JP2008106037A - Method for producing indole compound and indole compound - Google Patents

Abstract

【選択図】なしThe present invention provides a method for synthesizing an indole compound at a mild reaction temperature with a small amount of catalyst.
SOLUTION: A halogenated aniline (particularly 2-iodoaniline), a β-ketocarboxylic acid ester, a copper catalyst (such as cuprous iodide) and an additive (L-proline, ethylenediamine, N-methylglycine). , Thiophenecarboxylic acid, 1,1′-bi-2-naphthol, etc.) to produce an indole compound represented by the following general formula (III) at a mild reaction temperature (room temperature to 50 ° C.) how to.

[Selection figure] None

Description

  The present invention relates to a method for producing a novel indole compound and an indole compound.

Indole derivatives have excellent physiological activity and are useful as pharmaceuticals, agricultural chemicals, and electronic materials. Such an indole derivative is synthesized using a simple indole compound as a synthesis raw material. Therefore, it is important to develop a simple method for synthesizing indole compounds. As a simple method for synthesizing an indole compound, for example, a method for synthesizing a 2-substituted-3-indolecarboxylic acid ester is known (for example, see Non-Patent Document 1). In this method, cuprous iodide is used as a catalyst.
Suzuki (Sizuki, S), two others, “Convergent One-Pot Synthesis of 2,3-Dissynthesized Indoles”, Synthesis, Seam Chemistry (Themimeh) ), Germany, p. 616-617, 1984.

  However, the method described in Non-Patent Document 1 has a problem that excess cuprous iodide (1.5 equivalents) is used with respect to 2-iodoaniline and the reaction temperature is high (120 to 130 ° C.). . For this reason, development of the method of making it react at moderate reaction temperature with little usage-amount of a catalyst is desired.

  That is, the present invention has been made in view of the above problems, and an object thereof is to provide a method for synthesizing an indole compound at a mild reaction temperature with a small amount of catalyst used.

  That is, the present invention is as follows.

（式中、Ｈｒはハロゲン原子を示し、Ｒ^３は、置換されていてもよいアルキル基、シクロアルキル基、複素環基、アルケニル基、シクロアルケニル基、アルキニル基、アルコキシ基、アルキルチオ基、アリールエーテル基、アリールチオエーテル基、アリール基、ヘテロアリール基、シアノ基、カルボニル基、カルボキシル基、オキシカルボニル基、カルバモイル基を示し、ｎは、０から４の整数を示す。）
で表されるハロゲン化アニリンと、
下記一般式（ＩＩ）

（式中、Ｒ^１は、置換されていてもよいアルキル基、シクロアルキル基、複素環基、アルケニル基、シクロアルケニル基、アルキニル基、アルコキシ基、アルキルチオ基、アリールエーテル基、アリールチオエーテル基、アリール基、ヘテロアリール基、シアノ基、カルボニル基、カルボキシル基、オキシカルボニル基、カルバモイル基を示し、Ｒ^２は、電子吸引性基を示す。）
で表される化合物とを、触媒を用いて、下記一般式（ＩＩＩ）

（式中、Ｒ^１、Ｒ^２、Ｒ_３は、前記と同様である。）
で表されるインドール化合物を製造するものである。 The indole compound production method of the present invention comprises the following general formula (I):

(In the formula, Hr represents a halogen atom, and R ³ represents an optionally substituted alkyl group, cycloalkyl group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether. A group, an arylthioether group, an aryl group, a heteroaryl group, a cyano group, a carbonyl group, a carboxyl group, an oxycarbonyl group, and a carbamoyl group, and n represents an integer of 0 to 4.)
A halogenated aniline represented by:
The following general formula (II)

Wherein R ¹ is an optionally substituted alkyl group, cycloalkyl group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, aryl Group, heteroaryl group, cyano group, carbonyl group, carboxyl group, oxycarbonyl group, and carbamoyl group, and R ² represents an electron-withdrawing group.)
And a compound represented by the following general formula (III) using a catalyst:

(Wherein R ¹ , R ² and R ₃ are the same as described above.)
The indole compound represented by these is manufactured.

  The halogenated aniline is preferably 2-iodoaniline.

（式中、Ｒ_１は、置換されていてもよいアルキル基、シクロアルキル基、複素環基、アルケニル基、シクロアルケニル基、アルキニル基、アルコキシ基、アルキルチオ基、アリールエーテル基、アリールチオエーテル基、アリール基、ヘテロアリール基、シアノ基、カルボニル基、カルボキシル基、オキシカルボニル基、カルバモイル基を示し、Ｒ_２は、電子吸引性基を示し、Ｒ_３は、置換されていてもよいアルキル基、シクロアルキル基、複素環基、アルケニル基、シクロアルケニル基、アルキニル基、アルコキシ基、アルキルチオ基、アリールエーテル基、アリールチオエーテル基、アリール基、ヘテロアリール基、シアノ基、カルボニル基、カルボキシル基、オキシカルボニル基、カルバモイル基を示す。） The indole compound of the present invention is an indole compound represented by the following general formula (III).

Wherein R ₁ is an optionally substituted alkyl group, cycloalkyl group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, aryl Group, heteroaryl group, cyano group, carbonyl group, carboxyl group, oxycarbonyl group, carbamoyl group, R ₂ represents an electron-withdrawing group, R ₃ represents an optionally substituted alkyl group, cycloalkyl Group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, aryl group, heteroaryl group, cyano group, carbonyl group, carboxyl group, oxycarbonyl group, Represents a carbamoyl group.)

  The present invention can provide a method for synthesizing an indole compound at a moderate reaction temperature with a small amount of catalyst.

  The present invention is described in detail below.

で表されるハロゲン化アニリンにおいては、Ｈｒは、臭素、ヨウ素などのハロゲン原子を示す。好ましいハロゲン原子は、ヨウ素である。また、Ｒ^３は、置換されていてもよい例えばアルキル基、シクロアルキル基、複素環基、アルケニル基、シクロアルケニル基、アルキニル基、アルコキシ基、アルキルチオ基、アリールエーテル基、アリールチオエーテル基、アリール基、ヘテロアリール基、シアノ基、カルボニル基、カルボキシル基、オキシカルボニル基、カルバモイル基を示す。ｎは、０〜４を示す。 [Halogenated aniline]
In the present invention, the chemical formula (I)

In the halogenated aniline represented by Hr, Hr represents a halogen atom such as bromine or iodine. A preferred halogen atom is iodine. R ³ may be substituted, for example, an alkyl group, cycloalkyl group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, aryl group , A heteroaryl group, a cyano group, a carbonyl group, a carboxyl group, an oxycarbonyl group, and a carbamoyl group. n shows 0-4.

Examples of the alkyl group constituting R ³ include saturated aliphatic hydrocarbon groups having 1 to 20 carbon atoms, more preferably 1 to 6 carbon atoms. Specifically, alkyl groups such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, n-pentyl group, and n-hexyl group. More preferably, a methyl group, an ethyl group, an n-propyl group, an n-butyl group, and a tert-butyl group are exemplified. In addition, these alkyl groups may have a substituent such as a monochloromethyl group and a 2-hydroxy-2-phenylethyl group. There is no restriction | limiting in particular as a substituent, For example, an alkyl group, an aryl group, heteroaryl group, a halogen, a hydroxyl group etc. are mentioned.

Examples of the cycloalkyl group constituting R ³ include saturated alicyclic hydrocarbon groups having 3 to 20 carbon atoms. Specific examples include cycloalkyl groups such as cyclopropyl, cyclohexyl, norbornyl, and adamantyl. These cycloalkyl groups may have a substituent such as an alkyl group, an aryl group, a heteroaryl group, a halogen, or a hydroxyl group, similarly to the above alkyl group.

Examples of the heterocyclic group constituting R ³ include a group having an aliphatic ring having 2 to 20 carbon atoms and having an atom other than carbon in the ring. Specific examples include a group consisting of a pyran ring, a piperidine ring, and a cyclic amide. These heterocyclic groups may have a substituent such as an alkyl group, an aryl group, a heteroaryl group, a halogen, or a hydroxyl group, similarly to the above alkyl group.

Examples of the alkenyl group constituting R ³ include an unsaturated aliphatic hydrocarbon group having 2 to 20 carbon atoms. Specific examples include unsaturated aliphatic hydrocarbon groups containing a double bond such as a vinyl group, an allyl group, a butadienyl group, and a pentenyl group. Moreover, you may have a branch like 4-methyl-3-pentenyl group, 4,8-dimethyl-3,7-nonadiene group. Similarly to the alkyl group, it may have a substituent such as an alkyl group, an aryl group, a heteroaryl group, a halogen, or a hydroxyl group.

Examples of the cycloalkenyl group constituting R ³ include unsaturated alicyclic hydrocarbon groups containing a double bond having 2 to 20 carbon atoms. Specific examples include a cyclopentenyl group, a cyclopentadienyl group, and a cyclohexenyl group. Similarly to the alkyl group, it may have a substituent such as an alkyl group, an aryl group, or a heteroaryl group.

Examples of the alkynyl group constituting R ³ include unsaturated aliphatic hydrocarbon groups containing a triple bond having 2 to 20 carbon atoms. Specifically, an ethynyl group is exemplified. Similarly to the alkyl group, it may have a substituent such as an alkyl group, an aryl group, or a heteroaryl group.

Examples of the alkoxy group constituting R ³ include an aliphatic hydrocarbon group having an ether bond having 2 to 20 carbon atoms. Specifically, a methoxy group etc. are illustrated. The aliphatic hydrocarbon group may have a substituent such as an alkyl group, an aryl group, or a heteroaryl group, similarly to the above alkyl group.

As the alkylthio group constituting R ³ , an oxygen atom of an ether bond of the alkoxy group is substituted with a sulfur atom.

Examples of the aryl ether group constituting R ³ include an aromatic hydrocarbon group having an ether bond having 6 to 40 carbon atoms. Specifically, a phenoxy group and the like are exemplified. Similarly to the alkyl group, it may have a substituent such as an alkyl group, an aryl group, or a heteroaryl group.

The aryl thioether group constituting R ³ is one in which the oxygen atom of the ether bond of the aryl ether group is substituted with a sulfur atom.

Examples of the aryl group constituting R ³ include aromatic hydrocarbon groups having 6 to 40 carbon atoms. Specific examples include a phenyl group, a naphthyl group, a biphenyl group, a phenanthryl group, a terphenyl group, and a pyrenyl group. Similarly to the alkyl group, it may have a substituent such as an alkyl group, an aryl group, or a heteroaryl group.

Examples of the heteroaryl group constituting R ³ include aromatic groups having 2 to 30 carbon atoms and having atoms other than carbon in the ring. Specific examples include a furanyl group, a thiophenyl group, an oxazolyl group, a pyridyl group, and a quinolinyl group. Similarly to the alkyl group, it may have a substituent such as an alkyl group, an aryl group, or a heteroaryl group.

The cyano group, carbonyl group, carboxyl group, oxycarbonyl group, and carbamoyl group constituting R ³ may or may not have a substituent. Examples of the substituent include an alkyl group, a cycloalkyl group, an aryl group, and a heteroaryl group as described above.

においては、Ｒ^１は、置換されていてもよいアルキル基、シクロアルキル基、複素環基、アルケニル基、シクロアルケニル基、アルキニル基、アルコキシ基、アルキルチオ基、アリールエーテル基、アリールチオエーテル基、アリール基、ヘテロアリール基、シアノ基、カルボニル基、カルボキシル基、オキシカルボニル基、カルバモイル基を示し、Ｒ^２は、電子吸引性基を示す。Ｒ^１としては、具体的には、上記Ｒ^３と同様である。 [General Formula (II)]
In the present invention, the chemical formula (II)

In the formula, R ¹ represents an optionally substituted alkyl group, cycloalkyl group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, aryl group. , A heteroaryl group, a cyano group, a carbonyl group, a carboxyl group, an oxycarbonyl group, and a carbamoyl group, and R ² represents an electron-withdrawing group. Specifically, R ¹ is the same as R ³ described above.

The electron-withdrawing group is not particularly limited as long as it is a substituent that easily attracts electrons from the bonding atom side as compared with a hydrogen atom. Specifically, —CO ₂ CH ₃ , —CO ₂ C ₂ H ₅ , — ⁺ NH ₃ , —CF ₃ , —CCl ₃ , —NO ₂ , —CN, —CHO, —CO ₂ H, —SO ₂ Known electron-withdrawing groups such as CH ₃ and —SO ₃ H can be mentioned.

[catalyst]
The catalyst used in the present invention is a mixed catalyst of a copper catalyst and an additive. By using a mixed catalyst, the amount of copper catalyst used can be reduced, and an indole compound can be synthesized at a mild reaction temperature.

  A well-known copper catalyst can be used for a copper catalyst, and the thing of any state of copper (zero valence), copper (monovalent), and copper (divalent) may be sufficient as it. For example, a halogenated material such as cuprous iodide may be used.

  As additives, amino acids that may have a substituent, diamines such as ethylenediamine, thiophenecarboxylic acid, 1,1′-bi-2-naphthol (hereinafter referred to as “BINOL”), and the like can be used. . There is no restriction | limiting in particular as an amino acid which can be used, A well-known amino acid can be used. Specifically, any of neutral amino acids, acidic amino acids, and basic amino acids may be used. Preferred amino acids are neutral amino acids. Examples of neutral amino acids include L-proline, but are not limited thereto. Furthermore, it may be an amino acid having a substituent, such as N-methylglycine. A plurality of amino acids may be used. There is no restriction | limiting in particular as diamine which can be used, A well-known diamine can be used. Specific examples include 1,2-ethylenediamine.

  The amount of copper catalyst used is 0.05 to 0.6 equivalents, preferably 0.1 to 0.5 equivalents per equivalent of aniline halide. What is necessary is just to add an additive so that it may become 2 times amount of a copper catalyst.

式中、Ｒ^１、Ｒ^２、Ｒ^３は、上記と同様である。 [Production of indole compounds]
The indole compound represented by the following chemical formula (III) of the present invention is produced, for example, as follows.

In the formula, R ¹ , R ² and R ³ are the same as described above.

  In the present invention, sodium hydride, potassium carbonate, sodium carbonate, sodium hydrogen carbonate, cesium carbonate, potassium phosphate, triethylamine, tetramethylguanidine, 1,8-diazabicyclo [5.4.0] -7- You may react by adding bases, such as undecene (DBU). By adding such a base, acidic substances such as hydrogen iodide to be generated can be trapped (neutralized), and the carbonyl compound can be enolized to have nucleophilicity. A base is added so that it may become 0.5-5 equivalent with respect to 1 equivalent of halogenated anilines, Preferably it is 1-4 equivalent.

  Next, an organic solvent such as dimethyl sulfoxide (DMSO) is added. The organic solvent that can be used is not limited to DMSO, and includes known organic solvents such as tetrahydrofuran (THF), dichloromethane, acetonitrile, dichloroethane, and the like.

  A compound represented by the general formula (II) is dropped into a solution in which the above solution is kept at room temperature to 70 ° C., preferably room temperature to 50 ° C., and stirred. Next, aniline halide, cuprous iodide, and L-proline were added to this solution, and then the reaction vessel was filled with a nitrogen atmosphere and reacted at room temperature with stirring for 5 hours. The reaction mixture is washed with saturated ammonium chloride. The liquid after washing is extracted with an organic solvent such as ethyl acetate to obtain an organic layer. The obtained organic layer is dried using a desiccant such as anhydrous magnesium sulfate. From the obtained organic layer, the target product is fractionated by silica gel preparative thin layer chromatography and column chromatography. The kind of developing solvent, the mixing ratio, and the like vary depending on the amide compound obtained. Further, the number of chromatographs is not limited to one, and may be performed a plurality of times.

  When the method for producing an indole compound of the present invention is used, a novel indole compound can be easily produced. Moreover, even a conventionally known indole compound can be produced in good yield under mild conditions. When the indole compound of the present invention is used as a synthetic raw material, various indole derivatives can be obtained.

  EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited to this Example.

  The analysis and separation / purification of the compounds were performed using the following measuring devices and reagents.

Infrared absorption (IR) spectrum: JASCO FT / IR-460 plus (unless otherwise specified, samples were dissolved in chloroform and measured using a solution cell made of NaCl. Absorption wavelength was shown in cm ⁻¹ ).

  Nuclear magnetic resonance (NMR) spectrum: JEOL JMTC-400 / 54 / SS 400 MHz (Unless otherwise specified, tetramethylsilane (TMS) was used as an internal standard. Chemical shifts in the text are indicated by δ values. )

  Melting | fusing point measuring apparatus: BUCHI Melting point B-545 (The melting | fusing point in each Example is an uncorrected value.)

  Fast atom bombardment mass spectrometry (FAB-MS), high-resolution mass spectrum-high atom bombardment-fast atom bombardment (HRMS-FAB)

  Silica gel for column chromatography: BW-200 (Fuji Silysia)

Thin layer chromatography (TLC): MACHEREY-NAGEL DC-Fertigplatten SIL G-25 UV ₂₅₄ plate After TLC development, the compound was confirmed using the following reagents and color development method. Moreover, the color development method used in each Example used what was displayed with the following symbols.
UV: UV absorption I ₂ : Iodine coloring A: Anisaldehyde coloring M: Phosphomolybdic acid coloring V: Vanillin sulfate coloring

[Example 1]
(Synthesis of 2-chloromethyl-1H-indole-3-carboxylic acid methyl ester)
Sodium hydride (80 wt%, 18 mg, 0.46 mmol) was placed in a 10 mL eggplant-shaped flask, and dimethyl sulfoxide (DMSO) (1 mL) was added. To the solution kept at room temperature, methyl 3-oxo-4-chlorobutanoate (0.2 g, 1.33 mmol) is added dropwise as a compound represented by the general formula (II) and stirred. Next, after adding 2-iodoaniline (0.29 g, 1.32 mmol), cuprous iodide (44 mg, 0.23 mmol), L-proline (65.5 mg, 0.23 mmol) to this solution, The reaction vessel was filled with a nitrogen atmosphere and reacted at room temperature with stirring for 5 hours. The reaction mixture was washed with saturated ammonium chloride (5 mL). The liquid after washing was extracted with an organic solvent such as ethyl acetate to obtain an organic layer. The obtained organic layer was dried using a desiccant such as anhydrous magnesium sulfate. The obtained organic layer fractionated methyl 2-chloromethyl-1H-indole-3-carboxylate (38 mg) represented by the following general formula by silica gel preparative thin layer chromatography (yield 23%).

[Example 2]
(Synthesis of ethyl 2-naphthalen-2-yl-1H-indole-3-carboxylate)
As a compound represented by the general formula (II), ethyl 3-naphthalen-2-yl-3-oxopropanoate (0.1599 g, 0.66 mmol) was used, and 2-iodoaniline (0.14 g, 0.64 mmol) was used. In the same manner as in Example 1 except that was used, ethyl 2-naphthalen-2-yl-1H-indole-3-carboxylate (26 mg) represented by the following general formula was fractionated (yield 26%).
TLC: Rf = 0.5 (Hexane: EtOAc = 3: 1, UV, V)
IR (NaCl): νmax = 3007, 1677, 1521, 1451, 1309, 1263, 1218, 1147, 669
¹ H-NMR (CDCl ₃ ): 1.29 (3H, t, J = 7.1 Hz), 4.30 (2H, q, J = 7.1 Hz), 7.15 (1H, t, J = 7) .3 Hz), 7.25-7.29 (2H, m), 7.31-7.38 (2H, m), 7.53-7.62 (2H, m), 7.86-7.90. (2H, m), 8.06 (1H, d, J = 2.0 Hz), 8.25 (1H, d, J = 3.9), 9.90 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 14.1, 61.9, 111.0, 117.8, 123.7, 124.0, 124.2, 125, 4, 126.7, 127.4, 127 7, 127.8, 128.2, 128.4, 128.5, 128.6, 129.2, 129.4, 130.9, 131.3, 152.7

[Example 2 ']
(Synthesis of ethyl 2-naphthalen-2-yl-1H-indole-3-carboxylate)
In a 10 mL eggplant-shaped flask, ethyl 3-naphthalen-2-yl-3-oxopropanoate (0.1599 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol), BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL), and a balloon filled with argon for 5 minutes, The inside of the reaction vessel was replaced with argon gas. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a brown amorphous. Since the residue of the raw material was confirmed, purification was performed by silica gel column chromatography (hexane / ethyl acetate), and ethyl 2-naphthalen-2-yl-1H-indole-3-carboxylate represented by the above general formula as a brown oily substance (0.1504 g, yield: 80%) was obtained.

[Example 3]
(Synthesis of 2-t-butyl-1H-indole-3-carboxylic acid methyl ester)
Example 1 except that methyl pivaloyl acetate (0.1 g, 0.63 mmol) was used as the compound represented by the general formula (II) and 2-iodoaniline (0.21 g, 0.96 mmol) was used. In the same manner, methyl 2-t-butyl-1H-indole-3-carboxylate (49 mg) represented by the following general formula was fractionated (yield 33%).
TLC: Rf = 0.4 (Hexane: EtOAc = 3: 1, UV, V, A)
IR (NaCl): νmax = 3000, 1692, 1441, 1271, 1169, 1057, 763, 714, 651, 534
¹ H-NMR (CDCl ₃ ): 1.35 (9H, s), 3.72 (3H, s), 7.09 (1H, dt, J = 1.2, 7.6 Hz), 7.20 ( 1H, dd, J = 1.2, 7.6 Hz), 7.30 (1H, dt, J = 1.5, 8.0 Hz), 7.83 (1H, d, J = 7.6 Hz), 8 .84 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 27.5 (3 × CH ₃ ), 38.5, 52.5, 115.0, 125.0, 125.1, 125.7, 128.2, 129.1 130.6, 136.8, 173.0

[Example 3 ']
(Synthesis of 2-t-butyl-1H-indole-3-carboxylic acid methyl ester)
In a 10 mL eggplant-shaped flask, methyl pivaloyl acetate (0.1044 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol), BINOL (0.0344 g, 0 .12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol) and anhydrous DMSO (3 mL) were added, and the inside of the reaction vessel was replaced with argon gas using a balloon filled with argon for 5 minutes. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a yellow amorphous. Since the residue of the raw material was confirmed, it was purified by silica gel column chromatography (hexane / ethyl acetate), and methyl 2-t-butyl-1H-indole-3-carboxylate (0. 0184 g, yield: 13%).

[Example 4]
(Synthesis of ethyl 2-furan-2-yl-1H-indole-3-carboxylate)
As a compound represented by the general formula (II), ethyl 3-furan-2-yl-3-oxopropanoate (0.05 g, 0.27 mmol) was used, and 2-iodoaniline (0.09 g, 0.41 mmol) was used. In the same manner as in Example 1 except that was used, ethyl 2-furan-2-yl-1H-indole-3-carboxylate (37 mg) represented by the following general formula was collected (yield 35%).
TLC: Rf = 0.5 (Hexane: EtOAc = 3: 1, UV, V)
IR (NaCl): νmax = 3019, 1737, 1681, 1466, 1420, 1322, 1278, 1222, 1155, 1136, 1021, 773-750
¹ H-NMR (CDCl ₃ ): 1.49 (3H, t, J = 7.2 Hz), 4.45 (2H, q, J = 7.1 Hz), 6.54-6.57 (2H, m ), 7.36-7.49 (2H, m), 8.18 (1H, t, J = 1.7 Hz), 9.37 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 14.0, 61.5, 110.9, 112.6, 112.7, 114.5, 118.3, 121.9, 122.3, 123.4, 134 .8, 142.6, 147.0, 151.9, 167.0

[Example 4 ']
(Synthesis of ethyl 2-furan-2-yl-1H-indole-3-carboxylate)
In a 10 mL eggplant-shaped flask, ethyl 3-furan-2-yl-3-oxopropanoate (0.1202 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0 0.06 mmol), BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL), and reaction using a balloon filled with argon for 5 minutes. The inside of the container was replaced with argon gas. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a brown amorphous. Since the residue of the raw material was confirmed, purification was performed by silica gel column chromatography (hexane / ethyl acetate), and 2-furan-2-yl-1H-indole-3-carboxylic acid represented by the following general formula as a tan oil Ethyl (0.1461 g, yield: 95%) was obtained.

[Example 5]
(Synthesis of 2-thiophen-2-yl-1H-indole-3-carboxylic acid ethyl ester)
2 shown in the following general formula, except that ethyl thiophen-2-yl-3-oxopropanoate was used as the compound represented by the general formula (II) and 2-iodoaniline was used. -Ethyl thiophen-2-yl-1H-indole-3-carboxylate was fractionated (yield 46%).
TLC: Rf = 0.5 (Hexane: EtOAc = 3: 1, UV, V)
m. p. 168.8 ° C. (decomp)
IR (NaCl): νmax = 3529,3004,1610,1511,1178,1151,1047,821,719,661
¹ H-NMR (CDCl ₃ ): 1.30 (3H, t, J = 7.0 Hz), 4.21 (2H, q, J = 7.1 Hz), 6.75-6.84 (2H, m ), 7.56 (1H, dd, J = 3.9, 1.0 Hz), 7.68-7.76 (2H, m), 7.79 (2H, d, J = 0.1 Hz), 8 .01 (1H, d, 0.2 Hz), 9.79 (1 H, br s)
¹³ C-NMR (CDCl ₃ ): 14.1, 111.0, 117.8, 123.9, 124.2, 127.4, 128.4, 129.4, 131.3, 133.4

[Example 5 ']
(Synthesis of 2-thiophen-2-yl-1H-indole-3-carboxylic acid ethyl ester)
In a 10 mL eggplant-shaped flask, ethyl thiophen-2-yl-3-oxopropanoate (0.1308 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol) ), BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL), and a balloon filled with argon for 5 minutes. Was replaced with argon gas. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a yellow amorphous. Since the residue of the raw material was confirmed, purification was performed by silica gel column chromatography (hexane / ethyl acetate), and ethyl 2-thiophen-2-yl-1H-indole-3-carboxylate represented by the above general formula (light yellow crystals) ( 0.0108 g, yield: 7%).

[Example 6]
(Synthesis of 2- (2-bromophenyl) -1H-indole-3-carboxylate)
Except that ethyl 3- (2-bromophenyl) -3-oxopropanoate was used as the compound represented by the general formula (II) and 2-iodoaniline was used, the same general formula as below was used. The ethyl 2- (2-bromophenyl) -1H-indole-3-carboxylate shown in the above was fractionated (yield 9%).

[Example 7]
(Synthesis of methyl 2- (2-hydroxy-2-phenylethyl) -1H-indole-3-carboxylate)
As a compound represented by the general formula (II), methyl 5-hydroxy-5-phenyl-3-oxopentanoate (0.06 g, 0.27 mmol) was used, and 2-iodoaniline (0.09 g, 0.41 mmol) was used. In the same manner as in Example 1 except that was used, methyl 2- (2-hydroxy-2-phenylethyl) -1H-indole-3-carboxylate (33 mg) represented by the following general formula was collected (yield). 42%).
¹³ H-NMR (67.5 MHz, CDCl ₃ ): δ = 36.9, 51.0,
73.9, 104.6, 110.9, 121.4, 121.6, 122.5, 125.5, 126.5, 127.7, 128.5, 134.7, 143, 7,
145.0

[Example 8]
(Synthesis of methyl 2- (2-benzyloxy-ethyl) -1H-indole-3-carboxylate)
As a compound represented by the general formula (II), methyl 5-benzyloxy-3-oxopentanoate (0.06 g, 0.25 mmol) was used, and 2-iodoaniline (0.09 g, 0.41 mmol) was used. Except that, methyl 2- (2-benzyloxy-ethyl) -1H-indole-3-carboxylate (8 mg) represented by the following general formula was collected in the same manner as in Example 1.

[Example 9]
(Synthesis of methyl 2- (4,8-dimethyl-nona-3,7-dienyl) -1H-indole-3-carboxylate)
As the compound represented by the general formula (II), methyl 7,11-dimethyl-3-oxo-6,10-dodecadienoate (0.46 g, 1.83 mmol) was used, and 2-iodoaniline (0.2 g, 0 .91 mmol), except that methyl 2- (4,8-dimethyl-nona-3,7-dienyl) -1H-indole-3-carboxylate represented by the following general formula ( 52 mg) was collected (yield 17%).
¹³ H-NMR (67.5 MHz, CDCl ₃ ): δ = 15.9, 17.7,
25.7, 26.5, 27.4, 27.9, 39.6, 50.7, 103.8, 110.6, 121.4, 121.6, 122.3, 122.9, 124. 1,
127.1, 131.7, 134.5, 137.2, 148.2, 116.4

[Example 10]
(Synthesis of methyl 2- (3-butenyl) -1H-indole-3-carboxylate)
Except for using methyl 3-oxo-6-heptenoate (0.059 g, 0.38 mmol) as a compound represented by the general formula (II) and using 2-iodoaniline (0.055 g, 0.25 mmol). In the same manner as in Example 1, methyl 2- (3-butenyl) -1H-indole-3-carboxylate (13 mg) represented by the following general formula was fractionated (yield 22%).
¹³ H-NMR (67.5 MHz, CDCl ₃ ): δ = 27.3, 33.0, 50.8, 104.4, 110.7, 116.0, 121.4, 121.7, 122.4 , 127.0, 134.4, 137.3, 147.7, 166.3;
FAB MS: m / z (%) 229 (M ⁺ ).
HRMS-FAB: m / z [M + H] ⁺ calcd for C14H15O2N: 229.1269; found: 229.1186.

[Example 11]
Synthesis of methyl 2- (4-methyl-pent-3-enyl) -1H-indole-3-carboxylate
As a compound represented by the general formula (II), methyl 7-methyl-3-oxo-6-octenoate (please confirm) (0.92 g, 5.00 mmol) was used, and 2-iodoaniline (0.055 g, 0.25 mmol), except that methyl 2- (4-methyl-pent-3-enyl) -1H-indole-3-carboxylate (32 mg) represented by the following general formula was used. Preparative (yield 49%).
IR (NaCl): νmax = 3305, 2925, 1669, 1457, 1201, 1084, 749.
¹ H-NMR (CDCl ₃ ): 1.55 (3H, s), 1.61 (3H, s), 2.42 (2H, q, J = 7.3 Hz), 3.18 (2H, t, J = 7.3 Hz), 3.93 (3H, s), 5.16-5.22 (1 H, m), 7.16-7.25 (2 H, m), 7.28-7.32 ( 1H, m), 8.10-8.14 (1H, m), 8.69 (1H, s).
¹³ C-NMR (CDCl ₃ ): 17.6, 25.7, 27.5, 28.0, 50.7, 103.8, 110.6, 121.3, 121.6, 122.3, 122 .9, 127.1, 133.5, 134.5, 148.2, 166.4.
^{FAB-MS m / z (%} ): 258 (MH +, 72), 227 (M-OMe, 30), 188 (M-C 5 H 9, 100).
_{HRMS (FAB) m / z (} MH +): calcd for C 16 H 20 NO 2, 258.1494; found, 258.1438.

[Example 12]
(Synthesis of ethyl 2-methyl-1H-indole-3-carboxylate)
To a 10 mL eggplant flask, sodium hydride (60 wt%, 18 mg, 0.46 mmol) was added, and dimethyl sulfoxide (DMSO) (1 mL) was added. To a solution maintained at room temperature, methyl acetoacetate (0.2 g, 0.14 mmol) is added dropwise as a compound represented by the general formula (II) and stirred. Next, 2-iodoaniline (0.29 g, 0.13 mmol), cuprous iodide (44 mg, 0.23 mmol), L-proline (65.5 mg, 0.23 mmol) was added to this solution, The reaction vessel was filled with a nitrogen atmosphere and reacted at room temperature with stirring for 5 hours. The reaction mixture was washed with saturated ammonium chloride (5 mL). The liquid after washing was extracted with an organic solvent such as ethyl acetate to obtain an organic layer. The obtained organic layer was dried using a desiccant such as anhydrous magnesium sulfate. The obtained organic layer fractionated ethyl 2-methyl-1H-indole-3-carboxylate (38 mg) represented by the following general formula by silica gel preparative thin layer chromatography. The yield was 77%, which was higher than the literature yield (60%).

[Example 12]
(Synthesis of methyl 2-ethyl-1H-indole-3-carboxylate)
In a 10 mL eggplant flask, methyl propionyl acetate (0.0859 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol), BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol) and anhydrous DMSO (3 mL) were added, and the inside of the reaction vessel was replaced with argon gas using a balloon filled with argon for 5 minutes. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a yellow amorphous. Since the residue of the raw material was confirmed, purification was performed by silica gel column chromatography (hexane / ethyl acetate), and methyl 2-ethyl-1H-indole-3-carboxylate represented by the following general formula (0. 0719 g, yield: 60%).
TLC: Rf = 0.5 (Hexane: EtOAc = 3: 1, UV, V)
IR (NaCl): νmax = 3006, 1683, 1455, 1198, 1054, 787-773
¹ H-NMR (CDCl ₃ ): 1.31 (3H, t, J = 7.56 Hz), 3.16 (2H, q, J = 7.56 Hz), 3.92 (3H, s), 7. 13-7.38 (4H, m), 9.00 (br s)
¹³ C-NMR (CDCl ₃ ): 13.3, 21.2, 50.7, 103.2, 110.7, 121.2, 121.6, 122.2, 127.1, 134.5, 166 .5

[Example 13]
(Synthesis of methyl 2-isopropyl-1H-indole-3-carboxylate)
In a 10 mL eggplant flask, methyl 4-methyl-3-oxopentanoate (0.0952 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol) , BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL), and a balloon filled with argon for 5 minutes, Replaced with argon gas. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a yellow amorphous. Since the residue of the raw material was confirmed, it was purified by silica gel column chromatography (hexane / ethyl acetate), and methyl 2-isopropyl-1H-indole-3-carboxylate represented by the following general formula (0.0812 g) as yellow crystals. Yield: 62%).
TLC: Rf = 0.6 (Hexane: EtOAc = 3: 1, UV, V)
m. p. : 104.3 ° C
IR (NaCl): νmax = 3464, 1685, 1454, 1209, 1075, 772-742
¹ H-NMR (CDCl ₃ ): 1.36 (6H, d, J = 6.8 Hz), 3.9 (3H, s), 7.16-7.25 (2H, m), 7.36 ( 1H, dd, J = 0.02, 0.01), 8.11 (1H, d, J = 0.01 Hz), 9.15 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 21.7, 26.3, 50.7, 102.5, 110.9, 121.4, 121.5, 122.1, 127.0, 134.5, 153 .8, 166.4

[Example 13]
(Synthesis of methyl 2-nonyl-1H-indole-3-carboxylate)
In a 10 mL eggplant flask, methyl 3-oxo-laurate (0.1507 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol), BINOL ( 0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL), and a balloon filled with argon for 5 minutes. Replaced. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give an orange amorphous. Since the residue of the starting material was confirmed, purification was performed by silica gel column chromatography (hexane / ethyl acetate), and methyl brown 2-nonyl-1H-indole-3-carboxylate (0.1157 g, yield: 64%). )
TLC: Rf = 0.3 (Hexane: EtOAc = 5: 1, UV, V)
IR (NaCl): νmax = 2929, 2859, 1743, 1715, 1609, 1452, 1265, 1222, 1166, 773-747
¹ H-NMR (CDCl ₃ ): 0.87, (3H, t, J = 4.4 Hz), 1.31 (10H, t, J = 8.6 Hz), 1.59 (2H, t, J = 7.2 Hz), 2.52 (2 H, t, J = 7.4 Hz), 3.74 (3 H, s), 6.75 (1 H, d, J = 1.5 Hz), 7.18 (1 H, dd, J = 7.6, 2.3 Hz), 7.32 (1H, dd, J = 6.2, 3.1 Hz), 7.63 (1H, d, J = 9.3 Hz), 10.08 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 14.1, 22.6, 23.4, 28.9, 29.2, 29.3, 29.4, 31.8, 49.0, 114.7, 119 .9, 127.1, 127.3, 128.7, 129.3, 138.9, 139.4, 167.7

[Example 14]
(Synthesis of methyl 2-pyridine-1H-indole-3-carboxylate)
To a 10 mL eggplant flask, ethyl 3-oxo-pyridin-2-yl-propionate (0.1275 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0 0.06 mmol), BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL), and reaction using a balloon filled with argon for 5 minutes. The inside of the container was replaced with argon gas. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a reddish brown amorphous. Since the residue of the raw material was confirmed, purification was performed by silica gel column chromatography (hexane / ethyl acetate), and methyl 2-pyridine-1H-indole-3-carboxylate represented by the following general formula (0 0.095 g, yield: 50%).
TLC: Rf = 0.3 (Hexane: EtOAc = 3: 1, UV, V)
IR (NaCl): νmax = 3002,1737,1699,1592,1458-1443,1380,1324,1280,1222-1189,1139,1046,771.4-750.2
¹ H-NMR (CDCl ₃ ): 1.50 (3H, t, J = 7.3 Hz), 4.47 (2H, q, J = 7.2 Hz), 7.15 (2H, d, J = 8) .3 Hz), 7.26-7.38 (2 H, m), 7.95 (2 H, d, J = 8.8 Hz), 8.20 (1 H, d, J = 7.8 Hz), 8.84 (1H, d, J = 8.3 Hz), 10.33 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 14.1, 40.9, 117.9, 122.1, 123.9, 124.3, 127.3, 127.5, 128.4, 129.4, 131 2,133.5,137.0,149.0,152.8

[Example 15]
(Synthesis of methyl 2- (3-pentenyl) -1H-indole-3-carboxylate)
In a 10 mL eggplant flask, methyl 3-oxo-6-octenoate (0.1123 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol), Binol (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL) were added, and the reaction vessel was filled with argon using a balloon filled with argon for 5 minutes. Replaced with gas. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a yellow amorphous. Since the residue of the raw material was confirmed, it was purified by silica gel column chromatography (hexane / ethyl acetate), and methyl 2- (3-pentenyl) -1H-indole-3-carboxylate (0.0581 g, 40%) as yellow crystals. )
TLC: Rf = 0.3 (Hexane: EtOAc = 3: 1, UV, V)
m. p. : 62.9 ° C
IR (NaCl): νmax = 3455, 3016, 2946, 1685, 1546, 1453, 1338, 1269, 1205-1196, 1083, 774-750
¹ H-NMR (CDCl ₃ ): 1.62 (3H, dd, J = 2.0, 1.1 Hz), 2.38-2.43 (2H, m), 3.20 (2H, t, J = 7.4 Hz), 3.93 (3H, s), 5.42-5.51 (2H, m), 7.16-7.24 (2H, m), 7.30 (1H, d, J = 7.0 Hz), 8.12 (1H, d, J = 7.9, 1.4 Hz), 8.75 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 17.9, 31.9, 50.8, 103.7, 110.7, 121.3, 121.6, 122.3, 126.5, 127.0, 129 .7, 134.5, 148.1, 166.4

[Example 15]
(Synthesis of 2- (3-pentenyl) -1H-indole-3-carboxylic acid-2-isopropyl-5-methyl-cyclohexyl)
To a 10 mL eggplant flask, 3-oxo-6-octenoic acid-2-isopropyl-5-methyl-cyclohexyl (0.1943 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI ( 0.144 g, 0.06 mmol), BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol), anhydrous DMSO (3 mL), balloon filled with argon for 5 minutes The inside of the reaction vessel was replaced with argon gas. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a brown amorphous. Since the residue of the raw material was confirmed, purification was performed by silica gel column chromatography (hexane / ethyl acetate), and 2- (3-pentenyl) -1H-indole-3-carboxylate-2-isopropyl-5--5, which was a brown oily substance. Methyl-cyclohexyl (0.0772 g, 35%) was obtained.
TLC: Rf = 0.4 (Hexane: EtOAc = 3: 1, UV, V)
IR (NaCl): νmax = 2958,1682,1614,1457,1221,1210,785,774,760,744,731,669
¹ H-NMR (CDCl ₃ ): 0.80 (6H, d, J = 6.8 Hz), 1.14 (3H, d, J = 11.4 Hz), 1.54-1.58 (3H, m ), 1.63-1.68 (4H, m), 1.71-1.76 (3H, m), 2.04-2.13 (2H, m), 5.48-5.51 (2H) , M), 7.10-7.30 (4H, m)
¹³ C-NMR (CDCl ₃ ): 16.3, 17.9, 21.0, 22.1, 23.4, 26.2, 28.0, 31.4, 32.0, 34.3, 41 5,47.4,73.0,84.1,110.6,114.7,120.0,121.4,121.5,126.4,129.3,129.8,138.9 , 146.7

[Example 16]
(Synthesis of methyl 2-methyl-1H-indole-3-carboxylate)
In a 10 mL eggplant flask, methyl acetoacetate (0.0766 g, 0.66 mmol), 2-iodoaniline (0.1314 g, 0.6 mmol), CuI (0.144 g, 0.06 mmol), BINOL (0.0344 g, 0.12 mmol), Cs ₂ CO ₃ (0.1955 g, 0.6 mmol) and anhydrous DMSO (3 mL) were added, and the inside of the reaction vessel was replaced with argon gas using a balloon filled with argon for 5 minutes. After vigorous stirring at 50 ° C. for 4 hours, ethyl acetate (10 mL), sat. Liquid separation was performed with NH ₄ Cl (10 mL). Thereafter, the organic layer was washed with sat. Washed with NaCl and the aqueous layer was extracted again with ethyl acetate. The organic layers were combined, dried over Na ₂ SO ₄ and concentrated in vacuo to give a yellow amorphous. Since the residue of the raw material was confirmed, it was purified by silica gel column chromatography (hexane / ethyl acetate) to synthesize methyl 2-methyl-1H-indole-3-carboxylate represented by the following general formula as a pale yellow crystal ( 0.0885 g, yield 79%).
TLC: Rf = 0.30 (Hexane: EtOAc = 3: 1, UV, V, A)
m. p. 153.9 ° C. (decomp)
IR (NaCl): νmax = 3016, 1687, 1453, 1208, 1091 cm ^−1
1 H-NMR (CDCl ₃ ): 2.72 (3H, s), 3.93 (3H, s), 7.16-7.30 (3H, m), 8.08 (1H, d, J = 7.6 Hz), 8.67 (1H, br s)
¹³ C-NMR (CDCl ₃ ): 14.2, 50.8, 104.3, 110.5, 121.2, 121.7, 122.3, 127.1, 134.5, 144.2, 166 .6

表中、ａは、単離収率を、ｂは、消費された２−ヨードアニリンに基づく単離収率を、意味する。 [Example 17]
In the synthesis of methyl 2-methyl-1H-indole-3-carboxylate of Example 16, 1.1 equivalents (1.1 equiv.) Of methyl acetoacetate to 1 equivalent (1 equiv.) Of 2-iodoaniline The yield of methyl 2-methyl-1H-indole-3-carboxylate was obtained with the amount of CuI used, the type and amount of additive added, the type and amount of base used, and the reaction temperature changed. evaluated. The results are shown in Table 1. In Table 1, the synthesis conditions and yield corresponding to each entry number are shown. The mol% of CuI shows mol% with respect to 2-iodoaniline. Additive means an additive, “L-proline” means L-proline, H ₂ N / \ / NH ₂ means diethylamine, and MeHN / \ COOH means N-methylglycine. The mol% of additive indicates mol% with respect to 2-iodoaniline. “base” means a base, and the base equiv. Indicates an equivalent to 2-iodoaniline. Solvent indicates the solvent used in the reaction. temp means reaction temperature and yield means yield.

In the table, a means the isolated yield and b means the isolated yield based on the consumed 2-iodoaniline.

Table 1 shows that when L-proline is used, the yield of methyl 2-methyl-1H-indole-3-carboxylate increases as the amount of CuI used increases (entries 2, 3). It can be seen that when the amount of CuI used and the amount of additive used are large, the reaction proceeds even at room temperature (entries 3, 4). It can also be seen that the synthesis of methyl 2-methyl-1H-indole-3-carboxylate proceeds even if the additive is replaced with ethylenediamine, N-methylglycine, thiophenecarboxylic acid, or BINOL.

Claims (3)

The following general formula (I)

(In the formula, Hr represents a halogen atom, and R ³ represents a hydrogen atom, which may be substituted, an alkyl group, a cycloalkyl group, a heterocyclic group, an alkenyl group, a cycloalkenyl group, an alkynyl group, an alkoxy group, an alkylthio group. A group, an aryl ether group, an aryl thioether group, an aryl group, a heteroaryl group, a cyano group, a carbonyl group, a carboxyl group, an oxycarbonyl group, or a carbamoyl group, and n represents an integer of 0 to 4.)
A halogenated aniline represented by:
The following general formula (II)

(Wherein R ¹ is an optionally substituted alkyl group, cycloalkyl group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, An aryl group, a heteroaryl group, a cyano group, a carbonyl group, a carboxyl group, an oxycarbonyl group, and a carbamoyl group, and R ² represents an electron-withdrawing group.
And a compound represented by the following general formula (III) using a catalyst:

(Wherein R ¹ , R ² and R ³ are the same as described above.
The indole compound manufacturing method which manufactures the indole compound represented by these.   The indole compound production method according to claim 1, wherein the halogenated aniline is 2-iodoaniline. An indole compound represented by the following general formula (III).

Wherein R ₁ is an optionally substituted alkyl group, cycloalkyl group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, aryl Group, heteroaryl group, cyano group, carbonyl group, carboxyl group, oxycarbonyl group, carbamoyl group, R ₂ represents an electron-withdrawing group, R ₃ represents an optionally substituted alkyl group, cycloalkyl Group, heterocyclic group, alkenyl group, cycloalkenyl group, alkynyl group, alkoxy group, alkylthio group, aryl ether group, aryl thioether group, aryl group, heteroaryl group, cyano group, carbonyl group, carboxyl group, oxycarbonyl group, Represents a carbamoyl group.)