JP2019099537A - Method for producing nitrogen-containing heterocyclic compound - Google Patents

Abstract

To provide a method for producing a nitrogen-containing heterocyclic compound in high yield and with high purity.SOLUTION: A method for producing a nitrogen-containing heterocyclic compound includes lithiating a compound represented by general formula [1] using n-BuLi, and further reacting it with a compound represented by general formula [2], to obtain a compound represented by general formula [3] (Xis O or S; Rand Rare a substituent; A-Aindependently represent N or CR; R is H or a substituent, where, the number of A-AN is 1 or 2; mis an integer of 0-2; mis an integer of 0-4; R-Rindependently represent an alkyl group, a cycloalkyl group or aryl group; Rand Rmay be bound to each other to form a ring).SELECTED DRAWING: None

Description

  The present invention relates to a useful intermediate of an organic synthetic compound, in particular, a borate compound useful as a material for organic electroluminescence and a method for producing a nitrogen-containing heterocyclic compound derived therefrom.

  As a method of borate nitrogen-containing heterocyclic compounds such as azadibenzofuran, a method of halogenating azadibenzofuran and subsequently reacting with pinacolone diborate is described (see Patent Document 1). Alternatively, a method is disclosed in which a halogenated azadibenzofuran is reacted with n-BuLi (hereinafter also referred to as nBuLi) and subsequently reacted with isopropoxyboronic acid pinacol (see Patent Document 1). The former uses an expensive Pd catalyst and produces by-products derived from Suzuki coupling, and the latter, when anionizing with n-butyllithium, causes multiple sites to be anionized to produce by-products, etc. There was a problem. Therefore, when the synthesized borate compound is subjected to Suzuki coupling reaction with an aryl halide, there are problems such as a decrease in yield and a decrease in purity.

International Publication No. 2014/044722

  The present invention has been made to solve the above problems, and its object is to provide a method for producing a nitrogen-containing heterocyclic compound obtained in high yield and high purity.

  The above-mentioned subject was able to be solved by the following composition.

  1. The compound represented by the following general formula [1] is lithiated with n-BuLi, and the compound represented by the following general formula [2] is further reacted to obtain the compound represented by the following general formula [3] Method for producing a nitrogen-containing heterocyclic compound

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ and R ₂ represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents a hydrogen atom or a substituent. However, the number of N of A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2 and m ₂ is an integer of 0 to _4. R _{3 to} R ₅ are each independently Represents an alkyl group, a cycloalkyl group, or an aryl group, and R ₄ and R ₅ may combine with each other to form a ring)

  2. The method for producing a nitrogen-containing heterocyclic compound according to the above 1, wherein the addition amount of the n-BuLi is 0.85 to 0.99 in molar ratio to the general formula [1].

  3. The reaction is carried out at a reaction temperature of −20 ° C. to 10 ° C., by which the compound represented by the general formula [1] is lithiated with the n-BuLi, and the compound represented by the general formula [2] is further reacted. A process for producing the nitrogen-containing heterocyclic compound according to 1 or 2 above.

  4. In any one of 1 to 3 above, the general formula [1] is represented by the following general formula [8], and the general formula [3] is represented by the following general formula [9] The manufacturing method of the nitrogen-containing heterocyclic compound as described.

(Wherein, _{X 1} is _.R 1, _{R 2} is an integer of .m ₁ is 0 to 2 represents a substituent, _{m 2} is _.R 4 represents an integer of 0 to 4 representing an oxygen atom or a sulfur atom, R ₅ each independently represents an alkyl group, a cycloalkyl group or an aryl group, and R ₄ and R ₅ may combine with each other to form a ring)

  5. Without purifying the nitrogen-containing heterocyclic compound produced by the method for producing a nitrogen-containing heterocyclic compound according to any one of the items 1 to 4, a compound represented by the following general formula [4], and Pd A method for producing a nitrogen-containing heterocyclic compound, which comprises reacting in the presence of a catalyst and a phosphine ligand to obtain a compound represented by the following general formula [5].

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ and R ₆ each represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents a hydrogen atom or A represents a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4 and m ₆ is an integer of 0 to 4 X ₂ represents a chlorine atom, a bromine atom or an iodine atom, and n ₂ represents an integer of ₂ to 4.)

  6. The compound represented by the following general formula [6] and the Pd catalyst without purifying the nitrogen-containing heterocyclic compound produced by the method for producing a nitrogen-containing heterocyclic compound according to any one of the items 1 to 4 And a reaction in the presence of a phosphine ligand to obtain a compound represented by the following general formula [7], and a method of producing a nitrogen-containing heterocyclic compound.

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ , R ₇ and R ₈ represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents H ₁ represents a hydrogen atom or a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4, m ₇ and m ₈ are Each independently represents an integer of 0 to _3. X ₃ and X ₄ each independently represent a chlorine atom, a bromine atom or an iodine atom n ₃ and n ₄ each independently represent an integer of 1 to 2 A represents a simple bond or a divalent linking group.)

  7. Reacting a compound represented by the following general formula [3] with a compound represented by the following general formula [4] in the presence of a Pd catalyst and a phosphine ligand to obtain a compound represented by the following general formula [5] The manufacturing method of the nitrogen-containing heterocyclic compound which is characterized.

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ and R ₆ each represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents a hydrogen atom or A represents a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4 and m ₆ is an integer of 0 to 4 X ₂ represents a chlorine atom, a bromine atom or an iodine atom, n ₂ represents an integer of ₂ to 4. R ₄ and R ₅ each independently represent an alkyl group, a cycloalkyl group or an aryl group , R ₄ and R ₅ may combine with each other to form a ring.)

  8. Reacting a compound represented by the following general formula [3] with a compound represented by the following general formula [6] in the presence of a Pd catalyst and a phosphine ligand to obtain a compound represented by the following general formula [7] The manufacturing method of the nitrogen-containing heterocyclic compound which is characterized.

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ , R ₇ and R ₈ represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents H ₁ represents a hydrogen atom or a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4, m ₇ and m ₈ are Each independently represents an integer of 0 to _3. X ₃ and X ₄ each independently represent a chlorine atom, a bromine atom or an iodine atom n ₃ and n ₄ each independently represent an integer of 1 to 2 A represents a simple bond or a divalent linking group R ₄ and R ₅ each independently represent an alkyl group, a cycloalkyl group or an aryl group, and R ₄ and R ₅ are bonded to each other to form a ring You may form

  9. 7. The method for producing a nitrogen-containing heterocyclic compound according to 7 or 8 above, wherein the general formula [3] is represented by the following general formula [9].

(Wherein, _{X 1} is _.R 1, _{R 2} is an integer of .m ₁ is 0 to 2 represents a substituent, _{m 2} is _.R 4 represents an integer of 0 to 4 representing an oxygen atom or a sulfur atom, R ₅ each independently represents an alkyl group, a cycloalkyl group or an aryl group, and R ₄ and R ₅ may combine with each other to form a ring)

  10. The method for producing a nitrogen-containing heterocyclic compound according to any one of the items 5 to 9, wherein the phosphine ligand is represented by the following general formula [10].

(Wherein, R _{9 to} R ₁₁ each independently represent an alkyl group, a cycloalkyl group or an aryl group).

  11. 11. The method for producing a nitrogen-containing heterocyclic compound according to any one of the items 1 to 10, wherein all reactions are carried out in the same ether solvent.

  12. 11. The method for producing a nitrogen-containing heterocyclic compound according to any one of 1 to 11 above, wherein all the reaction is carried out in one pot.

  The method for producing a nitrogen-containing heterocyclic compound of the present invention can obtain a nitrogen heterocyclic compound in high yield and high purity.

It is a flowchart of the manufacturing method of the nitrogen-containing heterocyclic compound in this invention. It is a flowchart of the manufacturing method of the nitrogen-containing heterocyclic compound in this invention. It is a flowchart of the manufacturing method of the nitrogen-containing heterocyclic compound in this invention. FIG. 16 is a graph showing the relationship between the molar ratio of nBuLi to the exemplified compound 1-1 and the purity in Example 5. FIG.

Hereinafter, the present invention will be described in more detail.
As shown in FIG. 1, the method for producing a nitrogen-containing heterocyclic compound includes a step S101 of lithiation and a step S102 of obtaining a compound represented by the general formula [3].

The method for producing a nitrogen-containing heterocyclic compound is a method represented by the following general formula [1] and n-BuLi, followed by reaction with a compound represented by the following general formula [2] to obtain a compound represented by the following general formula [3] To obtain the compound represented by
The nitrogen-containing heterocyclic compound represented by the general formula [3] is a useful intermediate of an organic synthetic compound, in particular, a borate compound useful as a material for organic electroluminescence.

In the general formulas [1] to [3], X ₁ represents an oxygen atom or a sulfur atom. Among these, preferred is an oxygen atom.

In the general formulas [1] to [3], R ₁ and R ₂ each represents a substituent. Each of A _{1 to} A ₄ independently represents N or CR, and R represents a hydrogen atom or a substituent. However, the number of N of A _{1 to} A ₄ is 1 to 2, preferably 1.

The substituent represented by R ₁ , R ₂ and R is, for example, alkyl, cycloalkyl, alkenyl, aryl, acylamino, sulfonamide, alkylthio, arylthio, heterocyclic ring (eg, dibenzofuran ring, azadibenzofuran ring, Dibenzodiophen ring, carbazole ring, etc.) sulfonyl, sulfinyl, phosphonyl, acyl, carbamoyl, sulfamoyl, cyano, alkoxy, aryloxy, heterocyclic oxy, siloxy, acyloxy, carbamoyloxy, amino, alkylamino, imide, ureido, sulul Famoylamino, alkoxycarbonylamino, alkoxycarbonylamino, aryloxycarbonylamino, alkoxycarbonyl, aryloxycarbonyl, carboxyl, 2- (2-pyridyl) phenyl Each group such as phenyl and the like can be mentioned. Among these, preferred is an aryl group.

In general formulas [1] to [3], m ₁ represents an integer of 0 to ₂ , and m ₂ represents an integer of 0 to 4. Each of R _{3 to} R ₅ independently represents an alkyl group, a cycloalkyl group or an aryl group, preferably an alkyl group.
R ₄ and R ₅ may bond to each other to form a ring, preferably a tetramethylethylene group.

  The addition amount of n-BuLi is preferably 0.85 to 0.99 in molar ratio to the general formula [1]. Within this range, the compound represented by the general formula [3] can be obtained in higher yield and high purity. Further, the compound represented by the general formula [5] and the compound represented by the general formula [7] can be obtained in higher yield and high purity. The amount of n-BuLi added is preferably 0.90 or more, more preferably 0.93 or more in terms of molar ratio to the general formula [1], from the viewpoint of obtaining a nitrogen heterocyclic compound with higher yield and high purity. It is. The amount of n-BuLi added is more preferably 0.97 or less from the viewpoint of obtaining the nitrogen heterocyclic compound in higher yield and high purity. That is, the addition amount of n-BuLi is more preferably 0.93 to 0.99, and still more preferably 0.93 to 0.97.

  It is preferable to carry out the reaction temperature to which the compound represented by general formula [1] is lithiated with n-BuLi, and the compound represented by general formula [2] at -20 ° C to 10 ° C. If reaction temperature is -20 degreeC or more, the installation of ultra-low temperature is unnecessary and it is preferable from an installation viewpoint. On the other hand, if the reaction temperature is 10 ° C. or less, side reactions can be suppressed. The reaction temperature is more preferably −10 ° C. or more from the viewpoint of equipment. The reaction temperature is preferably 5 ° C. or less from the viewpoint of suppressing side reactions. That is, the reaction temperature is more preferably -10 ° C to 10 ° C, and still more preferably -10 ° C to 5 ° C.

  It is preferable that the said General formula [1] is represented by following General formula [8]. Moreover, it is preferable that the said General formula [3] is represented by following General formula [9].

In the general formulas [8] and [9], X ₁ represents an oxygen atom or a sulfur atom.
In the general formulas [8] and [9], R ₁ and R ₂ each represent a substituent.
In general formulas [8] and [9], m ₁ represents an integer of 0 to ₂ , and m ₂ represents an integer of 0 to 4.
In the general formulas [8] and [9], R ₄ and R ₅ each independently represent an alkyl group, a cycloalkyl group or an aryl group, and R ₄ and R ₅ may combine with each other to form a ring Good.

  As shown in FIG. 2, in the method for producing a nitrogen-containing heterocyclic compound, a step S101 of lithiation, a step S102 of obtaining a compound represented by the general formula [3], and a compound represented by the general formula [5] And obtaining step S103a.

The method for producing a nitrogen-containing heterocyclic compound is a reaction of a compound represented by the above general formula [3] and a compound represented by the following general formula [4] in the presence of a Pd catalyst and a phosphine ligand: ] The compound represented by these is obtained.
The nitrogen-containing heterocyclic compound represented by the general formula [5] is a nitrogen-containing heterocyclic compound derived from the compound represented by the general formula [3], which is a useful intermediate of organic synthetic compounds. In particular, nitrogen-containing heterocyclic compounds useful as materials for organic electroluminescence.

In the general formulas [4] and [5], X ₁ represents an oxygen atom or a sulfur atom. Among these, preferred is an oxygen atom.
In the general formulas [4] and [5], R ₁ , R ₂ and R ₆ each represent a substituent. Each of A _{1 to} A ₄ independently represents N or CR, and R represents a hydrogen atom or a substituent. However, the number of N of A _{1 to} A ₄ is 1 to 2, preferably 1.

The substituent groups represented by _{R 1, R 2, R 6} , R, for example, the same substituents as described in the general formula [1] to [3].

In general formulas [4] and [5], m ₁ represents an integer of 0 to 2, m ₂ represents an integer of 0 to 4, and m ₆ represents an integer of 0 to 4. X ₂ represents a chlorine atom, a bromine atom or an iodine atom. Among these, preferred are a bromine atom and an iodine atom.
In the general formulas [4] and [5], n2 represents an integer of ₂ to 4, and is preferably 3.

The compound represented by the general formula [3] is, as described above, lithiated with the compound represented by the general formula [1] and n-BuLi, and further reacted with the compound represented by the general formula [2] It is possible to use one obtained by However, as the compound represented by the general formula [3], those obtained by methods other than this method can also be used.
In any of the methods, the obtained compound represented by the general formula [3] can be used for the reaction with the compound represented by the general formula [4] without purification. However, it may be used after purification.

  As shown in FIG. 3, in the method for producing a nitrogen-containing heterocyclic compound, a step S101 of lithiation, a step S102 of obtaining a compound represented by the general formula [3], and a compound represented by the general formula [7] And obtaining step S103b.

The process for producing a nitrogen-containing heterocyclic compound is carried out by reacting the compound represented by the above general formula [3] with the compound represented by the following general formula [6] in the presence of a Pd catalyst and a phosphine ligand ] The compound represented by these is obtained.
The nitrogen-containing heterocyclic compound represented by the general formula [7] is a nitrogen-containing heterocyclic compound derived from the compound represented by the general formula [3], which is a useful intermediate of organic synthetic compounds. In particular, nitrogen-containing heterocyclic compounds useful as materials for organic electroluminescence.

In the general formulas [6] and [7], X ₁ represents an oxygen atom or a sulfur atom. Among these, preferred is an oxygen atom.
In the general formulas [6] and [7], R ₁ , R ₂ , R ₇ and R ₈ each represent a substituent. Each of A _{1 to} A ₄ independently represents N or CR, and R represents a hydrogen atom or a substituent. However, the number of N of A _{1 to} A ₄ is 1 to 2, preferably 1.

The substituent groups represented by _{R 1, R 2, R 7} , R 8, R, for example, the same substituents as described in the general formula [1] to [3].

In the general formulas [6] and [7], m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4 and m ₇ and m ₈ each independently represent an integer of 0 to 3. Each of X ₃ and X ₄ independently represents a chlorine atom, a bromine atom or an iodine atom. Among these, preferred are a bromine atom and an iodine atom.
In the general formulas [6] and [7], n ₃ and n ₄ each independently represent an integer of 1 to 2, preferably 1.

  In the general formulas [6] and [7], A represents a simple bond or a divalent linking group. The simple bond is a simple bond that directly bonds the substituents to be linked. Preferred among these are simple bonds.

  Examples of the divalent linking group represented by A include hydrocarbon groups such as alkylene, alkenylene, alkynylene and arylene. The divalent linking group represented by A may contain a hetero atom in addition to the above-mentioned hydrocarbon group, and may be a thiophene-2,5-diyl group or a pyrazine-2,3-diyl group. Or a divalent linking group derived from a compound having an aromatic heterocyclic ring (also referred to as a heteroaromatic compound) or a chalcogen atom such as oxygen or sulfur. Further, it may be a group which is linked via a hetero atom such as an alkylimino group, a dialkylsilanediyl group or a diarylgermandiyl group.

When R ₇ and R ₈ are adjacent to each other, they may form a ring with A.

The compound represented by the general formula [3] is, as described above, lithiated with the compound represented by the general formula [1] and n-BuLi, and further reacted with the compound represented by the general formula [2] It is possible to use one obtained by However, as the compound represented by the general formula [3], those obtained by methods other than this method can also be used.
In any of the methods, the obtained compound represented by the general formula [3] can be used for the reaction with the compound represented by the general formula [6] without purification. However, it may be used after purification.

Examples of the Pd catalyst include PdCl ₂ , Pd (OAc) ₂ , Pd (Pph ₃ ) ₄ , PdCl ₂ dppf, Pd (dba) ₂ , Pd / c and the like.
The amount of Pd catalyst used is preferably in the range of 0.01 to 0.3 mol, and more preferably 0.02 to 0.2 mol, per mol of the compound represented by the general formula [4] or the general formula [6]. It is particularly preferred to use in the range.

  Examples of phosphine ligands include trialkyl phosphines (for example, tri n-butyl phosphine, tri t-butyl phosphine, tricyclohexyl phosphine), and phosphines having at least one aryl group (for example, triphenyl phosphine, SPHOS, XPHOS, etc.) Be Among these, phosphine having one aryl group is preferable, and SPHOS is particularly preferable.

  The phosphine ligand is preferably used in the range of 0.01 to 0.3 mol, more preferably 0.02 to 0.2 mol, per 1 mol of the compound represented by the general formula [4] or the general formula [6]. Is particularly preferred.

  The phosphine ligand is preferably represented by the following general formula [10].

In the general formula [10], R _{9 to} R ₁₁ each independently represent an alkyl group, a cycloalkyl group or an aryl group.
Among the groups represented by R ₉ , preferred is a cycloalkyl group. Of the groups represented by R ₁₀ and R ₁₁ , preferred are alkyl groups.

  It is preferable to use a base in combination in the above reaction. Examples of the base include alkali metal salts (sodium carbonate, potassium carbonate, sodium hydrogen carbonate, cesium carbonate, cesium fluoride, sodium t-butoxide and the like), amine derivatives (triethylamine and the like) and the like.

It is preferred to carry out all reactions in the present invention with the same reaction solvent. That is, it is preferable that the reaction of lithiation with the compound represented by the general formula [1] and n-BuLi and the reaction of the compound in the subsequent steps be performed in the same reaction solvent. By performing all the reactions in the same reaction solvent, the economic efficiency is improved.
The reaction solvent is preferably an ether solvent, and examples thereof include diethyl ether, diisopropyl ether, THF, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, 1,4-dioxane and the like. Of these, preferred is THF.

N-BuLi is rapidly decomposed by the water contained in the solvent used for lithiation. For this reason, it is preferable to measure the water content of the solvent to be used in advance by the Karl-Fisher method or the like and correct the amount corresponding to n-BuLi to be decomposed and to add.
There are two types of measurement methods using the Karl Fischer method, volumetric titration and coulometric titration. In volumetric titration, a sample is dissolved in an alcohol-based solvent, reacted with KF reagent (iodine, sulfur dioxide, base), and the water content of the sample is determined from the volume consumed by the KF reagent. On the other hand, in the coulometric titration method, the sample is dissolved in a solvent (alcohol, sulfur dioxide, base, iodine ion), the iodine ion is converted to iodine by electric field oxidation and reacted, and the water content of the sample is measured from the amount of electricity consumed for electric field oxidation. It is a method.

  All reactions in the present invention are preferably performed in one pot. That is, it is preferable to carry out the reaction of lithiating the compound represented by the general formula [1] with n-BuLi and the reaction of the compound in the subsequent steps in one container. By performing all the reactions in one pot, the economic efficiency is improved. Moreover, it is preferable also from an equipment point of view to carry out all the reactions in one pot.

  Hereinafter, representative specific examples of the compound represented by the general formula [1] of the present invention will be shown, but the present invention is not limited thereto.

  Hereinafter, representative specific examples of the compound represented by the general formula [2] of the present invention will be shown, but the present invention is not limited thereto.

  Hereinafter, representative specific examples of the compound represented by the general formula [3] of the present invention will be shown, but the present invention is not limited thereto.

  Hereinafter, representative specific examples of the compound represented by the general formula [4] of the present invention will be shown, but the present invention is not limited thereto.

  Hereinafter, representative specific examples of the compound represented by the general formula [5] of the present invention will be shown, but the present invention is not limited thereto.

  Hereinafter, representative specific examples of the compound represented by the general formula [6] of the present invention will be shown, but the present invention is not limited thereto.

  Hereinafter, representative specific examples of the compound represented by the general formula [7] of the present invention will be shown, but the present invention is not limited thereto.

  Hereinafter, representative specific examples of the compound represented by the general formula [10] of the present invention will be shown, but the present invention is not limited thereto.

  EXAMPLES The present invention will be specifically described by way of examples, but the embodiments of the present invention are not limited thereto.

Example 1 (comparative example)
Synthesis of Exemplified Compound 5-3

Exemplified compound 1-1 16.9 g (0.10 mol) of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 30.5 g, AcOK 29.6 g, and DMSO 170 ml are added. And bubbling nitrogen for 20 minutes. To this suspension, 8.2 g of PdCl ₂ dppf was added, and the mixture was heated and stirred at 90 ° C. for 2 hours. Ethyl acetate was added, washed with water and then the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica gel, developing solution: ethyl acetate / toluene) to obtain 16.2 g of Exemplified compound 3-1. A solution of 5.2 g of the exemplified compound 4 and 9.2 g of potassium carbonate dissolved in 19 ml of pure water and 480 ml of THF were mixed, and nitrogen bubbling was performed for 20 minutes. To this suspension, 1.5 g of Pd (dba) _{2 and} 1.0 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The mixture was stirred for 5 hours under water cooling, and the precipitated crystals were filtered, washed with water and dried to obtain 7.7 g of gray crystals (yield: 23.9%, purity 98.9%).
The structures of Exemplified Compound 3-1 and Exemplified Compound 5-3 were confirmed by ¹ H NMR.

Exemplary Compound 3-1 ¹ H NMR (400 MHz, CDCl 3): 8.65 (d, 1 H), 8. 25 (d, 1 H), 7. 70 (d, 2 H), 7.56 (t, 1 H), 7.43 (t, 1 H), 1.45 (s, 12H)
Exemplary Compound 5-3 ¹ H NMR (400 MHz, CDCl 3): 8.84 (d, 3 H), 8. 78 (s, 3 H), 8. 36 (d, 3 H), 7. 77 (d, 3 H), 7. 70 (d, 3 H), 7.63 (t, 3H), 7.52 (t, 3H)

Example 2 (comparative example)
Synthesis of Exemplified Compound 5-3

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-1 is dissolved in 300 m of dehydrated THF, and cooled to -70 ° C. with a dry ice / acetone bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol The comparative compound 1-1) was added dropwise over 10 minutes. After stirring at room temperature for 2 hours, the solution was cooled again to -70 ° C, and a solution of 25.4 g of I ₂ dissolved in 50 ml of THF was added dropwise over 10 minutes and stirred at room temperature for 2 hours. The extract was washed with saturated brine and the solvent was evaporated under reduced pressure. Recrystallization was carried out with 100 ml of methanol to obtain 25.6 g of iodo compound. Next, 25.6 g of the obtained iodo compound is dissolved in 250 m of dehydrated THF, cooled to -70 ° C. with a dry ice / acetone bath, and 51.1 ml of 1.6 M nBuLi (× 0.95 molar ratio to iodine compound) for 10 min. It dripped at. The mixture was stirred at room temperature for 2 hours, cooled again to -70 ° C, 16.1 g of the exemplified compound 2-7 was added dropwise over 10 minutes, and stirred at room temperature for 1 hour. A solution of 450 ml of THF, 8.2 g of the exemplified compound 4-3, and 14.5 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.3 g of Pd (dba) _{2 and} 1.6 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The mixture was stirred for 5 hours under water cooling, and the precipitated crystals were filtered, washed with water and dried to obtain 9.8 g of gray crystals (yield 55.9%, purity 94.5%).

Example 3 (Invention)
Synthesis of Exemplified Compound 5-3

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-1 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 -1) was added dropwise over 10 min (the water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 10 ° C. A solution of 480 ml of THF, 9.5 g of the exemplified compound 4-3, and 16.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The precipitated crystals were filtered, washed with water and dried to obtain 14.4 g of gray crystals (yield 82.0%, purity 99.0%).

Example 4 (invention)
Synthesis of Exemplified Compound 5-3

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-1 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 -1) was added dropwise over 10 min (the water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 9.5 g of the exemplified compound 4-3, and 16.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The mixture was stirred for 5 hours under water cooling, and the precipitated crystals were filtered, washed with water and dried to obtain 15.0 g of gray crystals (yield 85.2%, purity 99.5%).

Example 5 (Invention)
Synthesis of Exemplified Compound 5-3

  The yield and the purity when the molar ratio of nBuLi to the exemplified compound 1-1 in Example 4 is changed as shown in Table 1 are shown in Table 1. The relationship between the molar ratio and the purity is shown in FIG. In addition, it is the same as that of Example 4 except this molar ratio. The purity was measured by HPLC under the following conditions.

[HPCL condition]
Column GL Sciences Inc. Inertsil ODS-3 5μm φ4.6mm x 250mm
Eluent CH ₂ Cl ₂ / acetonitrile 10/90 vol / vol
Oven temperature 40 ° C
Detection wavelength 254 nm
Flow rate 1 ml / min

  The results are shown in Table 1 and FIG.

  As shown in Table 1 and FIG. 4, 0.85 to 0.99 in molar ratio is found to be high in both yield and purity.

Example 6 (invention)
Synthesis of Exemplified Compound 5-3

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-1 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 -1) was added dropwise over 10 min (the water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 9.5 g of the exemplified compound 4-3, and 16.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. 3.7 g of PdCl ₂ dppf was added to this suspension and refluxed for 6 hours. The mixture was stirred for 5 hours under water cooling, and the precipitated crystals were filtered, washed with water and dried to obtain 13.2 g of gray crystals (yield 75.2%, purity 98.0%).

Example 7 (Invention)
Synthesis of Exemplified Compound 5-3

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-1 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 -1) was added dropwise over 10 min (the water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 9.5 g of the exemplified compound 4-3, and 16.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) ₂ and 2.2 g of XPhos were added and refluxed for 6 hours. The precipitated crystals were filtered, washed with water and dried to obtain 12.8 g of gray crystals (yield 73.2%, purity 98.1%).

Example 8 (Invention)
Synthesis of Exemplified Compound 5-5

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-1 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 -1) was added dropwise over 10 min (the water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 9.5 g of the exemplified compound 4-5, and 16.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. After washing with saturated brine, the solvent was evaporated under reduced pressure. Recrystallization with cyclohexane gave 14.2 g of gray crystals (yield 81%, purity 99.3%).
The structure of the exemplary compound 5-5 was confirmed by ¹ H NMR.

Exemplified compound 5-5 ¹ H NMR (400 MHz, CDCl 3): 8.80 (d, 1 H), 8. 47-8. 43 (m, 3 H), 8. 40 (d, 1 H), 8.33 (d, ¹ H), 8. 16 (d, 2 H) , 8.07 (d, 1H), 7.73-7.65 (m, 2H), 7.62 (t, 1H), 7.55-7.46 (m, 3H), 7.40 (t, 2H), 7.30-7.15 (m, 4H)

Example 9 (Invention)
Synthesis of Exemplified Compound 5-4

In a nitrogen stream, 24.5 g (0.10 mol) of Exemplified Compound 1-5 is dissolved in 390 m of dehydrated THF, and the ice water bath is put at −5 ° C., 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 The water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ^-4 mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 9.5 g of the exemplified compound 4-3, and 16.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The precipitated crystals were filtered, washed with water and dried to obtain 20.4 g of gray crystals (yield 83.2%, purity 99.5%).
The structure of the exemplary compound 5-4 was confirmed by ¹ H NMR.

Exemplary Compound 5-4 ¹ H NMR (400 MHz, CDCl 3): 9.14 (s, 3 H), 8. 76 (d, 3 H), 8.31 (d, 3 H), 7.74-7. 68 (m, 12 H), 7.58 (t, 3 H) , 7.08 (t, 3H), 6.97 (t, 6H)

Example 10 (Invention)
Synthesis of Exemplified Compound 7-1

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-1 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 -1) was added dropwise over 10 min (the water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 14.2 g of Exemplified Compound 6-1, and 18.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The precipitated crystals were filtered, washed with water and dried to obtain 19.1 g of gray crystals (yield 86.2%, purity 99.5%).
The structure of the exemplary compound 7-1 was confirmed by ¹ H NMR.

Exemplary Compound 7-1 ¹ H NMR (400 MHz, CDCl 3): 8.74 (d, 2 H), 8.31 (d, 2 H), 8. 20 (d, 4 H), 7. 93 (d, 4 H), 7.74-7.61 (m, 6 H) , 7.50 (t, 2H)

Example 11 (present invention)
Synthesis of Exemplified Compound 7-2

In a nitrogen stream, 24.5 g (0.10 mol) of Exemplified Compound 1-5 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 The water content of THF was measured by coulometric titration and was 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ^-4 mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 14.2 g of Exemplified Compound 6-1, and 18.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The precipitated crystals were filtered, washed with water and dried to obtain 24.9 g of gray crystals (yield 85.5%, purity 99.5%).
The structure of Exemplified Compound 7-2 was confirmed by ¹ H NMR.

Exemplified compound 7-2 ¹ H NMR (400 MHz, CDCl 3): 8.78 (d, 2 H), 8.31 (d, 2 H), 8.23 (d, 4 H), 8.00 (d, 4 H), 7. 89 (d, 4 H), 7.80 (d, 2H), 7.69 (d, 2H), 7.63-7.57 (m, 6H), 7.48 (t, 2H)

Example 12 (Invention)
Synthesis of Exemplified Compound 7-4

In a nitrogen stream, 24.5 g (0.10 mol) of Exemplified Compound 1-10 is dissolved in 390 m of dehydrated THF, adjusted to -5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 -10) was added dropwise over 10 minutes (the water content of THF was determined by coulometric titration to be 15 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-7 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 14.2 g of Exemplified Compound 6-1, and 18.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The precipitated crystals were filtered, washed with water and dried to obtain 24.6 g of gray crystals (yield: 84.5%, purity: 99.4%).
The structure of the exemplary compound 7-4 was confirmed by ¹ H NMR.

Exemplary Compound 7-4 ¹ H NMR (400 MHz, CF 3 COOD): 9.32 (d, 2 H), 9. 10 (s, 2 H), 9.00 (d, 4 H), 8. 86 (d, 2 H), 8. 78 (d, 2 H), 8. 66 (d, 4H), 8.55 (d, 2H), 8.22 (d, 4H), 8.06 (t, 4H), 7.97 (d, 2H)

Example 13 (Invention)
Synthesis of Exemplified Compound 7-6

In a nitrogen stream, 16.9 g (0.10 mol) of Exemplified Compound 1-2 is dissolved in 390 m of dehydrated THF, adjusted to −5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 (The water content of THF was 15 ppm when measured by coulometric titration. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻⁴ mol of water molecules. 0.20 ml was added as a correction amount. After stirring for 1 hour, 18.6 g of the exemplified compound 2-1 was added dropwise over 10 minutes, and the mixture was stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 15.6 g of the exemplified compound 6-7, and 18.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.8 g of the exemplified compound 10-1 were added, and the mixture was refluxed for 6 hours. The mixture was stirred for 5 hours under water cooling, and the precipitated crystals were filtered, washed with water and dried to obtain 17.8 g of gray crystals (yield 75.2%, purity 99.2%).

Example 14 (Invention)
Synthesis of Exemplified Compound 7-11

In a nitrogen stream, 18.6 g (0.10 mol) of Exemplified Compound 1-16 is dissolved in 390 m of dehydrated THF, adjusted to -5 ° C. with an ice water bath, and 59.4 ml of 1.6 M nBuLi (× 0.95 mol ratio to Exemplified Compound 1 (The water content of THF was measured by coulometric titration method and was 150 ppm. This corresponds to a corresponding amount of 1.6 M nBuLi solution per 3.25 × 10 ⁻³ mol of water molecules. Added 2.0 ml as a correction amount). After stirring for 1 hour, 17.2 g of Exemplified compound 2-8 was added dropwise over 10 minutes and stirred for 1 hour. During this time, the internal temperature was -10 ° C to 5 ° C. A solution of 480 ml of THF, 11.8 g of Example Compound 6-3, and 16.8 g of potassium carbonate dissolved in 30 ml of pure water was sequentially charged, and nitrogen bubbling was performed for 20 minutes. To this suspension, 2.7 g of Pd (dba) _{2 and} 1.9 g of the exemplified compound 10-4 were added, and the mixture was refluxed for 6 hours. The precipitated crystals were filtered, washed with water and dried to obtain 15.7 g of gray crystals (yield: 73.2%, purity: 99.1%).

  Identification of each compound in the examples was performed by MASS and NMR spectra, and it was confirmed that each was the target compound. Other exemplified compounds can also be synthesized according to the above method.

  As described above, according to the production method of the present invention, borate compounds which are useful intermediates of organic synthetic compounds and nitrogen-containing heterocyclic compounds derived therefrom can be obtained with high purity and high yield. In addition, the borate compounds obtained by the production method of the present invention and the nitrogen-containing heterocyclic compounds derived therefrom are particularly useful as materials for organic electroluminescence, and have excellent effects.

Claims (12)

The compound represented by the following general formula [1] is lithiated with n-BuLi, and the compound represented by the following general formula [2] is further reacted to obtain the compound represented by the following general formula [3] Method for producing a nitrogen-containing heterocyclic compound

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ and R ₂ represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents a hydrogen atom or a substituent. However, the number of N of A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2 and m ₂ is an integer of 0 to _4. R _{3 to} R ₅ are each independently Represents an alkyl group, a cycloalkyl group, or an aryl group, and R ₄ and R ₅ may combine with each other to form a ring)   The method for producing a nitrogen-containing heterocyclic compound according to claim 1, wherein the addition amount of the n-BuLi is 0.85 to 0.99 in molar ratio to the general formula [1].   The reaction is carried out at a reaction temperature of −20 ° C. to 10 ° C., by which the compound represented by the general formula [1] is lithiated with the n-BuLi, and the compound represented by the general formula [2] is further reacted. The manufacturing method of the nitrogen-containing heterocyclic compound of Claim 1 or Claim 2. The general formula [1] is represented by the following general formula [8], and the general formula [3] is represented by the following general formula [9] The manufacturing method of the nitrogen-containing heterocyclic compound as described in a term.

(Wherein, _{X 1} is _.R 1, _{R 2} is an integer of .m ₁ is 0 to 2 represents a substituent, _{m 2} is _.R 4 represents an integer of 0 to 4 representing an oxygen atom or a sulfur atom, R ₅ each independently represents an alkyl group, a cycloalkyl group or an aryl group, and R ₄ and R ₅ may combine with each other to form a ring) The compound represented by following General formula [4], without refine | purifying the nitrogen-containing heterocyclic compound manufactured by the manufacturing method of the nitrogen-containing heterocyclic compound as described in any one of Claims 1-4. A method for producing a nitrogen-containing heterocyclic compound, which comprises reacting in the presence of a Pd catalyst and a phosphine ligand to obtain a compound represented by the following general formula [5].

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ and R ₆ each represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents a hydrogen atom or A represents a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4 and m ₆ is an integer of 0 to 4 X ₂ represents a chlorine atom, a bromine atom or an iodine atom, and n ₂ represents an integer of ₂ to 4.) The compound represented by following General formula [6], without refine | purifying the nitrogen-containing heterocyclic compound manufactured by the manufacturing method of the nitrogen-containing heterocyclic compound as described in any one of Claims 1-4. A method for producing a nitrogen-containing heterocyclic compound, which is reacted in the presence of a Pd catalyst and a phosphine ligand to obtain a compound represented by the following general formula [7].

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ , R ₇ and R ₈ represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents H ₁ represents a hydrogen atom or a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4, m ₇ and m ₈ are Each independently represents an integer of 0 to _3. X ₃ and X ₄ each independently represent a chlorine atom, a bromine atom or an iodine atom n ₃ and n ₄ each independently represent an integer of 1 to 2 A represents a simple bond or a divalent linking group.) Reacting a compound represented by the following general formula [3] with a compound represented by the following general formula [4] in the presence of a Pd catalyst and a phosphine ligand to obtain a compound represented by the following general formula [5] The manufacturing method of the nitrogen-containing heterocyclic compound which is characterized.

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ and R ₆ each represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents a hydrogen atom or A represents a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4 and m ₆ is an integer of 0 to 4 X ₂ represents a chlorine atom, a bromine atom or an iodine atom, n ₂ represents an integer of ₂ to 4. R ₄ and R ₅ each independently represent an alkyl group, a cycloalkyl group or an aryl group , R ₄ and R ₅ may combine with each other to form a ring.) Reacting a compound represented by the following general formula [3] with a compound represented by the following general formula [6] in the presence of a Pd catalyst and a phosphine ligand to obtain a compound represented by the following general formula [7] The manufacturing method of the nitrogen-containing heterocyclic compound which is characterized.

(Wherein, X ₁ represents an oxygen atom or a sulfur atom. R ₁ , R ₂ , R ₇ and R ₈ represent a substituent. A _{1 to} A ₄ each independently represent N or CR, and R represents H ₁ represents a hydrogen atom or a substituent, provided that the number of N in A _{1 to} A ₄ is 1 to 2. m ₁ is an integer of 0 to 2, m ₂ is an integer of 0 to 4, m ₇ and m ₈ are Each independently represents an integer of 0 to _3. X ₃ and X ₄ each independently represent a chlorine atom, a bromine atom or an iodine atom n ₃ and n ₄ each independently represent an integer of 1 to 2 A represents a simple bond or a divalent linking group R ₄ and R ₅ each independently represent an alkyl group, a cycloalkyl group or an aryl group, and R ₄ and R ₅ are bonded to each other to form a ring You may form The method for producing a nitrogen-containing heterocyclic compound according to claim 7 or 8, wherein the general formula [3] is represented by the following general formula [9].

(Wherein, _{X 1} is _.R 1, _{R 2} is an integer of .m ₁ is 0 to 2 represents a substituent, _{m 2} is _.R 4 represents an integer of 0 to 4 representing an oxygen atom or a sulfur atom, R ₅ each independently represents an alkyl group, a cycloalkyl group or an aryl group, and R ₄ and R ₅ may combine with each other to form a ring) The method for producing a nitrogen-containing heterocyclic compound according to any one of claims 5 to 9, wherein the phosphine ligand is represented by the following general formula [10].

(Wherein, R _{9 to} R ₁₁ each independently represent an alkyl group, a cycloalkyl group or an aryl group).   The method for producing a nitrogen-containing heterocyclic compound according to any one of claims 1 to 10, wherein all reactions are carried out in the same ether solvent.   The method for producing a nitrogen-containing heterocyclic compound according to any one of claims 1 to 11, wherein all the reactions are carried out in one pot.

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