline (2-Picoline), 3-picoline (3-Picoline), 3-acetylpyridine (3-Acetylpyridine), 4-acetylpyridine (4-Acetylpyridine), 2-heptylamine (2- Heptylamine), Di-n-propylamine, 2-Phenylethylamine, Cyclooctylamine, Propionic acid, 3-Bromopropionic acid ), 2-Methylbutyric acid, Formic acid, Valeric acid, Trifluoroacetic acid, Bromoacetic acid, Acetic acid, Triclo Roacetic acid (Trichloroacetic acid) and 2-chloropropionic acid (2-Chloropropionic acid) a sensor array for detecting volatile organic compounds, characterized in that at least one material selected from the group consisting of.
A method for detecting a volatile organic compound using the fluorescent compound according to any one of claims 1 to 3.
The method of claim 8, wherein the method comprises: (a) exposing a volatile material to a sensor array for detecting a volatile organic compound to which a fluorescent compound is fixed, and then measuring a change in a fluorescence pattern; And
(b) learning the pattern change through a machine learning algorithm.
The detection method of claim 8, wherein in step (b), the RGB distance, hue value, or CIEDE2000 information of the pattern is learned through a machine learning algorithm.

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