Method for producing sulfonamide compound using sulfonyl triazolium

Abstract

The present invention provides a method for producing a sulfonamide compound, the method including reacting a compound having a group represented by formula 1 with a nitrogen-containing compound selected from an amine and ammonia or a salt thereof, and converting the group to a sulfonamide group corresponding to the nitrogen-containing compound.

Description

Method for producing sulfonamide compounds using sulfonyltriazolium

[0001] The present application relates to a method for producing a compound having a sulfonamide group. Further, the present application relates to a novel sulfonyltriazolium compound.

[0002] Sulfonamide compounds are widely used in pharmaceuticals and other compounds, and can generally be produced by reacting a nitrogen-containing compound such as an amine with a sulfonylating agent (Non-Patent Documents 1 and 2). Examples of sulfonylating agents include sulfonyl chloride (R-SO ２ Cl) is widely used (Non-Patent Documents 3 and 4).

[0003] It is known that the reaction between amines and sulfonylating agents may not proceed smoothly or may produce by-products due to steric and / or electronic factors near the reaction site. A method using sulfonylimidazolium salts as sulfonylating agents has been reported as a method applicable to amines with large steric hindrance (Non-Patent Documents 5 to 7). Other sulfonylating agents reported include sulfonylimidazoles, sulfonyltriazoles, sulfonylbenzotriazoles, sulfonylpyrazoles, and sulfonate esters of Oxyma (Non-Patent Documents 8 to 11).

[0004] WO 2022 / 149617 A1

[0005] Sosunovych, B. et al., Chem. Rec. 2023, e202300258;Shavan, M. et al., Tetrahedron, 2020, 76, 131662-13168;Shigeno, M. et al., Org. Lett. 2022, 24, 809-814;Thalji, RK et al., J.Am.Chem.Soc. 2001, 123, 9692-9693;Monjoint, P. et al., Tetrahedron Lett. 1984, 25, 3183-3186;O'connell, JF et al., J. Org. Chem. 1992, 57, 4775-4777;Vilkas, E., Bulletin de la Societe Chemiqute de France 1978, N0, 1-2;Connor, CG et al., Org. Process Res. Dev., 2021, 25, 608-615;Ramkumar, R. et al., ChemistrySelect. 2018, 3, 2306-2310;Katritzky, AR et al., J. Org. Chem. 2004, 69, 1849-1852;Palakurthy, NB et al., Eur. J. Org. Chem., 2013, 2627;Opitz, G. et al., Chem Ber. 1990, 123, 1563-1569;Willard, AL. et al., J. Comb. Chem. 2004, 6, 611-622。

[0006] As mentioned above, sulfonylating agents having various leaving groups have been investigated. However, in the case of sulfonamide bond formation using substrates or sulfonylating agents with extremely low reactivity, such as reactions using sterically hindered amines and / or amines with low nucleophilicity, or reactions introducing sterically hindered sulfonyl groups, existing methods using the above-mentioned imidazolium salts have problems that have not yet been solved by conventional methods, such as the inability to obtain the target sulfonamide compound in sufficient yield or the generation of large amounts of by-products. Furthermore, primary alkylsulfonyl halides or secondary alkylsulfonyl halides are known to decompose in the presence of triethylamine (Non-Patent Document 12). In particular, sulfonamidation using secondary sulfonyl halides is difficult, and conventional methods have problems that have not yet been solved, such as the inability to obtain the target sulfonamide compound in sufficient yield and / or the generation of large amounts of by-products (Non-Patent Document 13). In fact, according to the inventors' experiments, when sulfonamidation was performed using a combination of a secondary aniline substrate, which is less nucleophilic than an alkylamine, with a secondary alkylsulfonyl chloride or a secondary alkylsulfonylimidazolium salt, or a combination of an ortho-disubstituted primary aniline with a bulky sulfonyl chloride, the target product was confirmed only in low yield. A more versatile method for forming sulfonamide bonds that can be applied to such difficult combinations is needed.

[0007] For example, combinatorial synthesis techniques are used to produce compound libraries for pharmaceutical screening, and it has been reported that efficient library production is achieved by carrying out reactions using a mixture of many types of compounds as a substrate (Patent Document 1). When a mixture of many types of amine compounds is used as a substrate and a sulfonylating agent is used to produce many types of sulfonamide compounds, the yield of the corresponding sulfonamide compounds varies greatly depending on the reactivity of the substrates, and in some cases, it is expected that the target compound cannot be obtained. There is a need for a highly reactive sulfonylating agent that can be applied to various substrates and can produce the target sulfonamide compounds in good yield even with low-reactivity substrates.

[0008] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a method for producing a sulfonamide compound, which can improve the yield and / or suppress the production of by-products in a reaction for forming a sulfonamide bond from an amine and a sulfonyltriazolium salt. Another object of the present invention is to provide a method for synthesizing a compound, which includes the above method. Another object of the present invention is to provide a method for improving the yield and / or suppressing the production of by-products, which can be applied to a method for forming a sulfonamide bond from an amine and a sulfonyltriazolium salt.

[0009] The present inventors have discovered that in a reaction for preparing a sulfonamide compound from an amine and a sulfonylating agent by forming a sulfonamide bond through a condensation reaction between an amino group and a sulfonyl group, the reaction can proceed in high yield and / or with reduced by-product generation by improving the leaving group of the sulfonylating agent, thereby completing the present invention. Specifically, they have discovered that the use of a sulfonyltriazolium salt, the use of which has not previously been reported in sulfonamidation, allows the production of the desired sulfonamide compound in high yield and / or with reduced by-product generation. They have further discovered that these conditions are applicable to reactions for forming a sulfonamide bond from various amines and sulfonyltriazolium salts, thereby completing the present invention. In relation to several aspects of the present invention, the present specification discloses the following inventions.

[0010] [A-1] A method for producing a sulfonamide compound, comprising:

[0011]

[0012] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, and * represents a point of attachment, with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group into a sulfonamide group corresponding to the nitrogen-containing compound.

[0013] [A-2] A compound having a group represented by formula 1,

[0014]

[0015] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C７－１４ Aralkyl, C ６－１０ aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４ is as defined in [A-1], and X － is a counter anion.

[0016] [A-3] A compound having a group represented by formula 1,

[0017]

[0018] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４ is as defined in [A-1], and X － is a counter anion.

[0019] [A-4] X － is a halide anion, C optionally substituted with one or more halogen atoms １－６ Alkyl sulfonate anion, one or more C １－６ Benzene sulfonate anion optionally substituted with alkyl, and BF ４ － The method according to [A-2] or [A-3], selected from the group consisting of

[0020] [A-5] X－ are chloride anion, bromide anion, iodide anion, trifluoromethanesulfonate anion, methanesulfonate anion, p-toluenesulfonate anion, and BF ４ － The method according to [A-4], selected from the following:

[0021] [A-6] X － [A-7] The method according to [A-4], wherein R is a trifluoromethanesulfonate anion. ２ and R ４ are each independently a hydrogen atom and C １－６ The method according to any one of [A-1] to [A-6], wherein the alkyl is selected from the group consisting of alkyl.

[0022] [A-8]R １ The one or more substituents that the group represented by the formula (I) may have are a halogen atom, a cyano, C １－６ Alkyl, C １－６ Alkoxy, C ６－１０ Aryl, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-1] to [A-7], wherein the amino group is independently selected from the group consisting of an alkyl)aminocarbonyl, and a 4- to 8-membered cyclic aminocarbonyl.

[0023] [A-9]R １ The one or more substituents that the group represented by the formula (I) may have are a halogen atom, a cyano, C １－６Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-1] to [A-7], wherein the amino group is independently selected from the group consisting of an alkyl)aminocarbonyl, and a 4- to 8-membered cyclic aminocarbonyl.

[0024] [A-10]R ２ and R ４ are each independently selected from the group consisting of a hydrogen atom and methyl. [A-11] The method according to any one of [A-1] to [A-10], wherein the nitrogen-containing compound is selected from ammonia or a salt thereof, a primary amine, and a secondary amine.

[0025] [A-12] The method according to any one of [A-1] to [A-11], wherein the nitrogen-containing compound is selected from the group consisting of ammonia or a salt thereof, a primary amine having a nitrogen atom substituted with an aliphatic group, a primary amine having a nitrogen atom substituted with an aromatic group, a secondary amine having a nitrogen atom substituted with two aliphatic groups, a secondary amine having a nitrogen atom substituted with two aromatic groups, and a secondary amine having a nitrogen atom substituted with one aliphatic group and one aromatic group.

[0026] [A-13] The method according to any one of [A-1] to [A-12], wherein the nitrogen-containing compound contains one functional group capable of reacting with a group represented by formula 1 or a compound represented by formula 2. [A-14] The aromatic group is C ６－１０The method according to [A-12] or [A-13], wherein the heteroaryl is selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more substituents.

[0027] [A-15] The aromatic group is C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from the group consisting of halogen atoms, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ The method according to any one of [A-12] to [A-14], which is optionally substituted by one or more substituents independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S.

[0028] [A-16] The aromatic group is C ６－１０aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from the group consisting of halogen atoms, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ The method according to any one of [A-12] to [A-14], which is optionally substituted by one or more substituents independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S.

[0029] [A-17] The nitrogen-containing compound is represented by the formula A1 or A3

[0030] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; or R ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, and 5- to 10-membered heteroaryl C １－６ alkyl, each of which is optionally substituted by one or more substituents; R ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; X ａis O or S.

[0031] [A-18] The nitrogen-containing compound is represented by the formula A1 or A3

[0032] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; or R ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C１－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ cycloalkylalkyl, and C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents; R ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; X ａ is O or S.

[0033] [A-19] The nitrogen-containing compound is represented by the formula A1 or A3

[0034] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ Alkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted with one or more halogen atoms; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, and 5- to 10-membered heteroaryl C １－６ alkyl, each of which is selected from a halogen atom, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C１－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which may be optionally substituted with one or more halogen atoms; X ａ is O or S.

[0035] [A-20] The nitrogen-containing compound is represented by the formula A1 or A3

[0036] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C１－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted with one or more halogen atoms; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ cycloalkylalkyl, and C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which may be optionally substituted with one or more halogen atoms; X ａ is O or S.

[0037] [A-21] (1) Z １ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (2) Z ２ is N and Z １ is C-R ６ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (3) Z ３ is N and Z １ is C-R ６ and Z ２is C-R ７ and Z ４ is C-R ９ and Z ５ is C-R １０ (4) Z １ and Z ２ is N and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (5) Z １ and Z ４ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ５ is C-R １０ (6) Z １ and Z ５ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ４ is C-R ９ (7) Z ２ and Z ３ is N and Z １ is C-R ６ and Z ４ is C-R ９ and Z ５ is C-R １０ (8) Z ２ and Z ４ is N and Z １ is C-R ６ and Z ３ is C-R ８ and Z ５ is C-R １０ (9) Z １ , Z ３ , and Z ５ is N and Z ２ is C-R ７ and Z ４ is C-R ９ and (10) Z １is C-R ６ and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ The method according to any one of [A-17] to [A-20], wherein

[0038] [A-22] The nitrogen-containing compound represented by formula A1':

[0039]

[0040] [In the formula, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0041] [A-23] The nitrogen-containing compound represented by formula A1':

[0042]

[0043] [In the formula, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C１－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0044] [A-24] The nitrogen-containing compound represented by formula A1': [In the formula, R ５ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C１－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0045] [A-25] The nitrogen-containing compound represented by formula A1': [In the formula, R ５ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R１０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0046] [A-26] The nitrogen-containing compound represented by formula A1': [In the formula, R ５ is a hydrogen atom, and R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0047] [A-27] The nitrogen-containing compound has formula A2: [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; or R １１ and R １２ and together with the nitrogen atom to which they are bonded form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0048] [A-28] The nitrogen-containing compound has formula A2: [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents, or R １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0049] [A-29] The nitrogen-containing compound has formula A2:

[0050]

[0051] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; or R １１ and R １２ and together with the nitrogen atom to which they are bonded form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0052] [A-30] The nitrogen-containing compound has formula A2:

[0053]

[0054] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents, or R １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0055] [A-31] The nitrogen-containing compound has formula A2:

[0056] [In the formula, R １１ is a hydrogen atom, and R １２ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents.

[0057] [A-32] The nitrogen-containing compound has formula A2:

[0058] [In the formula, R １１ is a hydrogen atom, and R １２ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which may be substituted by one or more substituents.

[0059] [A-33] The nitrogen-containing compound has formula A2:

[0060]

[0061] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２and together with the nitrogen atom to which they are bonded form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0062] [A-34] The nitrogen-containing compound has formula A2:

[0063]

[0064] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0065] [A-35] The nitrogen-containing compound has formula A2:

[0066]

[0067] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ and together with the nitrogen atom to which they are bonded form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0068] [A-36] The nitrogen-containing compound has formula A2:

[0069]

[0070] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0071] [A-37] The nitrogen-containing compound has formula A2:

[0072]

[0073] [In the formula, R １１ is a hydrogen atom, and R １２ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-1] to [A-13], wherein the amino group is optionally substituted with one or more substituents selected from (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0074] [A-38] The nitrogen-containing compound has formula A2:

[0075]

[0076] [In the formula, R １１ is a hydrogen atom, and R １２ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-1] to [A-13], wherein the amino group is optionally substituted with one or more substituents selected from (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0077] [A-39] The nitrogen-containing compound is represented by formula A1, A2, or A3:

[0078]

[0079] [In the formula, R ５ ~R １２ , R ａ ~R ｃ , Z １ ~Z ５ , R ａ ~R ｃ , and X ａ The method according to any one of [A-1] to [A-38], wherein the compound is as defined in any one of [A-17] to [A-38].

[0080] [A-40] The nitrogen-containing compound represented by formula A1′ or A2:

[0081]

[0082] [In the formula, R ５ ~R １２ The method according to any one of [A-1] to [A-39], wherein the compound is as defined in any one of [A-17] to [A-38].

[0083] [A-41] The method according to any one of [A-1] to [A-40], comprising reacting a compound having a group represented by formula 1 or a compound represented by formula 2 with a nitrogen-containing compound selected from an amine and ammonia or a salt thereof in the presence of a base to obtain a sulfonamide compound.

[0084] [A-42] The method according to [A-41], wherein the base is an inorganic base or an organic base whose conjugate acid in water has a pKa of 10 or less. [A-43] The method according to [A-41] or [A-42], wherein the base is an organic base whose conjugate acid in water has a pKa of 10 or less.

[0085] [A-44] The method according to any one of [A-41] to [A-43], wherein the pKa in water of the conjugate acid of the organic base is 0 to 10, 3 to 10, 3 to 9, 3 to 8, or 5 to 7. [A-45] The organic base is represented by the formula B1, B2, B3, and B4:

[0086]

[0087] [In the formula, R １３ , R １４ , R １５ , R １６ and R １７ are each independently a hydrogen atom, C １－６ Alkyl, and C ６－１０ aryl, wherein said C １－６ Alkyl, and C ６－１０ The aryl may be substituted with one or more halogen atoms, and X １ , X ２ , and X ３ are each independently a nitrogen atom or CH, １８ is C １－６ Alkyl, and C ６－１０ aryl, R １９ is a hydrogen atom, C １－６ Alkyl, and C ６－１０ aryl; X ４ is NR ２１ or an oxygen atom, R ２０ and R ２１ are each independently, C １－６ alkyl, R２２ and R ２３ are each independently C １－６ Alkyl, and C ６－１０ aryl, R ２４ , R ２５ , R ２６ , R ２７ , and R ２８ are each independently a hydrogen atom, C １－６ Alkyl, C ６－１０ The method according to any one of [A-41] to [A-44], wherein the compound is at least one selected from the group consisting of compounds represented by the formula (I) and (II), wherein the compound is selected from the group consisting of aryl, a halogen atom, and cyano.

[0088] [A-46] The organic base is represented by the formulae B1′, B2′, B3′, and B4′:

[0089] [In the formula, R １３ , R １５ and R １７ are each independently a hydrogen atom and C １－６ alkyl, wherein said C １－６ The alkyl may be substituted with one or more halogen atoms, and X ２ and X ３ are each independently a nitrogen atom or CH, １８ is C １－６ alkyl, R １９ is C １－６ alkyl, R ２２ and R ２３ are each independently C １－６ The method according to any one of [A-41] to [A-45], wherein two or more compounds may be used, selected from the group consisting of compounds represented by the formula:

[0090] [A-47] The method according to any one of [A-41] to [A-45], wherein the organic base is selected from the group consisting of pyridine, 2-methylpyridine, 2,6-lutidine, 2,4-lutidine, 2,4,6-collidine, 2,6-di-tert-butylpyridine (DTBP), N-methylimidazole (NMI), 4-methyl-4H-1,2,4-triazole, and N-methylmorpholine (NMM), and two or more of these may be used.

[0091] [A-48] The method according to [A-41] or [A-42], wherein the base is an inorganic base. [A-49] The method according to any one of [A-41], [A-42], and [A-48], wherein the inorganic base is selected from the group consisting of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, barium carbonate, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, lithium phosphate, sodium phosphate, potassium phosphate, cesium phosphate, magnesium phosphate, calcium phosphate, and barium phosphate, and two or more of these may be used.

[0092] [A-50] The method according to any one of [A-1] to [A-49], wherein the reaction is carried out in the presence of a solvent. [A-51] The method according to [A-50], wherein the solvent is at least one selected from the group consisting of halogen-based solvents, nitrile-based solvents, amide-based solvents, ether-based solvents, and aromatic hydrocarbon-based solvents.

[0093] [A-52] The method according to [A-50] or [A-51], wherein the solvent is a halogenated solvent. [A-53] The method according to [A-51] or [A-52], wherein the halogenated solvent is at least one selected from the group consisting of dichloromethane, chloroform, and 1,2-dichloroethane.

[0094] [A-54] The method according to any one of [A-51] to [A-53], wherein the halogen-based solvent is dichloromethane. [A-55] The method according to [A-50] or [A-51], wherein the solvent is a nitrile-based solvent.

[0095] [A-56] The method according to [A-51] or [A-55], wherein the nitrile solvent is at least one selected from the group consisting of acetonitrile, propionitrile, and benzonitrile. [A-57] The method according to [A-50] or [A-51], wherein the solvent is an amide solvent.

[0096] [A-58] The method according to [A-51] or [A-57], wherein the amide solvent is at least one selected from the group consisting of N-methylpyrrolidone, N,N-dimethylacetamide, N,N-dimethylformamide, N,N-dimethylpropionamide, N,N-dimethylisobutyramide, N,N-diethylacetamide, N,N-diethylpropionamide, 1-ethyl-2-pyrrolidinone, 1-octyl-2-pyrrolidinone, 1-cyclohexyl-2-pyrrolidinone, and N-methylcaprolactam.

[0097] [A-59] The method according to [A-50] or [A-51], wherein the solvent is an ether-based solvent. [A-60] The method according to [A-51] or [A-59], wherein the ether-based solvent is at least one selected from the group consisting of tetrahydrofuran, diethyl ether, 2-methyltetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,3-dioxolane, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, and 4-methyltetrahydropyran.

[0098] [A-61] The method according to [A-50] or [A-51], wherein the solvent is an aromatic hydrocarbon solvent. [A-62] The method according to [A-51] or [A-61], wherein the aromatic hydrocarbon solvent is at least one selected from the group consisting of benzene, chlorobenzene, toluene, and xylene.

[0099] [A-63] The method according to any one of [A-1] to [A-62], wherein the reaction is carried out at a reaction temperature of 0° C. to 100° C. [A-64] The method according to [A-63], wherein the reaction temperature is 0° C. to 80° C., 10° C. to 60° C., 15° C. to 50° C., or 15° C. to 40° C.

[0100] [A-65] The method according to [A-63] or [A-64], wherein the reaction temperature is 15° C. to 40° C. [A-66] The method according to any one of [A-1] to [A-65], wherein the reaction is carried out by a solid phase method.

[0101] [A-67] The method according to any one of [A-1] to [A-65], wherein the reaction is carried out by a liquid phase method. [A-68] Formula 3:

[0102]

[0103] [In the formula, R ２ and R ４ is as defined in [A-1], and represents a point of attachment] to a group represented by formula 1 by alkylating the group represented by formula 1 with an alkylating agent, thereby obtaining a compound having a group represented by formula 1.

[0104] [A-69] Formula 4:

[0105] [In the formula, R １ , R ２ and R ４ is as defined in [A-2]] with an alkylating agent to obtain a compound represented by formula 2.

[0106] [A-70] The alkylating agent is a compound represented by the formula: R ３ -X [wherein, R ３ is C １－６ [A-71] The method according to any one of [A-67] to [A-69], wherein X is a compound represented by the formula (I) wherein X is a halogen atom, C optionally substituted with one or more halogen atoms, or C optionally substituted with one or more halogen atoms. １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ The method according to [A-70], selected from the following:

[0107] [A-72] X is a chlorine atom, a bromine atom, an iodine atom, trifluoromethanesulfonyloxy, methanesulfonyloxy, p-toluenesulfonyloxy, or —BF ４ The method according to [A-70], selected from the following:

[0108] [A-73] The method according to [A-70], wherein X is trifluoromethanesulfonyloxy. [A-74] The method according to any one of [A-68] to [A-73], wherein alkylation with an alkylating agent to obtain a compound having a group represented by formula 1 or a compound represented by formula 2, and conversion to a sulfonamide group with a nitrogen-containing compound are carried out in one pot.

[0109] [A-75] The method according to any one of [A-1] to [A-74], wherein a mixture of two or more nitrogen-containing compounds is reacted to obtain two or more sulfonamide compounds. [A-76] The method according to any one of [A-1] to [A-10], [A-41] to [A-65], and [A-68] to [A-75], wherein the nitrogen-containing compound is a resin for solid-phase synthesis to which an amine is bound via a linker.

[0110] [A-77] The method according to [A-76], wherein the amine bonded to the resin for solid phase synthesis via a linker is an amine specified in any one of [A-11] to [A-40]. [A-78] The method according to either [A-76] or [A-77], wherein a reaction is carried out using a mixture of two or more resins for solid phase synthesis, each of which has the same amine bonded thereto, but each of which has a different amine bonded thereto, to obtain two or more sulfonamide compounds.

[0111] [A-79] The method according to any one of [A-1] and [A-11] to [A-65], wherein the compound having a group represented by formula 1 is a resin for solid phase synthesis to which the compound having a group represented by formula 1 is bound via a linker.

[0112] [A-80] The method according to [A-79], wherein the compound having a group represented by formula 1 that is bound to the resin for solid phase synthesis via a linker is a compound having a group represented by formula 1 specified in any one of [A-2] to [A-10].

[0113] [A-81] Formula 3:

[0114] [In the formula, R ２ and R ４ is as defined in [A-1], and represents a point of attachment] to a group represented by formula 1 by alkylating the group represented by the formula (I) with an alkylating agent, thereby obtaining a resin for solid phase synthesis to which a compound having a group represented by formula 1 is bound via a linker.

[0115] [A-82] via a linker, Formula 4:

[0116] [In the formula, R １ , R ２ and R ４ is as defined in [A-2]] is alkylated with an alkylating agent to convert the solid phase synthesis resin to which a compound having a group represented by Formula 1 is bound via a linker.

[0117] [A-83] The alkylating agent is a compound represented by the formula: R ３ -X [wherein, R ３ is C １－６ [A-84] The method according to [A-81] or [A-82], wherein X is a compound represented by the formula (I) wherein X is a halogen atom, C optionally substituted with one or more halogen atoms, or C optionally substituted with one or more halogen atoms. １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ The method according to [A-83], selected from the following:

[0118] [A-85] X is a chlorine atom, a bromine atom, an iodine atom, trifluoromethanesulfonyloxy, methanesulfonyloxy, p-toluenesulfonyloxy, or —BF ４ The method according to [A-84], selected from the following:

[0119] [A-86] The method according to [A-84], wherein X is trifluoromethanesulfonyloxy. [A-87] The method according to any one of [A-79] to [A-86], wherein a reaction is carried out using a mixture of solid phase synthesis resins, each of which is bound to a compound having the same group represented by Formula 1, and each of which is bound to a different compound having the group represented by Formula 1, to obtain two or more sulfonamide compounds.

[0120] [B-1] A method for producing a compound constituting a compound library, the method comprising producing a sulfonamide compound by the method described in any one of [A-1] to [A-87].

[0121] [B-2] The method according to [B-1], wherein the production of a sulfonamide compound is carried out by a solid phase method. [B-3] The method according to [B-1] or [B-2], wherein the production of a sulfonamide compound is carried out by a split-mix method.

[0122] [B-4] The method according to [B-2] or [B-3], further comprising producing a sulfonamide compound using a resin for solid phase synthesis and cleaving the compound from the resin for solid phase synthesis.

[0123] [B-5] The method according to [B-1] or [B-2], wherein the production of sulfonamide compounds is carried out by a parallel method. [B-6] The method according to any one of [B-1] to [B-5], wherein the number of compounds constituting the compound library is 10 to 10,000, 10 to 1,000, or 10 to 100.

[0124] [C-1] A method for forming a sulfonamide bond, comprising:

[0125] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６alkyl or benzyl, and * represents an attachment point] with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group to a sulfonamide group corresponding to the nitrogen-containing compound.

[0126] [C-2] A compound having a group represented by formula 1,

[0127]

[0128] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４ is as defined in [C-1], and X － is a counter anion.

[0129] [C-3] The compound having a group represented by formula 1 is a compound having a group represented by formula 2:

[0130]

[0131] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０aryl, 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４ is as defined in [C-1], and X － is a counter anion.

[0132] [C-4]X － is a halide anion, C optionally substituted with one or more halogen atoms １－６ Alkyl sulfonate anion, one or more C １－６ Benzene sulfonate anion optionally substituted with alkyl, and BF ４ － The method according to [C-2] or [C-3], selected from the group consisting of:

[0133] [C-5]X － are chloride anion, bromide anion, iodide anion, trifluoromethanesulfonate anion, methanesulfonate anion, p-toluenesulfonate anion, and BF ４ － The method according to [C-4], wherein the compound is selected from the group consisting of:

[0134] [C-6]X － [C-7] The method according to [C-4], wherein R is a trifluoromethanesulfonate anion. ２ and R ４ are each independently a hydrogen atom and C １－６ The method according to any one of [C-1] to [C-6], wherein the alkyl is selected from the group consisting of alkyl.

[0135] [C-8]R １ The one or more substituents that the group represented by the formula (I) may have are a halogen atom, a cyano, C １－６ Alkyl, C １－６ Alkoxy, C ６－１０ Aryl, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C１－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [C-1] to [C-7], wherein the amino group is independently selected from the group consisting of a 4- to 8-membered cyclic aminocarbonyl, an alkylaminocarbonyl, and a 4- to 8-membered cyclic aminocarbonyl.

[0136] [C-9]R １ The one or more substituents that the group represented by the formula (I) may have are a halogen atom, a cyano, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [C-1] to [C-7], wherein the amino group is independently selected from the group consisting of a 4- to 8-membered cyclic aminocarbonyl, an alkylaminocarbonyl, and a 4- to 8-membered cyclic aminocarbonyl.

[0137] [C-10]R ２ and R ４are each independently selected from the group consisting of a hydrogen atom and methyl. [C-11] The method according to any one of [C-1] to [C-10], wherein the nitrogen-containing compound is selected from ammonia or a salt thereof, a primary amine, and a secondary amine.

[0138] [C-12] The method according to any one of [C-1] to [C-11], wherein the nitrogen-containing compound is selected from the group consisting of ammonia or a salt thereof, a primary amine having a nitrogen atom substituted with an aliphatic group, a primary amine having a nitrogen atom substituted with an aromatic group, a secondary amine having a nitrogen atom substituted with two aliphatic groups, a secondary amine having a nitrogen atom substituted with two aromatic groups, and a secondary amine having a nitrogen atom substituted with one aliphatic group and one aromatic group.

[0139] [C-13] The method according to any one of [C-1] to [C-12], wherein the nitrogen-containing compound contains one functional group capable of reacting with a group represented by formula 1 or a compound represented by formula 2. [C-14] The aromatic group is C ６－１０ The method according to [C-12] or [C-13], wherein the heteroaryl is selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents.

[0140] [C-15] The aromatic group is C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from the group consisting of halogen atoms, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ The method according to any one of [C-12] to [C-14], which is optionally substituted by one or more substituents independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S.

[0141] [C-16] The aromatic group is C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from the group consisting of halogen atoms, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C６－１０ The method according to any one of [C-12] to [C-14], which is optionally substituted by one or more substituents independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S.

[0142] [C-17] The nitrogen-containing compound is a compound represented by the formula A1 or A3

[0143] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; or R ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, and 5- to 10-membered heteroaryl C １－６ alkyl, each of which is optionally substituted by one or more substituents; R ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; X ａ is O or S.

[0144] [C-18] The nitrogen-containing compound is a compound represented by the formula A1 or A3

[0145] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; or R ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C４－１０ cycloalkylalkyl, and C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents; R ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; X ａ is O or S.

[0146] [C-19] The nitrogen-containing compound is represented by the formula A1 or A3

[0147] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted with one or more halogen atoms; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, and 5- to 10-membered heteroaryl C １－６ alkyl, each of which is selected from a halogen atom, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C１－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which may be optionally substituted with one or more halogen atoms; X ａ is O or S.

[0148] [C-20] The nitrogen-containing compound is represented by the formula A1 or A3

[0149] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted with one or more halogen atoms; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ cycloalkylalkyl, and C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C１－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which may be optionally substituted with one or more halogen atoms; X ａis O or S.

[0150] [C-21] (1) Z １ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (2) Z ２ is N and Z １ is C-R ６ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (3) Z ３ is N and Z １ is C-R ６ and Z ２ is C-R ７ and Z ４ is C-R ９ and Z ５ is C-R １０ (4) Z １ and Z ２ is N and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (5) Z １ and Z ４ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ５ is C-R １０ (6) Z １ and Z ５ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z４ is C-R ９ (7) Z ２ and Z ３ is N and Z １ is C-R ６ and Z ４ is C-R ９ and Z ５ is C-R １０ (8) Z ２ and Z ４ is N and Z １ is C-R ６ and Z ３ is C-R ８ and Z ５ is C-R １０ (9) Z １ , Z ３ , and Z ５ is N and Z ２ is C-R ７ and Z ４ is C-R ９ and (10) Z １ is C-R ６ and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ The method according to any one of [C-17] to [C-20], wherein

[0151] [C-22] The nitrogen-containing compound has the formula A1':

[0152]

[0153] [In the formula, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ Alkyl, C ６－１０aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C１－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0154] [C-23] The nitrogen-containing compound has the formula A1':

[0155]

[0156] [In the formula, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C１－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0157] [C-24] The nitrogen-containing compound has the formula A1':

[0158] [In the formula, R ５ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ Alkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C１－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0159] [C-25] The nitrogen-containing compound has the formula A1':

[0160] [In the formula, R ５ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C１－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0161] [C-26] The nitrogen-containing compound has the formula A1':

[0162] [In the formula, R ５ is a hydrogen atom, and R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted with one or more halogen atoms.

[0163] [C-27] The nitrogen-containing compound has the formula A2:

[0164] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; or R １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0165] [C-28] The nitrogen-containing compound has the formula A2:

[0166] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents, or R １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0167] [C-29] The nitrogen-containing compound has the formula A2:

[0168]

[0169] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; or R １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0170] [C-30] The nitrogen-containing compound has the formula A2:

[0171]

[0172] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents, or R １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0173] [C-31] The nitrogen-containing compound has the formula A2:

[0174]

[0175] [In the formula, R １１ is a hydrogen atom, and R １２ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents.

[0176] [C-32] The nitrogen-containing compound has the formula A2:

[0177]

[0178] [In the formula, R １１ is a hydrogen atom, and R １２ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which may be substituted by one or more substituents.

[0179] [C-33] The nitrogen-containing compound has the formula A2:

[0180]

[0181] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0182] [C-34] The nitrogen-containing compound has the formula A2:

[0183]

[0184] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C１－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0185] [C-35] The nitrogen-containing compound has the formula A2:

[0186]

[0187] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0188] [C-36] The nitrogen-containing compound has the formula A2:

[0189]

[0190] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ and form a 5- to 7-membered saturated heterocycle together with the nitrogen atom to which they are bonded, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0191] [C-37] The nitrogen-containing compound has the formula A2:

[0192]

[0193] [In the formula, R １１ is a hydrogen atom, and R １２ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [C-1] to [C-13], wherein the amino group is optionally substituted with one or more substituents selected from alkyl, cyclic, 4- to 8-membered aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0194] [C-38] The nitrogen-containing compound has the formula A2:

[0195]

[0196] [In the formula, R １１ is a hydrogen atom, and R １２ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [C-1] to [C-13], wherein the amino group is optionally substituted with one or more substituents selected from alkyl, cyclic, 4- to 8-membered aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0197] [C-39] The nitrogen-containing compound is represented by formula A1, A2, or A3:

[0198]

[0199] [In the formula, R ５ ~R １２ , R ａ ~R ｃ , Z １ ~Z ５ , R ａ ~R ｃ , and X ａ The method according to any one of [C-1] to [C-38], wherein the compound is as defined in any one of [C-17] to [C-38].

[0200] [C-40] The nitrogen-containing compound represented by formula A1′ or A2:

[0201]

[0202] [In the formula, R ５ ~R １２ The method according to any one of [C-1] to [C-39], wherein the compound is as defined in any one of [C-17] to [C-38].

[0203] [C-41] The method according to any one of [C-1] to [C-40], comprising reacting a compound having a group represented by formula 1 or a compound represented by formula 2 with a nitrogen-containing compound selected from an amine and ammonia or a salt thereof in the presence of a base to obtain a sulfonamide compound.

[0204] [C-42] The method according to [C-41], wherein the base is an inorganic base or an organic base whose conjugate acid in water has a pKa of 10 or less. [C-43] The method according to [C-41] or [C-42], wherein the base is an organic base whose conjugate acid in water has a pKa of 10 or less.

[0205] [C-44] The method according to any one of [C-41] to [C-43], wherein the pKa in water of the conjugate acid of the organic base is 0 to 10, 3 to 10, 3 to 9, 3 to 8, or 5 to 7. [C-45] The organic base is represented by the formula B1, B2, B3, and B4:

[0206]

[0207] [In the formula, R １３ , R１４ , R １５ , R １６ and R １７ are each independently a hydrogen atom, C １－６ Alkyl, and C ６－１０ aryl, wherein said C １－６ Alkyl, and C ６－１０ The aryl may be substituted with one or more halogen atoms, and X １ , X ２ , and X ３ are each independently a nitrogen atom or CH, １８ is C １－６ Alkyl, and C ６－１０ aryl, R １９ is a hydrogen atom, C １－６ Alkyl, and C ６－１０ aryl; X ４ is NR ２１ or an oxygen atom, R ２０ and R ２１ are each independently, C １－６ alkyl, R ２２ and R ２３ are each independently C １－６ Alkyl, and C ６－１０ aryl, R ２４ , R ２５ , R ２６ , R ２７ , and R ２８ are each independently a hydrogen atom, C １－６ Alkyl, C ６－１０ The method according to any one of [C-41] to [C-44], wherein the aryl is at least one selected from the group consisting of aryl, a halogen atom, and cyano.

[0208] [C-46] The organic base is represented by the formulae B1′, B2′, B3′, and B4′:

[0209] [In the formula, R １３ , R １５ and R １７ are each independently a hydrogen atom and C １－６ alkyl, wherein said C １－６The alkyl may be substituted with one or more halogen atoms, and X ２ and X ３ are each independently a nitrogen atom or CH, １８ is C １－６ alkyl, R １９ is C １－６ alkyl, R ２２ and R ２３ are each independently C １－６ The method according to any one of [C-41] to [C-45], wherein two or more compounds may be used, selected from the group consisting of compounds represented by the formula:

[0210] [C-47] The method according to any one of [C-41] to [C-45], wherein the organic base is selected from the group consisting of pyridine, 2-methylpyridine, 2,6-lutidine, 2,4-lutidine, 2,4,6-collidine, 2,6-di-tert-butylpyridine (DTBP), N-methylimidazole (NMI), 4-methyl-4H-1,2,4-triazole, and N-methylmorpholine (NMM), and two or more of them may be used.

[0211] [C-48] The method according to [C-41] or [C-42], wherein the base is an inorganic base. [C-49] The method according to any one of [C-41], [C-42], and [C-48], wherein the inorganic base is selected from the group consisting of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, barium carbonate, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, lithium phosphate, sodium phosphate, potassium phosphate, cesium phosphate, magnesium phosphate, calcium phosphate, and barium phosphate, and two or more of these may be used.

[0212] [C-50] The method according to any one of [C-1] to [C-49], wherein the reaction is carried out in the presence of a solvent. [C-51] The method according to [C-50], wherein the solvent is at least one selected from the group consisting of halogen-based solvents, nitrile-based solvents, amide-based solvents, ether-based solvents, and aromatic hydrocarbon-based solvents.

[0213] [C-52] The method according to [C-40] or [C-51], wherein the solvent is a halogenated solvent. [C-53] The method according to [C-41] or [C-42], wherein the halogenated solvent is at least one selected from the group consisting of dichloromethane, chloroform, and 1,2-dichloroethane.

[0214] [C-54] The method according to any one of [C-41] to [C-53], wherein the halogen-based solvent is dichloromethane. [C-55] The method according to [C-50] or [C-51], wherein the solvent is a nitrile-based solvent.

[0215] [C-56] The method according to [C-41] or [C-55], wherein the nitrile solvent is at least one selected from the group consisting of acetonitrile, propionitrile, and benzonitrile. [C-57] The method according to [C-40] or [C-41], wherein the solvent is an amide solvent.

[0216] [C-58] The method according to [C-41] or [C-57], wherein the amide solvent is at least one selected from the group consisting of N-methylpyrrolidone, N,N-dimethylacetamide, N,N-dimethylformamide, N,N-dimethylpropionamide, N,N-dimethylisobutyramide, N,N-diethylacetamide, N,N-diethylpropionamide, 1-ethyl-2-pyrrolidinone, 1-octyl-2-pyrrolidinone, 1-cyclohexyl-2-pyrrolidinone, and N-methylcaprolactam.

[0217] [C-59] The method according to [C-50] or [C-51], wherein the solvent is an ether-based solvent. [C-60] The method according to [C-41] or [C-59], wherein the ether-based solvent is at least one selected from the group consisting of tetrahydrofuran, diethyl ether, 2-methyltetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,3-dioxolane, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, and 4-methyltetrahydropyran.

[0218] [C-61] The method according to [C-50] or [C-51], wherein the solvent is an aromatic hydrocarbon solvent. [C-62] The method according to [C-51] or [C-61], wherein the aromatic hydrocarbon solvent is at least one selected from the group consisting of benzene, chlorobenzene, toluene, and xylene.

[0219] [C-63] The method according to any one of [C-1] to [C-62], wherein the reaction is carried out at a reaction temperature of 0° C. to 100° C. [C-64] The method according to [C-63], wherein the reaction temperature is 0° C. to 80° C., 10° C. to 60° C., 15° C. to 50° C., or 15° C. to 40° C.

[0220] [C-65] The method according to [C-63] or [C-64], wherein the reaction temperature is 15° C. to 40° C. [C-66] The method according to any one of [C-1] to [C-65], wherein the reaction is carried out by a solid phase method.

[0221] [C-67] ​​The method according to any one of [C-1] to [C-65], wherein the reaction is carried out by a liquid phase method. [C-68] Reaction formula 3:

[0222]

[0223] [In the formula, R ２ and R ４ is as defined in [C-1], and represents a point of attachment] to a group represented by formula 1 by alkylating the group represented by formula 1 with an alkylating agent, thereby obtaining a compound having a group represented by formula 1.

[0224] [C-69] Formula 4:

[0225] [In the formula, R １ , R ２ and R ４ is as defined in [C-2]] with an alkylating agent to obtain a compound represented by formula 2.

[0226] [C-70] The alkylating agent is a compound of the formula: R ３-X [wherein, R ３ is C １－６ [C-71] The method according to any one of [C-67] ​​to [C-69], wherein X is a halogen atom, a C optionally substituted with one or more halogen atoms, or a C １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ The method according to [C-70], wherein the compound is selected from the group consisting of:

[0227] [C-72] X is a chlorine atom, a bromine atom, an iodine atom, trifluoromethanesulfonyloxy, methanesulfonyloxy, p-toluenesulfonyloxy, or —BF ４ The method according to [C-70], wherein the compound is selected from the group consisting of:

[0228] [C-73] The method according to [C-70], wherein X is trifluoromethanesulfonyloxy. [C-74] The method according to any one of [C-68] to [C-73], wherein alkylation with an alkylating agent to obtain a compound having a group represented by formula 1 or a compound represented by formula 2 and conversion to a sulfonamide group with a nitrogen-containing compound are carried out in one pot.

[0229] [C-75] A method according to any one of [C-1] to [C-74], wherein a mixture of two or more nitrogen-containing compounds is reacted to obtain two or more sulfonamide compounds. [C-76] A method according to any one of [C-1] to [C-10], [C-41] to [C-65], and [C-68] to [C-75], wherein the nitrogen-containing compound is a resin for solid-phase synthesis to which an amine is bound via a linker.

[0230] [C-77] The method according to [C-76], wherein the amine bonded to the resin for solid phase synthesis via a linker is an amine specified in any one of [C-11] to [C-40]. [C-78] The method according to either [C-76] or [C-77], wherein a reaction is carried out using a mixture of two or more resins for solid phase synthesis, each of which has the same amine bonded thereto, but each of which has a different amine bonded thereto, to obtain two or more sulfonamide compounds.

[0231] [C-79] The method according to any one of [C-1] and [C-11] to [C-65], wherein the compound having a group represented by formula 1 is a resin for solid phase synthesis to which the compound having a group represented by formula 1 is bound via a linker.

[0232] The method according to [C-79], wherein the compound having a group represented by formula 1 that is bound to the resin for solid phase synthesis via the linker [C-80] is a compound having a group represented by formula 1 specified in any of [C-2] to [C-10].

[0233] [C-81] Formula 3:

[0234] [In the formula, R ２ and R ４ is as defined in [C-1], and represents a point of attachment] to a group represented by formula 1 by alkylating the group represented by formula 1 with an alkylating agent, thereby obtaining a resin for solid phase synthesis to which a compound having a group represented by formula 1 is bound via a linker.

[0235] via a [C-82] linker:

[0236] [In the formula, R １ , R ２ and R ４ is as defined in [C-2]] is alkylated with an alkylating agent to convert the solid phase synthesis resin to which a compound having a group represented by Formula 1 is bound via a linker.

[0237] [C-83] The alkylating agent is a compound of the formula: R ３ -X [wherein, R ３ is C １－６ [C-84] The method according to [C-81] or [C-82], wherein X is a halogen atom, a C optionally substituted with one or more halogen atoms, or a C １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ The method according to [C-83], wherein the compound is selected from the group consisting of:

[0238] [C-85] X is a chlorine atom, a bromine atom, an iodine atom, trifluoromethanesulfonyloxy, methanesulfonyloxy, p-toluenesulfonyloxy, or —BF ４ The method according to [C-83], wherein the compound is selected from the group consisting of:

[0239] [C-86] The method according to [C-83], wherein X is trifluoromethanesulfonyloxy. [C-87] The method according to any one of [C-79] to [C-86], wherein a reaction is carried out using a mixture of solid phase synthesis resins, each of which is bound to a compound having the same group represented by Formula 1, and each of which is bound to a different compound having the group represented by Formula 1, to obtain two or more sulfonamide compounds.

[0240] [D-1] Use of a compound having a triazolium group in a method for forming a sulfonamide bond, the compound comprising a compound of Formula 1:

[0241]

[0242] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６alkyl or benzyl, and * represents a point of attachment, with a nitrogen-containing compound selected from amines and ammonia or a salt thereof to convert the group into a sulfonamide group corresponding to the nitrogen-containing compound.

[0243] [D-2] A compound having a group represented by formula 1,

[0244]

[0245] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４ is as defined in [D-1], and X － is a counter anion.

[0246] [D-3] A compound having a group represented by formula 1,

[0247]

[0248] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４ is as defined in [D-1], and X － is a counter anion.

[0249] [D-4]X － is a halide anion, C optionally substituted with one or more halogen atoms １－６ Alkyl sulfonate anion, one or more C １－６ Benzene sulfonate anion optionally substituted with alkyl, and BF ４ － The use according to [D-2] or [D-3], selected from the following:

[0250] [D-5]X － are chloride anion, bromide anion, iodide anion, trifluoromethanesulfonate anion, methanesulfonate anion, p-toluenesulfonate anion, and BF ４ － The use according to [D-4], selected from:

[0251] [D-6]X － The use according to [D-4], wherein R is trifluoromethanesulfonate anion. ２ and R ４ are each independently a hydrogen atom and C １－６ The use according to any one of [D-1] to [D-6], wherein the alkyl is selected from the group consisting of alkyl.

[0252] [D-8]R １ The one or more substituents that the group represented by the formula (I) may have are a halogen atom, a cyano, C １－６ Alkyl, C １－６ Alkoxy, C ６－１０ Aryl, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C１－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to any one of [D-1] to [D-7], wherein the aminocarbonyl is independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0253] [D-9]R １ The one or more substituents that the group represented by the formula (I) may have are a halogen atom, a cyano, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to any one of [D-1] to [D-7], wherein the aminocarbonyl is independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0254] [D-10]R ２ and R ４[D-11] The use according to any one of [D-1] to [D-10], wherein the nitrogen-containing compound is selected from ammonia or a salt thereof, a primary amine, and a secondary amine.

[0255] [D-12] The use according to any one of [D-1] to [D-11], wherein the nitrogen-containing compound is selected from the group consisting of ammonia or a salt thereof, a primary amine in which the nitrogen atom is substituted with an aliphatic group, a primary amine in which the nitrogen atom is substituted with an aromatic group, a secondary amine in which the nitrogen atom is substituted with two aliphatic groups, a secondary amine in which the nitrogen atom is substituted with two aromatic groups, and a secondary amine in which the nitrogen atom is substituted with one aliphatic group and one aromatic group.

[0256] [D-13] Use according to any one of [D-1] to [D-12], wherein the nitrogen-containing compound contains one functional group capable of reacting with a group represented by formula 1 or a compound represented by formula 2. [D-14] The aromatic group is C ６－１０ The use according to [D-12] or [D-13], wherein the heteroaryl is selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which may be substituted with one or more substituents.

[0257] [D-15] The aromatic group is C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from the group consisting of halogen atoms, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ The use according to any one of [D-12] to [D-14], which is optionally substituted by one or more substituents independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S.

[0258] [D-16] The aromatic group is C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from the group consisting of halogen atoms, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C６－１０ The use according to any one of [D-12] to [D-14], which is optionally substituted by one or more substituents independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S.

[0259] [D-17] The nitrogen-containing compound is represented by the formula A1 or A3

[0260] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; or R ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, and 5- to 10-membered heteroaryl C １－６ alkyl, each of which is optionally substituted by one or more substituents; R ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; X ａ is O or S.

[0261] [D-18] The nitrogen-containing compound is represented by the formula A1 or A3

[0262] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; or R ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C４－１０ cycloalkylalkyl, and C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents; R ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; X ａ is O or S.

[0263] [D-19] The nitrogen-containing compound is represented by the formula A1 or A3

[0264] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted with one or more halogen atoms; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, and 5- to 10-membered heteroaryl C １－６ alkyl, each of which is selected from a halogen atom, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C１－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which may be optionally substituted with one or more halogen atoms; X ａ is O or S].

[0265] [D-20] The nitrogen-containing compound is represented by the formula A1 or A3

[0266] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted with one or more halogen atoms; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ cycloalkylalkyl, and C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C１－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which may be optionally substituted with one or more halogen atoms; X ａis O or S.

[0267] [D-21] (1) Z １ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (2) Z ２ is N and Z １ is C-R ６ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (3) Z ３ is N and Z １ is C-R ６ and Z ２ is C-R ７ and Z ４ is C-R ９ and Z ５ is C-R １０ (4) Z １ and Z ２ is N and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ (5) Z １ and Z ４ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ５ is C-R １０ (6) Z １ and Z ５ is N and Z ２ is C-R ７ and Z ３ is C-R ８ and Z４ is C-R ９ (7) Z ２ and Z ３ is N and Z １ is C-R ６ and Z ４ is C-R ９ and Z ５ is C-R １０ That is, 　 (8) Z ２ and Z ４ is N and Z １ is C-R ６ and Z ３ is C-R ８ and Z ５ is C-R １０ (9) Z １ , Z ３ , and Z ５ is N and Z ２ is C-R ７ and Z ４ is C-R ９ and (10) Z １ is C-R ６ and Z ２ is C-R ７ and Z ３ is C-R ８ and Z ４ is C-R ９ and Z ５ is C-R １０ The use according to any one of [D-17] to [D-20], wherein

[0268] [D-22] The nitrogen-containing compound has the formula A1':

[0269]

[0270] [In the formula, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ Alkyl, C６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which may be substituted with one or more halogen atoms.

[0271] [D-23] The nitrogen-containing compound has the formula A1':

[0272]

[0273] [In the formula, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which may be substituted with one or more halogen atoms.

[0274] [D-24] The nitrogen-containing compound has the formula A1':

[0275] [In the formula, R ５ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ Alkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C１－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which may be substituted with one or more halogen atoms.

[0276] [D-25] The nitrogen-containing compound has the formula A1':

[0277] [In the formula, R ５ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is selected from halogen atoms, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which may be substituted with one or more halogen atoms.

[0278] [D-26] The nitrogen-containing compound has the formula A1':

[0279] [In the formula, R ５ is a hydrogen atom, and R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０aryl, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which may be substituted with one or more halogen atoms.

[0280] [D-27] The nitrogen-containing compound has formula A2:

[0281] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; or R １１ and R １２ are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0282] [D-28] The nitrogen-containing compound has formula A2:

[0283] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents, or R １１ and R １２are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0284] [D-29] The nitrogen-containing compound has formula A2:

[0285]

[0286] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; or R １１ and R １２ are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0287] [D-30] The nitrogen-containing compound has formula A2:

[0288]

[0289] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is optionally substituted by one or more substituents, or R １１ and R １２are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0290] [D-31] The nitrogen-containing compound has the formula A2:

[0291]

[0292] [In the formula, R １１ is a hydrogen atom, and R １２ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5- to 10-membered heteroaryl C １－６ The use according to any one of [D-1] to [D-13], represented by the formula: alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents.

[0293] [D-32] The nitrogen-containing compound has formula A2:

[0294]

[0295] [In the formula, R １１ is a hydrogen atom, and R １２ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ The use according to any one of [D-1] to [D-13], wherein the aryl group is selected from the group consisting of aryl, ...

[0296] [D-33] The nitrogen-containing compound has formula A2:

[0297]

[0298] [In the formula, R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0299] [D-34] The nitrogen-containing compound has formula A2:

[0300]

[0301] [In the formula, R １１ and R１２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0302] [D-35] The nitrogen-containing compound has the formula A2:

[0303]

[0304] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O, N, and S.

[0305] [D-36] The nitrogen-containing compound has formula A2:

[0306]

[0307] [In the formula, R １１ and R １２ are each independently, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C１－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ R may be substituted by one or more substituents selected from: aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, or １１ and R １２ are taken together with the nitrogen atom to which they are attached to form a 5- to 7-membered saturated heterocycle, and the heterocycle may further contain a ring heteroatom selected from O and S.

[0308] [D-37] The nitrogen-containing compound has formula A2:

[0309]

[0310] [In the formula, R １１ is a hydrogen atom, and R １２ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is selected from halogen atoms, cyano, nitro, C ６－１０ Aryl, C １－６ Alkoxy, C ６-１０ Aryloxy, (C １－６alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to any one of [D-1] to [D-13], which is represented by the formula: [optionally substituted by one or more substituents selected from] (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0311] [D-38] The nitrogen-containing compound has formula A2:

[0312]

[0313] [In the formula, R １１ is a hydrogen atom, and R １２ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ aralkyl, each of which is selected from a halogen atom, cyano, nitro, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６alkyl)aminocarbonyl, di(C １－６ The use according to any one of [D-1] to [D-13], which is represented by the formula: [optionally substituted by one or more substituents selected from] (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0314] [D-39] The nitrogen-containing compound is represented by formula A1, A2, or A3:

[0315]

[0316] [In the formula, R ５ ~R １２ , R ａ ~R ｃ , Z １ ~Z ５ , R ａ ~R ｃ , and X ａ The use according to any one of [D-1] to [D-38], wherein the compound is as defined in any one of [D-17] to [D-38].

[0317] [D-40] The nitrogen-containing compound represented by formula A1′ or A2:

[0318]

[0319] [In the formula, R ５ ~R １２ The use according to any one of [D-1] to [D-39], represented by the formula (I) being as defined in any one of [D-17] to [D-38].

[0320] [D-41] Use according to any one of [D-1] to [D-40], in which a compound having a group represented by formula 1 or a compound represented by formula 2 is reacted with a nitrogen-containing compound selected from an amine and ammonia or a salt thereof in the presence of a base to obtain a sulfonamide compound.

[0321] [D-42] The use according to [D-41], wherein the base is an inorganic base or an organic base whose conjugate acid in water has a pKa of 10 or less. [D-43] The use according to [D-41] or [D-42], wherein the base is an organic base whose conjugate acid in water has a pKa of 10 or less.

[0322] [D-44] Use according to any one of [D-41] to [D-43], wherein the pKa in water of the conjugate acid of the organic base is 0 to 10, 3 to 10, 3 to 9, 3 to 8, or 5 to 7. [D-45] The organic base is represented by the formula B1, B2, B3, and B4:

[0323]

[0324] [In the formula, R １３ , R １４ , R １５ , R １６ and R １７ are each independently a hydrogen atom, C １－６ Alkyl, and C ６－１０ aryl, wherein said C １－６ Alkyl, and C ６－１０ The aryl may be substituted with one or more halogen atoms, and X １ , X ２ , and X ３ are each independently a nitrogen atom or CH, １８ is C １－６ Alkyl, and C ６－１０ aryl, R １９ is a hydrogen atom, C １－６ Alkyl, and C ６－１０ aryl; X ４ is NR ２１ or an oxygen atom, R ２０ and R ２１ are each independently, C １－６ alkyl, R ２２ and R ２３ are each independently C １－６ Alkyl, and C ６－１０ aryl, R ２４ , R ２５ , R ２６ , R ２７ , and R ２８ are each independently a hydrogen atom, C １－６ Alkyl, C ６－１０ The use according to any one of [D-41] to [D-44], wherein the compound is at least one selected from the group consisting of compounds represented by the formula (I) and (II), wherein the compound is selected from the group consisting of aryl, a halogen atom, and cyano.

[0325] [D-46] The organic base is represented by the formulae B1′, B2′, B3′, and B4′:

[0326] [In the formula, R １３ , R １５ and R １７ are each independently a hydrogen atom and C １－６ alkyl, wherein said C １－６ The alkyl may be substituted with one or more halogen atoms, and X ２ and X ３ are each independently a nitrogen atom or CH, １８ is C １－６ alkyl, R １９ is C １－６ alkyl, R ２２ and R ２３ are each independently C １－６ The use according to any one of [D-41] to [D-45], wherein two or more compounds may be used, selected from the group consisting of compounds represented by the formula:

[0327] [D-47] The use according to any one of [D-41] to [D-45], wherein the organic base is selected from the group consisting of pyridine, 2-methylpyridine, 2,6-lutidine, 2,4-lutidine, 2,4,6-collidine, 2,6-di-tert-butylpyridine (DTBP), N-methylimidazole (NMI), 4-methyl-4H-1,2,4-triazole, and N-methylmorpholine (NMM), and two or more of these may be used.

[0328] [D-48] The use according to [D-41] or [D-42], wherein the base is an inorganic base. [D-49] The use according to any one of [D-41], [D-42], and [D-48], wherein the inorganic base is selected from the group consisting of lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, barium carbonate, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, lithium phosphate, sodium phosphate, potassium phosphate, cesium phosphate, magnesium phosphate, calcium phosphate, and barium phosphate, and two or more of these may be used.

[0329] [D-50] The use according to any one of [D-1] to [D-49], wherein the reaction is carried out in the presence of a solvent. [D-51] The use according to [D-50], wherein the solvent is at least one selected from the group consisting of halogen-based solvents, nitrile-based solvents, amide-based solvents, ether-based solvents, and aromatic hydrocarbon-based solvents.

[0330] [D-52] The use according to [D-50] or [D-51], wherein the solvent is a halogenated solvent. [D-53] The use according to [D-51] or [D-52], wherein the halogenated solvent is at least one selected from the group consisting of dichloromethane, chloroform, and 1,2-dichloroethane.

[0331] [D-54] The use according to any one of [D-41] to [D-53], wherein the halogen-based solvent is dichloromethane. [D-55] The use according to [D-50] or [D-51], wherein the solvent is a nitrile-based solvent.

[0332] [D-56] The use according to [D-51] or [D-55], wherein the nitrile solvent is at least one selected from the group consisting of acetonitrile, propionitrile, and benzonitrile. [D-57] The use according to [D-50] or [D-51], wherein the solvent is an amide solvent.

[0333] [D-58] The use according to [D-51] or [D-57], wherein the amide solvent is at least one selected from the group consisting of N-methylpyrrolidone, N,N-dimethylacetamide, N,N-dimethylformamide, N,N-dimethylpropionamide, N,N-dimethylisobutyramide, N,N-diethylacetamide, N,N-diethylpropionamide, 1-ethyl-2-pyrrolidinone, 1-octyl-2-pyrrolidinone, 1-cyclohexyl-2-pyrrolidinone, and N-methylcaprolactam.

[0334] [D-59] The use according to [D-50] or [D-51], wherein the solvent is an ether-based solvent. [D-60] The use according to [D-51] or [D-59], wherein the ether-based solvent is at least one selected from the group consisting of tetrahydrofuran, diethyl ether, 2-methyltetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, 1,3-dioxolane, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, and 4-methyltetrahydropyran.

[0335] [D-61] The use according to [D-50] or [D-51], wherein the solvent is an aromatic hydrocarbon solvent. [D-62] The use according to [D-51] or [D-61], wherein the aromatic hydrocarbon solvent is at least one selected from the group consisting of benzene, chlorobenzene, toluene, and xylene.

[0336] [D-63] The use according to any one of [D-1] to [D-62], wherein the reaction is carried out at a reaction temperature of 0° C. to 100° C. [D-64] The use according to [D-63], wherein the reaction temperature is 0° C. to 80° C., 10° C. to 60° C., 15° C. to 50° C., or 15° C. to 40° C.

[0337] [D-65] The use according to [D-63] or [D-64], wherein the reaction temperature is 15° C. to 40° C. [D-66] The use according to any one of [D-1] to [D-65], wherein the reaction is carried out by a solid-phase method.

[0338] [D-67] The use according to any one of [D-1] to [D-65], wherein the reaction is carried out by a liquid phase method. [D-68] Formula 3:

[0339]

[0340] [In the formula, R ２ and R ４ is as defined in [D-1], and represents a point of attachment] to a group represented by formula 1 by alkylating the group represented by formula 1 with an alkylating agent, thereby obtaining a compound having a group represented by formula 1.

[0341] [D-69] Formula 4:

[0342] [In the formula, R １ , R ２ and R ４ is as defined in [D-2]] with an alkylating agent to obtain a compound represented by formula 2. The use according to any one of [D-1] to [D-67].

[0343] [D-70] The alkylating agent is a compound represented by the formula: R ３ -X [wherein, R ３ is C １－６ [D-71] The use according to any one of [D-67] to [D-69], wherein X is a compound represented by the formula (I) wherein X is an alkyl or benzyl group, and X is a leaving group. １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ The use according to [D-70], selected from the following:

[0344] [D-72] X is a chlorine atom, a bromine atom, an iodine atom, trifluoromethanesulfonyloxy, methanesulfonyloxy, p-toluenesulfonyloxy, or —BF ４ The use according to [D-70], selected from the following:

[0345] [D-73] The use according to [D-70], wherein X is trifluoromethanesulfonyloxy. [D-74] The use according to any one of [D-68] to [D-73], wherein alkylation with an alkylating agent to obtain a compound having a group represented by formula 1 or a compound represented by formula 2 and conversion to a sulfonamide group with a nitrogen-containing compound are carried out in one pot.

[0346] [D-75] The use according to any one of [D-1] to [D-74], wherein a reaction is carried out using a mixture of two or more nitrogen-containing compounds to obtain two or more sulfonamide compounds. [D-76] The use according to any one of [D-1] to [D-10], [D-41] to [D-65], and [D-68] to [D-75], wherein the nitrogen-containing compound is a resin for solid-phase synthesis to which an amine is bound via a linker.

[0347] [D-77] The use according to [D-76], wherein the amine bound to the solid-phase synthesis resin via a linker is an amine specified in any one of [D-11] to [D-40]. [D-78] The use according to either [D-76] or [D-77], wherein a reaction is carried out using a mixture of two or more solid-phase synthesis resins, each having the same amine bound thereto, but each having a different amine bound thereto, to obtain two or more sulfonamide compounds.

[0348] [D-79] The use according to any one of [D-1] and [D-11] to [D-65], wherein the compound having a group represented by formula 1 is a resin for solid phase synthesis to which the compound having a group represented by formula 1 is bound via a linker.

[0349] [D-80] The use according to [D-79], wherein the compound having a group represented by formula 1 that is bound to the resin for solid phase synthesis via a linker is a compound having a group represented by formula 1 specified in any one of [D-2] to [D-10].

[0350] [D-81] Formula 3:

[0351] [In the formula, R ２ and R ４is as defined in [D-1], and represents a point of attachment] to a group represented by formula 1 by alkylating the group represented by the formula with an alkylating agent, thereby obtaining a resin for solid phase synthesis to which a compound having a group represented by formula 1 is bound via a linker.

[0352] [D-82] via a linker:

[0353] [In the formula, R １ , R ２ and R ４ is as defined in [D-2]] is alkylated with an alkylating agent to convert the solid phase synthesis resin to which a compound having a group represented by Formula 1 is bound via a linker.

[0354] [D-83] The alkylating agent is a compound represented by the formula: R ３ -X [wherein, R ３ is C １－６ [D-84] The use according to [D-81] or [D-82], wherein X is a compound represented by the formula (I) wherein X is a halogen atom, C optionally substituted with one or more halogen atoms, or C １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ The use according to [D-83], selected from:

[0355] [D-85] X is a chlorine atom, a bromine atom, an iodine atom, trifluoromethanesulfonyloxy, methanesulfonyloxy, p-toluenesulfonyloxy, or —BF ４ The use according to [D-83], selected from:

[0356] [D-86] The use according to [D-83], wherein X is trifluoromethanesulfonyloxy. [D-87] The use according to any one of [D-79] to [D-86], wherein a reaction is carried out using a mixture of solid phase synthesis resins, each of which is bound to a compound having the same group represented by Formula 1, and each of which is bound to a different compound having the group represented by Formula 1, to obtain two or more sulfonamide compounds.

[0357] [E-1] Formula 2:

[0358] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４ is as defined in [A-1], and X － is a counter anion.

[0359] [E-2] Formula 2:

[0360] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ ~R ４is as defined in [A-1], and X － is a counter anion.

[0361] [E-3] The following formula: The compound according to [E-1] or [E-2], selected from the group consisting of:

[0362] [E-4] Below formula: The compound according to [E-1] or [E-2], selected from the group consisting of:

[0363] A method for producing the compound according to [F-1], [E-1] or [E-2], comprising:

[0364] [In the formula, R １ , R ２ and R ４ is as defined in [A-1]] to a compound of formula 2 by alkylating the compound with an alkylating agent.

[0365] In one aspect, the present invention makes it possible to improve the conversion rate and / or suppress the production of by-products in the reaction of a nitrogen-containing compound such as an amine with a sulfonylating agent to produce a sulfonamide compound.

[0366] In one aspect, the present invention is a method for producing a sulfonamide compound by reacting a nitrogen-containing compound such as an amine with a sulfonylating agent, the sulfonylating agent being a compound of Formula 1:

[0367] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ In one embodiment, the group represented by formula 1 may have a counter anion. In this reaction, the nitrogen atom of the nitrogen-containing compound and SO are bonded together, with the triazolinium moiety being eliminated.２ A bond is formed between the sulfur atoms of the aryl groups, forming a sulfonamide structure, resulting in a triazole compound:

[0368] is formed.

[0369] In one aspect of the present invention, the sulfonylating agent having a group represented by formula (1) is － X is a salt containing － is not particularly limited, but in one embodiment of the present invention, X － is a halide anion, C optionally substituted with one or more halogen atoms １－６ Alkyl sulfonate anion, one or more C １－６ Benzene sulfonate anion optionally substituted with alkyl, and BF ４ － is selected from.

[0370] In one aspect of the present invention, the sulfonylating agent having a group represented by formula (1) is represented by formula 3:

[0371] In one embodiment of the present invention, the alkylating agent is an alkylating agent represented by R ３ -X, where R ３ is C １－６ In one embodiment of the present invention, X is a halogen atom, a C alkyl group, for example, methyl, or benzyl, and X is a leaving group. １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ In one embodiment of the present invention, the group represented by formula (1) resulting from alkylation forms a salt having a counter anion derived from the eliminated X.

[0372] In one aspect, the present invention is a method for preparing a sulfonamide compound by reacting a nitrogen-containing compound, such as an amine, with a sulfonylating agent, wherein the nitrogen-containing compound has the formula A1:

[0373] In the formula, R ５ ~R １０ , and Z １ ~Z ５ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has the formula A1a:

[0374] [R in the formula ５ ~R １０ , and Z １ ~Z ５ is as defined herein, and represents a point of attachment.

[0375] In one aspect, the present invention is a method for preparing a sulfonamide compound by reacting a nitrogen-containing compound, such as an amine, with a sulfonylating agent, wherein the nitrogen-containing compound is represented by formula A1':

[0376]

[0377] In the formula R ５ ~R １０ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has the formula A1b:

[0378]

[0379] [In the formula, R in the formula ５ ~R １０ is as defined herein, and represents a point of attachment. In one aspect, the present invention provides a method for producing a sulfonamide compound by reacting a nitrogen-containing compound such as an amine with a sulfonylating agent, wherein the nitrogen-containing compound is a compound represented by formula A2:

[0380]

[0381] In the formula, R １１ and R １２ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has formula A2a:

[0382]

[0383] [In the formula, R １１ and R １２ is as defined herein, and represents a point of attachment. In one aspect, the present invention provides a method for producing a sulfonamide compound by reacting a nitrogen-containing compound such as an amine with a sulfonylating agent, wherein the nitrogen-containing compound is a compound represented by formula A3:

[0384] In the formula, R ａ ~R ｃ , and X ａ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has formula A3a:

[0385]

[0386] [In the formula, R ａ ~R ｃ , and X ａ is as defined herein, and represents a point of attachment.

[0387] In one aspect, the present invention is a method for producing a sulfonamide compound by reacting a nitrogen-containing compound such as an amine with a sulfonylating agent, the sulfonylating agent being a compound of Formula 2:

[0388] [In the formula, R １ ~R ４ , and X － is as defined herein]. By this reaction, a group: -SO ２ R １ A sulfonamide compound having the following structure is produced.

[0389] In one aspect of the present invention, the sulfonylating agent having a group of formula 2 is provided by the counter anion: X － X is a salt containing － is not particularly limited, but in one embodiment of the present invention, X －is a halide anion, C optionally substituted with one or more halogen atoms １－６ Alkyl sulfonate anion, one or more C １－６ Benzene sulfonate anion optionally substituted with alkyl, and BF ４ － is selected from.

[0390] In one aspect of the present invention, the sulfonylating agent having a group represented by formula 2 is a sulfonylating agent having a group represented by formula 4:

[0391] In one embodiment of the present invention, the alkylating agent is an alkylating agent represented by R ３ -X, where R ３ is C １－６ In one embodiment of the present invention, X is a halogen atom, a C alkyl group, for example, methyl, or benzyl, and X is a leaving group. １－６ Alkyl sulfonyloxy, one or more C １－６ benzenesulfonyloxy optionally substituted with alkyl, and -BF ４ In one embodiment of the present invention, the compound represented by formula 2 obtained by alkylation has a counter anion: X derived from the eliminated X. － and forming a salt having the formula:

[0392] In one aspect, the present invention is a method for preparing a sulfonamide compound by reacting a nitrogen-containing compound, such as an amine, with a sulfonylating agent, wherein the nitrogen-containing compound has the formula A1:

[0393] In the formula, R ５ ~R １０ , and Z １ ~Z ５ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has the formula A1c:

[0394]

[0395] [R in the formula １、 R ５ ~R １０ , and Z １ ~Z ５ is as defined herein.

[0396] In one aspect, the present invention is a method for preparing a sulfonamide compound by reacting a nitrogen-containing compound, such as an amine, with a sulfonylating agent, wherein the nitrogen-containing compound is represented by formula A1':

[0397] In the formula, R ５ ~R １０ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has the formula A1d:

[0398]

[0399] [In the formula, R １ , and R ５ ~R １０ In one aspect, the present invention relates to a method for producing a sulfonamide compound by reacting a nitrogen-containing compound such as an amine with a sulfonylating agent, wherein the nitrogen-containing compound is a compound represented by formula A2:

[0400]

[0401] In the formula, R １１ and R １２ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has formula A2a:

[0402] [In the formula, R １ , R １１ and R １２ is as defined herein. １ The group defined as may have one or more substituents, which do not affect the sulfonylation reaction. １One of the substituents of the group defined as: is a linker that covalently connects it to a resin for solid phase synthesis.

[0403] In one aspect, the present invention is a method for preparing a sulfonamide compound by reacting a nitrogen-containing compound, such as an amine, with a sulfonylating agent, wherein the nitrogen-containing compound is represented by formula A3:

[0404] In the formula, R ａ ~R ｃ , and X ａ is as defined herein. In one aspect of the invention, the resulting sulfonamide compound has formula A3b:

[0405]

[0406] [In the formula, R １ , R ａ ~R ｃ , and X ａ is as defined herein.

[0407] In one aspect of the present invention, ammonia or a salt thereof is used as the nitrogen-containing compound. Ammonia can be added to the reaction system as a solution or as a salt such as ammonium chloride.

[0408] In one aspect of the present invention, the sulfonylating agent can be used in an amount of 0.5 equivalents or more, 0.8 equivalents or more, 0.9 equivalents or more, 1.0 equivalents or more, 1.1 equivalents or more, 1.2 equivalents or more, 1.5 equivalents or more, 1.8 equivalents or more, 2 equivalents or more, 2.2 equivalents or more, 2.5 equivalents or more, 3 equivalents or more, 3.5 equivalents or more, 4.0 equivalents or more, 5.0 equivalents or more, 6.0 equivalents or more, 7.0 equivalents or more, 8.0 equivalents or more, 9.0 equivalents or more, or 10.0 equivalents or more relative to the nitrogen-containing compound, where the number of equivalents is calculated based on the number of groups represented by Formula 1 contained in the sulfonylating agent and the number of reactive sites contained in the nitrogen-containing compound.

[0409] In one aspect of the present invention, a sulfonylating agent, which is a compound having a group represented by Formula 1 or a compound represented by Formula 2, can be reacted with a nitrogen-containing compound in the presence of a base to obtain a target sulfonamide compound. The base may be an organic base or an inorganic base, and the organic base is not particularly limited as long as it is one that is commonly used to promote a sulfonylation reaction, and examples thereof include N,N-di(C １－６ (alkyl)aniline; aromatic 5- or 6-membered nitrogen-containing heterocyclic compounds such as N-methylimidazole, 4-methyl-4H-1,2,4-triazole, pyridine, 2-methylpyridine, 2,6-lutidine, 2,4-lutidine, 2,4,6-collidine, 2,6-di-tert-butylpyridine (DTBP), and 4-dimethylaminopyridine; and aliphatic heterocyclic compounds such as N-methylpiperidine, N-methylmorpholine, and N-methylpyrrolidine. Examples of inorganic bases include metal carbonates, metal bicarbonates, and metal phosphates, and examples of metals include alkali metals and alkaline earth metals. Specific examples of inorganic bases include lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, barium carbonate, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, lithium phosphate, sodium phosphate, potassium phosphate, cesium phosphate, magnesium phosphate, calcium phosphate, and barium phosphate. In one aspect of the present invention, the base added to promote the sulfonylation reaction can be used in an amount of 0.1 equivalents or more, 0.5 equivalents or more, 0.8 equivalents or more, 1 equivalent or more, 1.2 equivalents or more, 1.5 equivalents or more, 2 equivalents or more, or 2.5 equivalents or more relative to the sulfonylating agent, where the number of equivalents is calculated based on the number of groups represented by Formula 1 contained in the sulfonylating agent.

[0410] In one aspect of the present invention, the base is an organic base whose conjugate acid in water has a pKa of 10 or less, 9 or less, 8 or less, or 7 or less, or 0 or more, 1 or more, 2 or more, 3 or more, 4 or more, or 5 or more. In one aspect of the present invention, the pKa of the conjugate acid of the organic base in water is 0 to 10, 3 to 10, 3 to 9, 3 to 8, 3.2 to 7.9, or 5 to 7. Here, the pKa of the conjugate acid of the base can be determined by a conventional method, and for example, the value measured at 25°C according to the method described in Experimental Chemistry Lectures 5, "Thermal Measurement and Equilibrium," p. 460 (edited by the Chemical Society of Japan, published by Maruzen Co., Ltd.) can be used. As reference values, values ​​described in the publicly known literature Eur. J. Org.Chem. 2019, 6735-6748, Advanced Chemistry Development (ACD / Labs) Software V11.02 ((c) 1994-2019 ACD / Labs), calculated values ​​using ADMET predictor (version 11, parameters are all default values), values ​​described in the Sigma-Aldrich catalog, values ​​described in Chemical Book (https: / / www.chemicalbook.com), or values ​​described in PubChem (https: / / pubchem.ncbi.nlm.nih.gov) can be appropriately referenced. The pKa values ​​of the conjugate acids in water calculated using ADMET predictor (version 11) are, for example, 5.4 for pyridine, 6.6 for 2,6-di-tert-butylpyridine (DTBP), 6.8 for 2,6-lutidine, 7.9 for 2,4,6-collidine, 7.0 for N-methylimidazole (NMI), 3.2 for 4-methyl-4H-1,2,4-triazole, 7.7 for N-methylmorpholine (NMM), 10.4 for triethylamine, 12.3 for diazabicycloundecene (DBU), 14.8 for 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), and 10.3 for tert-butylimino-tri(pyrrolidino)phosphorane.

[0411] In one embodiment, by adding 1 equivalent or more of the nitrogen-containing compound used as a substrate, more than 1 equivalent of the nitrogen-containing compound can be used as a base to promote the reaction. In one embodiment, the nitrogen-containing compound can be used in an amount of 1.2 equivalents or more, 1.5 equivalents or more, 1.8 equivalents or more, 2 equivalents or more, 2.2 equivalents or more, 2.5 equivalents or more, 3 equivalents or more, or 3.5 equivalents or more relative to the sulfonylating agent.

[0412] In one embodiment of the present invention, the reaction of a nitrogen-containing compound with a sulfonylating agent can be carried out in a solvent selected from, for example, ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, 4-methyltetrahydropyran, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, 1,4-dioxane, and 1,3-dioxolane; halogenated solvents such as dichloromethane, 1,2-dichloroethane, and chloroform; nitrile solvents such as acetonitrile, propionitrile, and benzonitrile; and aromatic hydrocarbon solvents such as benzene, toluene, and xylene (a single solvent may be used, or a mixture of multiple solvents may be used).

[0413] In one aspect of the invention, the reaction can be carried out at a temperature of 0°C to 120°C, 0°C to 80°C, 0°C to 60°C, 0°C to 50°C, 0°C to 40°C, 10°C to 100°C, 10°C to 80°C, 10°C to 60°C, 10°C to 50°C, 10°C to 40°C, 15°C to 100°C, 15°C to 80°C, 15°C to 60°C, 15°C to 50°C, 15°C to 40°C, 20°C to 90°C, 25°C to 80°C, 30°C to 80°C, 35°C to 80°C, or 40°C to 80°C.

[0414] In one aspect, the present invention provides a method for preparing a sulfonamide compound, comprising:

[0415]

[0416] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R３ is C １－６ The method includes reacting a compound having a group represented by the formula (III): (alkyl or benzyl, and * represents an attachment point) with a nitrogen-containing compound selected from amines to convert the group to a sulfonamide group corresponding to the nitrogen-containing compound, wherein the nitrogen-containing compound is a resin for solid-phase synthesis to which the amine is bound via a linker. In one embodiment, the resin for solid-phase synthesis has the amine bound via a linker that allows the sulfonamide compound, a low molecular weight compound, to be cleaved after the sulfonamidation reaction. In one embodiment of the present invention, the method further includes, after the sulfonamidation reaction, cleaving the sulfonamide compound, a low molecular weight compound, by a linker cleavage reaction. In one embodiment, the method may further include, after the sulfonamidation reaction, converting or modifying the compound linked by the linker by one or more reactions, and then cleaving the sulfonamide compound, a low molecular weight compound, by a linker cleavage reaction.

[0417] In one aspect, the present invention provides a method for preparing a sulfonamide compound, comprising:

[0418]

[0419] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６and represents an attachment point] with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group into a sulfonamide group corresponding to the nitrogen-containing compound, wherein the compound having a group represented by Formula 1 is a resin for solid-phase synthesis to which the group represented by Formula 1 is bound via a linker. In one embodiment, the solid-phase synthesis resin is bonded to the compound having a group represented by Formula 1 via a linker that allows the sulfonamide compound, a low molecular weight compound, to be cleaved after the sulfonamidation reaction. In one embodiment of the present invention, the method further comprises, after the sulfonamidation reaction, cleaving the sulfonamide compound, a low molecular weight compound, by a linker cleavage reaction. In another embodiment of the present invention, the method may further comprise, after the sulfonamidation reaction, converting or modifying the compound linked by the linker by one or more reactions, and then cleaving the sulfonamide compound, a low molecular weight compound, by a linker cleavage reaction.

[0420] In one aspect, the present invention provides a method for preparing a sulfonamide compound comprising:

[0421] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl, and * represents a point of attachment, ３ -X [wherein, R ３ is C １－６ alkyl or benzyl, and X is a leaving group, to obtain a compound represented by formula 1:

[0422]

[0423] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３is C １－６ alkyl or benzyl, and represents a point of attachment; and

[0424]

[0425] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ and (iii) represents an alkyl or benzyl group, and · represents an attachment point, with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group into a sulfonamide group corresponding to the nitrogen-containing compound, wherein the compound having a group represented by Formula 3 is a resin for solid phase synthesis to which the group represented by Formula 3 is bound via a linker. In one embodiment, the resin for solid phase synthesis is bonded to a compound having a group represented by Formula 1 via a linker that allows for cleavage of the low molecular weight sulfonamide compound after the sulfonamidation reaction. In one embodiment of the present invention, the method further comprises, after the sulfonamidation reaction, cleaving the low molecular weight sulfonamide compound by a linker cleavage reaction. In one embodiment, the method may further comprise, after the sulfonamidation reaction, conversion or modification of the compound linked by the linker by one or more reactions, and then further comprising cleaving the low molecular weight sulfonamide compound by a linker cleavage reaction.

[0426] In this specification, C １－６ Alkyl is a linear or branched monovalent saturated aliphatic group having 1 to 6 carbon atoms. Specific examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, 1-methylpropyl, n-pentyl, isopentyl, 2-methylbutyl, 1,1-dimethylpropyl, 1-ethylpropyl, hexyl, 4-methylpentyl, and 2-ethylbutyl.

[0427] In this specification, the term "aryl" refers to a monovalent aromatic hydrocarbon ring group consisting of a single ring or fused rings that exhibits monovalent aromaticity. In this specification, an aryl consisting of a single ring is referred to as a monocyclic aryl, and an aryl consisting of a fused ring is referred to as a fused ring aryl. Examples of aryl include C ６ ~C １０ aryl, C ６ Aryl and C １０ Aryl is preferred, C ６ Aryl is more preferred. ６－１０ Examples of aryl include phenyl, 1-naphthyl and 2-naphthyl.

[0428] As used herein, the term "heteroaryl" refers to a monovalent aromatic heterocyclic group that contains at least one heteroatom in addition to carbon atoms and is composed of a single ring or fused rings exhibiting aromaticity. The number of atoms constituting the heteroaryl ring is, for example, 5 to 14 (5- to 14-membered heteroaryl), preferably 5 to 13 (5- to 13-membered heteroaryl), more preferably 5 to 10 (5- to 10-membered heteroaryl), and most preferably 5 to 7 (5- to 7-membered heteroaryl).

[0429] Examples of 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S include pyrrolyl, thienyl, furyl, pyridyl, thiazolyl, isothiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, indolyl, indolinyl, benzothiophenyl, benzofuranyl, benzisothiazolyl, benzisoxazolyl, indazolyl, benzimidazolyl, benzotriazolyl, azaindolyl, and imidazopyridyl.

[0430] As used herein, "heteroarylalkyl" refers to a group in which one or more hydrogen atoms of an "alkyl" are substituted with a "heteroaryl". As the heteroarylalkyl, for example, a group in which one hydrogen atom of an alkyl is substituted with a heteroaryl is preferred. As the heteroarylalkyl, for example, a 5- to 10-membered heteroaryl C １－６ alkyl, preferably 5- to 10-membered heteroaryl C1-C4 alkyl, and more preferably 5- to 10-membered heteroaryl C １－３ Alkyl is more preferred, and 5- to 10-membered heteroaryl C １－２ Specific examples of heteroarylalkyl include 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-furanylmethyl, 2-thienylmethyl, 3-thienylmethyl, 4-thiazolylmethyl, 2-(2-pyridyl)ethyl, 2-(3-pyridyl)ethyl, 2-(4-pyridyl)ethyl, 2-(6-quinolyl)ethyl, 2-(7-quinolyl)ethyl, 2-(6-indolyl)ethyl, 2-(5-indolyl)ethyl, and 2-(5-benzofuranyl)ethyl.

[0431] As used herein, the term "heterocyclyl" refers to a heterocyclic group containing, in addition to carbon atoms, preferably 1 to 5, more preferably 1 to 3 heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms, and sulfur atoms as ring-constituting atoms, and which may have a double and / or triple bond within the ring. The carbon atoms in the heterocyclyl ring may be oxidized to form a carbonyl.

[0432] In this specification, a heterocyclyl containing a single ring is referred to as a monocyclic heterocyclyl, a heterocyclyl containing a fused ring is referred to as a fused-ring heterocyclyl, and a heterocyclyl containing a spiro ring is referred to as a spirocyclic heterocyclyl. A heterocyclyl may form a fused ring with, for example, a saturated alicyclic ring such as a cyclopentane ring or a cyclohexane ring, an unsaturated alicyclic ring such as a cyclohexene ring, a saturated heterocyclic ring such as a tetrahydropyran ring, a dioxane ring, or a pyrrolidine ring, an aromatic hydrocarbon ring such as a benzene ring or a naphthalene ring, or a pyridine ring, a pyrimidine ring, or a pyrazine ring. For example, a heterocyclyl may form a spiro ring with a saturated alicyclic ring such as a cyclopentane ring or a cyclohexane ring, or a saturated heterocyclic ring such as a tetrahydropyran ring, a dioxane ring, or a pyrrolidine ring.

[0433] The number of atoms constituting the heterocyclyl ring is, for example, 3 to 14 (3- to 14-membered heterocyclyl), preferably 3 to 12 (3- to 12-membered heterocyclyl), more preferably 3 to 10 (3- to 10-membered heterocyclyl), and most preferably 4 to 7 (4- to 7-membered heterocyclyl).

[0434] Specific examples of heterocyclyl include azetidinyl, oxiranyl, oxetanyl, thietanyl, tetrahydrofuranyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, oxooxazolidinyl, dioxolanyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, 4-oxopyrrolidinyl, piperidinyl, 4-oxopiperidinyl, piperazinyl, dioxanyl, and rings in which one or more single bonds in these saturated heterocycles are replaced with double bonds or triple bonds.

[0435] In this specification, the salt of ammonia includes ammonium halide salts such as ammonium chloride, ammonium bromide, and ammonium iodide.

[0436] In this specification, C ２－６Alkenyl is a straight- or branched-chain monovalent group of 2 to 6 carbon atoms having one or more double bonds. Examples include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl), propen-2-yl, and 3-butenyl (homoallyl).

[0437] In this specification, C ２－６ Alkynyl means a straight or branched monovalent group of 2 to 6 carbon atoms having one or more triple bonds, and includes, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl.

[0438] In this specification, C ３－８ Cycloalkyl means a cyclic saturated aliphatic hydrocarbon group having 3 to 8 carbon atoms, examples of which include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0439] In this specification, C ４－１０ Cycloalkylalkyl is a C alkyl group substituted with a cyclic saturated aliphatic hydrocarbon group having 3 to 9 carbon atoms. １－７ It means alkyl, having a total of 4 to 10 carbon atoms. Examples include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 1-(cyclopropyl)ethyl, 1-(cyclobutyl)ethyl, 1-(cyclopentyl)ethyl, 1-(cyclohexyl)ethyl, 2-(cyclopropyl)ethyl, 2-(cyclobutyl)ethyl, 2-(cyclopentyl)ethyl, and 2-(cyclohexyl)ethyl.

[0440] In this specification, C ７－１４ Aralkyl means an alkyl substituted with an aryl having a total of 7 to 14 carbon atoms, examples of which include benzyl, 1-phenethyl, 2-phenethyl, 1-naphthylmethyl, 2-naphthylmethyl, and the like.

[0441] Examples of halide anions include fluoride ions, chloride ions, bromide ions, and iodide ions. １－６ Alkoxy is C １－６means an alkyl-O- group, where C １－６ Alkyl is as defined above. Specific examples include methoxy, ethoxy, 1-propoxy, 2-propoxy, n-butoxy, i-butoxy, sec-butoxy, and t-butoxy.

[0442] In this specification, (C １－６ Alkoxy)carbonyl is C １－６ means an alkoxy-C(═O)— group, where C １－６ Alkoxy is as defined above. １－６ Alkoxy)carbonylamino is C １－６ means an alkoxy-C(═O)NH— group, where C １－６ Alkoxy is as previously defined.

[0443] In this specification, (C ３－１４ cycloalkyl)(C １－３ Alkoxy)carbonylamino is C １－３ The alkoxy portion is C ３－１４ Cycloalkyl-substituted C １－３ It means an alkoxy-C(=O)NH- group, where C ３－１４ Cycloalkyl means a cyclic saturated aliphatic hydrocarbon group having 3 to 14 carbon atoms.

[0444] In this specification, (C １－６ Alkyl)carbonyl is C １－６ means an alkyl-C(═O)— group, where C １－６ Alkyl is as defined above. １－６ Alkoxy)carbonylamino "(C １－６ The term "alkoxy)carbonyl" is as previously defined.

[0445] In this specification, (C ６－１０ aryl)carbonyl "C ６－１０ "Aryl" is as defined above. ６－１０ aryl)carbonylamino "C ６－１０ "Aryl" is as previously defined.

[0446] As used herein, the "5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S" in the 5- to 10-membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N, and S is as defined above.

[0447] In this specification, di(C １－６ alkyl)amino "C １－６ The "alkyl" is as defined above and may be the same or different. In this specification, the 4- to 8-membered cyclic amino includes groups such as aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, which are bonded at the nitrogen atom.

[0448] As used herein, aminocarbonyl refers to -CONH ２ In this specification, (C １－６ alkyl)aminocarbonyl "C １－６ "Alkyl" is as previously defined.

[0449] In this specification, di(C １－６ alkyl)aminocarbonyl "C １－６ The "alkyl" and "alkyl" are as defined above and may be the same or different. As used herein, the 4- to 8-membered cyclic amino of the 4- to 8-membered cyclic aminocarbonyl is as defined above, and is bonded to the carbonyl via the nitrogen atom.

[0450] In the present specification, the term "halogen atom" refers to a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc. In the present invention, when a halogen atom is a substituent of an aryl, a heteroaryl, etc., preferred examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom. In the present invention, when a halogen atom is a substituent of an alkyl or a group containing an alkyl as a part thereof (alkoxy, alkenyl, alkylthio, etc.), preferred examples of the halogen atom include a fluorine atom. Specific examples of groups having a halogen atom as a substituent include trifluoromethyl, pentafluoroethyl, trifluoromethoxy, pentafluoroethoxy, trifluoromethylthio, and pentafluoroethylthio.

[0451] As used herein, the term "aromatic group" refers to an aromatic heterocyclic group and an aromatic carbocyclic group, for example, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S.

[0452] As used herein, "aliphatic group" refers to a hydrocarbon group, e.g., a linear, branched, cyclic, or partially cyclic C group, which may contain one or more double and / or triple bonds. １－２０ Alkyl, specifically linear, branched, cyclic, or partially cyclic C alkyl, which may contain one or more double and / or triple bonds. １－１０ Alkyl and the like.

[0453] As used herein, the term "optionally substituted" means that any substitutable position of a group is not substituted or is substituted with one or more functional groups. Such functional groups are not particularly limited, and examples thereof include deuterium, halogen, cyano, nitro, hydroxy, thio, amino, carboxy, oxo, sulfonyl, phosphoryl, boranyl, C １-６ Alkyl, C ２-６ Alkenyl, C ２-６ Alkynyl, C ３-６ Cycloalkyl, C ６-１０ Aryl, 5- to 14-membered heteroaryl, C ７-１４ Aralkyl, 5- to 10-membered heteroaryl C １-６ Alkyl, 3- to 14-membered heterocyclyl, C １-６ Alkoxy C １-６ Alkyl, C １-６ Alkylsulfanyl C １-６ Alkyl, C １-６ Alkylsulfinyl C １-６ Alkyl, C １-６ Alkylsulfonyl C １-６ Alkyl, C １-６ Carboxyalkyl, C ７-１４ Aralkoxy C １-６ Alkyl, C ３-８ Cycloalkyl C １-６ Alkyl, C ３-８ Cycloalkoxy C１-６ Alkyl, 5- to 10-membered heteroaryl C １-６ Alkyl, 4- to 7-membered heterocyclyl C １-３ Alkyl, 5- to 10-membered heteroaryl C １-６ Alkoxy C １-６ Alkyl, aminocarbonyl (the amino is -NH ２ , Mono C １-６ Alkylamino, DiC １-６ Alkylamino, N—C １-６ Alkyl-N—C ２-６ Alkenylamino, N—C １-６ Alkyl-N—C １-６ Alkoxy C １-６ alkylamino, or 4- to 8-membered cyclic amino), C １-６ Alkoxy, C ３-１０ Cycloalkoxy, C ６-１０ Aryloxy, 5- to 14-membered heteroaryloxy, C ６-１０ Aryl C １-１０ Alkoxy, 5- to 10-membered heteroaryl C １-６ Alkoxy, 3- to 14-membered heterocyclyloxy, 3- to 14-membered heterocyclyl C １-６ Alkoxy, C ２-６ Alkenyloxy, C １-６ Alkylsulfanyl, C １-６ Alkylsulfinyl, C １-６ Alkylsulfonyl, C ６-１０ arylsulfonyl, 5- to 14-membered heteroarylsulfonyl, (C １－６ Alkoxy)carbonyl, C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０The substituent is selected from the group consisting of a 5- to 10-membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N, and S, and acyl, and these functional groups may be further substituted with an acceptable functional group. The substituent may be selected from the group consisting of a substituent containing an oxygen atom, a substituent containing a nitrogen atom, a substituent containing a sulfur atom, a substituent containing a boron atom, a substituent containing a silicon atom, a substituent containing a phosphorus atom, and a substituent containing a zinc atom.

[0454] In the definitions provided herein, when a given group is substituted with one or more substituents, the number of such groups may range from one to the number of available positions, such as 1 to 5, 1 to 4, 1 to 3, 1 or 2, or 1 substituent.

[0455] As used herein, C may be substituted with one or more halogen atoms. １－６ The alkyl group may be, for example, C which may be substituted with one or more fluorine atoms. １－６ Alkyl, particularly trifluoromethyl, and difluoromethyl.

[0456] In one aspect of the present invention, the reaction time for the sulfonylation reaction can be appropriately set by those skilled in the art, and is set within the range of, for example, 1 minute to 96 hours, 5 minutes to 72 hours, 10 minutes to 48 hours, 15 minutes to 48 hours, or 30 minutes to 24 hours.

[0457] In one embodiment of the present invention, the sulfonylation reaction is followed by removal of impurities. Impurity removal can be performed by a method commonly used in the technical field of the present invention. Examples of impurities include impurities derived from the reaction reagents, unreacted reaction reagents, decomposition products resulting from the reaction, coexisting bases, and reaction solvents. Specific examples of impurities include triazole derivatives derived from the leaving group of the sulfonylating agent, bases added to the reaction, and solvents such as tetrahydrofuran. Examples of methods for removing impurities include liquid-liquid separation, vacuum distillation, a method using a solid-phase reagent, purification by normal-phase or reverse-phase silica gel column chromatography, and purification by GPC (molecular sieve chromatography).

[0458] Liquid-liquid separation for removing impurities can be carried out by methods commonly used in the technical field of the present invention. Liquid-liquid separation is not particularly limited as long as it is a combination of solvents that separate into multiple layers for the purpose of separating desired products from impurities (unwanted substances). For example, liquid-liquid separation can be carried out by combining a solvent selected from ester solvents such as ethyl acetate and isopropyl acetate; ether solvents such as diethyl ether, diisopropyl ether, t-butyl methyl ether, cyclopentyl methyl ether, 2-methyltetrahydrofuran, 4-methyltetrahydropyran, 1,2-dimethoxyethane, and diethyl ether; halogenated solvents such as dichloromethane, chloroform, and 1,2-dichloroethane; aromatic hydrocarbon solvents such as benzene and toluene; and hydrocarbon solvents such as hexane, cyclohexane, and heptane; with a solvent selected from water, an acidic aqueous solution such as an aqueous hydrochloric acid solution, and a basic aqueous solution such as an aqueous sodium bicarbonate solution. A single solvent may be used, or a mixture of multiple solvents may be used. Furthermore, if it is consistent with the purpose of separating desired products from impurities (unwanted substances), it can be carried out by combining organic solvents that separate into layers, such as a combination of hexane and acetonitrile.

[0459] The vacuum distillation to remove impurities can be carried out by a method commonly used in the technical field of the present invention. The vacuum distillation conditions can be appropriately set depending on the impurities to be removed. For example, the pressure may be 100 to 400 mbar, 50 to 100 mbar, 5 to 50 mbar, or 0.1 to 5 mbar, and the temperature may be 20 to 100°C, 25 to 50°C, or 35 to 45°C.

[0460] The removal of impurities using a solid-phase reagent can be carried out by a method commonly used in the technical field of the present invention, such as macroporous triethylammonium methylpolystyrene carbonate, macroporous polystyrene sulfonic acid, amine-supported silica gel, carboxylic acid-supported silica gel, etc.

[0461] In one embodiment of the present invention, the method includes removing impurities after the sulfonylation reaction performed by solid-phase synthesis. Examples of impurities include unreacted reaction reagents, impurities derived from reaction reagents, decomposition products cleaved from the solid-phase synthesis resin by the reaction, and coexisting bases. In particular, in addition to the above, examples of impurities include decomposition products cleaved from the solid-phase synthesis resin by decomposition of the alkoxybenzyl ether structure. Impurities can be removed by washing the solid-phase synthesis resin. For example, the solid-phase synthesis resin can be transferred to a filter-equipped column and washed with an NMP solution of DMEDA, NMP, an NMP solution of TBAHSO4 and DTBP, an NMP solution of DIPEA, a mixed solution of NMP and water, NMP, MeOH, DCM, or the like. These washes can be combined, and multiple washes can be repeated as needed.

[0462] In one aspect of the present invention, the nitrogen-containing compound used as the substrate for the sulfonylation reaction is a solid-phase synthesis resin to which a low-molecular-weight nitrogen-containing compound is linked via a linker. In one aspect of the present invention, the nitrogen-containing compound bound to the solid-phase synthesis resin used as the substrate for the sulfonylation reaction may be a plurality of different compounds. For example, the sulfonylation reaction can be carried out using a solid-phase synthesis resin to which two or more, three or more, four or more, five or more, seven or more, or ten or more different nitrogen-containing compounds are bound. The solid-phase synthesis resin used as the solid support is not particularly limited as long as it is a commonly used resin. Examples of such resins include CTC resin, Trt resin, SASRIN resin, Rink amide resin, Merrifield resin, Wang resin, and 2-(4-bromomethylphenoxy)ethyl polystyrene, as well as solid supports having any functional group, such as a carboxyl group, an amino group, an aminomethyl group, a hydroxy group, or a hydroxymethyl group, on polystyrene. Furthermore, any linker that covalently connects the carrier and a low-molecular-weight nitrogen-containing compound may be used, and the design may allow cleavage between the linker and the compound. The carrier is not particularly limited, and examples thereof include polystyrene and PEG (polyethylene glycol).

[0463] The technique and reaction conditions for binding a compound to a solid-phase synthesis resin can be appropriately determined by those skilled in the art based on methods described in publicly known literature. In one aspect of the present invention, a solid-phase synthesis resin to which a nitrogen-containing compound is bound can be prepared by supporting a nitrogen-containing compound or its precursor compound on a solid-phase synthesis resin. The compound can be supported on a solid-phase synthesis resin by forming a covalent bond through a reaction between a reactive group on the side chain of the solid-phase synthesis resin and a reactive group of the compound. In one aspect of the present invention, a solid-phase synthesis resin to which a nitrogen-containing compound as a substrate is bound can be prepared by chemically modifying a solid-phase synthesis resin supporting a precursor compound.

[0464] In one aspect of the present invention, the sulfonylating agent used in the sulfonylation reaction is a solid-phase synthesis resin to which a low-molecular-weight sulfonylating agent is linked via a linker. In one aspect of the present invention, the sulfonylating agents bound to the solid-phase synthesis resin used in the sulfonylation reaction may be multiple different compounds. For example, the sulfonylation reaction can be carried out using a solid-phase synthesis resin to which two or more, three or more, four or more, five or more, seven or more, or ten or more different sulfonylating agents are bound as the substrate. The solid-phase synthesis resin used as the solid-phase support is not particularly limited as long as it is a commonly used resin. Examples include CTC resin, Trt resin, SASRIN resin, Rink amide resin, Merrifield resin, Wang resin, and 2-(4-bromomethylphenoxy)ethyl polystyrene, as well as solid-phase supports having any functional group, such as a carboxyl group, an amino group, an aminomethyl group, a hydroxy group, or a hydroxymethyl group, on polystyrene. Furthermore, any linker that covalently connects the carrier and the sulfonylating agent may be used, and the design may allow cleavage between the linker and the compound. The carrier is not particularly limited, and examples thereof include polystyrene and PEG (polyethylene glycol).

[0465] The technique and reaction conditions for binding a compound to a solid-phase synthesis resin can be appropriately determined by those skilled in the art based on methods described in publicly known literature. In one aspect of the present invention, a solid-phase synthesis resin to which a sulfonylating agent is bound can be prepared by supporting a sulfonylating agent or its precursor compound on a solid-phase synthesis resin. The compound can be supported on a solid-phase synthesis resin by forming a covalent bond through a reaction between a reactive group on the side chain of the solid-phase synthesis resin and a reactive group of the compound. In one aspect of the present invention, a solid-phase synthesis resin to which a sulfonylating agent is bound can be prepared by chemically modifying a solid-phase synthesis resin supporting a precursor compound.

[0466] Those skilled in the art can appropriately determine the reaction conditions for cleaving a compound from a solid-phase synthesis resin based on the chemical structure of the solid-phase synthesis resin used. Reagents used for cleavage include, for example, hydrochloric acid, carboxylic acids such as trifluoroacetic acid (TFA), fluoroalcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP), as well as Bronsted acids with a pKa of 10 or less in water or any Lewis acid. In one embodiment, the compound cleaved from the solid-phase synthesis resin can be used as a screening compound for drug discovery.

[0467] In one aspect, the present invention provides a compound having a group represented by Formula 1 or a compound represented by Formula 2. The compound is useful as a sulfonylating agent used in the production of sulfonamide compounds. In one embodiment, the sulfonylating agent can be isolated after preparation and used. In one embodiment, the sulfonylating agent can be stored as a solution and added to a reaction system. In one embodiment, the sulfonylating agent can be prepared by alkylating a precursor triazole compound, and the resulting reaction mixture can be used as is.

[0468] In one aspect, the present invention provides a compound of formula 2:

[0469] [In the formula, R １is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, － is a counter anion.

[0470] In one aspect, the present invention provides a compound of formula 2:

[0471] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, － is a counter anion.

[0472] In one aspect, the present invention provides a compound of formula 1:

[0473]

[0474] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, and represents a point of attachment.

[0475] In one aspect, the present invention provides a method for producing a compound having a group represented by formula 1 or a compound represented by formula 2, comprising:

[0476] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl, and * represents a point of attachment, ３ -X [wherein, R ３ is C １－６ alkyl or benzyl, and X is a leaving group, to obtain a compound represented by formula 1:

[0477]

[0478] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, and * represents a point of attachment.

[0479] In one embodiment of the present invention, a compound having a group represented by formula 3 and a compound having formula: R ３The reaction with the alkylating agent represented by -X can be carried out in a solvent (a single solvent may be used, or a mixture of multiple solvents may be used) selected from ether solvents such as tetrahydrofuran, 2-methyltetrahydrofuran, 4-methyltetrahydropyran, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, cyclopentyl methyl ether, t-butyl methyl ether, 1,4-dioxane, and 1,3-dioxolane; halogenated solvents such as dichloromethane, 1,2-dichloroethane, and chloroform; nitrile solvents such as acetonitrile, propionitrile, and benzonitrile; and aromatic hydrocarbon solvents such as benzene, toluene, and xylene. In one aspect of the invention, the reaction can be carried out at a temperature of 0°C to 120°C, 0°C to 80°C, 0°C to 60°C, 0°C to 50°C, 0°C to 40°C, 10°C to 100°C, 10°C to 80°C, 10°C to 60°C, 10°C to 50°C, 10°C to 40°C, 15°C to 100°C, 15°C to 80°C, 15°C to 60°C, 15°C to 50°C, 15°C to 40°C, 20°C to 90°C, 25°C to 80°C, 30°C to 80°C, 35°C to 80°C, or 40°C to 80°C.

[0480] In one embodiment of the present invention, R ３ The alkylating agent represented by -X can be used in an amount of 0.8 equivalents or more, 0.9 equivalents or more, 1.0 equivalents or more, 1.1 equivalents or more, 1.2 equivalents or more, 1.5 equivalents or more, 1.8 equivalents or more, 2 equivalents or more, 2.2 equivalents or more, 2.5 equivalents or more, 3 equivalents or more, or 3.5 equivalents or more relative to the compound having a group represented by formula 3. Here, the number of equivalents is calculated based on the number of groups represented by formula 3 contained in the substrate compound.

[0481] In one aspect of the present invention, the compound having a group of formula 1 is a sulfonyl group, R ２ , and R ４ In one aspect of the present invention, the compound of formula 2 is a mixture of two positional isomers with respect to the group R ２ , and R ４ It is a mixture of two positional isomers with respect to the group:

[0482] In one aspect, the present invention provides a method for preparing a sulfonamide compound comprising:

[0483]

[0484] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, and represents the point of attachment; and / or a compound having a group represented by formula 5:

[0485]

[0486] [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, and * represents an attachment point] with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group to a sulfonamide group corresponding to the nitrogen-containing compound.

[0487] In one aspect, the present invention provides a method for preparing a sulfonamide compound comprising:

[0488]

[0489] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, － is a counter anion], and / or a compound represented by formula 6:

[0490] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, － is a counter anion] with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group into a sulfonamide group corresponding to the nitrogen-containing compound.

[0491] In one aspect, the present invention provides a method for preparing a sulfonamide compound comprising:

[0492]

[0493] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, － is a counter anion], and / or a compound represented by formula 6:

[0494]

[0495] [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, －is a counter anion] with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group into a sulfonamide group corresponding to the nitrogen-containing compound.

[0496] In one aspect of the present invention, the compound having a group represented by formula 5 is a sulfonyl group, R ２ , and R ４ In one aspect of the present invention, the compound of formula 6 is a mixture of two positional isomers with respect to the group R ２ , and R ４ It is a mixture of two positional isomers with respect to the group:

[0497] The present invention will be explained in more detail below using Reference Examples and Examples, but the present invention is not limited to these Examples.

[0498] EXAMPLES All starting materials, reagents, and solvents were obtained from commercial suppliers or synthesized using known methods. Reagents and solvents were of reagent quality or better and were used as obtained from various commercial sources unless otherwise noted.

[0499] The silica gel used for column chromatography was Biotage (registered trademark) SNAP ULtra, Biotage (registered trademark) Sfaer D (Duo) (60 μm), or Biotage (registered trademark) Sfaer HC D (Duo) (20 μm), etc. The amino silica gel used for column chromatography was Biotage (registered trademark) SNAP Isolute NH ２ (50 μm) or Biotage® SNAP Cartridge KP-NH, etc. were used as appropriate. As reverse-phase silica gel for column chromatography, Biotage® SNAP MLtra C18 (25 μm) or Biotage® Sfaer C18 (30 μm), etc. were used as appropriate.

[0500] １ H-NMR, １３ C-NMR spectra were measured using Me as an internal standard. ４ ​Measurements were carried out with or without Si using an appropriate instrument such as ECP-400 (manufactured by JEOL), Agilent 400-MR (manufactured by Agilent Technologies), AVANCE3 Cryo-TCI, AVANCE3 400, AVANCE3 HD 400, AVANCE NEO 400, AVANCE3 HD 300, AVANCE3 300, AVANCE2 300, or AVANCE NEO 300 (manufactured by Bruker) (s = singlet, brs = broad singlet, d = doublet, t = triplet, q = quartet, dd = double doublet, ddd = double double doublet, dt = double triplet, td = triple doublet, m = multiplet).

[0501] Unless otherwise specified, reaction tracking and purity measurement were performed by measuring retention time and performing mass spectrometry using 2020 (Shimadzu) under the analytical conditions shown in the table below.

[0502] The following abbreviations are used in the examples:

[0503]

[0504] The LCMS analysis conditions are shown in the table below.

[0505] The m / z [M+H] shown in the LCMS analysis results in the examples ＋ and (M+H) ＋ Unless otherwise specified, all values ​​shown are those detected in positive mode. Furthermore, the UV area % in LCMS is the value in PDA (190-400 nm or 210-400 nm) unless otherwise specified. When a specific wavelength (e.g., 299 nm) is listed, the UV area % is listed at wavelengths up to + / - 4 nm from the listed wavelength. Note that blanks or ND in the tables indicate values ​​below the detection limit.

[0506] The term "concentrated under reduced pressure" refers to removal of solvent by evaporation under reduced pressure using a rotary evaporator, a mechanical oil vacuum pump, or a mechanical oil-free vacuum pump. The term "dried overnight under reduced pressure" refers to removal of solvent by evaporation under reduced pressure using a rotary evaporator, a mechanical oil vacuum pump, or a mechanical oil-free vacuum pump.

[0507] The terms "overnight" and "overnight" refer to approximately 8 to 14 hours unless otherwise specified. The terms "room temperature" and "rt" refer to approximately 20 to 28°C unless otherwise specified. Solid-phase reactions can be carried out in any appropriate container, such as a glass vial that can be sealed with a cap equipped with Teflon (registered trademark) packing, a fritted filter, and a column with an appropriate stopper. The size of the container is appropriately selected so that there is sufficient space for the solvent and that there is enough room for effective stirring of the resin, taking into consideration that certain resins may swell significantly when treated with organic solvents.

[0508] Agitation in solid-phase reactions was carried out at 50-200 rpm using a suitable shaker (e.g., EYELA MMS-320, MMS-220H, Tokyo Rika Kikai Co., Ltd., or MyBL-100CS, AS ONE, or M-BR-104, TAITEC) or a stirring device (a combination of a separable flask, manufactured by Asahi Seisakusho Co., Ltd., and a sealing mixer UZU, manufactured by Nakamura Scientific Instruments Co., Ltd., and a centrifugal stirrer C-mix, manufactured by Aquatex Co., Ltd.) to ensure sufficient mixing, a factor generally recognized as important for the success of reactions on resins.

[0509] To monitor the progress of the reaction on the solid phase, the resin must be removed from the reaction vessel. To do so, a micropipette equipped with a pipette tip cut to an appropriate length was used to aspirate approximately 10 μL of resin, ensuring that the resin was included. The resin was then transferred onto the filter of a filter-equipped pipette tip (e.g., Thermo Scientific, ART Filter Tip ART20P, 2149P-05). The resin-supported compound was then cleaved from the resin using the following typical procedure for resin on a filter: After washing three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL), the resin was immersed in 0.02 M pentamethylbenzene in 10% TFA / DCM (0.05 mL) for 2 minutes. After filtration, the solid phase was washed with DMF (0.05 mL), MeCN (0.25 mL) was added to the filtrate, an LC sample was prepared, and the reaction progress was measured by LCMS.

[0510] The term "cleavage" from the solid phase refers to the desorption of a compound supported on the resin from the resin, for example, by treating the resin with a 10% TFA / DCM solution containing 0.02 M pentamethylbenzene, and recovering the supported compound in solution.

[0511] The compound numbers used in the examples are indicated by a combination of arbitrary letters, numbers, and symbols. Compounds supported on a solid phase are indicated by adding "1R" to the end, for example, "SP001-1R." In contrast, compounds cleaved from the solid phase are indicated by "SP001," omitting the "-1R."

[0512] Used in the chemical structure notation in the examples: The notation indicates a polystyrene resin, and indicates that the compound is supported on a solid phase.

[0513] Example of "-1R"

[0514] The amount of supported solid-phase compounds used in solid-phase synthesis is shown as a supported amount (mmol / g), which is calculated assuming that 100% of the extracted compound is supported on the solid phase.

[0515] Example 1: Substrate synthesis Example 1-1: Synthesis of solid-phase carboxylic acid (SP040-1R) Example 1-1-1: Synthesis of tert-butyl 4-[4-[[4-(4-ethoxycarbonylphenyl)phenoxy]methyl]phenoxy]piperidine-1-carboxylate (compound LP012)

[0516]

[0517] Under a nitrogen atmosphere, tert-butyl 4-[4-(hydroxymethyl)phenoxy]piperidine-1-carboxylate (B06, 1.00 g, 3.25 mmol), triethylamine (0.499 mL, 3.58 mmol), and DCM (16.3 mL) were added to a 100 mL three-neck flask, and the reaction vessel was cooled to 0°C. Methanesulfonyl chloride (B07, 0.266 mL, 3.42 mmol) was added, and the mixture was stirred at 0°C for 3 hours. Saturated aqueous sodium bicarbonate solution (4.9 mL) was added to the resulting mixture. The organic layer was extracted three times with dichloromethane (24 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue, ethyl 4-(4-hydroxyphenyl)benzoate (B08, 0.866 g, 3.58 mmol), cesium carbonate (2.12 g, 6.50 mmol), and NMP (12.0 mL) were mixed in a 100 mL three-neck flask under a nitrogen atmosphere and stirred at room temperature for 24 hours. Saturated aqueous ammonium chloride solution (6 mL) was added to the resulting mixture. The organic layer was extracted three times with ethyl acetate (10 mL), and then the resulting organic layers were combined and hexane (20 mL) was added. The organic layer was washed three times with water (15 mL) and once with saturated aqueous sodium chloride solution (15 mL), and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (0-25% ethyl acetate / hexane), and the resulting crude product was purified by silica gel column chromatography (NH-silica gel, dichloromethane / hexane, 0-100%). The obtained crude product was dissolved in ethyl acetate (100 mL) and hexane (200 mL), washed three times with water (200 mL) and once with a saturated aqueous sodium chloride solution (100 mL), and concentrated under reduced pressure to obtain the title compound LP012 (1.44 g, 2.71 mmol, 83%) as a white solid.

[0518]

[0519] Compound LP012 １ H-NMR (400MHz, CDCl ３) δ: 8.08 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.8 Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 7.06 (d, J=8.8Hz, 2H), 6.93 (d, J=8.4Hz, 2H), 5.04 (s, 1H), 4.50-4.45 (m, 1H), 4.40 (q, J=7.2Hz, 2H), 3.73-3.67 (m, 2H), 3.38-3.31 (m, 2H) H), 1.96-1.88 (m, 2H), 1.80-1.71 (m, 2H), 1.47 (s, 9H), 1.41 (t, J = 7.2Hz, 3H).

[0520] LCMS: m / z 554 [M+Na] ＋ . Retention time: 1.684 minutes (Analysis conditions FA05-1, 290 nm).

[0521] Example 1-1-2: Synthesis of ethyl 4-[4-[(4-piperidin-4-yloxyphenyl)methoxy]phenyl]benzoate (compound LP001)

[0522] Under a nitrogen atmosphere, tert-butyl 4-[4-[[4-(4-ethoxycarbonylphenyl)phenoxy]methyl]phenoxy]piperidine-1-carboxylate (LP012, 50.0 mg, 94.0 μmol), DIPEA (29.5 μL, 0.169 mmol), and THF (1.88 mL) were added to a 5 mL screw-cap vial, and the reaction vessel was cooled to 0°C. TMSOTf (20.4 μL, 0.113 mmol) was added, and the mixture was stirred at 0°C for 3 hours. Then, DIPEA (2.95 μL, 16.9 μmol) and TMSOTf (2.0 μL, 11 μmol) were added, and the mixture was stirred at 0°C for 1.5 hours. Triethylamine (26.2 μL) was added to the resulting mixture at 0°C, and the mixture was stirred at room temperature for 30 minutes. Water (847 μL), DMSO (1 mL), and formic acid (12.1 μL, 0.282 mmol) were added, and the mixture was purified by reverse-phase column chromatography (C18, 0-60% 0.1% formic acid acetonitrile solution / 0.1% formic acid aqueous solution). The resulting product was dissolved in dichloromethane (100 mL), washed three times with saturated aqueous sodium bicarbonate (50 mL), and once with saturated aqueous sodium chloride (50 mL). The mixture was concentrated under reduced pressure to give the title compound LP001 (19.8 mg, 0.046 mmol, 49%) as a white solid.

[0523]

[0524] Compound LP001 １ H-NMR (400MHz, CDCl ３ ) δ: 8.08 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 8.8 Hz, 2H), 7.3 6 (d, J=8.8Hz, 2H), 7.06 (d, J=8.8Hz, 2H), 6.94 (d, J=8.8Hz, 2H), 5.03 (s, 2H) , 4.42-4.36 (m, 3H), 3.15 (ddd, J=13.6, 4.8, 4.8Hz, 2H), 2.74 (ddd, J=13.6, 9 .2, 3.2Hz, 2H), 2.06-1.99 (m, 2H), 1.73-1.64 (m, 2H), 1.41 (t, J = 7.2Hz, 3H).

[0525] LCMS: m / z 432 [M+H] ＋. Retention time: 0.904 minutes (Analysis conditions FA05-1, 290 nm).

[0526] Example 1-1-3: Synthesis of compound SP040-1R

[0527] Amidation Reaction: Under a nitrogen atmosphere, carboxylic resin (SP000-1R) (loading amount 2.19 mmol / g, 1.00 g, 2.19 mmol) and NMP (15 mL) were added to a 20 mL glass vial and shaken at room temperature for 1 hour. Ethyl 4-[4-[(4-piperidin-4-yloxyphenyl)methoxy]phenyl]benzoate (LP001) (0.106 g, 0.246 mmol), piperidine (0.033 mL, 0.329 mmol), HOAt (0.298 g, 2.19 mmol), and DIC (0.341 mL, 2.19 mmol) were added and shaken at room temperature for 4 hours. Piperidine (1.30 mL, 13.1 mmol), HOAt (1.79 g, 13.1 mmol), and DIC (2.05 mL, 13.1 mmol) were added, and the mixture was shaken at room temperature overnight.

[0528] Solid-phase purification The reaction solution and the solid-phase suspension were all transferred onto a filter and washed three times with NMP (20 mL), three times with methanol (20 mL), and three times with DCM (20 mL). The obtained solid phase was dried overnight under reduced pressure to obtain compound SP039-1R (loading amount 0.200 mmol / g, 1.25 g, 0.250 mmol).

[0529] Hydrolysis Under a nitrogen atmosphere, compound SP039-1R (loading amount 0.200 mmol / g, 1.25 g, 0.250 mmol), THF (7.2 mL), methanol (0.8 mL), and an aqueous sodium hydroxide solution (5 M, 0.8 mL, 4.0 mmol) were placed in a 10 mL glass vial, and the mixture was shaken at 60°C for 6 hours.

[0530] Solid-Phase Purification The reaction solution and the solid phase suspension were all transferred onto a filter and washed three times with NMP (20 mL), three times with water (20 mL), three times with HOAt (0.2 M NMP solution, 20 mL), three times with NMP (20 mL), three times with methanol (20 mL), and three times with DCM (20 mL). The obtained solid phase was dried overnight under reduced pressure to obtain compound SP040-1R (loading amount 0.201 mmol / g, 1.16 g, 0.232 mmol).

[0531] Reaction tracking: A suspension (10 μL) of the reaction mixture and solid phase was transferred onto a filter and washed three times with NMP (0.1 mL), three times with methanol (0.1 mL), and three times with DCM (0.1 mL). The filter was then immersed in 0.2 M pentamethylbenzene in 10% TFA / DCM (0.05 mL) for 5 minutes. After filtration, the solid phase was washed with NMP (0.05 mL). Acetonitrile (0.25 mL) was added to the filtrate. An LC sample was prepared and analyzed by LCMS to measure the reaction progress. 100% of the target product, SP040, was observed.

[0532]

[0533] Compound SP040 Maximum wavelength 294 nm Retention time: 0.775 minutes (Analysis conditions FA05-1, 299 nm)

[0534] Example 1-2: Synthesis of solid phase amine compound Example 1-2-1: Synthesis of compound SP004-1R

[0535]

[0536] Under a nitrogen atmosphere, compound SP040-1R (0.201 mmol / g, 450 mg) and NMP (6.75 mL) were placed in a 20 mL glass vial and shaken at room temperature for 1 hour. 3-(aminomethyl)aniline (B01) (76 μL, 0.68 mmol), Oxyma (96 mg, 0.68 mmol), and DIC (105 μL, 0.675 mmol) were added, and the mixture was shaken at room temperature for 9 hours.

[0537] The reaction solution and the suspension of the solid phase were all transferred to a filter-equipped column, filtered, and then washed three times with NMP (6 mL), three times with MeOH (6 mL), and three times with DCM (6 mL). The obtained solid phase was dried under reduced pressure to obtain compound SP004-1R (0.197 mmol / g, 450 mg).

[0538] A portion of compound SP004-1R was transferred onto a filter chip and washed three times with NMP (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The chip was immersed in a 10% TFA / DCM solution of pentamethylbenzene (0.02 M, 0.05 mL) for 5 minutes, filtered, washed with NMP (0.05 mL), and the combined filtrate was diluted with MeCN (0.5 mL) and analyzed by LCMS. SP004 was detected at 98%. The analysis was performed at a wavelength of 290 nm (±4 nm).

[0539]

[0540] Compound SP004 LRMS: m / z 319 [M+H] ＋ Retention time: 0.707 minutes (Analysis conditions RPAmideTFA05, 290 nm).

[0541] Example 1-2-2: Synthesis of compound SP002-1R

[0542] Solid-phase-supported Ar-NHMe (SP002-1R) was synthesized by condensation of solid-phase-supported carboxylic acid (SP040-1R) (400 mg) with 3-(aminomethyl)-N-methylaniline (B02) (82 mg, 0.60 mmol) in the same manner as in Example 1-2-1. Solid-phase purification and reaction tracking (target compound: SP002) were also performed in the same manner as in Example 1-2-1, and the target compound, SP002, was observed in an amount of 95.7%.

[0543]

[0544] Compound SP002 LRMS: m / z 333 [M+H] ＋ Retention time: 0.679 minutes (analysis conditions FA05-1, 290 nm).

[0545] Example 1-2-3: Synthesis of compound SP001-1R

[0546] Amide condensation: SP040-1R (0.201 mmol / g, 6.5 g) and DCM (98 mL) were added to a 100 mL glass vial under a nitrogen atmosphere and shaken at room temperature for 1 hour. B10 (938 mg, 2.61 mmol), DIPEA (455 μL, 2.61 mmol), NMI (417 μL, 5.23 mmol), and PipClU (943 mg, 2.61 mmol) were added and shaken at room temperature for 2.5 hours.

[0547] Solid-phase purification The reaction solution and the solid phase suspension were all transferred onto a filter, and the filter was washed three times with NMP (100 mL), three times with NMP-water (1 / 1, 100 mL), three times with NMP (100 mL), swelled for one hour with 20% piperidine in DMF (100 mL), three times with NMP (100 mL), three times with methanol (100 mL), three times with DCM (100 mL), and three times with heptane (100 mL). The resulting solid phase was dried overnight under reduced pressure to obtain compound SP001-1R (loading amount 0.198 mmol / g, 7.28 g).

[0548] After drying, a small amount of the solid phase was transferred onto a filter tip and washed three times with DCM (0.1 mL). The solid was then immersed in a 10% TFA / DCM solution of pentamethylbenzene (0.2 M, 0.05 mL) for 5 minutes, filtered, and washed with DMF (0.05 mL). The combined filtrate was diluted with MeCN (0.2 mL) and analyzed by LCMS. The target product SP001 was confirmed to be 97.4%.

[0549]

[0550] Compound SP001 LRMS: m / z 297 [M+H] ＋ Retention time: 0.561 min (analysis conditions FA05-1, 299 nm).

[0551] Example 1-2-4: Synthesis of compound SP003-1R

[0552] Compound SP003-1R (loading amount 0.198 mmol / g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g) and B11 in the same manner as in Example 1-2-3. SP003-1R was immersed in a 10% TFA / DCM solution (0.05 mL) containing 0.2 M pentamethylbenzene for 5 minutes, and DMF (0.050 mL) and MeCN (0.20 mL) were added. The filtrate was filtered and analyzed by LCMS. 98.0% of the target compound SP003 was observed.

[0553]

[0554] Compound SP003 LRMS: m / z 297 [M+H] ＋ Retention time: 0.551 min (analysis conditions FA05-1, 299 nm).

[0555] Example 1-2-5: Synthesis of compound SP009-1R

[0556] Amide condensation: SP040-1R (0.201 mmol / g, 6 g) and DCM (90 mL) were added to a 100 mL filter column under a nitrogen atmosphere and shaken at room temperature for 1 hour. B19 (1.80 g, 4.83 mmol), PyAOP (2.52 g, 4.83 mmol), and DIPEA (15.6 g, 12.1 mmol) were added and shaken at room temperature for 3 hours.

[0557] After the reaction mixture was filtered under reduced pressure, DMF-water (1 / 1, 90 mL) was added, the mixture was shaken for 1 minute, and then filtered under reduced pressure. This procedure was repeated four times. The resulting solid phase was washed four times with DMF (90 mL) and dried under reduced pressure.

[0558] Fmoc Removal: Under a nitrogen atmosphere, the solid phase obtained by the above-mentioned amide condensation, piperidine (12 mL), and DMF (48 mL) were added to a 100 mL filter column, and the column was shaken at room temperature for 30 minutes.

[0559] After the reaction mixture was filtered under reduced pressure, DMF (90 mL) was added, the mixture was shaken for 1 minute, and the mixture was filtered under reduced pressure. This procedure was repeated four times. The resulting solid phase was washed four times with MeOH (90 mL), four times with DCM (90 mL), and four times with heptane (90 mL). The resulting solid phase was dried under reduced pressure to obtain compound SP009-1R (5.64 g).

[0560] Reaction Tracking The dried solid phase was separated in the same manner as in Example 1-2-3 and subjected to LCMS measurement, whereby the target product SP009 was observed at 99.4%.

[0561]

[0562] Compound SP009 LRMS: m / z 311 [M+H] ＋ Retention time: 0.666 minutes (analysis conditions FA05-2, 299 nm). Compounds SP009-01R and SP009 are sometimes referred to as compounds SP094-01R and SP094, respectively.

[0563] Example 1-2-6: Synthesis of compound SP010-1R

[0564] Compound SP010-1R (5.42 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 5.5 g) and B20 (1.51 g, 4.42 mmol) in the same manner as in Example 1-2-5.

[0565] The dried solid phase was separated in the same manner as in Example 1-2-3 and subjected to LCMS measurement, whereby the target product SP010 was observed at 98.0%.

[0566] Compound SP010 LRMS: m / z 299 [M+H] ＋ Retention time: 0.694 minutes (analysis conditions FA05-2, 299 nm). Compounds SP010-01R and SP010 are sometimes referred to as compounds SP096-01R and SP096, respectively.

[0567] Example 1-2-7: Synthesis of compound SP005-1R Example 1-2-7-1: Synthesis of compound SP045-1R

[0568] Compound SP045-1R (loading amount 0.195 mmol / g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g) and B12 in the same manner as in Example 1-2-3. SP045-1R was immersed in a 10% TFA / DCM solution (0.05 mL) containing 0.05 M pentamethylbenzene for 5 minutes, and NMP (0.10 mL) and MeCN (0.25 mL) were added. The filtrate was filtered and analyzed by LCMS. 97.4% of the target compound SP045 was observed.

[0569]

[0570] Compound SP045 LRMS: m / z 367 [M+H] ＋ Retention time: 0.917 minutes (analysis conditions FA05-1, 299 nm).

[0571] Example 1-2-7-2: Synthesis of compound SP041-1R

[0572] Under a nitrogen atmosphere, compound SP045-1R (loading amount 0.195 mmol / g, 5.0 g), pentamethylbenzene (1.45 g, 9.75 mmol), pyrrolidine (4.03 mL, 48.8 mmol), and DCE (75.0 mL) were added to a 100 mL column and stirred at room temperature for 1 hour. ３ ) ４ (113 mg, 98 μmol) was added, and the mixture was shaken at room temperature for 2 hours.

[0573] Solid-phase purification: The reaction mixture and solid phase suspension were purified three times with NMP (100 mL) and 0.3 M N-acetylcysteine ​​in NMP:H. ２ The solid phase was washed three times with a 0.2 M DIPEA / NMP solution (100 mL), three times with NMP (100 mL), three times with methanol (100 mL), three times with DCM (100 mL), and three times with heptane (100 mL), and the resulting solid phase was dried under reduced pressure overnight to obtain compound SP041-1R (loading amount 0.197 mmol / g, 4.71 g).

[0574] After drying, a small amount of the solid phase was transferred onto a filter tip and washed three times with NMP (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The solid was then immersed in 0.05 M pentamethylbenzene in 10% TFA / DCM solution (0.05 mL) for 5 minutes, and NMP (0.10 mL) and MeCN (0.25 mL) were added. The filtrate was filtered and analyzed by LCMS. 96.8% of the target product, SP041, was observed.

[0575]

[0576] Compound SP041 LRMS: m / z 283 [M+H] ＋ Retention time: 0.472 minutes (analysis conditions FA05-1, 299 nm).

[0577] Example 1-2-7-3: Synthesis of compound SP005-1R

[0578] Amide condensation: Under a nitrogen atmosphere, the solid-phase amine substrate (SP041-1R) (loading amount 0.197 mmol / g, 200 mg, 0.0394 mmol) and NMP (3 mL) were placed in a 4 mL glass vial and shaken at room temperature for 1 hour. B13 (52.1 mg, 0.315 mmol), HOAt (42.9 mg, 0.315 mmol), and DIC (49.1 μL, 0.315 mmol) were added, and the mixture was shaken at room temperature for 3 hours.

[0579] Solid-Phase Purification The reaction solution and the solid-phase suspension were all transferred onto a filter and washed three times with NMP (4 mL), three times with NMP / water (1 / 1, 4 mL), three times with NMP (4 mL), three times with methanol (4 mL), three times with DCM (4 mL), and three times with heptane (4 mL). The obtained solid phase was dried overnight under reduced pressure to obtain compound SP005-1R (loading amount 0.193 mmol / g).

[0580] Reaction tracking: A suspension (12 μL) of the reaction mixture and solid phase was transferred onto a filter and washed three times with NMP (0.1 mL), three times with methanol (0.1 mL), and three times with DCM (0.1 mL). The filter was then immersed in a 10% TFA / DCM solution (0.05 mL) containing 0.05 M pentamethylbenzene for 5 minutes. After filtration, the solid phase was washed with NMP (0.05 mL), and acetonitrile (0.5 mL) was added to the filtrate. An LC sample was prepared and analyzed by LCMS to measure the reaction progress. The target product, SP005, was observed at 96.9%.

[0581]

[0582] Compound SP005 LRMS: m / z 430 [M+H] ＋ Retention time: 0.808 minutes (analysis conditions FA05-1, 299 nm).

[0583] Example 1-2-8: Synthesis of compound SP006-1R Example 1-2-8-1: Synthesis of compound SP042-1R

[0584] Compound SP042-1R (loading amount 0.193 mmol / g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (B09) in the same manner as in Example 1-2-3.

[0585] SP042-1R was immersed in a 10% TFA / DCM solution (0.05 mL) containing 0.2 M pentamethylbenzene for 5 minutes, and filtered with DMA (0.20 mL). 50 μL of the filtrate was diluted with MeCN (0.25 mL) and subjected to LCMS measurement, whereby the target compound SP042 was observed at 94.3%.

[0586]

[0587] Compound SP042 LRMS: m / z 416 [M+H] ＋ Retention time: 1.235 minutes (analysis conditions FA05-1, 299 nm).

[0588] Example 1-2-8-2: Synthesis of compound SP006-1R

[0589] Suzuki Coupling Reaction: Under a nitrogen atmosphere, a 4 mL glass vial was charged with the solid-phase amine substrate (SP042-1R) (loading: 0.193 mmol / g, 150 mg, 0.0290 mmol) and THF (2.25 mL) and shaken at room temperature for 1 hour. B14 (20.6 mg, 0.090 mmol), CataCXium A Pd G4 (22.4 mg, 0.030 mmol), water (8.2 μL, 0.45 mmol), and P2tBu (CAS: 111324-03-9) (2 M THF solution, 67.8 μL, 0.136 mmol) were added and shaken at 60°C for 1.5 hours.

[0590] Solid-phase purification: The reaction mixture and the solid-phase suspension were all transferred onto a filter and purified by elution with NMP (3 mL) three times, NMP / water (1 / 1, 3 mL) three times, 0.2 M NAC in NMP / water (1 / 1, 3 mL) three times, and 0.05 M TBAHSO ４ The solid phase was washed three times with 3 mL of NMP / DTBP (1 / 1), three times with 3 mL of NMP (0.05 M NMM), three times with 3 mL of NMP / water (1 / 1), three times with 3 mL of NMP, three times with 3 mL of methanol, three times with 3 mL of DCM, and three times with 3 mL of heptane. The resulting solid phase was dried overnight under reduced pressure to obtain compound SP006-1R (loading amount 0.200 mmol / g, 163.7 mg).

[0591] Reaction tracking: A suspension (10 μL) of the reaction mixture and solid phase was transferred onto a filter and washed three times with DMF (0.1 mL), three times with methanol (0.1 mL), and three times with DCM (0.1 mL). The filter was then immersed in a 10% TFA / DCM solution (0.05 mL) containing 0.2 M pentamethylbenzene for 2 minutes. After filtration, the solid phase was washed with DMF (0.05 mL), and acetonitrile (0.2 mL) was added to the filtrate. An LC sample was prepared and analyzed by LCMS to measure the reaction progress. The target product, SP006, was observed at 93.5% yield.

[0592]

[0593] Compound SP006 LRMS: m / z 437 [M+H] ＋ Retention time: 1.255 minutes (analysis conditions FA05-1, 299 nm).

[0594] Example 1-2-9: Synthesis of compound SP092-1R

[0595] Compound SP092-1R (4.84 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 5 g) and B29 (0.646 g, 4.08 mmol) in the same manner as in Example 1-2-3. The dried solid phase was separated in the same manner as in Example 1-2-3 and subjected to LCMS measurement, whereby 98.5% of the target compound SP092 was observed.

[0596]

[0597] Compound SP092 LRMS: m / z 320 [M+H] ＋ Retention time: 0.690 minutes (analysis conditions FA05-2).

[0598] Example 1-2-10: Synthesis of compound SP098-1R

[0599] Compound SP098-1R (5.51 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 6 g) and B33 (1.79 g, 5.32 mmol) in the same manner as in Example 1-2-5. The dried solid phase was separated in the same manner as in Example 1-2-3 and subjected to LCMS measurement, whereby 99.8% of the target compound SP098 was observed.

[0600]

[0601] Compound SP098 LRMS: m / z 311 [M+H] ＋ Retention time: 0.707 minutes (analysis conditions FA05-2).

[0602] Example 1-2-11: Synthesis of compound SP100-1R Compound SP100-1R (6.13 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 6 g) and B34 (1.55 g, 4.8 mmol) in the same manner as in Example 1-2-5. The dried solid phase was separated in the same manner as in Example 1-2-3 and subjected to LCMS measurement, whereby 99.7% of the target compound SP100 was observed. Compound SP100 LRMS: m / z 297 [M+H] ＋ Retention time: 0.642 minutes (analysis conditions FA05-2).

[0603] Example 1-2-12: Synthesis of compound SP104-1R

[0604] Compound SP104-1R (6.02 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 6 g) and B35 (1.87 g, 4.8 mmol) in the same manner as in Example 1-2-5. The dried solid phase was separated in the same manner as in Example 1-2-3 and subjected to LCMS measurement, whereby 99.7% of the target compound SP104 was observed.

[0605]

[0606] Compound SP104 LRMS: m / z 325 [M+H] ＋ Retention time: 0.675 minutes (analysis conditions FA05-2).

[0607] Example 1-2-13: Synthesis of compound SP102-1R Example 1-2-13-1: Synthesis of compound LP013

[0608] Amide condensation: Under a nitrogen atmosphere, a solution of piClU (6.06 g, 16.8 mmol) and NMI (1.38 g, 16.8 mmol) in acetonitrile (17 mL) was added to a mixture of B37 (900 mg, 4.2 mmol), B36 (7.07 g, 16.8 mmol), and DCM (27 mL), and the mixture was stirred at room temperature for 16 hours. Water was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound LP015 (1.8 g, 65%).

[0609] Mitsunobu Reaction Under a nitrogen atmosphere, toluene (85 mL) was added to LP015 (3.4 g, 5.9 mmol) and B06 (2.61 g, 8.49 mmol), and the mixture was cooled to 0°C. Triphenylphosphine (6.14 g, 23.4 mmol) and DIAD (CAS: 2446-83-5, 2.37 g, 11.7 mmol) were added, and the mixture was stirred at room temperature for 16 hours. Water was added to the reaction solution, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound LP014 (1.32 g, 26%).

[0610] Under a nitrogen atmosphere, a solution of LP014 (900 mg, 1.03 mmol) in ethyl acetate (9 mL) was cooled to 0°C. A solution of HMDS (CAS: 999-97-3, 167 mg, 1.03 mmol) in ethyl acetate (2.25 mL) and a solution of TMSOTf (CAS: 27607-77-8, 345 mg, 1.55 mmol) in ethyl acetate (2.25 mL) were added, and the mixture was stirred at room temperature for 1 hour. After cooling the reaction solution to 0°C, a solution of hydrogen chloride in 1,4-dioxane (4 M, 1.03 mmol) was added, and the mixture was purified by reverse-phase silica gel column chromatography to obtain the title compound LP013 (317 mg, 40%).

[0611] Example 1-2-13-2: Synthesis of compound SP102-1R

[0612] Amidation Reaction: Under a nitrogen atmosphere, carboxylic resin (SP000-1R) (loading amount 1.61 mmol / g, 1.75 g, 2.19 mmol) and NMP (26 mL) were added to a 50 mL filter column and shaken at room temperature for 1 hour. HOAt (0.384 g, 2.82 mmol), LP013 (0.32 g, 0.42 mmol), and DIC (356 mg, 2.82 mmol) were added and shaken at room temperature for 4 hours. Piperidine (601 mg, 7.05 mmol), HOAt (768 mg, 5.64 mmol), and DIC (712 mg, 5.64 mmol) were added and shaken at room temperature for 16 hours.

[0613] Solid-phase purification: The reaction mixture and the solid-phase suspension were transferred onto a filter and washed five times with NMP (35 mL). Fmoc removal: DMF (14 mL) and piperidine (3.5 mL) were added to the resulting solid phase, and the mixture was shaken at room temperature for 30 minutes.

[0614] Solid-phase purification The reaction solution and the solid-phase suspension were all transferred onto a filter and washed three times with DMF (35 mL), three times with methanol (35 mL), three times with DCM (35 mL), and three times with heptane (35 mL). The obtained solid phase was dried under reduced pressure overnight to obtain compound SP102-1R (2.09 g).

[0615] Reaction tracking was carried out using the same experimental procedures as in Example 1-1-3. As a result, the target product SP102 was observed at 99.2%.

[0616] Compound SP102 LRMS: m / z 359 [M+H] ＋ Retention time: 0.773 minutes (Analysis conditions FA05-2, 299 nm)

[0617] Example 1-3: Synthesis of liquid phase amine compound Example 1-3-1: Synthesis of compound LP001

[0618] Under a nitrogen atmosphere, LP001 (500 mg, 1.16 mmol), NMM (0.51 mL, 4.6 mmol), PyAOP (1.21 g, 2.32 mmol), and DMF (5.4 mL) were added to a 10 mL vial. B03 (754 mg, 2.32 mmol) was added and the mixture was shaken at room temperature for 5 hours. To the resulting mixture, a pH 7 aqueous buffer solution (5 mL) and DCM (10 mL) were added. The organic layer was extracted twice with dichloromethane (5 mL), dried over sodium sulfate, and concentrated under reduced pressure. DCM (4 mL) and piperidine (1 mL) were added to the resulting residue and the mixture was shaken at room temperature for 24 hours. The reaction mixture was purified by silica gel column chromatography (ethyl acetate / hexane) to obtain the title compound LP002 (467 mg, 0.904 mmol, 78%).

[0619]

[0620] Compound LP002 LRMS: m / z 517 [M+H]＋ Retention time: 1.012 minutes (analysis conditions FA05-1, 299 nm).

[0621] Example 1-3-2: Synthesis of compound LP003

[0622] Compound LP003 (410 mg, 753 μmol, 65%) was synthesized using compound LP001 (500 mg, 1.16 mmol) and B04 (819 mg, 2.32 mmol) in the same manner as in Example 1-2-3.

[0623]

[0624] Compound LP003 LRMS: m / z 545 [M+H] ＋ Retention time: 1.039 minutes (analysis conditions FA05-1, 299 nm).

[0625] Example 1-4: Synthesis of sulfonylating reagent Example 1-4-1: Synthesis of sulfonylbenzotriazole (A22)

[0626] Under a nitrogen atmosphere, 1,2,3-benzotriazole (2.12 g, 17.8 mmol), A03 (1.30 g, 7.12 mmol), DIPEA (3.1 mL, 18 mmol), and DCM (7 mL) were added to a 30 mL vial and shaken at room temperature for 15 hours. The reaction mixture was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound A22 (1.60 g, 6.03 mmol, 85%).

[0627]

[0628] Compound A22 LRMS: m / z 266 [M+H] ＋ Retention time: 1.168 minutes (analysis conditions FA05-1).

[0629] Example 1-4-2: Synthesis of sulfonylimidazolium salt (A07)

[0630] Under a nitrogen atmosphere, A03 (2.00 g, 10.9 mmol), DIPEA (2.86 mL, 16.4 mmol), imidazole (2.24 g, 32.8 mmol), and DCM (7.0 mL) were added to a 20 mL vial and stirred at room temperature for 15 hours. The reaction solution was purified by silica gel column chromatography (1-80% ethyl acetate / hexane), and the resulting crude product and DCM (7.0 mL) were added to a 20 mL vial and cooled to 0°C. MeOTf (2.4 mL, 22 mmol) was added, and the mixture was stirred at room temperature for 15 hours. The precipitated white solid was washed twice with DCM / hexane (2 / 1, 5 mL) and then dried under reduced pressure to obtain the title compound A07 (1.95 g, 5.15 mmol, 47%).

[0631]

[0632] Compound A07 １ H-NMR (400MHz, CD ３ CN) δ: 8.99 (brs, 1H), 7. 71 (dd, J=2.0, 2.0Hz, 1H), 7.56 (dd, J=2.0, 2.0Hz, 1H), 3.93 (s, 3H), 3.77 (ddt, J=12.0, 3.4, 3.4Hz, 1H), 2.14 -2.09 (m, 3H), 1.92-1.87 (m, 2H), 1.71-1.66 (m, 2H), 1.56 (ddd, J=12.4, 12.4, 3.6Hz, 1H), 1.40-1.17 (m, 3H). LCMS: m / z 229 [M-OTf － ] ＋ . Retention time: 0.473 minutes (Analysis conditions: Analysis conditions FA05-1).

[0633] Example 2: Synthesis of sulfonyltriazolium salt Example 2-1: Synthesis of sulfonyltriazole Example 2-1-1: Synthesis of sulfonyltriazole (A02)

[0634]

[0635] A 120 mL glass vial was charged with sulfonyl chloride (A03) (10.0 g, 54.7 mmol), 1,2,4-triazole (11.3 g, 164 mmol), DIPEA (14.3 mL, 82.1 mmol), and DCM (27 mL), and the mixture was shaken at room temperature for 15 hours. The resulting mixture was purified by silica gel column chromatography (silica gel, ethyl acetate / hexane, 1-80%) to give the title compound A02 (10.9 g, 50.6 mmol, 93%).

[0636]

[0637] Compound A02 １ H-NMR (400MHz, CDCl ３ ) δ: 8.65 (s, 1H), 8.15 (s, 1H), 3.51 (ddt, J=12.0, 3.4, 3.4Hz, 1H), 2.02-1 91 (m, 4H), 1.74-1.71 (m, 1H), 1.62-1.52 (m, 1H), 1.35-1.17 (m, 3H). LCMS: m / z 216 [M+H] ＋ . Retention time: 0.827 minutes (Analysis conditions FA05-1).

[0638] Example 2-1-2: Synthesis of sulfonyltriazole (A05)

[0639] The same experimental procedure as in Example 2-1-1 was performed, and sulfonyltriazole (A05) (1.36 g, 5.93 mmol, 83%) was obtained as a single compound using sulfonyl chloride (A03) (1.30 g, 7.12 mmol) and 3-methyl-1H-1,2,4-triazole (1.18 g, 14.2 mmol).

[0640]

[0641] Compound A05 １ H-NMR (400MHz, CDCl ３) δ: 8.51 (s, 1H), 3.47 (ddt, J=12.0, 3.6, 3.6Hz, 1H), 2.49 (s, 3H), 2.03-1 90 (m, 4H), 1.75-1.70 (m, 1H), 1.62-1.52 (m, 2H), 1.35-1.14 (m, 3H). LCMS: m / z 230 [M+H] ＋ . Retention time: 0.897 minutes (Analysis conditions: Analysis conditions FA05-1).

[0642] Example 2-1-3: Synthesis of sulfonyltriazole (A06)

[0643] The same experimental procedure as in Example 2-1-1 was performed using sulfonyl chloride (A03) (1.30 g, 7.12 mmol) and 3,5-dimethyl-1,2,4-triazole (1.38 g, 14.2 mmol) to obtain sulfonyltriazole (A06) (1.22 g, 5.01 mmol, 70%).

[0644]

[0645] Compound A06 １ H-NMR (400MHz, CDCl ３ ) δ: 3.52 (ddt, J=12.0, 3.4, 3.4Hz, 1H), 2.67 (s, 3H), 2.39 (s, 3H), 2.05 -1.90 (m, 4H), 1.75-1.71 (m, 1H), 1.64-1.54 (m, 2H), 1.35-1.16 (m, 3H). LCMS: m / z 244 [M+H] ＋ . Retention time: 0.913 minutes (Analysis conditions FA05-1).

[0646] Example 2-1-4: Synthesis of sulfonyltriazole (A09)

[0647] The same experimental procedure as in Example 2-1-1 was performed using sulfonyl chloride (A10) (2.00 g, 14.0 mmol) and 1,2,4-triazole (2.91 g, 42.1 mmol), to obtain sulfonyltriazole (A09) (2.46 g, 13 mmol, 96%). １ H-NMR (400MHz, CDCl ３) δ: 9.26 (s, 1H), 8.46 (s, 1H), 4.08-3.98 (m, 1H), 1.27 (d, J = 6.8Hz, 6H). LCMS: m / z 176 [M+H] ＋ . Retention time: 0.597 minutes (Analysis conditions: Analysis conditions FA05-1).

[0648] Example 2-1-5: Synthesis of sulfonyltriazole (A12)

[0649] The same experimental procedure as in Example 2-1-1 was carried out, and sulfonyltriazole (A12) (0.934 g, 3.2 mmol, 40%) was obtained using sulfonyl chloride (A13) (2.04 g, 8.01 mmol) and 1,2,4-triazole (1.66 g, 24.0 mmol). １ H-NMR (400MHz, CDCl ３ ) δ: 8.67 (s, 1H), 8.12 (s, 1H), 7.88 (dd, J=8.0, 1.6Hz, 1H), 7.82-7.78 (m, 2H), 7.59-7.50 (m, 2H) ), 7.39 (dd, J = 7.6, 7.6 Hz, 1H), 7.30 (d, J = 6.8 Hz, 1H), 3.96-3.92 (m, 2H), 3.56-3.52 (m, 2H). LCMS: m / z 288 [M+H] ＋ . Retention time: 1.048 minutes (Analysis conditions FA05-1).

[0650] Example 2-1-6: Synthesis of sulfonyltriazole (A15)

[0651] The same experimental procedure as in Example 2-1-1 was carried out, and sulfonyltriazole (A15) (1.41 g, 5.61 mmol, 70%) was obtained using sulfonyl chloride (A16) (1.75 g, 8.01 mmol) and 1,2,4-triazole (1.66 g, 24.0 mmol). １ H-NMR (400MHz, CDCl ３ ) δ: 8.80 (s, 1H), 8.00 (s, 1H), 7.03 (s, 2H), 2.67 (s, 6H), 2.33 (s, 3H). LCMS: m / z 252 [M+H] ＋ . Retention time: 1.061 minutes (Analysis conditions FA05-1).

[0652] Example 2-1-7: Synthesis of sulfonyltriazole (A27)

[0653] The same experimental procedure as in Example 2-1-1 was carried out using sulfonyl chloride (A26) (8.0 g, 28 mmol) and 1,2,4-triazole (7.8 g, 0.11 mol) to obtain sulfonyltriazole (A27) (8.49 g, 26.8 mmol, 95%). １ H-NMR (400MHz, CDCl ３ ) δ: 8.67 (s, 1H), 8.16 (s, 1H), 4.27 (brs, 2H), 3.66 (ddd, J=12.0, 4.0, 3.6, Hz, 1H), 2.732 (brs, 2H), 1.95 (d, J=14.0Hz, 2H), 1.78 (dddd, J=12.8, 12.4, 12.0, 4.8, Hz, 2H), 1.45 (s, 9H). LCMS: m / z 315 [MH] － . Retention time: 0.925 minutes (Analysis conditions FA05-1).

[0654] Example 2-1-8: Synthesis of sulfonyltriazole (A32)

[0655] The same experimental procedure as in Example 2-1-1 was carried out using sulfonyl chloride (A31) (1 g, 5 mmol) and 1,2,4-triazole (1 g, 0.02 mol) to obtain sulfonyltriazole (A32) (678 mg, 3.12 mmol, 60%). １ H-NMR (400MHz, CDCl ３ ) δ: 8.67 (s, 1H), 8.17 (s, 1H), 4.10 (ddd, J=11.6, 4.0, 1.6, Hz, 2H), 3.77 (ddd, J=11.6, 4.4, 4.0, Hz, 1H), 3.38 (ddd, J=11.6, 11.6, 2.4, Hz, 2H), 2.02-1.86 (m, 4H). LCMS: m / z 218 [M+H] ＋ . Retention time: 0.552 minutes (Analysis conditions: Analysis conditions FA05-1).

[0656] Example 2-2: Synthesis of sulfonyltriazolium salt Example 2-2-1: Synthesis of sulfonyltriazolium salt (A01)

[0657] A 30 mL glass vial was charged with A02 (1.00 g, 4.65 mmol) and DCM (9.2 mL) and cooled to 0 °C. MeOTf (680 μL, 6.04 mmol) was added at 0 °C, followed by shaking at room temperature for 6 hours. The precipitated white solid was washed twice with DCM / hexane (2 / 1, 20 mL) and dried under reduced pressure to obtain the title compound A01 (1.36 g, 3.58 mmol, 77%).

[0658] １ H-NMR (400MHz, CD ３ CN) δ: 9.89 (s, 1H), 8.79 (s, 1H), 3.98 (s, 3H), 3.96-3.88 (m, 1H), 2.18-2.15 (m, 2H), 1.92-1.87 (m, 2H), 1.71-1.59 (m, 3H), 1.41-1.18 (m, 3H).

[0659] １３ C-NMR (100MHz, CD ３ CN) δ: 157.7, 157.0, 75.9, 45.8, 36.3, 34.9, 34.8. LCMS: m / z 230 [M-OTf － ] ＋ . Retention time: 0.491 minutes (Analysis conditions: Analysis conditions FA05-1).

[0660] Example 2-2-2: Synthesis of sulfonyltriazolium salt (A04)

[0661] The same experimental procedure as in Example 2-2-1 was carried out using sulfonyltriazole (A05) (200 mg, 872 μmol) and MeOTf (196 μL, 1.74 mmol), to obtain sulfonyltriazolium salt (A04) (175 mg, 444 μmol, 51%) as a single compound. LCMS: m / z 244 [M+H] ＋ . Retention time: 0.533 minutes (Analysis conditions: Analysis conditions FA05-1).

[0662] Example 2-2-3: Synthesis of sulfonyltriazolium salt (A11)​​

[0663] The same experimental procedure as in Example 2-2-1 was carried out using sulfonyltriazole (A12) (934 mg, 3.25 mmol) and MeOTf (476 μL, 4.23 mmol) to obtain sulfonyltriazolium salt (A11) (923 mg, 2.04 mmol, 63%).

[0664] １ H-NMR (400MHz, (CD ３ ) ２ SO) δ: 9.52 (s, 2H), 8.05 (d, J = 8.4Hz, 1H), 7.93-7.91 (m, 1H), 7.77 (d, J = 8.4Hz, 1H), 7.59- 7.50 (m, 2H), 7.44-7.37 (m, 2H), 3.90 (s, 3H), 3.38-3.33 (m, 2H), 2.83-2.79 (m, 2H).

[0665] １３ C-NMR (100MHz, (CD ３ ) ２ SO) δ: 144.8, 137.1, 133.9, 131.7, 129.1, 127.1, 126.6, 126.5, 126.2, 126.16, 126.11, 123.8, 121.1 (q, J=320.9Hz), 52.7, 34.0, 29.2.

[0666] Example 2-2-4: Synthesis of sulfonyltriazolium salt (A14)

[0667] The same experimental procedure as in Example 2-2-1 was carried out using sulfonyltriazole (A15) (1.41 g, 5.61 mmol) and MeOTf (821 μL, 7.29 mmol), to obtain sulfonyltriazolium salt (A14) (2.03 g, 4.89 mmol, 87%).

[0668] １ H-NMR (400MHz, CDCl ３ ) δ: 9.49 (s, 2H), 6.76 (s, 2H), 3.89 (s, 3H), 2.50 (s, 6H), 2.17 (s, 3H). １３ C-NMR (100MHz, (CD ３ ) ２ ​​​SO) δ: 136.3, 134.6, 132.1, 127.3, 126.4, 120.4, 111.0 (q, J=320.1Hz), 23.9, 13.0, 10.7.

[0669] Example 3: Sulfonamidation reaction in liquid phase Example 3-1: Investigation of sulfonamidation conditions Example 3-1-1: Effect of sulfonyltriazolium salt (A01) on the sulfonamidation of amine substrates (LP001, LP002, and LP003)

[0670] Sulfonamidation was carried out using an amine substrate (LP001, LP002, or LP003) and a sulfonyl triazolium salt (A01) or sulfonyl chloride (A03). The structures of the amine substrates (LP001, LP002, and LP003) used are shown in Table 3-1-1, the structures of the sulfonylating agents (A01 and A03) used are shown in Table 3-1-2, and the results obtained are shown in Table 3-1-3. The analytical results of the compounds listed in Table 3-1-3 are shown in Table 3-1-4. The experimental procedure (Run 1 in Table 3-1-3) when a sulfonyl triazolium salt (A01) was used as the sulfonylating agent and 2,4,6-collidine was used as the base is shown below as an example.

[0671] Sulfonamidation reaction of an amine substrate (LP001) with a sulfonyl triazolium salt (A01) (example of reaction procedure)

[0672] Under a nitrogen atmosphere, LP001 (10 mg, 23.2 μmol), DCM (0.46 mL), sulfonyl triazolium salt (A01) (17.6 mg, 46.3 μmol), and 2,4,6-collidine (9.2 μL, 70 μmol) were added to a 0.6 mL glass vial, and the mixture was shaken at room temperature for 24 hours.

[0673] The reaction solution (3 μL) was sampled and diluted with MeCN (1 mL) and analyzed by LCMS to measure the progress of the reaction. The analysis was performed by cutting out at a wavelength of 299 nm (±4 nm). The reaction results are shown in Table 3-1-2.

[0674]

[0675]

[0676]

[0677]

[0678] The results shown in Table 3-1-3 confirmed that when a sulfonyltriazolium salt (A01) was used in the sulfonamidation of amine substrates (LP001, LP002, and LP003), the target product was obtained with higher purity than when a sulfonyl chloride (A03) was used (Runs 1, 4, and 7 in Table 3-1-3).

[0679] Example 4: Sulfonamidation reaction on solid phase Example 4-1: Investigation of sulfonamidation conditions Example 4-1-1: Effect of sulfonyltriazolium salts (A01, A04, A11, A14) on sulfonamidation of solid phase aniline substrate (SP002-1R)

[0680]

[0681] Under a nitrogen atmosphere, SP002-1R (0.196 mmol / g, 20 mg, 3.9 μmol), DCM (0.4 mL), 2,4,6-collidine (7.9 μL, 59 μmol), and sulfonyl triazolium salt (A01) (15.0 mg, 40 μmol) were placed in a 0.6 mL glass vial, and the mixture was shaken at room temperature for 24 hours.

[0682] 12 μL of the reaction mixture and solid phase suspension was transferred onto a filter tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in 10% TFA / DCM solution (0.1 M, 50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and analyzed by LCMS to measure the reaction progress. Analysis was performed at a wavelength of 299 nm (± 4 nm).

[0683] Similarly, sulfonamidation was carried out using sulfonylating agents (A02, A03, A04, A07, A11, A13, A14, A16, A22) and bases (2,4,6-collidine, triethylamine, or 4-methyl-4H-1,2,4-triazole). The structures of the sulfonylating agents used (A02, A03, A04, A07, A11, A13, A14, A16, A22) are shown in Table 4-1-1, and the results obtained are shown in Table 4-1-2. The analytical results of the compounds listed in Table 4-1-2 are also shown in Table 4-1-3.

[0684]

[0685]

[0686]

[0687] As shown in the results in Table 4-1-2, when sulfonyltriazolium salts (A01, A04, A11) were used as sulfonylating agents (Runs 1, 2, and 9 in Table 4-1-2), the target product was obtained in higher purity compared to conditions using sulfonyl chloride (Runs 3, 6, and 10 in Table 4-1-2). When known sulfonylating agents such as sulfonyltriazole (A02) (Run 3 in Table 4-1-2), sulfonylbenztriazole (A22) (Run 8 in Table 4-1-2), and sulfonylimidazolium salt (A07) (Run 7 in Table 4-1-2), or conditions using sulfonyl chloride and 4-methyl-4H-1,2,4-triazole (Run 5 in Table 4-1-2), the target product was not confirmed or only obtained in low yield. When a sulfonyltriazolium salt (A014) was used as the sulfonylating agent (Run 11 in Table 4-1-2), the target compound was confirmed to have a purity equivalent to that obtained under conditions using sulfonyl chloride (A16) (Run 12 in Table 4-1-2).

[0688] Example 4-1-2: Examination of the range of base application in sulfonamidation using solid-phase aniline substrate (SP002-1R) and sulfonyl triazolium salt (A01)

[0689] The same experimental procedures as in Example 4-1-1 were carried out to carry out sulfonamidation using the solid-phase aniline substrate (SP002-1R) and the sulfonyltriazolium salt (A01). The results are shown in Table 4-1-4.

[0690]

[0691] The results in Table 4-1-4 indicate that sulfonamidation of the solid-phase aniline substrate (SP002-1R) using a sulfonyltriazolium salt (A01) proceeded without the use of a base (Run 1 in Table 4-1-4). Furthermore, pyridine-based bases (Runs 2 to 4 in Table 4-1-4), azole-based bases (Runs 5 and 6 in Table 4-1-4), and tertiary amines with a calculated pKa value of the conjugate acid of 10 or less, such as NMM (Run 7 in Table 4-1-4), as well as inorganic bases (Runs 13 and 14 in Table 4-1-4), allowed the target product (SP016) to be obtained with higher purity than under conditions using sulfonyl chloride (Runs 4 to 6 in Table 4-1-2). ３ It was confirmed that when organic bases with conjugate acids having calculated pKa values ​​of 10 or more, such as N, DBU, BTMG, and BTPP (Runs 8 to 11 in Table 4-1-4) and strong bases such as LiHMDS (Run 12 in Table 4-1-4), the target product was observed only in low yield or was not obtained at all.

[0692] Example 4-1-3: Effect of sulfonyl triazolium salts (A01, A04, A11, A14) on sulfonamidation of solid-phase amine substrate (SP001-1R)

[0693] Sulfonamidation was carried out using the solid-phase amine substrate (SP001-1R) in the same manner as in Example 4-1-1. The results are shown in Table 4-1-5. The analytical results of the compounds listed in Table 4-1-5 are shown in Table 4-1-6.

[0694]

[0695]

[0696] As shown in the results in Table 4-1-5, when a sulfonyltriazolium salt (A01, A04, A14) was used as the sulfonylating agent (Runs 1, 2, and 11 in Table 4-1-5), the target product was obtained with a higher purity than under conditions using sulfonyl chloride (Runs 3, 6, and 12 in Table 4-1-5). When a sulfonyltriazolium salt (A011) was used as the sulfonylating agent (Run 9 in Table 4-1-5), the target product was confirmed to have a purity equivalent to that under conditions using sulfonyl chloride (Run 10 in Table 4-1-5). It was confirmed that the purity of the target product was lower when sulfonyltriazole (Run 3 in Table 4-1-5), sulfonylbenztriazole (Run 8 in Table 4-1-5), sulfonylimidazolium salt (Run 7 in Table 4-1-5), which are known sulfonylating agents, or when sulfonyl chloride and 4-methyl-4H-1,2,4-triazole were used (Run 5 in Table 4-1-5), than when a triazolium salt (A01 or A04) was used (Runs 1 and 2 in Table 4-1-5).

[0697] Example 4-1-4: Effect of sulfonyl triazolium salts (A01, A11) on sulfonamidation of solid-phase amine substrate (SP003-1R)

[0698] Sulfonamidation was carried out using the solid-phase amine substrate (SP003-1R) in the same manner as in Example 4-1-1. The results are shown in Table 4-1-7. The analytical results of the compounds listed in Table 4-1-7 are shown in Table 4-1-8.

[0699]

[0700]

[0701] As shown in the results in Table 4-1-7, when sulfonyltriazolium salts (A01, A11) were used as sulfonylating agents (Runs 1 and 4 in Table 4-1-7), it was confirmed that the target product could be obtained with higher purity compared to conditions using sulfonyl chlorides (Runs 2 and 5 in Table 4-1-7) or sulfonylimidazolium salts (Run 3 in Table 4-1-7).

[0702] Example 4-1-5: Effect of sulfonyltriazolium salts (A01, A11) on sulfonamidation of solid-phase aniline substrate (SP004-1R)

[0703] Sulfonamidation was carried out using the solid-phase amine substrate (SP004-1R) in the same manner as in Example 4-1-1. The results are shown in Table 4-1-9. The analytical results of the compounds listed in Table 4-1-9 are shown in Table 4-1-10.

[0704]

[0705]

[0706] As shown in the results in Table 4-1-9, when sulfonyltriazolium salts (A01, A11) were used as sulfonylating agents (Runs 1 and 4 in Table 4-1-9), it was confirmed that the target product could be obtained with higher purity compared to conditions using sulfonyl chlorides (Runs 2 and 5 in Table 4-1-9) or sulfonylimidazolium salts (Run 3 in Table 4-1-9).

[0707] Example 4-1-6: Effect of sulfonyltriazolium salt (A14) on sulfonamidation of solid-phase aniline substrate (SP005-1R)

[0708] The same experimental procedures as in Example 4-1-1 were carried out to carry out sulfonamidation using a solid-phase aniline substrate (SP005-1R). The results are shown in Table 4-1-11.

[0709]

[0710] Compound SP027 LRMS: m / z 612 [M+H] ＋ Retention time: 1.067 minutes (analysis conditions FA05-1, 299 nm).

[0711] As shown in the results in Table 4-1-11, it was confirmed that the target product was obtained with higher purity when a sulfonyltriazolium salt (A14) was used as a sulfonylating agent (Run 1 in Table 4-1-11) compared with the condition using sulfonyl chloride (Run 2 in Table 4-1-11).

[0712] These results demonstrate that triazolium salts (A14) are effective for the sulfonamidation of solid-phase aniline substrates such as SP005-1R, which are ortho-disubstituted, bulky, and expected to have low reactivity. While this example illustrates the use of a substrate (SP005-1R) with methyl groups at the 2- and 6-positions as an example of a bulky substrate, it is anticipated that the use of sulfonyltriazolium salts rather than sulfonyl chlorides will provide better results for a wider range of substrates that are similarly bulky around the reaction site.

[0713] Example 4-1-7: Effect of sulfonyltriazolium salt (A14) on sulfonamidation of solid-phase aniline substrate (SP006-1R)

[0714] The same experimental procedures as in Example 4-1-1 were carried out to carry out sulfonamidation using the solid phase amine substrate (SP006-1R). The results are shown in Table 4-1-12.

[0715]

[0716] Compound SP028 LRMS: m / z 619 [M+H] ＋ Retention time: 1.419 minutes (analysis conditions FA05-1, 299 nm).

[0717] As shown in the results in Table 4-1-12, it was confirmed that the target product was obtained with higher purity when a sulfonyltriazolium salt (A14) was used as a sulfonylating agent (Run 1 in Table 4-1-12) compared with the condition using sulfonyl chloride (Run 2 in Table 4-1-12).

[0718] These results demonstrate that triazolium salt (A14) is effective for the sulfonamidation of solid-phase aniline substrates such as SP006-1R, which have a t-Bu group at the ortho position and are expected to be bulky and have low reactivity. While this example illustrates the use of a substrate (SP006-1R) with a t-Bu group at the 2-position as an example of a bulky substrate, it is anticipated that the use of sulfonyltriazolium salts rather than sulfonyl chlorides will provide better results for a wider range of substrates that are similarly bulky around the reaction site.

[0719] Example 4-1-8: Effect of solvent on sulfonamidation of solid-phase amine substrate (SP041-1R) with sulfonyl triazolium salt (A01)

[0720] Under a nitrogen atmosphere, SP041-1R (0.197 mmol / g, 20 mg, 3.9 μmol), DCM (0.4 mL), and 2,4,6-collidine (7.2 mg, 59 μmol) were placed in a 0.6 mL glass vial and shaken at room temperature for 30 minutes. Sulfonyl triazolium salt (A01) (14.9 mg, 39.4 μmol) was added and the mixture was shaken at room temperature for 30 minutes.

[0721] 12 μL of the reaction solution and solid phase suspension was transferred onto a filter-equipped tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in a 10% TFA / DCM solution (0.1 M, 50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement of the solution to measure the reaction progress, followed by cutting out and analyzing at a wavelength of 299 nm (± 4 nm). The results obtained are shown in Run 1 in Table 4-1-13. The results of a similar experiment using THF, DMA, and DCM / MeCN (3 / 1) as solvents are shown in Runs 2 to 4 in Table 4-1-13.

[0722]

[0723] Compound SP047 LRMS: m / z 429 [M+H] ＋ Retention time: 1.012 minutes (analysis conditions FA05-1, 299 nm). The results in Table 4-1-13 show that for sulfonamidation using triazolium salts, chlorinated solvents such as DCM, ether solvents such as THF, amide solvents such as DMA, and a mixed solvent of DCM and MeCN are applicable. The solvents used are not limited to those mentioned above.

[0724] Example 4-1-9: Effect of sulfonyltriazolium salt (A01) on sulfonamidation of solid-phase heteroarylamine substrate (SP092-1R)

[0725] Under a nitrogen atmosphere, SP092-1R (0.196 mmol / g, 20 mg, 3.9 μmol), DCM (0.4 mL), and 2,4,6-collidine (7.7 μL, 59 μmol) were placed in a 0.6 mL glass vial and shaken at room temperature for 30 minutes. Sulfonyl triazolium salt (A01) (14.9 mg, 39.2 μmol) was added, and the mixture was shaken at room temperature for 6 hours.

[0726] 12 μL of the reaction solution and solid phase suspension was transferred onto a filter-equipped tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in a 10% TFA / DCM solution (0.1 M, 50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement of the solution to measure the reaction progress, followed by excision analysis at a wavelength of 299 nm (± 4 nm). The results obtained are shown in Run 1 in Table 4-1-14. The results of a similar reaction using sulfonyl chloride (A03) as the sulfonylation reagent and triethylamine as the base are shown in Run 2 in Table 4-1-14.

[0727]

[0728]

[0729] Compound SP093 LRMS: m / z 466 [M+H] ＋ Retention time: 0.841 minutes (analysis conditions FA05-1, 299 nm). As shown in the results in Table 4-1-14, it was confirmed that the target product was obtained with a higher purity than when a sulfonyltriazolium salt (A01) was used as the sulfonylating agent (Run 1 in Table 4-1-14) or when a sulfonyl chloride (A03) was used (Run 2 in Table 4-1-14).

[0730] These results demonstrate that triazolium salt (A14) is effective for sulfonamidation of heteroarylamine substrates with low reactivity, such as SP092-1R. While this example illustrates SP092-1R as an example of a heteroarylamine, it is anticipated that the use of sulfonyltriazolium salts rather than sulfonyl chlorides will provide better results when other heteroarylamines are used as substrates.

[0731] Example 4-2: Confirmation of the scope of application of sulfonamidation reaction using triazolium salts Example 4-2-1: Sulfonamidation reaction using solid-phase supported amine substrates, which are expected to be relatively bulky and have low reactivity

[0732] Sulfonamidation was carried out using a sulfonyl triazolium salt (A01) on solid-phase amine substrates (SP094-1R, SP096-1R, SP098-1R, SP100-1R, SP102-1R, SP104-1R). For comparison, sulfonamidation was also carried out using solid-phase amine substrates (SP094-1R, SP096-1R) and sulfonyl chloride (A03). The results are shown in Table 4-2-1. The product structures and analytical results are shown in Table 4-2-2. As a representative example, the reaction procedure when using the solid-phase amine substrate (SP094-1R) is illustrated below.

[0733]

[0734] Under a nitrogen atmosphere, SP094-1R (0.197 mmol / g, 20 mg, 3.9 μmol), DCM (0.4 mL), and 2,4,6-collidine (7.8 μL, 59 μmol) were placed in a 0.6 mL glass vial and shaken at room temperature for 30 minutes. Sulfonyl triazolium salt (A01) (15.0 mg, 39.6 μmol) was added, and the mixture was shaken at room temperature for 8 hours.

[0735] 12 μL of the reaction solution and solid phase suspension was transferred onto a filter-equipped tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in a 10% TFA / DCM solution (0.1 M, 50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement of the solution to measure the reaction progress, followed by excision analysis at a wavelength of 299 nm (± 4 nm). The results obtained are shown in Table 4-2, Run 1. The results of a similar reaction using sulfonyl chloride (A03) as the sulfonylation reagent and triethylamine as the base are shown in Table 4-2-2, Run 2.

[0736]

[0737]

[0738] The results shown in Table 4-2-2 confirm that the target product can be obtained with higher purity when compared to when a sulfonyl triazolium salt (A01) is used as the sulfonylating agent (Runs 1 and 3 in Table 4-2-2) and when a sulfonyl chloride (A03) is used (Runs 2 and 4 in Table 4-2-2). Furthermore, by performing sulfonamidation of solid-phase amine substrates (SP098-1R, SP100-1R, SP102-1R, SP104-1R) under sulfonamidation conditions using a sulfonyl triazolium salt (A01) as the sulfonylating agent, the corresponding sulfonamides (SP099, SP101, SP103, SP105) can be observed.

[0739] These results demonstrate that triazolium salt (A01) is effective for sulfonamidation of solid-phase-supported amine substrates that are expected to be relatively bulky and have low reactivity, such as SP094-1R, SP096-1R, SP098-1R, SP100-1R, SP102-1R, and SP104-1R. While this example illustrates the use of SP094-1R, SP096-1R, SP098-1R, SP100-1R, SP102-1R, and SP104-1R as examples of relatively bulky solid-phase-supported amine substrates, it is anticipated that the use of sulfonyl triazolium salts rather than sulfonyl chlorides will provide better results when other bulky solid-phase-supported amine substrates are used.

[0740] Example 5: Experiment to confirm that sulfonamidation proceeds when sulfonyltriazole is activated in situ and used as a sulfonyltriazolium salt without isolation (examination of one-pot reaction)

[0741] Example 5-1: Sulfonamidation of amine substrates (LP001 and LP002) Example 5-1-1: An experiment to confirm that the sulfonamidation of amine substrate (LP001) proceeds when sulfonyltriazole (A09) is activated with MeOTf before use.

[0742]

[0743] Under a nitrogen atmosphere, A09 (17.1 mg, 97.3 μmol), DCM (0.1 mL), and MeOTf (8.9 μL, 81 μmol) were added to a 0.6 mL glass vial and shaken at room temperature for 2 hours. LP001 (10.0 mg, 23.2 μmol), 2,4,6-collidine (15.3 μL, 116 μmol), and DCM (0.3 mL) were added and shaken at room temperature for 24 hours.

[0744] A 3 μL aliquot of the reaction mixture was diluted with MeCN (1 mL) and analyzed by LCMS to measure the reaction progress. The reaction was then analyzed by cutting out the aliquot at a wavelength of 299 nm (±4 nm). To compare the progress of the reaction with that when sulfonyl chloride (A10) was used as the sulfonylating agent, sulfonamidation was carried out using LP001 and A10 as follows.

[0745]

[0746] Under a nitrogen atmosphere, LP001 (10.0 mg, 23.2 μmol), A10 (10.8 μL, 97.3 μmol), 2,4,6-collidine (15.3 μL, 116 μmol) and DCM (0.3 mL) were added to a 0.6 mL glass vial and shaken at room temperature for 24 hours.

[0747] 3 μL of the reaction mixture was collected and diluted with MeCN (1 mL) for LCMS analysis to measure the progress of the reaction, and the analysis was performed at a wavelength of 299 nm (±4 nm). The results are shown in Table 5-1-1.

[0748]

[0749]

[0750] Compound LP005 LRMS: m / z 538 [M+H] ＋ Retention time: 1.499 minutes (analysis conditions FA05-1, 299 nm).

[0751] As shown in the results in Table 5-1-1, it was confirmed that by activating sulfonyltriazole (A09) with MeOTf and then using it for the sulfonamidation of an amine substrate (LP001), the target product (LP005) could be obtained with higher purity than under conditions using sulfonyl chloride (Run 2 in Table 5-1-1).

[0752] Example 5-1-2: An experiment to confirm that the sulfonamidation of an amine substrate (LP002) proceeds when sulfonyltriazole (A09) is activated with MeOTf before use.

[0753]

[0754] The same experimental procedure as in Example 5-1-1 was performed, and sulfonyltriazole (A09) was activated with MeOTf, followed by sulfonamidation of the amine substrate (LP002). As in Example 5-1-1, the results were compared with those obtained when sulfonyl chloride (A10) was used as the sulfonylating agent. The results are shown in Table 5-1-2.

[0755]

[0756]

[0757] Compound LP007 LRMS: m / z 623 [M+H] ＋ Retention time: 1.460 minutes (Analysis conditions FA05-1, 299 nm).

[0758] As shown in the results in Table 5-1-2, it was confirmed that by activating sulfonyltriazole (A09) with MeOTf and then using it for the sulfonamidation of an amine substrate (LP002), the target product (LP007) could be obtained with higher purity than under the conditions using sulfonyl chloride (Run 2 in Table 5-1-2).

[0759] Example 5-2: Sulfonamidation of solid-phase amine substrate (SP001-1R) Example 5-2-1: An experiment in which sulfonyltriazoles (A02, A05, and A06) were reacted with an activator (MeOTf or EtOTf), and then the solid-phase amine substrate (SP001-1R) was sulfonamidated without isolation, and the results were compared with those obtained when sulfonyl chloride (A03) was used.

[0760] Sulfonyltriazoles (A02, A05, and A06) were activated with MeOTf or EtOTf, followed by sulfonamidation of the solid-phase amine substrate (SP001-1R). Similar experiments were also performed using sulfonyl chlorides, and the results were compared. The results are shown in Table 5-2-1. The analytical results for the compounds listed in Table 5-2-1 are shown in Table 5-2-2. The experimental procedure for activating sulfonyltriazole (A06) with MeOTf followed by sulfonamidation of the solid-phase amine substrate (SP001-1R) (Run 5 in Table 5-2-1) is shown below as an example.

[0761] Example of sulfonamidation of solid-phase amine substrate (SP001-1R) after activation of sulfonyltriazole (A06) with MeOTf (example of reaction procedure)

[0762] Under a nitrogen atmosphere, A06 (24.1 mg, 99.0 μmol), DCM (0.1 mL), and MeOTf (8.7 μL, 79.2 μmol) were added to a 0.6 mL glass vial and shaken at room temperature for 2 hours. SP001-1R (20.0 mg, 0.198 mmol / g, 3.96 μmol), 2,4,6-collidine (7.9 μL, 59.4 μmol), and DCM (0.3 mL) were added and shaken at room temperature for 24 hours.

[0763] 12 μL of the reaction solution and solid phase suspension was transferred onto a filter-equipped tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in a 10% TFA / DCM solution (50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement of the solution to measure the reaction progress, followed by excision analysis at a wavelength of 299 nm (± 4 nm). The results are shown in Table 5-1-1. In addition, to compare the progress of the reaction with that when sulfonyl chloride (A03) was used as the sulfonylating agent, sulfonamidation was performed using the solid phase amine substrate (SP001-1R) and sulfonyl chloride A03 as follows.

[0764] Example of sulfonamidation of solid-phase amine substrate (SP001-1R) with sulfonyl chloride (A03) (example of reaction procedure)

[0765] Under a nitrogen atmosphere, SP001-1R (20.0 mg, 0.198 mmol / g, 3.96 μmol), A03 (11.5 μL, 79.2 μmol), 2,4,6-collidine (7.9 μL, 60 μmol), and DCM (0.3 mL) were added to a 0.6 mL glass vial and shaken at room temperature for 24 hours.

[0766] 12 μL of the reaction solution and solid phase suspension was transferred onto a filter-equipped tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in a 10% TFA / DCM solution (50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and analyzed by LCMS to measure the reaction progress. The results are shown in Table 5-2-1.

[0767]

[0768] As shown in the results in Table 5-2-1, it was confirmed that the target product (SP011) could be obtained with higher purity by activating sulfonyltriazoles (A02, A05, A06) with MeOTf or EtOTf and then using them for the sulfonamidation of the solid-phase amine substrate (SP001-1R) compared to the condition using sulfonyl chloride (Run 7 in Table 5-2-1).

[0769] Example 5-2-2: An experiment in which sulfonyltriazole (A09) was activated with MeOTf, and the solid-phase amine substrate (SP001-1R) was subjected to sulfonamidation, and the results were compared with those obtained when sulfonyl chloride (A10) was used.

[0770]

[0771] The same experimental procedures as in Example 5-2-1 were carried out, and sulfonamidation of the solid-phase amine substrate (SP001-1R) was carried out after activating sulfonyltriazole (A09) with MeOTf. The results were compared with those obtained when sulfonyl chloride (A10) was used as the sulfonylating agent, as in Example 5-2-1. The results are shown in Table 5-2-2.

[0772]

[0773] As shown in the results in Table 5-2-2, it was confirmed that by activating sulfonyltriazole (A09) with MeOTf and then using it for the sulfonamidation of the solid-phase amine substrate (SP001-1R), the target product (SP013) could be obtained with higher purity than under conditions using sulfonyl chloride (Run 2 in Table 5-2-2).

[0774]

[0775] Compound SP013 LRMS: m / z 403 [M+H] ＋ Retention time: 0.900 minutes (Analysis conditions FA05-1, 299 nm).

[0776] Example 5-3: An experiment in which sulfonyltriazole (A09) was activated with MeOTf, and the solid-phase aniline substrate (SP002-1R) was subjected to sulfonamidation, and the results were compared with those obtained when sulfonyl chloride (A10) was used.

[0777]

[0778] The same experimental procedures as in Example 5-2-1 were carried out, and sulfonamidation of the solid-phase aniline substrate (SP002-1R) was carried out after activating sulfonyltriazole (A09) with MeOTf. The results were compared with those obtained when sulfonyl chloride (A10) was used as the sulfonylating agent, as in Example 5-2-1. The results are shown in Table 5-2-2.

[0779]

[0780] As shown in the results in Table 5-3, it was confirmed that the target product (SP017) was obtained with higher purity when sulfonyltriazole (A09) was activated with MeOTf and then used for the sulfonamidation of the solid-phase aniline substrate (SP002-1R) compared to the condition using sulfonyl chloride (Run 2 in Table 5-3).

[0781]

[0782] Compound SP017 LRMS: m / z 439 [M+H] ＋ Retention time: 0.976 minutes (analysis conditions FA05-1, 299 nm).

[0783] Example 5-4: An experiment in which sulfonyltriazole (A10) was activated with MeOTf, and the solid-phase amine substrate (SP003-1R) was subjected to sulfonamidation, and the results were compared with those obtained when sulfonyl chloride (A10) was used.

[0784]

[0785] The same experimental procedures as in Example 5-2-1 were carried out, and sulfonamidation of the solid-phase amine substrate (SP003-1R) was carried out after activating sulfonyltriazole (A09) with MeOTf. The results were compared with those obtained when sulfonyl chloride (A09) was used as the sulfonylating agent, as in Example 5-2-1. The results are shown in Table 5-4.

[0786]

[0787] As shown in the results in Table 5-4, it was confirmed that by activating sulfonyltriazole (A09) with MeOTf and then using it for the sulfonamidation of the solid-phase amine substrate (SP003-1R), the target product (SP022) was obtained with higher purity than under the conditions using sulfonyl chloride (Run 2 in Table 5-4).

[0788]

[0789] Compound SP022 LRMS: m / z 403 [M+H] ＋ Retention time: 0.836 minutes (analysis conditions FA05-1, 299 nm).

[0790] Example 5-5: An experiment in which sulfonyltriazole (A09) was activated with MeOTf and subjected to sulfonamidation of a solid-phase aniline substrate (SP004-1R), and the results were compared with those obtained when sulfonyl chloride (A10) was used.

[0791]

[0792] The same experimental procedures as in Example 5-2-1 were carried out, and sulfonamidation of the solid-phase aniline substrate (SP004-1R) was carried out after activating sulfonyltriazole (A09) with MeOTf. The results were compared with those obtained when sulfonyl chloride (A10) was used as the sulfonylating agent, as in Example 5-2-1. The results are shown in Table 5-5.

[0793]

[0794] As shown in the results in Table 5-5, it was confirmed that by activating sulfonyltriazole (A09) with MeOTf and then using it for the sulfonamidation of the solid-phase aniline substrate (SP004-1R), the target product (SP025) was obtained with higher purity than under the conditions using sulfonyl chloride (Run 2 in Table 5-5).

[0795]

[0796] Compound SP025 LRMS: m / z 425 [M+H] ＋ Retention time: 0.920 minutes (Analysis conditions FA05-1, 299 nm).

[0797] Example 5-6: Experiment in which sulfonamidation of solid-phase amine substrate (SP041-1R) was carried out by activating sulfonyltriazole (A26) with MeOTf

[0798] Under a nitrogen atmosphere, SP041-1R (20.0 mg, 0.197 mmol / g, 3.94 μmol), 2,4,6-collidine (9.1 μL, 69 μmol), and DCM (0.2 mL) were added to a 0.6 mL glass vial and shaken at room temperature for 30 minutes. A solution of A27 (24.9 mg, 78.8 μmol), DCM (0.2 mL), and MeOTf (6.5 μL, 59 μmol) previously shaken at room temperature for 2 hours was added, and the mixture was shaken at room temperature for 6 hours.

[0799] 12 μL of the reaction solution and solid phase suspension was transferred onto a filter tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in a 10% TFA / DCM solution (50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and the reaction progress was measured by LCMS measurement. The target product SP111 was 71% and SP112 was 25%.

[0800]

[0801] Compound SP111 LRMS: m / z 528 [MH] - Retention time: 1.032 minutes (analysis conditions FA05-1, 299 nm).

[0802]

[0803] Compound SP112 LRMS: m / z 430 [M+H] ＋ Retention time: 0.639 minutes (analysis conditions FA05-1, 299 nm).

[0804] Examples 5-7: Experiments in which sulfonyltriazole (A32) was activated with MeOTf and sulfonamidation of solid-phase amine substrates (SP041-1R, SP001-1R, SP002-1R, SP003-1R, SP004-1R) was carried out

[0805] Using the same experimental procedures as in Example 5-6, sulfonamidation of solid-phase amine substrates (SP041-1R, SP001-1R, SP002-1R, SP003-1R, and SP004-1R) was carried out using sulfonyltriazole (A32). The results are shown in Table 5-6. The structures and analytical results of the products are shown in Table 5-7.

[0806]

[0807]

[0808] Example 6: Example of sulfonamidation reaction using the mixture as a reaction raw material

[0809] Under a nitrogen atmosphere, SP041-1R (0.197 mmol / g, 20 mg, 3.9 μmol), SP002-1R (0.196 mmol / g, 20 mg, 3.9 μmol), and DCM (0.8 mL) were placed in a 1.5 mL glass vial and shaken at room temperature for 30 minutes. 2,4,6-Collidine (15.6 μL, 118 μmol) and sulfonyl triazolium salt (A01) (29.9 mg, 78.8 μmol) were added, and the mixture was shaken at room temperature for 8 hours.

[0810] A 12 μL aliquot of the reaction mixture and solid phase suspension was transferred onto a filter tip and washed three times with DMF (0.1 mL), three times with MeOH (0.1 mL), and three times with DCM (0.1 mL). The mixture was immersed in 10% TFA / DCM solution (50 μL) for 5 minutes, filtered, washed with DMF (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and the reaction progress was measured by LCMS. The target product SP047 was observed at 42.6% and SP016 at 49.0%.

[0811] Compound SP047 LRMS: m / z 429 [M+H] ＋ Retention time: 2.109 minutes (analysis conditions FA05-long, 299 nm).

[0812] Compound SP016 LRMS: m / z 479 [M+H] ＋ Retention time: 2.317 minutes (analysis conditions FA05-long, 299 nm).

Claims

1. A method for preparing a sulfonamide compound, comprising: [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, and * represents a point of attachment, with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group into a sulfonamide group corresponding to the nitrogen-containing compound.

2. A compound having a group represented by formula 1 is a compound having a group represented by formula 2: [In the formula, R １ is C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl, 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, and 5- to 10-membered heteroaryl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, － is a counter anion.

3. X － is a halide anion, C optionally substituted with one or more halogen atoms １－６ Alkyl sulfonate anion, one or more C １－６ Benzene sulfonate anion optionally substituted with alkyl, and BF ４ － The method of claim 2, wherein the compound is selected from the group consisting of:

4. The method according to any one of claims 1 to 3, wherein the nitrogen-containing compound is selected from ammonia or a salt thereof, a primary amine, and a secondary amine.

5. The method according to any one of claims 1 to 4, wherein the nitrogen-containing compound is selected from the group consisting of ammonia or a salt thereof, a primary amine in which the nitrogen atom is substituted with an aliphatic group, a primary amine in which the nitrogen atom is substituted with an aromatic group, a secondary amine in which the nitrogen atom is substituted with two aliphatic groups, a secondary amine in which the nitrogen atom is substituted with two aromatic groups, and a secondary amine in which the nitrogen atom is substituted with one aliphatic group and one aromatic group.

6. The method according to any one of claims 1 to 5, wherein the nitrogen-containing compound contains one functional group capable of reacting with the group represented by formula 1 or the compound represented by formula 2.

7. The nitrogen-containing compound is represented by formula A1, A2, or A3: [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z ３ is C-R ８ or N, Z ４ is C-R ９ or N, Z ５ is C-R １０ or N, R ５ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ Alkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; or R ５ and R １０ together with the nitrogen atom and carbon atom to which they are attached form a 5- to 7-membered non-aromatic heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; R １１ and R １２ are each independently a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, 5-10 membered heteroaryl C １－６ alkyl, and 3- to 14-membered heterocyclyl containing one or more ring heteroatoms independently selected from O, N, and S, each of which is optionally substituted by one or more substituents; or R １１ and R １２ together with the nitrogen atom to which they are attached form a 5- to 7-membered saturated heterocycle, which may further contain ring heteroatoms selected from O, N and S; R ａ is a hydrogen atom, C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, and 5- to 10-membered heteroaryl C １－６ alkyl, each of which is optionally substituted by one or more substituents; R ｂ , and R ｃ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６ Alkyl, C １－６ Alkoxy, (C １－６ alkoxy)carbonyl, (C １－６ alkoxy)carbonylamino, (C ３－１４ cycloalkyl)(C １－３ alkoxy)carbonylamino, (C １－６ alkyl)carbonyl, (C １－６ alkyl)carbonylamino, (C ６－１０ aryl)carbonyl, (C ６－１０ aryl)carbonylamino, di(C １－６ alkyl)amino, 4- to 8-membered cyclic amino, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ alkyl)aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted by one or more substituents; X ａ The method according to any one of claims 1 to 6, wherein:

8. The method according to any one of claims 1 to 7, wherein a compound having a group represented by formula 1 or a compound represented by formula 2 is reacted with a nitrogen-containing compound selected from an amine and ammonia or a salt thereof in the presence of a base to obtain a sulfonamide compound.

9. The method of claim 8, wherein the base is an inorganic base or an organic base whose conjugate acid has a pKa of 10 or less in water.

10. The method according to any one of claims 1 to 9, wherein the reaction is carried out by a solid phase method.

11. The method according to any one of claims 1 to 9, wherein the reaction is carried out by a liquid phase method.

12. Equation 3: [In the formula, R ２ and R ４ is as defined in claim 1, and represents a point of attachment] to a group represented by formula 1 by alkylating with an alkylating agent to obtain a compound having a group represented by formula 1.

13. Equation 4: [In the formula, R １ , R ２ and R ４ is as defined in claim 1] with an alkylating agent to obtain a compound of formula 2.

14. The method according to claim 12 or 13, wherein alkylation with an alkylating agent to obtain a compound having a group represented by formula 1 or a compound represented by formula 2 and conversion to a sulfonamide group with a nitrogen-containing compound are carried out in one pot.

15. The method according to any one of claims 1 to 14, wherein the reaction is carried out using a mixture of two or more nitrogen-containing compounds to obtain two or more sulfonamide compounds.

16. A method for producing a compound constituting a compound library, the method comprising producing a sulfonamide compound by the method of any one of claims 1 to 15.

17. A method for forming a sulfonamide bond, comprising: [In the formula, R ２ and R ４ are each independently a hydrogen atom, C １－６ Alkyl and C ６－１０ aryl; R ３ is C １－６ alkyl or benzyl, and * represents an attachment point] with a nitrogen-containing compound selected from amines and ammonia or salts thereof to convert the group to a sulfonamide group corresponding to the nitrogen-containing compound.

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