Method for producing sulfonamide compound using 4-aminopyridine derivative

Abstract

The present invention provides a method for producing a sulfonamide compound, the method comprising reacting a sulfonating agent and 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, wherein the base is a compound represented by formula 1, and the sulfonating agent is a sulfonyl halide or a sulfonic acid anhydride.

Description

Method for producing sulfonamide compounds using 4-aminopyridine derivatives

[0001] The present application relates to a method for producing a compound having a sulfonamide group (sulfonamide compound). Further, the present application relates to the use of a 4-aminopyridine derivative in the production of a compound having a sulfonamide group.

[0002] The formation of sulfonamide bonds from amines is an extremely important reaction in forming the basic skeletons of various organic compounds, such as pharmaceuticals, pesticides, and polymer compounds. This reaction has been studied for a long time, and numerous reaction conditions have been developed (Non-Patent Documents 1 and 2). Among these, the most widely used method is the construction of sulfonamide bonds using sulfonyl halides, such as sulfonyl chloride, which are readily available as sulfonylating agents. In this case, a base such as triethylamine is often used in conjunction with the sulfonyl halide to neutralize the acid (HX, or hydrogen chloride (HCl) if the sulfonyl halide is sulfonyl chloride) generated during the sulfonamidation reaction (Non-Patent Documents 2 and 3). Another known method is the addition of a catalytic amount of 4-dimethylaminopyridine (DMAP) as an additive to promote the sulfonylation reaction (Non-Patent Document 4). Condensation methods that improve reactivity include the use of sulfonylimidazolium salts, sulfonyltriazoles, or sulfonate esters of Oxyma as sulfonylating agents (Non-Patent Documents 5-11).

[0003] WO 2022 / 149617 A1

[0004] Sosunovych, B. et al., Chem. Rec. 2023, e202300258; Shavan, M. et al., Tetrahedron, 2020, 76, 131662-131689; Shigeno, M. et al., Org. Lett. 2022, 24, 809-814; Thalji, RK et al. 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; Connor, CG et al., Org. Process Res. Dev., 2021, 25, 608-615; Vilkas, E., Bulletin de la Societe Chimiqute de France 1978,N0, 1-2; Katritzky, AR et al., J. Org. Chem., 2004, 69, 1849-1852; Ramkumar, R. et al., Chemistry Select, 2018, 3, 2306-2310; Palakurthy, NB et al., Eur. J. Org. Chem., 2013, 2627-2633.

[0005] As described above, although sulfonamidation using sulfonyl halides is widely known, there are still unresolved problems. Specifically, when sulfonamide bond formation is performed using substrates with extremely low reactivity, such as sterically hindered amines, sulfonyl halides, and / or amines with low nucleophilicity, even with the above-mentioned existing method using a catalytic amount of 4-dimethylaminopyridine, the target sulfonamide compound cannot be obtained in sufficient yield and / or a large amount of by-products is generated.

[0006] Although attempts have been made to improve the reactivity of sulfonylating agents by changing them from sulfonyl halides to sulfonylimidazolium salts, sulfonyl halides, typified by sulfonyl chlorides, are extremely versatile in terms of availability, and a method that enables the direct use of sulfonyl halides as sulfonylating agents is extremely valuable.

[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] In one aspect, the present invention aims to provide a more versatile method that uses a sulfonyl halide, typified by a highly available sulfonyl chloride, as a sulfonylating agent, and that is capable of supplying a target sulfonamide compound in high yield and high purity even when using the above-mentioned low-reactivity substrate.

[0009] The present inventors have discovered that in a reaction for preparing a sulfonamide compound from an amine and a sulfonyl halide, typically a sulfonyl chloride, by forming a sulfonamide bond through a condensation reaction between an amino group and a sulfonyl group using a base, the reaction proceeds in high yield and / or with suppressed generation of by-products by using a base having a specific chemical structure, and have completed the present invention. Specifically, the present inventors have discovered that the use of 4-aminopyridine within a specific basicity range as a base allows the production of the desired sulfonamide compound in high yield and / or with suppressed generation of by-products. Furthermore, the present inventors have discovered that these conditions are applicable to reactions for forming a sulfonamide bond from various amines and sulfonyl halides, typically sulfonyl chlorides, and have completed the present invention. In connection with several aspects of the present invention, the present specification discloses the following inventions.

[0010] [A-1] A method for producing a sulfonamide compound, comprising reacting a nitrogen-containing compound selected from an amine and ammonia or a salt thereof with a sulfonylating agent in the presence of a base to obtain a sulfonamide compound, wherein the base is a compound represented by Formula 1:

[0011]

[0012] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６alkyl)carbonyl, (C １－６ wherein the sulfonylating agent is a sulfonyl halide or a sulfonic acid anhydride.

[0013] [A-2] The method according to [A-1], wherein the base is used in an amount of 1 equivalent or more relative to the nitrogen-containing compound. [A-3] The method according to [A-1] or [A-2], wherein the base is used in an amount of 1.0 equivalent or more, 1.1 equivalents or more, 1.2 equivalents or more, 1.3 equivalents or more, 1.4 equivalents or more, or 1.5 equivalents or more relative to the nitrogen-containing compound.

[0014] [A-4] The base represented by the formula 1 is a base represented by the formula 2:

[0015] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl, and X is selected from the group consisting of O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ The method according to any one of [A-1] to [A-3], wherein n is selected from the group consisting of aryl, aryl(alkoxy), aryl(carbonyl), and aryl(benzyl), and n is an integer of 1 to 3.

[0016] [A-5] The method according to [A-4], wherein n is 1. [A-6] The method according to [A-4], wherein the base represented by formula 1 is a base represented by formula 3:

[0017] [A-7] The method according to any one of [A-1] to [A-5], wherein the sulfonylating agent is represented by the formula: R １ SO ２ Y is a sulfonyl halide represented by R １ is C １－１０ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ The method according to any one of [A-1] to [A-6], wherein Y 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; and Y is selected from the group consisting of F, Cl, Br, and I.

[0018] [A-8]R １ Each of the groups defined as １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to [A-7], which is optionally substituted with one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0019] [A-9]R １ Each of the groups defined as 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, (C１－６ 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, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to [A-7], which is optionally substituted with one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0020] [A-10] The method according to any one of [A-1] to [A-9], wherein the sulfonylating agent is a sulfonyl chloride. [A-11] R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０ aryl), —CH ２ -(C ７－１４ aralkyl), C ６－１０ The method according to any one of [A-7] to [A-10], wherein Y 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, and Y is Cl.

[0021] [A-12]R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０aryl), —CH ２ -(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 the group consisting of halogen atoms, cyano, C １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-7] to [A-10], which is optionally substituted with one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0022] [A-13]R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０ aryl), —CH ２ -(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 the group consisting of halogen atoms, 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, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-7] to [A-10], which is optionally substituted with one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0023] [A-14]R １ But -CH ２ -(C １－９ alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), C ６－１０ The method according to any one of [A-7] to [A-10], wherein Y 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, and Y is Cl.

[0024] [A-15]R １ But -CH ２ -(C １－９ alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), 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, C １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-7] to [A-10], which is optionally substituted with one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0025] [A-16]R １ But -CH ２ -(C １－９ alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), 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, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [A-7] to [A-10], which is optionally substituted with one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0026] [A-17] The method according to any one of [A-1] to [A-16], wherein the nitrogen-containing compound is selected from ammonia or a salt thereof, a primary amine, and a secondary amine. [A-18] The method according to any one of [A-1] to [A-17], wherein the nitrogen-containing compound is selected from the group consisting of ammonia or a salt thereof, a primary amine whose nitrogen atom is substituted with an aliphatic group, a primary amine whose nitrogen atom is substituted with an aromatic group, a secondary amine whose nitrogen atom is substituted with two aliphatic groups, a secondary amine whose nitrogen atom is substituted with two aromatic groups, and a secondary amine whose nitrogen atom is substituted with one aliphatic group and one aromatic group. [A-19] The method according to any one of [A-1] to [A-17], wherein the nitrogen-containing compound is selected from the group consisting of a secondary amine whose nitrogen atom is substituted with two aliphatic groups, a secondary amine whose nitrogen atom is substituted with two aromatic groups, and a secondary amine whose nitrogen atom is substituted with one aliphatic group and one aromatic group.

[0027] [A-20] The method according to any one of [A-1] to [A-19], wherein the nitrogen-containing compound contains one functional group capable of reacting with a sulfonylating agent. [A-21] The aromatic group is C ６－１０ The method according to any one of [A-18] to [A-20], 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.

[0028] [A-22] 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 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-18] to [A-21], 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-23] 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 １－３alkoxy)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 The method according to any one of [A-18] to [A-21], 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.

[0030] [A-24] The nitrogen-containing compound is represented by the formula A1 or A3

[0031] [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 ６－１０aryl 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, 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 ａ 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, 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 is O or S.

[0032] [A-25] The nitrogen-containing compound is represented by the formula A1 or A3

[0033] [In the formula, Z １ is C-R ６ or N, Z ２ is C-R ７ or N, Z３ 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, (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, C２－６ 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 １－６ 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 5-10 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.

[0034] [A-26] The nitrogen-containing compound is represented by formula A1 or A3:

[0035] [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 ３－１４ 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 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, 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, C１－６ 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, (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 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.

[0036] [A-27] The nitrogen-containing compound is represented by formula A1 or A3:

[0037] [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 １－３alkoxy)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 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 ６－１０aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted 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 １－６ 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 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.

[0038] [A-28] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0039] [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 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 ６-１０Aryloxy, (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(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 ２－６Alkenyl, 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 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 ３－１４cycloalkyl)(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 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.

[0040] [A-29] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0041] [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 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 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 １－６ alkoxy)carbonylamino, (C３－１４ 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.

[0042] [A-30] The nitrogen-containing compound is represented by formula A1 or A3:

[0043] [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, and R ６ , R ７ , R ８ , R ９ , and R １０ are each independently a hydrogen atom, a halogen atom, cyano, nitro, C １－６Alkyl, 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, 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; R ａ is a hydrogen atom, and 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 with one or more halogen atoms; X ａ is O or S.

[0044] [A-31] (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 １and 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 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 [A-24] to [A-30], wherein

[0045] [A-32] The nitrogen-containing compound has formula A2:

[0046] [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 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.

[0047] [A-33] The nitrogen-containing compound has formula A2:

[0048] [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, and 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-34] The nitrogen-containing compound has formula A2:

[0050] [In the formula, R １１and 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, 5-10 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.

[0051] [A-35] The nitrogen-containing compound has formula A2:

[0052] [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, and 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.

[0053] [A-36] The nitrogen-containing compound has formula A2:

[0054] [In the formula, R １１ is a hydrogen atom, and R １２ is C １－６ Alkyl, C２－６ 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.

[0055] [A-37] 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, and C ７－１４ aralkyl, each of which may be substituted by one or more substituents.

[0057] [A-38] The nitrogen-containing compound has formula A2:

[0058] [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 ６-１０Aryloxy, (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; 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.

[0059] [A-39] The nitrogen-containing compound has formula A2:

[0060] [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, 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, (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 is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; 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.

[0061] [A-40] The nitrogen-containing compound has formula A2:

[0062] [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 １－６alkyl)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; 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.

[0063] [A-41] The nitrogen-containing compound has formula A2:

[0064] [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, 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; １１ and R １２and 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-42] The nitrogen-containing compound has formula A2:

[0066] [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, (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-20], wherein the amino group is optionally substituted with one or more substituents selected from (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0067] [A-43] The nitrogen-containing compound has formula A2:

[0068] [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, 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 The method according to any one of [A-1] to [A-20], wherein the amino group is optionally substituted with one or more substituents selected from (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0069] [A-44] The nitrogen-containing compound is represented by formula A1, A2, or A3:

[0070] [In the formula, R ５ ~R １２ , Z １ ~Z ５ , R ａ ~R ｃ , and X ａ The method according to any one of [A-1] to [A-43], wherein the compound is as defined in any one of [A-24] to [A-43].

[0071] [A-45] The method according to any one of [A-1] to [A-44], wherein the reaction is carried out in the presence of a solvent. [A-46] The method according to [A-45], 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.

[0072] [A-47] The method according to [A-45] or [A-46], wherein the solvent is a halogenated solvent. [A-48] The method according to [A-46] or [A-47], wherein the halogenated solvent is at least one selected from the group consisting of dichloromethane, chloroform, and 1,2-dichloroethane.

[0073] [A-49] The method according to any one of [A-46] to [A-48], wherein the halogen-based solvent is dichloromethane. [A-50] The method according to [A-45] or [A-46], wherein the solvent is a nitrile-based solvent.

[0074] [A-51] The method according to [A-46] or [A-50], wherein the nitrile solvent is at least one selected from the group consisting of acetonitrile, propionitrile, and benzonitrile. [A-52] The method according to [A-45] or [A-46], wherein the solvent is an amide solvent.

[0075] [A-53] The method according to [A-46] or [A-52], 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.

[0076] [A-54] The method according to [A-45] or [A-46], wherein the solvent is an ether-based solvent. [A-55] The method according to [A-46] or [A-54], 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.

[0077] [A-56] The method according to [A-45] or [A-46], wherein the solvent is an aromatic hydrocarbon solvent. [A-57] The method according to [A-46] or [A-56], wherein the aromatic hydrocarbon solvent is at least one selected from the group consisting of benzene, chlorobenzene, toluene, and xylene.

[0078] [A-58] The method according to any one of [A-1] to [A-57], wherein the reaction is carried out at a reaction temperature of 0° C. to 100° C. [A-59] The method according to [A-58], 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.

[0079] [A-60] The method according to [A-58] or [A-59], wherein the reaction temperature is 15° C. to 40° C. [A-61] The method according to any one of [A-1] to [A-60], wherein the production of a sulfonamide compound is carried out by a solid phase method. [A-62] The method according to any one of [A-1] to [A-60], wherein the production of a sulfonamide compound is carried out by a liquid phase method.

[0080] [A-63] The method according to any one of [A-1] to [A-62], wherein a mixture of two or more nitrogen-containing compounds is reacted to obtain two or more sulfonamide compounds. [A-64] The method according to any one of [A-1] to [A-16] and [A-45] to [A-60], wherein the nitrogen-containing compound is a resin for solid-phase synthesis to which an amine is bound via a linker.

[0081] [A-65] The method according to [A-64], wherein the amine bonded to the resin for solid phase synthesis via a linker is an amine specified in any one of [A-17] to [A-44]. [A-66] The method according to either [A-64] or [A-65], 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.

[0082] [A-67] The method according to any one of [A-1] to [A-6] and [A-17] to [A-60], wherein the sulfonylating agent is a resin for solid phase synthesis to which a sulfonyl halide is bound via a linker.

[0083] [A-68] A sulfonyl halide bonded to a resin for solid phase synthesis via a linker is represented by the formula: R １ SO ２ The method according to [A-67], wherein Y is a sulfonyl halide represented by the formula (I).

[0084] [A-69] The method according to either [A-67] or [A-68], wherein the same sulfonyl halide is bound to each resin for solid phase synthesis via a linker, and a mixture of two or more resins for solid phase synthesis to which different sulfonyl halides are bound is used to carry out a reaction, thereby obtaining two or more sulfonamide compounds.

[0085] [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-69].

[0086] [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.

[0087] [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.

[0088] [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.

[0089] [C-1] A method for forming a sulfonamide bond, comprising reacting a nitrogen-containing compound selected from an amine and ammonia or a salt thereof with a sulfonylating agent in the presence of a base to obtain a sulfonamide compound, wherein the base is a compound represented by Formula 1:

[0090]

[0091] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ wherein the sulfonylating agent is a sulfonyl halide or a sulfonic acid anhydride.

[0092] [C-2] The method according to [C-1], wherein the base is used in an amount of 1 equivalent or more relative to the nitrogen-containing compound. [C-3] The method according to [C-1] or [C-2], wherein the base is used in an amount of 1.0 equivalent or more, 1.1 equivalents or more, 1.2 equivalents or more, 1.3 equivalents or more, 1.4 equivalents or more, or 1.5 equivalents or more relative to the nitrogen-containing compound.

[0093] [C-4] The base represented by the formula 1 is a base represented by the formula 2:

[0094] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl, and X is selected from the group consisting of O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ The method according to any one of [C-1] to [C-3], wherein n is selected from the group consisting of aryl, aryl(alkoxy), aryl(carbonyl), and aryl(benzyl), and n is an integer of 1 to 3.

[0095] [C-5] The method according to [C-4], wherein n is 1. [C-6] The method according to [C-4], wherein the base represented by formula 1 is a base represented by formula 3: [wherein X is O or CO].

[0096] [C-7] The sulfonylating agent is a compound of the formula: R １ SO ２ Y is a sulfonyl halide represented by R １ is C １－１０ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０The method according to any one of [C-1] to [C-6], wherein Y 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; and Y is selected from the group consisting of F, Cl, Br, and I.

[0097] [C-8]R １ Each of the groups defined as １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to [C-7], wherein the amino group is optionally substituted with one or more substituents independently selected from the group consisting of alkyl, cyclic, 4- to 8-membered aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0098] [C-9]R １ Each of the groups defined as 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 ６－１０aryl)carbonyl, (C ６－１０ aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to [C-7], wherein the amino group is optionally substituted with one or more substituents independently selected from the group consisting of alkyl, cyclic, 4- to 8-membered aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0099] [C-10] The method according to any one of [C-1] to [C-9], wherein the sulfonylating agent is a sulfonyl chloride. [C-11] R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０ aryl), —CH ２ -(C ７－１４ aralkyl), C ６ - １０ The method according to any of [C-7] to [C-10], wherein Y 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, and Y is Cl.

[0100] [C-12]R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０ aryl), —CH ２ -(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 the group consisting of halogen atoms, cyano, C １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [C-7] to [C-10], wherein the aminocarbonyl is optionally substituted with one or more substituents independently selected from the group consisting of 4- to 8-membered cyclic aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0101] [C-13]R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０ aryl), —CH ２ -(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 the group consisting of halogen atoms, cyano, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [C-7] to [C-10], wherein the aminocarbonyl is optionally substituted with one or more substituents independently selected from the group consisting of 4- to 8-membered cyclic aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0102] [C-14]R １ But -CH ２ -(C １－９ alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), C ６－１０ The method according to any of [C-7] to [C-10], wherein Y 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, and Y is Cl.

[0103] [C-15]R １ But -CH ２ -(C １－９ alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), 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, C １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The method according to any one of [C-7] to [C-10], wherein the aminocarbonyl is optionally substituted with one or more substituents independently selected from the group consisting of 4- to 8-membered cyclic aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0104] [C-16]R １ But -CH ２ -(C １－９ alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), 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, 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, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６The method according to any one of [C-7] to [C-10], wherein the aminocarbonyl is optionally substituted with one or more substituents independently selected from the group consisting of 4- to 8-membered cyclic aminocarbonyl, 4- to 8-membered cyclic aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0105] [C-17] The method according to any one of [C-1] to [C-16], wherein the nitrogen-containing compound is selected from ammonia or a salt thereof, a primary amine, and a secondary amine. [C-18] The method according to any one of [C-1] to [C-17], wherein the nitrogen-containing compound is selected from the group consisting of ammonia or a salt thereof, a primary amine whose nitrogen atom is substituted with an aliphatic group, a primary amine whose nitrogen atom is substituted with an aromatic group, a secondary amine whose nitrogen atom is substituted with two aliphatic groups, a secondary amine whose nitrogen atom is substituted with two aromatic groups, and a secondary amine whose nitrogen atom is substituted with one aliphatic group and one aromatic group. [C-19] The method according to any one of [C-1] to [C-17], wherein the nitrogen-containing compound is selected from the group consisting of a secondary amine whose nitrogen atom is substituted with two aliphatic groups, a secondary amine whose nitrogen atom is substituted with two aromatic groups, and a secondary amine whose nitrogen atom is substituted with one aliphatic group and one aromatic group.

[0106] [C-20] The method according to any one of [C-1] to [C-19], wherein the nitrogen-containing compound contains one functional group capable of reacting with a sulfonylating agent. [C-21] The aromatic group is C ６－１０ The method according to any one of [C-18] to [C-20], wherein the aryl 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.

[0107] [C-22] 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 １－６alkoxy)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 The method according to any one of [C-18] to [C-21], 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.

[0108] [C-23] 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 １－６alkyl)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-18] to [C-21], 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.

[0109] [C-24] The nitrogen-containing compound represented by Formula A1 or Formula A3:

[0110] [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 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, 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 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; Rｂ , 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].

[0111] [C-25] The nitrogen-containing compound is represented by Formula A1 or Formula A3:

[0112] [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, 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, (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 5-10 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 １－６ 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].

[0113] [C-26] The nitrogen-containing compound is represented by Formula A1 or Formula A3:

[0114] [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 ３－１４ 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 ５and 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 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 １－６alkyl, 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, (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 ７－１４Aralkyl, 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].

[0115] [C-27] The nitrogen-containing compound represented by Formula A1 or Formula A3:

[0116] [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, (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 5-10 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, C３－８ 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 １－６ 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 ４－１０Cycloalkylalkyl, 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].

[0117] [C-28] The nitrogen-containing compound is represented by Formula A1 or Formula A3:

[0118] [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 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, (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 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 ６－１０aryl and 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S, each of which is optionally substituted with one or more halogen atoms; R ａ 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, 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, (C １－６ alkyl)carbonylamino, (C ６－１０aryl)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].

[0119] [C-29] The nitrogen-containing compound represented by Formula A1 or Formula A3:

[0120] [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 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 １－６alkoxy)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 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, C３－８ 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 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 １－６ 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 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].

[0121] [C-30] The nitrogen-containing compound has the formula A1:

[0122] [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, 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 5-10 membered heteroaryl containing one or more ring heteroatoms independently selected from O, N and S; R ａ is a hydrogen atom, and 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, C６－１０ 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].

[0123] [C-31] (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) Z１ 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 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-24] to [C-30], wherein

[0124] [C-32] The nitrogen-containing compound has the formula A2:

[0125] [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, C３－８ 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.

[0126] [C-33] The nitrogen-containing compound has formula A2:

[0127] [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, and 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.

[0128] [C-34] The nitrogen-containing compound has the formula A2:

[0129] [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, C７－１４ 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.

[0130] [C-35] The nitrogen-containing compound has the formula A2:

[0131] [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, and 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.

[0132] [C-36] The nitrogen-containing compound has the formula A2:

[0133] [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 １－６alkyl, 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.

[0134] [C-37] The nitrogen-containing compound has formula A2:

[0135] [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, and C ７－１４ aralkyl, each of which may be substituted by one or more substituents.

[0136] [C-38] The nitrogen-containing compound has the formula A2:

[0137] [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 １－６alkyl)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; 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.

[0138] [C-39] The nitrogen-containing compound has the formula A2:

[0139] [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, 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(C１－６ R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; 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.

[0140] [C-40] The nitrogen-containing compound has the formula A2:

[0141] [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, 5-10 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 １－６R is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; 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.

[0142] [C-41] The nitrogen-containing compound has the formula A2:

[0143] [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, 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; １１ and R １２and 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.

[0144] [C-42] The nitrogen-containing compound has the formula A2:

[0145] [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 １－６ 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-20], wherein the amino group is optionally substituted with one or more substituents selected from a 4- to 8-membered cyclic aminocarbonyl, an alkylaminocarbonyl, and a 4- to 8-membered cyclic aminocarbonyl.

[0146] [C-43] The nitrogen-containing compound has the formula A2:

[0147] [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, 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 The method according to any one of [C-1] to [C-20], wherein the amino group is optionally substituted with one or more substituents selected from a 4- to 8-membered cyclic aminocarbonyl, an alkylaminocarbonyl, and a 4- to 8-membered cyclic aminocarbonyl.

[0148] [C-44] The nitrogen-containing compound is represented by formula A1, A2, or A3:

[0149] [In the formula, R ５ ~R １２ , Z １ ~Z ５ , R ａ ~R ｃ , and X ａ [C-45] The method according to any one of [C-1] to [C-44], wherein the reaction is carried out in the presence of a solvent.

[0150] [C-46] The method according to [C-45], wherein the solvent is at least one selected from the group consisting of halogenated solvents, nitrile solvents, amide solvents, ether solvents, and aromatic hydrocarbon solvents. [C-47] The method according to [C-44] or [C-46], wherein the solvent is a halogenated solvent.

[0151] [C-48] The method according to [C-46] or [C-47], wherein the halogen-based solvent is at least one selected from the group consisting of dichloromethane, chloroform, and 1,2-dichloroethane.

[0152] [C-49] The method according to any one of [C-46] to [C-48], wherein the halogen-based solvent is dichloromethane. [C-50] The method according to [C-45] or [C-46], wherein the solvent is a nitrile-based solvent.

[0153] [C-51] The method according to [C-46] or [C-50], wherein the nitrile solvent is at least one selected from the group consisting of acetonitrile, propionitrile, and benzonitrile.

[0154] [C-52] The method according to [C-45] or [C-46], wherein the solvent is an amide solvent. [C-53] The method according to [C-46] or [C-52], 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.

[0155] [C-54] The method according to [C-45] or [C-46], wherein the solvent is an ether-based solvent. [C-55] The method according to [C-46] or [C-54], 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.

[0156] [C-56] The method according to [C-45] or [C-46], wherein the solvent is an aromatic hydrocarbon solvent. [C-57] The method according to [C-46] or [C-56], wherein the aromatic hydrocarbon solvent is at least one selected from the group consisting of benzene, chlorobenzene, toluene, and xylene.

[0157] [C-58] The method according to any one of [C-1] to [C-57], wherein the reaction is carried out at a reaction temperature of 0° C. to 100° C. [C-59] The method according to [C-58], 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.

[0158] [C-60] The method according to [C-58] or [C-59], wherein the reaction temperature is 15° C. to 40° C. [C-61] The method according to any one of [C-1] to [C-60], wherein the production of a sulfonamide compound is carried out by a solid-phase method.

[0159] [C-62] The method according to any one of [C-1] to [C-60], wherein the production of a sulfonamide compound is carried out by a liquid phase method. [C-63] The method according to any one of [C-1] to [C-62], wherein a mixture of two or more nitrogen-containing compounds is reacted to obtain two or more sulfonamide compounds.

[0160] [C-64] The method according to any one of [C-1] to [C-16] and [C-45] to [C-60], wherein the nitrogen-containing compound is a resin for solid phase synthesis to which an amine is bound via a linker.

[0161] [C-55] The method according to [C-64], wherein the amine bonded to the resin for solid phase synthesis via a linker is an amine specified in any one of [C-17] to [C-44]. [C-66] The method according to either [C-64] or [C-65], 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.

[0162] [C-67] ​​The method according to any one of [C-1] to [C-6] and [C-17] to [C-60], wherein the sulfonylating agent is a resin for solid phase synthesis to which a sulfonyl halide is bound via a linker.

[0163] The sulfonyl halide bonded to the resin for solid phase synthesis via the linker [C-68] is a compound represented by the formula: R １ SO ２ The method according to [C-67], wherein Y is a sulfonyl halide represented by the formula (I).

[0164] [C-69] The method according to either [C-67] ​​or [C-68], wherein the same sulfonyl halide is bound to each resin for solid phase synthesis via a linker, and a mixture of two or more resins for solid phase synthesis to which different sulfonyl halides are bound is used to carry out a reaction, thereby obtaining two or more sulfonamide compounds.

[0165] [D-1] A compound for use as a base in a sulfonamide-forming reaction in which a nitrogen-containing compound selected from an amine and ammonia or a salt thereof is reacted with a sulfonylating agent, the compound comprising the compound of Formula 1:

[0166]

[0167] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is Rｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ the base being selected from the group consisting of (alkoxy)carbonyl, and benzyl.

[0168] [D-2] The base represented by the formula 1 is a base represented by the formula 2:

[0169] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl, and X is selected from the group consisting of O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ The compound according to [D-1], which is represented by the formula: wherein n is an integer of 1 to 3 and n is selected from the group consisting of aryl, aryl(alkoxy), aryl(carbonyl), and aryl(benzyl).

[0170] [D-3] The compound according to [D-2], wherein n is 1. [D-4] The compound according to [D-3], wherein the base represented by formula 1 is a compound represented by formula 3: [In the formula, X is O or CO].

[0171] [E-1] Use of a base in a sulfonamide-forming reaction in which a nitrogen-containing compound selected from an amine and ammonia or a salt thereof is reacted with a sulfonyl halide, wherein the base is a compound represented by formula 1:

[0172]

[0173] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ The above use, wherein the compound is a compound represented by the formula (I) selected from the group consisting of (alkoxy) carbonyl, and benzyl.

[0174] [E-2] The use according to [E-1], in which the base is used in an amount of 1 equivalent or more relative to the nitrogen-containing compound. [E-3] The use according to [E-1] or [E-2], in which the base is used in an amount of 1.0 equivalent or more, 1.1 equivalents or more, 1.2 equivalents or more, 1.3 equivalents or more, 1.4 equivalents or more, or 1.5 equivalents or more relative to the nitrogen-containing compound.

[0175] [E-4] The base represented by the formula 1 is a base represented by the formula 2:

[0176] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl, and X is selected from the group consisting of O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６The use according to any one of [E-1] to [E-3], wherein the compound is a compound represented by the formula (I) selected from the group consisting of (alkoxy)carbonyl, and benzyl, and n is an integer of 1 to 3.

[0177] [E-5] The use according to [E-4], wherein n is 1. [E-6] The base represented by formula 1 is a compound represented by formula 3:

[0178] [Wherein, X is O or CO]. [E-1] - [E-5] The use according to any one of [E-1] to [E-5], represented by the formula:

[0179] [E-7] The sulfonylating agent is a compound represented by the formula: R １ SO ２ Y is a sulfonyl halide represented by R １ is C １－１０ Alkyl, 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 [E-1] to [E-6], wherein Y 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; and Y is selected from the group consisting of F, Cl, Br, and I.

[0180] [E-8]R １ Each of the groups defined as １－６ Alkyl, 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 ６－１０aryl)carbonylamino, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to [E-7], which is optionally substituted by one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0181] [E-9]R １ Each of the groups defined as 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, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to [E-7], which is optionally substituted by one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0182] [E-10] The use according to any one of [E-1] to [E-9], wherein the sulfonylating agent is a sulfonyl chloride. [E-11] R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C６－１０ aryl), —CH ２ -(C ７－１４ aralkyl), C ６ - １０ The use according to any one of [E-7] to [E-10], wherein Y 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, and Y is Cl.

[0183] [E-12]R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０ aryl), —CH ２ -(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 the group consisting of halogen atoms, cyano, C １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６The use according to any one of [E-7] to [E-10], which is optionally substituted by one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0184] [E-13]R １ But -CH ２ -(C １－９ alkyl), -CH ２ -(C ２－５ alkenyl), -CH ２ -(C ２－５ alkynyl), cyclopropyl, C ４－１０ cycloalkylalkyl, —CH ２ -(C ６－１０ aryl), —CH ２ -(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 the group consisting of halogen atoms, 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, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to any one of [E-7] to [E-10], which is optionally substituted by one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0185] [E-14]R １ But -CH ２ -(C １－９alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), C ６－１０ The use according to any one of [E-7] to [E-11], wherein Y 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, and Y is Cl.

[0186] [E-15]R １ But -CH ２ -(C １－９ alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), 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, C １－６ Alkyl, 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, 5-10 membered heteroarylcarbonylamino containing one or more ring heteroatoms independently selected from O, N and S, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to any one of [E-7] to [E-10], which is optionally substituted by one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0187] [E-16]R １ But -CH ２ -(C １－９alkyl), cyclopropyl, -CH ２ -(C ６－１０ aryl), 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, 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, aminocarbonyl, (C １－６ alkyl)aminocarbonyl, di(C １－６ The use according to any one of [E-7] to [E-10], which is optionally substituted by one or more substituents independently selected from the group consisting of (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0188] [E-17] The use according to any one of [E-1] to [E-16], wherein the nitrogen-containing compound is selected from ammonia or a salt thereof, a primary amine, and a secondary amine. [E-18] The use according to any one of [E-1] to [E-17], wherein the nitrogen-containing compound is selected from the group consisting of ammonia or a salt thereof, a primary amine whose nitrogen atom is substituted with an aliphatic group, a primary amine whose nitrogen atom is substituted with an aromatic group, a secondary amine whose nitrogen atom is substituted with two aliphatic groups, a secondary amine whose nitrogen atom is substituted with two aromatic groups, and a secondary amine whose nitrogen atom is substituted with one aliphatic group and one aromatic group. [E-19] The use according to any one of [E-1] to [E-17], wherein the nitrogen-containing compound is selected from the group consisting of a secondary amine whose nitrogen atom is substituted with two aliphatic groups, a secondary amine whose nitrogen atom is substituted with two aromatic groups, and a secondary amine whose nitrogen atom is substituted with one aliphatic group and one aromatic group.

[0189] [E-20] The use according to any one of [E-1] to [E-18], wherein the nitrogen-containing compound contains one functional group capable of reacting with a sulfonylating agent. [E-21] The use according to any one of [E-1] to [E-18], wherein the aromatic group is C ６－１０ The use according to any one of [E-18] to [E-20], 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.

[0190] [E-22] 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 ６-１０ Aryloxy, 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 The use according to any one of [E-18] to [E-21], 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.

[0191] [E-23] 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, C４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ The use according to any one of [E-18] to [E-21], 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.

[0192] [E-24] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0193] [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 １－６Alkyl, 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, 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, (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 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].

[0194] [E-25] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0195] [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].

[0196] [E-26] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0197] [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, 5-10 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].

[0198] [E-27] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0199] [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].

[0200] [E-28] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0201] [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 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 5-10 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 C １－６ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C７－１４ 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, (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 ３－８Cycloalkyl, 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].

[0202] [E-29] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0203] [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 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(C１－６ 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, 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 C １－６ Alkyl, C２－６ 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 １－６ 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 ２－６Alkynyl, 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].

[0204] [E-30] The nitrogen-containing compound is represented by formula A1 or formula A3:

[0205] [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, 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 １－６alkyl)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; R ａ is a hydrogen atom, and 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 may be optionally substituted with one or more halogen atoms; X ａ is O or S].

[0206] [E-31] (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 Z ４ is C-R ９ (7) Z ２ and Z ３is 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 use according to any one of [E-24] to [E-30], wherein

[0207] [E-32] The nitrogen-containing compound has formula A2:

[0208] [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 R１１ 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.

[0209] [E-33] The nitrogen-containing compound has formula A2:

[0210] [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, and C ７－１４ aralkyl, 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 and S.

[0211] [E-34] The nitrogen-containing compound has formula A2:

[0212] [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, 5-10 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 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, N, and S.

[0213] [E-35] The nitrogen-containing compound has formula A2:

[0214] [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, and C ７－１４ aralkyl, 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 and S.

[0215] [E-36] The nitrogen-containing compound has formula A2:

[0216] [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 The use according to any one of [E-1] to [E-20], 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.

[0217] [E-37] The nitrogen-containing compound has formula A2:

[0218] [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, and C ７－１４ The use according to any one of [E-1] to [E-20], wherein the aryl group is selected from the group consisting of aryl, ...

[0219] [E-38] The nitrogen-containing compound has formula A2:

[0220] [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 １－６alkyl)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; 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.

[0221] [E-39] The nitrogen-containing compound has formula A2:

[0222] [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 is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; 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.

[0223] [E-40] The nitrogen-containing compound has formula A2:

[0224] [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, 5-10 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 is optionally substituted by one or more substituents selected from alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl; 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, N, and S.

[0225] [E-41] The nitrogen-containing compound has formula A2:

[0226] [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, 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; 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.

[0227] [E-42] The nitrogen-containing compound has formula A2:

[0228] [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 １－６ 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 use according to any one of [E-1] to [E-20], which is represented by the formula: [optionally substituted by one or more substituents selected from] (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0229] [E-43] The nitrogen-containing compound has formula A2:

[0230] [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 ４－１０cycloalkylalkyl, 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 The use according to any one of [E-1] to [E-20], which is represented by the formula: [optionally substituted by one or more substituents selected from] (alkyl)aminocarbonyl, and 4- to 8-membered cyclic aminocarbonyl.

[0231] [E-44] The nitrogen-containing compound is represented by formula A1, A2 or A3:

[0232] [In the formula, R ５ ~R １２ , Z １ ~Z ５ , R ａ ~R ｃ , and X ａ [E-45] The use according to any one of [E-1] to [E-44], wherein the reaction is carried out in the presence of a solvent.

[0233] [E-46] The use according to [E-45], wherein the solvent is at least one selected from the group consisting of halogenated solvents, nitrile solvents, amide solvents, ether solvents, and aromatic hydrocarbon solvents. [E-47] The use according to [E-45] or [E-46], wherein the solvent is a halogenated solvent.

[0234] [E-48] The use according to [E-46] or [E-47], wherein the halogenated solvent is at least one selected from the group consisting of dichloromethane, chloroform, and 1,2-dichloroethane. [E-49] The use according to any one of [E-46] to [E-48], wherein the halogenated solvent is dichloromethane.

[0235] [E-50] The use according to [E-45] or [E-46], wherein the solvent is a nitrile solvent. [E-51] The use according to [E-46] or [E-50], wherein the nitrile solvent is at least one selected from the group consisting of acetonitrile, propionitrile, and benzonitrile.

[0236] [E-52] The use according to [E-45] or [E-46], wherein the solvent is an amide solvent. [E-53] The use according to [E-46] or [E-52], 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.

[0237] [E-54] The use according to [E-45] or [E-46], wherein the solvent is an ether-based solvent. [E-55] The use according to [E-46] or [E-54], 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.

[0238] [E-56] The use according to [E-45] or [E-46], wherein the solvent is an aromatic hydrocarbon solvent. [E-57] The use according to [E-46] or [E-56], wherein the aromatic hydrocarbon solvent is at least one selected from the group consisting of benzene, chlorobenzene, toluene, and xylene.

[0239] [E-58] The use according to any one of [E-1] to [E-57], wherein the reaction is carried out at a reaction temperature of 0° C. to 100° C. [E-59] The use according to [E-58], 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.

[0240] [E-60] The use according to [E-58] or [E-59], wherein the reaction temperature is 15° C. to 40° C. [E-61] The use according to any one of [E-1] to [E-60], wherein the production of a sulfonamide compound is carried out by a solid-phase method.

[0241] [E-62] The use according to any one of [E-1] to [E-60], wherein the production of a sulfonamide compound is carried out by a liquid phase method. [E-63] The use according to any one of [E-1] to [E-62], wherein a reaction is carried out using a mixture of two or more nitrogen-containing compounds to obtain two or more sulfonamide compounds.

[0242] [E-64] The use according to any one of [E-1] to [E-16] and [E-45] to [E-60], wherein the nitrogen-containing compound is a resin for solid-phase synthesis to which an amine is bound via a linker. [E-65] The use according to [E-64], wherein the amine bound to the resin for solid-phase synthesis via a linker is an amine specified in any one of [E-17] to [E-44].

[0243] [E-66] Use according to either [E-64] or [E-65], in which a reaction is carried out using a mixture of two or more solid phase synthesis resins, each of which has the same amine bound thereto, but each of which has a different amine bound thereto, to obtain two or more sulfonamide compounds.

[0244] [E-67] The use according to any one of [E-1] to [E-6] and [E-17] to [E-60], wherein the sulfonylating agent is a resin for solid-phase synthesis to which a sulfonyl halide is bound via a linker.

[0245] [E-68] A sulfonyl halide bonded to a resin for solid phase synthesis via a linker is represented by the formula: R １ SO ２ The use according to [E-67], wherein Y is a sulfonyl halide.

[0246] [E-69] Use according to either [E-67] or [E-68], in which the same sulfonyl halide is bound to each resin for solid phase synthesis via a linker, and a reaction is carried out using a mixture of two or more resins for solid phase synthesis, each of which has a different sulfonyl halide bound thereto, to obtain two or more sulfonamide compounds.

[0247] 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.

[0248] 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 in the presence of a base, wherein the base is a compound represented by Formula 1:

[0249]

[0250] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ In one embodiment, the sulfonylating agent is selected from the group consisting of sulfonyl halides and sulfonic acid anhydrides.

[0251] As used herein, sulfonyl halides are those of the formula: —SO ２ In this specification, sulfonic acid anhydride refers to a compound having a group represented by the formula: -SO ２ -O-SO ２ The nitrogen-containing compound is a compound having a structure represented by the formula -HN-, which has a chemical structure corresponding to a compound obtained by dehydration condensation of a sulfonic acid. In this specification, the nitrogen-containing compound is a compound selected from amines and ammonia or salts thereof, which has a structure represented by the formula: -HN- and is capable of forming a sulfonamide bond upon reaction with a sulfonating agent. In one aspect of the present invention, the nitrogen-containing compound is ammonia (NH ３ ), primary amines, and secondary amines. In one embodiment, the substituent on the nitrogen atom of the primary and secondary amines is a substituent that connects a carbon atom to the nitrogen atom. In one aspect of the invention, the sulfonyl halide is a sulfonyl halide of the formula: -SO ２ In one aspect of the present invention, the sulfonylating agent is a sulfonyl chloride having a group represented by the formula: １ -SO ２ a sulfonyl halide represented by the formula: １ -SO ２ -O-SO ２ -R １ In this case, a sulfonic acid anhydride represented by the formula: １ is C １－１０ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８Cycloalkyl, 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 by one or more substituents.

[0252] In one aspect of the invention, the nitrogen-containing compound has the formula A1:

[0253] [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 ３－１４ 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 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, C ６－１０aryl, and 5-10 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. In one embodiment of the present invention, the nitrogen-containing compound is a compound of formula A1, wherein R ５ , Z １ , Z ２ , Z ３ , Z ４ , and Z ５ is as defined herein.

[0254] In one aspect of the invention, the nitrogen-containing compound has the formula A1:

[0255] [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 ６－１０aryl)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, C ６－１０aryl, and 5-10 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. In one embodiment of the present invention, the nitrogen-containing compound is a compound of formula A1, wherein R ５ , Z １ , Z ２ , Z ３ , Z ４ , and Z ５ is as defined herein.

[0256] In one aspect of the invention, the reaction of a sulfonylating agent with a nitrogen-containing compound provides a compound of formula A1a:

[0257] [wherein R １ , R ５ , Z １ , Z ２ , Z ３ , Z ４ , and Z ５ is as defined herein] to produce a sulfonamide compound of the formula:

[0258] In one aspect of the invention, the nitrogen-containing compound has the formula A3:

[0259] [In the formula, 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. In one embodiment of the present invention, the nitrogen-containing compound is a compound of formula A3, wherein R ａ , Rｂ , R ｃ , and X ａ is as defined herein.

[0260] In one aspect of the invention, the nitrogen-containing compound has the formula A3:

[0261] [In the formula, 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 １－６ 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 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. In one embodiment of the present invention, the nitrogen-containing compound is a compound of formula A3, wherein R ａ , R ｂ , R ｃ , and X ａ is as defined herein.

[0262] In one aspect of the invention, the reaction of a sulfonylating agent with a nitrogen-containing compound provides a compound of formula A3a:

[0263] [wherein R and R ａ , R ｂ , R ｃ , and X ａ is as defined herein.

[0264] In one aspect of the invention, the nitrogen-containing compound has the formula A2:

[0265] [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 ４－１０Cycloalkylalkyl, 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 a ring heteroatom selected from O, N and S. In one embodiment of the present invention, the nitrogen-containing compound is a compound represented by formula A2, wherein R １１ and R １２ is as defined herein.

[0266] In one aspect of the invention, the nitrogen-containing compound has the formula A2:

[0267] [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, and C ７－１４ aralkyl, 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 attached form a 5- to 7-membered saturated heterocycle, which may further contain a ring heteroatom selected from O and S. In one embodiment of the present invention, the nitrogen-containing compound is a compound represented by formula A2, wherein R １１ and R １２ is as defined herein.

[0268] In one aspect of the invention, the reaction of a sulfonylating agent with a nitrogen-containing compound provides a compound of formula A2a:

[0269] [In the formula, R１ , R １１ and R １２ is as defined herein] to produce a sulfonamide compound of the formula:

[0270] 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.

[0271] 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.

[0272] In one aspect of the present invention, the target sulfonamide compound is obtained by reacting a nitrogen-containing compound in the presence of a base, which is a compound represented by Formula 1. Here, the base 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.

[0273] 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).

[0274] 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.

[0275] In one aspect, the present invention provides a method for producing a sulfonamide compound, comprising reacting a nitrogen-containing compound selected from an amine and ammonia or a salt thereof with a sulfonylating agent in the presence of a base to obtain the sulfonamide compound, wherein the base is a compound represented by Formula 1:

[0276]

[0277] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄmay be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ the sulfonylating agent is a sulfonyl halide or a sulfonic acid anhydride; and the nitrogen-containing compound is a resin for solid-phase synthesis to which an amine is bound via a linker. In one embodiment, the amine is bound to the resin for solid-phase synthesis via a linker that allows for cleavage of a sulfonamide compound, a low molecular weight compound, after the sulfonamidation reaction. In one embodiment of the present invention, the method further comprises cleaving the sulfonamide compound, a low molecular weight compound, by a linker cleavage reaction after the sulfonamidation reaction. In one embodiment, the method may further comprise converting or modifying the compound linked by the linker by one or more reactions after the sulfonamidation reaction, and then further comprising cleaving the sulfonamide compound, a low molecular weight compound, by a linker cleavage reaction.

[0278] In one aspect, the present invention provides a method for producing a sulfonamide compound, comprising reacting a nitrogen-containing compound selected from an amine and ammonia or a salt thereof with a sulfonylating agent in the presence of a base to obtain the sulfonamide compound, wherein the base is a compound represented by Formula 1:

[0279]

[0280] [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄis R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ and the sulfonylating agent is a resin for solid phase synthesis to which a sulfonyl halide or a sulfonic acid anhydride is bound via a linker. In one embodiment, the resin for solid phase synthesis is bonded to a sulfonyl halide or a sulfonic acid anhydride via a linker that allows cleavage of a low molecular weight sulfonamide compound after a 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 of the present invention, the method further comprises, after the sulfonamidation reaction, converting or modifying 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.

[0281] 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.

[0282] In the present specification, the 6- to 8-membered non-aromatic heterocycle is not particularly limited, and is, for example, a nitrogen-containing non-aromatic heterocycle containing one nitrogen atom as a ring atom and optionally containing one or more heteroatoms selected from nitrogen atoms, oxygen atoms, and sulfur atoms as ring atoms, for a total of 6 to 8 ring atoms. Specific examples include an azetidine ring, a pyrrolidine ring, a piperidine ring, a morpholine ring, a thiomorpholine ring, a homomorpholine ring, a homothiomorpholine ring, a homopiperidine ring, and N-(C １－６ alkyl)piperazine ring, etc.

[0283] 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.

[0284] In this specification, the salt of ammonia includes ammonium halide salts such as ammonium chloride, ammonium bromide, and ammonium iodide.

[0285] In this specification, C ２－６ Alkenyl 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).

[0286] 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.

[0287] 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.

[0288] 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.

[0289] 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.

[0290] 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 monocyclic or fused ring that exhibits aromaticity. In this specification, a heteroaryl composed of a single ring is referred to as a monocyclic heteroaryl, and a heteroaryl composed of a fused ring is referred to as a fused-ring heteroaryl. 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). 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.

[0291] 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 １－２Specific 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.

[0292] 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.

[0293] 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.

[0294] 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).

[0295] 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.

[0296] Examples of halide anions include fluoride ions, chloride ions, bromide ions, and iodide ions. １－６ Alkoxy is C １－６ means 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.

[0297] 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 previously defined.

[0298] In this specification, (C １－６ Alkoxy)carbonylamino is C １－６ means an alkoxy-C(═O)NH— group, where C １－６ Alkoxy is as previously defined.

[0299] 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 ３－１４Cycloalkyl means a cyclic saturated aliphatic hydrocarbon group having 3 to 14 carbon atoms.

[0300] 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 previously defined.

[0301] In this specification, (C １－６ Alkoxy)carbonylamino "(C １－６ The term "alkoxy)carbonyl" is as previously defined.

[0302] In this specification, (C ６－１０ aryl)carbonyl "C ６－１０ "Aryl" is as previously defined.

[0303] In this specification, (C ６－１０ aryl)carbonylamino "C ６－１０ "Aryl" is as previously defined.

[0304] 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.

[0305] In this specification, di(C １－６ alkyl)amino "C １－６ "Alkyl" is as previously defined and may be the same or different.

[0306] In this specification, 4- to 8-membered cyclic amino includes groups such as aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, which are bonded via a nitrogen atom.

[0307] As used herein, aminocarbonyl refers to -CONH ２ means.

[0308] In this specification, (C １－６ alkyl)aminocarbonyl "C １－６"Alkyl" is as previously defined.

[0309] In this specification, di(C １－６ alkyl)aminocarbonyl "C １－６ "Alkyl" is as previously defined and may be the same or different.

[0310] 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.

[0311] 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.

[0312] 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.

[0313] 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.

[0314] 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, 5-10 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 C １-６ 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 ３-１０Cycloalkoxy, 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 ６－１０ The 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.

[0315] 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.

[0316] 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. １－６Alkyl, specifically trifluoromethyl, difluoromethyl and the like.

[0317] 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.

[0318] 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).

[0319] 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.

[0320] 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.

[0321] 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.

[0322] 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.

[0323] 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).

[0324] 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.

[0325] 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).

[0326] 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.

[0327] 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.

[0328] 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 base used in the production of sulfonamide compounds. In one embodiment, the base can be synthesized by a known method or can be commercially obtained.

[0329] 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.

[0330] 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.

[0331] 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.

[0332] 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).

[0333] Unless otherwise specified, reaction tracking and purity measurement were performed by measuring retention times and performing mass spectrometry using 2020 (Shimadzu) under the analytical conditions shown in the table below.

[0334] The following abbreviations are used in the examples:

[0335] The LCMS analysis conditions are shown in the table below. ​

[0336] 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.

[0337] 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.

[0338] 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.

[0339] 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.

[0340] 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 representative 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.

[0341] 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.

[0342] 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."

[0343] 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.

[0344] Example of "-1R"

[0345] 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.

[0346] 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)

[0347]

[0348] 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.

[0349]

[0350] 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). LCMS: m / z 554 [M+Na] ＋ Retention time: 1.684 minutes (Analysis conditions FA05-1, 290 nm).

[0351] Example 1-1-2: Synthesis of ethyl 4-[4-[(4-piperidin-4-yloxyphenyl)methoxy]phenyl]benzoate (compound LP001)

[0352]

[0353] 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.

[0354]

[0355] 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).

[0356] LCMS: m / z 432 [M+H] ＋Retention time: 0.904 minutes (analysis conditions FA05-1, 290 nm).

[0357] Example 1-1-3: Synthesis of compound SP040-1R

[0358]

[0359] 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.

[0360] 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).

[0361] 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.

[0362] 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).

[0363] 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.

[0364]

[0365] Compound SP040 Maximum wavelength 294 nm Retention time: 0.775 minutes (Analysis conditions FA05-1, 299 nm).

[0366] Example 1-2: Synthesis of solid phase amine compound Example 1-2-1: Synthesis of compound SP002-1R

[0367] 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%.

[0368]

[0369] Compound SP002 LRMS: m / z 333 [M+H] ＋Retention time: 0.679 minutes (analysis conditions FA05-1, 290 nm).

[0370] Example 1-2-2: Synthesis of compound SP001-1R

[0371] 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.

[0372] 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).

[0373] 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%.

[0374]

[0375] Compound SP001 LRMS: m / z 297 [M+H] ＋ Retention time: 0.561 min (analysis conditions FA05-1, 299 nm).

[0376] Example 1-2-3: Synthesis of compound SP009-1R

[0377] 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.

[0378] 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.

[0379] 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.

[0380] 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).

[0381] 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%.

[0382]

[0383] Compound SP009 LRMS: m / z 311 [M+H] ＋ Retention time: 0.666 minutes (analysis conditions FA05-2, 299 nm).

[0384] Example 1-2-4: Synthesis of compound SP010-1R

[0385] 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 1-2-3.

[0386] 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%.

[0387]

[0388] Compound SP010 LRMS: m / z 299 [M+H] ＋ Retention time: 0.694 minutes (analysis conditions FA05-2, 299 nm).

[0389] Example 1-2-5: Synthesis of compound SP005-1R Example 1-2-5-1: Synthesis of compound SP045-1R

[0390] 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.

[0391] 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 then filtered and subjected to LCMS measurement. 97.4% of the target product, SP045, was observed.

[0392]

[0393] Compound SP045 LRMS: m / z 367 [M+H] ＋ Retention time: 0.917 minutes (analysis conditions FA05-1, 299 nm).

[0394] Example 1-2-5-2: Synthesis of compound SP041-1R

[0395] 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.

[0396] 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).

[0397] 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.

[0398]

[0399] Compound SP041 LRMS: m / z 283 [M+H] ＋ Retention time: 0.472 minutes (analysis conditions FA05-1, 299 nm).

[0400] Example 1-2-5-3: Synthesis of compound SP005-1R

[0401] 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.

[0402] 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).

[0403] 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%.

[0404]

[0405] Compound SP005 LRMS: m / z 430 [M+H] ＋ Retention time: 0.808 minutes (analysis conditions FA05-1, 299 nm).

[0406] Example 1-2-6: Synthesis of compound SP006-1R Example 1-2-6-1: Synthesis of compound SP042-1R

[0407] 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.

[0408] 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%.

[0409]

[0410] Compound SP042 LRMS: m / z 416 [M+H] ＋ Retention time: 1.235 minutes (analysis conditions FA05-1, 299 nm).

[0411] Example 1-2-6-2: Synthesis of compound SP006-1R

[0412] 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.

[0413] Solid-phase purification: The reaction mixture and the solid-phase suspension were all transferred onto a filter, and the filter was washed three times with NMP (3 mL), three times with NMP / water (1 / 1, 3 mL), three times with a solution of NAC (0.2 M) in NMP / water (1 / 1, 3 mL), and three times with TBAHSO. ４The solid phase was washed three times with a solution of NMM / DTBP (1 / 1, 0.05 M) in NMP (3 mL), three times with a solution of NMM (0.05 M) in NMP (3 mL), three times with NMP / water (1 / 1, 3 mL), three times with NMP (3 mL), three times with methanol (3 mL), three times with DCM (3 mL), and three times with heptane (3 mL). The resulting solid phase was dried under reduced pressure overnight to obtain compound SP006-1R (loading amount 0.200 mmol / g, 163.7 mg).

[0414] 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.

[0415]

[0416] Compound SP006 LRMS: m / z 437 [M+H] ＋ Retention time: 1.255 minutes (Analysis conditions FA05-1, 299 nm).

[0417] Example 1-2-7: Synthesis of compound SP007-1R Example 1-2-7-1: Synthesis of compound SP043-1R

[0418] Compound SP043-1R (loading amount 0.193 mmol / g, 5.32 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 5.00 g) and 3-bromo-4-methyl-aniline (B15) (0.748 g, 4.02 mmol) in the same manner as in Example 1-2-3.

[0419] SP043-1R was immersed in a 10% TFA / DCM solution (0.05 mL) containing 0.05 M pentamethylbenzene for 5 minutes, and the filtrate was filtered with DMF (0.50 mL). The filtrate was diluted with MeCN (0.25 mL) and subjected to LCMS measurement, whereby the target compound SP043 was observed at 99.9%.

[0420]

[0421] Compound SP043 LRMS: m / z 382, ​​384 [M+H] ＋ Retention time: 1.220 minutes (analysis conditions FA05-1, 299 nm).

[0422] Example 1-2-7-2: Synthesis of compound SP007-1R

[0423] Under a nitrogen atmosphere, a solid-phase ArBr substrate (SP043-1R) (loading amount 0.194 mmol / g, 500 mg, 97.0 μmol), NaSbF ６ To the mixture was added tBuXPhosPd G4 (CAS: 1599466-89-3) (78.4 mg, 97.0 μmol) and BTPP (178 μL, 582 μmol), and the mixture was shaken at 60°C for 15 hours.

[0424] Solid-Phase Purification The reaction solution and the solid-phase suspension were all transferred onto a filter and washed three times with DMF / water (10 mL), three times with a solution of PIX (0.01 M) in DMF (10 mL), three times with DMF / water (1 / 1, 10 mL), three times with DMF (10 mL), three times with DCM (10 mL), and three times with heptane (10 mL). The obtained solid phase was dried under reduced pressure overnight to obtain compound SP007-1R (loading amount 0.196 mmol / g, 495 mg).

[0425] Reaction tracking: A suspension (12 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), followed by immersion in 10% TFA / DCM solution (0.05 mL) for 5 minutes. After filtration, the solid phase was washed with DMF (0.05 mL), and acetonitrile (0.5 mL) was added to the filtrate. An LC sample was prepared and the reaction progress was measured by LCMS. As a result, the target product SP007 was observed at 96.0%.

[0426]

[0427] Compound SP007 LRMS: m / z 333 [M+H] ＋ Retention time: 0.888 minutes (analysis conditions FA05-1, 299 nm).

[0428] Example 1-2-8: Synthesis of compound SP008-1R Example 1-2-8-1: Synthesis of compound SP044-1R

[0429]

[0430] Compound SP044-1R (loading amount 0.155 mmol / g) was synthesized using compound SP040-1R (loading amount 0.159 mmol / g) and B16 in the same manner as in Example 1-2-3.

[0431] SP044-1R was immersed in a 10% TFA / DCM solution (0.05 mL) for 5 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.25 mL) and subjected to LCMS measurement, whereby 80.4% of the target compound SP044 was observed.

[0432]

[0433] Compound SP044 LRMS: m / z 369, 371 [M+H] ＋ . Retention time: 1.005 minutes (analysis conditions FA05-1, 299 nm).

[0434] Example 1-2-8-2: Synthesis of compound SP008-1R

[0435] Compound SP008-1R (loading amount 0.156 mmol / g) was synthesized using compound SP044-1R (loading amount 0.155 mmol / g) by the same method as in Example 1-2-7-2. SP008-1R was immersed in a 10% TFA / DCM solution (0.05 mL) for 5 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement, whereby 95.8% of the target compound SP008 was observed.

[0436]

[0437] Compound SP008 LRMS: m / z 320 [M+H] ＋Retention time: 0.692 minutes (analysis conditions FA05-1, 299 nm).

[0438] Example 1-2-9: Synthesis of compound SP049-1R Example 1-2-9-1: Synthesis of compound SP113-1R

[0439] Compound SP113-1R was synthesized using compound SP040-1R (loading amount 0.201 mmol / g) and B25 in the same manner as in Example 1-2-3. SP113-1R was immersed in a 10% TFA / DCM solution (0.05 mL) containing 0.02 M pentamethylbenzene for 5 minutes, and the filtrate was filtered with DMF (0.05 mL), diluted with MeCN (0.25 mL), and subjected to LCMS measurement. The target compound SP113 was observed at 99.6%.

[0440]

[0441] Compound SP113 LRMS: m / z 368 [M+H] ＋ Retention time: 1.161 minutes (analysis conditions FA05-1, 299 nm).

[0442] Example 1-2-9-2: Synthesis of compound SP049-1R

[0443] Compound SP049-1R (loading amount 0.194 mmol / g) was synthesized using compound SP113-1R (loading amount 0.201 mmol / g) and B22 in the same manner as in Example 1-2-6-2. SP049-1R was immersed in a 10% TFA / DCM solution (0.05 mL) for 5 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement, whereby 96.8% of the target compound SP049 was observed.

[0444]

[0445] Compound SP049 LRMS: m / z 397 [M+H] ＋ Retention time: 0.927 minutes (analysis conditions FA05-1, 299 nm).

[0446] Example 1-2-10: Synthesis of compound SP074-1R

[0447] Compound SP074-1R was synthesized using compound SP041-1R (loading amount 0.198 mmol / g) and B23 in the same manner as in Example 1-2-5-3. SP074-1R was immersed in a 10% TFA / DCM solution (0.05 mL) for 5 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement, revealing 94.7% of the target compound SP074.

[0448]

[0449] Compound SP074 LRMS: m / z 423 [M+H] ＋ Retention time: 0.739 minutes (analysis conditions FA05-1, 299 nm).

[0450] Example 1-2-11: Synthesis of compound SP078-1R

[0451] Compound SP078-1R was synthesized using compound SP041-1R (loading amount 0.198 mmol / g) and B24 in the same manner as in Example 1-2-5-3. SP078-1R was immersed in a 10% TFA / DCM solution (0.05 mL) for 5 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement, revealing 98.2% of the target compound SP078.

[0452]

[0453] Compound SP078 LRMS: m / z 451 [M+H] ＋ Retention time: 0.689 minutes (analysis conditions FA05-1, 299 nm).

[0454] Example 1-2-12: Synthesis of compound SP087-1R Example 1-2-12-1: Synthesis of compound SP085-1R

[0455] Fmoc-removal reaction: Under a nitrogen atmosphere, Fmoc-PAL AM resin (loading amount 0.67 mmol / g, 15 g, 10 mmol), DMF (120 mL) and piperidine (30 mL) were added to a 200 mL filter column, and the column was shaken at room temperature for 5 hours.

[0456] Solid-phase purification The reaction solution was filtered under reduced pressure and then washed three times with DMF / water (1 / 1, 150 mL), three times with DMF (150 mL), three times with methanol (150 mL), three times with DCM (150 mL), and three times with heptane (150 mL). The resulting solid phase was dried under reduced pressure overnight to give solid-phase-supported amine SP114-1R.

[0457] Amide Condensation SP114-1R (0.79 mmol / g, 3.0 g, 2.4 mmol), B28 (2.6 g, 7.1 mmol), DMF (36 mL), NMM (2.3 mL, 21 mmol), and PyAOP (3.7 g, 7.1 mmol) were added to a 100 mL filter column and shaken at room temperature for 24 hours.

[0458] Solid-phase purification The reaction solution was filtered under reduced pressure, washed three times with DMF / water (1 / 1, 60 mL), three times with DMF (60 mL), three times with methanol (60 mL), three times with DCM (60 mL), and three times with heptane (60 mL), and the resulting solid phase was dried under reduced pressure overnight to obtain SP115-1R.

[0459] Fmoc Deprotection Reaction DMF (36 mL) and piperidine (12 mL) were added to a 100 mL filter column containing the dried SP115-1R, and the column was shaken at room temperature for 5 hours.

[0460] Solid-phase purification The reaction solution was filtered under reduced pressure, washed three times with DMF / water (1 / 1, 60 mL), three times with DMF (60 mL), three times with methanol (150 mL), three times with DCM (150 mL), and three times with heptane (150 mL), and the resulting solid phase was dried under reduced pressure overnight to obtain SP085-1R.

[0461] Reaction tracking: A suspension (12 μL) of the reaction mixture and solid phase was transferred onto a filter and washed three times with DMF (0.1 mL) and three times with DCM (0.1 mL), after which the filter was immersed in 30% TFA / HFIP solution (0.05 mL) for 10 minutes. After filtration, the solid phase was washed with DMF (0.05 mL), and acetonitrile (0.5 mL) was added to the filtrate. An LC sample was prepared and the reaction progress was measured by LCMS. As a result, 57.7% of the target product SP085 was observed.

[0462]

[0463] Compound SP085 LRMS: m / z 137 [M+H] ＋ Retention time: 0.341 minutes (analysis conditions FA05-1).

[0464] Example 1-2-12-2: Synthesis of compound SP086-1R

[0465] Amide condensation SP085-1R (0.72 mmol / g, 200 mg, 0.144 mmol), B26 (139 mg, 0.576 mmol), DMF (4 mL), NMM (0.13 mL, 1.2 mmol), and PyAOP (300 mg, 0.576 mmol) were added to a 6 mL filter column and shaken at room temperature for 24 hours.

[0466] Solid-phase purification The reaction solution was filtered under reduced pressure, washed three times with DMF / water (1 / 1, 4 mL), three times with DMF (4 mL), three times with methanol (4 mL), three times with DCM (4 mL), and three times with heptane (4 mL), and the resulting solid phase was dried under reduced pressure overnight.

[0467] To a 6 mL filter column containing the dried solid phase, DMI (372 μL, 3.46 mmol) and DCM (3.5 mL) were added. A solution of TMSOTf (156 μL, 864 μmol) and 2,6-lutidine (150 μL, 1.30 mmol) in DCM (0.5 mL) was added, and the mixture was shaken at room temperature for 30 minutes.

[0468] Solid-phase purification The reaction solution was filtered under reduced pressure, washed three times with DMF / water (1 / 1, 4 mL), three times with DMF (4 mL), three times with methanol (4 mL), three times with DCM (4 mL), and three times with heptane (4 mL), and the resulting solid phase was dried under reduced pressure overnight to obtain SP086-1R.

[0469] Reaction tracking: A suspension (12 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), followed by immersion in 30% TFA / HFIP solution (0.05 mL) for 10 minutes. After filtration, the solid phase was washed with DMF (0.05 mL), and acetonitrile (0.5 mL) was added to the filtrate. An LC sample was prepared and the reaction progress was measured by LCMS. As a result, 92.4% of the target product SP086 was observed.

[0470]

[0471] Compound SP086 LRMS: m / z 339 [MH] - Retention time: 1.119 minutes (analysis conditions FA05-1).

[0472] Example 1-2-12-3: Synthesis of compound SP087-1R

[0473] Compound SP087-1R was synthesized using compounds SP086-1R and B21 in the same manner as in Example 1-2-7-2. SP087-1R was immersed in a 30% TFA / HFIP solution (0.05 mL) for 10 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.25 mL) and subjected to LCMS measurement, revealing 95.4% of the target compound SP087.

[0474] Compound SP087 LRMS: m / z 369 [M+H] ＋ Retention time: 0.653 minutes (analysis conditions FA05-1).

[0475] Example 1-2-13: Synthesis of compound SP090-1R Example 1-2-13-1: Synthesis of compound SP089-1R

[0476] Compound SP089-1R was synthesized using SP085-1R (0.72 mmol / g, 200 mg, 0.144 mmol) and B27 in the same manner as in Example 1-2-12-2. SP089-1R was immersed in a 30% TFA / HFIP solution (0.05 mL) for 10 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.5 mL) and subjected to LCMS measurement, revealing 98.4% of the target compound, SP089.

[0477]

[0478] Compound SP089 LRMS: m / z 383 [MH] - Retention time: 1.104 minutes (analysis conditions FA05-1).

[0479] Example 1-2-13-2: Synthesis of compound SP090-1R

[0480] Compound SP090-1R was synthesized using compounds SP089-1R and B21 by the same method as in Example 1-2-7-2. SP090-1R was immersed in a 30% TFA / HFIP solution (0.05 mL) for 10 minutes, and the filtrate was filtered with DMF (0.05 mL). The filtrate was diluted with MeCN (0.25 mL) and subjected to LCMS measurement, whereby the target compound SP090 was observed at 95.0%.

[0481]

[0482] Compound SP090 LRMS: m / z 413 [M+H] ＋ Retention time: 0.700 minutes (analysis conditions FA05-1).

[0483] Example 1-2-14: Synthesis of compound SP050-1R

[0484] Compound SP050-1R (4.8 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 5 g) and B29 (0.70 g, 4.1 mmol) in the same manner as in Example 1-2-3.

[0485] The dried solid phase was separated in the same manner as in Example 1-2-3 and subjected to LCMS measurement, whereby the target SP050 was observed at 99.3%.

[0486] Compound SP50 LRMS: m / z 334 [M+H] ＋ Retention time: 0.728 minutes (analysis conditions FA-02).

[0487] Example 1-2-15: Synthesis of compound SP051-1R

[0488] Compound SP051-1R (5.9 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 6 g) and B30 (0.86 g, 4.8 mmol) in the same manner as in Example 1-2-14. The dried solid phase was separated in the same manner as in Example 1-2-14 and subjected to LCMS measurement, whereby 98.2% of the target product SP051 was observed.

[0489]

[0490] Compound SP51 LRMS: m / z 340 [M+H] ＋ Retention time: 0.488 minutes (analysis conditions FA-02).

[0491] Example 1-2-16: Synthesis of compound SP052-1R

[0492] Compound SP052-1R (5.9 g) was synthesized using compound SP040-1R (loading amount 0.201 mmol / g, 6 g) and B31 (0.83 g, 4.8 mmol) in the same manner as in Example 1-2-14. The dried solid phase was separated and subjected to LCMS measurement in the same manner as in Example 1-2-14, and the target compound SP052 was observed at 99.6%.

[0493]

[0494] Compound SP052 LRMS: m / z 334 [M+H] ＋ Retention time: 0.736 minutes (analysis conditions FA-02).

[0495] Example 1-3: Synthesis of liquid phase amine compound Example 1-3-1: Synthesis of compound LP009

[0496] Under a nitrogen atmosphere, LP001 (1.00 g, 2.32 mmol), B05 (420 mg, 2.78 mmol), HOAt (378 mg, 2.78 mmol), DIC (435 μL, 2.78 mmol), and DMF (5 mL) were added to a 20 mL vial, and the mixture was shaken at room temperature for 15 hours. The reaction solution was purified by silica gel column chromatography (MeCN / H ２ 0) to give the title compound LP009 (623 mg, 1.1 mmol, 46%).

[0497]

[0498] Compound LP009 LRMS: m / z 565 [M+H] ＋ Retention time: 1.409 minutes (analysis conditions FA05-1, 299 nm).

[0499] Example 2: Sulfonamidation reaction in liquid phase Example 2-1: Investigation of sulfonamidation conditions Example 2-1-1: Effect of base on sulfonamidation of liquid phase aniline substrate (LP009)

[0500]

[0501] Under a nitrogen atmosphere, LP009 (10.0 mg, 17.7 μmol), DCM (0.2 mL), sulfonyl chloride (A19) (8.1 mg, 27 μmol), and 4-morpholinopyridine (4-MoPy, 5.8 mg, 35 μmol) for Run 1, triethylamine (4.9 μL, 35 μmol) for Run 2, and triethylamine (4.9 μL, 35 μmol) and DMAP (0.43 mg, 3.5 μmol) for Run 3 were placed in a 0.6 mL glass vial and shaken at room temperature for 24 hours.

[0502] 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 by cutting out at a wavelength of 299 nm (±4 nm). The reaction results are shown in Runs 1 to 3 in Table 2-1-1.

[0503]

[0504] From the results shown in Table 2-1-1, it can be seen that the use of 4-morpholinopyridine (4-MoPy) as a base in the sulfonamidation of the liquid-phase aniline substrate (LP009) results in a higher yield than Et ３ The target product (LP010) was obtained in higher purity than when N or DMAP was used.

[0505]

[0506] Compound LP010 LRMS: m / z 831 [M+H] ＋ Retention time: 1.799 minutes (analysis conditions FA05-1, 299 nm).

[0507] Example 3: Sulfonamidation reaction on solid phase Example 3-1: Investigation of sulfonamidation conditions Example 3-1-1: Sulfonamidation of solid phase aniline substrate (SP002-1R) Example 3-1-1-1: Effect of base on sulfonamidation of solid phase aniline substrate (SP002-1R) with Ar sulfonyl chlorides (A17, A18, A16, A19, A20)

[0508]

[0509] Under a nitrogen atmosphere, SP002-1R (0.196 mmol / g, 20 mg, 3.9 μmol), DCM (0.4 mL), and 4-morpholinopyridine (9.7 mg, 59 μmol) for Run 1, triethylamine (8.2 μL, 59 μmol) for Run 2, and triethylamine (8.2 μL, 59 μmol) and DMAP (96 μg, 0.78 μmol) for Run 3 were added to a 0.6 mL glass vial and shaken at room temperature for 1 hour. 4-Methoxybenzenesulfonyl chloride (A17) (8.1 mg, 39 μmol) was added, and Runs 1 to 3 were shaken at room temperature for 24 hours.

[0510] 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 reaction results are shown in Runs 1 to 3 in Table 3-1-1-1.

[0511] Similar experimental procedures were also carried out to obtain sulfonyl chlorides (A18, A15, A19, A20) and bases (4-MoPy, Et ３ N, DMAP) was used to carry out sulfonamidation. When sulfonyl chloride (A19) was used, the reaction was carried out using 4-methoxypyridine (5.9 μL, 59 μmol) or 1-pyridin-4-ylpiperidin-4-one (10.4 mg, 58.8 μmol) in addition to the above-mentioned base. The structures of the sulfonyl chlorides (A18, A15, A19, A20) used are shown in Table 3-1-1-2, and the results obtained are shown in Table 3-1-1. The analytical results of the compounds listed in Table 3-1-1-1 are shown in Table 3-1-1-3.

[0512]

[0513]

[0514]

[0515] As shown in Table 3-1-1-1, conditions using 4-morpholinopyridine or 1-pyridin-4-ylpiperidin-4-one as a base afforded the target product in purity equal to or higher than that of commonly used conditions using triethylamine or DMAP. In particular, when bulky sulfonyl chlorides such as A18 or A19 were used as sulfonylating agents, conditions using 4-morpholinopyridine or 1-piperidin-4-ylpiperidin-4-one (Runs 4, 10, and 11 in Table 3-1-1-1) afforded the target product in higher yield than commonly used conditions using triethylamine or DMAP (Runs 5, 6, 12, and 13 in Table 3-1-1-1). These results demonstrate the effectiveness of using 4-morpholinopyridine or 1-pyridin-4-ylpiperidin-4-one as a base in sulfonamidation using bulky sulfonyl chlorides, which are expected to have low reactivity.

[0516] Example 3-1-1-2: Effect of base on sulfonamidation of solid-phase aniline substrate (SP002-1R) with alkylsulfonyl chloride (A23)

[0517] Under a nitrogen atmosphere, SP002-1R (0.196 mmol / g, 20 mg, 3.9 μmol) and DCM (0.4 mL) were added to a 0.6 mL glass vial and shaken at room temperature for 1 hour. Cyclopropanesulfonyl chloride (A23) (4.0 μL, 0.039 mmol) and 4-morpholinopyridine (9.7 mg, 59 μmol) were added for Run 1, DIPEA (10 μL, 59 μmol) for Run 2, and DMAP (7.2 g, 59 μmol) for Run 3 were added, and Runs 1 to 3 were all shaken at room temperature for 24 hours.

[0518] 12 μL of the reaction solution and solid phase suspension was transferred onto a filter-equipped tip and washed three times with DMA (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) containing 0.05 M pentamethylbenzene for 5 minutes, filtered, washed with DMA (50 μL), and the combined filtrate was diluted with MeCN (0.5 mL) and analyzed by LCMS to measure the reaction progress. The reaction results are shown in Runs 1 to 3 in Table 3-1-2.

[0519]

[0520]

[0521] Compound SP046 LRMS: m / z 437 [M+H] ＋ Retention time: 0.951 min (analysis conditions FA05-1, 299 nm).

[0522] The results in Table 3-1-2 confirm that the use of 4-morpholinopyridine as a base (Run 1 in Table 3-1-2) allows the target compound SP046 to be obtained with higher purity than when DIPEA or DMAP was used (Runs 2 and 3 in Table 3-1-2).

[0523] Example 3-1-2: Effect of base on sulfonamidation of solid-phase aniline substrate (SP007-1R)

[0524]

[0525] Sulfonamidation was carried out using the solid-phase aniline substrate (SP007-1R) and sulfonyl chlorides (A18, A19) in the same manner as in Example 3-1-1. The results are shown in Table 3-1-4. The analytical results of the compounds listed in Table 3-1-4 are shown in Table 3-1-5.

[0526]

[0527]

[0528] The results in Table 3-1-4 indicate that when a bulky sulfonyl chloride such as A18 or A19 is used as a sulfonylating agent, the conditions using 4-morpholinopyridine (Runs 1 and 4 in Table 3-1-4) are effective, and the target product can be obtained with higher purity than the conditions using triethylamine or DMAP, which are known as general methods (Runs 2, 3, 5, and 6 in Table 3-1-4).

[0529] In this example, 2-tert-butylbenzenesulfonyl chloride (A18) and 2,4,6-triisopropylbenzenesulfonyl chloride (A19) were used as examples of bulky sulfonyl chlorides. However, this is not intended to be limiting, and it is readily conceivable that the use of 4-morpholinopyridine as a base will give better results than the use of triethylamine, or triethylamine and DMAP, for similarly bulky sulfonyl chlorides with a wider substrate range that are bulky around the reaction site.

[0530] Example 3-1-3: Effect of base on sulfonamidation of solid-phase aniline substrate (SP008-1R)

[0531] Sulfonamidation was carried out using the solid-phase aniline substrate (SP008-1R) and sulfonyl chlorides (A18, A19) in the same manner as in Example 3-1-1. The results are shown in Table 3-1-6. The analytical results of the compounds listed in Table 3-1-6 are also shown in Table 3-1-7.

[0532]

[0533]

[0534] The results in Table 3-1-6 indicate that when a bulky sulfonyl chloride such as 2-tert-butylbenzenesulfonyl chloride (A18) or 2,4,6-triisopropylbenzenesulfonyl chloride (A19) is used as a sulfonylating agent, the conditions using 4-morpholinopyridine (Runs 1 and 4 in Table 3-1-6) are effective, and the target product can be obtained with higher purity than the conditions using triethylamine or DMAP, which are known as general methods (Runs 2, 3, 5, and 6 in Table 3-1-6). In this example, 2-tert-butylbenzenesulfonyl chloride (A18) and 2,4,6-triisopropylbenzenesulfonyl chloride (A19) were used as examples of bulky sulfonyl chlorides. However, this is not intended to be limiting, and it is readily conceivable that the use of 4-morpholinopyridine as a base will give better results than the use of triethylamine, or triethylamine and DMAP, for similarly bulky sulfonyl chlorides with a wider substrate range that are bulky around the reaction site.

[0535] Example 3-1-4: Effect of base on sulfonamidation using benzylsulfonyl chloride (A21)

[0536] Sulfonamidation was carried out using the solid-phase aniline substrate (SP002-1R) or solid-phase amine substrate (SP001-1R) and sulfonyl chloride (A21) in the same manner as in Example 3-1-1. The results are shown in Table 3-1-8. The analytical results of the compounds listed in Table 3-1-7 are shown in Table 3-1-9.

[0537]

[0538]

[0539] The results in Table 3-1-8 indicate that when a relatively unstable sulfonyl chloride such as A21, which is known to decompose under basic conditions, is used as the sulfonylating agent, the conditions using 4-morpholinopyridine (Runs 1 and 4 in Table 3-1-8) are effective, and the target product can be obtained in higher purity than the conditions using triethylamine or DMAP, which are known as common methods (Runs 2, 3, 5, and 6 in Table 3-1-8). This example illustrates the use of phenylmethanesulfonyl chloride (A21) as an example of a sulfonyl chloride that decomposes under basic conditions. However, it is not limited to this example, and it is easily conceivable that the use of 4-morpholinopyridine as a base will give better results than the use of triethylamine, or triethylamine and DMAP, for a wider range of sulfonyl chlorides that are similarly unstable under basic conditions.

[0540] Example 3-1-5: Effect of base on sulfonamidation of solid-phase amine substrate (SP009-1R)

[0541] The same experimental procedures as in Example 3-1-1 were carried out to carry out sulfonamidation using the solid phase amine substrate (SP009-1R) and sulfonyl chloride (A19). The results are shown in Table 3-1-10.

[0542]

[0543] The results in Table 3-1-10 show that the conditions using 4-morpholinopyridine (Run 1 in Table 3-1-10) give the target product (SP037) at the same level as the conditions using triethylamine or DMAP, which are known as general methods (Runs 2 and 3 in Table 3-1-10).

[0544]

[0545] Compound SP037 LRMS: m / z 577 [M+H] ＋ Retention time: 1.400 minutes (Analysis conditions FA05-1, 299 nm).

[0546] Example 3-1-6: Effect of base on sulfonamidation of solid-phase amine substrate (SP010-1R)

[0547] The same experimental procedures as in Example 3-1-1 were carried out to carry out sulfonamidation using the solid phase amine substrate (SP010-1R) and sulfonyl chloride (A19). The results are shown in Table 3-1-11.

[0548]

[0549] The results in Table 3-1-11 show that the conditions using 4-morpholinopyridine (Run 1 in Table 3-1-11) give the target product (SP038) at the same level as the conditions using triethylamine or DMAP, which are known as general methods (Runs 2 and 3 in Table 3-1-10).

[0550]

[0551] Compound SP038 LRMS: m / z 565 [M+H] ＋ Retention time: 1.376 minutes (analysis conditions FA05-1, 299 nm).

[0552] Example 3-1-7: Effect of base on sulfonamidation of solid-phase heteroarylamine substrate (SP049-1R)

[0553] Under a nitrogen atmosphere, SP049-1R (0.194 mmol / g, 20 mg, 3.9 μmol), chloroform (0.4 mL), and 4-morpholinopyridine (9.6 mg, 58 μmol) for Run 1, and triethylamine (8.1 μL, 58 μmol) and DMAP (95 μg, 0.78 μmol) for Run 2 were added to a 0.6 mL glass vial and shaken at room temperature for 30 minutes. A33 (9.5 mg, 39 μmol) was added, and Runs 1 and 2 were shaken at 80°C for 24 hours.

[0554] 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 reaction results are shown in Runs 1 to 2 in Table 3-1-12.

[0555]

[0556]

[0557] Compound SP053 LRMS: m / z 605 [M+H] ＋ Retention time: 1.281 minutes (analysis conditions FA05-1, 299 nm).

[0558] The results in Table 3-1-12 confirmed that the target compound SP053 could be obtained by using 4-morpholinopyridine as a base (Run 1 in Table 3-1-12). On the other hand, the target compound could not be obtained when triethylamine and DMAP, which are conventionally known for sulfonamidation (Run 2 in Table 3-1-12), were used. This indicates that the sulfonamidation conditions using 4-morpholinopyridine as a base are effective for low-reactivity heteroarylamines such as SP049-1R. While this example illustrates the use of SP049-1R as a substrate, as an example of a low-reactivity heteroarylamine, it is anticipated that the use of 4-morpholinopyridine as a base will provide better results than the use of triethylamine and DMAP for a wider range of similarly low-reactivity heteroarylamines.

[0559] Example 3-1-8: Sulfonamidation of solid-phase heteroarylamine substrate (SP049-1R) with Ar sulfonyl chlorides (A35, A36, A37, A38, A39)

[0560] Under a nitrogen atmosphere, a chloroform (100 μL) solution of SP049-1R (0.194 mmol / g, 20 mg, 3.9 μmol) and 4-morpholinopyridine (9.6 mg, 58 μmol) was added to a 0.6 mL glass vial and shaken at room temperature for 30 minutes. A chloroform (100 μL) solution of A35 (7.4 mg, 39 μmol) was added and shaken at 60°C for 6 hours.

[0561] 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 reaction results are shown in Run 1 in Table 3-1-14.

[0562] Similarly, sulfonamidation was carried out using sulfonyl chlorides (A36, A37, A38, A39) using the same experimental procedure. The structures of the sulfonyl chlorides used (A35, A36, A37, A38, A39) are shown in Table 3-1-13, and the results obtained are shown in Table 3-1-14. The analytical results of the compounds listed in Table 3-1-14 are also shown in Table 3-1-15.

[0563]

[0564]

[0565]

[0566] From the results shown in Table 3-1-14, by using 4-morpholinopyridine as a base, the corresponding target compounds SP054, SP055, SP056, and SP058 could be observed even in the sulfonamidation of a solid-phase-supported heteroarylamine with low reactivity such as SP049-1R.

[0567] Example 3-1-9: Sulfonamidation of solid-phase heteroarylamine substrate (SP050-1R) with Ar sulfonyl chlorides (A35, A36, A37, A38, A39)

[0568] Sulfonamidation was carried out using the solid-phase heteroarylamine substrate (SP050-1R) and sulfonyl chlorides (A35, A36, A37, A38, and A39) in the same manner as in Example 3-1-8. The results are shown in Table 3-1-16. The analytical results of the compounds listed in Table 3-1-16 are shown in Table 3-1-17.

[0569]

[0570]

[0571] Example 3-1-10: Sulfonamidation of solid-phase heteroarylamine substrate (SP051-1R) with Ar sulfonyl chlorides (A35, A36, A37, A38, A39)

[0572] Sulfonamidation was carried out using the solid-phase heteroarylamine substrate (SP051-1R) and sulfonyl chlorides (A35, A36, A37, A38, and A39) in the same manner as in Example 3-1-8. The results are shown in Table 3-1-18. The analytical results of the compounds listed in Table 3-1-18 are also shown in Table 3-1-19.

[0573]

[0574]

[0575] Example 3-1-11: Sulfonamidation of solid-phase heteroarylamine substrate (SP052-1R) with Ar sulfonyl chlorides (A35, A36, A37, A38, A39)

[0576] Sulfonamidation was carried out using the solid-phase heteroarylamine substrate (SP052-1R) and sulfonyl chlorides (A35, A36, A37, A38, and A39) in the same manner as in Example 3-1-8. The results are shown in Table 3-1-20. The analytical results of the compounds listed in Table 3-1-20 are also shown in Table 3-1-21.

[0577]

[0578]

[0579] Example 3-1-12: Sulfonamidation of solid-phase heteroarylamine substrate (SP074-1R) with Ar sulfonyl chlorides (A35, A36, A37)

[0580] Sulfonamidation was carried out using the solid-phase heteroarylamine substrate (SP074-1R) and sulfonyl chlorides (A35, A36, A37) in the same manner as in Example 3-1-8. The results are shown in Table 3-1-22. The analytical results of the compounds listed in Table 3-1-22 are shown in Table 3-1-21.

[0581]

[0582]

[0583] Example 3-1-13: Sulfonamidation of solid-phase heteroarylamine substrate (SP078-1R) with Ar sulfonyl chlorides (A35, A36, A37)

[0584] Sulfonamidation was carried out using the solid-phase heteroarylamine substrate (SP078-1R) and sulfonyl chlorides (A35, A36, A37) in the same manner as in Example 3-1-8. The results are shown in Table 3-1-24. The analytical results of the compounds listed in Table 3-1-24 are shown in Table 3-1-25.

[0585]

[0586]

[0587] Example 3-1-14: Example of sulfonamidation using solid-phase-supported amine SP087-1R and sulfonyl chloride (A30)

[0588] Under a nitrogen atmosphere, SP087-1R (0.619 mmol / g, 20 mg, 12.4 μmol), chloroform (0.1 mL), and 4-morpholinopyridine (18.3 mg, 111 μmol) were placed in a 0.6 mL glass vial and shaken at room temperature for 30 minutes. A solution of A30 (23.1 mg, 74.3 μmol) in chloroform (0.3 mL) was added, and the mixture was shaken at 60°C for 15 hours.

[0589] 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) and three times with DCM (0.1 mL). The mixture was immersed in 30% TFA / HFIP 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 determine the reaction progress. 88.5% of the target product, SP088, was observed.

[0590]

[0591] Compound SP088 LRMS: m / z 643 [M+H] ＋ Retention time: 1.099 minutes (Analysis conditions FA05-1, 299 nm)

[0592] Example 3-1-15: Example of sulfonamidation using solid-phase-supported amine SP090-1R and sulfonyl chloride (A30)

[0593] The same experimental procedure as in Example 3-1-15 was carried out to carry out sulfonamidation using the solid phase heteroarylamine substrate (SP090-1R) and sulfonyl chloride (A30), and the target product SP091 was observed at 83.9%.

[0594]

[0595] Compound SP091 LRMS: m / z 687 [M+H] ＋ Retention time: 1.165 minutes (Analysis conditions FA05-1, 299 nm)

[0596] Example 3-2: Example of sulfonamidation using solid-supported sulfonyl chloride

[0597] Under a nitrogen atmosphere, SP041-1R (0.197 mmol / g, 20 mg, 3.9 μmol), chloroform (0.4 mL), and 2,4,6-trimethylpyridine (7.8 μL, 59 μmol) were added to a 0.6 mL glass vial and shaken at room temperature for 30 minutes. A34 (12.5 mg, 39.4 μmol) was added to the reaction mixture and shaken at room temperature for 2 hours. 4-Morpholinopyridine (9.7 mg, 59 μmol) and A29 (8.5 μL, 79 μmol) were added to the reaction mixture and shaken at 60°C for 5 hours.

[0598] 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 analyzed by LCMS to determine the reaction progress. 79% of the target product, SP084, was observed.

[0599]

[0600] Compound SP084 LRMS: m / z 634 [M+H] ＋ Retention time: 2.705 minutes (analysis conditions FA05-long, 299 nm).

[0601] Example 4: Example of sulfonamidation reaction using the mixture as a reaction raw material

[0602] 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 chloroform (0.8 mL) were placed in a 1.5 mL glass vial and shaken at room temperature for 30 minutes. A19 (23.9 mg, 78.8 μmol) and 4-morpholinopyridine (19.4 mg, 118 μmol) were added, and the mixture was shaken at 60°C for 8 hours.

[0603] 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. 36.9% of the target product SP048 and 53.2% of SP031 were observed.

[0604]

[0605] Compound SP048 LRMS: m / z 549 [M+H] ＋ Retention time: 3.268 minutes (analysis conditions FA05-long, 299 nm).

[0606] Compound SP031 LRMS: m / z 599 [M+H] ＋ Retention time: 3.321 minutes (analysis conditions FA05-long, 299 nm).

Claims

1. A method for producing a sulfonamide compound, comprising reacting a nitrogen-containing compound selected from an amine and ammonia or a salt thereof with a sulfonylating agent in the presence of a base to obtain a sulfonamide compound, wherein the base is a compound represented by Formula 1: [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ wherein the sulfonylating agent is a sulfonyl halide or a sulfonic acid anhydride.

2. The method according to claim 1, wherein the base is used in an amount of at least 1 equivalent relative to the nitrogen-containing compound.

3. The sulfonylating agent is a compound of the formula: R １ SO ２ Y is a sulfonyl halide represented by R １ is C １－１０ Alkyl, C ２－６ Alkenyl, C ２－６ Alkynyl, C ３－８ Cycloalkyl, C ４－１０ Cycloalkylalkyl, C ７－１４ Aralkyl, C ６－１０ 3. The method of claim 1 or 2, wherein Y is selected from the group consisting of 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; and Y is selected from the group consisting of F, Cl, Br, and I.

4. The method according to any one of claims 1 to 3, wherein the sulfonylating agent is a sulfonyl chloride.

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

6. The method according to any one of claims 1 to 5, 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.

7. The method according to any one of claims 1 to 6, wherein the nitrogen-containing compound contains one functional group capable of reacting with a sulfonylating agent.

8. 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; ａ is O or S.

9. The method according to any one of claims 1 to 8, wherein the reaction is carried out in the presence of a solvent.

10. The method according to any one of claims 1 to 9, wherein the sulfonamide compound is produced by a solid phase method.

11. The method according to any one of claims 1 to 9, wherein the sulfonamide compound is produced by a liquid phase method.

12. The method according to any one of claims 1 to 11, wherein the reaction is carried out using a mixture of two or more nitrogen-containing compounds to obtain two or more sulfonamide compounds.

13. A method for producing a compound constituting a compound library, the method comprising producing a sulfonamide compound by the method according to any one of claims 1 to 12.

14. A method for forming a sulfonamide bond, comprising reacting a nitrogen-containing compound selected from an amine and ammonia or a salt thereof with a sulfonylating agent in the presence of a base to obtain a sulfonamide compound, wherein the base is a compound represented by Formula 1: [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ wherein the sulfonylating agent is a sulfonyl halide or a sulfonic acid anhydride.

15. Use of a base in a sulfonamide-forming reaction in which a nitrogen-containing compound selected from an amine and ammonia or a salt thereof is reacted with a sulfonyl halide, wherein the base is a compound represented by Formula 1: [In the formula, R ａ and R ｂ are each independently a hydrogen atom, a halogen atom, or C １－６ alkyl; R ｃ and R ｄ are each independently C １－６ alkyl, or R ｃ and R ｄ is R ｃ and the nitrogen atom to which R ｄ may be bonded to X to form a 6- to 8-membered non-aromatic heterocycle, and X is O, NR ｅ , S, SO, SO ２ and CO, R ｅ is C optionally substituted with one or more halogen atoms １－６ Alkyl, (C １－６ alkyl)carbonyl, (C １－６ The above use, wherein the compound is a compound represented by the formula (I) selected from the group consisting of (alkoxy) carbonyl, and benzyl.

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