Method for producing condensed polycyclic aromatic compounds having an ethynyl group

Abstract

To provide a production method of an aromatic compound having an ethynyl group, with which a coupling reaction can be simply and inexpensively conducted by using a condensed polycyclic aromatic compound having nitrogen.SOLUTION: In a production method of a condensed polycyclic aromatic compound having an ethynyl group as shown in the general formula (3), a coupling reaction of the condensed polycyclic aromatic compound, derived from a nitrogen-containing heterocycle and a halogenated benzene ring, with an ethynyl compound is conducted in a nitrogen-containing organic solvent in the presence of an amine, together with palladium carbon, a phosphorus compound, and a copper compound. (In formula, a ring N indicates a nitrogen-containing heterocycle, and A indicates a hydrocarbon group having a hydroxy group or a trialkylsilyl group.)SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing a condensed polycyclic aromatic compound having an ethynyl group. [Background technology]

[0002] Coupling reactions using aromatic halides and palladium catalysts are important for forming new carbon-carbon bonds. For example, in the Sonogashira coupling reaction, aromatic halides and ethynyl compounds are coupled using a palladium catalyst to synthesize ethynylbenzene compounds in which the ethynyl compound is bonded to the aromatic ring. The palladium catalysts used here are generally organic palladium catalysts such as dichlorobis(triphenylphosphine)palladium and tetra(triphenylphosphine)palladium.

[0003] On the other hand, fused polycyclic rings consisting of nitrogen-containing heterocycles and benzene rings have various structures, such as 1H-indazole, 3H-indazole, indole, etc. The Sonogashira coupling of compounds containing halogen atoms in the fused polycyclic rings with acetylene compounds is used as an intermediate for pharmaceuticals, etc.

[0004] For example, in the Sonogashira coupling of 5-bromo-1H-indazole with ethynyltrimethylsilane as an intermediate in the complement system for age-related macular degeneration (AMD), a very large amount of palladium catalyst (2.78 mol %) is used relative to the starting indazole, but the yield is only 49%, posing a significant challenge to industrialization. The palladium catalyst used here is dichlorobis(triphenylphosphine)palladium, which has a palladium chloride structure. The palladium catalyst is unstable and easily hydrolyzed with water, making it difficult to handle in the reaction (see Patent Document 1).

[0005] Furthermore, in a Sonogashira coupling using 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole, which is obtained by protecting 5-bromo-1H-indazole, an intermediate for a breast cancer treatment, with 2-tetrahydropyran, the yield was only 49%, despite the fact that the amount of palladium catalyst used was a large 1.97 mol% relative to the raw material, making industrial production in this reported example appear difficult. The palladium catalyst used here also has the palladium chloride structure described above, and is a catalyst that is unstable and difficult to handle (see Patent Document 2).

[0006] Thus, there has been a demand for a production method for introducing an ethynyl group in a coupling reaction of a fused polycyclic aromatic compound having a nitrogen-containing heterocycle, which can be synthesized simply and inexpensively and in high yield. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Special Publication No. 2015-522006 [Patent Document 2] Special Publication No. 2018-516250 Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to produce an aromatic compound having an ethynyl group, which is a fused polycyclic aromatic compound having a nitrogen-containing heterocycle, by a simple procedure and in high yield. [Means for solving the problem]

[0009] The present invention relates to a compound represented by the following general formula (1): [ka] (In the formula, cyclic N represents a nitrogen-containing heterocycle, and X represents a halogen atom.) and a condensed polycyclic aromatic compound represented by the following general formula (2 [ka] (In the formula, A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group.) In a coupling reaction with an ethynyl compound represented by the following general formula (3), the coupling reaction is carried out in the presence of an amine, together with palladium carbon, a phosphorus compound, and a copper compound, in a nitrogen-containing organic solvent: [ka] (In the formula, cyclic N represents a nitrogen-containing heterocycle, and A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group.) The present invention relates to a method for producing a condensed polycyclic aromatic compound having an ethynyl group represented by the formula: [Effects of the Invention]

[0010] The method for producing a fused polycyclic aromatic compound having an ethynyl group of the present invention can synthesize the target fused polycyclic aromatic compound having an ethynyl group in high yield by performing Sonogashira coupling using palladium on carbon as a catalyst, and since the compound can be produced by a simple procedure, it can be provided industrially at a low cost.

[0011] Furthermore, the condensed polycyclic aromatic compounds having an ethynyl group obtained by the present invention can be used as raw materials for fine chemicals, pharmaceutical and agricultural chemicals, resins and plastics, and electronic and optical materials. DETAILED DESCRIPTION OF THE INVENTION

[0012] The production method of the present invention will be described in detail below. In this specification, the following general formula may be referred to as "cyclic N" and represents a nitrogen-containing heterocycle. [ka]

[0013] The raw material used in the present invention is a nitrogen-containing fused polycyclic aromatic compound represented by the following general formula (1). [ka] (In the formula, cyclic N represents a nitrogen-containing heterocycle, and X represents a halogen atom.)

[0014] Here, the nitrogen-containing condensed polycyclic aromatic compound represented by general formula (1) specifically refers to a halogen derivative of an aromatic compound containing a nitrogen-containing heterocycle, such as isoindole, 3H-indole, indole, 1H-indazole, isoquinoline, quinoline, isoquinoline, phthalazine, quinoxaline, quinazoline, cinnoline, etc. In particular, halogen derivatives of isoindole, indole, or 1H-indazole are particularly preferred because the raw materials are easily available and inexpensive.

[0015] X represents a halogen atom, such as chlorine, bromine, or iodine. In terms of reactivity in a coupling reaction, chlorine atoms generally have low reactivity and the coupling reaction hardly proceeds, so bromine and iodine are preferred, and iodine is particularly preferred as X because iodine is highly reactive but expensive.

[0016] Particularly preferred nitrogen-containing fused polycyclic aromatic compounds include 5-bromoisoindole, 6-bromoisoindole, 5-bromoindole, 6-bromoindole, 5-bromo-1H-indazole, and 6-bromo-1H-indazole.

[0017] In the present invention, the coupling reaction proceeds by adding raw materials, that is, a nitrogen-containing fused polycyclic aromatic compound, palladium on carbon, a phosphorus compound, a copper compound, and an amine, to a nitrogen-containing organic solvent as a reaction solvent, and then adding dropwise or pouring in an ethynyl compound represented by the following general formula (2) with stirring, and heating the mixture. [ka] (In the formula, A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group.)

[0018] Here, the nitrogen-containing organic solvent used as the reaction solvent is preferably N,N-dimethylacetamide, dimethylformamide, or N-methyl-2-pyrrolidone, and particularly preferably N,N-dimethylacetamide, which has a high reactivity.

[0019] Because the halogen amine salt produced in the coupling reaction must be stirred in a slurry state, the nitrogen-containing organic solvent is preferably used in an amount 3 to 10 times by mass, and particularly preferably 3 to 7 times by mass, relative to the nitrogen-containing condensed polycyclic aromatic compound used as the raw material. If the amount of the nitrogen-containing organic solvent used is less than 3 times by mass, compounds such as dimers formed by coupling of the ethynyl compounds used in the reaction are undesirably produced as by-products.

[0020] The palladium-carbon used in coupling reactions is a carrier on which palladium (zerovalent) is dispersed and supported, also known as palladium-carbon. Palladium-carbon can be used in either dry or wet forms. Because dry palladium-carbon readily ignites in air, wet forms are preferred for industrial applications. The type of palladium-carbon affects the reactivity of the coupling reaction, and commercially available palladium-carbon from N.E. Chemcat Corporation is particularly preferred due to its high reactivity. Among the palladium-carbons from N.E. Chemcat Corporation, Type NE, Type K, and Type E are particularly preferred, as they offer high reaction yields. Among these, Type E is particularly preferred, as it allows for a reduced amount of palladium-carbon to be used.

[0021] Palladium on carbon is an expensive catalyst, so it is preferably used in an amount of 1.5 mol % or less relative to the number of moles of the nitrogen-containing condensed polycyclic aromatic compound, and more preferably 1.0 mol % or less, which allows for less use and cheaper production.

[0022] The phosphorus compound used in the coupling reaction is preferably an organic phosphorus compound, and is preferably a hydrocarbon phosphine compound such as triphenylphosphine, trimethylphosphine, triethylphosphine, or tri-n-propylphosphine, which is widely available. Triphenylphosphine is particularly preferred because it is generally available at low cost and is easy to handle as a granular powder. The amount of the phosphorus compound used is preferably 4.0 equivalents or more relative to palladium carbon, and more preferably 4.0 to 8.0 equivalents, which is sufficient to form a palladium complex.

[0023] A copper compound is used as a reaction initiator, and copper iodide, which is widely available, is preferred. The amount of the copper compound used is preferably 0.1 to 1.0 equivalents, more preferably 0.1 to 0.5 equivalents, based on palladium carbon.

[0024] In the Sonogashira coupling reaction, amines are added to trap the halogen by-products produced in the reaction. As the amine, alkylamines are preferred, and tertiary amines such as trimethylamine, triethylamine, tri-n-propylamine, and tri-n-butylamine, and secondary amines such as diisobutylamine, diisopropylamine, and diethylamine are preferred. Triethylamine, diisopropylamine, and diisobutylamine are more preferred because they are inexpensive, easily available, have low boiling points, and can be removed by concentration.

[0025] The amount of amine to be added is preferably 1.0 to 5.0 equivalents, more preferably 1.0 to 3.0 equivalents, relative to the nitrogen-containing condensed polycyclic aromatic compound as the raw material.

[0026] The ethynyl compound used is a compound represented by the following general formula (2): When A in the general formula (2) is a hydrocarbon group having a hydroxyl group, the ethynyl compound is preferably a compound represented by the following general formula (4): [ka] (In formula (4), R 1 , R 2 indicates a hydrogen atom or a hydrocarbon group) In general formula (4), R 1 , R 2 may be the same or different. 1 , R 2 is preferably a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, such as hydrogen, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an n-pentyl group, etc. Preferred examples of the ethynyl compound represented by general formula (4) include 2-propyn-1-ol, 2-methyl-3-butyn-2-ol, 3-butyn-2-ol, 3-methyl-4-pentyn-3-ol, 4-pentyn-3-ol, 4-methyl-5-hexyn-4-ol, 5-hexyn-4-ol, etc.

[0027] When A in the general formula (2) is a trialkylsilyl group, the ethynyl compound is preferably a compound represented by the following general formula (5): [ka] (In formula (5), R 1 ,R 2 ,R 3 indicates a hydrocarbon group) In general formula (5), R 1 ,R 2 ,R 3 may be the same or different. 1 ,R 2 ,R 3 is preferably an alkyl group having 1 to 5 carbon atoms, such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an n-pentyl group, etc. Preferred examples of the ethynyl compound represented by general formula (5) include trimethylsilylacetylene, triethylsilylacetylene, triisopropylsilylacetylene, etc.

[0028] In view of industrial availability, the ethynyl compound represented by the general formula (2) is more preferably 2-methyl-3-butyn-2-ol, 3-butyn-2-ol, or 2-propyn-1-ol.

[0029] The amount of the ethynyl compound used is preferably 1.0 to 5.0 equivalents relative to the halogen of the condensed polycyclic aromatic compound as a raw material, and more preferably 1.0 to 3.0 equivalents, since an excess amount will result in excessive by-production of compounds such as dimers of ethynyl compounds resulting from the reaction between ethynyl compounds.

[0030] In the Sonogashira coupling reaction, a nitrogen-containing compound (solvent), a condensed polycyclic aromatic compound (raw material), palladium on carbon (catalyst), a copper compound (reaction initiator), and an amine (halogen trap) are added to a reactor, followed by the dropwise addition of an ethynyl compound and heating. The reaction temperature is preferably 30°C or higher, where the reaction proceeds easily, and more preferably 50°C or higher, where the reaction proceeds more smoothly.

[0031] The coupling reaction can be monitored by analyzing the reaction with a gas chromatograph or high performance liquid chromatography. The reaction time for the coupling reaction is preferably 1 hour or more, more preferably 2 hours or more.

[0032] After the coupling reaction is completed, the mixture is cooled, water is added to dissolve the amine salt, and the amine salt is extracted with an organic solvent such as toluene or ethyl acetate to obtain a compound represented by the following general formula (3): [ka] (In the formula, cyclic N represents a nitrogen-containing heterocycle, and A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group.) In this case, the palladium carbon used in the reaction can be easily removed by filtration.

[0033] A in the general formula (3) is the same as A in the general formula (2), and therefore further explanation is omitted. In addition, examples of the condensed polycyclic aromatic compound having an ethynyl group represented by the general formula (3) include 5-(3-hydroxy-3-methyl-1-butyn-1-yl)isoindole, 6-(3-hydroxy-3-methyl-1-butyn-1-yl)isoindole, 5-(3-hydroxy-1-butyn-1-yl)isoindole, 6-(3-hydroxy-1-butyn-1-yl)isoindole, 5-(trimethylsilylethynyl)isoindole, 6-(trimethylsilylethynyl)isoindole, 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole, 6-(3-hydroxy-3-methyl-1-butyn-1-yl)indole, 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole,

[0033] Examples of the hydroxy-1-butyn-1-yl indole include 6-(3-hydroxy-1-butyn-1-yl)indole, 6-(3-hydroxy-1-butyn-1-yl)indole, 5-(trimethylsilylethynyl)indole, 6-(trimethylsilylethynyl)indole, 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole, 6-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole, 5-(3-hydroxy-1-butyn-1-yl)-1H-indazole, 6-(3-hydroxy-1-butyn-1-yl)-1H-indazole, 5-(trimethylsilylethynyl)-1H-indazole, and the like.

[0034] The ethynyl-containing fused polycyclic aromatic compound represented by general formula (3) obtained by the present invention can easily remove the substituent A bonded to the terminal of the ethynyl group by, for example, using alkaline conditions. Thus, in the present invention, an ethynyl-containing fused polycyclic aromatic compound can be synthesized simply by introducing palladium on carbon and carrying out the Sonogashira coupling reaction, making it possible to provide useful ethynyl-containing fused polycyclic aromatic compounds. [Example]

[0035] The present invention will be specifically described below with reference to examples. In the examples, the reaction yield (area %) of the aromatic compound having an ethynyl group represented by the general formula (3) was measured by analyzing using HPLC (high performance liquid chromatography) under the following conditions, and the area % was measured as the fraction of the peak area of ​​each compound relative to the area obtained by subtracting the peak area of ​​the nitrogen-containing organic solvent from the total peak area.

[0036] Here, the reaction yield of the aromatic compound having an ethynyl group represented by general formula (3) (referred to as the "coupling product" in the following calculation formula) is a numerical value indicating the extent to which the reaction to obtain the target coupling product from the raw material, the nitrogen-containing condensed polycyclic aromatic compound represented by general formula (1) (referred to as the "raw material" in the following calculation formula), has progressed, and was calculated as follows: Area% of coupling body / (area% of coupling body + area% of raw material) x 100(%) <Purity analysis> Column: YMC-Pack ODS-AM (250 x 4.6 mm I.D.) Eluent: Solution A - acetonitrile; Solution B - 0.1% phosphoric acid aqueous solution Analysis temperature: 40℃ Flow rate: 1mL / min Mobile phase: (1) Analysis of the reaction mixture with 2-methyl-3-butyn-2-ol (MBYO): A / B = 30 / 70 (10-minute hold) → 70 / 30 (gradient up to 30 minutes) → 70 / 30 (10-minute hold) (2) Analysis of reaction solution with trimethylsilylacetylene (TMSA): A / B = 50 / 50 (10-minute hold) → 80 / 20 (gradient up to 30 minutes) → 80 / 20 (10-minute hold) Injection volume: 0.5μL Detector: UV (254 nm) Analysis time: 40 minutes Sample preparation: 0.1 g of sample was weighed into a 20 mL volumetric flask and made up to volume with acetonitrile. The reagents used in the experiments were commercially available. Palladium on carbon (Pd / C) manufactured by N.E. Chemcat Corporation was purchased from Fujifilm Wako Pure Chemical Industries.

[0037] [Example 1] Synthesis of 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole using palladium on carbon A 200 mL flask equipped with a stirrer and a condenser was charged with 5.0 g (25.5 mmol) of 5-bromoindole (5-BID), 25 g (5 equivalents / 5-BID) of N,N-dimethylacetamide (DMAc), 1.19 g (0.255 mmol, 1.0 mol% / 5-BID) of 5% palladium on carbon (Pd / C; Type K, Pd content 5.2% by mass, 44% by mass water content), 0.334 g (1.28 mmol) of triphenylphosphine, 0.0607 g (0.319 mmol) of copper(I) iodide, and 5.16 g (51.0 mmol, 2.0 equivalents / 5-BID). 4.29 g (51.0 mmol, 2.0 equivalents / 5-BID) of 2-methyl-3-butyn-2-ol was added dropwise at 20-30 °C. After the dropwise addition, the mixture was placed in an oil bath and reacted at a temperature of 70-75°C for 24 hours. After 24 hours, the reaction mixture was analyzed by high-performance liquid chromatography (HPLC). The reaction yield of the target 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole was 88.7%. The HPLC retention time of 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole was 15.8 minutes. GC / MS analysis revealed an m / z value of 199 (molecular weight after dehydration with HO). Similarity analysis identified the product as 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole.

[0038] [Example 2] Synthesis of 5-(trimethoxysilylethynyl)indole using palladium on carbon A 200 mL flask equipped with a stirrer and a condenser was charged with the raw materials described in Example 1, and 5.01 g (51.0 mmol, 2.0 equivalents / 5-BID) of trimethylsilylacetylene instead of 2-methyl-3-butyn-2-ol was added dropwise at 20-30°C. The reaction was then carried out for 24 hours as in Example 1. After 24 hours, the reaction solution was analyzed by high-performance liquid chromatography (HPLC). The reaction yield of the target 5-(trimethoxysilylethynyl)indole was 86.0%. The HPLC retention time of 5-(trimethoxysilylethynyl)indole was 25.3 minutes, and m / z = 213 was determined by GC / MS analysis. Based on similarity search, the product was identified as 5-(trimethoxysilylethynyl)indole.

[0039] [Example 3] Synthesis of 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole using palladium on carbon A 200 mL flask equipped with a stirrer and a condenser was charged with 5.0 g (25.4 mmol) of 5-bromoindazole (5-BIZ), 25 g (5 equivalents by weight / 5-BIZ) of N,N-dimethylacetamide (DMAc), 1.19 g (0.254 mmol, 1.0 mol% / 5-BIZ) of 5% palladium on carbon (Pd / C; Type K, Pd content 5.2% by weight, 44% by weight water content), 0.333 g (1.27 mmol) of triphenylphosphine, 0.0604 g (0.317 mmol) of copper(I) iodide, and 5.14 g (50.8 mmol, 2.0 equivalents / 5-BIZ). 2-Methyl-3-butyn-2-ol (50.8 mmol, 2.0 equivalents / 5-BIZ) was added dropwise at 20 to 30 °C. After the dropwise addition, the mixture was placed in an oil bath and reacted at a reaction temperature of 70-75°C for 24 hours. After 24 hours, the reaction mixture was analyzed by high-performance liquid chromatography (HPLC). The reaction yield of the target 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole was 79.2%. The HPLC retention time of 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole was 5.5 minutes, and the m / z value was 200 based on GC / MS analysis. Similarity analysis identified the product as 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole.

[0040] [Comparative Example 1] Synthesis of 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole using bis(triphenylphosphine)palladium(II) dichloride (BTPD) An experiment was carried out in the same manner as in Example 1, except that 0.179 g (0.255 mmol, 1.0 mol% / 5-BID) of bis(triphenylphosphine)palladium(II) dichloride (BTPD) was added to a 200 mL flask equipped with a stirrer and a condenser. After 24 hours, the reaction mixture was analyzed by high-performance liquid chromatography (HPLC), and the reaction yield of the target 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole was found to be 67.9%.

[0041] Comparative Example 2 Synthesis of 5-(trimethoxysilylethynyl)indole using bis(triphenylphosphine)palladium(II) dichloride (BTPD) An experiment was carried out in the same manner as in Example 2, except that in a 200 mL flask equipped with a stirrer and a condenser, 0.179 g (0.255 mmol, 1.0 mol% / 5-BID) of bis(triphenylphosphine)palladium(II) dichloride (BTPD) was used instead of the palladium on carbon (Pd / C) described in Example 2. After 24 hours, the reaction solution was analyzed by high-performance liquid chromatography (HPLC), and the reaction yield of the target 5-(trimethoxysilylethynyl)indole was found to be 70.2%.

[0042] Comparative Example 3 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole with bis(triphenylphosphine)palladium(II) dichloride (BTPD) An experiment was carried out in the same manner as in Example 3, except that a 200 mL flask equipped with a stirrer and a condenser was charged with 0.178 g (0.254 mmol, 1.0 mol% / 5-BIZ) of bis(triphenylphosphine)palladium(II) dichloride (BTPD) instead of the palladium on carbon (Pd / C) described in Example 3. After 24 hours, the reaction solution was analyzed by high-performance liquid chromatography (HPLC), and the reaction yield of the target 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole was found to be 69.8%.

[0043] The results of the examples and comparative examples are summarized in the table below. The reaction yield was higher when palladium on carbon was used than when bis(triphenylphosphine)palladium(II) dichloride (BTPD), which is a commonly used product in Sonogashira coupling reactions, and it is clear that this method is advantageous for industrial production.

[0044] [Table 1]

[0045] As shown in the table above, the use of palladium carbon as a catalyst allows for the synthesis of the target ethynyl compound with a higher reaction yield than the commonly used BTPD catalyst. Therefore, the target product can be obtained in higher reaction yield, making it possible to produce the product more cheaply.

[0046] After the coupling reaction, the reaction mixture is cooled, extracted with a non-aqueous organic solvent such as ethyl acetate, washed with water several times, and the organic solvent is concentrated. After that, recrystallization or distillation can be performed to obtain the desired aromatic ethynyl compound, such as 5-(3-hydroxy-3-methyl-1-butyn-1-yl)indole, 5-(trimethoxysilylethynyl)indole, or 5-(3-hydroxy-3-methyl-1-butyn-1-yl)-1H-indazole. [Industrial Applicability]

[0047] The method for producing an aromatic compound having an ethynyl group of the present invention uses palladium on carbon as a catalyst, thereby allowing the Sonogashira coupling reaction to proceed efficiently and in high yield, thereby enabling the production of an aromatic compound having an ethynyl group.

[0048] The aromatic compounds having an ethynyl group of the present invention can be used to synthesize aromatic compounds having an ethynyl group that are useful as raw materials for pharmaceuticals and electronic materials, and can be used as useful compounds as raw materials for fine chemicals, pharmaceutical and agricultural chemicals, resin and plastic materials, electronic information materials, and optical materials.

Claims

1. The following general formula (1) 【Chemistry 1】 (In the formula, the ring N represents a nitrogen-containing heterocycle, and X represents bromine.) and a fused polycyclic aromatic compound which is a derivative of indole or 1H-indazole, represented by the following general formula (2): 【Chemistry 2】 (In the formula, A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group.) In a coupling reaction with an ethynyl compound represented by the following general formula (3), the coupling reaction is carried out in N,N-dimethylacetamide together with palladium on carbon, a phosphorus compound which is a hydrocarbon phosphine compound, and copper iodide in the presence of an amine selected from tertiary alkylamines or secondary alkylamines: 【Transformation 3】 (In the formula, cyclic N represents a nitrogen-containing heterocycle, and A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group.) A method for producing a condensed polycyclic aromatic compound having an ethynyl group represented by the formula:

2. A method for producing a condensed polycyclic aromatic compound having an ethynyl group according to claim 1, wherein the ethynyl compound is selected from the group consisting of 2-propyn-1-ol, 2-methyl-3-butyn-2-ol, 3-butyn-2-ol, trimethylsilylacetylene, triethylsilylacetylene, and triisopropylsilylacetylene.

3. A method for producing a condensed polycyclic aromatic compound having an ethynyl group described in claim 1 or 2, wherein the amine is selected from the group consisting of triethylamine, diisopropylamine, and diisobutylamine.

4. A method for producing a condensed polycyclic aromatic compound having an ethynyl group described in claim 1 or 2, wherein the phosphorus compound is selected from the group consisting of triphenylphosphine, trimethylphosphine, triethylphosphine, and tri-n-propylphosphine.

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