WO2007074553A1

WO2007074553A1 - CATALYST CAPABLE OF ALLOWING STRECKER REACTION TO PROCEED STEREOSELECTIVELY AND METHOD FOR STEREOSELECTIVELY PRODUCING α-AMINONITRILE DERIVATIVE USING THE SAME

Info

Publication number: WO2007074553A1
Application number: PCT/JP2006/314023
Authority: WO
Inventors: Keiji Maruoka; Takashi Ooi
Original assignee: Nagase & Co., Ltd.; Kyoto University
Priority date: 2005-12-26
Filing date: 2006-07-07
Publication date: 2007-07-05
Also published as: JPWO2007074553A1; JP5344523B2

Abstract

According to the invention, a catalyst for a strecker reaction comprising a quaternary ammonium salt and a method for stereoselectively producing an α-aminonitrile derivative using the same are provided. By using the α-aminonitrile derivative obtained by the invention, an optically active α-amino acid and a derivative thereof, which were difficult to produce by a conventional alkylation reaction can be easily produced.

Description

TECHNICAL FIELD The present invention relates to a catalyst capable of stereoselectively proceeding a Strecker reaction, and a method for stereoselectively producing an α-amino nitrile derivative using the catalyst.

The present invention relates to a catalyst capable of allowing a Strecker reaction to proceed stereoselectively.

Light

The present invention further relates to a method for stereoselectively producing an α-amino nitrile derivative using the catalyst. Background art

The α-alkyl mono α-amino acid represented by the formula H ₂ NCH (R) COOH is a very important naturally occurring α-amino acid. α-Alkyl-α-amino acids in which the α-carbon has an L configuration are constituents of proteins (polypeptide chains) present in animals, plants, microorganisms, and the like. In addition, D-form of α-alkyl-α-amino acid is present as a component of non-protein compounds in plants, fungi and microorganisms. From these properties, α-alkyl mono α-amino acids can be used as peptides with enhanced activity, effective enzyme inhibitors, and chiral building blocks to synthesize compounds with various biological activities. Possible use. For such non-protein ct-amino acids, synthetic methods for selectively constructing the α-carbon stereochemistry have been studied, but no practical method has yet been found.

Chiral phase transfer catalysts that enable stereoselective alkylation of glycine derivatives are gaining importance in the field of process chemistry due to their ease of use and their wide range of applications. Many studies have been conducted on the design of phase transfer catalysts, mainly using cinchona alkaloid derivatives. Several useful methods have been reported (eg, Shioiri, T. et al., Stimulatin Concepts in Chemistry, Vogtle, F. et al., WILEY-VCH: Weinheim, 2000 p. 123 and O'Donnell, M , Aldrichimica Acta, 2001, 34 卷, p. 3). However, in the reaction using such a phase transfer catalyst, there are various problems such as using a halogen-based solvent, requiring a long time for the reaction, and requiring low temperature conditions.

The present inventors have prepared an optically active quaternary ammonium salt having axial asymmetry, and phase-transfer catalyst for synthesizing α-alkyl mono-α-amino acids and α, monodialkyl mono-α-amino acids in a stereoselective manner. (Japanese Patent Application No. 2 0 0 1—4 8 8 6 6 and Japanese Patent Application Laid-Open No. 2 0 0 3—8 1 9 7 6; 0ο i, T. et al., J. Am. Chem Soc., 2000, 122, p. 5228). For example, the following formula:

(Where P h F ₃ represents a 3, 4, 5-trifluorophenyl group)

The spiro compound represented by the formula is very effective for stereoselectively producing an α_alkyl-α_7 mino acid derivative from a glycine derivative.

However, not all of the desired α-amino acids and derivatives thereof can be produced by such an alkylation reaction. That is, depending on the structure of the compound serving as the substrate, the alkylation reaction may not proceed appropriately. For example, when a low-reactivity alkyl halide such as tert-butyl bromide is used as an alkylating agent, the alkylation reaction does not proceed and the halide remains to obtain the desired glycine derivative. Is difficult. Therefore, among α-amino acids or derivatives thereof, particularly non-natural α- In the production of amino acids or derivatives thereof, it is desired to expand the practically manufacturable variations. Disclosure of the invention

The present invention relates to a catalyst for the production of α-amino nitrile derivatives in a stereoselective manner, which can easily produce α-amino acids and derivatives thereof, which have been difficult with conventional alkylation reactions, and the production thereof. The purpose is to provide a method.

The present invention provides the following formula (1 — 1) or formula (1-2):

(1-1) Provided is a catalyst comprising an optically active quaternary ammonium salt represented by (1 -2) and capable of proceeding with a stereoselective Strecker reaction,

Where R ¹ and R ¹ 'are independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a C alkyl group which may be branched and may be substituted with a halogen atom) Is)

(iii) a cyano group;

(iv) a ditro group;

(V) force rubermoyl group;

(vi) N- (Ci-C alkyl) force rubamoyl group; (vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group which may be branched and may be substituted with a haguchi atom);

(ix) a halogen atom;

(X) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6;

(xi) a C _{2 to} C ₆ alkenyl group which may form a branch or a ring and may be substituted with a halogen atom;

(xii) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6;

(xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is

May be branched and may be substituted by a halogen atom C i to C ₄ alkyl group,

A CC ₅ alkoxy group which may be branched and optionally substituted with a halogen atom,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom, which may be branched and substituted with a norogen atom, or an alkyl group), a nitrite group, a rubamoyl group, N— (. ) Force rubermoyl group, N, N —di (C ₁ -C ₄ alkyl) carbamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) An alkyl group) which may be substituted with an aryl group, Ciano group,

_-NR 30 _R 31 (wherein R 30 and R 31 are each independently a hydrogen atom or a C _{1 to} C ₄ alkyl group which may be branched and substituted with a halogen atom) )

Nitoguchi,

Canoleva Moinole group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group that may be branched and substituted with a halogen atom), and

Halogen atom

An aralkyl group optionally substituted with at least one group selected from the group consisting of:

(xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is

Ci C alkyl group which may be branched and may be substituted with a halogen atom,

Ci to C ₅ alkoxy group which may be branched and may be substituted with a halogen atom,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci Cd alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or an alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (C ₁ -C ₄ alkyl) a strong rubamoyl group, N, N-di (Ci C alkyl) force rubermoyl group, or one NHCOR ¹⁹ (here R ¹⁹ is a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R 30 and R 31 are each independently a hydrogen atom, or may be branched and may be substituted with a halogen atom. is there) ,

Nitro group,

Force rubymoyl group,

N-alkyl) strong rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom, or a C -alkyl group optionally branched and substituted with a halogen atom), and

Halogen atom

A heteroaralkyl group optionally substituted with at least one group selected from the group consisting of:

(XV) aryl group, where the aryl group is

It may be branched and may be substituted with a halogen atom

Anolekir group,

Ci Cs alkoxy group which may be branched and may be substituted with a halogen atom,

Halogen atoms, branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group, Shiano group, _NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) Mouth group, Forced rubamoyl group, N— (C ₁ -C ₄ alkyl) Forced rubamoyl group, N, N —Di (C ₁ -C ₄ alkyl) Forced rubamoyl group, or —NHCOR ¹⁹ (where R ¹⁹ is hydrogen An aryl group which may be branched or substituted with a halogen atom, which may be substituted with an alkyl group),

Ciano group,

_-NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl which may be branched and may be substituted with a halogen atom) )

Nitro group,

Force rubymoyl group,

N- (C C alkyl) strong rubermoyl group,

N, N-di (di-alkyl) Force rubamoyl group, _Λ- NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C alkyl group which may be branched and substituted with a halogen atom) ), And

Halogen atom

May be substituted with at least one group selected from the group consisting of: O- (CH ₂ ) _p -0- (where p is 1 or 2 Which may be substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,

A C Cs alkoxy group which may be branched and may be substituted with a halogen atom,

A halogen atom, which may be branched and substituted with a halogen atom Ci C alkyl group, cyano group, one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or branched and substituted with a halogen atom. Or a C ₁ -C ₄ alkyl group), a nitrite group, a strong rubermoyl group, N— (CC alkyl) canolevamoinole group, N, N —di (dialkyl), a strong rubermoyl group, or one An aryl group, optionally substituted with NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci C alkyl group which may be branched and optionally substituted with a halogen atom),

Ciano group,

_ _NR 30 _R 31 (wherein R ^3D and R ³¹ are each independently a hydrogen atom or a CC alkyl group that may be branched and substituted with a halogen atom) ,

Nitro group,

Force ruby moinole group,

N— (C Cd alkyl) force rubermoyl group,

N, N—di (dialkyl), rubamoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a 'C i to C ₄ alkyl group which may be branched and substituted with a halogen atom'), and

Halogen atom

A heteroaryl group optionally substituted with at least one group selected from the group consisting of:

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom) A C ₄ alkyl group);

A group selected from the group consisting of: R ⁸ , R ⁸ ', R and R ⁹ ' are each independently

Is a hydrogen atom;

Is a halogen atom;

A C i Cs alkyl group which may be substituted with a halogen atom and a Z or aryl group, and which may form a no or branched or ring; or

A C Cs alkoxy group, which may be substituted with a halogen atom and / or an aryl group, and / or which may form a branch or a ring;

R ² , R ² ′, R ³ , R ³ ′, R ⁴ , R ⁴ ′, R ⁵ , R ⁵ ′, R ⁶ , R ⁶ ′, R ¹⁰ and R ¹ ° ′ are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or may be branched and substituted with a halo atom! Is an alkyl group);

(iii) a cyano group;

(iv) a ditro group;

(V) force rubermoyl group;

(vi) N- (di-alkyl) strong rubermoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C i to C ₄ alkyl group which may be branched and substituted with a halogen atom);

(ix) a halogen atom;

(X) may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6; (Xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;

(xii) it may also be substituted by branched or better and a halogen atom to form a ring Rere, alkynyl group C ₂ -C _6;

An alkyl group which may be branched and optionally substituted with a halogen atom,

A halogen atom, which may be branched and may be substituted with a halogen atom, an alkyl group, a cyano group, a single NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, which may be branched and substituted with a norogen atom, or an alkyl group), a nitrite group, a rubamoyl group, or an N— (dialkyl) force. Rubamoyl group, N, N

—Di (di-alkyl), or rubamoyl group, or NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom, or may be branched and substituted with a halogen atom. May be substituted with), aryl group,

Ciano group,

_{_NR} 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted c _{1 to} c ₄ alkyl group. Is)

Nitro group,

Force rubymoyl group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group, N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Neurogen atom

It may be branched and may be substituted with a halogen atom

An alkyl group,

A C to C ₅ alkoxy group which may be branched and optionally substituted with a halogen atom,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom, or a C ₁ -C ₄ alkyl group which may be branched and substituted with a norogen atom), a nitrite group, a strong rubamoyl group, N— ˜Alkyl) Forced rubermoyl group, N, N —Di (C ₁ -C ₄ alkyl) Forced rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and a halogen atom) A Ci to C ₄ alkyl group which may be substituted with), an aryl group,

Ciano group,

_{_NR} 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom), Nitro group,, canole vainole group,

N— (. Alkyl) Force rubermoyl group,

N, N—di (dialkyl), rubamoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C alkyl group that may be branched and substituted with a halogen atom), and

Halogen atom

(XV) aryl group, where the aryl group is

Ci C ₅ alkoxy group which may be branched and may be substituted with a halogen atom,

Halogen atom, which may be branched and may be substituted with a halogen atom Alkyl group, cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, an N-alkyl) force rubermoyl 、, Ν, -Ν

—Di (di-alkyl) rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) Optionally substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ^3G and R ³¹ are each independently hydrogen Or a C ₁ -C ₄ alkyl group that may be branched and substituted with a halogene atom),

Nitro group,

Force rubymoyl group,

N— (Ci C alkyl) force rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C 1, c ₄ alkyl group which may be branched and substituted with a halogen atom),

A halogen atom, and

-S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ^2Q may be branched and optionally substituted with a halogen atom) C ₁ -C ₄ alkyl Base)

May be substituted with at least one group selected from the group consisting of or _0— (CH ₂ ) _m —0— (where m is 1 or 2) Optionally substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

A halogen atom, which may be branched and optionally substituted with a halogen atom, an alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom; Or a nitro group, a carbamoyl group, a N- (dialkyl) group, a rubermoyl group, N, N —Di (CC alkyl) substituted with a rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) May have been, Ryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R ³¹ are each independently a permanent atom or a branched and optionally substituted halogen atom) )

Nitro group,

Force ruby moyl group, '

-(C C alkyl) strong rubermoyl group,

N, N—di (dialkyl), rubamoyl group,

Halogen atom

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom) ~C ₄ alkyl group);

A group selected from the group consisting of:

1 ⁷ぉ 1 ⁷ ′ are independent

(i) It may form a branch or a ring and may be substituted with a halogen atom, C! ~ Ji ^ alkyl group;

(ii) may be branched or ringed and substituted with a halogen atom May, alkenyl C ₂ -C _12;

(iii) it may also be substituted by branched or better and a halogen atom to form a ring Rere, alkynyl group C ₂ -C _12;

(iv) an aryl group,

It may be branched and may be substituted with a halogen atom. An alkyl group,

A C ₁ -C ₅ anoalkoxy group which may be branched and optionally substituted with a halogen atom,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a carbamoyl group, N_ (Ci C alkyl) carbamoyl Group, N, N —di (Ci-C ₄ alkyl) force rubamoyl group, or —NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) A C ₁ -C ₄ alkyl group) which may be substituted with an aryl group,

Ciano group,

_{_NR} 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted c _{1 to} c ₄ alkyl group. )

Nitoguchi,

Force ruby moinole group,

N- arnolekill) force ruber moyl group,

N, N—di (C ₁ -C ₄ alkyl) canolemoinole group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or branched Well and it is substituted with a halogen atom Ru good C i~C ₄ alkyl group Kadea also), and

Halogen atom

An aryl group optionally substituted with at least one group selected from the group consisting of:

(V) a heteroaryl group, wherein the heteroaryl group is

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or a Ci C alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (C ₁ -C ₄ alkyl) force rubamoyl Group, N, N

—Di (C CA alkyl) carbamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom) An aryl group, optionally substituted with '

Ciano group,

_{_NR} 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom),

Nitro group,

Force rubymoyl group,

N- (C ₁ ~C ₄ alkyl) Karupamoiru groups, N, N—di (ji 丄 ~ ji ^! Alkyl) force rubamoyl group,

Halogen atom

An optionally substituted heteroaryl group with at least one group selected from the group consisting of:

(vi)-(CH ₂ ) _n OCONR ²¹ R ²² (where R ²¹ and R ²² are independently

(1) hydrogen atom,

(2) branched also be well and good Ci -C ₄ alkyl group optionally substituted by a halogen atom,

(3) a C _{2 to} C ₆ alkenyl group which may form a branch or a ring and may be substituted with a halogen atom;

(4) a C ₂ -C ₆ alkynyl group which may form a branch or a ring and may be substituted with a halogen atom;

(5) An aralkyl group, where the aralkyl portion constituting the aralkyl group is.

Branched even if well and good to c ₄ alkyl group optionally substituted by a halogen atom,

May be branched and may be substituted by a halogen atom C j to c ₅ alkoxy group,

A halogen atom, which may be branched and may be substituted with a halogen atom, an alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently hydrogen; Or a Ci C ₄ alkyl group which may be branched and may be substituted with a divalent atom) Nitro group, strong rubermoyl group, N- (ji-ji alkyl) strong rubermoyl group, N, N-di (Ci C alkyl) strong rubermoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom, or A Ci Cd alkyl group that may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³⁰ and R ³¹ are each independently a hydrogen atom or a C _{1 to} C ₄ alkyl group which may be branched and substituted with a halogen atom) )

Nitro group,

Canoleva Moinole group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C i to C ₄ alkyl group that may be branched and substituted with a halo atom), and

Halogen atom

(6) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is

May be branched and may be substituted by a halogen atom C j -C ₄ alkyl group,

May be branched and may be substituted by a halogen atom C i -C ₅ alkoxy group,

A halogen atom, which may be branched and substituted with a halogen atom Ci C alkyl group, Ciano group, one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or branched and substituted with a halogen atom. also it is good or C i~C ₄ alkyl group), a nitro group, a force Rubamoiru group, N- (Ci~C ₄ alkyl) force Rubamoiru group, N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru Or a single NHCOR ¹⁹ where R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom. It ’s okay,…

Ciano group,

_ _NR 30 _R 3 1 (wherein, R 30 and _r31 are each independently either hydrogen atom, or branched even if well and with or which may be substituted Ci～C ₄ alkyl group by a halogen atom is there) ,

Nitro group,

Force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N-di (dialkyl-dialkyl) strong rubamoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a ci to C ₄ alkyl group which may be branched and substituted with a halo atom), and

Halogen atom

(7) an aryl group, the aryl group

May be branched and may be substituted by a halogen atom C i -C ₄ alkyl group,

C may be branched and may be substituted with a halogen atom ~C ₅ alkoxy group,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom or , Or branched and optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (dialkyl) a strong rubamoyl group; N, N —Di (C! To C ₄ alkyl) force rubermoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom C ₁ -C ₄ alkyl group is one) may be substituted with, § re Ichiru group,

Ciano group,

_{_NR} 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom),

Nitro group,

Rubamoyl group,

N- (. Alkyl) 'force rubermoyl group,

N, N-di (Ci C alkyl) force rubermoyl group,

Halogen atom

An aryl group optionally substituted with at least one group selected from the group consisting of

(8) a heteroaryl group, wherein the heteroaryl group is

C ₁ may be branched and may be substituted with a haguchigen atom ~c ₄ alkyl group,

It may be branched and may be substituted with a halogen atom

~c ₅ alkoxy group,

A halogen atom, which may be branched and substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or a C ₄ to C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitro group, a rubamoyl group, N— (C _{1 to} C ₄ alkyl) force rubamoyl group; N, N—di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and a halogen atom) A C ₁ -C ₄ alkyl group which may be substituted with), an aryl group,

Ciano group,

-NR ³⁰ R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halo atom) )

Nitro group,

Canoleva Moinole group, '

N— (C ₁ -C ₄ alkyl) force rubamoyl group,

N, N—di (C ₁ -C ₄ alkynole) force rumomoire group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), and

Halogen atom

A heteroaryl group optionally substituted with at least one group selected from the group consisting of: A group selected from the group consisting of, and n is an integer from 1 to 1 2);

(vii)-(CH ₂ ) _n CONR ¹² R ¹³ (where R ¹² and R ¹³ are each independently

(1) hydrogen atom,

(2) branched optionally substituted in well and halogen atoms have C i -C ₄ alkyl group,

(3) an aryl group, the aryl group

May be branched and may be substituted by a halogen atom C j -C ₅ alkoxy group,

Halogen atoms, branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group, Shiano group, _NR ³⁰ R ³¹ (wherein, R ³⁰ and R ^31, each independently, A hydrogen atom, or a C i to C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitro group, a rubamoyl group, N— (C _{1 to} C ₄ alkyl) N, N—di (di-alkyl)! Carpamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or branched and substituted with a halogen atom) Which may be an alkyl group), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R 30 and R 31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom) ),

Nitro group, Force ruby moinole group,

N- (Ci C alkyl) strong rubermoyl group,

N, N—di (C ₁ -C ₄ alkyl) canolamoyl group,,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group which may be branched and substituted with a halo atom), and

Halogen atom

(4) a heteroaryl group, wherein the heteroaryl group is

Branched even if well and good -C ₄ alkyl group optionally substituted by a halogen atom,

Branched even if Ji may and may be substituted with a halogen atom丄-C ₅ alkoxy group,

A halogen atom, which may be branched and substituted with a halogen atom, an alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently hydrogen, A C ₄ alkyl group that may be branched or substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (di-alkyl) a strong rubamoyl group; N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted by a halogen atom) _{1 to} C ₄ alkyl groups), aryl groups,

Ciano group,

_-NR 30 _R 3 1 (wherein R 30 and R 3 1 are each independently a hydrogen atom or may be branched and substituted with a halogen atom. Is also good or C ₁ -C ₄ alkyl group),

Nitro group,

Force ruby moinole group,

N- (C ₁ ~C ₄ alkyl) Karupamoiru groups,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C to C ₄ alkyl group which may be branched and substituted with a halo atom), and

Halogen atom

A heteroaryl group optionally substituted with at least one group selected from the group,

A group selected from the group consisting of, and n is an integer from 1 to 1 2);

(viii)-(CH ₂ ) _n NR ¹² COR ¹³ (where R ¹² and R ¹³ are each independently

(1) permanent atoms,

(2) a C _{4 to} C ₄ alkyl group which may be branched and optionally substituted with a haguchi atom,

(3) an aryl group, the aryl group

May be branched and may be substituted with C port Gen atoms CJ -C ₄ alkyl group,

May be branched and may be substituted with a halogen atom -C ₅ alkoxy group,

A halogen atom, which may be branched and may be substituted with a halogen atom; an alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom; Or may be branched And an optionally substituted ci to C ₄ alkyl group with a halogen atom), a nitro group, a strong rubamoinole group, an N— (Ci to C ₄ alkyl) force rubamoyl group; N, N—di (C ₁ to C ₄ alkyl) a strong rubermoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom, or a C 1 to C ₄ alkyl group which may be branched and substituted with a halogen atom) An aryl group, which may be substituted with

Ciano group,

Nitro group,

Canoleva Moinole group,

N- (C C alkyl) strong rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

(4) a heteroaryl group, wherein the heteroaryl group is

Ci may be branched and may be substituted with a halogen atom

~C ₄ alkyl group,

It may be branched and may be substituted with a halogen atom

~C ₅ alkoxy group,

A halogen atom, which may be branched and substituted with a halogen atom Ci C alkyl group, Ciano group, one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or branched and substituted with a halogen atom. Nitro group, carbamoyl group, N- (C alkyl) force rubamoyl group; N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (this) R ¹⁹ is a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R ³¹ are each independently a hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom) ),

Nitro group,

Force rubymoyl group,

N- (.! ~ Ji alkyl) force ruberamoyl group,

N, N—di (C ₁ -C ₄ alkyl) force rubamoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C to C ₄ alkyl group which may be branched and substituted with a halogen atom), and

Ro, atom atom

(ix) — (CH ₂ ) _n NR ¹² R ¹³ (where R ¹² and R ¹³ are each independently (1) hydrogen atom,

(3) an aryl group, the aryl group

A halogen atom, which may be branched and substituted with a halogen atom, an alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently hydrogen, A C or C ₄ alkyl group which may be branched or substituted with a divalent atom), a nitro group, a rubamoyl group, an N- (di-alkyl) carbamoyl group N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom); It may be an alkyl group) or an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R ^3Q and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) )

Nitro group,

Force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N-di (di-alkyl) rubamoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or branched And may be a c ₁ -c ₄ alkyl group which may be substituted with a halogen atom), and

Halogen atom

(4) a heteroaryl group, wherein the heteroaryl group is

A C ₄ -C ₄ alkyl group which may be branched and optionally substituted with a halogen atom,

A halogen atom, which may be branched and optionally substituted with a halogen atom, an alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom, or branched and have also is how well and Ha port Gen atom substituted C ₁ optionally -C ₄ 7 alkyl group), a nitro group, a force Rubamoiru group, N- (Ji ~ Ji ^! alkyl) power Rubamoyl group; N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or branched and substituted with a halogen atom) Which may be a C _{1 to} C ₄ alkyl group), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a C i to C ₄ alkyl group which may be branched and substituted with a halogen atom) )

Nitro group,

Carpamoyl group,

N- (ji ~ anorekiru) canolepamoyl group, , N-di (C Ca alkyl) force rubermoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a Ci Ca alkyl group that may be branched and substituted with a halogen atom), and

Halogen atom

(X) — (CH ₂ ) _n Y-OR ¹² (where Y is a divalent saturated hydrocarbon group which may be branched, and R ¹² is

(1) hydrogen atom,

(2) branched optionally may and substituted by a halogen atom which may have C -C ₄ alkyl group,

(3) an aryl group, the aryl group

Branched optionally substituted in well and halogen atoms have Cj -C ₄ alkyl group,

A halogen atom, which may be branched and optionally substituted with a halogen atom, an alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom, Or a C i to C ₄ alkyl group which may be branched and substituted with a divalent atom), a nitro group, a carbamoyl group, N— (C ₁ -C ₄ alkyl) carbamoyl group; N: N-di (di-alkyl) rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or a branched and halogen atom. An optionally substituted C ₁ -C ₄ alkyl group), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted halogen atom) )

Nitro group,

Force ruby moinole group,

N- (Ci C alkyl) strong rubermoyl group,

N, N—di (C L C alkyl) force rubermoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C 1, C ₄ alkyl group which may be branched and substituted with a halo atom), and

Halogen atom

(4) a heteroaryl group, wherein the heteroaryl group is

It may be branched and may be substituted with a halogen atom.丄~C ₄ alkyl group,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom; Or a Ci C alkyl group that may be branched and substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (Ci C alkyl) a strong rubamoyl group; N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) It may be substituted with an alkyl group), an aryl group,

Ciano group,

_ _NR 3 O _r31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) )

Nitro group,

Force rubymoyl group,

N- (ji ~ anorekiru) force rubamoyl group,

N, N—di (C ₁ -C ₄ alkynole) force rubamoyl group,

Halogen atom,

Force:> optionally substituted with at least one group selected from the group consisting of heteroaryl groups,

(xi) — (CH ₂ ) _n — OR ¹² (where R ¹² is

(1) hydrogen atom,

(2) branched and may also be optionally substituted by a halogen atom C j -C ₄ alkyl group,

(3) an aryl group, the aryl group

C i may be branched and substituted with a halogen atom ~C ₄ alkyl group,

Ci may be branched and may be substituted with a halogen atom

~C ₅ alkoxy group,

Haguchigen atom, which may be branched and substituted with a halogen atom. An alkyl group, a cyano group, one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom, or may be branched and substituted with a halogen atom, C ₁ N, N-di (Ci C alkyl) force rubamoyl group, or — NHCOR ¹⁹ (this is ~ C ₄ alkyl group), nitro group, force rubermoyl group, N— (dialkyl) R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

Nitro group,

Force ruby moinole group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (dialkyl), rubamoyl group,

Halogen atom

An aryl group optionally substituted with at least one group selected from the group consisting of (4) Heteroariru a group, the Heteroariru group optionally branched Ci -C ₄ be substituted or a well and a halogen atom are alkyl group,

_{May be} branched and may be substituted with a halogen atom, a C5-analkoxy group,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom; Or a C to C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitro group, a rubamoyl group, N- (ji-ji alkyl) rubamoyl Group; N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) Which may be substituted with a Ci C alkyl group), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ), '

Nitro group,

Force rubymoyl group,

N— (C ₁ -C ₄ alkyl) force rubamoyl group,

N, N-di (Ci C alkyl) force rubermoyl group,

Halogen atom A heteroaryl group optionally substituted with at least one group selected from the group consisting of:

(xii)-(CH ₂ ) _n — S— R ¹² (where R ¹² is

(1) hydrogen atom,

(2) branched even if well and Ha port Gen may be substituted with atoms C i -C ₄ alkyl group,

(3) an aryl group, the aryl group

It may be branched and may be substituted with a halogen atom

~C ₄ alkyl group,

May be branched and may be substituted by a halogen atom C -C ₅ alkoxy group,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a C alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom, Or a C _{4 to} C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (CC alkyl) a strong rubamoyl group; N., N— Di (C ₁ -C ₄ alkyl) strong rubermoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom) May be substituted with), aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R 30 and R 3 i are each independently a hydrogen atom or a Ci to C alkyl group which may be branched and substituted with a halogen atom) is there) , Nitro group,

Force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (C C alkyl) force rubermoyl group,

Halogen atom

(4) a heteroaryl group, wherein the heteroaryl group is

May be branched and may be substituted by a halogen atom C -C ₅ alkoxy group,

Ha port Gen atoms, branched C ₁ may be substituted in good and Ha port Gen atoms optionally -C ₄ alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ^31, Each independently a hydrogen atom, or a C to C ₄ alkyl group which may be branched and substituted with a divalent atom), a nitro group, a strong rubermoyl group, N— ( C ₁ -C ₄ alkyl) force rubamoyl group; N, N—di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or branched) A Ci to C ₄ alkyl group which may be substituted with a halogen atom), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R 30 and R 3 i are independently Hydrogen atom or is or branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group),

Nitro group,

Force rubymoyl group,

N— (ji-ji alkyl) strong rubermoyl group,

N, N-dialkyl) strong rubermoyl group,

Halogen atom

(xiii) — (CH ₂ ) _n -SO-R ¹² (where R ¹² is

(1) hydrogen atom,

(2) branched even if well and Ha port Gen atoms optionally substituted C丄-C ₄ alkyl group,

(3) an aryl group, the aryl group

A halogen atom, which may be branched and substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently May be a hydrogen atom or branched. And a C i to C ₄ alkyl group optionally substituted with a divalent atom), a nitro group, a strong rubamoyl group, N— (C ₁ -C ₄ alkyl) a strong rubamoyl group; N, N—di (C ₁ -C ₄ alkyl) Carpamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) ) May be substituted with

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted C _{1 to} C ₄ atom. An alkyl group),

Nitro group,

Force rubymoyl group,

N— (di: ~. Alkyl) force rubermoyl group,

N, N-di (. Alkyl) force rubermoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C to C ₄ alkyl group which may be branched but may be substituted with a divalent atom), and

Halogen atom

(4) a heteroaryl group, wherein the heteroaryl group is

It may be branched and substituted with a halogen atom

~C ₄ alkyl group,

Ci may be branched and may be substituted with a halogen atom

~C ₅ alkoxy group,

A halogen atom, which may be branched and substituted with a halogen atom Ci C alkyl group, Ciano group, one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or branched and substituted with a haguchine atom. Ci CaT alkyl group), nitro group, strong rubamoyl group, N— (C ₁ -C ₄ alkyl) .strong rubamoyl group; , Or one NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) Yo!

Ciano group,

_-NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom),

Nitro group,

Carpamoinole group,

N- (ji-ji alkyl) rubamoyl group,

New ', N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C _{} to} C ₄ alkyl group which may be branched and substituted with a halogen atom), and

Halogen atom

A group selected from the group consisting of and n is an integer from 1 to 12); and

(xiv)-(CH ₂ ) _n -S0 ₂ -R ¹² (where R ¹² is

(1) hydrogen atom, (2) C i may be branched and substituted with a halogen atom

~c ₄ alkyl group,

(3) an aryl group, the aryl group

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom; Or a C to C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitro group, a rubamoyl group, N— (C _{1 to} C ₄ alkyl) carbamoyl Group; N, N-di (CC alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom C _{1 to} C ₄ alkyl groups), aryl groups,

Ciano group,

_-N R 30 _R 3 1 (wherein R ³⁰ and R. ³¹ each independently represents a hydrogen atom, or may be branched and may be substituted with a halogen atom. C _{1 to} C ₄ An alkyl group),

Nitro group,

Canoleva Moinole group,

N- (ji-ji alkyl) Carpamoinole group,

N, N-di (Ci to C ₄ alkyl) force ruberamoinole group,

NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci Ca alkyl group that may be branched and substituted with a halogen atom) And)

Halogen atom

(4) a heteroaryl group, wherein the heteroaryl group is

A halogen atom, which may be branched and optionally substituted with a halogen atom, a CC alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom or Or a Ci to C ₄ alkyl group which may be branched and may be substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (dialkyl) and a strong rubamoyl group; N, N-di (di-alkyl) rubamoyl group, or one NHCOR ¹⁹ (where R ¹ ' ⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) Ci A Cd alkyl group), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein ³ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom) ),

Nitro group,

Carpamoyl group, '

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N—di (Ci-C ₄ alkyl) force rubermoyl group, -NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a _4- alkyl group that may be branched and substituted with a halo atom), and

Halogen atom

Or a group selected from the group consisting of

R ⁷ and R ⁷ 'together are one (CH ₂ ) _m- (where m is an integer from 2 to 8);

(Where R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , R ²⁹ , R ³² , R ³³ and R ³⁴ are each independently

Hydrogen atom;

A Ci Cs alkyl group which may form a branch or a ring and may be substituted with a halogen atom; A c _{2 to} c ₈ alkenyl group which may form a branch or ring and / or may be substituted with a halogen atom;

It may form a branched or cyclic, and Roh or it may also be substituted with a halogen atom Les ,, C ₂ -C ₈ alkynyl group;

Nono androgenic ₄ alkyl force may be replaced by an atom \ halogen atom ₃ alkoxy force may be substituted with a substituted alkyl group which C ₁ optionally -C ₄ substituted by a halogen atom May be a aryl group \ a cyan group, a halogen atom, a nitro group, or one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom or branched. well and be substituted with a halogen atom is either good Ci～C ₄ alkyl group) or be, or C ₂ -C ₈ alkylene group or configured comprising a cyclic amino group a ring, in substituted May also be an aryl group;

Ha port Gen atoms or an optionally substituted C ~ C ₄ alkyl group, or C port Gen atom substituted by C ₁ optionally -C ₃ alkoxy group, or Shiano group, or a halogen atom, a nitro group — NR ³ ° R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom or branched and optionally substituted by a halogen atom. A C ₁ -C ₄ alkyl group) or a cyclic amino group comprising a ring with a C ₂ -C ₈ alkylene group, or a heteroaryl group optionally having a aryl moiety;

Or halogen atom - which Ji may be substituted Ji Wiarukiru group, or C port Gen atom substituted by C ₁ optionally -C ₃ alkoxy group, or Shiano group force halogen atom, or a nitro group, _NR ³ ° R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group, or an aralkyl group optionally having an aryl moiety; Ha port Gen atoms or an optionally substituted C ~ C ₄ alkyl group, Nono port Gen atom in either an optionally substituted Ci C ₃ alkoxy group, or Shiano group force \ halogen atom, or a nitro group, _NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl which may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group, or may be substituted with a heteroaryl moiety having a heteroaryl moiety;

(C ₁ -C ₃ alkoxy) carbonyl group;

Canolemoyl group;

N— (Ci C alkyl) strong rubermoyl group; and

N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group (wherein the same alkyl group may be the same or different from each other) is a group selected from the group consisting of:

Represents a divalent group selected from the group consisting of and

X— is a halide anion.

In one embodiment, R ¹ and R ¹ ′ of the optically active quaternary ammonium salt of the catalyst are each independently

(XV) aryl group, where the aryl group is

Ci to C ₄ alkyl group which may be branched and may be substituted with a halogen atom,

Ci C ₅ alkoxy group which may be branched and optionally substituted with a halogen atom,

Halogen atom, which may be branched and optionally substituted with a halogen atom Ci C alkyl group, cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently hydrogen An atom or an alkyl group which may be branched and substituted with a halogen atom) Mouth group, force rubermoyl group, N— (Ci C alkyl) force rubermoyl group, N, N—di (C ₁ -C ₄ alkyl) force rubermoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ^3C) and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl that may be branched and substituted with a halogen atom )

Nitro group,

Force ruby moinole group,

N- (ji-ji alkyl) rubamoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

It is.

In one embodiment, R ⁷ and R ⁷ ′ of the optically active quaternary ammonium salt of the catalyst are each independently (i) branched or ring-formed and substituted with a halogen atom. Which may be a C -dialkyl group;

In one embodiment, the optically active quaternary ammonium salt of the catalyst is It is a compound represented by the above formula (I 1 1).

The present invention also provides the following formula (II):

And a method for stereoselectively producing an _α -amino nitrile derivative represented by the formula:

The following formula (III):

And the following formula (IV)

R 42

(I V)

Is an optically active quaternary ammonium salt in the presence of an alkali metal cyanide and an acid, which has one of the following formulas (1-1) or (1-2): :

And reacting in a solvent containing an optically active quaternary ammonium salt represented by:

Here, in the equations (1-1) and (1-2), ^{^{R \ R 1 ', R 2}} , R 2', R 3, R 3 ', R 4, R 4', R 5, R 5 ', RR 6', R 8, R 8 ', R 9, R 9 ', R ¹⁰ and R ¹⁰ ' are each independently the same as defined for the catalyst above,

R ⁷ and R ⁷ ′ are each independently a monovalent organic group or together represent a divalent organic group, and

X— is a halide anion,

In formula (I I) and formula (I I I),

R ⁴¹ is

(1) may form a branch or a ring, and may be substituted with Z or a halogen atom,

An alkyl group;

(2) may form a branched or cyclic, and / or halogen atoms may be substituted, C ₂ -C ₂₀ alkenyl group;

(3) C ₂ -C ₂ , which may form a branch or ring, and may be substituted with a no or halogen atom. An alkynyl group;

(4) good C ₁ -C ₄ alkyl radical force which may be substituted with a halogen atom, halogen atom or笸換which may be C ~ C ₃ alkoxy group, it may be substitution with a halogen atom An aryl group optionally substituted by an alkyl group of Ci C, a cyano group, a halogen atom, a nitro group, _NR ³ ° R ³¹ (where R ³ ° and R ³¹ are independently The ring may be a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a divalent atom), or a C ₂ -C ₈ alkylene group A cyclic amino group, which may be substituted with an aryl group;

(5) C port Gen atom or optionally substituted C i to C ₄ alkyl group, Nono port gain down atoms or optionally substituted C ₁ -C ₃ alkoxy group, or Shiano group, halo gen An atom, a nitro group, or an NR ³⁰ R ³¹ (wherein R ^{3 G} and R ³¹ are each independently a hydrogen atom or a branched and halogen atom) Ci C alkyl group optionally substituted with) or C ₂ ~

A cyclic amino group that forms a ring with a C ₈ alkylene group, or an aryl group that may be substituted with a heteroaryl group;

(6) Alkyl group that may be substituted with a halogen atom, Cj Cg alkoxy group that may be substituted with a halogen atom, a cyano group, a halogen atom, a nitro group, — NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl which may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C ₂ to C ₈ alkylene group, or an aralkyl group having an aryl moiety, which may be substituted with:

(7) a halogen atom or a substituted Ji may ~ Ji alkyl group,. Halogen atoms or optionally substituted C ₁ -C ₃ alkoxy group, or Shiano group, or a halo gen atom, a nitro group _NR ³⁰ R ³¹ (wherein R ³⁰ and R ^{31 each} independently represent a hydrogen atom, or may be branched and substituted with a halogen atom, C _{1 to} C Which is a ₄ alkyl group) or a cyclic amino group comprising a ring with a C ₂ -C ₈ alkylene group, or a heteroaralkyl group optionally having a heteroaryl moiety;

(8) (C ₁ ~C ₃ alkoxy) carbonyl group;

(9) force / levamoyl group;

(10) N- (Ci C alkyl) carbamoyl group; and

(11) N, N-di (Ji丄~ Ji alkyl) force Rubamoiru group (wherein, Ci～C ₄ alkyl group may be either the same or different from each other) is a group selected from the group consisting of) ;

Represents a group selected from the group consisting of

In formula (I I) and formula (I V),

R ⁴² is (1) a hydrogen atom;

(2) may be branched or ringed, and may be substituted with Z or a halogen atom; ^ Alkyl group;

(3) a Ci to C ₈ alkoxy group which may form a branch or a ring, and may be substituted with a no or halogen atom;

(4) C ₂ -C ₂ , which may form a branch or a ring, and / or may be substituted with a halogen atom. An alkenyl group;

(5) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₂ -C ₂₀ alkynyl group;

(6) C ₁ -C ₄ alkyl group optionally substituted with a halogen atom, C Cg alkoxy group optionally substituted with a halogen atom, or C substituted with a halogen atom C an aryl group optionally substituted with an alkyl group of j to C ₄ , a cyano group, a halogen atom, a nitro group, or one NR ^{3 ()} R ³¹ (where R ^3G and R ³¹ are each independently A hydrogen atom, or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) Force \ or C ₂ -C ₈ alkylene group constitutes a ring A cyclic amino group, which may be substituted with an aryl group;

(7) C port Gen atoms or an optionally substituted C ~ C ₄ alkyl group, C port gain down atoms or an optionally substituted C Cg alkoxy group, or Shiano group, or a halo gen atom, a nitro NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) in a), or may be substituted with a cyclic amino functionalized consisting constituting the ring C ₂ ~ C ₈ alkylene group or have a Ariru moiety, Heteroariru group;

(8) Alkyl group optionally substituted with a halogen atom, C ₁ -C ₃ alkoxy group optionally substituted with a halogen atom, Cyan group, NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom) Or a cyclic amino group formed by forming a ring with a C ₂ to C ₈ alkylene group, or an aralkyl group having an aryl moiety, which may be substituted with ;

(9) Ci to C ₄ alkyl group optionally substituted with a halogen atom, or _{3 to} alkoxy groups optionally substituted with a nocturnal gen atom, a cyano group or a halogen atom , A nitro group, or ——NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom) A C i -C ₄ alkyl group) or a cyclic amino group comprising a ring with a C ₂ -C ₈ alkylene group, or a heteroaralkyl group optionally having a heteroaryl moiety;

(10) (C ₁ ~C ₃ alkoxy) carbonyl group;

(11) force rubamoyl group;

(12) N- (C ₁ -C ₄ alkyl) strong rubamoyl group;

(13) N, N-di (Ji-Ji alkyl) force Rubamoiru group (wherein, Ci C ₄ alkyl group may be either the same or different from each other) a group selected from the group consisting of); and

(14) — SO ₂ R ⁴³

(Where R ⁴³ is

(i) may form a branched or cyclic, and Z or halogen atoms may be substituted, C ₁ -C ₈ alkyl group;

(ii) may form a branched or cyclic, and Z or halogen atoms may be substituted, C ₂ -C ₈ alkenyl group;

(iii) may form a branched or ring, optionally substituted with Oyopi Roh or halo gen atom, C ₂ -C ₈ alkynyl group; (iv) CC alkyl group which may be substituted with a halogen atom, Ci Cg alkoxy group which may be substituted with a halogen atom C ₁ -C ₄ alkyl group which may be substituted with a halogen atom An optionally substituted aryl group, cyano group, halogen atom, nitro group, one NR ³ ° R ³¹ (where R ³ ° and R ³¹ are each independently a hydrogen atom, Or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), or a cyclic amino group formed by forming a ring with a C ₂ -C ₈ alkylene group Or an aryl group optionally substituted by

(V) C to C ₄ alkyl group optionally substituted with a halogen atom, C _{1 to} C ₃ alkoxy group optionally substituted with a norogen atom \ Cyan group, halogen atom or nitro group , — NR ³ . R ³¹ (wherein R ³ and R ³¹ are each independently a hydrogen atom or a 0 to 0 alkyl group which may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group, or a heteroaryl group having an aryl moiety, which may be substituted with:

(vi) C 1, C ₄ alkyl group optionally substituted with a halogen atom \ C _{1 to} C ₃ alkoxy group optionally substituted with a halogen atom, Cyan radical \ halogen atom, nitro _NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group, or an aralkyl group having an aryl moiety, which may be substituted with:

(vii) Ci C alkyl group optionally substituted with a halogen atom \ C Cg alkoxy group optionally substituted with a halogen atom, cyano group, halogen atom, nitro group, or NR ³⁰ R ³¹ (Where R ³ ° and R ³¹ are each independently a hydrogen atom or may be branched and A Ci C alkyl group that may be substituted with a rogen atom) or a cyclic amino group that forms a ring with a c _{2 to} c ₈ alkylene group, or a heteroaryl moiety that may be substituted with Having a heteroaralkyl group;

(viii) (C ₁ ~C ₃ alkoxy) carbonyl group;

(ix) force rubermoyl group;

(x) N- (C ₁ -C ₄ alkyl) strong rubamoyl group; or

(xi) N, N-di (Ci C alkyl) force rubamoyl group (wherein the C _{1 to} C ₄ alkyl groups may be the same or different from each other) and are selected from the group consisting of: ;

Is)

Represents a group selected from the group

In the formula (I I)

* Indicates a newly generated asymmetric center.

The present invention also provides the following formula (V):

A method for stereoselectively producing an α-amino nitrile derivative represented by the formula:

The following formula (VI):

Is an optically active quaternary ammonium salt in the presence of an alkali metal cyanide, which has one of the following formulas (1-1) or (1-2):

(I 1) (1 -2)

Here, the formulas (1-1) and (1-2) are the same as those defined in the method for stereoselectively producing the α-aminominotolyl derivative represented by the formula (II). And.

In formula (V) and formula (V I),

R ⁴¹ is

(1) may form a branch or a ring and / or may be substituted with a halogen atom,

An alkyl group;

(2) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₂ -C ₂₀ alkenyl group;

(3) may form a branched or cyclic, and or may be substituted by halogen atom, C ₂ -C ₂₀ alkynyl group;

(4) C ₁ -C ₄ alkyl group optionally substituted with a halogen atom, ₃ alkoxy groups optionally substituted with a halogen atom, or Ci C alkyl optionally substituted with a halogen atom An aryl group optionally substituted by a group, a cyano group, a halogen atom, a nitro group, or one NR ³ ° R ³¹ (where R ^3Q and R ³¹ are each independently a hydrogen atom, Or a Ci C alkyl group that may be branched and substituted with a divalent atom) or a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group. An aryl group optionally substituted by

(5) C port Gen atoms or an optionally substituted Ci～C ₄ alkyl group, C inlet gate down atoms which may be optionally C ₁ -C ₃ alkoxy group power substituted with, or Shiano group, Nono b Gen An atom, a nitro group, or one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom). May be an alkyl group) force, or C ₂ ~

(6) substituted with C port Gen atom les, or optionally C ~ C ₄ alkyl group, C port gain down atoms optionally Ci optionally substituted with C ₃ alkoxy groups force, or Shiano group, Bruno, mouth NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or branched and substituted with a halogen atom) in any good C ₁ -C ₄ alkyl group) or be, or C ₂ ~ C ₈ alkylene group or a cyclic amino group formed by constituting the ring, in which may be substituted, having Ariru portion, Ararukiru Group;

(7) C port Gen atoms or which may be C ~ C ₄ alkyl group substituted, Ha port gain down atoms or optionally substituted Ci～C ₃ alkoxy force Shiano group, or Nono b Gen atoms , Nitro group -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted halogen atom) ₁ -C is ₄ or alkyl group) or C ₂ ~ C ₈ alkylene group or structure to become cyclic amino group the ring, in which may be substituted, having Heteroariru moiety, Heteroararukiru group;

(8) (C ₁ ~C ₃ alkoxy) carbonyl group;

(9) force rubamoyl group;

(10) N- (C ₁ -C ₄ alkyl) strong rubamoyl group; and

(11) N, N-di (di-alkyl) rubamoyl group (where C ₁ -C ₄ alkyl groups may be the same or different from each other) and are selected from the group consisting of:

Represents a group selected from the group consisting of

R ⁴³

(i) a Ci Cs alkyl group which may form a branch or a ring and / or may be substituted with a halogen atom;

(ii) may form a branched or cyclic, and may be substituted by Bruno or halogen atom, C ₂ -C ₈ alkenyl group;

(iii) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₂ -C ₈ alkynyl group;

(iv) a halogen atom or a substituted Ji may ~ Ji alkyl group, Ji Nono Rogge emissions atom or optionally substituted C ₁ -C ₃ alkoxy group, it may be substitution with a halogen atom An aryl group optionally substituted with the same alkyl group, a cyan group, a halogen atom, a nitro group, _NR ^3Q R ³¹ (where R ^3Q and R ³¹ are each independently a hydrogen atom or branched Ru good C ~ C ₄ alkyl group Kadea substituted in well and Ha port Gen atoms optionally), or C ₂ -C ₈ cyclic amino formed by constituting the ring with an alkylene group An aryl group optionally substituted by a group or.

(V) may be substituted with C port Gen atoms C i to C ₄ or an alkyl group, Ha port gain down atoms or substituted by C ₁ optionally -C ₃ alkoxy group, or Shiano group, halo gen An atom, a nitro group, or one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom). Which may be a C ₁ -C ₄ alkyl group) or a cyclic amino group comprising a ring with a C ₂ -C ₈ alkylene group, or may be substituted with a heteroaryl group having an aryl moiety;

(vi) Ci C alkyl group optionally substituted with a halogen atom or halogen NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each a C ₁ -C ₃ alkoxy group, a cyan group, a nitrogen atom, a nitro group, Each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) or a C ₂ -C ₈ alkylene group A cyclic amino group that forms a ring with, or an aryl group that may be substituted with an aryl moiety;

(vii) C ₁ -C ₄ alkyl group optionally substituted with a halogen atom, or optionally substituted with a nitrogen atom, ₃ to ₃ alkoxy groups, cyan groups, halogen atoms, nitro NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or may be branched and substituted with a halogen atom. ₄ alkyl or a is) or groups, or C ₂ -C ₈ alkylene group or a cyclic amino group formed by constituting the ring, in which may be substituted, having Heteroariru moiety, Heteroararukiru group;

(viii) (C ₁ ~C ₃ alkoxy) carbonyl group;

(ix) force rubermoyl group;

(X) N- (Ci C alkyl) strong rubermoyl group; or

(xi) N, N-dialkyl) Forced rubermoyl group (where Ci ~ C

₄ alkyl groups may be the same or different from each other) and are selected from the group consisting of:

Is)

Represents a group selected from the group consisting of and

In equation (V)

* Indicates a newly generated asymmetric center.

The present invention also provides the following formula (V):

/ S0 ₂ R ⁴³ A method for stereoselectively producing an α-amino nitrile derivative represented by the formula:

The following formula (XXV III):

Is an optically active quaternary ammonium salt in the presence of an alkali metal cyanide, represented by the following formula (1-1) or formula (I—

2) One of the formulas:

X

Here, the formulas (1-1) and (1-2) are the same as those defined in the method for stereoselectively producing the α-amino nitrile derivative represented by the above formula (II). And

Formula (V) is the same as that defined in the method for stereoselectively producing the α-amino nitrile derivative represented by the above formula (V),

In the formula (XXV I I I)

R ⁴¹ and R ⁴³ are the same as those defined in the method for stereoselectively producing the monoaminonitrile derivative represented by the above formula (V), and R ¹¹ is either an optionally substituted Ci C alkyl group by a halogen atom, optionally substituted with a halogen atom C ₁ -C ₃ alkoxy groups force \ halogen atom C ₁ may be substituted with ~ C ₄ alkyl group or optionally substituted § aryl group, or Shiano group, or a halogen atom, or a nitro group, one NR ³⁰ R ³¹ (wherein, R ³ ° and R ³¹ are each independently A hydrogen atom, or a Ci C alkyl group that may be branched and substituted with a halogen atom) Force \ or a ring formed of a C _{2 to} C ₈ alkylene group An amino group or an aryl group optionally substituted by

In one embodiment, in a method for producing the one of c Amino nitrile derivatives stereoselectively, the above formula (1 1) or formula (1-2) is the same as the catalyst _p

The present invention also provides a method for producing an optically active amino acid or derivative thereof,

Formula (II) obtained by the above method:

Hydrolyzing an optically active c-amino nitrile derivative represented by the following:

R ⁴¹ and R ⁴² are the same as those defined in the method for stereoselectively producing the α-aminonitrile derivative represented by the above formula (II). The present invention also provides a method for producing an optically active α-amino acid or derivative thereof,

Formula (V) obtained by the above method:

Hydrolyzing an optically active a_amino nitrile derivative represented by the following:

here,

R ⁴¹ and R ⁴³ are the same as those defined in the method for stereoselectively producing the a-amino nitrile derivative represented by the above formula (V). The present invention also provides the following formula (I-1b):

A process for producing a compound represented by

The following formula (XX I I-1 b):

Is reacted in a solvent in the presence of tetramethylpiperidinemagnesium, and bromine is added to form the following formula (XX III-1 b):

Obtaining a compound represented by:

The compound represented by the formula (XX I I I -1 b) is reacted with a metal hydride in a solvent to form the following formula (XX I V— 1 b):

Obtaining a compound represented by:

The compound represented by the formula (XX I V-1 b) is reacted with PB r ₃ in a solvent to form the following formula (XXV— 1 b):

Obtaining a compound represented by:

The compound represented by the formula (XXV— lb) is reacted with R ^7b — NH ₂ in a solvent. Let the following formula (XXV I-1 b)

Obtaining a compound represented by:

At least one compound represented by the formula (XXV I— lb) represented by Ri—B (OH) ₂ or R ^ —B (OH) ₂ in a solvent in the presence of a palladium catalyst. Reaction with a boronic acid derivative of the following formula (XXV II-lb):

(XXV II—lb)

Obtaining a compound represented by:

Reacting the compound represented by the formula (XXV II—lb) with an alkyl halide represented by R ^7b′— X in a solvent;

Including

here,

In the formula (I 1 1 b) and the formula (XXV I I-1 b),

1 ¹ 1 ¹ ¹ 'is the same as defined in the catalyst represented by the above formula (1-1),

Formula (I 1 lb), Formula (XX II—lb), Formula (XXV II—lb), Formula (XX IV— lb), Formula (XXV— lb), Formula (XXV I— lb) and Formula

(XXV I I-1 b)

R ² R ² ′ R ³ R ³ ′ R ⁴ R ⁴ ′ R ⁵ R ⁵ ′ R ⁶ , and R ⁶ ′ are the same as those defined in the catalyst represented by the above formula (1 _ 1). In the formula (I—lb) and the R ^7b '—X,

R ^{7 b} ′ (i) may form a branch or a ring, and may be substituted with a halogen atom, C ₁ C ₃ . X is a halogen atom,

In formula (XX I I-1 b) and formula (XX I I I-1 b),

R ⁵ ° and R ⁵ ° 'are each independently a C i C ₂ alkyl group that may form a branch or ring and may be substituted with a halogen atom, and

In Formula (XXV I— lb), Formula (XXV II— lb) and R ^7b — NH ₂ ,

R ^7b is a C ₁ C ₃₀ alkyl group which may form a branch or a ring and may be substituted with a halogen atom.

In one embodiment, the compound represented by the above formula (I- l b) and the above formula

In the compound represented by (XXV II— lb), R ¹ and R ¹ ′ are each independently the same as defined in the (XV) aryl group (the catalyst represented by the above formula (1-1)). )

The present invention also provides the following formula (XXV I — 1 b):

(XXV I 1 b)

Wherein the compound is a synthetic intermediate of a compound represented by the above formula (I 1 lb),

here,

R ² , R ² ′, R ³ , R ³ ′, R ⁴ , R ⁴ ′, R ⁵ , R ⁵ ′, R ⁶ , R ⁶ ′ and R ^7b are represented by the above formula (I-1) The same as defined in the catalyst. The present invention also provides the following formula (XXV II-1 b):

here,

R ¹ , R ¹ ′ R ² , R ² ′, R ³ , R ³ ′, R ⁴ , R ⁴ ′, R ⁵ , R ⁵ ′, R ⁶ , R ⁶ ′ and R ^7b ′ are represented by the above formula (I The same as defined for the catalyst represented by _l).

The present invention also provides the following formula (I-2b):

A method for producing a compound represented by the formula:

The following formula (XX I I— 2 b):

Is reacted in a solvent in the presence of teramera piperidine magnesium, and bromine is added to form the following formula (XX I I 1-2b):

Obtaining a compound represented by:

The compound represented by the formula (XX I I I -2 b) is reacted with a metal hydride in a solvent to form the following formula (XX I V— 2 b):

Obtaining a compound represented by:

The compound represented by the formula (XX IV-2 b) is reacted with PB r ₃ in a solvent. Let the following formula (XXV— 2 b):

Obtaining a compound represented by:

Formula a compound represented by (XXV- 2 b), in a solvent, R ^7b - is reacted with NH ₂ by the following formula (XXV I- 2 b):

Obtaining a compound represented by:

The compound represented by the formula (XXV I— 2 b) is represented by R ¹ — B (OH) ₂ or R ¹ ′ — B (OH) ₂ in a solvent in the presence of a palladium catalyst. Reaction with at least one boronic acid derivative yields the following formula (XXV II -2 b):

(XXV II— 2 b)

Obtaining a compound represented by:

Reacting the compound represented by the formula (XXV II-2b) with at least one alkyl halide represented by R ^7b '-X in a solvent;

Including

here,

In formula (I— 2 b) and formula (XXV I I-2 b),

R ¹ and R ¹ ′ are the same as those defined in the catalyst represented by the above formula (1-2),

Formula (I 1 2 b), Formula (XX II-2 b), Formula (XX III— 2 b), Formula (XX I V-2 b), Formula (XXV— 2 b), Formula (XXV I— 2 b) and the expression

(XXV I I-2 b)

R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ and R ¹⁰ ′ are the same as defined in the catalyst represented by the above formula (1-2),

In formula (XX I I—2 b) and formula (XX I I I—2 b),

R ⁵ ° and R ⁵ ° 'are each independently, may form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _12, and

In the formula (XXV I-2 b), formula (XXV II-2 b) and the R ^7b _NH ₂ ,

R ^7b is an alkyl group which may form a branch or a ring and may be substituted with a halogen atom.

In one embodiment, R ¹ and R ¹ ′ of the compound represented by the above formula (I—2 b) and the compound represented by the above formula (XXV II—2 b) are an (XV) aryl group (above It is the same as defined in the catalyst represented by formula (1-2).

The present invention also provides the following formula (XXV I-2 b): (XXV I 1 2 b)

Wherein the compound is a synthetic intermediate of a compound represented by the above formula (I 1 2 b),

here,

R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ , R ¹⁰ ′ and R ^7b are the same as those defined in the catalyst represented by the above formula (1-2).

The present invention also provides the following formula (XXV I I-2 b):

RR ¹ ′, R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ , R ¹⁰ ′ and R ^7b are the same as those defined in the catalyst represented by the above formula (1-2). .

According to the present invention, stereoselectivity can be provided for the reaction product in the Strecker reaction. In particular, according to the present invention, an α-amino nitrile derivative can be produced stereoselectively and easily. Also obtained by the present invention Using the α-amino nitrile derivative produced by Nikkei Patent Office 24.8.2006, the predetermined optically active ct monoamino acid and / or its derivative can be easily produced. Brief Description of Drawings

Fig. 1 shows the chiral ammonium salt ((R)-after recrystallization obtained in Example 4.

This is the ORTE P diagram in the X-ray structural analysis for 1 PF ₆ ). Solvent molecules (THF) and all hydrogen atoms are omitted for clarity.

Fig. 2 shows the chiral ammonium salt ((R) — after recrystallization obtained in Example 4.

2 is an ORTEP diagram for X-ray structural analysis of a). Solvent molecules (CH ₂ C 1 ₂ ) and all hydrogen atoms are omitted for clarity. BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, terms used in the present specification are defined.

The term “an alkyl group of Ci Cn that may form a branch or a ring” (where n is an integer) is any linear alkyl group having 1 to n carbon atoms, any alkyl group having 3 to n carbon atoms Includes branched alkyl groups and any cyclic alkyl group having 3 to n carbon atoms. For example, arbitrary linear alkyl groups having 1 to 6 carbon atoms include methyl, ethyl, n-propyl, n-butynole, n-pentyl, and n_hexyl, and any linear alkyl group having 3 to 6 carbon atoms. Examples of branched alkyl groups include isopropyl, isobutyl, tert-butyl, isopentyl, etc., and 3 carbon atoms

Examples of the optional cyclic alkyl group of ˜6 include cycloptyl, cyclopentyl, cyclohexyl and the like. Further, for example, the term “branches or rings may be formed and / or substituted with halogen atoms,

"Cj C alkyl group" refers to a linear alkyl group having 1 to 12 carbon atoms, any branched alkyl group having 3 to 12 carbon atoms, and any cyclic alkyl group having 3 to 12 carbon atoms. And the hydrogen atom at any of these positions is a halogen atom

Replacement paper (Rule 26) 67/1 may be substituted. Such alkyl groups include _n- heptyl

Replacement paper (Rule 26) Soheptyl, n-octyl, isooctyl, n-decyl, n-dodecyl and the like.

In addition, in N— (C ₁ -C ₄ alkyl) strong rubamoyl group and N, N—di (di--C ₄ alkyl) strong rubamoyl, rCi C alkyl ”is a linear alkyl group of Ci to C ₄ or C ₃ refers to branched chain alkyl group ~ C _4.

The term “C ₂ -C _n alkenyl group which may form a branch or a ring” (where n is an integer) means any straight chain alkenyl group having 2 to n carbon atoms, 3 to n carbon atoms It includes any branched alkenyl group and any cyclic alkenyl group having 3 to n carbon atoms. For example, as an arbitrary straight chain alkenyl group having 2 to 6 carbon atoms, ethenyl, 1_propeninole, 2-propenyl, 1_buteninole, 2-buteninole, 1-penteninole, 2— Penteninole, 3_penteninole, 4_penteninole, 1-hexenyl and the like, and as an arbitrary branched chain alkenyl group having 3 to 6 carbon atoms, isopropenyl, 1-methyl _ 1 _ Propenyl, 1_Methyl_2—Propeninole, 2-Metinore, 1-Propeninole, 2-Methinore_2-Propropenole, 1-Methyl-2-butenyl, etc., and 3 carbon atoms Examples of the cyclic alkenyl group of ˜6 include cyclobutenyl, cyclopentenyl, cyclohexenyl and the like. Further, for example, the term “a C _{2 to} C ₁₂ alkenyl group which may form a branch or a ring and may be substituted with a no or halogen atom” has ₂ to ₁₂ carbon atoms. Including a straight-chain alkenyl group, an arbitrary branched alkenyl group having 3 to 12 carbon atoms, and an arbitrary cyclic alkenyl group having 3 to 12 carbon atoms, wherein a hydrogen atom at any position thereof is substituted with a halogen atom. It may be. Examples of such an alkenyl group include 1-heptenyl, 2_heptul, 1-octul, 1-decenyl, 1_dodecel and the like.

The term "may form a branched or cyclic alkynyl group of C ₂ -C _n"

(Where n is an integer) is an arbitrary linear alkynyl group having 2 to n carbon atoms, 4 carbon atoms 69

Includes any branched chain alkynyl group of ˜n and any cyclic alkynyl group of 4 to n carbon atoms. For example, any straight chain alkynyl group having 2 to 6 carbon atoms includes ethynole, 1_probule, 2-probule, 1-butynyl, 2-butynyl, 1-pentul, 1-hexyl, etc. Examples of the arbitrary branched alkynyl group having 4 to 6 include 1-methyl-1,2-propynyl and the like, and examples of the cyclic alkynyl group having 4 to 6 carbon atoms include cyclopropyl ether and cyclobutyl ether. Is mentioned. Further, for example, the term “a C _{2 to} C ₁₂ alkynyl group which may form a branch or a ring and / or be substituted with a halogen atom” has 2 to 12 carbon atoms. A straight chain alkynyl group, an arbitrary branched alkynyl group having 4 to 12 carbon atoms, and an arbitrary cyclic alkynyl group having 4 to 12 carbon atoms, wherein a hydrogen atom at any position is substituted with a halogen atom May be. Examples of such alkynyl groups include 1-heptul, 1-otatur, 1-decynyl, 1-dodecynyl and the like.

The term “optionally branched alkoxy group having ˜O” (where n is an integer) means an alkoxy group having any linear alkyl group having 1 to n carbon atoms and any branch having 3 to n carbon atoms. Includes alkoxy groups with chain alkyl groups. Examples include methyloxy, ethyloxy, n_propyloxy, isopropyloxy, tert-butyloxy and the like.

In the present invention, examples of the term “aralkyl group” include benzyl, phenyl, naphthylmethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl and 2-phenylbutyl.

Examples of the term “heteroaralkyl group” in the present invention include pyridylmethyl, indolylmethyl, furylmethyl, chenylmethyl, pyrrolylmethyl, 2-pyridylethyl, 1-pyridylethyl and 3-chenylpyl pills. In the present invention, examples of the term “aryl group” include phenyl, naphthyl anthryl, phenanthryl and the like.

Examples of the term “heteroaryl group” in the present invention include pyridyl, pyrrolinole, imidazolyl, furyl, indolyl, benzothiophene 1 2 r, cenyl, oxazolyl, thiazolyl, 3, 4-methylenedioxyphenyl 3, 4- And ethylenedioxyphenyl and tetrazolyl. In the present invention, examples of the term “halogen atom” include chlorine atom, bromine atom, iodine atom and fluorine atom. In the present invention, the term “halide anion” means a halogen ion, and examples thereof include a chloride ion, a bromide ion, an iodide ion, and a fluoride ion. .

In the present invention, the term “C ₃ -C _n aryl group or substituted aryl group which may form a branch or a ring” (where n is an integer) is an aryl group, or 1 and / or 2 and Z Alternatively, it means an arbitrary substituted aryl group having 4 to n total carbon atoms having a substituent at the 3-position. For example, 2-ptenyl, 1-cyclopentylmethyl, 3-methyl_2-butyr and the like can be mentioned.

In the present invention, the term “optionally branched C _{3 to} C _n propargyl group or substituted propargyl group” (where n is an integer) ′ is a propargyl group or substituted at the 1- and 3-positions Any total carbon number with groups 4 ~! ! Substitution of propargyl group means. For example, 2-buthur, 3-trimethylsilyl-2-propynyl and the like can be mentioned.

In the following, in this specification,

"Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,

Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group, A halogen atom, which may be branched and may be substituted with a halogen atom, an alkyl group, a cyano group, a single NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or a C ₁ -C ₄ alkyl group that may be branched and substituted with a nonogen atom), a nitrite group, a strong rubamoyl group, N— (〇〇〇 ₄ alkyl) force Rubamoiru group, New, New chromatography di (Ci~C ₄ alkyl) force Rubamoiru group or a NHCOR ¹⁹ (where,, R ¹⁹ is also substituted with a well and a halogen atom are either hydrogen, or branched An optionally substituted C ₁ -C ₄ alkyl group), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R 30 and R 3 i are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) ,

Nitro group,

Force rubymoyl group,

N- (di-alkyl) force rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom), and

Halogen atom

The “group of forces” may be abbreviated as “group (Q)”.

Further, in the present specification,

“Alkyl group optionally substituted with halogen atom, C Cs alkoxy group optionally substituted with halogen atom, cyano group, halogen atom, nitro group, _NR ³⁰ R ³¹ (where R ³ ° and R ³¹ it 72 each independently a hydrogen atom, or a C i C alkyl group that may be branched and substituted with a halogen atom), or C ₂ -C

_The description that may be substituted with a cyclic amino group comprising a ring with ₈ alkylene groups or may be described as “may be substituted with a predetermined substituent A”. is there.

Hereinafter, the present invention will be described in detail.

The catalyst of the present invention can cause the Strecker reaction to proceed stereoselectively.

The term “Strecker reaction” in the present specification is based on a chemical reaction discovered by the German chemist Strecker in 1850, and the synthesis of c-amino nitrile derivatives. And a method for synthesizing α-amino acids and Z or derivatives thereof using the monoaminonitryl derivative. For example, (1) a reaction process between an aldehyde or ketone and a cyanating agent; (2) a reaction process between an aldimine derivative obtained from the reaction of an aldehyde with an amine and a cyanating agent; (3) a ketone and A reaction process between a ketimine derivative obtained by reaction with a amine and a cyanating agent; and (4) aldimine generated in the reaction system by acting a cyano alkali on α-amide sulfone, which is the precursor of the aldimine derivative. A chemical reaction including variations of the reaction process such as the reaction process of a derivative and a cyanating agent. Furthermore, the term “the Strecker reaction can proceed stereoselectively” in the present specification means that α-aminonitrile and its derivatives, and α-amino acid and its derivatives obtained in the Strecker reaction. Each can be produced stereoselectively (ie in a non-racemic state).

Furthermore, the “catalyst capable of proceeding Strecker reaction stereoselectively” of the present invention 73 is a catalyst capable of producing an optically active reaction product in the Strecker reaction.For example, α-amino nitrile and its derivative, and α-amino acid and its derivative are stereoselectively selected in the Strecker reaction, respectively. A compound or drug that can catalyze its stereoselective reaction when it is produced (ie, in a non-racemic state), or a compound or drug that can promote the stereoselective synthesis of the reaction product in a Strecker reaction (So-called stereoselective reaction accelerator). In other words, it is used as a catalyst for stereoselective Strecker reaction.

The catalyst of the present invention that can cause the Strecker reaction to proceed stereoselectively is represented by any one of the following formulas (1-1) or (1_2):

(1-1) (1 -2)

It consists of an optically active quaternary ammonium salt represented by

Here, in the above formulas (1-1) and (1-2), R ¹ and R ¹ ′ are independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and may be substituted with a halogen atom) is there)

(iii) a cyano group;

(iv) a ditro group;

(V) force rubermoyl group; (vi) N- (C CA alkyl) force rubermoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHC OR ^{1 9} (wherein, R ¹⁹ is either hydrogen, or is or branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group);

(ix) a halogen atom;

(X) C ₁ -C ₆ alkyl group which may form a branch or a ring and may be substituted with a halogen atom;

(xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be substituted with at least one group selected from the group (Q); an aralkyl group;

(xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is optionally substituted with at least one group selected from group (Q);

(XV) aryl group, wherein the aryl group may be substituted with at least one group selected from the group (Q), or the 3rd and 4th positions are combined together. An aryl group optionally substituted with O_ (CH ₂ ) _P -0- (wherein p is 1 or 2);

(xvi) a heteroaryl group, which may be substituted with at least one group selected from group (Q); and

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° is a C j -C ₄ alkyl group which may be branched and may be substituted with a halogen atom);

A group selected from the group consisting of:

Preferably, each independently

(XV) aryl group, wherein the aryl group may be substituted with at least one group selected from group (Q), or the 3rd and 4th positions are combined O— (CH ₂ ) _p —O— (wherein p is 1 or 2), an aryl group;

Alternatively, in the present invention, it is preferable that R ¹ and R ¹ ′ of the quaternary ammonium salt represented by the above formula (1-1) or (1-2) have the same force. Furthermore, in the above formula (1-1) and formula (1-2),

R ⁸ , R ⁸ ', R ⁹ and R ⁹ ' are each independently

Is a hydrogen atom;

Is a halogen atom;

It may be substituted with a halogen atom and or Ariru groups, and or may form a branched or ring, or a C ₁ -C ₅ alkyl group; or

A Ci Cs alkoxy group which may be substituted with a divalent atom and a Z or aryl group, and which may form a Z or branched or ring;

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a Ci C alkyl group that may be branched and may be substituted with a halogen atom) ) (iii) a cyano group;

(iv) a nitro group;

(V) force rubermoyl group;

(vi) N- (. 丄 ~ ji alkyl) force ruberamoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom, or a Ci to C ₄ alkyl group which may be branched and substituted with a halo atom);

(ix) a halogen atom;

(X) to form a branched or ring may be substituted in Yogu and halogen atom, an alkyl group of C ₁ -C _6;

(xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;

(xii) to form a branched or ring may be substituted in good and Ha port Gen atoms, alkynyl group of C ₂ -C _6;

(xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be substituted with at least one group selected from the group (Q);

(xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is optionally substituted with at least one group selected from the group (Q);

(XV) aryl group, where the aryl group is

Group (Q) and one S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom) The alkyl group may be substituted with at least one group selected from the group consisting of: or the 3rd and 4th positions together (CH ₂ ) _m —O— (wherein m is 1 or 2), an aryl group;

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ^2Q may be branched and substituted with a halogen atom) ₄ alkyl group);

A group selected from the group consisting of

Alternatively, in the present invention, it is preferable that R ² and R ² ′ of the quaternary ammonium salt represented by the above formula (1-1) or (1-2) are the same. Alternatively, in the present invention, it is preferable that R ³ and R ³ ′ of the quaternary ammonium salt represented by the above formula (1-1) or (1_2) are the same. Alternatively, in the present invention, it is preferable that R ⁴ and R ⁴ ′ of the quaternary ammonium salt represented by the above formula (1-1) or formula (1-2) are the same. In other words, in the present invention, it is preferable that R ⁵ and R ⁵ ′ of the quaternary ammonium salt represented by the above formula (1-1) or formula (1-2) have the same force S. Alternatively, in the present invention, R ⁶ and R ⁶ ′ of the quaternary ammonium salt represented by the above formula (1-1) or (1-2) are preferably the same. Further, in the above formulas (1-1) and (1-2), R ⁷ and R ⁷ ′ are each independently a monovalent group (for example, a monovalent organic group), or Together, they represent a divalent group (eg, a divalent organic group), and X_ is a halide anion.

Examples of the optically active quaternary ammonium salt represented by the above formula (1-1) or formula (I-12) include, for example, an α-aminonitrinole derivative described below and / or an α-amino acid and its derivative. Stereoselectively (preferably excellent optical purity 78) Useful as a catalyst or stereoselective reaction accelerator in the Strecker reaction for production. More specifically, the α-amino nitrile derivative represented by the formula (II) is obtained by the Strecker reaction using the aldehyde represented by the formula (III) and the amine represented by the formula (IV). For the stereoselective production, the α-amino nitrile derivative represented by the formula (V) is stereoselectively selected by a Strecker reaction using an aldimine derivative represented by Ζ or the formula (VI). When an optically active quaternary ammonium salt represented by the above formula (1-1) or (1-2) is used as a catalyst (for example, a phase transfer catalyst) for production, the quaternary ammonium salt Ammonium part of the cation:

Contributes to cyanation in the Strecker reaction, and the following binaphthyl

(Where R ¹ R ¹ ' _Λ R ² , R ² ', R ³ , R ³ ', R ⁴ , R ⁴ ', R ⁵ , R ⁵ ', R ⁶ and R ⁶ ' are each independently As defined above), or or

(Wherein R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ and R ¹⁰ ′ are each independently the same as the groups defined above). Force Stereoselectivity of the Strecker reaction Donate. Accordingly, in one embodiment, R ⁷ and R ⁷ ′ in the quaternary ammonium salt represented by the formula (1-1) or the formula (1-2) are, in one embodiment, an ammonium moiety and a binaphthyl moiety of the cation. It is a group that can retain the catalytic activity and selectivity derived from the biphenyl moiety (or does not inhibit both the catalytic activity and selectivity). R ⁷ and R ⁷ ′ in the quaternary ammonium salt are, for example, a monovalent organic group or a divalent organic group that is inactive as compared with the ammonium moiety and binaphthyl moiety, or the ammonium moiety and biphenyl moiety. obtain. In other words, R ⁷ and R ⁷ ′ do not have to be reactive groups themselves (or themselves), but in the production of α-amino nitrile derivatives and / or amino acids or their derivatives as described below. Any group that does not adversely affect the reaction may be used. Alternatively, a quaternary ammonium salt represented by the above formula (1-1) or formula (1-2) is a catalyst for stereoselectively producing an α-amino nitrile derivative described later (preferably a phase transfer catalyst). ) In the above formula (1-1) or formula (I 1 2)., R ⁷ and R ⁷ 'are each independently

(i) a C ₁ -C ₃₀ alkyl group which may form a branch or a ring and may be substituted with a halogen atom;

(ii) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _12;

(iii) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _12;

(iv) an aryl group, wherein the aryl group is optionally substituted with at least one group selected from the group (Q);

(V) a heteroaryl group, which is selected from the group (Q) 80 heteroaryl groups optionally substituted with at least one selected group;

(vi)-(CH ₂ ) _n OCONR ²¹ R ²² (where R ²¹ and R ²² are each independently

(1) hydrogen atom,

(2) may be branched and may be substituted with a halogen atom

~C ₄ alkyl group,

(3) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;

(4) a c _{2 to} c ₆ alkynyl group which may form a branch or a ring and may be substituted with a halogen atom;

(5) an aralkyl group, which may be substituted with at least one group selected from the aryl group force group (Q) constituting the aralkyl group;

(6) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is substituted with at least one group selected from the group (Q); a heteroaralkyl group;

(7) an aryl group, wherein the aryl group may be substituted with at least one group selected from the group (Q), an aryl group, and

(8) a heteroaryl group, wherein the heteroaryl group may be substituted with at least one group selected from the group (Q),

(vii) — (CH ₂ ) _n CONR ¹² R ¹³ (where R ¹² and R ¹³ are each independently

(1) hydrogen atom, 81

(2) branched 〇 may be substituted in good and halogen atoms have丄to c ₄ alkyl group,

(3) an aryl group, wherein the aryl group may be substituted with at least one group selected from the group (Q), an aryl group, and

(4) a heteroaryl group, wherein the heteroaryl group may be substituted with at least one group selected from the group (Q),

(1) hydrogen atom,

(3) an aryl group, the aryl group optionally substituted with at least one 1 selected from the group (Q), an aryl group, and

(4) a heteroaryl group, wherein the heteroaryl group may be placed in at least one group selected from the group (Q),

(ix)-(CH ₂ ) _n NR ¹² R ¹³ (where R ¹² and R ¹³ are each independently

(1) hydrogen atom,

(2) branched and may also be optionally substituted by a halogen atom C j -C ₄ alkyl group, 82

(X) — (CH ₂ ) _n Y—OR ¹² (where Y is a divalent saturated hydrocarbon group of Ci C which may be branched, and R ¹² is

(1) hydrogen atom,

(2) branched even if well and halogen atom may be substituted Cj -C ₄ alkyl group,

(4) a heteroaryl group, which may be substituted with at least one group selected from group (Q),

Force, a group selected from a group, and η is an integer from 1 to 12);

(xi)-(CH ₂ ) _n — OR ¹² (where R ¹² is

(1) hydrogen atom,

(4) a heteroaryl group, wherein the heteroaryl group is group (Q) A heteroaryl group optionally substituted with at least one group selected from:

(xii)-(CH ₂ ) _n — S—R ¹² (where R ¹² is

(1) hydrogen atom,

(2) may be branched and may be substituted with C port Gen atom C j -C ₄ alkyl group,

(xiii) — (CH ₂ ) _n — SO— R ¹² (where R ¹² is

(1) hydrogen atom,

A group selected from the group consisting of and n is an integer from 1 to 12); and 84

(xiv)-(CH ₂ ) _n — S〇 ₂ — R ¹² (where R ¹² is

(1) hydrogen atom,

(2) branched even if Ji may and may be substituted with a halogen atom丄-C ₄ alkyl group,

Or a group (monovalent organic group) selected from the group consisting of: or R ⁷ and R ⁷ 'are taken together to form one (CH ₂ ) _m- (where m is from 2 to 8 Is an integer);

R ³³ 85 and R ³⁴ are each independently

Hydrogen atom;

It may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₁ -C ₈ alkyl group;

May be branched or ringed, and or may be substituted with a halogen atom, C ₂ -C ₈ alkenyl group;

It may form a branched or cyclic, and Z or a halogen atom may be substituted, C ₂ -C ₈ alkynyl group;

Or substituted Ji ~ Ji may alkyl force \ halogen atom with optionally substituted c ₁ even though to c ₃ alkoxy group with a halogen atom, an alkyl group optionally Ci C may be substituted with a halogen atom An aryl group that may be substituted with, a cyano group, a halogen atom, a nitro group, or one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom or branched And may be substituted with a halogen atom or an alkyl group) or a cyclic amino group formed of a C _{2 to} C ₈ alkylene group to form a ring, or substituted with (That is, a predetermined substituent A, an aryl group optionally substituted with a C ₄ to C ₄ alkyl group optionally substituted with a halogen atom, or optionally substituted) , Aryl group;

A heteroaryl group having an aryl moiety optionally substituted with a predetermined substituent A;

An aralkyl group having an aryl moiety which may be substituted with a predetermined substituent A;

A heteroara / lequinole group optionally having a heteroaryl moiety optionally substituted with the given substituent A;

(C ₁ -C ₃ alkoxy) carbonyl group;

Strong rubermoyl group; N— (Ji ~. Alkyl) Forced rubermoyl group;

N, N-di (Ci C alkyl) force rubermoyl group (wherein the C _{1 to} C ₄ alkyl groups may be the same or different from each other) and are selected from the group consisting of:

Represents a divalent group (divalent organic group) selected from the group consisting of forces.

Alternatively, in the present invention, R ⁷ and R ⁷ ′ of the quaternary ammonium salt represented by the above formula (1-1) or formula (1-2) each independently form a branch or a ring. It is preferably an alkyl group of C 丄 to ^ which may be substituted with a halogen atom. Further preferred R ⁷ and R ⁷ ′ are each independently an alkyl group which may be branched or formed a ring and may be substituted with a halogen atom, or a branch or A C _{13 to} C ₃₀ alkyl group which may form a ring and may be substituted with a halogen atom (even more preferably, it may form a branch or a ring and may be substituted with a halogen atom) Good C ₁₃ -C ₂₂ alkyl group). Alternatively, in the quaternary ammonium salt represented by the above formula (1-1) or formula (1-2), R ⁷ and R ⁷ ′ may each independently form a branch or a ring and The lower limit of the number of carbon atoms constituting the alkyl group which may be substituted with a halogen atom is preferably 1 or more, more preferably 3 or more, or preferably 13 or less. Furthermore, still more preferably 15 or more, still more preferably 17 or more, still more preferably 18 or more, and the upper limit of the number of carbon atoms constituting the alkyl group is preferably 30 or less, more preferably The force is 22 or less, more preferably 21 or less, and even more preferably 20 or less, or preferably 12 or less, more preferably 8 or less, and even more preferably 5 or less.

Alternatively, in the present invention, it is represented by the above formula (1-1) or formula (1-2). It is preferable that the force is the same as R ⁷ and R ⁷ 'of the quaternary ammonium salt. The quaternary ammonium salt represented by the above formula (1-1) or formula (1-2) used in the present invention and a production method thereof are disclosed in, for example, JP-A-2001-48866 and JP-A-2002-326992. JP-A 2003-81976, WO 2005/0073196, etc. are known to those skilled in the art.

Alternatively, among the quaternary ammonium salts used in the present invention, some of the quaternary ammonium salts included in the formula (I 1-2) (hereinafter referred to as quaternary ammonium salts (I-2a) or The compound (may be abbreviated as 1-2a) can be produced, for example, as follows.

The quaternary ammonium salt (I-2a) used in the present invention is, for example, the following formula (V I I)

In the presence of an acid scavenger in an organic solvent, the compound represented by

The following formula (VIII)

In where _c that represented can be prepared by reacting a secondary Amin, in the above formula (VII),

R ⁸ , R ⁸ ', R ⁹ and R ⁹ ' are each independently

Is a hydrogen atom;

Is a halogen atom; A C ₁ to C ₅ alkyl group which may be substituted with a halogen atom and a z or aryl group, and may form a no or branched or ring; or

A C ₁ -C ₅ alkoxy group which may be substituted with a halogen atom and / or an aryl group and which may form a no or branched or ring;

R ^1Q and R ^1Q 'are independently

Is a halogen atom;

It may be substituted with a halogen atom Contact Yopi / or Ariru group, and Roh or may form a branched or ring, or a C -C ₅ alkyl group;! Or

A Cr Cs alkoxy group that may be substituted with a halogen atom and a Z or aryl group, and may form a no or branched or ring;

R ¹ and R ¹ 'are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom, or may be branched and substituted with a halogen atom). Is based)

(iii) a cyano group;

(iv) a ditro group;

(V) force rubermoyl group;

(vi) N- (C ₁ -C ₄ alkyl) strong rubamoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom) 89);

(ix) a halogen atom;

(X) an alkyl group of c _{1 to} c ₆ which may form a branch or a ring and may be substituted with a halogen atom;

(xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety may be substituted with at least one group selected from the group (Q);

An (XV) aryl group, wherein the aryl group may be substituted with at least one group selected from the group (Q), or the 3, 4 positions are combined An aryl group optionally substituted by 0_ (CH ₂ ) _p -O- (wherein p is 1 or 2);

(xvi) a heteroaryl group, which is optionally substituted with at least one group selected from the group (Q); and

(xvii)-S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ^2Q may be branched and substituted with a halogen atom) ~C ₄ alkyl group);

A group selected from the group consisting of and

Z is a halogen atom. 90 On the other hand, in the above formula (VIII),

Shaku ⁷ shobi 1 ⁷ 'each independently

(i) an alkyl group which may form a branch or a ring and may be substituted with a halogen atom;

(ii) a C _{2 to} C ₁₂ alkenyl group which may form a branch or a ring and may be substituted with a halogen atom;

(V) a heteroaryl group, wherein the heteroaryl group may be substituted with at least one group selected from the group (Q);

(vi) — (CH ₂ ) _n OCONR ²¹ R ²² (where R ²¹ and R ²² are independently

(1) hydrogen atom,

(2) ^ · may be branched and substituted with a halogen atom to a C ₄ alkyl group,

(3) to form a branched or ring may be substituted with at best or halogen atom, an alkenyl group of C ₂ -C _6;

(4) may form a branched or cyclic and may be toying substituted with a halogen atom, an alkynyl group of C ₂ -C _6;

(5) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be substituted with at least one group selected from the group (Q), an aralkyl group;

(6) A heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is substituted with at least one group selected from the group (Q) 91 may be a heteroaralkyl group;

(1) hydrogen atom,

(3) an aryl group, which is selected from the group (Q) An aryl group optionally substituted with at least one group, and

(1) hydrogen atom,

(2) Ci which may be branched and may be substituted with a halogen atom

~C ₄ alkyl group,

(X) — (CH ₂ ) _n Y—OR ¹² (where Y is a C ₁ -C ₄ divalent saturated hydrocarbon group which may be branched, and R ¹² is

(1) hydrogen atom,

(4) a heteroaryl group, wherein the heteroaryl group is group (Q) A heteroaryl group optionally substituted with at least one group selected from

(xi)-(CH ₂ ) _n -OR ¹² (where R ¹² is

(1) hydrogen atom,

(2) branched optionally substituted in well and halogen atoms have C丄-C ₄ alkyl group,

(xii)-(CH ₂ ) _n -SR ¹² (where R ¹² is

(1) hydrogen atom,

(2) branched even if Ji may and may be substituted with a halogen atom -C ₄ alkyl group,

A group selected from the group consisting of, and n is an integer from 1 to 1 2); (xiii)-(CH ₂ ) _n — SO— R ¹² (where R ¹² is

(1) hydrogen atom,

(xiv)-(CH ₂ ) _n -S0 ₂ -R ¹² (where R ¹² is

(1) hydrogen atom,

A force \ which is a group selected from the group consisting of

R ⁷ and R ⁷ 'together are one (CH ₂ ) _a- (where m is an integer from 2 to 8);

(Wherein R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ , R ²⁹ , R ³² , R ³³ and R ³⁴ are each independently defined for the above compound (1-2) The same as

It represents a divalent group selected from the group consisting of forces.

In the present invention, all of R ⁸ , R ⁸ ′, RR ⁹ ′, R ¹⁰ , and R ¹⁰ ′ of the quaternary ammonium salt (1-2a) preferably form a branch or a ring. Or a C ₁ -C ₅ alkoxy group which may be substituted with a halogen atom. In consideration of easy availability or synthesis, all of R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ , and R ¹ ^Q ′ of the compound represented by the formula (VII) are measurable. A toxi group is preferred.

Alternatively, in the present invention, R ¹ and R ¹ ′ forces of the compound represented by the above formula (VII) are preferably independently

(XV) aryl group, wherein the aryl group may be substituted with at least one group selected from group (Q), or the 3rd and 4th positions are combined O— (CH ₂ ) _p -O- (where p is 1 or 2) 96 may be substituted, aryl group;

It is.

The compound of the above formula (V I I) can be synthesized using, for example, the following first method, second method, or third method.

As the first method, first, the following formula (I X):

(Wherein R ⁸ , 19 ^{9 and} 11 ⁽⁾ are each independently the same as the group defined above) and a compound represented by the above is dissolved in an organic solvent (eg, black mouth form). Add N-bromosuccinimide (NBS) to the solution and heat under reflux. As a result, a compound of the formula (X) in which the 2-position is brominated can be obtained. A specific example of the compound of formula (IX) is 3, 4, 5-trimethoxybenzoic acid, which is commercially available from Aldrich, for example.

Next, the compound of formula (X) obtained above is converted into acid chloride by reacting with (i) SOC l ₂ for example, and then (ii) (S) — or (R ) — 1, 1 ′ —Bi-2-naphthol can be reacted to obtain a compound of the following formula (XI). In this reaction,

By using either (S) — 1, 1, 1-bi-2-naphthol or (R) — 1, 1 '-bi-2-naphthol,

The absolute configuration (S form or R form) of the compound of (VII) can be easily selected. 97

In the above description, an example using one type of compound represented by the formula (X) has been described, but the present invention is not particularly limited thereto. In addition to the compound of the formula (X), a compound represented by the formula (X) but different from each other (that is, having R ⁸ 'instead of R ⁸ (different from R ⁸ ) and replacing R ⁹ using 'have, and Roh or in place of R ^1C) differs from ^{^{(R 1Q) R 1 Q'}} ( different from R ⁹⁾ R ⁹ having the formula (X) compound) to By the following formula (XI) ':

Compound represented by (XI) '(wherein R ⁸ , R ⁸ ', R ⁹ , 'R ⁹ ', R ¹⁰ and R ¹⁰ 'are each independently the same as defined above) Can also be easily manufactured.

When referring to the compound represented by the formula (XI) again, the compound of the formula (XI) obtained above is then heated and refluxed with active copper powder suspended in an organic solvent (for example, DMF). Can be converted to a compound represented by the formula (XII) coupled within the molecule. The compound represented by the formula (XII) is added to a THF suspension containing lithium aluminum hydride and stirred for a predetermined time. 98

(XI) (XII) (XIII) Further, by reacting the biphenyldimethanol compound represented by the formula (XIII) with a halogenating agent such as phosphorus tribromide (PB r ₃ ), XIV) (that is, a compound included in the above formula (VII), in which R ¹ and R ¹ ′ are both hydrogen atoms) can be obtained.

(XIII) (XIV)

(Where Z is a halogen atom) In the present invention, among the compounds represented by the formula (VII), when it is desired to obtain a compound in which R ¹ and R ¹ ′ are hydrogen atoms, The compound of the above formula (XIV) can be used as it is. On the other hand, among the compounds represented by the above formula (VII), when it is desired to obtain a compound in which 1 ^{1 and} 1 ¹ ′ are groups other than a hydrogen atom, the above formula ( The compound of VII) can be produced. For simplicity, the case where R ¹ and R ¹ ′ are the same will be described.

Reaction Scheme 1> Referring to Reaction Scheme 1 above, the compound represented by the formula (X I V) thus obtained is dehalogenated by means well known in the art, and the formula

The compound of (XV) is used. Next, the compound represented by the formula (XV) is dissolved in an organic solvent such as pyridine, and bromine is added thereto, whereby the 3-position and the 3′-position are represented by the formula (XVI). Can be converted to a compound.

Thereafter, the compound of formula (XVI) is represented by R ¹ — B (OH) ₂ or R ¹ ′ — B (OH) ₂ in the presence of a palladium catalyst in an organic solvent such as THF. It is subjected to a Suzuki-Miyaura coupling reaction with certain boronic acid derivatives, where R ¹ and R are each independently the same as defined above. This produces a compound of formula (XV II) in which the bromine atoms at the 3 and 3 'positions are replaced by R ¹ or R groups. The resulting compound of formula (XV II) is finally halogenated by means well known in the art, and R ¹ (and Z or R ¹ ′) is a group other than a hydrogen atom. The compound represented by these can be manufactured. Next, the second method for synthesizing the compound of the above formula (VII) will be described.

The second method uses a commercially available ellagic acid as a starting material. That is, using the starting material, the following formula (XV III) can be obtained by the method of 0. T. Schmidt et al. ):

(XVIII)

(Wherein R ⁸ , R ⁹ and R ^1D are the same as the groups defined above), an optically active form of a dicarboxylic acid compound represented by Alternatively, the compound represented by the above formula (XV III) can also be obtained, for example, by treating the compound represented by the above formula (XII) with a basic aqueous solution. According to these methods, either the S-form or R-form of the compound represented by the above formula (XV III) can be selectively produced. Thereafter, the compound of the above formula (VII) can be produced through the following reaction scheme 2. For simplicity, the case where R ¹ and R ¹ ′ are the same will be described. 101

<Reaction Scheme 2> Referring to Reaction Scheme 2 above, for the obtained compound of formula (XV III), the dicarboxylic acid moiety of the compound is divalent with BH 3 · Me ₂ S in an organic solvent such as THF. Converted to methanol (compound represented by formula (XIX)). The compound of formula (XIX) is then reacted with bromine in an organic solvent such as pyridine to produce a compound of formula (XX) in which the 3rd and 3 'positions are brominated.

Thereafter, the compound of the formula (XX) is represented by R ¹ — B (OH) ₂ or R ¹ ′ -B (OH) ₂ in the presence of a palladium catalyst in an organic solvent such as THF. The boronic acid derivatives of the species (wherein R ¹ and R ¹ ′ are each independently the same as the groups defined above) and Suzuki-Miyaura coupling reaction. This produces a compound of formula (XX I) in which the bromine atoms at positions 3 and 3 are replaced by R ¹ or R groups. 102 The resulting compound of formula (XX I) is finally reacted with a halogenating agent such as phosphorus tribromide (PB r ₃ ) so that R ¹ (and R ¹ ') It can be converted to a compound represented by the above formula (VII) which is a group other than

Next, the third method for synthesizing the compound of the formula (V I I) used in the present invention will be described.

The third method is similar to the second method in the following formula:

(XVIII)

(Wherein R ⁸ , R ⁹ and R ^1Q are the same as the groups defined above), and a method using an optically active form of a dicarboxylic acid compound represented by Through the following reaction scheme 3, the compound of the above formula (VII) is produced. For simplicity, the case where R ¹ and R ¹ ′ are the same will be described.

103

<Reaction Scheme 3> Referring to Reaction Scheme 3 above, for the obtained compound of formula (XV III), the dicarboxylic acid moiety of the compound is halogenated in the presence of an organic base in an organic solvent such as acetone. Converted to ester (compound represented by formula (XXX)) by alkyl. In addition, with respect to the obtained compound of the formula (XV III), the dicarboxylic acid part of the compound is treated with thionyl chloride to obtain an acid chloride, and then treated with an alcohol in the presence of an organic base such as pyridine. As a result, it is converted to an ester (compound represented by the formula (XXX)). The compound of formula (XXX) is then reacted with bromine in an organic solvent such as acetonitrile to produce a compound of formula (XXX I) brominated at the 3 and 3 ′ positions.

Thereafter, the compound of formula (XXX I) is represented by at least 1 represented by R — B (OH) ₂ or R ¹ ′ -B (OH) ₂ in the presence of a palladium catalyst in an organic solvent such as DME. A boronic acid derivative of the species (where R ¹ and R ¹ 'are each 104 independently, as defined above) and subjected to Suzuki-Miyaura coupling reaction. More specific examples of the boronic acid derivative include 3,4,5-trifluorophenylboronic acid. This produces a compound of formula (XXX II) in which the bromine atoms at the 3 and 3 'positions are substituted with R ¹ or R groups.

Further, the obtained compound of the formula (XXX II) is reduced with dimethanol (formula (LA XX I)).

The resulting compound of the formula (XX I) is finally reacted with a halogenating agent such as phosphorus tribromide (PB r ₃ ) so that R ¹ (and Z or R ¹ ') It can be converted to a compound represented by the above formula (VII) which is a group other than

Thus, the compound of the above formula (V I I) can be efficiently produced using the first method, the second method, or the third method.

On the other hand, in the method for producing the quaternary ammonium salt (I-2a) used in the present invention, many of the secondary amines of the above formula (VIII) are commercially available and are easily available. It can be selected appropriately.

Examples of the organic solvent used in the reaction process for the production of the quaternary ammonium salt (1-2a) used in the present invention include nitrile solvents (for example, acetonitrile, propionitrile, etc.), ether solvents ( For example, dioxane, tetrahydrofuran, isopropyl etherol, jetyl ether, dimethoxyethane, 2-methoxetyl ether, alcohol solvents (eg, methanol, ethanol, n-propanol, isopropanol, n-butanol) And tert-butanol). In the present invention, in particular, acetonitrile is preferable. Acid scavengers include potassium carbonate and sodium carbonate. 105 Inorganic bases such as thorium, potassium bicarbonate, sodium bicarbonate.

In the above reaction, the secondary amine of the formula (V I I I) is preferably used in an amount of 0.9 to 4 equivalents, more preferably 1 to 3 equivalents, relative to the compound of the formula (V I I). The acid scavenger is preferably used in an amount of 1 to 4 equivalents, more preferably about 1 to 2 equivalents, relative to the compound of formula (V I I). The reaction of the compound of formula (V I I) with the secondary amine of formula (V I I I) is carried out in the presence of an acid scavenger with stirring in a suitable organic solvent. The reaction temperature is preferably from room temperature to the boiling point of the organic solvent, and more preferably the reaction is carried out under heating and reflux. The reaction time is preferably 30 minutes to 24 hours, more preferably 6 to 12 hours. At this time, the organic solvent is preferably used in an amount of 5 to 50 times, more preferably 5 to 30 times the volume (mL) Z mass (g) ratio with respect to the compound of formula (V I I). After completion of the reaction, the reaction mixture is isolated and purified by extraction with dichloromethane, dichloroethane, chloroform, etc., silica gel force chromatography, etc. to obtain the quaternary ammonium salt (I-2a) used in the present invention. Obtainable.

The compound of the quaternary ammonium salt (I-2a) in which X thus obtained is a halide anion is in a pure form with respect to axial asymmetry, and is a catalyst (eg, , Phase transfer catalyst). Here, “pure with respect to axial asymmetry” means that, among various isomers considered based on axial asymmetry, the presence of one specific isomer is higher than that of other isomers. Preferably, the specific one abundance of the isomer is 90% or more, more preferably 95% or more, and even more preferably 98% or more.

Alternatively, the catalyst that can be used in the Strecker reaction of the present invention is represented by the following formula (I-1b) or formula (I-2b): 106

(I-1 b) It consists of a quaternary ammonium salt represented by either (I -2 b).

here,

In formula (I 1 1 b) and formula (I-2b),

R ¹ and R ¹ 'are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom, or may be branched and may be substituted with a halogen atom, C _{1 to} C _{4 is} an alkyl group)

(iii) a cyano group;

(iv) a ditro group;

(V) force rubermoyl group;

(vi) N- (C ₁ -C ₄ alkyl) strong rubamoyl group;

(vii) N, N-di (di-alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom);

(ix) a halogen atom;

(X) a C ₁ to C ₆ alkyl group which may form a branch or a ring and may be substituted with a halogen atom; (Xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;

(xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety may be substituted with at least one group selected from the group (Q); a heteroaralkyl group;

(XV) aryl group, wherein the aryl group may be substituted with at least one group selected from the group (Q), or the 3, 4 position is combined _0_ (CH ₂ ) _p -0- (where p is 1 or 2) may be replaced by an aryl group;

(xvii) -S (O) _n -R ²⁰ (where n is 0, '1, or 2, and R ² ° may be branched and substituted with a halogen atom) ci -C ₄ alkyl group);

A group selected from the group consisting of:

R ^7b and R ^7b ′ are each independently (i) an alkyl group which may form a branch or a ring and may be substituted with a halogen atom, and X is a halogen atom. An atom, and

X is a halogenated anion.

Furthermore, in the above formulas (I 1 1 b) and (I-2 b), R ⁸ , R ⁸ ', R ⁹ and R ⁹ ' are each independently

Is a hydrogen atom;

Is a halogen atom;

A Ci Cs alkyl group which may be substituted with a halogen atom and / or an aryl group and / or may form a branch or a ring; or

A C ₁ -C ₅ alkoxy group that may be substituted with a C atom atom and a no or aryl group and / or may form a branch or ring; and

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom, or may be branched and substituted with a halogen atom). An alkyl group);

(iii) a cyano group;

(iv) nitro;

(V) canolemoyl group;

_{(vi) N- (C 1 ~C} 4 alkyl) Karupamoiru group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or an alkyl group which may be branched and may be substituted with a halogene atom);

(ix) a halogen atom;

) May form a branched or cyclic and may be substituted with a halogen atom, an alkyl group of C ₁ -C _6; (Xi) may form a branched or cyclic and may be substituted with a halogen atom, an alkenyl group of C ₂ -C _6;

(XV) aryl group, where the aryl group is

Group (Q) and one S (O) _n -R ²⁰ where n is 0, 1, or 2 and R ^2G may be branched and substituted with a halogen atom Ci Which may be substituted with at least one group selected from the group consisting of ˜C ₄ alkyl groups), or O— (CH ₂ ) _m −0- ( Where m is 1 or 2) and may be substituted with les, aryl groups;

It is a group selected from the group consisting of forces.

The quaternary ammonium salt represented by the above formula (1-1b) or formula (I 1-2b) can be produced, for example, as follows. 110 First, the following formula (XX II 1 1 b) or formula (XX II

(XX I I 1 b) (XX I I-2 b)

(Where R ¹ R ¹ *, R ² , R ² ', R ³ , R ³ ', R ⁴ , R ⁴ ', R ⁵ , R ⁵ ',

R ⁶ , R ⁶ ′, R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ and R ¹⁰ ′ are each independently the same as defined above, and R ^5G and R ⁵ ° ′ Each independently may form a branch or ring and may be substituted with a haguchigen atom

C ₁ -C ₁₂ alkyl group) is reacted in a solvent in the presence of tetramethylpiperidinemagnesium (Mg (TMP) ₂ ), and bromine is added. Formula (XX III-1 b) or Formula (XX

I I I-2 b):

(XX I I I 1 b) (XX I I I-2 b)

(Where R ² , R ² ′, R ³ , R ³ ′, R ⁴ , R ⁴ ′, R ⁵ , R ⁵ ′, R ⁶ , R ⁶ ′, R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ , R ¹⁰ ′, R ⁵⁰ , and R ⁵⁰ ′ are each independently the same as the groups defined above). The compound represented by the above formula (XX II—lb) or the compound represented by the above formula (XX I 1-2b) is, for example, the following formula:

The known dicarboxylic acid represented by the above formula can be easily obtained by esterification by a method well known to those skilled in the art.

A compound represented by the above formula (XX I I—l b) or a compound represented by the above formula (XX I I-2 b), and tetramethylpiperidine magnesium (Mg (T

The solvent used in the reaction with MP) ₂ ) is not particularly limited, but is preferably an organic solvent, and examples thereof include tetrahydrofuran (THF).

The amount of the compound represented by the above formula (XX II-1b) or the formula (XX I 1-2b), tetramethylpiperidinemagnesium, and bromine with respect to the solvent to be used is not particularly limited. Usage can be set. Furthermore, the above reaction can be carried out at a temperature of preferably room temperature or lower, more preferably 1 1 to 1 85 ° C. '

In this way, a compound represented by the above formula (XX I I I 1 b) or formula (XX I I I -2 b) can be obtained. The obtained compound represented by the formula (XX II 1-1 b) or the formula (XX III -2 b) is purified by means known to those skilled in the art (for example, column chromatography), if necessary. May be performed.

Next, by reacting the compound represented by the formula (XX III-1b) or the formula (XX III-2b) with a metal hydride in a solvent, the following formula (XX IV-1b) Or the formula (XX IV— 2 b): 112

(XX I V- 1 b) (XX I V- 2 b)

(Where R ² , R 2 R ³ , RR ⁴ , R ⁴ ', R ⁵ , R ⁵ ', R ⁶ , R ⁶

R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ , and R ¹⁰ ′ are each independently the same as the group defined above).

The metal hydride that can be used in the above process using the compound represented by the formula (XX III-1b) or the formula (XX III-2b) is not particularly limited, but for example, diisobutylaluminum hydride. (DI BAH), and lithium aluminum hydride. It is preferable to use diisobutylaluminum hydride because the reaction in the above process is relatively easy to proceed.

The solvent that can be used in the above step using the compound represented by the formula (XX III-1b) or the formula (XX III-2b) is not particularly limited, but is preferably an organic solvent. Examples thereof include black mouth form, dichloromethane, tetrahydro mouth furan, methyl t-butyl ether (MTBE), and cyclopentinole methyl ether (CPME).

The amount of the compound represented by the above formula (XXIIII-1b) or the formula (XXIIII-2b) and the metal hydride to the solvent to be used can be arbitrarily set by those skilled in the art. Furthermore, the above reaction can be carried out preferably at room temperature or less, more preferably at a temperature of -5 to 5 ° C.

In this way, the above formula (XX IV— 1 b) or formula (XX IV— 2 b) 113 can be obtained. The obtained compound represented by the formula (XX IV—lb) or the formula (XX IV—2 b) can be purified using means well known to those skilled in the art (for example, column chromatography), if necessary. May be done.

Next, by reacting the compound represented by the formula (XX IV— lb) or the formula (XX IV— 2 b) with PB r ₃ in a solvent, the following formula (XXV — 1 b) or formula ( XXV— 2 b):

(XXV- 1 b) (XXV- 2 b)

^{^{(Wherein, R 2, R 2, R}} 3, R 3, R 4, R 4, R 5, R., R 6, R., R 8, R 8 ', R 9, R 9', R 10 , And R ¹⁰ ′ are each independently the same group as defined above).

The solvent that can be used in the above step using the compound represented by the formula (XX I V — lb) or the formula (XX I V — 2 b) is not particularly limited, but is preferably an organic solvent. And dichloromethane. The amount of the compound represented by the above formula (XX IV—lb) or the formula (XX IV—2 b) and PB r ₃ with respect to the solvent to be used can be arbitrarily set by those skilled in the art. Furthermore, the above reaction can be carried out preferably at a temperature below room temperature, more preferably from 15 to 5.

In this way, a compound represented by the above formula (XXV—lb) or formula (XXV—2b) can be obtained. The resulting formula (XXV—lb) or formula 114

The compound represented by (XXV-2b) may be purified using means well known to those skilled in the art (for example, column chromatography), if necessary. Then, the equation (XXV- lb) or Formula (XXV- 2 b) represented by reduction compounds, the solvent, R ^7b - by reaction with NH _2, the following formula (XXV I- 1 b

(XXV I— l b) (XXV I— 2 b)

(Where R ² , R ² ′, R ³ , R ³ ′, R ⁴ , R ⁴ , R ⁵ , R., R ⁶ , R ⁶ , R ⁸ , R ⁸ ′, R ⁹ , R ⁹ ′, R ¹⁰ and R ¹⁰ ′ are each independently the same as defined above, and R ^7b may form a branch or a ring and may be substituted with a halogen atom. compounds represented by ~ Ji ₃₀ alkyl group) is synthesized.

The formula (XXV- lb) or may be used in Equation (XXV- 2 b) are use of the compound represented by the above process, R ^7b - the compound represented by NH ₂ (wherein, R ^{7 b} is a branched Or an alkyl group of from ₃₀ to ₃₀ which may be ring-formed and may be substituted with a halogen atom) is, for example, methylamine, ethylamine, n-propylamine, n_ptylamine and isobutyl Amins are mentioned. Methylamine is preferably used because the reaction in the above process tends to proceed relatively smoothly.

The solvent that can be used in the above step using the compound represented by the formula (XXV—lb) or the formula (XXV — 2 b) is not particularly limited, but is preferably an organic solvent, such as tetrahydrafuran. . 115 The above formula for the solvent used (XXV- lb) or Formula (XXV_ 2 b) compounds and R ⁷ represented by ^b - the amount of the compound represented by NH ₂ particularly limited Sarezu, those skilled in the art optionally Usage can be set. Further, the above reaction can be carried out at a temperature of preferably room temperature or lower, more preferably from 15 ° C to 5 ° C.

In this way, a compound represented by the above formula (XXV I—l b) or formula (XXV I—2 b) can be obtained. The obtained compound represented by the formula (XXV I—lb) or the formula (XXV I—2 b) can be purified by means known to those skilled in the art (for example, column chromatography), if necessary. You can do it.

Next, the compound represented by the formula (XXV I-1 b) or the formula (XXV I-2 b) is reacted with Rt- B (OH) ₂ or R ¹ 'in a solvent in the presence of a palladium catalyst. — By reacting with at least one boronic acid derivative represented by B (OH) ₂ (wherein R ¹ and R ¹ ′ are each independently the same group as defined above), The following formula (XXV II-1 b) or formula (XXV II-2 b):

(XXV I I— l b) (XXV I I— 2 b)

(Where R ¹ R ¹ ′, R ² , R ² ′, R ³ , R ³ ′, R ⁴ , R ⁴ ′, R ⁵ , R ⁵ ′, R ⁶ , R ⁶ ′, R ⁸ , R ⁸ ', R ⁹ , R ⁹ ', R ¹⁰ , R ¹⁰ 'and R ^7b are each independently the same as the group defined above). The compound represented by the formula (XXV—lb) or formula (XXV—2 b) is used. The above process is called a so-called Suzuki Miyaura coupling reaction, which is known to those skilled in the art.

The boronic acid derivative used in the above step is not particularly limited. 4 bis (4-trifluoromethylphenyl) 1 1-naphthylboronic acid. These boronic acid derivatives are known per se and are commercially available, or T. Kara ikawa et al., Tetrahedron Letters, 1997, 38, p. 7087-7090 or J. Yin et al., Journal. Those skilled in the art can easily synthesize them from the method described in the American Chemical Society, 2000, 122, p.12 051-12052.

Examples of palladium catalysts that can be used in the above process include tetrakis triphenylphosphine palladium catalyst (P d (PPh ₃ ) ₄ ); and palladium acetate (P d (OAc) ₂ ) and triphenylphosphine (PP h ₃ ) and a catalyst generated by adding to the reaction system. Further, the solvent that can be used is not particularly limited, but is preferably an organic solvent, and examples thereof include dimethylformamide (DMF).

The amount of the compound represented by the above formula (XXV I _lb) or the formula (XXV 1-2 b), the boronic acid derivative, and the palladium catalyst used with respect to the solvent to be used is not particularly limited, and can be arbitrarily determined by those skilled in the art The usage amount can be set. Furthermore, the reaction can be carried out preferably under reflux, more preferably at a temperature of 80 ° (: ˜10).

In this way, a compound represented by the above formula (XXV II—lb) or formula (XXV I 1-2b) can be obtained. The obtained compound represented by the formula (XXV I 1-1b) or the formula (XXV II-2b) is purified by means well known to those skilled in the art (for example, column chromatography), if necessary. Can be done. 117 After that, the compound represented by the formula (XXV II-1 b) or the formula (XXV II-2 b) is R ^7b ′ —X (where R ^7b ′ is as defined above) in a suitable solvent. It is made to react with the alkyl halide represented by these. Specific examples of the alkyl halide include, for example, methyl iodide.

The amount of the alkyl halide used for the compound represented by the formula (XXV I I-1b) or the formula (XXV I I 1 2b) can be arbitrarily set by those skilled in the art. Furthermore, the above reaction can be preferably carried out at room temperature.

In this way, a quaternary ammonium salt represented by the formula (I-1b) or the formula (I_2b), which is a catalyst capable of stereoselectively progressing the Strecker reaction, can be obtained. The obtained quaternary ammonium salt may be purified using means well known to those skilled in the art (for example, column chromatography), if necessary.

The quaternary ammonium salt used in the present invention is preferably in a pure form with respect to axial asymmetry. Here, “pure with respect to axial asymmetry” means that among various stereoisomers considered based on axial asymmetry, the presence of one specific isomer is higher than that of the other isomers. Preferably, the specific one existing ratio of the isomer is 90% or more, more preferably 95% or more, and still more preferably 98% or more. Furthermore, the quaternary ammonium salt used in the present invention can function as a catalyst (preferably a phase transfer catalyst) in a Strecker reaction.

Note that the catalyst of the present invention that can cause the Strecker reaction to proceed stereoselectively is not necessarily limited to the optically active quaternary ammonium salt included in the above formula (I-1) or formula (1-2). For example, other optically active quaternary ammonium salts (including optically active cinchona alkanoide type quaternary ammonium salts) and optically active phase transfer catalysts complexed with metal or metal atoms, etc. Also

(Wherein R is H or an aryl group and Z is C 1 or Br in the above formula representing the other optically active quaternary ammonium salt) 119

, Or

And optically active quaternary ammonium salts represented by 120

Next, a method for producing an α-amino nitrile derivative in a stereoselective manner using the optically active quaternary ammonium compound represented by the formula (1-1) or the formula (1-2) as a phase transfer catalyst. An example (hereinafter sometimes referred to as method (Α)) will be described.

The amideaminotolyl derivative that can be produced by the method (ii) of the present invention includes, for example, the following formula (II):

(here,

R ⁴¹ is

(1) an alkyl group that may form a branch or a ring, and / or may be substituted with a halogen atom;

(2) may form a branched or cyclic, and Ζ or halogen atom may be substituted, C ₂ -C ₂₀ alkenyl group;

(3) may form a branched or cyclic, and / or halogen atoms may be substituted, C ₂ -C ₂₀ alkynyl group;

(4) a predetermined substituent A, an aryl group which may be substituted with an alkyl group, an aryl group which may be substituted with an alkyl group, or an aryl group;

(5) a heteroaryl group having an aryl moiety that may be substituted with a predetermined substituent A;

(6) an aralkyl group having an aryl moiety which may be substituted with a predetermined substituent A;

(7) a heteroaralkyl group which may be substituted with a predetermined substituent A and has a heteroaryl moiety; 121

(8) (C ₁ ~C ₃ alkoxy) carbonyl group;

(9) force rubamoyl group;

(10) N- (C ₁ -C ₄ alkyl) strong rubamoyl group; and

(11) N, N-di (Ci C alkyl) carbamoyl group (wherein the C ₁ to C ₄ alkyl groups may be the same or different from each other) and are selected from the group consisting of:

Represents a group selected from the group consisting of

R ⁴² is

(1) a hydrogen atom;

(2) may form a branched or ring, optionally substituted with Oyopi or halogen atom, C ₁ -C ₂₀ alkyl group;

(3) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₁ -C ₈ alkoxy group;

(4) may form a branched or cyclic, and or may be substituted by halogen atom, C ₂ -C ₂₀ alkenyl group;

(5) may form a branched or cyclic, and or may be substituted by halogen atom, C ₂ -C ₂₀ alkynyl group;

(6) a predetermined substituent A, an aryl group that may be substituted with a Ci to C ₄ alkyl group that may be substituted with a halogen atom, or an aryl group that may be substituted with

(7) A heteroaryl group having an aryl moiety that may be substituted with a predetermined substituent A;

(8) an aralkyl group having an aryl moiety which may be substituted with a predetermined substituent A;

(9) a heteroalkenyl / le group having a heteroaryl moiety which may be substituted with a predetermined substituent A; 122

(10) (C ₁ ~C ₃ alkoxy) carbonyl group;

(11) force rubamoyl group;

(12) N- (C ₁ -C ₄ alkyl) strong rubamoyl group;

(13) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group (wherein the same ₄ alkyl group may be the same or different from each other) is a group selected from the group consisting of ;; And

(14) -S0 ₂ R ⁴³

(Where R ⁴³ is

(ii) may form a branched or cyclic, and / or halogen atoms may be substituted, C ₂ -C ₈ alkenyl group;

(iii) may form a branched or cyclic, and or halo gen atoms may be substituted, C ₂ -C ₈ alkynyl group;

(iv) a predetermined substituent A or an aryl group that may be substituted with C to the same alkyl group that may be substituted with a halogen atom; an aryl group that may be substituted with an aryl group;

(V) a heteroaryl group having an aryl moiety which may be substituted with a predetermined substituent A;

(vi) an aralkyl group having an aryl moiety which may be substituted with a predetermined substituent A;

(vii) a heteroaralkyl group having a heteroaryl moiety, which may be substituted with a predetermined substituent A;

(viii) (C ₁ ~C ₃ alkoxy) carbonyl group;

(ix) force rubermoyl group;

(x) N- (di-alkyl) strong rubermoyl group; or (xi) N, N-di (dialkyl) rubamoyl group (wherein the alkyl group may be the same or different from each other) is a group selected from the group consisting of: ;

Is)

Represents a group selected from the group consisting of and

* Represents an asymmetric center).

The method (A) of the present invention will be described in detail. The c-amino nitrile derivative represented by the above formula (II) is represented by the following formula (III):

And the following formula (IV):

_R 42

An amine represented by H ₂ N _(IV) and an optically active quaternary ammonium salt represented by the above formula (1-1) or formula (1 _2) in the presence of an alkali metal cyanide and an acid It can be produced by reacting in a solvent containing it (for example, in a solvent containing or suspending the optically active quaternary ammonium salt). here,

In formula (III), R ⁴¹ is the same as defined above,

In the formula (IV), R ⁴² is the same as defined above.

In the method (A) of the present invention, examples of the aldehyde represented by the formula (III) include η-butyl aldehyde, n-pentyl aldehyde, benzaldehyde, cyclopentylcarboxaldehyde, pivaloaldehyde, and An example is octaoctanecarboxaldehyde. Examples of the amine represented by the formula (IV) include aniline, p-methoxyaniline, benzylamine, butylamine, and allylamin. · 124 The above alkali metal cyanide is a kind of cyanating agent used in the overall Strecker reaction, and examples thereof include lithium cyanide, sodium cyanide, and potassium cyanide. Furthermore, examples of the acid include weak acids such as formic acid and acetic acid. Preferably, water is used as a solvent, and the acid is preferably used in the form of an aqueous solution. This is to increase the solubility of the aldehyde of formula (III) and / or the amine of formula (IV).

Aldehyde of formula (III), amine of formula (IV), alkali in the presence of the above acid and an optically active quaternary ammonium salt represented by formula (I 1 1) or formula (I 1 2) The amount of these reaction components used in the reaction of the metal cyanide can be appropriately set by those skilled in the art. In addition, the reaction temperature in this reaction can also be appropriately set by those skilled in the art.

According to the method (A) of the present invention, the α-amino nitrile derivative represented by the desired formula (I I) can be produced stereoselectively (preferably with excellent optical purity) by the above reaction. The resulting monoaminonitrile derivative of formula (I I) may be purified by means known to those skilled in the art, if necessary.

Next, a method for producing an α-amino nitrile derivative in a stereoselective manner using an optically active quaternary ammonium compound represented by the formula (1-1) or the formula (1-2) as a phase transfer catalyst. Another example (hereinafter referred to as method (方法)) will be explained.

The ct-amino nitrile derivative that can be produced by the method (ii) of the present invention includes, for example, the following formula (V):

125

(Where R ⁴¹ is

(1) an alkyl group which may form a branch or a ring and / or may be substituted with a halogen atom;

(2) may form a branched or cyclic, and may be substituted by Bruno or halogen atom, C ₂ -C ₂₀ alkenyl group;

(4) a predetermined substituent A, an aryl group that may be substituted with the same alkyl group that may be substituted with a halogen atom, or an aryl group that may be substituted with

(7) a heteroaralkyl group which may be substituted with a predetermined substituent A and has a heteroaryl moiety;

(8) (C ₁ ~C ₃ alkoxy) carbonyl group;

(9) force rubamoyl group;

(10) N- (di-alkyl) carbamoyl group; and

(11) N, N—di (C ₁ -C ₄ alkyl) force rubermoyl group (where Ci to C

Represents a group selected from the group consisting of

R ⁴³

(i) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₁ -C ₈ alkyl group; 126

(Ii) may form a branched or cyclic, and or may be substituted by halogen atom, C ₂ -C ₈ alkenyl group;

(iv) a predetermined substituent A, an aryl group which may be substituted with an alkyl group of Ci C which may be substituted with a halogen atom, or an aryl group which may be substituted with

(V) a heteroaryl group having an aryl moiety that may be substituted with a predetermined substituent A;

(viii) (C ₁ ~C ₃ alkoxy) carbonyl group;

(ix) force rubermoyl group;

(x) N- (Ci C alkyl) strong rubermoyl group; or

(xi) N, N-di (Ci C alkyl) force rubamoyl group (wherein the C _{1 to} C ₄ alkyl groups may be the same or different from each other) and are selected from the group consisting of:

Is)

Represents a group selected from the group consisting of and

* Represents an asymmetric center).

The method (B) of the present invention will be described in detail. The α-aminonitrile derivative represented by the above formula (V) is represented by the following formula (V I):

(V I)

127

(Wherein R ⁴¹ and R ⁴³ are each independently the same as the group defined above) in the presence of an alkali metal cyanide, the above formula (1-1) or The reaction is carried out in a solvent containing an optically active quaternary ammonium salt represented by the formula (1-2) (for example, in a solvent containing or suspending the optically active quaternary ammonium salt). Can be manufactured.

The aldimine derivative of the formula (VI) used in the method (B) of the present invention is similar to the aldehyde of the formula (III) and the amine of the formula (IV) used in the above method (A). The aldimine derivative of the formula (VI) used in the method (B) of the present invention is itself stable and can be used in a solvent described later. It is preferable that the compound be soluble.

Aldimine derivatives represented by the formula (VI) that can be used in the method (B) of the present invention are known to those skilled in the art and described in, for example, F. Chemla et al., Synthesis, 2000, p. Those skilled in the art can arbitrarily synthesize them according to the procedure of

The alkali metal cyanide that can be used in the method (B) of the present invention is a kind of cyanating agent that is generally used in the Strecker reaction. Examples of the cyanating agent include cyanine lithium, sodium cyanide, and potassium cyanide. Can be mentioned. It is preferable to use potassium cyanide because the reaction proceeds more smoothly.

The solvent used in the method (B) of the present invention is preferably an organic solvent, a mixed solvent of an organic solvent and water, or a two-phase solvent. Examples of the organic solvent include tonoleene, mesitylene, methinolet tert-butyl. Nore etherenole, cyclopentinomethyl ether, and xylene. It is preferable to use toluene as the organic solvent. In addition, when the organic solvent and water are mixed, the volume ratio thereof is not particularly limited, but preferably 10 Z1 (v / v) to 1 10 128

(vZv).

The amount of the optically active quaternary ammonium salt represented by the above formula (1-1) or formula (1-2) used in the method (B) of the present invention is also the aldimine derivative of the formula (VI) used. Although it is not necessarily limited because it may vary depending on the type and amount used, it is preferably 0.005 mol ⁰ / mol per 1 mol of the aldimine derivative of the formula (VI). ~ A 10 mole ^_0/0, more preferably 0.01 mol ⁰ /. ~ It is a 5 mol ^_0/0.

Furthermore, in the above reaction step of the method (B) of the present invention, for example, at a suitable temperature from 30 ° C. to room temperature, preferably from 20 ° C. to 10 ° C., for example, in air or inert. Performed in a gas (eg, argon or nitrogen gas) atmosphere. This step can be carried out with stirring for an appropriate time until the reaction proceeds sufficiently. The reaction time is not necessarily limited, but is, for example, 30 minutes to 48 hours, preferably 1 hour to 24 hours.

In this manner, the α_amino nitrile derivative represented by the formula (V) can be produced stereoselectively (preferably with an excellent optical purity) by using the method (B) of the present invention. The obtained monoaminonitrile derivative of the formula (V) may be purified by means known to those skilled in the art, if necessary. Ku-aminoaminotolyl derivative production method (C)>

Next, a method for producing an α-amino nitrile derivative in a stereoselective manner using the optically active quaternary ammonium compound represented by the formula (1-1) or the formula (1-2) as a phase transfer catalyst. Another example of the above (hereinafter sometimes referred to as method (C)) will be described.

Α-Aminonitrile derivatives that can be produced by the method (C) of the present invention include, for example, the following formula (V):

(Here, R ⁴¹ and R ⁴³ are each independently the same as the group defined in the description of the method (B)).

The method (C) of the present invention will be described in detail. The α-aminonitrile derivative represented by the above formula (V) is represented by the following formula (XXV III): '

(Wherein R ⁴¹ and R ⁴³ are each independently the same as defined above, and R ¹¹ may be substituted with a halogen atom. C ₁ -C ₄ alkyl force \ halogen atom or optionally substituted C ₁ -C ₃ alkoxy group, an alkyl group which may be substituted Ariru group Ci~ may be substituted by a halogen atom C ₄ , Cyano group, halogen atom, nitro group, _NR ³⁰ R ³¹ (where R ³ ° and R ³¹ are each independently a hydrogen atom or may be branched. And a C CA alkyl group that may be substituted with a halogen atom), or a cyclic amino group that forms a ring with a C ₂ to C ₈ alkylene group, or an aryl group that may be substituted with In the presence of alkali metal cyanide, In a solvent containing an optically active quaternary ammonium salt represented by either the above formula (1-1) or formula (I 1-2) (for example, containing the optically active quaternary ammonium salt) Or in a suspended solvent).

The α-amide sulfonate of the formula (XXV I I I) used in the method (C) of the present invention is a kind of a precursor of the aldimine derivative of the above formula (V I).

Similar to the aldehyde of formula (III) and the amine of formula (IV) used in (Α) and the aldimine derivative of formula (V) used in the above method (Β), in the broad Strecker reaction A substrate that can be used. Method of the present invention 130

The α-amide sulfone of the formula (XXV I I I) used in (C) is preferably a compound that is stable per se and is soluble in the solvent described below.

The α-amide sulfone represented by the formula (XXV III) that can be used in the method (C) of the present invention is known to those skilled in the art. For example, F. Chemla et al., Synthesis, 2000, p. 75- Those skilled in the art can arbitrarily synthesize them according to the procedure described in 77.

The alkali metal cyanide that can be used in the method (C) of the present invention is a kind of cyanating agent used in the overall Strecker reaction, and examples thereof include lithium cyanide, sodium cyanide, and potassium cyanide. Can be mentioned. The solvent used in the method (C) of the present invention is preferably an organic solvent, a mixed solvent of an organic solvent and water or a two-phase solvent, and examples of the organic solvent include tonolene, mesitylene, methyl-t- Butyl ether, cyclopentyl methyl ether, and xylene. It is preferable to use toluene as the organic solvent. In addition, when the organic solvent and water are mixed, their volume ratio is not particularly limited, but is preferably 10Z1 (v / v) 1Z10 (v / v).

The amount of the optically active quaternary ammonium salt represented by the above formula (I 1) or formula (I 1-2) used in the method (C) of the present invention is also determined by the amount of the aldimine derivative of the formula (VI) used. Although it is not necessarily limited because it may vary depending on the type and amount used, it is preferably 0.005 mol ⁰ / mol per 1 mol of ct-amide sulfone of the formula (XXV III). ~ A 10 mole ^_0/0, more preferably 0.01 mol ⁰ /. ~ It is a 5 mol ^_0/0.

Further, in the above reaction step of the method (C) of the present invention, for example, at a suitable temperature from 30¾ to room temperature, preferably from 20X: -10, for example, in air or an inert gas (for example, argon Or nitrogen gas) It is performed in an atmosphere. In this step, the reaction can be carried out with stirring for an appropriate time until the reaction proceeds sufficiently. The reaction time is not necessarily limited, but is, for example, 30 minutes to 48 hours, preferably 1 hour to 24 hours.

In this manner, the _α -amino nitrile derivative represented by the formula (V) can be produced stereoselectively (preferably with an excellent optical purity) using the method (C) of the present invention. The obtained α-amino nitrile derivative of the formula (V) may be purified by means known to those skilled in the art, if necessary.

In the present invention, an optically active α-aminominotolyl derivative represented by the optically active formula (II) obtained from the above method (Α) or the above method (Β) or (C) is obtained. An optically active α-amino acid and Ζ or a derivative thereof can be easily produced using an α-amino nitrile derivative represented by the formula (V).

Specifically, the formula (II) or formula (V) obtained from the above:

(Wherein R ^{4 1} , R ^{4 2} and R ^{4 3} are the same as the groups defined above), the optically active α_aminonitrinole derivative represented by . The acid used in the production of this optically active α_amino acid and / or its derivative is not particularly limited as long as it is an acid used for hydrolysis to obtain a monoamino acid and および or its derivative in the Strecker reaction in general. Without limitation, examples include hydrochloric acid and sulfuric acid. Hydrolysis using such an acid is well known in the art, and those skilled in the art can use the appropriate optical acid to produce the desired optically active α-amino acid and Ζ or so from the optically active α-amino nitrile derivative. 132 derivatives can be obtained.

In addition, each of the above-described methods (A) to (C) of the present invention using the optically active quaternary ammonium salt represented by the above formula (1-1) or (1-2) and the present invention. The relationship with method (D) can be expressed using the following reaction scheme.

Or its induction ^ff

(卜 2)

Monium salt Referring to the above reaction scheme, in the method (A) of the present invention, by using the aldehyde of formula (III) as a starting material, the above formula (1-1) or formula (1-2) can be used. The α-amino nitrile derivative represented by the formula (II) is stereoselectively produced by a reaction (Strecker reaction) in the presence of an optically active quaternary ammonium salt opacifying agent. obtain.

In the method (ii) of the present invention, an optically active quaternary ammonium salt and cyanide represented by the above formula (1-1) or formula (1-2) are obtained by using an aldimine derivative of the formula (VI). The reaction (Strecker reaction) is carried out in the presence of an agent, and the α-amino nitrile derivative represented by the formula (V) is stereoselectively produced. 133 get. Here, the aldimine derivative of the above formula (VI) can be easily synthesized from the aldehyde of the formula (III) by using a method well known to those skilled in the art.

That is, when synthesizing an aldimine derivative of formula (VI) from an aldehyde of formula (III), for example, when R ⁴¹ constituting formula (VI) is a relatively large atomic group, By directly reacting (P rl) with an amine represented by aldehyde and R ⁴³ SO ₂ NH ₂ (where R ⁴ ³ is the same as the group defined above), the formula ( The aldimine derivative of VI) can be obtained. Alternatively, the aldehyde of formula (III) is reacted with, for example, ammine represented by R ⁴³ S 0 ₂ NH ₂ and R ¹¹ SO ₂ Na in the presence of formic acid and water (P r 2) From this, the α-amide sulfone represented by the formula (XXV III) is synthesized, and then reacted with a base (P r 3) to easily convert the aldimine derivative of the formula (VI). Obtainable.

On the other hand, in the method (C) of the present invention, for example, the CK_amide sulfone of the formula (XXV III) obtained by using the method of (P r 2) is directly converted into the above formula (I-1) or By reacting in the presence of an optically active quaternary ammonium salt represented by the formula (1-2) and a cyanating agent, an α-amino nitrile derivative of the formula (V) can be produced stereoselectively. . In this method (C), first, α-amide sulfone of formula (XXV III) and a cyanating agent react preferentially, and in the reaction system, an aldimine derivative represented by formula (VI) is used as an intermediate. Is considered to be generated. Next, this intermediate aldimine of the formula (VI) is further added in the presence of an optically active quaternary ammonium salt represented by the above formula (1-1) or formula (1-2) and a cyanating agent. The target α-amino nitrile derivative of the formula (V) can be obtained stereoselectively by reaction (Strecker reaction).

Then, it can be obtained by any of the above methods (A), () or (C). Furthermore, the desired optically active _α -amino acid or derivative thereof can be efficiently produced by hydrolyzing the monoaminonitrile derivative of the formula (II) or the formula (V) with an acid.

In this way, even if the target optically active α-amino acid and / or derivative thereof is a derivative having a predetermined structure that has been considered difficult in the conventional alkylation process, this optically active single amino acid. And Ζ or its derivatives can be produced efficiently and arbitrarily without any structural constraints.

Further, in the method for producing a minominotolyl derivative of the present invention, a person skilled in the art can obtain at least three reaction variations (methods (Α) to (C)) according to the type of substrate used. An appropriate method can be arbitrarily selected. For this reason, the production efficiency of the α-amino nitrile derivative of the formula (V) can be increased according to the type. Example

Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.

In the following examples, the measurement was performed under the following conditions unless otherwise specified.

Infrared (IR) spectrum was measured with an IRP estige-21 1 spectrometer manufactured by Shimadzu Corporation. The iH NMR spectrum was measured with a J NM—FX 400 (400 MHz) spectrometer manufactured by JEOL. Chemical shifts were measured in ppm using tetramethylsilane as an internal standard. ^{The 13} C NMR spectrum was measured with a JNM-FX 40 0 (10 OMH z) spectrometer manufactured by JEOL Ltd. using complete proton decoupling. Chemical shifts were measured in ppm with the residual solvent as internal standard. 135 High-performance liquid chromatography (HPLC) was performed using a Shimadzu 1 OA apparatus using Daicel Chemical Industries's Chira 1 pak AD—H (4.6 mm × 2.5 cm column). High resolution mass spectrum (HRMS) was measured using Mariner 8295AP I_T OF workstation manufactured by Applied Biosystems and JMS-HX100 manufactured by JEOL Ltd. The optical rotation was measured with a DIP-1000 digital polarimeter manufactured by JASCO Corporation. In the following thin layer chromatography (TLC) analysis, a precoated TLC plate (silica gel 60 GF ₂₅₄ , 0.25 mm) manufactured by Merck was used. The product was purified by flash-force ram chromatography using silica gel 60 (Merck 1.093 93. 9025, 230 mesh to 400 mesh).

Reagents: (a) S0CI ₂ ; ί-BuCH ₂ 0H, CH ₂ CI ₂ ; (b) Mg (TMP) ₂ , THF; Br ₂

(c) DIBAH. CH ₂ CI ₂ ; (d) PBr ₃ , CH ₂ CI ₂ ; (e) MeNH ₂ aq, THF Example 1-1: (R) -2,2, -bis (carboxylic acid neo Pentyl ester) -1,1, -binaphthyl ((R) -8)>

To the thionyl chloride (5 mL) in a 3 OmL round-bottom flask, add (R) -1, Γ-pinanaphthyl-2,2, -dicarboxylic acid (1.7 1 g, 5. Ommo 1 Z Tanabe Seiyaku Co., Ltd.) At a temperature of 0 ° C, and the mixture is added under an argon atmosphere for 3 hours. Refluxed for 136 hours. Excess thionyl chloride was removed under reduced pressure, and neopentyl alcohol (1.76 g, 2 Ommo 1) in distilled CH ₂ C 1 ₂ (5 ml) and pyridine (1 ml) were subsequently added. The mixture was heated to reflux for 2 hours. This was quenched with 1 N cold hydrochloric acid and phase separated. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over Na ₂ SO ₄ and concentrated. The residue was purified by flash column chromatography using silica gel (ethyl acetate / hexane = 1: 10 (volume ratio) was used as the eluent), and the compound ((R) — 8) Replace (2.32 g, 4.8 Omm o 1) to 9

Obtained in 6% yield.

Table 1 shows the analytical results of the obtained compound (R) -8.

table 1

Analysis results for Compound (R) — 8 _

Ή NR (400 MHz, CDCI ₃ ) 58.21 (2H, d, J = 8.7 Hz, ArH), 7.99 (2H, d, J = 8.7 Hz, ArH), 7.92 (2H, d, J = 7.9 Hz, ArH) , 7.49 (2H, ddd, J = 1.2, 7.1, 8.3 Hz, ArH), 7.22 (2H, ddd, J = 1.2. 7.1, 7.9 Hz, ArH), 7.06 (2H, d, J = 8.3 Hz. ArH) 3.64 (2H, d, J = 10.4 Hz, CH ₂ ), 3.60 (2H, d, J = 10.4 Hz, CH ₂ ), 0.64 (18H, s, ί-Bu) ppm;

¹³ C NMR (100 MHz, CDCI ₃ ) (5166.9, 139,7, 134.9. 132.9, 127.8, 127.6, 127.5, 127.2, 126.6, 126.2, 74.5, 31.2, 26.3 ppm;

IR (Neat) 3065, 2957, 2868, 1724, 1703, 1595, 1464, 1368, 1321, 1277, 1236, 1136, 1118, 766 cm "¹;

Calculated as HRMS (ESI-TOF) C ₃₂ H ₃₅ 0 ₄ ([M + H] +): 483.2546, found: 483.2530;

[Hi] _D ²⁹ + 32.6 ° (c 1.00, CHCI ₃ )

First, tetramethylpiperidinemagnesium (Mg (TMP) ₂ ) was prepared by the procedure described in Oi et al., The journal of Organic Chemistry, 2003, No. 68, p.4576-4578.

Conducted in a THF solution of Mg (TMP) ₂ (0.31M) (48.4ml) 137 A distilled THF solution (3. OmL) of the compound ((R) —8) (1. 74 g, 3. Ommo 1) obtained in Example 1-1 was added dropwise at 0 ° C under an argon atmosphere. The mixture was stirred for 12 hours at room temperature. After cooling to 78, bromine

(1.58 ml, 3 Ommo 1) was added and stirring was continued for 1 hour at room temperature. The resulting mixture was poured into 1 N cold hydrochloric acid, washed with saturated aqueous Na ₂ S0 ₃ and extracted with ethyl acetate. The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by flash column chromatography using silica gel (Ethylnohexane acetate = 1:20 to 1:10 (volume ratio) was used as the eluent) to obtain the compound (R ) -9 (1.24 g, 2. 1 3 mm o 1) in 71% yield.

Table 2 shows the analysis results of Compound (R) —.9 obtained.

Table 2

Analysis results for Compound (R) — 9

TH NMR (400 MHz, CDCI ₃ ) (58.23 (2H, s, ArH), 7.81 (2H, d, J = 8.3 Hz, ArH), 7,53-7.49 (2H, m, ArH), 7.35-7.31 ( 2H, m, ArH), 7.18 (2H, d, J = 8.3 Hz, ArH), 3.58 (2H, d, J = 10.4 Hz, CH ₂ ), 3.41 (2H, d, J = 10.4 Hz, CH ₂ ) , 0.62 (18H, s, ί-Bu) ppm;

¹³ C NMR (100 MHz, CDCI ₃ ) 5166.3, 134.2. 134.0, 133.9, 132.2, 131.1,

127.9, 127.4, 127.3, 126.9, 116.1, 75.1, 31.0, 26.2 ppm;

IR (thin film) 3065, 2955, 2868, 1730, 1582, 1567, 1441, 1368,

1279, 1248, 1157, 1134, 989, 959, 887, 752 cm— ';

HR S (ESI-TOF) Calculated as C ₃₂ H ₃₂ Br ₂ 0 ₄ Na ([M + Na] +): 661.0536, found: 661.0560;

[a] _D ²⁸ + 76.7 ° _ (c 1.00, CHCI ₃ )

<Example 1-3: (R) -2,6-Dibromo-4-methyl-4,5-dihydro-3H-4-azacyclohepta [2,1-a; 3, 4-a, Synthesis of dinaphthalene ((R) —10)> Example 1 1-2 In a solution of (R)-9 (1. 17 g, 2. Ommo 1) in dichloromethane (6. OmL) Diisobutylaluminum hydride (DI BAH) (1. OM in toluene, 8.8 mL) was added dropwise at 0 ° C. and the mixture was stirred at room temperature until the reaction was complete. This mixture The 138 product was treated with 1 N hydrochloric acid at 0 ° C. and extracted with ethyl acetate. The precipitate formed during the extraction was dissolved in a small amount of THF. The combined organic extracts were dried over Na ₂ SO ₄ and concentrated. The resulting crude (R) -3,3, -dibromo_2,2, -bis (hydroxymethyl) -1,1, -binaphthyl was used for subsequent bromination without further purification. (R) -3,3, -Dibromo-2,2, -bis (hydroxymethyl) -1,1, -binaphthyl in dichloromethane (6. OmL) was cooled to 0 ° C and PB r 3 (0. 50 ml, 4.8 mm o 1) was added dropwise. The reaction mixture was stirred for 1 hour at room temperature and poured in a saturated N a HC_〇 ₃ aqueous solution 0 ° C. Performs an extraction operation with acetic acid Echiru, and the combined extracts were Drying at & ₂ 30 _4. The solvent was removed and the resulting crude bis (promide) was dissolved in THF and cooled to 0 ° C. This solution is then mixed with 28% monomethylamine

(MeNH ₂ ) aqueous solution was added and the mixture was stirred for 1. h. After removing the volatile components, the residue is flash column chromatographed on silica gel.

(Methanol Z Dichloromethane = 1: 100 (volume ratio) was used as the eluent) and the compound (R) — 10 was obtained as a slightly yellowish powder.

(538 mg, 1.28 mm o 1 (3 steps)) was obtained in a yield of 64%.

Table 3 shows the analysis results of the obtained compound (R) -10.

Table 3 '

Reagents: (a) NBS, CH ₂ CI ₂ ; (b) ArB (OH) ₂ , Pd (OAc) ₂ , PPh ₃ , Cs ₂ C0 ₃ , DMF

(c) H ₂ S0 ₄ aq; NaN0 ₂ aq; KI aq (d) n-BuLi, THF; B (OMe) ₃ ; 1N HCI For 2-phenyl-1-naphthylboronic acid (W _2D ), Prepared according to the method described by T. Kamikawa et al. (Supra) and]. Yin et al. Example 2-1: Synthesis of 2,4_dibromo-1-naphthylamine (W _3A )> In a solution of 1-naphthylamine (7 16 mg, 5. Ommo 1) in dichloromethane (15 m 1), N-bromosuccin Imide (NB S) (1.91 g, 10.5 mmo 1) was added in small portions at 0 ° C. After stirring for 30 minutes at the same temperature, the mixture was poured into saturated aqueous NaHCO ₃ and extracted with ethyl acetate. The organic layer was dried over Na ₂ S0 ₄ and concentrated. The residue was purified by flash column chromatography using silica gel (dichloromethane hexane = 1: 3 to 1: 2 (volume ratio) was used as the eluent). Naphthylamine (W _3A ) (1.07 g, 3.55 mmol) was obtained in 71% yield.

<Example 2-2: Synthesis of 2,4-diphenyl-1-naphthylamine (W _3B )> 2,4-Dibromo-1-naphthy obtained in Example 2-1 in DMF (3 mL) Luamine (30 lmg, 1. Ommo 1), phenylboronic acid (233 mg, 2.4 mmo 1), palladium acetate (1 1.6 mg, 0.05 mmo 1) A mixture of 140 triphenylenophosphine (40.1 mg, 0.15 mm o 1) and C s ₂ C0 ₃ (987 mg, 3. Ommo 1) was degassed and placed under an argon atmosphere. The mixture was stirred at 90 ° C for 12 hours. After cooling to room temperature, the resulting mixture was poured into water and extracted with ethyl acetate. The organic extract was dried over Na ₂ SO ₄ . The solvent was distilled off, and the residue was purified by flash column chromatography using silica gel (ethyl acetate / hexane = 1: 30 to 1:10 was used as eluent) and 2,4-diphenyl was used. 1-Na Fuchiruamin _{(W 3B) (201 mg,} 0. 68mmo 1) was obtained in 68% yield.

Table 4 shows the analytical results of the obtained compound (W _3B ) (2,4-diphenyl-1-naphthylamine).

Table 4

<Example 2-3—Synthesis of 1-yodo-2,4-diphenylnaphthalene (W _3C )> 2,4-Diphenyl-1-naphthylamine (W _3B ) (2 01 mg, O. 68 mmo 1) was charged to a round bottom flask equipped with a reflux condenser and treated with 6N H ₂ SO ₄ (2 mL). The mixture was stirred at 50 ° C. for 8 hours. After cooling to 0, NaN0 ₂ (7 Omg, 1. Ommo 1) in water (lmL) was added to it and stirring was continued for another 30 minutes at the same temperature. Next, power iodide (451 mg, 2. 72) in water (1 ml) 141 mmo 1) was added and the whole mixture was heated to reflux for 4 hours. After cooling to room temperature, Na ₂ SO ₃ was added and extracted with ethyl acetate. The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by flash column chromatography on silica gel using dichloromethane / hexane = 1: 1 00 (volume ratio as eluent) to give 1-yode_2,4_diphenyl as a white solid. Lunaphthalene (W _3C ) (2 1 8 mg, 0. 541111110 1) was obtained in 79% yield.

<Example 2-4: Synthesis of 2,4-diphenyl-1-naphthylboronic acid (W _3D )> 1-yodo-2,4-diphenylnaphthalene (W _3C ) obtained in Example 2-3 (218 mg, 0.54 mmo 1) in distilled THF (1. Oml) solution with n BuLi (1.6 M hexane solution, 0.371 mL, 0.594 mm o 1) at -78 And the solution was stirred for 30 minutes. At the same temperature, trimethoxyboron (120 1, 1.08 mmo 1) was added at once, 1 N hydrochloric acid was added, and stirring was continued for several hours at room temperature. The resulting mixture was extracted with ethyl acetate and the organic phase was dried over Na ₂ SO ₄ . After distilling off the volatile components, the residue was purified by flash column chromatography using silica gel (Ethyl acetate / hexane = 1: 4 to 1: 3 (volume ratio) was used as the eluent) 2,4-Diphenyl-1-naphthylboronic acid (W ₃ _D ) (147 mg, 0.454 mmo 1) was obtained in 84% yield.

Table 5 shows the analysis results for the obtained compound (W _3D ) (2,4-diphenyl-1-naphthylboronic acid). 142 Table 5

2,4-bis (4-trifluoromethylphenyl) -1-naphthylamine (W ₄ ) in the same manner as in Example 2-2 except that 4-trifluoromethylphenylboronic acid was used instead of phenylboronic acid. _B ) was obtained.

Table 6 shows the analysis results of the obtained compound (W _{4 B} ) (2,4-bis (4-trifluoromethylphenyl) _1_naphthylamine).

Table 6

<Example 2-6: Synthesis of 1-odo-2,4-bis (4-trifluoromethylphenyl) naphthalene (W _{4 C} )>- 143 Instead of 2,4-diphenyl-1-naphthylamine (W _3B ) obtained in Example 2-2, 2,4-bis (4-trifluoromethylphenol obtained in Example 2-5 was used. 2) 1-Nodo-2,4-bis (4-trifluoromethylphenyl) naphthalene (W _4C ) was obtained in the same manner as in Example 2_3 except that _1_naphthylamine was used. Table 7 shows the analytical results of the obtained compound (W _4C ) (1-chloro-2,4-bis (4-trifluoromethylphenyl) naphthalene).

Table 7

Analysis result of the compound (W _4C ) obtained in this example

¹ H NMR (400 MHz, CDCI ₃ ) (58.45 (1H, d, J = 8.3 Hz, ArH), 7.80-7.71 (5H, m, ArH), 7.68-7.64 (1H, m, ArH), 7.61 (2H , d, J = 7.9 Hz, ArH), 7.55-7.51 (3H, m, ArH), 7.32 (1H, s, NH ₂ ) ppm;

1 ³ C NMR (100 MHz, CDCI ₃ ) 5148.8, 144.1, 142.9, 142.8, 139.3, 134.9,

133.8, 130.9, 130.1, 129.8 (q. ² J _C -F = 33 Hz), 129.7, 129.7 (q, ² J _C — _F = 33 Hz), 128.3, 127.7, 127.2, 125.9, 125.2-125.1 (m, ³ J _c _p), 124.9- 124.8 (m, CF) .123.9 (q, _C -F = 271 Hz), 103,7 ppm;

IR (thin film) 3067, 3049. 1618, 1549, 1406, 1319, 1163, 1123, 1107, 1065, 1018, 968, 837, 762 cm— ¹ ;

_{_{HRMS (FAB) C 24 H 13}} F 6 Calculated as I (IT): 541.9961, Found: _541.9959-

Example 2_7: Synthesis of 2,4-bis (4-trifluoromethylphenyl) _1_naphthyl boronic acid (w _4D )>

Instead of 1-yodo-2,4-diphenyl dinitraphthalene (W _3C ) obtained in Example 2-3, 1-yodo-2,4-bis (4 The same procedure as in Example 2-4, except that -trifluoromethyl) naphthalene (W _4C ) was used and the stirring time after adding n_Bu Li was changed to 15 minutes instead of 30 minutes. , 4-bis (4-trifluoromethylphenyl) -1-naphthylboronic acid (W _4D ) was obtained.

Table 8 shows the analytical results of the obtained compound (W _4D ) (2,4-bis (4-trifluoromethylphenyl) -1-naphthylboronic acid). 144 Table 8

A flame-dried 2 m 1 vial with a rubber septum, compound (R) -10 (46.8 mg, 0. lmmol), 2-biphenylboron obtained in Example 1_3 Acid (W _1D ) (475 mg, 0.24 mmol, Aldrich), Palladium acetate (2.3 mg, 0.01 mm o 1), Triphenylenophosphine (6.7 mg, 0.03 mm o 1) ), C s ₂ C0 ₃ (98.8 mg, 0.3 mm o 1) and dry DMF (0.6 mL). The mixture was degassed and brought to an argon atmosphere several times, then heated to 90 ° C. and stirred for 12 hours. After cooling to room temperature, the resulting mixture was poured into saturated N a HC0 ₃ solution and extracted with dichloromethane. The organic extract was dried over Na ₂ SO ₄ and concentrated. The residue was purified by flash column chromatography using silica gel (Ethyl acetate Z-dichloromethane _/ hexane = 1: 2: 10 to 1: 2: 5 (volume ratio) was used as eluent) Symmetric product (major) and asymmetric diastereomer Compound (R) — 1 1 was obtained as a mixture with (minor) (note that the diastereo ratio was 4: 1 and another possible symmetric diastereomer was not detected by ¹ H NMR. This process has not been optimized yet). This mixture was used as such in the next step.

Table 9 shows the analysis results of the obtained compound (R) 11.

The stereoisomer mixture of the compound (R) -1 1 obtained in Example 3-1 was dissolved in methyl iodide (2. Oml), and this solution was stirred for 8 hours. Excess methyl iodide is removed and the residue is flushed with silica gel Stereochemically pure title compound (R) — 1 (484mg, 0. 146), purified by ram chromatography (using methanol dichloromethane = 1:50 to 1:20 (volume ratio) as eluent). 64mmo 1) was obtained with a yield of 64% (2 steps).

Table 10 shows the analysis results of Compound (R) -1 obtained.

Table 10

Example 3-3: Preparation of Catalyst Precursor Z Compound (Synthesis of (R) -12 a)> 2-Phenyl-1-naphthyl prepared in Example 2 instead of 2-biphenylpoic acid Compound ((R)-1 2 a) was obtained in good yield in the same manner as in Example 3 _ 1 except that boronic acid (W _2D ) (0.24mmo 1) 'was used. The diastereo ratio was 3.3: 1, and another possible symmetric diastereomer was not detected by ¹ H NMR).

Table 11 shows the analysis results of the obtained compound ((R) -12a). 147

The compound (R) — 1 2 a obtained in Example 3-1 The compound (R) — 1 2 a stereoisomer mixture obtained in Example 3-3 was used instead of the stereoisomer mixture of 1 1. Except for the above, stereochemically pure title compound (R) 1-2a was obtained in a yield of 70% (2 steps) in the same manner as in Example 3-2.

Table 12 shows the analysis results of the obtained compound (R) — 2 a. 148 Table 12

Example 3-5: Preparation of Catalyst Precursor Synthesis of Compound ((R) — 12 b) Instead of 2-biphenylpolonic acid, the 2,4-diphenyl compound obtained in Example 2-4 Example 3_ except that 1-naphthylboronic acid (W _3D ) was used

In the same manner as in 1, a compound ((R) -12b) was obtained.

Table 13 shows the analysis results of the obtained compound ((R) — 1 2 b).

Table 13

Analysis result of compound (R) — 1 2 b obtained in this example '実施 NMR (400 MHz, CDCI ₃ ) δ 7.99-7.94 (6H, m, ArH), 7.87 (2H, d, J = 7.9 Hz , ArH), 7.60-7,58 (4H, m, ArH), 7.54 (2H, s, ArH). 7.53-7.48 (4H, m, ArH), 7.46-7.39 (8H, m, ArH), 7, 25-7,21 (2H, m, ArH), 7.11- 7.09 (4H, m, ArH), 7.01-6.90 (8H, m, ArH), 3,27 (2H, d, J = 12.5 Hz, ArCH ₂ ), 2.60 (2H, d, J = 12.5 Hz. ArCH ₂ ), 1,38 (3H, s, CH ₃ ). . m;

Calculated as HRMS (ESI-TOF) C ₆₇ H ₄₈ N ([M + H] +): 866.3788, found: 866.3781

<Example 3-6: Preparation of catalyst Synthesis of chiral ammonium iodide ((R) -2b)> 149

The compound (R) -12 obtained in Example 3-1 Instead of the mixture of stereoisomers (R) -11 of 1, the compound (R) -12b obtained in Example 3-5 was used. Except for the above, stereochemically pure title compound (R) -2b was obtained in a yield of 68% (2 steps) in the same manner as in Example 3-2.

Table 14 shows the analysis results of the obtained compound (R) -2 b.

Table 14

Analysis result of compound (R) -2b obtained in this example NMR (400 MHz, CDCI ₃ ) 68.31 (2H, s, ArH), 8.05—8.01 (4H, m, ArH), 7.93 (2H, d , J = 7.5 Hz, ArH), 7.71-7.65 (6H, m, ArH), 7.61 (2H, s. ArH), 7.51-7.35 (12H, m, ArH), 7.21 (4H, d, J = 7.5 Hz , ArH), 7.00 (4H, m, J = 7.5 Hz, ArH), 6,89-6,85 (4H, m, ArH), 4.08!

Hz, ArCH ₂ ), 2.73 (2H, d, J = 13.1 Hz, ArCH ₂ ), 2.54 |

, ³ C NMR (100 MHz, CDC 1 ₃ ) 5141.7, 140.2, 139.7, 138.7, 137.2, 135. '133.4, 132.8, 132.0, 131.5, 131.1, 130.2, 130.0, 129.5, 128, 2 | 128.0, 127.9, 127.7 , 127.3, 127.2, 127.1, 126.9, 126.8, 126.6, 126.0, 125.5, 125.4, 62.0, 51.4 ppm;

IR (thin film) 3401, 3053, 3024, 2995, 2926, 2857, 2185, 1587, 1493, 1030, 907, 878, 760, 729 cm "';

Calculated as HRMS (ESI-TOF) C ₆₈ H ₅₀ N (M +): 880.3935, found: 880, 3938;

[a] _D ³⁰ + 354 ° (c 0.20, CHCI ₃ )

Example 3-7: Preparation of Catalyst Precursor Synthesis of Z Compound ((R) — 12 c)> This compound ((R)-1 2 c) was converted to Suzuki Miyau found by Colobert. Lacoupling conditions (Colobert, F. et al., European journal of Organic Chemistry, 2005, p. 1113-1128). That is, 150

2,2-bis (4-trifluoromethylphenyl) -1-naphthylboronic acid (W _4D ) (W.D.) obtained in Example 2_7 instead of 2-biphenylpooric acid 24 mmo 1), except that C s F (7.2 equivalents) dried under reduced pressure before use was used instead of C s C0 ₃ and the reaction mixture was stirred for 24 hours instead of 12 hours. In the same manner as in Example 3-1, compound ((R) -12c) was obtained.

Table 15 shows the analysis results of the obtained compound ((R) -12c).

Table 15

(Where A r ¹ and A r are both p—CF ₃ —C ₆ H ₄ )

In place of the stereoisomer mixture of the compound (R) — 1 1 obtained in Example 3-1, the stereoisomer mixture of the compound (R) — 1 2 c obtained in Example 3-7 was used. The stereochemically pure title compound (R) -2 (: was obtained in a yield of 63% (2 steps) in the same manner as in Example 3-2 except that it was not.

The analysis results of the obtained compound (R) — 2 c are shown in Table 16.

Table 16

Example 4: X-ray structural analysis of chiral ammonium salt ((R)-1 -PF ₆ ) and chiral ammonium salt ((R) -2 a)>

To a solution of the chiral ammonium salt ((R) — 1) obtained in Example 3-2 in CH ₂ C 1 ₂ and H ₂ 0 (volume ratio 1: 1), 1.5 equivalents of KPF ₆ was added. The CH ₂ C 1 ₂ layer was washed with water and concentrated. The residue was purified by flash column chromatography using silica gel (methanol / CH ₂ C 1 ₂ = 1:50 to 1:20 (volume ratio) as eluent) to obtain chiral ammonium salt ((R ) — 1— PF ₆ ) was obtained. This salt ((R) -1-PF ₆ ) was recrystallized with a THF hexane solvent system at 0 ° C.

Analytical results of the recrystallized chiral ammonium salt ((R) — 1 _PF ₆ ) 152 is shown in Table 17.

Table 1 7

On the other hand, the chiral ammonium salt ((R) _2a) obtained in Example 3-4 was recrystallized with a THF hexane solvent system.

Chiral ammonium salt obtained above ((R) — 1— PF ₆ and (R)

-2 a) single crystal was fixed to Cryo Loop (manufactured by Hampton Research Co. LTD.). Using the X-ray diffraction data of Mo Κα X-rays monochromated by graph items (（= 0.71075 angstroms), the maximum value of 20 is set to the imaging plate up to 55.0 ° and 50.0 °, respectively. Collected with a single crystal automatic X-ray structural analyzer (R—AX IS RAP ID, manufactured by Rigaku Corporation). All calculations were performed using Rigaku Corporation and the Crystal Structur 'e software package from Molecular Structure Corporation. The initial structure was solved by the direct method and refined by the full matrix least square method of SIR-2002. All non-hydrogen atoms and hydrogen atoms were refined as anisotropic and isotropic temperature factors, respectively. From the crystallographic data, Fig. 1 (ORTE P diagram of recrystallized chiral ammonium salt ((R)-1 -PF ₆ )) and Fig. 2 (recrystallized chiral ammonium salt ((R ) —2 The ORTE P diagram of a))) and Table 18. 153 Table 1 8

As shown in Fig. 1, Fig. 2 and Table 18, it can be seen that all chiral ammonium salts have an absolute configuration.

<Reference Example 1: Synthesis of Ν-sulfodileumine precursor> a .S0 ₂ Mes b .S0 ₂ Mes

MesS0 ₂ NH ₂ ► l ►

R S0 ₂ tol RH Reagents: (a) RCHO, p-To l S0 ₂ Na, HC0 ₂ H, H ₂ 0; (b) NaHC0 ₃ aq., CH ₂ CI ₂ Above N-mesitylenesulfonylimine is added to Chemla, F. et al., Synthesis, 200

It was synthesized as follows according to the procedure described in Year 0, p. 75-77. 154 <Reference Example 1 1 1 a: Synthesis of N- (mesitylenesulfoninole) -a- (p-toluenesulfonyl) cyclenohexenoremethinoleamine>

Cyclohexanecarboxaldehyde (363 μ 1, 3. Ommo 1), mesitylenesulfonamide (598 mg, 3. Ommo 1) and sodium p-toluenesulfinate in formic acid (3 mL) and water (3 mL) A mixture of (481 mg, 3. Ommo 1) was stirred at room temperature for 12 hours. The resulting white precipitate was filtered off and washed with water and hexane. The filtrate was then recrystallized from ethyl acetate Z-hexane to give the title compound (30 1 mg, 2.0 1 mmo 1) as a crystallized product in a yield of 67%.

The analysis results of the obtained title compound are shown in Table 19.

Table 1 9

Reference Example 1 1 1 b: Synthesis of cyclohexanecarboxaldehyde N- (mesitylenesulfonyl) imine (3a)>

Reference Example 1-1 N- (mesitylenesulfonyl) -a- (p-toluenesulfonyl) cyclohexylmethylamine (90 1 mg, 2.0 1 mm o 1) obtained in 1a was added to CH ₂ C 1 ₂ (2 ml) was dissolved. Then the solution was added saturated N a HC0 ₃ solution (LML), and the mixture was stirred for 1 hour. The phases were separated, and the aqueous phase was extracted with CH _₂ C 1 _2. Drying the combined organic phases NaHCO ₃ And concentrated under reduced pressure to give cyclohexanecarboxaldehyde N— (mesitylenesrephoninole) imine (3a) (566 mg, 1.93 mm o 1) in 96% yield. It was.

Table 20 shows the analysis result of the obtained compound (3a).

Table 20

The title compound was obtained in good yield in the same manner as in Reference Example 1 — 1a except that cyclooctanecarboxaldehyde was used instead of cyclohexanecarboxaldehyde.

Table 21 shows the analysis results of the obtained title compound.

Table 21

156

Reference Example 1-1 In place of N- (mesitylenesulfonyl) -a- (p-toluenesulfonolinole) hexylmethylamine obtained in 1a Reference Example 1 1-2 N- In the same manner as Reference Example 1-1b except that (mesitylenesulfonino) -a- (p-toluenesulfonyl) cyclooctylmethylamine was used )

Table 22 shows the analysis results of the obtained compound (3b).

Table 22

Reference Example 1— 3 a: Synthesis of N- (mesitylenesulfonyl) -2-methyl-1- (p-toluenesulfonyl) propylamine>

The title compound was obtained in the same manner as in Reference Example 1-1a except that isobutyl aldehyde was used in place of cyclohexanecarboxaldehyde.

Table 23 shows the analysis results of the obtained title compound. 157 Table 23

<Reference Example 1-3b: Synthesis of isobutyl aldehyde N- (mesitylenesulfonyl) imine (3c)> ·

N- obtained in Reference Example 1-1 _a (mesitylene sulfonyl) - α_ (ρ- toluene sulfonyl) instead of cyclohexyl methyl § Min to consequent opening, obtained in Reference Example 1-3 a N- (Mesitylenesulfonyl ) Isobutyl aldehyde N- (mesitylenesulfonyl) imine (3c) was obtained in the same manner as Reference Example 1-1b except that -2-methyl-l_ (p-toluenesulfoninole) propylpyramine was used. It was.

Table 24 shows the analysis result of the obtained compound (3c).

Table 24

158 <Reference Example 1_4a: Synthesis of N- (mesitylenesulfonyl) -3-phenyl-l- ( _p- toluenesulfonyl) propylamine>

The title compound was obtained in the same manner as in Reference Example 1-11, except that 3-phenylpropionaldehyde was used instead of cyclohexanecarboxaldehyde.

Table 25 shows the analysis results of the obtained title compound.

Table 25

Reference Example 1 1-1 Instead of N- (mesitylenesulfonyl) -ct_ (p-toluenesulfonyl) cyclohexylmethylamine obtained in 1a Reference Example 1-11 N- (mesitylenesulfonyl) obtained in 4a ) 3-Phenylpropionaldehyde N- (mesitylenesulfonyl) imine in the same manner as Reference Example 1-1b except that -3-phenyl-1- (p-toluenesulfonyl) propylamine was used 3 d) was obtained.

Table 26 shows the analysis result of the obtained compound (3d). 159 Table 26

Reference Example 1-5 a: Synthesis of N- (mesitylenesulfonyl) -3-methyl-l- (p-toluenesulfonyl) ptylamine>

The title compound was obtained in the same manner as in Reference Example 1-1a except that isovaleraldehyde was used instead of cyclohexanecarboxaldehyde.

The analysis results of the obtained title compound are shown in Table 27.

Table 27

Reference Example 1-1 In place of N- (mesitylenesulfonyl) -α- (P-toluenesulfonyl) cyclohexylmethylamine obtained in 1a, Reference Example 1-5a In the same manner as in Reference Example 1—lb, except that N- (mesitylensnorphonyl) -3-methinole-1- (p-tonoleensnolephonyl) butyramine was used, the isovaleraldehyde N- (Mesitylenesulfonyl) imine (3e) was obtained.

Table 28 shows the analysis result of the obtained compound (3 e).

Table 28

Reference Example 1-6: Synthesis of pivalaldehyde N- (mesitylenesulfonyl) imine (3 f)>

In a round-bottomed flask equipped with a Dean Stark containing molecular sieves 3 A, benzene (15 m) containing a mixture of pivalaldehyde (343 zl, 3. Ommo 1) and mesitylene sulfonamide (598 mg, 3.0 mm o 1) l) was heated to reflux for 2 hours. BF ₃ 'ethanol (63/1, 0.5 mmo 1) was then added and the reflux continued for an additional 15 hours. The resulting mixture was cooled to room temperature and filtered through a small amount of silica gel using an ethyl acetate hexane solution. The solvent was removed, and the residue mixture was purified by flash column chromatography on silica gel (using ethylacetate Z-hexane = 1: 4 (volume ratio) as eluent) to give the title compound (3 f) was obtained as a white solid (43 lmg, 1.8 mmol, yield 60%).

Table 29 shows the analysis result of the obtained compound (3 f). 161 Table 29

Reference Example 1-7: Synthesis of 2-methyl-2-phenylpropionaldehyde N- (mesitylenesulfonyl) imine (3 g)>

The title compound (3 g) was obtained in the same manner as in Reference Example 1-6 except that 2-methyl-2-phenylpropionaldehyde was used instead of pivalaldehyde. Table 30 shows the analysis results.

Table 30

The title compound (3 h) was obtained in the same manner as in Reference Examples 1 to 16 except that 1-adamantancarboxaldehyde was used instead of pivalaldehyde. Table 31 shows the analysis result of the obtained compound (3 f). 162 Table 31

(3a) or (3 ') (4a) or (4')

For the following Examples 5-1 to 5-6 and Comparative Example 1 1 1 and 1 _2, either the aldimine derivative (3 a) or (3 ′) described later as a starting material based on the above reaction scheme The α-amino nitrile derivative (4a) or (4 ') was synthesized as follows through one reaction of asymmetric stress.

Cyclohexanecarboxaldehyde N- (mesitylenesulfonyl) imine (3 a) (58.7 mg, 0.20 mg) obtained in Reference Example 1-1 b in toluene (1 ml) and water (3 ml) mm o 1), and a mixture of chiral ammonium iodide (R) -2 c (2.6 mg, 0.002 mm o 1) obtained in Example 3_8 as a phase transfer catalyst, Cool to ° C and 2M KCN 163 aqueous solution (1 50 / zl, 0.3 mmo 1, 1.5 equivalents) was added dropwise. The reaction mixture was stirred vigorously at the same temperature for 2 hours. Then, by the addition of saturated NH ₄ C 1 aqueous solution, and the mixture was extracted with CH _₂ C 1 _2. The combined extracts were dried with Na ₂ so ₄ . The solvent was distilled off, and the crude product was purified by flash column chromatography using silica gel (Ethyl acetate Z hexane = 1: 4 (volume ratio) was used as eluent) and N- (Mesitylenesulfonyl) -c (cyanano) cyclohexylenomethylamine (4a) (57. Omg, 0.178 mm o 1) was obtained in a yield of 89%.

Table 32 and Table 33 show the analysis results of the obtained compound (4a). The absolute configuration of the obtained compound was converted to the corresponding amino nitrile hydrochloride as shown in Reference Example 2; after (7) ft, Effenberger, F. et al., Tetrahedron Asymmetry, 1996, No. 7, p. It was determined by comparing with the optical rotation values described in .607-618.

Table 32

The stirring time of the reaction mixture was set to 4 hours instead of 2 hours, and the amount of 2 K aqueous KCN solution added dropwise was changed from 1.5 equivalents to 1.2 equivalents. Except the 164 in the same manner as in Example 5-1 N - (mesitylene-sulfonyl) - _alpha - a (Xia Roh) hexyl methyl § Min cyclohexane (4 a) was obtained in 89% yield. Further, the obtained compound (4a) was analyzed in the same manner as in Example 5-1. Table 33 shows the analysis result of the compound (4a) obtained in this example. Example 5-3: Synthesis of α-aminominotolyl derivative (A3)〉

As a phase transfer catalyst, instead of the chiral ammonium iodide (R) — 2 c obtained in Example 3-8, the chiral ammonium iodide (R) -2 b (obtained in Example 3-6 instead of 2 c) 1 mol%), the stirring time of the reaction mixture was set to 4 hours instead of 2 hours, and the amount of 2M aqueous KCN added dropwise was changed from 1.5 equivalents to 1.2 equivalents. Except for the above, N- (mesitylenesulfonyl) -α .- (cyano) cyclohexylmethylamine (4 a) was obtained in a yield of 90% in the same manner as in Example 5-1. Further, the obtained compound (4a) was analyzed in the same manner as in Example 5-1. Table 33 shows the analysis result of the compound (4a) obtained in this example.

As a phase transfer catalyst, the chiral ammonium iodide (R) -2 obtained in Example 3-4 instead of the chiral ammonium iodide (R) -2c obtained in Example 3-8 Using a (1 mol%), set the stirring time of the reaction mixture to 4 hours instead of 2 hours, and add 21 ^ 1: aqueous solution from 1.5 equivalents to 1.2 equivalents N- (mesitylenesulfonyl) -α- (cyano) cyclohexylmethylamine (4a) was obtained in a yield of 83% in the same manner as in Example 5-1, except for changing to. Further, the obtained compound (4a) was analyzed in the same manner as in Example 5-1. Table 33 shows the analysis result of the compound (4a) obtained in this example. 165

As a phase transfer catalyst, the chiral ammonium iodide obtained in Example 3-8 (R) — 2 c instead of the chiral ammonium iodide obtained in Example 3 _ 2 (R) — 1 (1 mol%) was used, the stirring time of the reaction mixture was set to 8 hours instead of 2 hours, and the amount of 2 kg of KCN aqueous solution added dropwise was 1.

Except for the change from 5 equivalents to 1.2 equivalents, the yield of Ν- (mesitylenesulfonyl) -α- (cyano) cyclohexylmethylamine (4 a) was obtained in the same manner as in Example 5-1. Obtained at 1%. The obtained compound (4a) was analyzed in the same manner as in Example 5_1. Table 33 shows the analysis result of the compound (4a) obtained in this example.

Instead of cyclohexanecarboxaldehyde N- (mesitylenesulfonyl) imine (3a) obtained in Reference Example 1-1b, cyclohexanecarboxaldehyde prepared by a method known in the art. Using N- (p-toluenesulfonyl) imine as a phase transfer catalyst, obtained in Example 3-2 instead of chiral ammonium iodide (R) _2 c obtained in Example 3- Example 5— except that chiral ammonium iodide (R) — 1 (1 ′ mol%) was used and the amount of 2M aqueous KCN added dropwise was changed from 1.5 equivalents to 1.2 equivalents. The same operation as in 1 was performed to obtain N- (p-toluene sulphononole) -hy- (cyan) cyclohexylmethylamine (4 ′) in a yield of 84%. The obtained compound (4 ′) was analyzed in the same manner as in Example 5-1. Table 33 shows the analysis result of the compound (4 ′) obtained in this example. Comparative Example 1-1: Synthesis of α-Aminonitrile Derivative (Α7)〉

Reference Example 1 1-cyclohexanecarboxaldehyde N- (medium obtained in 1b 166 Cyclohexanecarboxalaldehyde N- (p-toluenesulfonyl) imine (0.20mmol) was used in place of Citylenesulfonyl) imine (3a) and was obtained in Examples 3-8 as a phase transfer catalyst. instead chiral ammonium Niu Muyo © product (R) -2 c were, using a known tetra Petit Luan Moniumuburomi de (TBAB) (5 mol ^_0/0) in the art, the time when the reaction mixture is stirred for 2 Set the time to 30 minutes instead of the time and change the amount of 2M KCN aqueous solution to be dropped from 1.5 equivalents to 1.2 equivalents. Xylmethylamine (4 ′) was obtained in a yield of 76%. The obtained compound (4 ′) was analyzed in the same manner as in Example 5-1. Table 33 shows the analysis results of the compound (4 ′) obtained in this comparative example. Comparative Example 1-2: Synthesis of α-Aminonitrile Derivative (Α8)>

Reference Example 1-1 In place of cyclohexane hexanealdehyde N- (mesitylenesulfonyl) imine (3a) obtained in 1b, cyclohexanecarboxaldehyde N- (p-toluenesulfonyl) imine ( 0.20 mmol) was used as a phase transfer catalyst in place of the chiral ammonium fluoride (R) —2 c obtained in Example 3-8, without adding any catalyst and stirring the reaction mixture. Same as Example 5-1 except that the stirring time was set to 30 minutes instead of 2 hours, and the amount of 2 M aqueous solution to be dropped was changed from 1.5 equivalents to 1.2 equivalents. Thus, N- (p-toluenesulfonyl) -α- (cyano) cyclohexylmethylamine (4,) was obtained in a yield of 15%. The obtained compound (4 ′) was analyzed in the same manner as in Example 5-1. Table 33 shows the analysis result of the compound (4 ′) obtained in this Comparative Example. 167 Table 33

(* 1) Not measured

As shown in Table 33, the asymmetric Strecker reaction using the catalysts of the present invention ((R) — 1, (R) — 2 a, (R) —2 b and (R) — 2 c) Both show that the reaction product can be produced stereoselectively. It can also be seen that in this reaction, the reaction product can be produced in a superior yield compared to a system using TBAB, which is a conventional phase transfer catalyst. Furthermore, among the catalysts of the present invention, in particular, the (R) — 2 a, (R) — 2 b, and (R) _2 c catalysts can produce reaction products with better optical purity. I understand.

<Example 6: Asymmetric Strecker reaction of an aldimine derivative under phase transfer conditions using aqueous KCN solution (B)> '

S0 _₂ es .S0 ₂ Mes

HN '

Catalyst ((R) -2c) (1 mol W)

R ⁶ヽH 2M KCN solution (1.5 equivalents ¾) R ⁶¹ヽCN

Toluene-water, 0 ° C

(4b) to (4h) For the following Examples 6-1 to 5-7, any of the aldimine derivatives (3b) to (3h) prepared according to the above examples as starting materials based on the above reaction scheme By using one, α-amino nitrotrinole derivatives (4 b) to (4 h) are combined as follows through an asymmetric Strecker reaction. 168 completed. Example 6-1: Synthesis of N- (mesitylenesulfonyl) -α- (cyan) cyclomethylmethylamine (4 b) (B 1)>

Cyclooctanecarboxaldehyde N- (mesitylenesulfonyl) imine obtained in Reference Example 1-2b in toluene (1 ml) and water (3 ml)

(3 b) of (0.2 Ommo 1) and the chiral ammonium iodide (R)-2 c (2.6 mg, 0.0 2 mmo 1) obtained in Example 3_ 8 as a phase transfer catalyst The mixture was cooled to 0 ° C. and 2 M aqueous KCN (150 μ 1, 0.3 mmo 1, 1.5 equivalents) was added dropwise. The reaction mixture was stirred vigorously at the same temperature for 2 hours. Then, by the addition of saturated NH ₄ C 1 solution, the element mixture was extracted with CH _₂ C 1 _2. The combined extracts were dried with Na ₂ SO ₄ . The solvent was distilled off, and the crude product was purified by flash column chromatography using silica gel (ethyl ethanyl acetate = 1: 4 (volume ratio) as eluent). (Mesitylenesulfonyl) -ct- (cyano) cyclooctylmethylamine (4b) was obtained in a yield of 88%.

The analysis results of the obtained compound (4b) are shown in Table 34 and Table 41.

Table 34

169 Example 6-2: Synthesis of N- (mesitylenesulfonyl) _1_ciano-2-methylpropylamine (4 c) (B 2)>

Instead of cyclooctanecarboxaldehyde N- (mesitylenesulfonyl) imine (3 b) obtained in Reference Example 1-2 b, isobutyl aldehyde N- (mesitylene) obtained in Reference Example 1-3 b Similar to Example 6_1 except that sulfonyl) imine (3 c) was used and the time for stirring the reaction mixture was set to 3 hours instead of 2 hours. Mesitylene sulfonyl) -1-cyano-2-methylpropylamine (4c) was obtained in a yield of 85%.

Tables 35 and 41 show the analysis results of the obtained compound (4c).

Table 35

Example 6-3: Synthesis of N- (mesitylenesulfonyl) -1-siano-3-phenylpropylamine (4 d) (B 3)>

Reference Example 1-1 3-Phenylpropionaldehyde N obtained in Reference Example 11-4b instead of cyclooctanecarboxaldehyde N- (mesitylenesulfol) imine (3b) obtained in 2b -(Mesitylenesulfonolinole) imine (3 d) was used in the same manner as in Example 6-1, except that the title N- 170 Lensulfonyl) -1-ciano-3-phenylpropylamide (4d) was obtained in an yield of 1%.

The analysis results of the obtained compound (4d) are shown in Table 36 and Table 41.

Table 36 Analysis results of the compound (4d) obtained in this example

HPLC analysis: DAICEL Chiralpak AD-H, 2-propanol / hexane = 1:10, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 20.0 min (minor) and 22.0 min (major);

[Hi] D ²⁷ -2.20. _{(. c 1.00 CHCI 3, 90} % ee);

'Η NMR (400 MHz.CDCI ₃ ) 57.31-7.21 (3H, m, ArH), 7.12-7.10 (2H, m, ArH), 6.98 (2H, s, ArH), 4.93 (1H, br, NH), 4.07 (1H, dt, J = 7.1, 9.4 Hz. NHC), 2, 79 (2H, t, J = 7.5 Hz, ArCH ₂ ), 2.59 (6H, s, ArCH ₃ ), 2.31 (3H, s, ArCH _{. 3), 2.12 (2H,} m CH 2) ppm;

^{, 3} C NMR (100 MHz, CDCI ₃ ) 5143.2. 139.1, 138.5, 132,6, 132.2, 128,8, 128.3, 126.8, 117.1, 43,5, 35.7, 31.3, 23,0, 21.1 ppm;

IR (thin film) 3277, 3028, 2974, 2926, 2245, 1603, 1566, 1454, 1333, 1155, 1098, 1057, 853, 748 cm— ';

_{HRMS (ESI-TOF) C 19} H 22 N 2 0 2 SNa ([M + Na] +) as Calculated: 365.1295, Found: 365.1294

Instead of cyclooctanecarboxaldehyde N- (mesitylenesulfonyl) imine (3 b) obtained in Reference Example 1 _ 2 b, isovaleraldehyde N- (obtained in Reference Example 1-5 b Example 6-1 except that mesitylenesulfonyl) imine (3 e) (0.2 Ommo 1) was used and the time for stirring the reaction mixture was set to 3 hours instead of 2 hours. The title N- (mesitylenesulfonyl) -1-ciano-3-methylbutyramine (4e) was obtained in a yield of 82%.

Tables 37 and 41 show the analysis results of the obtained compound (4 e). 171 Table 37

Analysis result of compound (4e) obtained in this example

HP [C analysis: DAICEL Chiralpak AD-H, 2-propanol 1 / hexane = 1:10, flow rate = 0.5 mL / min, λ = 254 ππι, retention time; 13.0 min (minor) and 15.9 min (major);

[H] D ²⁹ -31.6 ° (c 1.00. CHCI _3. 88% ee);

¹ H NMR (400 MHz.CDCI ₃ ) (57.00 (2H, s, ArH), 5,26 (1H, d, J = 8.7 Hz, NH), 4.16-4.10 (1H, m, NHC), 2.65 (6H , s, ArCH ₃ ), 2.31 (3H, s, ArCH ₃ ), 1.83 (1H, m, C, (CH ₃ ) ₂ ), 1.71-1.70 (2H, m, CH ₂ ), 0.93 (3H, d, J = 6.7 Hz, CH ₃ ), 0.90 (3H, d, J = 6.7 Hz, CH ₃ ) ppm;

¹ C NMR (100 MHz, CDCI ₃ ) 5143.1, 139.1, 132.6, 132.1, 117.5, 42.7, 42.5, 24.5, 23.0, 21.9, 21.8, 21.1 ppm;

IR (thin film) 3281, 2961. 2872. 2245, 1605, 1566, 1454, 1331, 1159, 1086, 1057, 907. 853 cm— ':

HRMS (ESI-TOF) C, 5 H 22 N 2 0 2 SNa ([M + Na] +) as Calculated: 317.1293, Found: 317.1294

In place of cyclooctanecarboxaldehyde N- (mesitylenesulfonyl) imine (3 b) obtained in Reference Example 1 _ 2 b, pivalaldehyde N-(mesitylene sulfonate) obtained in Reference Example 1-6 Nole) imine (3 f) (0.20 mmo 1) and the time for stirring the reaction mixture was set to 3 hours instead of 2 hours. The title N- (mesitylenesulfonyl) -1-siano_2,2-dimethylpropylamine (4f) was obtained in 94% yield.

Table 38 and Table 41 show the analysis results of the obtained compound (4 f). 172 Table 38 Analysis results of compound (4 f) obtained in this example

¾ "¾ · 分析: DAICEL Chiralpak AD-H, 2-propanol / hexane = 1:10, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 11.5 min (minor) and 13.4 min (major):

[a] _D ²⁹ -60.4 ° (c 1.00, CHCI ₃ , 94% ee);

Ή NMR (400 MHz, CDCI ₃ ) 57.00 (2H, s, ArH), 5, 12 (1H, d, J = 10.3 Hz, NH), 3.74 (1H, d, J = 10.3 Hz, NHC / Z), 2,66 (6H, s, ArCH ₃ ), 2.31 (3H, s, ArCH ₃ ) .1.06 (9H, s, ί-Bu) ppm;

¹³ C NMR (100 MHz, CDCI ₃ ) 5143.1, 138.9, 132.7, 132,2, 116.4, 54,4, 35.3, 25.8, 23.1, 21.1 ppm:

IR (thin film) 3277, 2970, 2941, 2874, 2247, 1605, 1566, 1470. 1402, 1333, 1159, 1094, 1057, 907, 853 cm "¹;

HRMS (ESI-TOF) Calculated as C ₁₅ H ₂₂ N ₂ 0 ₂ SNa ([M + Na] +): 317.1284, found: 317.1294

In place of cyclooctanecarboxaldehyde N- (mesitylenesulfonyl) imine (3 b) obtained in Reference Example 1 _ 2 b, 2-methyl _2_phenylpropion obtained in Reference Example 1-7 Example 6 except that aldehyde N- (mesitylenesulfonyl) imine (3 g) (0.2 Ommo 1) was used and the time for stirring the reaction mixture was set to 8 hours instead of 2 hours. — In the same manner as in 1, the title N- (mesitylenesulfonyl) -1-siano_2-methyl-2-phenylpropylamine (4 g) was obtained in a yield of 95%.

The analysis results of the obtained compound (4 g) are shown in Table 39 and Table 41. 173 Table 39

Reference Example 1-2 Instead of cyclooctanecarboxaldehyde N- (mesitylenesulfonyl) imine (3b) obtained in b, 1-adamantancarboxaldehyde obtained in Reference Example 1-8 N- (mesitylenesulfonyl) imine

(3 h) In the same manner as in Example 6-1 except that (0.2 Ommo 1) was used and the time for stirring the reaction mixture was set to 8 hours instead of 2 hours, the title N -(Mesitylenesulfonyl)-α- (Cyano) adamantylmethylamine

(4 h) was obtained in 98% yield.

Tables 40 and 41 show the analysis results of the obtained compound (4 h). 174 Table 40

Table 4 1

As shown in Table 41, when the catalyst of the present invention ((R) — 2 c) is used, an extremely long reaction time is not required for various aldimine derivatives through an asymmetric Strecker reaction. It can be seen that the desired α-amino nitrile derivative can be produced with high yield and optical purity. In particular, the present invention is As a result, the asymmetric Strecker reaction can proceed more appropriately for a substrate having an α-tert-alkyl substituent such as piperaldimine (Example 6-5 to Example 6-7). it can. As a result, tert-mouth isine and its various analogs can be produced enantiose-selectively in high yield, and many useful properties that have been difficult with asymmetric alkylation from glycine derivatives in the past. It turns out that a chiral building block can also be manufactured easily.

, So

HN '

, CN

(4a)

(95¾ee) 90% (2 steps)

HCI / ether (99% ee) Cl °

, CN

(7)

_{^{[a] D 29 = + 8.14}} (c 1.00 MeOH.) (S) were charged in a round-bottomed flask, N- obtained in Example 5-1 (Meshichirensu Ruhoniru) - _alpha - (Shiano) cyclohexyl Methylamine (4 a) (57. Omg, 0.1 78 mmo 1, 95% ee) was mixed with 0 · 15 M methanesulfonic acid TF AZ thioadisol (volume ratio 9: 1, 2 ml at room temperature) ) Solution was added and the solution was stirred for 2 hours. After removing volatile components under reduced pressure, 176 Compound was dissolved in CH ₂ C 1 ₂ and K ₂ C0 ₃ (98.9 mg, 0.7 1 2 mmo 1), water (1 ml) and benzoyl chloride (3 1 / l, 0.2 67 mmo) 1) was added continuously. The organic layer was dried over Na ₂ S 0 ₄ and concentrated. The crude product was purified by flash column chromatography using silica gel (Ethyl acetate hexane = 1:10 to 1: 4 was used as the eluent), and N- (benzoyl) -hy- (cyan) ) Cyclohexylmethylamine (6) (39 Omg, 0.16 Ommo 1) was obtained in 90% yield without loss of enantioselectivity.

Table 42 shows the analysis results of the obtained compound (6).

Table 42 Analysis results of compound (6) obtained in this reference example

HPLC analysis: DAICEL Chiralpak AD-H, 2-propanol / hexane = 1:25, f flow rate = 0.5 mL / min, S = 254 ran. Retention times: 51.8 min (/?) And 55.9 min

Ή NMR (400 MHz, CDCI ₃ ) <5 7.78-7.77 (2H, m, Ph), 7.57-7.55 (1H, m,

Ph), 7.48-7.46 (2H, m, Ph), 6.37 (1H, br d, J = 8.9 Hz, NH), 5.04

(1H, dd, J = 6.5, 8.9 Hz, CH), 1.97-1.71 (6H, m, CH and CH ₂ ),

1.33-1.17 (5H, m, CH ₂ ) ppm Also, for the intermediate cyclohexylamino nitrinole (5), the mesitylenesulfonyl group was deprotected and flash force ram chromatography using silica gel (elution) As a solution, ethyl acetate hexane acetate = 1: 2 to 1: 1 (volume ratio) was used. This ct-cyclohexylaminonitrile (5) was charged into a round bottom flask and treated with a dioxane solution (4 M) of HC 1. Volatile components were removed, and the residual product was washed with jetyl ether and dried under reduced pressure to give hydrochloride (7).

Table 43 shows the analysis results of α-cyclohexylaminonitryl ( ₅₎ . 177 Table 43

Analysis results of compound (5) obtained in this reference example

¹ H NMR (400 MHz, CDCI ₃ ) 6 3.52 (1H, d, J = 6.0 Hz, CH ₂ ), 1.89- 1,79 (4H, m, CH and CH ₂ ). 1.73-1.69 (1H, m, CH ₂ ), 1.65-1.56 (3H, | m, CH ₂ and NH ₂ ). 1.34-1.08 (5H, m, CH ₂ ) ppm;

[a] _D ²⁹ +8, 14 ° (c 1.00, eOH, 95% ee) In the above, for the absolute configuration, a-cyclohexylamino 2 was used using the values reported in Effenberger, F. et al. (supra). Based on a comparison of optical rotations of tolylhydrochloride (7), it was confirmed to be S form.

(3a) (4a)

For the following Examples 7-1 to 7-4, based on the above reaction scheme, by using the aldimine derivative (3a) prepared according to the above example as a starting material, α-amino through an asymmetric Strecker reaction Nitrile derivatives

(4a) was synthesized as follows.

Cyclohexanecarboxaldehyde N- (mesitylenesulfonyl) imine (3 a) (58.7 mg, 0.20 mm) obtained in 1 lb of Reference Example 1 in toluene (1 ml) and water (3 ml) o 1), and the chiral ammonium iodide (R) — 1 (1 molecule) obtained in Example 3-2 as a phase transfer catalyst. Le. / o) was cooled to 0 ° C., and 2M aqueous KCN solution (150 jul, 0.3 mmo 1, 1.5 equivalents) was added dropwise. The reaction mixture was stirred vigorously at the same temperature for 8 hours. Then, by the addition of saturated NH ₄ C 1 aqueous solution, and the mixture was extracted with CH _₂ C 1 _2. The combined extracts were dried over N a ₂ S0 _4. The solvent was distilled off, and the crude product was purified by flash column chromatography using silica gel (using ethyl acetate hexane = 1: 4 (volume ratio) as eluent) and N- (mesitylene) (Sulfonyl) -α- (ciano) cyclohexylmethylamine (4a) was obtained in a yield of 81%.

The absolute configuration of the obtained compound was determined by derivatization to the hydrochloride (7) as described above and comparison with the values related to optical rotation described in Effenberger, F. et al. (Supra).

The results of this example are shown in Table 44. Example 7-2: Asymmetric Strecker reaction of aldimine derivatives under phase transfer conditions using KCN aqueous solution (C 2)>

First, a chiral ammonium salt having the following structure ((R) -13 a) using the methods described in JP 2001-48866 A and JP 2003-81 976 ′

((R) -13a)

Next, the chiral ammonium obtained in Example 3-2 was used as a phase transfer catalyst. Instead of iodide (R) — 1, the above chiral ammonium salt ((R) — 13 a) (1 mol%) was used, and the time for stirring the reaction mixture was changed to 10 hours instead of 8 hours. N- (mesitylenesulfonyl) -α- (cyan) cyclohexylmethylamine (4a) was obtained in a yield of 83% in the same manner as in Example 7-1 except that the time was set. Further, the obtained compound (4a) was analyzed in the same manner as in Example 7-1. The results of this example are shown in Table 44.

First, a chiral ammonium salt ((R) -13b) having the following structure was synthesized using the methods described in JP-A-2001-48866 and JP-A-2003-81976.

((R) -13b)

Next, instead of the chiral ammonium iodide (R) — 1 obtained in Example 3 _ 2 as a phase transfer catalyst, the above chiral ammonium salt ((R)-1 3 b) (1 mol%) And the time for stirring the reaction mixture was set to 10 hours instead of 8 hours, in the same manner as in Example 7-1, to N- (mesitylenesulfonyl) -α- (cyano) cyclohexane. Xylmethylamine (4a) was obtained in 83% yield. Further, the obtained compound (4a) was analyzed in the same manner as in Example 7-1. The results of this example are shown in Table 44. 180 Example 7-4: Asymmetric Strecker reaction of aldimine derivative under phase transfer conditions using KCN aqueous solution (C4)〉

First, a chiral ammonium salt ((R)-14) having the following structure was synthesized using the method described in International Publication No. 2005/00731 No. 96 pamphlet.

((R) -14) Next, instead of the chiral ammonium iodide (R) — 1 obtained in Example 3-2 as a phase transfer catalyst, the above chiral ammonium salt ((R) — 1 4 ) (1 mol%) was used in the same manner as in Example 7-1, except that N- (mesitylenesulfoninole) -α- (cyan) cyclohexylmethylamine (4a) was obtained in a yield of 69%. It was. Further, the obtained compound (4′a) was analyzed in the same manner as in Example 7-1. The results of this example are shown in Table 44.

First, a chiral ammonium salt ((R) — 15 a) having the following structure was synthesized using the method described in International Publication No. 2005/00731 96 pamphlet.

(() -15a)

Next, instead of the chiral ammonium iodide (R) _1 obtained in Example 3-2 as a phase transfer catalyst, the above chiral ammonium salt ((R) — 15 a) (1 mol%) was used. The reaction mixture was stirred and the reaction mixture was stirred for 6 hours instead of 8 hours as in Example 7_1. Xylmethylamine (4a) yield 7

Obtained at 7%. Further, the obtained compound (4a) was analyzed in the same manner as in Example 7-1. The results of this example are shown in Table 44.

First, a chiral ammonium salt ((R) — 15 b) having the following structure was synthesized using the method described in WO2005 / 00731 No. 96 pamphlet.

((R) -15b)

Next, instead of the chiral ammonium iodide (R) — 1 obtained in Example 3-2 as a phase transfer catalyst, the above chiral ammonium salt ((R)-1 5 b) N- (mesitylenesulfonyl)-was used in the same manner as in Example 7-1 except that (1 mol%) was used and the time for stirring the reaction mixture was set to 6 hours instead of 8 hours. _α- (Cyano) cyclohexylmethylamine (4 a) was obtained in a yield of 72%. Furthermore, the obtained compound (4a) was analyzed in the same manner as in Example 7-1. The results of this example are shown in Table 44.

Table 4 4

As shown in Table 4-4, the chiral ammonium salts used in Examples 7-1 to 7-6 all functioned as catalysts in the asymmetric Strecker reaction, and the product yield was excellent. It can be seen that it can be manufactured. Furthermore, any of the chiral ammonium salts used in Example 7_1 to Example 7-6 functions as a catalyst or a stereoselective reaction accelerator that can stereoselectively advance the asymmetric Strecker reaction. You can see that <Example 8: Synthesis of a catalyst capable of proceeding with other stereoselective asymmetric streching reaction>

By using the following Reference Example 3-1 to Reference Example 3-7 and Example 8-1, other compounds useful as a catalyst capable of asymmetrically proceeding the asymmetric Strecker reaction of the present invention can be obtained. Manufactured. Reference Example 3—1: Starting material for the synthesis of quaternary ammonium salt (compound 3 2 a) Synthesis>

(31a) (32a)

To a solution of 3,4,5-trimethoxybenzoic acid (compound 31 a) (21.22 g, 100 mmol) in CHC 1 ₃ (200 mL), add N-bromosuccinimide (NB S) (21. 36 g, 12 Ommo 1) was added. The solution was heated at reflux for 8 hours. Then removed CHC 1 ₃ under reduced pressure, the residue was dissolved in 1 N of N a OH solution (1 50m l). After I washed 3 times with CHC 1 ₃ (1 5mL), acidified the alkaline solution with concentrated hydrochloric acid. The resulting precipitate was collected by filtration, washed with 1 N HC 1 and dried to give the title compound 32a (2-bromo-3,4,5-trimethoxybenzoic acid) (23. 3 g, 8 Ommo 1 Z yield: 80%). Table 45 shows the NMR spectrum of the obtained Compound 32a.

Table 45

NMR spectrum of compound 32a

400 Hz NMR (CDCI ₃ ) (57,40 (1H, s, Ar-H), 3,97 (3H, s, 0CH ₃ ), 3.91 (3H, s, 0CH ₃ ), 3.90 (3H, s, 0CH ₃ ),

<Reference Example 3-2: Starting material for the synthesis of quaternary ammonium salt (compound 3

3 a) Synthesis>

In a two-necked flask under an argon atmosphere, the compound 32a (2.33 g, 8. Ommo 1) and thionyl chloride SOC 1 ₂ (6 mL) obtained in Reference Example 3-1 were charged. The reaction mixture was heated at reflux for 4 hours. Then, excess thionyl chloride was distilled off under reduced pressure. To the residue were added THF (15 mL), pyridine (1.5 mL) and (S) -1, Γ-bi-2-naphthol (1.14 g, 4. Ommo 1). After refluxing for 3 hours, 1 N NaOH and then 1 N HC 1 were added to the reaction mixture and extracted with ether. The organic layer was dried over Na ₂ SO ₄ and concentrated. The residue was purified by silica gel column chromatography (ether hexane = 1Z1 as eluent), and the title compound 33a ((S) _2,2, -bis (2-bromo-3,4,5-trimethoxybenzoyl) was obtained. ) -1,1, -binaphthalene) (3.33 g, 4. Ommo 1) was obtained in quantitative yield. Table 46 shows the NMR spectrum of the obtained compound 33a.

Table 46

NMR spectrum of compound 33a

400 MHz 'Η NMR (CDCI ₃ ) S 8.04 (2H, d, J = 8.8 Hz, Nap-H), 7.94]

(2H, d, J = 8.4 Hz, Nap-H), 7.63 (2H, d, J = 8.8 Hz, Nap-H), 7.48

(2H, m, Nap-H), 7.37 (4H, m, Nap-H), 6.31 (2H, s, Ar-H), 3,83 (6H, s, 0CH ₃ ), 3.73 (6H, s, OCH3), 3.35 (6H, s, 0CH ₃ ).

A suspension of 50% (based on compound 33a) of active Cu powder (11.8 g, 184 mmo 1) in DMF (6 OmL) was gently refluxed under heating with vigorous stirring. Then to this mixture D dimension of compound 33 a (3.33 g, 4. Ommo l) obtained in Reference Example 3-2

MF (5 OmL) solution was added over 7 hours under argon atmosphere. After heating to reflux for 12 hours, the reaction mixture was filtered and DMF was removed under reduced pressure. The residue was partially purified by silica gel column chromatography (eluent, hexane / ethyl acetate = 2Zl), mixture of intramolecular coupling product (compound 34a) and debrominated by-product Got. This was used directly in the next reduction step without further purification.

Compound 34 a (partially purified product) obtained above was added dropwise at 0 ° C to a suspension of THF (15 mL) containing Li A 1 H ₄ (0.760 g, 16 mm o 1). did. The reaction mixture was stirred at room temperature for 4 hours and then carefully quenched with 1 N cold HC1. The mixture was extracted with ethyl acetate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate as eluent) to give the title compound 35a ((S) _4,5,6,4,5,6,6, -Hexametoxibiphenyl-2,2 ^? -Dimethano

o ∞

(0. 790 g, 2. Ommo 1 yield: 50%). Table 47 shows the NMR spectrum of the obtained Compound 35a.

Table 47

NMR spectrum of compound 35a

R (CDCI ₃ ) δ 6.89 (2H, s, Ar-H), 4.19 (4H, 0CH ₃ ), 3.89 (6Η, s, 0CH ₃ ), 3.68 (6H, s, enantiomeric excess by HP LC analysis Measured (Da ice 1 Ch ira

1 c e 1 OD, hexane 2-propanol = 8: 1, flow rate = 0.5 mL / min, retention time: R-form = 23. 1 min, form = 35.2 min). The absolute configuration was determined by comparing the retention time with the retention time of a sample synthesized separately by a known means (J. Org. Chem., 2003, 68, 9533).

(94% with respect to compound 35a) To a solution of compound 35a (0.790 g, 2.0 mm o 1) obtained in Reference Example 3-3 in CH ₂ C 1 ₂ (5 mL), tribromide Phosphorus (0. 380 mL, 4.0 mm o 1) was added at zero. The reaction mixture was stirred at room temperature for 1 hour. Subsequently, water was added to this and extracted with ether. The organic layer was washed with brine, dried over Na ₂ S 0 ₄ , concentrated, and compound 36a ((S) _4,5,6,4,5,6, _hexamethyoxybiphenyl) -2,2, -dimethylbumid). This was used in the next reduction step without further purification.

Compound 6a obtained above was added to a THF suspension (15 mL) of Li A 1 H ₄ (0.190 g, 4.0 mm o 1) at 0 ° C. . The reaction mixture was stirred at room temperature for 4 hours. Carefully entangled with 1 N cold HC 1 and extracted with ethyl acetate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent, hexane acetate ethyl ester = 3 1) to give the title compound 3 7 a ((S) -4, 5, 6, 4, , 5,6, -hexamethoxybiphenyl_2,2, -dimethane) (0.690 g, 1.9 mmo 1 Z yield: 94%). Table 48 shows the NMR spectrum of the obtained Compound 37a.

Table 48 NMR spectrum of compound 37a

400 MHz ¹ H NMR (CDCI ₃ ) 6 6.60 (2H, s, Ar-H). 3.88 (6H, s, 0CH ₃ ), 3.87 (6H, s, 0CH ₃ ), 3.68 (6H, s, 0CH ₃ ) , 1.95 (6H, s, ArCH ₃ ). 187

<Reference Example 3-5: Starting material for synthesis of quaternary ammonium salt (compound 3

8 Synthesis of a)

(37a) (38a)

Reference Example 3 4 obtained in Compound 3 7 a (0. 6 90 g , 1. 88 mm o 1) and pyridine (0. 760mL, 9. 4mmo 1) to CHC 1 ₃ (5 mL) solution of Bromine (0.480 ml, 9.4 mm o 1) was added dropwise at 0 ° C. After stirring for 30 minutes, the reaction mixture was poured into saturated aqueous Na ₂ SO ₃ and extracted with ether. The combined organic layers were washed with 1 N HC 1 and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1) to give the title compound 38a ((S) _3,3, _dibromo-4,5,6,4, , 5,6, -Hexamethoxybiphenyl-2,2, -dimethane) (0.980 g, 1.88 mmo 1) was obtained in quantitative yield. Table 49 shows the NMR spectrum of the obtained Compound 38a.

Table 49

NMR spectrum of compound 38a

400 MHz ^] NMR (CDCI ₃ ) 6 3,96 (6H, s, 0CH ₃ ), 3.91 (6H, s, 0CH ₃ ).

3.65 (6H, s, 0CH ₃ ), 2.02 (6H, s, ArCH ₃ ).

<Reference Example 3-6: Starting Material for Synthesis of Quaternary Ammonium Salt (Compound 3 9 a

188 Compound 38 a (0.52 1 g, 1. Ommol) obtained in Reference Example 3-5, 3,4,5-Trifunoleorhopheninoreboronic acid (0.704 g, 4.0 mmo) 1), palladium acetate (0.0449 g, 0.2 Ommo 1), tri-o-tolyl phosphine (0.244 g, 0.8 Ommo 1), potassium phosphate n hydrate (1.69 g, 8. A mixture of Ommo 1) and THF (1 OmL) was heated and stirred at 75 ° C under an argon atmosphere. After confirming the disappearance of the starting material by TLC, the suspension was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane hexane acetate = 5Zl) to give the title compound 39a ((S) -3, 3, -bis (3,4,5-trifluoropheny). -4, 5, 6, 4 ', 5', 6, -hexamethoxybiphenyl-2,2, -dimethane) (0.

560 g, 0.9 Ommo 1 Z yield: 90%). Table 50 shows the NMR spectrum of the obtained compound 39a.

Table 50

NMR spectrum of Compound 39a

400 MHz ¹ H NMR (CDCI ₃ ): 56.88 (4H, m, Ar-H), 3.92 (6H, s, 0CH ₃ ), 3.74 (6H, s, 0CH ₃ ), 3.71 (6H, s, 0CH ₃ ) , 1.67 (6H, s, ArCH ₃ ).

(39a) (40a) Compound 39 a (0.560 g, 0.9 Ommo obtained in Reference Example 3-6

1), N-bromosquinimide (0.352 g, 1.98 mmo 1) and A solution of 189 and 2,2, -azobisisobutyronitrile (AIBN; 0.0 1 48 g, 0.09 mm o 1) in benzene (5 mL) was heated at 80 ° C. for 4 hours. Saturated Na ₂ S0 ₃ solution was added to quench the reaction and extracted with ether. The organic layer was dried over 3 ₂ 3 ₄ and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 5Zl as eluent) to give the title compound 40a ((S) -3,3, -bis (3,4,5, -tri Fluorophenyl) -4,5,6,4,5,6, -hexamethoxybiphenyl-2,2, -dimethylbromide) (0.7 02 g 0.9mmo 1) was obtained in quantitative yield . The NMR spectrum of the obtained compound 40a is shown in Table 51.

Table 51

NMR spectrum of Compound 40a ―

400 MHz 'Η NMR (CDCI ₃ ) δ 7.08 (2H, s, Ar-H), 7.00 (2H, s, Ar-H), 3.95 _ (10H, m, 0CH ₃ , ArCH ₂ ), 3.87 _ (6H , _s, 0CH, _3.73 (6H, s, 0CH ₃ ).

(40a) ((S) -31)

Reference Example 3-7 Acetonitrile suspension of 40 0 a (0.1 5 6 g, 0.2 Ommo 1) and potassium carbonate (0.0 5 5 3 g, 0.4 Ommo 1) obtained in Reference Example 3-7 Dibutylamine (0.06 7 mL, 0.4 Ommo 1) was added to the liquid (5 mL) under an argon atmosphere. The reaction mixture was heated at 80 ° C. for 10 hours. It was then poured into HB r aqueous solution of 1 N, and extracted with CH _₂ C 1 _2. The organic layer was dried over Na ₂ S0 ₄ and concentrated under reduced pressure. Silica gel force on the residue 190 Purification by ram chromatography (methanol CH ₂ C 1 ₂ = lZl 0 as eluent) gave the title optically active quaternary ammonium bromide (compound (S)-3 1) (S form) Obtained (0.148 g, 0.1 78 mmo 1 yield: 89%). The R isomer can also be synthesized using the same procedure as described above. Table 52 shows the NMR spectrum of the compound (S) -31 obtained in this example.

Table 52

Example 8— Compound obtained in 1 (S) — 31 N MR spectrum

400 MHz ¹ H NMR (CDCI ₃ ) (57,27 (2H, s, Ar-H), 7.08 (2H, s, Ar-H). 4.33 (2H, d, J = 12.8 Hz, ArCH ₂ ), 4 , 04 (6H, s, 0CH ₃ ), 3.90 (8H, m, 0CH ₃ , ArCH ₂ ), 3.75 (6H, s, 0CH ₃ ), 2.97 (2H, m, NCH ₂ ), 2,78 (2H, m, NCH ₂ ), 1.86 (4H, m, CH ₂ ), 1.09 (2H, m, CH ₂ ), 0.77 (6H, dd, J = 1.2, 7.2 Hz, CH ₃ ), 0, 23 (2H, m , CH ₂ ).

The compound (S) -31 produced as described above is also useful as a catalyst or a stereoselective reaction accelerator capable of proceeding the stereoselective stereoselective reaction of the present invention. Reference Example 4 _a: Synthesis of α-amidosulfone (4-a) (N- (mesitylenesulfoninole) -α- (ρ-toluenesulfonyl) hexylmethylamine)> Cyclohexanecarboxaldehyde HC0 containing a mixture of sulfoxide (363 / i L, 3. Ommol), mesitylenesulfonamide (598 mg, 3. Ommo1) and sodium p-toluenesulfinate (481 mg, 3. Ommo1) A solution of ₂ H (4.5 mL) and water (4.5 mL) was stirred at room temperature for 12 hours. The resulting white precipitate was filtered off and washed with water and hexane. Then, the precipitate was recrystallized with ethyl acetate / hexane to obtain the crystalline title compound (4-a) (301 mg, 2.01 mm o 1, 67% yield).

Table 53 shows the analysis results of the obtained compound (41a). 191 Table 53

<Reference Example 4_b: Synthesis of α-amidosulfone (4-b) (N- (mesitylenesulfonyl) -α- (ρ-toluenesulfonyl) cyclooctylmethylamine)> Reference Example 4_ The title compound (4_b) was obtained in the same manner as in Reference Example 4-a except that cyclooctanecarboxaldehyde was used instead of hexanecarboxaldehyde.

Table 54 shows the analysis results of the obtained compound (4-1-b).

Table 54

Analysis results of compound (4 b) obtained in this reference example

^] H NMR (400 MHz, CDCI ₃ ) d 7.53 (2H, d, J = 8.1 Hz, ArH), 7.07 (2H, d, J = 8.1 Hz, ArH), 6.83 (2H, s, ArH), 5.30 ( 1H, d, J = 10.3 Hz, NH), 4.55 (1H, dd, J = 2.6, 10.3 Hz, NHC), 2.68-2.63 (1H, m. C (CH ₂ ) ₂ ), 2.44 (6H, s, ArCH ₃ ), 2.36 (3H, s, ArCH ₃ ), 2.29 (3H, s, ArCH ₃ ), 2.03-1.98 (1H, m, CH ₂ ), 1.73-1.68 (1H, m, CH ₂ ). 1.36 (12H, m, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 144.4, 141.8, 137.6, 135.8, 134.4, 131.6, 129.4, 128.4, 78.6, 36.8, 32.1, 27.1, 26.6, 26.5, 26.3, 25.8, 24.7, 22.9, 21.8, 21.0 ppm

IR (thin film) 3399, 3291, 3028, 2920, 2853, 1599, 1566, 1447, 1333, 1150, 1123, 1082, 912, 887, 812, 731 cm " ¹

Calculated as HRMS (ESI-TOF) C ₂₅ H ₃₅ N0 ₄ S ₂ Na ([M + Na] ⁺ ): 500.1900, Found: 500.1889. 192 <Reference Example 4> c: Synthesis of α-amide sulfone (41 c) (Ν- (mesitylenesulfonyl) -2-methyl-1- (ρ-toluenesulfonyl) propylamine)> Reference Example 4_a The title compound (41c) was obtained in the same manner as in Reference Example 4-a except that isobutyl aldehyde was used in place of the used hexane hexane aldehyde.

Table 55 shows the analysis results of the obtained compound (4 c).

Table 55

Reference Example 4—d: α-amidosulfone (4—d) (N- (mesitylenesulfoninole) -α- (ρ-toluenesulfonyl)-[N- (benzyloxycarbonyl) -4-pi Synthesis of Peridinyl] methylamine)

Reference Example 4—Reference Example 4—except that N- (benzyloxycarbonyl) -4-piperidinylcarboxaldehyde was used in place of the oral hexanecarboxaldehyde used in a. In the same manner as a, the title compound (4-d) was obtained. Table 56 shows the analysis results of the obtained compound (4-d). 193 Table 56

Reference Example 4—e: Synthesis of α-Amidosulfone (4-e) (N- (mesitylenesulfonyl) -3-phenyl-1- (p-toluenesulfonyl) propylamine)> Used in Reference Example 4_a The title compound (4-e) was obtained in the same manner as in Reference Example 4_a except that hydrocinnamaldehyde was used in place of cyclohexanecarboxaldehyde.

Table 57 shows the analysis results of the obtained compound (41-e).

194 Table 5 7

Results of analysis of the compound (4e e) obtained in this reference example

, H NMR (400 MHz, CDCI ₃ ) d 56 (2H, d, J = 8.3 Hz, ArH), 7 · 29 7.25 (2H, m, Ph), 7.22-7.18 (1Η, m, Ph), 7.12— 7.09 (4H, m, Ph and ArH), 6.84 (2H, s, ArH), 5.26 (1H, br, NH), 4.66-4.60 (1H, m, NHC), 2.85-2.78 (1H, m, CH ₂ ), 2.70-2.51 (2H, m, CH ₂ ), 2.44 | (6H, s, ArCH ₃ ), 2.37 (3H, s, ArCH ₃ ). 2.30 (3H, s, ArCH ₃ ), 2.07- | 1.97 ( 1H, m, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 144.9, 142.0, 139.6, 137.9, 135.1, 132.9, 131.7, 129.4, 128.8, 128.5, 128.3, 126.3, 73.1, 31.3, 30.7, 23.0, 21.8, 21.1 ppm

IR (thin film) 3273, 3061, 3028, 2976, 2940, 2866, 1599, 1566, 1454, 1331, 1302, 1155, 1146, 1082, 853 cm " ¹

Calculated as HRMS (ESI-TOF) C ₂₅ H ₂₉ N0 ₄ S ₂ Na ([M + Na] ⁺ ): 494.1430, Found: 494.1432.

<Reference Example 4—f: Synthesis of α-amidosulfone (4_ f) (N- (mesitylenesulfonyl) -3-methyl- 卜 (p-toluenesulfoninole) ptylamine)> Used in Reference Example 4a The title compound (41f) was obtained in the same manner as in Reference Example 4-a except that isopentyl aldehyde was used in place of hexanecarboxaldehyde.

Table 58 shows the analysis results of the obtained compound (41-f).

Table 58

195 <Reference Example 4— _g : Synthesis of _α- Amidosulfone (4—g) (N- (Mentylenesulfonyl) -l- (p-toluenesulfonyl) heptylamine]>

Reference compound 4- (g) was obtained in the same manner as Reference example 4-a, except that heptyl aldehyde was used instead of cyclohexanecarboxaldehyde used in reference example 4-a.

Table 59 shows the analysis result of the obtained compound (41 g).

Table 59

<Reference Example 4—h: Synthesis of α-amidesulfone (4-h ′) (N- (mesitylenesulfonyl) -2-phenyl-1- (p-tonoleenesulfonyl) ethylamine)> Reference Example 4— The title compound (41 h) was obtained in the same manner as in Reference Example 4-a, except that phenylacetoaldehyde was used in place of the cyclohexanecarboxaldehyde used.

Table 60 shows the analysis results of the obtained compound (4 h). 196 Table 60

Reference Example 4—i: α-Amidosulfone (4—i) (N- (2,3,6_Limethyl-4-methoxybenzenesulfinole) -3-phenyl-1- (p-toluenesulfonoxy) Synthesis of Lu) propylamine)>

To a suspension of THF (6 OmL) containing Na H (2. 40 g, 6 Ommo 1), 2, 3, 5-trimethylphenol (5.56 g, 4 Ommo 1) was added at 0 ° C. The mixture was added dropwise and the mixture was stirred for 1 hour. Me I (5 mL) was then added dropwise and the reaction mixture was stirred for an additional 3 hours. This was taentied with water and extracted with jetyl ether. Volatiles were removed, and the residue was purified by flash column chromatography using silica gel (ethyl acetate Z-hexane = 1: 20 (volume ratio) was used as eluent). 2, 3, 5 -Trimethylanisole (5.53 g, 36.8 mmo 1) was obtained as a colorless liquid (yield 92%).

The CH ₂ C 1 ₂ solution of 2,3,5-trimethylaninol (1M solution, 36.8 mmo 1) is cooled to 0 ° C, and the CH ₂ C 1 ₂ solution of Kuroguchi Sulfuric Acid (3M solution) Liquid, 1 1 Ommo 1) was added dropwise at this temperature. After stirring for 1 hour, 197 quenched by the sum N a HC0 ₃ solution, the aqueous layer after the liquid separation was put extracted with acetic acid Echiru. The combined organic layers were concentrated to obtain 4-methoxy-2,3,6_trimethylbenzene sulfonic acid chloride. This was dissolved in THF, cooled to 0 ° C., 25% aqueous ammonia (8 mL) was added, and the mixture was stirred for 2 hours. After removing volatiles, the residual solid was washed with water and hexane, and 4-methoxy-2,3,6-trimethylbenzenesulfonamide (5.99 g, 26.1 mm o 1) was added. Obtained as a white solid (71% yield over 2 steps).

Next, 3-phenylpropyl aldehyde (6. Ommo 1), 4-methoxy-2,3,6-trimethylbenzenesulfamide (3.) was added in HCO ₂ H (9 mL) and water (9 mL). Omm o 1) and sodium p-toluenesulfinate (6 Ommo 1) were mixed. After stirring this mixture at room temperature for 24 hours, the resulting white precipitate was filtered and washed with water and hexane. The precipitate was purified by recrystallization from THF hexane to obtain the title compound (4_i). The analysis results of the obtained compound (41-i) are shown in Table 61.

Table 6 1 Results of analysis of the compound (4—ί) obtained in this reference example

¹ Η R (400 MHz, CDCI ₃ ) d 7,56 (2H, d, J = 8.2 Hz, ArH), 7.29 7.27 (2H, m. Ph), 7.22-7.20 (1H, m, Ph), 7.13- 7.08 (4H, m, Phi and ArH), 6.42 (1H, s, ArH), 5.20-5.17 (1H, m, NH), 4.66-4.63 (1H, m, NHC), 3,84 (3H, s, 0CH ₃ ), 2.89-2.82 (1H, m, CH ₂ ), 2.75-

2.67 (1H, m, CH ₂ ), 2.61-2.57 (1H, m, CH ₂ ), 2.42 (3H, s, ArCH ₃ ), 2.39 (3H, s, ArCH ₃ ), 2.33 (3H, s, ArCH ₃ ), 2.10 (3H, s, ArCH ₃ ),

2.09-1.99 (3H, m, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 159.3, 144.9, 139.8, 138.0, 137.6, 133.2, 130.3, 129.4, 128.8, 128.6, 128.4, 126.4, 125.1, 111.9, 73.0, 55.5, 31.2, 30.8, 24.2, 21.6 , 18.2, 12.0 ppm

IR (thin film) 3269, 3061, 3026. 2938, 2864, 2848, 1585, 1562, 1495, 1454, 1381, 1302, 1290. 1179, 1115. 1082, 1044, 1030, 1016, 988, 953, 916, 872 cm " ¹

HRMS (ESI-TOF) Calculated as C ₂₆ H ₃₁ N0 ₅ S ₂ Na ([M + Na] ⁺ ): 524.1541, Found: 524.1536, 198

<Reference Example 4—j: α-amide sulfone (41-j) (N- (2,3,6-trimethyl-4-methoxybenzenesulfonyl) -3-methinole-1- (p-toluenesulfoninole) Synthesis of ptylamine)

Reference title 4-i The title compound (41-j) was obtained in the same manner as Reference example 41-i except that isopropyl aldehyde was used in place of propyl aldehyde.

Table 62 shows the analysis results of the obtained compound (4-j).

Table 62

Analysis results of the compound (4〗) obtained in this reference example ti NR (400 MHz, CDCI ₃ ) d 7.54 (2H, d, J = 8.2 Hz, ArH), 7.06 (2H, d, J = 8.0 Hz , ArH), 6.42 (1H, s, ArH), 5.02 (1H, d, J = 9.9 Hz, NH), 4.76-4.70 (1H, m, NHC), 3.84 (3H, s, ArOCH ₃ ), 2.46 ( 3H, s, ArCH ₃ ), 2.41 (3H, s, ArCH ₃ ), 2.32 (3H, s, ArCH ₃ ), 2.11 (3H, s, ArCH ₃ ), 2.08-2.01 (1H, m, CH ₂ ), 1.85-1.75 (1H, m, C〃 (CH ₃ ) ₂ ), 1.70-1.63 (1H, m, CH ₂ ), 0.97 (3H, d, J = 6.7 Hz, CH ₃ ), 0.93 (3H, d, J = 6.7 Hz, CH ₃ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 159.1, 144.7, 137.8, 137.4, 133.1, 130.8, 129,3, 128,8, 124.9, 111.8, 72.6, 55.4, 37.7, 24.1, 24.0, 23.3, 21.5, 21.0 , 18.2, 11.9 ppm

IR (thin film) 3271, 2961, 2870, 1585, 1562, 1464, 1429, 1385, 1310, 1302, 1236, 1179, 1146, 1119, 1082, 1045, 1016, 955,

907, 841. 812, 731, 704 cm " ¹

HR S (ESI-TOF) Calculated as C ₂₂ H ₃₁ N 0 ₅ S ₂ Na ([M + Na] ⁺ ): 476.1536, measured: 476.1527.

Reference Example 4 1 k: α-Amidosulfone (4—k) (N- (2, 3, 6-trimethyl-4-methoxybenzenesulfinole)-1- (p-toluenesulfoninole) heptyla Min) Synthesis>

Reference Example 41 The title compound (41k) was obtained in the same manner as Reference Example 41-i, except that heptylaldehyde was used instead of propylaldehyde used in i.

Table 63 shows the analysis results of the obtained compound (41k). 199 Table 63

Reference Example 4—1: c—amide sulfone (4-1) (N- (2,3,6-trimethylol-4-methoxybenzenesulfonol))-2-phenyl-l- (p-toluenesulfo Nyl) ethylamine)>

The title compound (4_ 1) was obtained in the same manner as in Reference Example 4-i except that phenylacetaldehyde was used in place of propyl aldehyde used in Reference Example 4-i. '

Table 64 shows the analysis results of the obtained compound (41).

200 Table 64

Analysis results of the compound (4 I) obtained in this reference example

^] H (400 MHz, CDCI ₃ ) d 7.73 (2H, d, J = 8.2 Hz, Ar-H), 7.22! (2H, d, J = 8.0 Hz, Ar-H), 7.11-7.03 (5H, m, Ph), 6,29 (1H, s, Ar-H), 5.28 (1H, d, J = 10.4 Hz, NH), 4.87-4.84 (1H, m, NHC /), 3.81 (3H, s, OCH3), 3.61 (1H, dd, J = 4.2, 14.4 Hz, CH ₂ ), 3.10 | (1H, dd, J = 9.3, 14.4 Hz, CH ₂ ), 2.38 (3H, s, ArCH ₃ ), 2.32 ( 3H, s, ArCH ₃ ), 2.21 (3H, s, ArCH ₃ ), 2.00 (3H, s, ArCH ₃ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 159.0, 145.2, 137.7, 137.1, 133.9, 132.9, 130.3, 129.5. 129.5, 129.3, 128.3. 127.1, 124.9, 111.8, 74.5, 55.4, 34.3, 24.2, 21.7, 18.1 , 11.9 ppm

IR (thin film) 3291, 3063, 3028, 2940. 2870, 2847, 1587, 1562, 1497, 1456, 1435, 1381, 1335, 1304, 1179. 1148,

1082, 1030, 1016, 935, 907, 843, 814, 739, 702 cm " ¹

HRMS (ESI-TOF) Calculated as C ₂₅ H ₂₉ N0 ₅ S ₂ Na ([+ Na] ⁺ ): 510.1379, found: _510.1379.

Example 9-1: Asymmetric Strecker reaction under phase transfer conditions using various α-amide sulfones (D 1)> Mes

201 N- (mesitylenesulfoninole) -a- (p-tonoreensnorehoninore) hexinoleme tylamamine obtained in Reference Example 4a in toluene (l mL) and water (3 ml) (4 — a) (8 9. 9 mg, 0.20 mm o 1) and the chiral ammonium iodide obtained in Example 3 — 8 ((R) — 2 c) (2.6 mg, The mixture of 0. 0 0 2mmo 1) was cooled to 0 and 2M aqueous KCN solution (1 0 5 / i L, 0.21 Ommo 1, 1.05 eq) was added dropwise. The reaction mixture was stirred vigorously at the same temperature for 2 hours. Then, by the addition of saturated NH ₄ C 1 aqueous solution, and the mixture was extracted with CH _₂ C 1 _2. The combined extracts were dried at & ₂ 30 ₄ . The solvent was distilled off, and the crude product was purified by flash column chromatography using silica gel (using ethyl acetate hexane = 1: 4 (volume ratio) as eluent) and N- (mesitylene sulfate). (Honyl) _ _α- (Cyano) cyclohexylmethylamine (S form) (similar to the product obtained in Example 5-1) is quantitative (6 4. lmg, 0.2 mm o To 1)

The product obtained in this example was analyzed by HP LC (Daicel C hira 1 pak AD-H, 2_propanol hexane = 1: 10, flow rate 0.5 mLZ min, eh = 2 54 nm, Retention times; 13.3 minutes (R) and 14.7 minutes (S)). The optical purity of the compound was 97% ee.

Table 65 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example.

202 Table 65

Example 9 1-1 Analysis results of the product obtained in 1

HPLC analysis: DAICEL Chiralpak AD-H. 2-propanol / hexane = 1:10, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 13.3 min (1 and 14.7 min)

(S)

'Η NMR (400 MHz. CDCI ₃ ) (56.99 (2H, s, ArH), 5.37 (1H, d, J = 9.1 Hz, NH), 3.92 (1H, dd, J = 6.7, 9.1 Hz, NHC /) , 2.65 (6H, s, ArCH ₃ ), 2.31 (3H, s, ArCH ₃ ), 1.86-1.67 (6H, m, CH and GH ₂ ). 1.29- 1.06 (5H, m, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) (5143.0, 139.0, 132.7, 132.1, 116,5, 49.5, 41.2, 29.0, 28.4, 25.7, 25.4, 25.3, 23.0. 21.1 ppm

IR (thin film) 3275, 3028, 2930, 2855, 2253. 1602, 1566, 1450, 1330, 1157, 1091, 1057, 904, 852, 731 cm " ¹

HRMS (ESI-TOF) Calculated as C ₁₇ H ₂₄ N ₂ 0 ₂ SNa ([M + Na] +): 343.1454, found: 343.1451 Example 9-2: Interphase with various α-amide sulfones Asymmetric Strecker reaction under transfer conditions (D 2)>

Reference Example 4 In place of N- (mesitylenesulfonyl) -α- (ρ-toluenesulfonyl) cyclohexylmethylamine (4_ a) obtained in a, N-(obtained in Reference Example 4-b N- (mesitylenesulfonyl) -α-, in the same manner as in Example 9-1, except that mesitylenesulfonyl) -α- (p-toluenesulfonyl) cyclooctylmethylamine (4-b) was used. (Ciano) cyclooctylmethylamine (S form) (which is the same compound as the product obtained in Example 6-1) was obtained in a yield of 99%.

The product obtained in this example was analyzed by HP LC (Daicel Ch iralpak AD-H, 2-propanol Z-hexane = 1:10, flow rate 0 · 5 mL / min, e = 254 nm, retention time 14.6 minutes (minor) and 17.9 minutes (major)). The optical purity of the compound was 98% ee.

Table 66 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example. 203 Table 66

Analysis results of the product obtained in Example 9-2

HPLC analysis: DAICEL Chiralpak AD-H, 2-propanol / hexane = 1:10, flow rate = 0,5 mL / min, λ = 254 nm, retention time; 14.6 min (minor) and 17.9 min (major) )

Ή NMR (400 MHz.CDCI ₃ ) <57.00 (2H, s. ArH), 5.12-5.07 (1H, m, NH), 3.94 (1H, dd, J = 5.9, 9.5 Hz, NHCi, 2.65 (6H, s , ArCH ₃ ), 2.31 (3H, s, ArCH ₃ ), 1.92 (1H, br, C〃 (CH ₂ ) ₂ ), 1.73-1.40 (12H, m, CH ₂ ) ppm

^{, 3} C NMR (100 MHz, CDCI ₃ ) (5143.1, 139.0, 132.8. 132,2, 116.8, 50.5, 41.0, 29.4, 29.1, 26.3, 26.3, 26.2, 25.5, 25.1, 23.1, 21.1 ppm;

IR (thin film) 3277, 3028, 2920, 2853, 2245, 1605, 1566, 1447, 1333, 1157, 1057, 907, 853, 733 cm— '

HRMS (ESI-TOF) Calculated as C ₁₉ H ₂₈ N ₂ 0 ₂ SNa ([M + Na] +): 371.1766, Found: 371.1764

Reference Example 4—In place of N- (mesitylenesulfonyl) -α- (ρ-toluenesulfonyl) cyclohexylmethylamine (41a) obtained in a, N- In the same manner as in Example 9-1, except that (mesitylenesulfonyl) -2-methinole-1- (p-toluenesulfonyl) propylamine (4-c) was used, N- (mesitylenesulfonyl) -1_Ciano-2-methylpropylamine (S form) (the same compound as the product obtained in Example 6-2) was obtained in a yield of 99%.

The product obtained in this example was analyzed by HPLC (Daicel Ch ira 1 pak AD-H, 2-propanol Z-hexane = 1:10, flow rate 0.5 mLZ, e = 254 nm, retention Time: 13.7 minutes (minor) and 15.5 minutes (major)). The optical purity of the compound was 97% ee.

Table 67 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example. 204 Table 67

Reference Example 4—Instead of N- (mesitylenesulfonyl) -α- (ρ-toluenesulfonyl) cyclohexylmethylamine (4-a) obtained in a, Reference Example 4 1 N- Example 9-1 except that (mesitylenesulfonol) -a- (p-toluenesulfoel)-[Ν- (benzyloxycarbonyl) -4-piperidinyl] methylamine (4_d) was used Similarly, N- (mesitylenesulfonyl) -α- (ciano)-[[-(benzyloxycarbonyl) -4-piperidinyl] methylamine (S form) was obtained.

The product obtained in this example was analyzed by HP LC (Daicel Ch iralpak AD-H, 2-propanol hexane = 1: 3, flow rate 0.5 mLZ, min = 254 nm, retention time; 16 2 minutes (minor) and 18.5 minutes (major)). The optical purity of the compound was 99% ee.

Table 68 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example. 205 Table 68

Analysis of the product obtained in Example 9-4 ^

HPLC analysis: DAICEL Chiralpak AD-H, 2-propanol / hexane = 1: 3, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 16.2 min (minor) and 18.5 min (major)

[a] _D ²⁵ 1,88. (c 1.00, CHCI ₃ , 99% ee)

¹ H NMR (400 MHz, CDCI ₃ ) d 7.37-7.28 (5H, m, Ph), 6.98 (2H, s, ArH), 5.92 (1H, d, J = 9.9 Hz, NH), 5.10 (2H. S , PhCH ₂ ), 4.23 (2H, br, CH ₂ ), 3.92-3.90 (1H, m, NHC), 2.73 (2H, br, CH ₂ ), 2.63 (6H, s, ArCH ₃ ), 2.29 (3H, s, ArCH ₃ ), 1.88-1.83 (3H, m. CH ₂ and CH), 1.37-1.19 (2H, m, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 155.0, 143.2, 139.1, 136.4, 132.7, 132.2, 128.4, 128.0, 127.8, 116.1, 67.3. '43.2, 39.6, 22.9, 20.9 ppm; IR (thin film) 3225 ,:

2860, 2251.

1674, 1605, 1566, 1472, 1435, 1335, 12 2 I229. 1157.

1134, 1088, 1057, 1020, 910, 854, 731 cm— ¹

HRMS (ESI-TOF) Calculated as C ₂₄ H ₂₉ N ₃ 0 ₄ SNa ([M + Na] ⁺ ): 478.1771, actual value: 478.1771. 2 7

Reference Example 4 In place of N- (mesitylenesulfonyl) -α_ (ρ-toluenesulfonyl) cyclohexylmethylamine (4_a) obtained in a Reference Example 41 1 N- (mesitylene) obtained in e N- (mesitylenesulfonyl) -1- 1-ciano-in the same manner as in Example 9-1, except that (sulfonyl) -3-phenyl-l- (p-toluenesulfonyl) propylamine (4-e) was used. Yield of 3-phenylpropylamine (S form) (same compound as the product obtained in Example 6-3) 9

Obtained at 9%.

The product obtained in this example was analyzed by HPLC (Daicel Ch ira 1 pak AD-H, 2-propanol / hexane = 1:10, flow rate 0.5 mLZ min, eh = 254 nm, retention Time; 20. 0 minutes (minor) and 22.0 minutes (major)). The optical purity of the compound was 94% ee.

The analysis results of the product obtained in this example are shown in Table 69, and the results in this example are shown. 206 is shown in Table 77.

Table 69

Analysis result of the product obtained in Example 9-15

HPLC analysis: DAICEL Chiralpak AD-H, 2-propanol / hexane = 1:10, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 20.0 min (minor) and 22.0 min (major)

'Η 隱 (400 MHz, CDCI ₃ ) 57.31-7.21 (3H, m, ArH), 7.12-7.10 (2H, m, ArH), 6.98 (2H, s, ArH), 4,93 (1H, br, NH ), 4,07 (1H, dt, J = 7.1.

9.4 Hz, NHC, 2. 79 (2H, t, J = 7.5 Hz, ArCH ₂ ), 2.59 (6H, s, ArCH ₃ ), 2,31 (3H, s, ArCH ₃ ), 2:12 (2H, m, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) 5143.2. 139.1, 138.5, 132.6, 132.2. 128.8, 128.3, 126.8, 117.1, 43.5, 35.7, 31.3, 23.0, 21.1 ppm

IR (thin film) 3277, 3028, 2974, 2926, 2245, 1603, 1566, 1454, 1333, 1155, 1098, 1057, 853, 748 cm " ¹

HRMS (ESI-TOF) Calculated as C ₁₉ H ₂₂ N ₂ 0 ₂ SNa ([M + Na] +): 365.1295, found: 365.1294

Reference Example 4 Instead of N- (mesitylenesulfonyl) -a- (p-toluenesulfonyl) cyclohexylmethylamine (4 _a) obtained in _a, Reference Example 4 N- ( N- (mesitylenesulfonyl) -1-cyano-3 in the same manner as in Example 9-1, except that mesitylenesulfonyl) -3-methyl_l- (p-toluenesulfonyl) ptyramine (4-f) was used. -Methylptylamine (S form) (the same compound as the product obtained in Example 6-4) was obtained in a yield of 99%.

The product obtained in this example was analyzed by HPLC (Daicel Ch ira 1 pak AD-H, 2-propanol / hexane = 1:10, flow rate 0.5 mLZ min, e = 254 nm, retention Time; 13.0 minutes (minor) and 15.9 minutes (major)). The optical purity of the compound was 9 l% e e.

Table 70 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example. 207 Table 70

Reference Example 4— Instead of N- (mesitylenesulfonyl) -ct- (p-toluenesulfonyl) cyclohexylmethylamine (4-a) obtained in a, N- N- (mesitylenesulfonyl) -1-siano-heptylamine in the same manner as Example 9_1 except that (mesitylenesulfonyl) -1- (p-toluenesulfonyl) heptylamine (41 g) was used. (S-form) was obtained with a yield of 96%.

The product obtained in this example was analyzed by HPLC (Daicel Ch ira 1 pak AD-H, 2-propanol nohexane = 1:10, flow rate 0.5 mLZ, e = 254 nm, retention Time; 13. 1 minute (minor) and 1 5.1 minutes (major)). The optical purity of the compound was 8.4% _ee .

Table 71 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example. 208 Table 7 Analysis results of the product obtained in Example 9-7

HPLC analysis: DAICEL Chiralpak AD-H, 2-propanol 1 / hexane = 1:10, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 13.1 min (minor) and

15.1 minutes (major)

[a] _D ²⁶ -25.7 ° (c 1.00, CHCI ₃ , 84% ee)

'Η NMR (400 MHz, CDCI ₃ ) d 7.00 (2H, s, ArH), 5.19 (1H, d, J =

7.0 Hz, NH), 4.13-4.07 (1H, m. NHC /), 2.65 (6H, s, ArCH ₃ ). 2.31 (3H, s, ArCH ₃ ), 1.83-1.79 (2H, m, CH ₂ ), 1.43-1.40 (2H, br, CH ₂ ), 1.28-1.19 (6H, br, CH ₂ ), 0.87 (3H, t, J = 6.8 Hz, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 143.2, 139.2, 132.8, 132.2, 117.4, 43.9, 33.9, 31.3, 28.2, 25.0, 22.9, 22.4, 21.0 ppm

IR (thin film) 3275, 3028, 2955, 2928, 2859, 2245, 1605,

1566, 1456, 1429, 1406, 1381, 1335, 1188, 1157, 1090, 1057,

1034, 853 cm— ¹

HRMS (ESI-TOF) Calculated as C ₁₇ H ₂₆ N ₂ 0 ₂ SNa ([M + Na] ⁺ ): 345.1606, found: 345.1607.

Reference Example 4—Instead of N- (mesitylenesulfonyl) -α- (ρ-toluenesulfonyl) cyclohexylmethylamine (41a) obtained in a, N- N- (mesitylenesulfonyl) -1_ in the same manner as in Example 9_1 except that (mesitylenesulfonyl) -2-phenyl-l- (p-toluenesulfonyl) ethylamine (41 h) was used. Cyan-2-phenylethylamine (S form) was obtained with a yield of 93%.

The product obtained in this example was analyzed by HPLC (Daicel Ch ira 1 pak AD-H, 2_propanol / hexane = 1: 10, flow rate 0.5 mL / min, e = 254 nm, Retention time; 21.3 minutes (minor) and 26.4 minutes (major)). The optical purity of the compound was 85% ee.

Table 72 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example. 209 Table 72

Analysis results of the product obtained in Example 9-8

HPLC analysis: DAICEL Chiralpak AD-H, 2-propanol 1 / hexane = 1:10, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 21.3 min (minor) and

26.4 minutes (major)

[a] _D ²⁸ -43.0 ° (c 1.00, CHCI ₃ , 85% ee)

^] W NMR (400 MHz, CDCI ₃ ) d 7.38-7.32 (3H, m, ArH), 7.26-7.22 (2H, m, ArH), 6.95 (2H, s, ArH), 4.84 (1H, d, J = 9.4 Hz, NH). 4.43- 4.37 (1H, m, WWCff), 3.12-3.10 (2H, m, CH ₂ ), 2.55 (6H, s, ArCH ₃ ), 2.30 (3H, s, ArCH ₃ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 143.3, 139.2, 132.9, 132.5, 132.3, 129.5, 129.2, 128.2, 116.8, 44.9, 39.6, 22.8, 21.0 ppm

IR (thin film) 3277, 3030, 2978, 2940, 2855, 2247, 1605, 1566. 1497, 1456, 1404, 1333, 1188, 1157, 1094, 1057, 1032, 939, 903, 853, 748, 700 cm — ¹

HRMS (ESI-TOF) Calculated as C ₁₈ H ₂₀ N ₂ 0 ₂ SNa ([+ Na] ⁺ ): 351.1134, Found: 351.1138. Example 9-9: Using various ct-amide sulfones Asymmetric Strecker reaction under phase transfer conditions (D9)>

Reference Example 4 Instead of N- (mesitylenesulfonyl) -ct- (p-toluenesulfonyl) cyclohexylmethylamine (4-a) obtained in _a, N-obtained in Reference Example 4-i Example 9-1 1 except that (2,3,6-trimethyl-4-methoxybenzenesulfonyl) -3-phenyl-l- (p-toluenesulfonyl) propylamine (4-i) was used. In the same manner as above, N_ (2,3,6-trimethyl-4-methoxybenzensulfonyl) -1-ciano-3-phenylpropylamine (S form) was obtained in a yield of 98%.

The product obtained in this example was analyzed by HP LC (Daicel Ch ira 1 pak OD-H, 2_propanol nohexane = 1: 3, flow rate 0.5 mL / min, E = 254 nm, Retention time; 22.1 min (minor) and 31.9 min (major)). The optical purity of the compound was 96% ee.

The analysis results of the product obtained in this example are shown in Table 73, and the results in this example are shown in Table 77. 210 Table 73

Analysis results of the products obtained in Examples 9-9

HPLC analysis: DAICEL Chiralpak 0D-H, 2-propanol 1 / hexane = 1: 3, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 22.1 min (minor) and

31.9 minutes (major)

[a] _D ²⁴ -5.57 ° (c 1.00, CHCI ₃ , 96% ee)

¹ H NMR (400 MHz, CDCI ₃ ) d 7.28-7.24 (2H, m, ArH), 7.22-7.19 (1H, m, ArH), 7.09 (2H, d, J = 7.0 Hz, ArH), 6.58 (1H , s, ArH), 5.30 (1H, d, J = 9.4 Hz, NH), 4.05-3.99 (1H, m, NHC /), 3.85 (3H, s, 0CH ₃ ), 2.77 (2H, t, J = 7.4 Hz, ArCH ₂ ), 2.61 (3H, s, ArCH ₃ ), 2.55 (3H, s, ArCH ₃ ), 2.15-2.08 (2H, m, CH ₂ ) ppm

¹³ C NMR (100 MHz, CDCI ₃ ) d 159.9, 139.2, 139.0, 138.8, 128.7, 128.4, 127.6, 126.7, 125.7, 117.5, 112.2, 55.5, 43.3, 35.4, 31.1, 24.2, 18.0, 12.0 ppm

IR (thin film) 3275, 3026, 2940, 2849, 2251, 1585, 1560, 1497, 1454, 1447, 1379, 1308, 1275, 1179, 1144, 1121, 1016, 988,

914. 870, 843, 735, 700 cm " ¹

HRMS (ESI-TOF) Calculated as C ₂₀ H ₂₄ N ₂ 0 ₃ SNa ([M + Na] ⁺ ): 395.1400, measured: _395.1390. 'Example 9-10: Various α— Asymmetric Strecker reaction under phase transfer conditions using amide sulfone (D 10)>

Reference Example 4 In place of N- (mesitylenesulfonyl) -α_ (ρ-toluenesulfonyl) cyclohexylmethylamine (41a) obtained in a, N- (obtained in Reference Example 4-j 2, 9, 6-trimethyl-4-methoxybenzenesulfoyl) -3-methyl-l- (p-toluenesulfonyl) butyramine (41) Same as Example 9-1, except that 4- (i) was used As a result, N- (2,3,6-trimethyl-4-methoxybenzenesulfonyl) -1-siano-3-methylbutyramine (S form) was obtained in a yield of 99%. The product obtained in this example was analyzed by HPLC (Chiralpak OD-H, 2-propanol Z-hexane, manufactured by Daicel Corp. = 1: 3, flow rate 0 · 5 mlZ, min = 254 nm, retention time; 14 3 minutes (minor) and 1 1.0 minutes (major)). The optical purity of the compound was 92% ee.

Table 74 shows the analysis result of the product obtained in this example, and Table 77 shows the result in this example. 211 Table 74

Example 9-1 1 (Results of analysis of the product obtained

HPLC analysis: DAICEL Chiralpak 0D-H, 2-propanol I / hexane = 1: 3, flow rate = 0.5 mL / min, λ = 254 nm, retention time; 11.0 min (minor) and

14.3 minutes (major)

[a] _D ²² -33.9 ° (c 1.00, CHCI ₃ , 92% ee)

¹ H NMR (400 MHz. CDCI ₃ ) d 6.61 (1H, s, ArH), 5.24 (1H. D, J =

9.2 Hz. NH), 4.13-4.07 (1H, m. NHC / Z), 3.86 (3H, s, 0CH ₃ ), 2.69 (3H, s, ArCH ₃ ), 2.59 (3H, s, ArCH ₃ ), 2.16 (3H, s, ArCH ₃ ), 1.84 (1H, sept, J = 6.8 Hz, C / (CH ₃ ) ₂ ), 1.70-1.66 (2H, m, CH ₂ ), 0.92 (3H, d, J = 6.8 Hz, CH ₃ ), 0.89 (3H, d, J = 6.8 Hz, CH ₃ ) ppm

13,

C NMR (100 MHz. CDCI ₃ ) d 160.0, 139.1, 139.0, 127.7, 125.7,

117.8, 112.2, 55.5. 42.6, 42.4, 24.4, 24.3, 21.8, 21.7, 18.0. 11.9 ppm

IR (thin film) 3277, 2959, 2940, 2872, 2851, 2255, 1585,

1560, 1464, 1445, 1381, 1308, 1273, 1179, 1140, 1119, 1086, 1015, 988, 914, 841, 812, 731 cm— ¹

HRMS (ESI-TOF) Calculated as C ₁₆ H ₂₄ N ₂ 0 ₃ SNa ([M + Na] +): 347.1400, measured: 347.1407.

Reference Example 4— Instead of N- (mesitylenesulfonyl) -α- (ρ-toluenesulfonyl) cyclohexylmethylamine (4-a) obtained in a, N- In the same manner as in Example 9-1, except that (2, 3, 6-trimethyl-4-methoxybenzenesulfonyl) -1_ (p-toluenesulfonyl) heptylamine (4-k) was used, N- ( 2,3,6-Trimethyl-4-methoxybenzenesulfonyl) -1-ciano-heptylamine (S form) was obtained in a yield of 96%.

The product obtained in this example was analyzed by HPLC (Daicel Ch ira 1 pak OD-H, 2-propanol Z-hexane = 1: 3, flow rate 0.5 ml LZ, eh = 254 nm, Retention time; 25.9 minutes (minor) and 1 5 · 5 minutes (major)). The optical purity of the compound was 89% ee.

The analysis results of the product obtained in this example are shown in Table 75, and the results in this example are shown. 212 is shown in Table 77.

Table 75

Example 9_12: Asymmetric Strecker reaction under phase transfer conditions using various α-amide sulfones (D 1 2)〉

Reference Example 4 In place of N- (mesitylenesulfonyl) -α- (ρ-toluenesulfonyl) cyclohexylmethylamine (4_ a ') obtained in a, N- obtained in Reference Example 4-1 Example 9-1 1 except that (2,3,6-trimethyl-4-methoxybenzenesulfonyl) -2-phenyl-l- (p-toluenesulfonyl) ethylamine (4-1) was used. In the same manner as above, N- (2, 3,6-trimethyl-4-methoxybenzensulfonyl) -1-cyano-2-phenylethylamine (S form) was obtained in a yield of 86%.

The organism obtained in this example was analyzed by HPLC (Daicel Ch ira 1 pak OD-H, 2-propanolnohexane = 1: 3, flow rate 0 · 5 mL min, f = 254 nm, retention time; 22 9 minutes (minor) and 16.7 213 minutes (major)). The optical purity of the compound was 86% ee.

The results of analysis of the product obtained in this example are shown in Table 76, and the results in this example are shown in Table 77.

Table 7 6

214 Table 7 7

(* 1) Yield of product (S form) in each example described in the right column of the table using amide amide sulfone

(* 2) Yield of product (S form) in the examples in parentheses using aldimine derivatives

(* 3) Optical purity of the product (S form) in each example described in the right column of the table using monoamide sulfone

(* 4) Optical purity of the product (S form) in the examples in parentheses using aldimine derivatives

(* 5) without As shown in Table 7 7 measurements when using α- amidosulfonic the starting material (actual施例₉ _ _1-9 - ₉₎ Both the obtained _alpha - aminonitrile derivative Yield and optical purity increased significantly. In producing the same c-amino nitrile derivative, the yield and optical purity of the derivative were compared between when α-amidosulfone was used as the starting material and when the aldimine derivative was used. (Example 9-1 and Example 5-1 and Example 9-2 and 215 Example 6-1, Example 9-13 and Example 6-2, Example 9-15, Example 6-3, and Example 9-16, Example 6-4), all starting materials When α-amide sulfone was used as the yield, the yield and optical purity of the resulting product were further improved. Therefore, when the chiral ammonium salt of the present invention is used as a phase transfer catalyst, this amid sulfone is directly synthesized from α-amido sulfone by the conventionally known method without synthesizing the aldimine derivative directly. Example 9_! It can be seen that the desired α-amino nitrile derivative can also be efficiently produced by using it in the range of ˜9_9.

((R)-1)

N- (mesitylenesulfoninole) -α- (ρ-toluenesulfonyl) hexylmethylamine (4-a) (89) in toluene (lmL) and water (3 ml) 9 mg, 0.20 mm o 1) and the mixture of chiral ammonium iodide ((R) — 1) (1.5 mg, 0.002 mmo 1) obtained in Example 3 1 2 to 0 Then, 2M KCN aqueous solution (105 / z L, 0.21 Ommo 1, 1.05 equivalent) was added dropwise. Reaction mixture The 216 compound was stirred vigorously at the same temperature for 1.5 hours. Then, by the addition of saturated NH ₄ C 1 aqueous solution, and the mixture was extracted with CH _₂ C 1 _2. The combined extracts were dried with Na ₂ 30 ₄ . The solvent was distilled off, and the crude product was purified by flash column chromatography using silica gel (using ethylacetate Z-hexane = 1: 4 (volume ratio) as eluent) and N- (mesitylene sulfonyl ) -H- (Cyano) cyclohexylmethylamine (S form) was obtained in a yield of 99% (63.4 mg, 0.20 mm o 1).

The product obtained in this example was subjected to HPLC analysis and spectrum analysis in the same manner as in Example 9-11. The optical purity of the compound was 63% ee. Table 78 shows the results obtained in this example.

In the same manner as in Example 10-1, except that the amount of the aqueous KCN solution used in Example 10-1 was changed to 1.2 equivalents, Ν- (mesitylenesulfonyl) -a- (cyano) cyclohexylmethyl Amine (S form) was obtained with a yield of 99%. The optical purity of the obtained Ν- (mesitylenesulfonyl) -α- (cyan) hexylmethylamine was 61%. The results obtained in this example are shown in Table 78. <Example 10-3: Asymmetric Strecker reaction of α-amide sulfone under phase transfer conditions in various aqueous KCN solutions (Ε 3)>

In the same manner as in Example 10-1, except that the amount of the KCN aqueous solution used in Example 10-1 was changed to 2.0 equivalents, and the reaction time was changed to 2 hours instead of 1.5 hours. -(Mesitylenesulfonyl) -α- (siano) cyclohexylmethylamine (S form) was obtained in a yield of 99%. The optical purity of the obtained Ν- (mesitylene sulfonyl) -α- (cyan) hexylmethylamine was 60%. 217 The results obtained in this example are shown in Table 78.

The amount of the aqueous KCN solution used in Example 10-1 was changed to 1.5 equivalents. Reference Example 4- N- (mesitylenesulfonyl) -a- (p-toluenesulfonanol) cyclohexyl obtained in a Example 1 0— 1 except that N-mesitylene norhonylimine (3 a) was used instead of ^ / methy ^^ amine (4—a) and the reaction time was changed to 8 hours instead of 1.5 hours. In the same manner as above, N- (mesitylenesulfonyl) -α- (ciano) cyclohexylmethylamine (4 ′) (S form) was obtained in a yield of 81%. The optical purity of the obtained product was 57% ee. Table 78 shows the results obtained in this example.

Table 78

As shown in Table 78, the chiral ammonium iodide ((R) — 1) obtained in Example 3_2, which is one of the catalysts of the present invention, also started from α-amidosulfone. When used as a substance, it can be seen that the product can be obtained in an excellent yield. Also, the amount of KCN used is almost the same as the starting substrate, and the product can be obtained in an excellent yield. I was able to get it. Industrial applicability

According to the present invention, by causing the Strecker reaction to proceed stereoselectively, The reaction product can be produced stereoselectively. In particular, the optically active α-amino nitrile derivative obtained by the present invention can easily produce a hyperamino acid having a predetermined structure and its derivative, which has been difficult in the conventional alkylation reaction. The single amino acid and its derivatives synthesized in this way have a variety of biological activities in designing a peptide having enhanced activity (pharmacological activity, physiological activity, etc.) and as an effective enzyme inhibitor. It plays an important and special role as a chiral building block for the synthesis of compounds. Therefore, it is useful for the development of new foods and medicines.

Claims

219. Claims comprising an optically active quaternary ammonium salt represented by the following formula (1-1) or formula (1-2): Catalyst capable of stereoselective progress of the Strecker reaction: here, R1 and R1 ′ are Each independently (i) a hydrogen atom; (ii) -NR30R31 (where R3 ° and R31 are Each independently Hydrogen atom or Or a C C alkyl group which may be branched and may be substituted with a halogen atom) (iii) a cyano group; (iv) Niburo; (V) canolevamoyl group; (vi) N- (C1-C4 alkyl) force rubamoyl group; (vii) N, N-di (C1-C4 alkyl) force rubamoyl group; (viii) -NHCOR19 (where R19 is a hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom); (ix) a halogen atom; (X) may be branched or ringed and substituted with a halogen atom 220 may be, Ci Ce alkyl group; (xi) may form a branch or a ring and may be substituted with a halogen atom, A C2-C6 alkenyl group; (xii) may be branched or ringed and may be substituted with a halogen atom; A C2-C6 alkynyl group; (xiii) an aralkyl group, here, The aryl moiety constituting the aralkyl group is Ci-C4 alkyl group which may be branched and may be substituted with a halogen atom, A C Cs alkoxy group which may be branched and may be substituted with a halogen atom, A halogen atom, Ci C alkyl group which may be branched and may be substituted with a halogen atom, Cyan, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) Nito Koki, Force rubymoyl group, N_ (C1-C4 alkyl) force rubermoyl group, N, N—di (C1-C4 alkyl) force rubermoyl group, Or one NHCOR19 (where, R19 is a hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom. Ariel group, Ciano group, _N R 30 R 31 (where R30 and R31 are Each independently Hydrogen atom or Or it may be branched and may be substituted with a halogen atom or a C1-C4 alkyl group). Nitro group, Carpamoyl group, N— (Ci C alkyl) force rubermoyl group, N, N-di (C1-C4 alkyl) force rubermoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom) And optionally substituted with at least one group selected from the group consisting of halogen atoms, Aralkyl group; (xiv) a heteroaralkyl group having a heteroaryl moiety, here, The hetero reel part is A C1-C4 alkyl group which may be branched and optionally substituted with a halogen atom, A C1-C5 alkoxy group which may be branched and optionally substituted with a halogen atom, A halogen atom, A C1-C4 alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C1-C4 alkyl group which may be branched and may be substituted with a norogen atom). Nito Koki, Force rubymoyl group, N— (ji ~ anorekiru) force rubamoyl group, N, N—di (C1-C4 alkyl) force rubermoyl group, Or one NHCOR19 (where, R 19 is a hydrogen atom or Or a C1-C4 alkyl group which may be branched and substituted with a halogen atom). Ariel group, Ciano group, _N R 30 R 31 (where R3 ° and R31 are Each independently Hydrogen atom or Or it may be branched and substituted with a halogen atom. 222 is a C1-C4 alkyl group), Nitro group, Force rubymoyl group, N— (C1-C4 alkyl) force rubermoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a C 4 to C 4 alkyl group which may be branched and may be substituted with a halogen atom). And optionally substituted with at least one group selected from the group consisting of halogen atoms, Heteroaralkyl group; (XV) Allele group, here, The aryl group is Ci C alkyl group which may be branched and may be substituted with a halogen atom, A C Cs alkoxy group which may be branched and may be substituted with a halogen atom, A halogen atom, Ci C alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, _NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a Ci Ca alkyl group which may be branched and may be substituted with a halogen atom) Nito Koki, Force rubymoyl group, N— (Ci C alkyl) carbamoyl group, N, N—di (C1-C4 alkyl) force rubermoyl group, Or — NHCOR19 (where R 19 is a hydrogen atom or Or it may be branched and may be substituted with a halogen atom. Which is an alkyl group) Ariel group, Ciano group, 223 _ N R 30 R 31 (where R3 ° and R31 are Each independently Hydrogen atom or Or it may be branched and may be substituted with a halogen atom or a C1-C4 alkyl group). Nika Higuchi, Force rubymoyl group, Ν- (C1-C4 alkyl) rubamoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R 19 is a hydrogen atom or Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom) And may be substituted with at least one group selected from the group consisting of halogen atoms, Or 3, 4th place together O— (CH2) p-O- (where, p is 1 or 2), Areal group; (xvi) a heteroaryl group, The heteroaryl group may be branched and may be substituted with a halogen atom, an alkyl group; A C to C 5 alkoxy group which may be branched and optionally substituted with a halogen atom, A halogen atom, It may be branched and substituted with a halogen atom An alkyl group, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) Nito Koki, Force rubymoyl group, N— (C1-C4 alkyl) force rubermoyl group, N, N—di (C1-C4 alkyl) carbamoyl group, Or one NHCOR19 (where, R 19 is a hydrogen atom or Or may be branched and substituted with a halogen atom 224 may be substituted with an alkyl group), Ariel group, Ciano group, _ N R 30 R 31 (where R3 ° and R31 are Each independently Hydrogen atom or Alternatively, it may be branched and substituted with a halogen atom. ~. An alkyl group), Nitro group, Force rubymoyl group, N- (C1-C4 alkyl) canolamoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a C 4 to C 4 alkyl group which may be branched and may be substituted with a halogen atom). And optionally substituted with at least one group selected from the group consisting of halogen atoms, Heteroaryl group; And (xvii) -S (O) n-R20 (where n is 0, 1, Or 2 and And R 2. Is a C4 alkyl group which may be branched and may be substituted with a halogen atom); A group selected from the group consisting of: R8, R8 ', R9, And R9 ' Each independently Is a hydrogen atom; Is a halogen atom; May be substituted with a ha atom atom and a Z or aryl group, And or may form a branch or ring, Ci Cs alkyl group; Or Optionally substituted with a halogen atom and a Z or aryl group, And or may form a branch or ring, Ci Cg alkoxy group; • 9, R2, R2 ', R3, R3 ', R4, R4 ', R5, R5 ', R6, R6 ', R10 and R1Q 'are Each independently (i) a hydrogen atom; (ii) -NR30R31 (where R3t) and R31 are Each independently Hydrogen atom or Or a Ci C alkyl group which may be branched and may be substituted with a halogen atom); (iii) a cyano group; (iv) a ditro group; (V) force rubermoyl group; (vi) N- (. ~ Ji alkyl) strong rubermoyl group; (vii) N, N-di (C1-C4 alkyl) force rubamoyl group; (viii) -NHCOR19 (where R19 is a hydrogen atom, Or a C to C 4 alkyl group which may be branched and optionally substituted with a halo atom); (ix) a halogen atom; (X) It may form a branch or a ring and may be substituted with a halogen atom, , A C1-C6 alkyl group; (xi) may form a branch or a ring and may be substituted with a halogen atom, A C2-C6 alkenyl group; (xii) may form a branch or a ring and may be substituted with a halogen atom, A C2-C6 alkynyl group; (xiii) an aralkyl group, here, The aryl moiety constituting the aralkyl group is 226 may be branched and may be substituted with a halogen atom ○ to ○ alkyl group, Ci to C 5 alkoxy group which may be branched and may be substituted with a halogen atom, A halogen atom, A C1-C4 alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) Nito Koki, Force ruby moinole group, N— (. ~ Ji alkyl) force ruberamoyl group, N, N—di (C1-C4 alkyl) force rubermoyl group, Or one NHCOR19 (where, R 19 is a hydrogen atom or Or a Ci C alkyl group which may be branched and may be substituted with a halogen atom). Ariel group, Ciano group, _ N R 30 R 31 (where R3 ° and R31 are Each independently Hydrogen atom or Or a nitro group which may be branched and may be substituted with a halogen atom. 'Power ruber moyl group, N— (C1-C4 alkyl) force rubermoyl group, N, N-di (Ci C alkyl) force rubermoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a Ci to c4 alkyl group which may be branched and may be substituted with a halogen atom) And optionally substituted with at least one group selected from the group consisting of halogen atoms, A 227 aralkyl groups; (xiv) a heteroaralkyl group having a heteroaryl moiety, Where the hetero reel part is A C1-C4 alkyl group which may be branched and optionally substituted with a halogen atom, Ci to C5 alkoxy group which may be branched and may be substituted with a haguchi atom, A halogen atom, Ci C alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, _NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) Nito Carpamoyl group, N— (C C alkyl) strong rubermoyl group, N, N-di (C1-C4 alkyl) strong rubermoyl group, Or one NHCOR19 (where, R 19 is a hydrogen atom or Or a C1-C4 alkyl group which may be branched and substituted with a halogen atom). Ariel group, Ciano group, _ N R 30 R 31 (where R30 and R31 are Each independently Hydrogen atom or Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N- (C1-C4 alkyl) force rubermoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom. 228) And optionally substituted with at least one group selected from the group consisting of halogen atoms, Heteroaralkyl group; (XV) Allele group, here, The aryl group is It may be branched and may be substituted with an atom atom C! ~ C4 alkyl group, Ci-C5 alkoxy group which may be branched and may be substituted with a halogen atom, A halogen atom, A C1-C4 alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C C alkyl group which may be branched and may be substituted with a halogen atom) Nito Koki, Carpamoyl group, N— (0-4 alkyl) force rubermoyl group, N, N—di (C1-C4 alkyl) force rubermoyl group, Or one NHCOR19 (where, R 19 is a hydrogen atom or Or it may be branched and may be substituted with a halogen atom. Ariel group, 'Siano group, -N R 30 R 31 (where R 30 and R31 are Each independently Hydrogen atom or Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force ruby moinole group, N- (C1-C4 alkyl) force rubermoyl group, N, N—di (C C d alkynole) force rubermoyl group, 229 -NHCOR19 (where R19 is a hydrogen atom, Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom) A halogen atom, And — S (O) n-R20 (where n is 0, 1, Or 2 and R2 ° may be branched and may be substituted with at least one group selected from the group consisting of Ci to C4 alkyl group optionally substituted with a halogen atom, Or 3, 4th place is together 0_ (CH2) m-0- (where, m is 1 or 2) Areal group; (xvi) a heteroaryl group, The heteroaryl group may be branched and may be substituted with a halogen atom, a C1-C4 alkyl group, It may be branched and may be substituted with a halogen atom C! ~ C5 alkoxy group, A halogen atom, Ci CA alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, _NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C C alkyl group which may be branched and optionally substituted with a halogen atom), Nito Koki, Force rubymoyl group, N— (C CA alkyl) force rubermoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, Or one NHCOR19 (where, R19 is a hydrogen atom, Or a C1-C4 alkyl group which may be branched and substituted with a halogen atom). Ariel group, Ciano group, _N R30R31 (Where R3Q and R31 are Each independently Hydrogen 230 atoms or Or an alkyl group which may be branched and substituted with a halogen atom) Nitoguchi, Force rubymoyl group, N- (. 丄 -ji alkyl) strong rubermoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R 19 is a hydrogen atom or Or a C alkyl group which may be branched and may be substituted with a halogen atom) And optionally substituted with at least one group selected from the group consisting of halogen atoms, Heteroaryl group; And (xvii) -S (O) n-R20 (where n is 0, 1, Or 2 and And R2 ° may be branched and may be substituted with a halogen atom (~ C4 alkyl group)); A group selected from the group consisting of: 1¾7 joy! ^ 7 'is independent (i) may be branched or ringed and may be substituted with a parogen atom, An alkyl group of C i Cgo; (ii) may form a branch or a ring and may be substituted with a halogen atom, A C2-C12 alkenyl group; (iii) may form a branch or a ring and may be substituted with a halogen atom, A C2-C12 alkynyl group; (iv) Aaryl group, The aryl group may be branched and may be substituted with a halogen atom. 231 Ci Cs ananoloxy group which may be branched and optionally substituted with a halogen atom, A halogen atom, A C C alkyl group which may be branched and optionally substituted by a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) Nito Koki, Force rubymoyl group, N— (C1-C4 alkyl) force rubermoyl group, N, N—di (C1-C4 alkyl) force rubermoyl group, Or one NHCOR19 (where, R 19 is a hydrogen atom or Or a C1-C4 alkyl group which may be branched and substituted with a halogen atom). Ariel group, Ciano group, -N R 30 R 31 (where R 30 and R 31 are Each independently Hydrogen atom or Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N— (C1-C4 alkyl) force rubermoyl group, 'N, N—di (C1-C4 anoalkyl) -NHCOR19 (where R19 is a hydrogen atom, Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom) And optionally substituted with at least one group selected from the group consisting of halogen atoms, A reel group; (V) a heteroaryl group, The heteroaryl group is 232 an alkyl group which may be branched and optionally substituted with a halogen atom, Ci to C 5 anoalkoxy group which may be branched and may be substituted with a halogen atom, A halogen atom, A C C alkyl group which may be branched and optionally substituted by a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C1-C4 alkyl group which may be branched and may be substituted with a norogen atom). Nito Koki, Carpamoyl group, N— arnolekill) force rubermoyl group, N, N—di (Ci-C4 alkyl) force rubermoyl group, Or one NHCOR19 (where, R19 is a hydrogen atom, Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom). Ariel group, Ciano group, _ N R 30 R 31 (where R3G and R31 are Each independently Hydrogen atom or Or may be branched and may be substituted with a halogen atom). Nitro group, Canoleva Moinole group, N- (ji-ji alkyl) rubamoyl group, N, N—Di (C! ~ C4 alkyl) strong rubermoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a c to c4 alkyl group which may be branched and may be substituted with a halogen atom) And optionally substituted with at least one group selected from the group consisting of halogen atoms, What 233 terror reel group; (vi)-(CH2) nOCONR21R22 (where R21 and R22 are independent, (1) hydrogen atom, (2) an alkyl group which may be branched, (3) It may form a branch or a ring and may be substituted with a halogen atom, A C2-C6 alkenyl group; (4) It may form a branch or a ring and may be substituted with a halogen atom, A C2-C6 alkynyl group; (5) an aralkyl group, Ci to c4 alkyl group in which the aryl moiety constituting the aralkyl group may be branched and may be substituted with a halogen atom, A C to C5 alkoxy group which may be branched and optionally substituted with a halogen atom, Haguchigen atom, Ci Cd alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N_ (Ci-C4 alkyl) force rubermoyl group, N, N—di (. ~ Ji alkyl) force ruberamoyl group, Or one NHCOR19 (Here, R 19 is a hydrogen atom or Or a C1-C4 alkyl group that may be branched and substituted with a halogen atom). Ariel group, Ciano group, _ N R 30 R 31 (where R3 ° and R 3 i are Each independently 234 hydrogen atom or Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Canoleva Moinole group, N-alkyl) strong rubermoyl group N, N-di (ji-ji alkyl) rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a C to C 4 alkyl group which may be branched and may be substituted with a haguchi atom). And optionally substituted with at least one group selected from the group consisting of halogen atoms, Aralkyl group; (6) a heteroaralkyl group having a heteroaryl moiety, The heteroaryl moiety is Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom, A Cj to C5 anoalkoxy group which may be branched and may be substituted with a halogen atom, Haguchigen atom, Ci C alkyl group which may be branched and may be substituted with a haguchi atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or it may be branched and may be substituted with a halogen atom (it is an alkyl group), Nitro group, Force rubymoyl group, N— (C1-C4 arnolequinole) N, N-dialkyl) strong rubermoyl group, Or one NHCOR19 (Here, R 19 is a hydrogen atom or Or an alkyl group that may be branched and substituted with a halogen atom). 235 aryl group, Ciano group, -N R 30 R 31 (where R3 ° and R31 are Each independently A hydrogen atom, Or it may be branched and may be substituted with a halogen atom. An alkyl group), Nitro group, Carpamoyl group, N- (C! ~ C4 alkyl) strong rubermoyl group, N, N—di (Ci C alkyl) carpamoyl group, I NHCOR19 (Where R 19 is a hydrogen atom or Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom) And optionally substituted with at least one group selected from the group consisting of halogen atoms, Heteroaralkyl group; (7) Allele group, A Ci to C4 alkyl group which may be branched and substituted with a halogen atom, Ci-C5 alkoxy group which may be branched and may be substituted with a halogen atom, Haguchigen atom, A C1-C4 alkyl group which may be branched and may be substituted with a haguchi atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C i to C 4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Carpamoyl group, N— (di-alkyl) strong rubermoyl group; N: N-di (C1-C4 alkyl) force rubamoyl group, Or one NHCOR19 (this 236 where R 19 is a hydrogen atom or Or an aryl group which may be branched and is a Ci C alkyl group which may be substituted with a halogen atom. Ciano group, _N R 30 R 31 (where R 30 and R 31 are Each independently A hydrogen atom, Or a C C alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Canoleva Moinole group, N- (C1-C4 alkyl) force rubermoyl group, N, N-di (Ci C alkyl) force rubermoyl group, -NHCOR19 (where R 19 is a hydrogen atom or Or a C to C 4 alkyl group which may be branched and may be substituted with a haguchi atom). And optionally substituted with at least one group selected from the group consisting of halogen atoms, A reel group, And (8) a heteroaryl group, The heteroaryl group may be branched and optionally substituted with a halogen atom to a C4 alkynole group, Ci to C 5 alkoxy group which may be branched and may be substituted with a halogen atom, Haguchigen atom, A C1-C4 alkyl group which may be branched and may be substituted with a haguchi atom, Ciano group, One NR3. R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C1-C4 alkyl group which may be branched and may be substituted with a haguchigen atom) 237 Nitro group, Force rubymoyl group, N— (. ~ Ji alkyl) carbamoyl group; N, N-di (C1-C4 alkyl) force rubamoyl group, Or one NHCOR19 (here, R19 is a hydrogen atom, Or a C1-C4 alkyl group which may be branched and substituted with a halogen atom). , Ariel group, Ciano group, _ N R 30 R 31 (where R3 ° and R31 are Each independently A hydrogen atom, Or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Canoleva Moinole group, N— (dialkyl-dialkyl) strong rubermoyl group, N, N-di (ji-ji alkyl) rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a C i to C 4 alkyl group which may be branched and may be substituted with a divalent atom). And at least one group selected from the group consisting of and a halogen atom may be substituted, He terror reel group, A group selected from the group consisting of: And n is an integer from 1 to 1 2); (vii)-(CH2) nCONR12R13 (where R12 and R13 are each independently (1) hydrogen atom, (2) a C 4 to C 4 alkyl group which may be branched and optionally substituted with a haguchi atom, 238 (3) Allele group, The aryl group may be branched and may be substituted with a halogen atom; A C 丄 -C5 anoalkoxy group which may be branched and may be substituted with a halogen atom, A halogen atom, An alkyl group that may be branched and may be substituted with a halogen atom; Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N— (C1-C4 alkyl) force rubamoyl group; N, N-di (Ci C alkyl) force rubermoyl group, Or one NHCOR19 (here, R 19 is a hydrogen atom or Or a Ci C alkyl group which may be branched and may be substituted with a halogen atom). , Ariel group, Ciano group, _ N R 30 R 31 (where R30 and R31 are Each independently A hydrogen atom, Or it may be branched and may be substituted with a halogen atom. An alkyl group), '' Nitro group, Canolevamoyl group, N— (Ci-C4 alkyl) force ruberamoyl group, N, N-dialkyl) strong rubermoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a C to C 4 alkyl group which may be branched and may be substituted with a haguchi atom). And halogen atoms 239 may be substituted with at least one group selected from the group consisting of 239, A reel group, And (4) a heteroaryl group, A Ci to C4 alkyl group which may be branched and substituted with a halogen atom, Ci to C5 alkoxy group which may be branched and may be substituted with a halogen atom, Haguchigen atom, A C L C alkyl group which may be branched and may be substituted with a haguchi atom, Ciano group, _NR30R3 1 (where R30 and R31 are Each independently A hydrogen atom, Or a C 4 to C 4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N— (Ci C alkyl) carbamoyl group; N, N-di (C1-C4 alkyl) force rubamoyl group, Or one NHCOR19 (here, R 19 is a hydrogen atom or Or a C1-C4 alkyl group that may be branched and substituted with a halogen atom). Ariel group, Ciano group, -N R30R31 (where R30 and 31 are Each independently A hydrogen atom, Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Canoleva Moinole group, N- (C1-C4 alkyl) force rubermoyl group, N, N-di (ji-ji alkyl) rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a c1-c4 alkyl group which may be branched and may be substituted with a halo atom. 240) And may be substituted with at least one group selected from the group consisting of halogen atoms, , He terror reel group, A group selected from the group consisting of: And n is an integer from 1 to 1 2); '(viii) — (CH2) nNR12COR13 (where R 12 and R 13 are each independently (1) hydrogen atom, (2) Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom, (3) A reel group, The aryl group may be branched and optionally substituted with a halogen atom to a C4 alkyl group, A C i C 5 anorecoxy group which may be branched and optionally substituted with a halogen atom, A halogen atom, A C CA alkyl group which may be branched and optionally substituted with a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N_ (C1-C4 alkyl) force rubermoyl group; N, N-di (Ci-C4 alkyl) force rubamoyl group, Or one NHCOR19 (Here, R 19 is a hydrogen atom or Or it may be branched and may be substituted with a halogen atom. Which is an alkyl group) Ariel group, Ciano group, 241 _NR30R3i (where R3 ° and R31 are Each independently A hydrogen atom, Or a Ci C alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N— (Ci-C4 alkyl) force ruberamoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) And optionally substituted with at least one group selected from the group consisting of halogen atoms, A reel group, And (4) a heteroaryl group, The heteroaryl group may be branched and optionally substituted with a halogen atom, a C1-C4 anolenoquine group, A C5 alkoxy group which may be branched and may be substituted with a halogen atom, A halogen atom, Ci C alkyl group which may be branched and may be substituted with a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C i to C 4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Force rubymoyl group, N— (C1-C4 alkyl) carbamoyl group; N, N-dialkyl) carbamoyl group, Or one NHCOR19 (Here, R 19 is a hydrogen atom or Or a Ci C alkyl group that may be branched and optionally substituted with a halogen atom). 242 aryl group, Ciano group, _N R 30 R 31 (where R3 ° and R31 are Each independently A hydrogen atom, Or a Ci C alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Canoleva Moinole group, N—Alkynore) Forced rubermoyl group, N, N-di (di-alkyl) carpamoyl group, -NHCOR19 (where R19 is a hydrogen atom, Or a C i to C 4 alkyl group which may be branched and may be substituted with a divalent atom). And optionally substituted with at least one group selected from the group consisting of halogen atoms, Heterol group, A group selected from the group consisting of: And n is an integer from 1 to 1 2); (ix)-(CH2) nNR12R13 (where R1'2 and R13 are each independently (1) hydrogen atom, (2) a C4 alkyl group which may be branched and may be substituted with a halogen atom, (3) A reel group, A Cj to C4 alkyl group which may be branched and substituted with a halogen atom, It may be branched and may be substituted with a halogen atom 243 to C5 ananoloxy group, A halogen atom, A C1-C4 alkyl group which may be branched and optionally substituted with a halogen atom, Ciano group, NR30R31 (where R30 and R31 are Each independently A hydrogen atom, Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) Nitro group, Carpamoyl group, N— (di-alkyl) strong rubermoyl group; N, N-di (O ~ O4 alkyl) force rubermoyl group, Or one NHCOR19 (Here, R 19 is a hydrogen atom or Or C which may be branched and may be substituted by a halogen atom Which is a -C4 alkyl group) Ariel group, Ciano group, _N R 30 R 31 (where R3 ° and R31 are Each independently A hydrogen atom, Or an alkyl group which may be branched and may be substituted with a halogen atom) . Nitro group, force ruberinole group, N- (Ci C alkyl) force rubermoyl group, N, N-di (C! C alkyl) carbamoyl group, -NHCOR19 (where R19 is a hydrogen atom or branched) And a ci to C 4 alkyl group which may be substituted with a halogen atom), and an aryl group which may be substituted with at least one group selected from the group consisting of halogen atoms And (4) a heteroaryl group, which may be branched and substituted with a halogen atom C j 244 to C4 alkyl group, optionally branched and optionally substituted with a halogen atom to C5 alkoxy group, halogen atom, optionally branched and optionally substituted with a halogen atom C1 to C4 An alkyl group, a cyano group, and one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom, or may be branched and may be substituted with a haguchine atom, C i to C N- (Ci C alkyl) force rubamoyl group; N, N—di (C1-C4 alkyl) force rubamoyl group, or one NHCOR19 (where R 19 may be a hydrogen atom, or may be branched and may be substituted with a halogen atom, or may be substituted with an alkyl group), an aryl group, a cyano group, or _NR 30 R 31 (where R3 ° and Each of R31 is independently a hydrogen atom, or a branched and halogen-substituted alkyl group), a nitro group, a canolevamoinole group, 'N- (C1 ~ C4 alkyl) Forced rubamoyl group, N, N-di (C1 ~ C4 alkyl) Forced rubamoyl group, -NHCOR19 (wherein R19 may be a hydrogen atom or may be branched and substituted with a haguchigen atom) An optionally substituted Ci-C4 alkyl group), and a heteroaryl group optionally substituted with at least one group selected from the group consisting of halogen atoms, (X) — (CH2) nY—OR12 (where Y is an optionally branched Ci C) group selected from the group consisting of 245 R12 is (1) a hydrogen atom, (2) a Ci-C4 alkyl group which may be branched and substituted with a halogen atom, (3) aryl The aryl group may be branched and may be substituted with a halogen atom to a C4 alkyl group, may be branched and may be substituted with a halogen atom Ci to C5 alkoxy A group, a halogen atom, an optionally branched Ci C alkyl group, a cyano group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom, or It may be branched and substituted with a haguchi atom N- (C1-C4 alkyl) force rubamoyl group; N, N-di (C1-C4 alkyl) force rubamoyl group, 'or one NHCOR19 ( Here, R 19 is a hydrogen atom, or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), an aryl group, a cyano group A group, -NR 30 R 31 (wherein R 3 ° and R 31 are each independently a hydrogen atom or a branched and optionally substituted C1-C4 alkyl group. ) Nitro group, 246 Canolemoyl group, N— (dialkyl to dialkyl), rubamoyl group, N, N—di (C1 to C4 alkyl), rubamoyl group, —NHCOR19 (where R 19 is a hydrogen atom or branched) And a Ci C alkyl group optionally substituted with a halogen atom), and an aryl group optionally substituted with at least one group selected from the group consisting of halogen atoms, and (4 ) A heteroaryl group, which may be branched and optionally substituted with a halogen atom, a C to C4 alkyl group, optionally branched and substituted with a halogen atom Good C i to C 5 alkoxy group, halogen atom, CC alkyl group which may be branched and optionally substituted with halogen atom, cyano group, _NR30R31 (where R30 and R31 are Each independently a hydrogen atom, or a Ci'Ca alkyl group that may be branched and substituted with a halogen atom), a nitro group, a strong rubamoyl group, N_ (C1-C4 anoalkyl) ) Carpamoyl group; N, N-di (C1-C4 alkyl) force rubamoyl group, or one NHCOR19 (where R 19 may be a hydrogen atom or branched and substituted with a halogen atom) May be substituted with a Ci C alkyl group), aryl group, cyano group, _NR 30 R 31 (where R30 and R31 are each independently a hydrogen atom) Or may be branched and substituted with a halogen atom 247 may also be a C1-C4 alkyl group), a ditro group, a strong rubamoyl group, N- (C1-C4 alkyl) a carbamoyl group, N, N-dialkyl) a strong rubamoyl group, -NHCOR19 (where R19 Is a hydrogen atom, or a C 1 -C 4 alkyl group which may be branched and substituted with a halogen atom, and at least one group selected from the group consisting of halogen atoms An optionally substituted heteroaryl group, a group selected from the group consisting of and n is an integer from 1 to 1 2); (xi)-(CH2) n-OR12 (where R12 is (1) a hydrogen atom, (2) optionally branched and substituted with a halogen atom, C] to C4 alkyl group, (3) an aryl group, wherein the aryl group is C i to C4 alkyl optionally substituted with a halogen atom A C 1 -C 4 alkyl group, which may be branched and optionally substituted with a halogen atom, a C 5 alkoxy group, a halogen atom, a branched and optionally substituted with a halogen atom, A cyano group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom). 248 Nitro group, strong rubamoyl group, N— (C1-C4 alkyl) strong rubamoyl group; N, N-di (C1-C4 alkyl) strong rubamoyl group, or — NHCOR19 (where R19 is a hydrogen atom, or May be branched and substituted with a halogen atom, which may be a Ci Cd alkyl group), an aryl group, a cyano group, _N R 30 R 31 (where R3Q and Each of R31 is independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitro group, a canolemoinole group, N— ( C1-C4 alkyl) Carpamoyl group, N, N-di (C-C4 alkyl) force rubamoyl group, -NHCOR19 (wherein R19 may be a hydrogen atom or may be branched and substituted with a halogen atom) C i to C 4 alkyl group And an aryl group that may be substituted with at least one group selected from the group consisting of a halogen atom, and (4) a heteroaryl group, wherein the heteroaryl group may be branched And optionally substituted with a halogen atom-C4 alkyl group, optionally branched and optionally substituted with a halogen atom Ci-C5 alkoxy group, halogen atom, optionally branched and halogen Ci C alkyl group optionally substituted with an atom, cyano group, one NR30R31 (where R30 249 and R31 are each independently a hydrogen atom or a C i to C 4 alkyl group which may be branched and substituted with a halogen atom), a nitro group, a rubamoyl group, N— (Ci C alkyl) force rubamoyl group; N, N—di (C: to C4 alkyl) force rubamoyl group, or —NHCOR19 (where R 19 may be a hydrogen atom or branched and Which may be substituted with a halogen atom, which is a C1-C4 alkyl group), an aryl group, a cyano group, _N R 30 R 31 (where R 30 and R 31 are Each independently a hydrogen atom, or a C i to C 4 alkyl group which may be branched and substituted with a halogen atom), a ditoxyl group, a rubamoinore group, N -(C1-C4 alkyl) strong rubermoyl group, N, N-di Alkyl) a rubamoyl group, -NHCOR19 (wherein R19 is a hydrogen atom or a Ci-C4 alkyl group which may be branched and substituted with a haguchi atom), and 'Is a heteroaryl group optionally substituted with at least one group selected from the group consisting of halogen atoms, a group selected from the group consisting of and n is an integer from 1 to 12) (Xii)-(CH2) n— S— R12 (where R12 is (1) a hydrogen atom, (2) branched and optionally substituted with a halogen atom) 250 to C4 alkyl group, (3) an aryl group, which may be branched and substituted with a halogen atom ~ C4 alkyl group, optionally branched and with a halogen atom Optionally substituted ~ C5 alkoxy group, halogen atom, optionally branched and optionally substituted with a halogen atom ~ alkyl group, cyano group, one NR30R31 (where R30 and R31 are Each independently a hydrogen atom, or a C to C 4 alkyl group which may be branched and substituted with a disulfide atom), a nitro group, a rubamoyl group, N— (Ci C alkyl) force rubamoyl group; N, N-di (C1-C4 alkyl) force rubamoyl group, or one NHCOR19 (where R 19 may be a hydrogen atom or branched and substituted with a halogen atom) Have been An aryl group, an aryl group, a cyano group, _N R 30 R 31 (wherein R 30 and R 31 are each independently a hydrogen atom or branched) Which may be substituted with a halogen atom and is a c1 to c4 alkyl group), a nitro group, a canolebuyl group, N- (C1 to C4 alkynole), a rubamoyl group, N, N—di ( Ci to C4 alkyl) Forced rubermoinole group, -NHCOR19 (wherein R19 is a hydrogen atom, or a Ci to C4 alkyl group that may be branched and substituted with a haguchi atom) ) , and 251 an aryl group optionally substituted with at least one group selected from the group consisting of halogen atoms, and (4) a heteroaryl group, wherein the heteroaryl group may be branched and is a halogen atom. Ci-c4 alkyl group which may be substituted, Ci-C5 alkoxy group which may be branched and substituted with a halogen atom, halogen atom, which may be branched and substituted with a halogen atom An alkyl group, a cyano group, and one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom, or may be branched and substituted with a halogen atom, C1 to A C4 alkyl group), a nitro group, a strong rubamoyl group, N— (dialkyl), a strong rubamoyl group; N, N—di (C1-C4 alkyl) a strong rubamoyl group, Or NHCOR19 (wherein R 19 may be a hydrogen atom, or may be branched and substituted with a halogen atom, which is an alkyl group). ,, Aryl group, cyano group, -NR 30 R 31 (wherein R3 ° and R31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom) A C alkyl group), a nitro group, a carpamoinole group, an N- (dialkyl), a rubamoyl group, an N, N-dialkyl) a rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom, or Branching And a C to C 4 alkyl group which may be substituted with a halogen atom), and may be substituted with at least one group selected from the group consisting of halogen atoms, A teloaryl group, a group selected from the group consisting of: and n is an integer from 1 to 12;; (xiii)-(CH2) n—SO—R12 (where R12 is (1) A hydrogen atom, (2) an optionally branched Ci-C4 alkyl group optionally substituted with a halogen atom, and (3) an aryl group, wherein the aryl group may be branched and a halogen atom Ci to C4 alkyl group optionally substituted with, Ci to C5 alkoxy group optionally branched and substituted with a halogen atom, 'parogen atom, optionally branched and substituted with a halogen atom Ci C alkyl group, Cyan _NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitro group , Carbamoyl group, N— (C1-C4 alkyl) force rubamoyl group; N, N-di (C1-C4 alkyl) carbamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or branched) And may be substituted with a halogen atom, which may be an alkyl group), an aryl group, a cyan group, 253 _ NR 30 R 31 (where R30 and R31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom to 匚 alkyl group) , Nitro group, canolemoinole group, N— (C1 to C4 alkyl) force rubamoyl group, N, N—di (C1 to C4 alkyl) force rubamoyl group, —NHCOR19 (where R19 is a hydrogen atom or branched) And a C to C 4 alkyl group optionally substituted with a halogen atom), and an aryl group optionally substituted with at least one group selected from the group consisting of halogen atoms, And (4) a heteroaryl group, which may be branched and may be substituted with a halogen atom to a C4 alkyl group, which may be branched and a haguchi atom CJ-C5 alkoxy group which may be substituted, halogen atom, Ci C alkyl group which may be branched and optionally substituted with halogen atom, cyano group, _NR30R31 (where R30 and R31 are Each independently a hydrogen atom, or a C i to C 4 alkyl group which may be branched and substituted with a divalent atom), a nitro group, a carbamoyl group, N— ( C1-C4 anoalkyl) Forced rubermoyl group; N, N-di (Ci C alkyl) Forced rubermoyl group, or one NHCOR19 (where R19 may be a hydrogen atom or branched and substituted with a halogen atom) Which is a C1-C alkyl group which may be substituted), 254 aryl group, cyan group, _N R 30 R 31 (wherein R 3 Q and R 31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom C 1 ~ C4 alkyl group), ditro group, canolemomoire group, N- (C1 ~ C4 alkyl) force rubamoyl group, N, N-di (. Alkyl) force rubamoyl group, -NHCOR19 (where, R19 Is a hydrogen atom or a C i to C 4 alkyl group which may be branched and substituted with a halo atom), and at least one group selected from the group consisting of halogen atoms And a heteroaryl group selected from the group consisting of and n is an integer from 1 to 12); and (xiv)-(CH2) n-SOz-R12 (Where R12 is (1) hydrogen atom, (2) branched) Ci-C4 alkyl group optionally substituted with a halogen atom, (3) an aryl group, the aryl group may be branched and optionally substituted with a halogen atom A C4 alkyl group, a Ci to C5 alkoxy group which may be branched and optionally substituted with a halogen atom, 255 halogen atom, which may be branched and optionally substituted with a halogen atom, an alkyl group, a cyano group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or branched; Or a Ci C alkyl group optionally substituted with a halogen atom), a nitro group, a strong rubamoyl group, N— (C1 to C4 alkyl) a strong rubamoyl group; N, N—di (C1 to Substituted with a strong rubermoyl group or one NHCOR19 (where R 19 is a hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom) An aryl group, a cyano group, _NR 30 R 31 (wherein R30 and R31 are each independently a hydrogen atom or a branched and substituted halogen atom) Good Ci ~ C4 alkyl group), nitro group, canolevamoy / re group, N- (dialkyl), rubamoyl group, N, N-di (dialkyl) carpamoyl group, -NHCOR19 (where, R19 is a hydrogen atom, or a Ci to C 4 alkyl group which may be branched and substituted with a halogen atom), and at least one group selected from the group consisting of halogen atoms An aryl group, and (4) a heteroaryl group, which may be branched and substituted with a halogen atom, a C4 alkyl group, 256 may be branched and may be substituted with a halogen atom Ci to C 5 anoloxy group, halogen atom, may be branched and may be substituted with a halogen atom A group, _NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), a nitro group , Carpamoyl group, N— (C1-C4 alkyl) force rubamoyl group; N, N-di (. Alkyl) force rubamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or branched) And may be substituted with a halogen atom, which is a C1-C4 alkyl group), a aryl group, a cyano group, _NR 30 R 31 (where R3 ° And R31 is Each independently a hydrogen atom, which may be branched and substituted with a halogen atom, or an alkyl group), a nitro group, a strong rubamoyl group, N- (C1-C4 alkyl) ) Force rubermoyl group, N, N-di (CC alkyl) Force rubermoyl group, -NHCOR19 (where R19 may be a hydrogen atom or may be branched and substituted with a halogen atom) An alkyl group), and a heteroaryl group, optionally substituted with at least one group selected from the group consisting of halogen atoms, and a group selected from the group consisting of n and 1 to 1 Is an integer of 2 257; a force that is a group selected from the group consisting of: or R7 and R7 ′ together are one (CH2) m- (where m is an integer from 2 to 8); (Where R23, R24, R25, R26, R27, R28, R29, R32, R33 and R34 are each independently a hydrogen atom; 'may form a branch or ring, and Z or halogen May be substituted with an atom, C1-C8 alkyl group; may be branched or ring-formed, and may be substituted with a halogen atom or a c2-c8 alkenyl group; branched or C2-C8 alkynyl group which may form a ring, and may be substituted with a halogen atom or C2-C8 alkynyl group which may be substituted with a halogen atom C1-C4 alkyl group which is substituted with a halogen atom Ci Cg alkoxy group power Exchange 258 may be an aryl group which is optionally substituted with an alkyl group of C i to C 4, a cyano group, a halogen atom or a nitro group, _NR3 ° R31 (where R30 and R 31 Each independently is a hydrogen atom or a C i to C 4 alkyl group which may be branched and substituted with a halogen atom), or a C2 to C8 alkylene group A cyclic amino group constituting the ring, or may be substituted with an aryl group; an alkyl group that may be substituted with a nodogen atom, or a substituent with a nodogen atom Good C1-C3 alkoxy group, cyano group, halogen atom, nitro group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or branched and C optionally substituted by halogen atom A certain ring is a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, or may be substituted with a heteroaryl group having an aryl moiety; C1-C3 alkoxy group optionally substituted with a C 4 alkyl group, a C atom alkyl atom, a cyan group, a halogen atom, a nitro group, or one NR30R31 (where R30 and R31 are respectively Each independently a hydrogen atom or a C 2 -alkyl group which may be branched and substituted with a halogen atom), and a certain group comprises a C 2 -C 8 alkylene group to form a ring. A cyclic amino group, which may be substituted with, an aryl moiety, an aralkyl group; a C1-C4 alkyl group which may be substituted with a halogen atom, or a halogen atom. C1-C3 Arco Xi group, cyan group, halogen atom, nitro group, one NR3 ° R31 (wherein R30 and R31 are each independently a hydrogen atom or a branched and halogen atom) Is an alkyl group optionally substituted with a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, or may be substituted with 259 Heteroaryl moiety having heteroaryl moiety; (C Cs alkoxy) carbonyl group; canolemoinole group; N- (C1-C4 alkyl) force rubamoyl group; and N, N-di (C1-C4 alkyl) force rubermoyl group And the alkyl group, which may be the same or different from each other, is a group selected from the group consisting of: and a divalent group selected from the group consisting of: It is a chemical anion. 2. R1 and R1 ′ forces of the optically active quaternary ammonium salt are each independently an (XV) aryl group, wherein the aryl group may be branched and substituted with a halogen atom. Also good. ~ 〇 Alkyl group, which may be branched and optionally substituted with a halogen atom C ~ C5 alkoxy group, halogen atom, which may be branched and optionally substituted with a halogen atom C1 ~ C4 An alkyl group, a cyano group, _NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a C1-C4 alkyl group that may be branched and substituted with a halogen atom) Nitto group, force rumomoyl group, N— (C1-C4 alkyl) force rubermoyl group, N, N—di (dialkyl) force rubermoyl group, or one NHCOR19 (where R19 is a hydrogen atom) Or an alkyl group which may be branched and may be substituted with a halogen atom), an aryl group, 260 Cyan group, _ NR 30 R 31 (where 尺ョ ^ ぉぉそれぞれそれぞれそれぞれそれぞれそれぞれそれぞれそれぞれそれぞれそれぞれそれぞれぉぉぉぉぉ 30 ぉ 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 ここ 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 (30 30 30 30 ここ NR ここここここここここここここここ 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 30 NR 30 30 30 30 30 NR NR NR NR NR NR ~ 〇 Alkyl group), ditro group, strong ruberamoyl group, N- (CC alkyl) carbamoyl group, N, N-di (C1-C4 alkyl) strong rubermoyl group, -NHCOR19 (where R19 is Substituted with at least one group selected from the group consisting of a hydrogen atom or a Ci-C4 alkyl group which may be branched and substituted with a halogen atom), and a halogen atom Or may be substituted together with O— (CH2) p-0- (wherein p is 1 or 2) in the 3, 4 position together, an aryl group; The catalyst according to claim 1, wherein 3. The R7 and R7 ′ forces of the optically active quaternary ammonium salt are each independently (i) an alkyl group of the same type that may form a branch or a ring; The catalyst described. Four. The catalyst according to any one of claims 1 to 3, wherein the optically active quaternary ammonium salt is a compound represented by the formula (1-1). Five. The following formula (I I): 261 Is a method for stereoselectively producing an α-amino nitrile derivative represented by the following formula (III): aldehyde represented by the following formula (III): 0, H (III), and the following formula (IV) : Is an optically active quaternary ammonium salt in the presence of an alkali metal cyanide and an acid, which has one of the following formulas (1-1) or (1-2): (1 -1) (1 -2) includes an optically active quaternary ammonium salt-containing solvent, and includes the following formulas (1-1) and (1 —2) In R1 and R1 ′ are each independently (i) a hydrogen atom; 262 (ii) -NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom) (iii (Vi) N- (C1-C4 alkynole) force rubamoyl group; (vii) N, N-di (C1-C4 alkyl) force rubamoyl group (Viii) -NHCOR19 (wherein R19 is a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom); (ix) a halogen atom; '(χ) May be branched or ringed and may be substituted with a halogen atom; C Ce alkyl group; (xi) may be branched or ringed and substituted with a halogen atom; A C2-C6 alkenyl group; (xii) may be branched or ring formed? An alkynyl group of C2 to C6; (xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be branched and halogenated. C1-C4 alkyl group which may be substituted with an atom, Ci-C5 alkoxy group which may be branched and may be substituted with a halogen atom, a halogen atom, an optionally branched and halogen atom Ci C alkyl group optionally substituted with, Cyano group, one NR30R31 (where R30 and 263 and R31 are each independently a hydrogen atom, or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N -(C1-C4 alkyl) force rubamoyl group, N, N —di (dialkyl) force rubamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or may be branched and a halogen atom) An aryl group, an aryl group, a cyano group, _NR 30 R 31 (where R3 ° and R31 are each independently A hydrogen atom, or a Ci to C4 alkyl group which may be branched and substituted with a halogen atom), ditro group, strong rubermoyl group, N— (di-alkyl) alkyl rubermoyl Group, N, N—di Alkyl) a strong rubermoyl group, -NHCOR19 (wherein R19 is a hydrogen atom or a ci to c4 alkyl group which may be branched and substituted with a halogen atom), and a halogen atom An aralkyl group optionally substituted with at least one group selected from the group consisting of: (xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is branched An alkyl group which may be substituted with a halogen atom, may be branched and may be substituted with a halogen atom C1 to C5 264 an alkoxy group, a halogen atom, a Ci C alkyl group that may be branched and substituted with a halogen atom, a cyan group, one NR30R31 (where R3 and R31 are each independently A hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (C1-C4 alkyl) a strong rubamoyl group, N, N-di (di-alkyl) or rubamoyl group, or NHCOR19 (wherein R 19 is a hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom) May be substituted with an aryl group, a cyano group, _NR 30 R 31 (where R3 ° and R31 are each independently a hydrogen atom or branched and Gen atom Ci-C4 alkyl group which may be substituted), nitro group, carpamoyl group, N— (dialkyl) rubamoyl group, N, N-di (. Ji alkyl) force rubamoy ' A group consisting of a hydrogen atom, -NHCOR19 (wherein R 19 is a hydrogen atom, or a CiC alkyl group that may be branched and substituted with a halogen atom), and a halogen atom And (XV) aryl group, wherein the aryl group may be branched and substituted with a halogen atom, which may be substituted with at least one group selected from C1 ~ C4 265 Alkyl group, which may be branched and optionally substituted with a halogen atom Ci to C 5 arnoleoxy group, halogen atom, which may be branched and optionally substituted with a halogen atom C1 to C4 alkyl Group, cyan group, or NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a Ci to C4 alkyl group which may be branched and substituted with a halogen atom) Nitto group, force rumomoyl group, N— (C1-C4 alkyl) force rumomoyl group, N, N—di (C1-C4 alkyl) force rubermoyl group, or one NHCOR19 (where R 19 is hydrogen) An aryl or a Ci C alkyl group that may be branched and optionally substituted with a halogen atom), an aryl group, a cyano group, _N R 30 R 31 (where , R3 ° and R31 Each independently represents a hydrogen atom or a branched or substituted halogen atom, which is a c1 to c4 alkyl group), a nitro group, a rubamoinole group, N- (C1 ~ C4 alkyl) Forced rubermoyl group, N, N-di (ji 丄 ~ di anorekil) Canolemomoinole group, -NHCOR19 (where R19 may be a hydrogen atom or may be branched and substituted with a halogen atom) Or a C i C alkyl group) and at least one group selected from the group consisting of a halogen atom, or O- ( CH2) p-0- (where p is 1 267 or 2), an aryl group; (xvi) a heteroaryl group, which may be branched and substituted with a halogen atom Ci ~ C4 alkyl group, which may be branched and optionally substituted with a halogen atom Ci C 5 alkoxy group, halogen atom, which may be branched and optionally substituted with a halogen atom C1 to C4 NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom) Nitto group, force rubermoyl group, N— (C1-C4 alkyl) canolemomoyl group, N, N—di (dialkyl) force rubermoyl group, or one NHCOR19 (where R 19 is a hydrogen atom) Or Or a Ci C alkyl group that may be branched and optionally substituted with a halogen atom), an aryl group, a cyano group, _NR 30 R 31 (where R30 And R 3 i each independently represents a hydrogen atom or a C i to C 4 alkyl group which may be branched and substituted with a halogen atom), a nitro group, a canremomoire group, N— (C1 to C4 alkyl) force rubamoyl group, N, N—di (〇 to ○ alkyl) force rubamoyl group, —NHCOR19 (where R19 may be a hydrogen atom or branched and a halogen atom) Is an optionally substituted C1-C4 alkyl group), and 267 a heteroaryl group optionally substituted with at least one group selected from the group consisting of halogen atoms; and (xvii) -S (O) n-R20 (where n is 0, 1, or 2) And R 2 ° may be branched and may be substituted with a halogen atom, which is a C4 alkyl group, and is a group selected from the group consisting of: R8, R8 ′, R9 , And R9 ′ are each independently a hydrogen atom; a halogen atom; optionally substituted with a halogen atom and / or an aryl group; and Z or forming a branch or ring Or a C i Cs alkyl group; or a C1-C5 alkoxy group that may be substituted with a divalent atom and a Z or aryl group, and / or that may form a branch or ring; Yes, R2, R2 ', R3, R3 ', R R4', R5, R5 ', R6, R6', R10 and R1 Q 'are each independently (i) a hydrogen atom; (ii) -NR30R31 (where R30 and R31 are each independently A hydrogen atom, or a Ci to C4 alkyl group which may be branched and substituted with a halogen atom); (iii) a cyano group; (iv) a ditro group; (V ) Force ruberamoyl group; (vi) N- (C1-C; 1 alkyl) force ruberamoyl group; 268 (vii) N, N-di (C1-C4 alkyl) force rubamoyl group; (viii) -NHCOR19 (wherein R19 may be a hydrogen atom or may be branched and substituted with a haguchigen atom) (Ix) a halogen atom; (X) a C1 to C6 group that may form a branch or a ring and may be substituted with a haguchigen atom. An alkyl group; (xi) a C2-C6 alkenyl group which may form a branch or a ring and may be substituted with a halogen atom; (xii) a branch or a ring which may form a halogen atom A C2-C6 alkynyl group which may be substituted by: (xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be branched and substituted with a halogen atom It may be. ~. An alkyl group, which may be branched and optionally substituted with a halogen atom, a C1-C5 alkoxy group, a halogen atom, a C1-C4 alkyl group which may be branched and optionally substituted with a halogen atom, Cyan group, _NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom) Nitto group, Carpamoyl group, N— (C1-C4 alkyl) Forced rubamoyl group, N, N—Di (Dialkyl) Forced rubamoyl group, or NHCOR19 (where R19 is a hydrogen atom or branched A Ci Ca alkyl group which may be substituted with a halogen atom and may be substituted with an aryl group, 269 Cyan group, '_ NR 30 R 3 1 (where R30 and R31 are each independently a hydrogen atom or a CC alkyl group that may be branched and substituted with a halogen atom) Nitro group, canolemoyl group, N— (di-alkyl) rubamoyl group, N, N-di (C1-C4 alkyl) rubamoyl group, —NHCOR19 (where R19 is a hydrogen atom, or A C i to c4 alkyl group which may be branched and substituted with a halogen atom), and may be substituted with at least one group selected from the group consisting of a halogen atom, (Xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety may be branched and substituted with a halogen atom Ci Cs may be branched and may be substituted with a halogen atom Ci Cs alkanoloxy group, C atom atom, Ci C alkyl group may be branched and may be substituted with a halogen atom, Cyan group NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom), Oral group, Carpamoyl group, N— (C1-C4 alkyl) Forced rubamoyl group, N, N—Di (Dialkyl) Forced rubamoyl group, or NHCOR19 (here 270, R19 may be a hydrogen atom, or may be branched and substituted with a halogen atom, and may be substituted with an aryl group, a cyano group,- NR 30 R 31 (wherein R 30 and R 31 are each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), Nitro group, force / levamoyl group, N- (di-alkyl) N- (C-alkyl) N, N-di (dialkyl) force-rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom or branched) Or a Ci to C4 alkyl group optionally substituted with a halogen atom), and optionally substituted with at least one group selected from the group consisting of a halogen atom, Teloaralkyl group; (XV) aryl group, wherein the aryl group may be branched and may be substituted with a halogen atom. The alkyl group may be branched and may be a halogen atom. 5 optionally substituted alkoxy group, halogen atom, optionally branched and substituted with halogen atom Ci Ca alkyl group, cyano group, _NR30R31 (where R30 and R31 are each Independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom) 271 mouth group, canolemoyl group, N— (di- to alkynole) force rubamoyl group, N, N — di (Ci C alkyl) force rubamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or branched) An alkyl group which may be substituted with a halogen atom), an aryl group, a cyano group, _N R 30 R 31 (where R3 ° and R31 are respectively Independently, a hydrogen atom, which may be branched and substituted with a halogen atom, is an alkyl group), a ditro group, a rubamoinole group, N- (C1-C4 alkyl) ) Force rubamoyl group, N, N-di (di-alkyl). Force rubamoyl group, -NHCOR19 (where R19 may be a hydrogen atom, or may be branched and substituted with a halogen atom). Is it an alkyl group? ), A halogen atom, and — S (O) n— R2 ° (where n is 0, 1, 'or 2 and R 2 ° may be branched and substituted with a halogen atom) May be substituted with at least one group selected from the group consisting of, or the 3rd and 4th positions together may be one of 0_ (CH2) m-hi (here And m is 1 or 2. The aryl group; (xvi) a heteroaryl group, wherein the heteroaryl group may be branched and substituted with a halogen atom Ci C alkyl group, which may be 272 Ci may be branched and may be substituted with a halogen atom Ci to C 5 anorecordoxy group, halogen atom, Ci C alkyl group that may be branched and may be substituted with a halogen atom, cyan group NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), Nitto group, strong rubermoyl group, N— (C1-C4 alkyl) strong rubermoyl group, N, N-di (C1-C4 alkyl) strong rubermoyl group, or one NHCOR19 (where R 19 is a hydrogen atom, Or may be branched and may be substituted with a halogen atom, and may be substituted with an aryl group, an aryl group, a cyano group, -NR30R31 (where R30 and R31 are , Respectively It is a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitro group, a cananolamoyl group, N- (C1-C4 alkyl) Force rubermoyl group, 'N, N-di (di- to alkyl) Force rubermoyl group, -NHCOR19 (where R19 may be a hydrogen atom, or may be branched and substituted with a halogen atom) And a heteroaryl group optionally substituted with at least one group selected from the group consisting of a halogen atom; and (xvii) -S (O) -R20 (wherein , N is 0, 1, or 2, and And R 2 ° is a group selected from the group consisting of: a C1-C4 alkyl group which may be branched and optionally substituted with a halogen atom; and R7 and R7 ′ are each independently A monovalent organic group or together represent a divalent organic group, and X is a halide anion, and in formulas (II) and (III), R41 is ( 1) may form a branch or ring, and may be substituted with Z or a halogen atom, a C1-C20 alkyl group; (2) may form a branch or ring, and Z or halogen A C2-C20 alkenyl group optionally substituted with an atom; (3) a C2-C20 alkynyl group optionally branched or formed with a Z or halogen atom; (4) May be substituted with halogen atoms A C1-C4 alkyl group, a c1-c3 alkoxy group optionally substituted with a halogen atom, an aryl group optionally substituted with an alkyl group of CC optionally substituted with a halogen atom, or a cyano group Group, halogen atom, nitro group, or NR3 ° R31 (where. R3G and R31 are each independently a hydrogen atom or a C-C4 alkyl group which may be branched and substituted with a halogen atom) force \ or C2- A cyclic amino group formed by forming a ring with a C8 alkylene group, which may be substituted with an aryl group; (5) a C to C4 alkyl group optionally substituted with a halogen atom, or C Cs alkoxy group, cyano group, halogen atom, nitro group, or —NR30R31 (wherein R3 ° and R31 are each independently hydrogen Atoms or may be branched and halogen atoms Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, or a heteroaryl having an aryl moiety, which may be substituted with (6) Ci-C4 alkyl group optionally substituted with a halogen atom, C1-C3 alkoxy group optionally substituted with a halogen atom, a cyan group, a halogen atom, nitro — NR3 ° R31 (wherein R3 ° and R31 are each independently a hydrogen atom or a C Cd alkyl group which may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, or may be substituted with a aralkyl group having an aryl moiety; (7) C to C 4a which may be substituted C1-C3 alkoxy group optionally substituted with an alkyl group, a halogen atom, a cyan group, a halogen atom, a nitro group, _NR3 ° R31 (where R3 and R31 are each Independently a hydrogen atom, or a C1-C4 alkyl group that may be branched and substituted with a halogen atom), or a ring formed of a C2-C8 alkylene group An amino group, which may be substituted with a heteroaryl moiety having a heteroaryl moiety; (8) (C1-C3 alkoxy) carbonyl group; (9) force rubamoyl group; (10) N- (Ci-C4 Alkyl) carbamoyl group; and (11) N, N-di (di-alkyl). Force rubamoyl group (where C1-C4 alkyl groups may be the same or different from each other). Group consisting of; In the formula (I I) and the formula (I V), R42 represents a group selected from the group 275 (1) Hydrogen atom; (2) Branched or ring-formed, and optionally substituted with Z or a halogen atom, the same alkyl group; (3) Branched or ring-formed And optionally substituted with Z or a halogen atom, C1-C8 alkoxy group; (4) optionally branched or formed a ring, and or optionally substituted with a halogen atom, A C2-C20 alkenyl group; (5) may be branched or ringed and / or may be substituted with a halogen atom; a C2-C20 alkynyl group; (6) substituted with a haguchi atom A C i to C 4 alkyl group, a C to C 3 alkoxy group optionally substituted with a haguchigen atom, or a C1 to C4 alkyl group optionally substituted with a haguchigen atom. An optionally substituted aryl group, cyan group, or A gen atom, a nitro group, -NR30R31 (wherein R3 ° and R31 are each independently a hydrogen atom or a Ci Ca alkyl group that may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, an aryl group; (7) an optionally substituted C i C ~ C 4 alkyl group, Ci C 3 alkoxy group optionally substituted with a halogen atom, cyan group, halogen atom, nitro group, or one NR30R31 (where R30 and R31 are Each independently a hydrogen atom, or may be branched and substituted with a halogen atom, or an alkyl group) or a C2-C8 alkylene group to form a ring Or a cyclic amino group formed by Can have, we have a Ariru moiety, Heteroariru group; (8) may be substituted with C port Gen atoms C ~ C 4 or alkyl group, optionally substituted with C port gain down atoms Ci～C. Alkoxy group, cyano group, halo 276 gen atoms, nitro groups, or one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or may be branched and substituted with a halogen atom. An alkyl group), or a cyclic amino group comprising a ring formed from a C2 to C8 alkylene group, or an aryl group having an aryl moiety; (9) a halogen atom; May be substituted. ~ 〇 Alkyl group power, C1-C3 alkoxy group optionally substituted with a halogen atom, cyano group, halogen atom, nitro group, — NR30R31 (where R30 and R31 are Each independently a hydrogen atom, or an alkyl group which may be branched and substituted with a halogen atom), or a cyclic amino comprising a ring composed of a C2-C8 alkylene group A heteroaralkyl group having a heteroaryl moiety; (10) (C1-C3 alkoxy) carbonyl group; (11) strong rubamoyl group; (12) N- (C1-C4 alkyl) (13) N, N-di (C1-C4 alkyl) force rubamoyl group (wherein Ci-C4 alkyl groups may be the same as or different from each other) ); And '(14) SO 2R 43 wherein R 43 is (i) optionally formed with a branch or ring, and optionally substituted with Z or a halogen atom. 08 alkyl group; (ii) the branch or ring And optionally substituted with a Z or halogen atom, a C2-C8 alkenyl group; (iii) optionally formed with a branch or ring, and / or substituted with a halogen atom An optionally substituted C2-C8 alkynyl group; 277 (iv) Ci C alkyl group optionally substituted with a halogen atom, c1 to c3 alkoxy group optionally substituted with a halogen atom, or optionally substituted with a halogen atom CC An aryl group, a cyan group, a halogen atom, a nitro group, or one NR3 ° R31 (wherein R3 ° and R31 are each independently a hydrogen atom, Or a C1-C4 alkyl group that may be branched and substituted with a halogen atom), or a cyclic amino group formed by forming a ring with a C2-C8 alkylene group, or substituted with An aryl group; (V) a C to C 4 alkyl group optionally substituted with a halogen atom, a C 1 to C3 alkoxy group optionally substituted with a halogen atom, a cyan group , Halogen atom, nitro group, one NR30R31 (Wherein R30 and R31 are each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom) or C2 A cyclic amino group that forms a ring with a C8 alkylene group, or an aryl group that may be substituted with a heteroaryl group; (vi) a C1-C4 alkyl group that may be substituted with a halogen atom A C1-C3 alkoxy group which may be substituted with a norogen atom, a cyan group, a halogen atom, a nitro group, or one NR30R31 (where R3 ° and R31 are each independently a hydrogen atom Or an alkyl group which may be branched and may be substituted with a halogen atom), or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, orA aralkyl group having an aryl moiety; (vii) an alkyl group which may be substituted with a halogen atom, a Ci to C 3 alkoxy group which may be substituted with a halogen atom, a cyan group or a halogen atom , A nitro group, or one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or may be branched and Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, which may be substituted with a rogen atom, or a heteroaryl moiety (Viii) (C1-C3 alkoxy) carbonyl group; (ix) force rubamoyl group; (x) N- (C1-C4 alkyl) force rubamoyl group; or (xi) N, N-di ( Ci C alkyl) A group selected from the group consisting of rubamoyl groups (wherein Ci C alkyl groups may be the same or different from each other). And in formula (II), * indicates a newly generated asymmetric center. 6. The following formula (V): Is a method for stereoselectively producing an α-amino nitrile derivative represented by the following formula (V I): Is an optically active quaternary ammonium salt in the presence of an alkali metal cyanide, which has the following formula (1-1) or formula (1-2) 279 includes the step of reacting in a solvent containing an optically active quaternary ammonium salt represented by (1 -1) (1 -2), wherein: In 1) and formula (1-2), R1 and R1 ′ are each independently (i) a hydrogen atom; (ii) -NR30R31 (wherein R30 and R31 are each independently a hydrogen atom; Or a C1-C4 alkyl group which may be branched and may be substituted with a halogen atom) (iii) a cyano group; (iv) a ditro group; (V) a cananolamoyl group; ) N-alkyl) force rubamoyl group; (vii) N, N-di (C1-C4 alkyl) force rubamoyl group; (viii) -NHCOR19 (where R19 may be a hydrogen atom or branched and A C to C 4 alkyl group which may be substituted with a halogen atom); (ix) a halogen atom; (X) forming a branch or ring It may and may be substituted with a halogen atom, an alkyl group of C1 -C6; 280 (Xi) C2-C6 alkenyl group which may form a branch or ring and may be substituted with a halogen atom; (Xii) may have a branch or ring and is substituted with a halogen atom An alkynyl group of C2 to C6; (xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be branched and substituted with a halogen atom; C1 to C4 alkyl group, which may be branched and may be substituted with a halogen atom C1 to C5 an aralkoxy group, halogen atom, which may be branched and may be substituted with a halogen atom To alkyl group, cyano group, one NR30R31 (wherein R30 and R31 each independently represents a hydrogen atom or may be branched and substituted with a nitrogen atom) N_ (C1-C4 alkyl) force rubamoyl group, N, N-di (C1-C4 alkyl) force rubermoyl group, or — NHCOR19 (where R 19 Is a hydrogen atom or an alkyl group which may be branched and may be substituted with a halogen atom) ', an aryl group, a cyano group, _NR 30 R 31 (here And R3 ° and R31 are each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitro group, Power ruberamoinole group, N- (ji ~ alkyl) carbamoyl group, 281 N, N-di (C1 to C4 alkyl) strong rubamoyl group, —NHCOR19 (wherein R19 is a hydrogen atom, or may be branched and substituted with a halogen atom, a C to C4 alkyl group) An aralkyl group optionally substituted with at least one group selected from the group consisting of halogen atoms; (xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl The moiety may be branched and may be substituted with a halogen atom C1-C4 alkyl group, may be branched and may be substituted with a halogen atom 5 alkoxy group, halogen atom, branched Ci C alkyl group, cyano group, _NR30R31 (wherein R30 and R31 are each independently a hydrogen atom, which may be optionally substituted with a halogen atom) Or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N- (di-alkyl) a strong rubermoyl group, N , N —di (di-alkyl) rubamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom, or may be branched and substituted with a halogen atom C1-C4 alkyl group) May be substituted with a aryl group, a cyano group, _NR 30 R 31 (where 1 ^ 3 ° and 1 ^ 31 are each independently a hydrogen atom or branched) And may be substituted with a halogen atom, which is an alkyl group), 282 Nitto group, canolemoyl group, N- (C1-C4 alkyl) force rubamoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R19 is a hydrogen atom or branched) Or a ci to c4 alkyl group optionally substituted with a halogen atom), and optionally substituted with at least one group selected from the group consisting of halogen atoms, An aralkyl group; (XV) an aryl group, wherein the aryl group may be branched and may be substituted with a halogen atom Ci to C4 alkyl group, optionally branched and halogenated Ci C 5 alkoxy group optionally substituted with atoms, halogen atom, branched and optionally substituted with halogen atoms Alkyl group, cyano group, _NR30R31 (where R30 Each independently represents a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a carbamoyl group, N — (Ji ~ ji alkyl) force ruberamoyl group, N, N —di (C1 to C4 alkyl) force rubermoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or may be branched and halogen atom) An aryl group, a cyano group, _NR 30 R 31 (wherein R30 and R31 are each independently a hydrogen atom, which may be a C1-C4 alkyl group optionally substituted) A 283 atom, or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitro group, a rubamoyl group, N- (C1-C4 anoalkyl) canolevamoi / le Group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R19 may be a hydrogen atom, or may be branched and substituted with a halogen atom) Ci-C4 An alkyl group), and may be substituted with at least one group selected from the group consisting of a halogen atom, or O- (CH2) p-0 -(Wherein p is 1 or 2) optionally substituted by an aryl group; (xvi) a heteroaryl group, wherein the heteroaryl group may be branched and substituted with a halogen atom The same alkyl group, min Ci to C 5 alkoxy group which may be substituted with a halogen atom, a halogen atom, a Ci C alkyl group which may be branched and may be substituted with a halogen atom, a cyan group, NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), a nitro group, a force Rubamoyl group, N— (C1-C4 alkyl) force rubamoyl group, N, N—di (Ci C alkyl) force rubermoyl group, or one NHCOR19 (where R 19 may be a hydrogen atom or may be branched) And a Ci to C4 alkyl group that may be substituted with a halogen atom). 284 aryl group, cyan group, _ NR 30 R 31 (where R 3 and R 31 are each independently a hydrogen atom or may be branched and substituted with a halogen atom) N- (Ci C alkyl) force rubamoyl group, N, N-di (dialkyl) carbamoyl group, one NHCOR19 (where R 19 is hydrogen) Or a C i C alkyl group that may be branched and substituted with a halogen atom), and substituted with at least one group selected from the group consisting of halogen atoms A heteroaryl group; and (xvii) -S (O) n-R20 (where n is 0, 1, or 2 and R2 ° may be branched and substituted with a halogen atom) Ci to C4 alkyl group which may be A group selected from the group consisting of: R8, R8 ′, R9, and R9 ′ each independently a hydrogen atom; a halogen atom; a halogen atom and a no or aryl group And / or a Ci Cs alkyl group that may be substituted with and / or may form a branch or a ring; or may be substituted with a halogen atom and / or an aryl group, and 285 or a C1-C5 alkoxy group that may form a branch or a ring; and R2, R2 ', R3, R3', R4, R4 ', R5, R5', R6, R6 ', R10 and R1G ′ is independently (i) a hydrogen atom; (ii) -NR30R31 (where R3C) and R31 are each independently a hydrogen atom or a branched and halogen atom. (Iii) a cyano group; (iv) a nitro group; (V) a strong rubamoyl group; (vi) an N- (C1-C4 alkyl) strong rubamoyl group. (Vii) N, N-di (C to 04 alkyl) force rubamoyl group; (viii) -NHCOR19 (wherein R19 is a hydrogen atom or may be branched and substituted with a halogen atom); (Ix) a halogen atom; (X) may be branched or formed a ring and substituted with a halogen atom. C1-C6 alkyl group; (xi) C2-C6 alkenyl group which may form a branch or ring and may be substituted with a halogen atom; (xii) branch or A C2-C6 alkynyl group which may form a ring and may be substituted with a halogen atom; (xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group is branched. May be substituted with a halogen atom! ~ Ji ^ 286 alkyl group, optionally branched and optionally substituted with a halogen atom Ci to C 5 alkoxy group, halogen atom, optionally branched and optionally substituted with a halogen atom Ci C alkyl group , Ciano group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom) ), Nitro group, carbamoyl group, N— (Ci C alkyl) force rubamoyl group, N, N—di (CC alkyl) force rubamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or branched) An aryl group, a cyano group, or _NR 30 R 31 (where R3 ° and R31 are substituted with a halogen atom, which is a C1-C4 alkyl group which may be substituted with a halogen atom) Is that Each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom) a nitro group, a carpamoinole group, N- (C1-C4 ananolyl) ) Forced rubermoyl group, N, N-di (C1-C4 alkyl) Forced rubermoyl group, -NHCOR19 (where R 19 may be a hydrogen atom or may be branched and substituted with a halogen atom) a alkanoleno group which may be substituted with at least one group selected from the group consisting of a halogen atom, and a C1-C4 alkyl group; 287 (xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is a Ci C alkyl group that may be branched and substituted with a halogen atom, and may be branched and C1-C5 alkoxy group optionally substituted with a halogen atom, halogen atom, optionally branched and optionally substituted with a halogen atom Alkyl group, cyano group, one NR30R31 (where, R30 and R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a carbamoyl group, N— ( C1-C4 alkyl) force rubamoyl group, N, N —dialkyl) force rubamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or may be branched) An aryl group which may be substituted with a halogen atom), an aryl group, a cyano group, _NR 30 R 31 (where R3 ° and R31 are each independently A hydrogen atom, which may be branched and may be substituted with a halogeni atom, a c1-c4 alkyl group), a nitro group, a force rubamoyl group, an N- (C1-C4 alkyl) force Rubamoyl group, N, N-di (C1-C4 alkyl) Forced rubermoyl group, -NHCOR19 (where R19 is a hydrogen atom or a C alkyl group which may be branched and substituted with a halogen atom) ), And 288, a heteroaralkyl group optionally substituted with at least one group selected from the group consisting of halogen atoms; (XV) aryl group, wherein the aryl group may be branched Ci-C4 alkyl group which may be substituted with halogen atom, Ci Cs alkoxy group which may be branched and may be substituted with halogen atom, halogen atom, which may be branched and halogen atom Alkyl group, cyano group, _NR30R31 (wherein R30 and R31 each independently represents a hydrogen atom or may be branched and substituted with a halogen atom) Nitto group, strong rubamoyl group, N— (C1-C4 alkyl) strong rubamoyl group, N, N—di (C1-C4 alkyl) strong rubamoyl group, Is an NHCOR19 (wherein R 19 is a hydrogen atom or a Ci to C4 alkyl group which may be branched and substituted with a halogen atom), an aryl group , Sano group, _NR 30 R 3 1 (wherein R 30 and R 31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom) Nitro group, carpamoinole group, N- (dialkyl), rubamoyl group, N, N-di (C1-C4 alkyl) rubamoyl group, -NHCOR19 (where R19 is hydrogen) Whether it is an atom or branched 289 and optionally substituted with a halogen atom, which is a C to the same alkyl group), a halogen atom, and —S (O) n-R20 (where n is 0, 1, or 2; R 2 ° may be branched and may be substituted with at least one group selected from the group consisting of 4 to 4 alkyl groups that may be substituted with halogen atoms, Alternatively, the 3- and 4-positions may be substituted together with O— (CH2) m-0- (where m is 1 or 2), an aryl group; (xvi) a heteroaryl group. The heteroaryl group may be branched and substituted with a halogen atom C! C4 alkyl group, which may be branched and optionally substituted with a halogen atom C to C5 an aralkoxy group, halogen atom, which may be branched and optionally substituted with a halogen atom C1 to C4 alkyl group, cyano group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or may be branched and substituted with a halogen atom. C! CaT alkyl) Nitto group, forceful rubamoyl group, N— (di-alkyl) force rubamoyl group, N, N—di (C1-C4 alkyl) force rubamoyl group, or one NHCOR19 (where R19 is A hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), an aryl group, a cyano group, _NR 3 o R 3 i (where R 30 Beauty R31 are each independently be substituted or a well and a halogen atom are either hydrogen, or branched 290 or C1-C4 alkyl group), nitro group, strong ruberamoyl group, N— (Ci C alkyl) strong rubermoyl group, N, N—di (C1-C4 alkyl) strong rubermoyl group, -NHCOR19 And R19 is a hydrogen atom or a Ci-C4 alkyl group which may be branched and substituted with a halogen atom), and at least one selected from the group consisting of a halogen atom A heteroaryl group optionally substituted by a group; and '(xvii) -S (O) n-R20 (where n is 0, 1, or 2 and R 2 ° is branched) And a C1 to C4 alkyl group optionally substituted with a halogen atom); a group selected from the group consisting of: R7 and R7 ′ are each independently a monovalent organic group Or together represent a divalent organic group, and X Is a halide anion, and in formulas (V) and (V I), R41 is (1) may be branched or ringed and may be substituted with Z or a halogen atom, An alkyl group; (2) may form a branch or ring, and may be substituted with Z or a halogen atom, C2-C20 alkenyl group; (3) may form a branch or ring, And a C2-C20 alkynyl group which may be substituted with no or a halogen atom; 291 (4) Ci to C4 alkyl group optionally substituted with haguchigen atom, Ci Cg alkoxy group optionally substituted with haguchigen atom, or substituted with haguchigen atom It may be an aryl group optionally substituted with a C1-C4 alkyl group, a cyano group, a halogen atom, a nitro group, or one NR3 ° R31 (where 1 3 £> push 1 ^ 31 Each independently represents a hydrogen atom, or a C1-C4 alkyl group which may be branched and substituted with a halogen atom, or a ring having a C2-C8 alkylene group. An aryl group; an aryl group; (5) a C i to C 4 alkyl group that may be substituted with a halogen atom or a halogen atom C1-C3 alkoxy group, cyano group, nitrogen atom, nitro group, -NR30R3 1 (wherein R30 and R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom) Or a cyclic amino group comprising a ring with a C2 to C8 alkylene group, or may be substituted with a heteroaryl group having an aryl moiety; (6) may be substituted with a halogen atom Ci to C4 alkyl group, Ci to C3 alkoxy group optionally substituted with a nocturnal gen atom, cyano group, halogen atom, nitro group, _NR30R31 (where R3. And Each of R31 is independently a hydrogen atom, or a branched-and optionally substituted with a halogen atom (O to O alkyl group), or a C2 to C8 alkylene group. A cyclic amino group comprising a ring, or May be conversion has Ariru moiety, Ararukiru group; (7) C port Gen atoms or an optionally substituted C ~ C 4 alkyl group, optionally substituted with C port gain down atoms. 03Alkoxy group power \ Cyan group, halogen atom, nitro group, one NR30R31 (where R30 and R31 are each independently a hydrogen atom or branched and halogenated) Atom 292 or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, or a heterocyclic group having a heteroaryl moiety, or a heteroaralkyl group having a heteroaryl moiety. (8) (C1-C3 alkoxy) carbonyl group; (9) strong rubamoyl group; (10) N- (C1-C4 alkyl) strong rubamoyl group; and (11), N-di (di-alkyl) A group selected from the group consisting of: a carpamoyl group (wherein 1 to 4 alkyl groups may be the same or different from each other); and R43 represents ( i) may be branched or ring, and may be substituted with Z or a halogen atom, a C1-C8 alkyl group; (ii) may be branched or ringed, and Z or halogen Substituted with atoms (Iii) a C2-C8 alkenyl group; (iii) a C2-C8 alkynyl group which may form a branch or a ring and may be substituted with Z or a halogen atom; C1-C4 alkyl group which may be substituted with C1-C3 alkoxy group which may be substituted with a nodule gen atom, or a C1-C4 group which may be substituted with a C-cage atom An aryl group optionally substituted with an alkyl group, a cyan group, a halogen atom, a nitro group, or one NR3 ° R31 (wherein 1 3 £ 1 and 131 are each independently a hydrogen atom Or a C1-C4 alkyl group which may be branched and substituted with a divalent atom), or a cyclic amino group comprising a C2-C8 alkylene group to form a ring. Optionally substituted with an aryl group; (V) substituted with a vicinal atom Even though it may C1~C4 alkyl group or, (c) opening gate A C1-C3 alkoxy group, a cyano group, a halogen atom, a nitro group, or one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom) Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, which may be branched and may be substituted with a halogen atom. Optionally substituted, having an aryl moiety, heteroaryl group; (vi) optionally substituted with a halogen atom, alkyl group power \ optionally substituted with a halogen atom C1-C3 alkoxy group Or a cyano group, a halogen atom, a nitro group, or one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or branched and substituted with a halogen atom) Even though Or a cyclic amino group comprising a ring composed of a C2 to C8 alkylene group, or an aryl group having an aryl moiety; (vii) halogen Ci-C4 alkyl group optionally substituted with an atom, C1-C3 alkoxy group optionally substituted with a halogen atom, a cyano group, a halogen atom, a nitro group, or one NR30R31 (here R30 and R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), or a ring having a C2-C8 alkylene group. Or a heterocyclic amino group having a heteroaryl moiety; (viii) (C1-C3 alkoxy) carbonyl group; (ix) canolamoyl group; (x ) N- (Ci-C4 alkyl) force rubamoyl group; or (xi) N, N-di (C1-C4 alkyl) force rubamoyl group (where C1-C4 alkyl groups may be the same or different from each other) Good) is a group selected from the group consisting of: 294 represents a group selected from the group consisting of: and in formula (V) * represents a newly generated asymmetric center. 7. The following formula (V) A method for stereoselectively producing a ct-amino nitrile derivative represented by the following formula (XXV I I I): Is an optically active quaternary ammonium salt in the presence of an alkali metal cyanide, which has one of the following formulas (1-1) or (I-2): Reacting in a solvent containing an optically active quaternary ammonium salt represented by X (1-1) (1 -2), 295 where, in formula (1-1) and formula (1-2), R1 and R1 ′ are each independently (i) a hydrogen atom; (ii) -NR30R31 (where R3 ° and R31 are Each independently a hydrogen atom or a C j -C 4 alkyl group which may be branched and substituted with a halogen atom) (iii) a cyano group; (iv) a nitro group; (Vi) N- (Ci-C4 alkyl) strong rubamoyl group; (vii) N, N-di (di-alkyl) strong rubamoyl group; (viii) -NHCOR19 (where R19 is A hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom); (ix) a halogen atom; (X) may form a branch or a ring And a C1-C6 alkyl group optionally substituted with a halogen atom; (xi) may be branched or formed a ring? A C2-C6 alkenyl group optionally substituted with a halogen atom; (xi i) may be branched or ring-formed and may be substituted with a halo atom, C2-C6 alkynyl A group; (xiii) an aralkyl group, wherein the aryl moiety constituting the aralkyl group may be branched and may be substituted with a halogen atom, Ci to C 4 alkyl group, branched Ci C 5 which may be substituted with a halogen atom 296 Alkoxy group, halogen atom, Ci C alkyl group, Cyano group, which may be branched and substituted by halogen atom, one NR30R31 (where R30 and R31 are each independently hydrogen Or an alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (di-alkyl) a strong rubamoyl group, N, N —Di (di-alkyl) or rubamoyl group, or one NHCOR19 (where R19 is a hydrogen atom, or a Ci-C4 alkyl group that may be branched and substituted with a halogen atom) ) May be substituted with an aryl group, a cyano group, _NR 30 R 31 (wherein R 30 and each independently represents a hydrogen atom or a branched and haguchine atom) Put in May be substituted C1-C4 alkyl group), ditro group, carpamoyl group, N— (C1-C4 alkynole) force rubermoyl group, N, N-di (C1-C4 alkyl) force rubermoyl group , -NHCOR19 (where R19 is a hydrogen atom or a Ci to C4 alkyl group which may be branched and substituted with a halogen atom), and a halogen atom. An aralkyl group optionally substituted with at least one group selected from: (xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is 297 Alkyl group which may be branched and may be substituted with a halogen atom Ci-C 5 alkoxy group which may be branched and may be substituted with a halogen atom, a halogen atom, C1-C4 alkyl group, Cyano group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or branched, which may be branched and may be substituted with a halogen atom. Or a C1-C4 alkyl group which may be substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N-alkyl) a strong rubamoyl group, N, N —di (C1-C4 alkyl) ) A rubamoyl group, or one NHCOR19 (wherein R 19 is a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom) Good Aryl group, cyan group, '-NR30R 31 (wherein R3 ° and R31 are each independently a hydrogen atom or may be branched and substituted with a halogen atom. C1-C4 N- (C1-C4 alkyl) force rubamoyl group, N, N-di (ji-ji alkyl) force rubamoyl group, -NHCOR19 (where R19 is an alkyl group) A hydrogen atom or a c1-c4 alkyl group which may be branched and substituted with a halogen atom), and substituted with at least one group selected from the group consisting of halogen atoms May, to 298 teloaralkyl group; (XV) aryl group, wherein the aryl group may be branched and may be substituted with a halogen atom C1-C4 alkyl group, optionally branched And a C1-C5 alkoxy group which may be substituted with a halogen atom, a halogen atom, a C1-C4 alkyl group which may be branched and substituted with a halogen atom, a cyan group, one NR30R31 (where R30 and R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a cananolamoyl group, N- (Ji ~. Alkyl) force rubermoyl group, N, N —di (ji ~ alkyl) force rubermoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or may be branched and halogen) Which is a C1-C4 alkyl group which may be substituted with a child), an aryl group, a cyano group, _N R 30 R 31 (where R3 ° and R31 are each independently , A hydrogen atom, or a Ci C alkyl group which may be branched and substituted with a halogen atom), a nitro group, a rubamoyl group, N— (C1-C4 alkyl) a rubamoyl group , N, N-dialkyl) Forced rubermoyl group, —NHCOR19 (where R19 is a hydrogen atom or a C i C alkyl group which may be branched and substituted with a halogen atom) ) , and 299 may be substituted with at least one group selected from the group consisting of halogen atoms, or O- (CH2) p-0- (where p is 1 Or an aryl group; (xvi) a heteroaryl group, which may be branched and substituted with a halogen atom. Ci to C 4 alkyl A C1-C5 alkoxy group that may be branched and substituted with a halogen atom, a halogen atom, a C1-C4 alkyl group that may be branched and optionally substituted with a halogen atom, Cyan group, one NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom) ), Nito, Koki, Rubamoyl group, N— (ji 丄 ~ ji ^! Alkyl) Rubamoinore group, N, N — Di (C1 ~ C4 alkyl) Rubamoyl group, or one NHCOR19 (where R 19 is a hydrogen atom or branched) An aryl group, a cyano group, _ NR 30 R 31 (where R30 is an optionally substituted C 1 -C 4 alkyl group optionally substituted with a halogen atom) And R31 are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), a nitro group, a force rubamoyl group, N- (C1˜ C4 alkyl) strong rubamoyl group, N, N-di (C1-C4 alkyl) strong rubamoyl group, 300 —NHCOR19 (wherein R19 is a hydrogen atom or a Ci Ca alkyl group that may be branched and substituted with a halogen atom), and selected from the group consisting of halogen atoms A heteroaryl group optionally substituted with at least one group; and (xvii) -S (O) n-R20 (where n is 0, 1, or 2 and R2 is branched). And a group selected from the group consisting of R8, R8 ′, R9, and R9 ′ are each independently a group selected from the group consisting of Cj to C4 alkyl groups optionally substituted with a halogen atom. With a hydrogen atom. A halogen atom; a force that is a Ci Cg alkyl group, optionally substituted with a halogen atom and / or aryl group, and optionally forming a Z or branched or ring; Optionally substituted with a halogen atom and a no or aryl group, and may form Z or a branched or ring, (^ to 5 alkoxy groups; and R2, R2 ', R3, R3', R4, R4 ′, R5, R5 ′, R6, R6 ′, R10 and R1 ° ′ are each independently (i) a hydrogen atom; (ii) -NR30R31 (where R30 and R31 are each independently (I) a hydrogen atom or a Ci to C4 alkyl group which may be branched and may be substituted with a halogen atom); (iii) a cyan group; (iv) Nitto group; (V) force rubamoyl group; (vi) N- (C1-C4 alkyl) force rubamoyl group; (vii) N, N-di (C1-C4 alkyl) force rubamoyl group; ) -NHCOR19 (wherein R19 is a hydrogen atom or a C to C 4 alkyl group which may be branched and substituted with a halo atom); (ix) a halogen atom; (X) an alkyl group of C Ce which may form a branch or a ring and may be substituted with a halogen atom; (xi) may have a branch or a ring and is substituted with a halogen atom (Xii) a C2-C6 alkynyl group which may form a branch or a ring and may be substituted with a halogen atom; (xiii) an aralkyl group Wherein the aryl moiety constituting the aralkyl group may be branched and halogenated. Ci-C4 alkyl group optionally substituted with an atom, may be branched and optionally substituted with a halogen atom. 05 Alkoxy group, halogen atom, optionally branched and substituted with a halogen atom C1-C4 alkyl group, cyano group, one NR30R31 (where R30 and R31 are each independently A hydrogen atom or a C1-C4 alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N- (di-ji alkyl) a strong rubermoyl group , N, N—di (dialkyl) force rubermoyl group, or one NHCOR19 (here 302, R 19 is a hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom), an aryl group, a cyano group, _N R 30 R 31 (wherein R 30 and R 31 are each independently a hydrogen atom or a C i to C 4 alkyl group which may be branched and substituted with a halogen atom) ) Nitro group, strong rubamoyl group, N- (Ci-C4 alkyl) strong rubamoyl group, N, N-di (C1-C4 alkynole) strong rubamoyl group, -NHCOR19 (where R 19 is a hydrogen atom or branched) A C alkyl group optionally substituted with a halogen atom), and an aranolenole group optionally substituted with at least one group selected from the group consisting of halogen atoms; (xiv) Heteroary A heteroaralkyl group having an alkyl moiety, wherein the heteroaryl moiety may be branched and substituted with a halogen atom. Alkyl group, optionally branched and optionally substituted with a halogen atom 5 Alkoxy group, halogen atom, optionally branched and optionally substituted with a halogen atom C1-C4 alkyl group, cyano group NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or may be branched and 303 Ci C alkyl group optionally substituted with a halogen atom), Nitto group, strong rubamoyl group, N— (C1 to C4 alkyl) strong rubamoyl group, N, N — di (Ci to C4 alkyl) ). Substituted with a strong rubermoyl group, or with one NHCOR19 (wherein R 19 is a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom). Or aryl group, cyano group, _ NR 30 R 31 (where R3 ° and R31 are each independently a hydrogen atom, or may be branched and substituted with a halogen atom). Nitro group, carbamoyl group, N- (. Ji alkyl) carbamoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, -NHCOR19 (where R19 is Substituted with at least one group selected from the group consisting of a hydrogen atom, or a C 4-4 alkyl group which may be branched and substituted with a halogen atom) Is A heteroaralkyl group, which may be a (XV) aryl group, wherein the aryl group may be branched and substituted with a halogen atom. , May be branched and may be substituted with a halogen atom C1 to (5 alkoxy group, halogen atom, may be branched and substituted with a halogen atom CC alkyl group, cyan group, _NR30R31 (wherein R30 and R31 are each independently a hydrogen atom or may be branched and substituted with a halogen atom) N- (C1-C4 alkyl) force rubamoyl group, N, N-di (C1-C4 alkyl) force rubamoyl group, or one NHCOR19 (where R19 Is a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom), an aryl group, a cyano group, _NR 30 R 31 (where , R3 ° and R31 are each independently a hydrogen atom or a branched and optionally substituted with a halogen atom, a 0 to 0 alkyl group), a nitro group, a rubamoyl group , N- (Ci C (Rukyl) Forced rubermoyl group, N, N-di (C1-C4 alkyl) Forced rubermoyl group, -NHCOR19 (where R19 may be a hydrogen atom or may be branched and substituted with a halogen atom) 'Is a C i to C4 alkyl group), a halogen atom, and — S (O) n-R20 (where n is 0, 1, or 2 and R 2 ° is branched) And may be substituted with at least one group selected from the group consisting of C1 to C4 alkyl groups optionally substituted with a halogen atom, or the 3, 4 positions together. One O— (CH2) m-0- (wherein m is 1 or 2), an aryl group; 305 (xvi) a heteroaryl group, wherein the heteroaryl group may be branched and optionally substituted with a halogen atom Ci C alkyl group, optionally branched and substituted with a halogen atom C1-C5 arnoleoxy group, halogen atom, optionally branched and substituted with halogen atom Alkyl group, cyano group, one NR30R31 (where R30 and Each of R31 is independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— ( C1-C4 alkyl) force rubamoyl group, N, N-di (Ci C alkyl) force rubamoyl group, or one NHCOR19 (where R 19 may be a hydrogen atom or branched and substituted with a halogen atom) Even if Which is preferably a C1-C4 alkyl group), an aryl group, a cyano group, _NR 30 R 31 (where R30 and R 3 i are each independently a hydrogen atom, or It may be branched and may be substituted with a halogen atom. It is an alkyl group.), Nitto mouth group, Canolevamoyl group, N- (Ci-C4 alkyl) Forced rubermoyl group, N, N— Di (C1-C4 alkyl) force rubermoyl group, -NHCOR19 (where R19 is a hydrogen atom, or a C i-C 4 alkyl group which may be branched and substituted with a haguchi atom) ) And halogen atoms A heteroaryl group optionally substituted with at least one group selected from the group consisting of: 306; and (xvii) -S (O) n-R20 (where n is 0, 1, or 2) And R 2 ° is a group selected from the group consisting of: a C1-C4 alkyl group which may be branched and optionally substituted with a halogen atom; and R7 and R7 ′ are each independently And X— is a halide anion, and in Formula (V) and Formula (XXV III), R41 is a monovalent organic group or together represents a divalent organic group. , (1) may be branched or ring, and may be substituted with Z or a halogen atom, the same alkyl group; (2) may be branched or ring; and Or C2-C20 alkeni optionally substituted with a halogen atom Group; (3) may form a branched or cyclic, and Z or may be substituted with a halogen atom, C2 to C20 alkynyl groups; optionally substituted by (4) c port Gen atoms C An alkyl group optionally substituted with a halogen atom, a Ci Cg alkoxy group optionally substituted with a halogen atom, an aryl group optionally substituted with a C1-C4 alkyl group optionally substituted with a halogen atom, or a cyan group , A halogen atom, a nitro group, or one NR3 ° R31 (wherein R3Q and R31 each independently represents a hydrogen atom or may be branched and substituted with a halogen atom, C1 to A C4 alkyl group), or a cyclic amino group formed by a C2-C8 alkylene group, which may be substituted with a aryl group; (5) substituted with a halogen atom May be a C-C4 alkyl group Ci Cg alkoxy group which may be substituted with 307 atoms \ Cyan group, nitro group, nitro group, or NR30R31 (where R30 and R31 are each independently hydrogen Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, which may be branched and may be branched and may be substituted with a halogen atom. A heteroaryl group having an aryl moiety; (6) a Ci to C4 alkyl group optionally substituted with a halogen atom, or a C1 to C3 alkoxy group optionally substituted with a halogen atom , A cyano group, a halogen atom, a nitro group, _NR30R31 (where R30 and R31 are each independently a hydrogen atom or branched and substituted with a halogen atom) C1 ~ C4 Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, or an aryl group having an aryl moiety; (7) a haguchi atom C-C4 alkyl group optionally substituted with C1-C3 alkoxy group optionally substituted with a halogen atom, cyano group, halogen atom, nitro group, _NR30R31 (here And R30 and R31 are each independently a hydrogen atom or a C1-C4 alkyl group which may be branched and substituted with a halogen atom) or C2 A cyclic amino group that forms a ring with a C8 alkylene group, or a heteroaralkyl group that may be substituted with a heteroaryl moiety; (8) (C1-C3 alkoxy) carbonyl group; (9) a rubamoyl group ; (10) N- (ji Alkyl) strong rubermoyl group; and (11) N, N-di (C1-C4 alkyl) strong rubermoyl group (wherein the C1-C4 alkyl groups may be the same or different from each other). Group) A group selected from the group consisting of 308, wherein R43 is (i) optionally branched or ring-formed, and / or optionally substituted with a halogen atom, Ci to C8 alkyl group; ii) a C2-C8 alkenyl group that may be branched or ringed and may be substituted with a halogen atom; (iii) may be branched or ringed and and or a halogen atom A C2-C8 alkynyl group which may be substituted; (iv) a C-C4 alkyl group which may be substituted with a halogen atom, a C1-C3 which may be substituted with a halogen atom NR3 (5R31 (where R 1 is an aryl group, a cyan group, a halogen atom, a nitro group, an alkyl group optionally substituted with a C1-C4 alkyl group, which may be substituted with an alkoxy group, or a halogen atom). , R3 ° and R31 are each independently Or a C-C4 alkyl group which may be branched and substituted with a divalent atom), or a cyclic structure comprising a C2-C8 alkylene group An amino group, optionally substituted with an aryl group; (V) optionally substituted with a C-C4 alkyl group optionally substituted with a hydrogen atom or optionally substituted with a nitrogen atom 3 Alkoxy group, cyano group, halogen atom, nitro group, one NR3 ° R31 (wherein R30 and R31 each independently represent a hydrogen atom or may be branched and O may be substituted with a halogen atom or an alkyl group), or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, or may be substituted with an aryl moiety. A heteroaryl group; (vi) with a haguchi atom C1-C4 alkyl group which may be substituted, Ci-C3 alkoxy group which may be substituted with a phenoxy atom, Cyan group, halogen atom, nitro group, _NR30R31 (here R30 and R31 are 309 each independently a hydrogen atom, or a C1-C4 alkyl group that may be branched and substituted with a halogen atom), or a C2-C8 alkylene group, A cyclic amino group, which may be substituted with, an aryl moiety, an aralkyl group; (Vii) a C! C alkyl group which may be substituted with a halogen atom, or a halogen atom; Ci ~ C3 alkoxy group, cyano group, halogen atom, nitro group, or one NR30R31 (where R30 and R31 are each independently a hydrogen atom or may be branched) And a C1-C4 alkyl group that may be substituted with a halogen atom), or a cyclic amino group that forms a ring with a C2-C8 alkylene group, or a heteroaryl moiety that may be substituted with The (Viii) (C1-C3 alkoxy) carbonyl group; (ix) force rubamoyl group; (x) N- (C1-C4 alkyl) force rubamoyl group; or (xi) N, N-di (C1 A group selected from the group consisting of: a group selected from the group consisting of Ci-C4 alkyl groups, which may be the same or different from each other); In the formula (XXV III), R11 is a C alkyl group that may be substituted with a halogen atom, or a Ci to C3 alkoxy group that may be substituted with a halogen atom, or a halogen atom. An aryl group, a cyano group, a halogen atom, a nitro group, or an NR30R31 (wherein R3 ° and R31 are each independently substituted with an optionally substituted Ci C alkyl group) A hydrogen atom or a minute And may be substituted with a halogen atom. Or a cyclic amino group formed by forming a ring with a C2 to C8 alkylene group, an aryl group, and in formula (V), * is A method that shows the newly generated chiral center. 8. A method for producing an optically active α-amino acid or a derivative thereof, wherein the formula (I I) obtained by the method according to claim 5: A step of hydrolyzing an optically active α-amino nitrile derivative represented by the following formula: wherein R41 may form a branch or a ring, and or (2) an optionally substituted alkyl group; (2) a C2-C20 alkenyl group which may form a branch or ring and / or may be substituted with a halogen atom; (3) A C2-C20 alkynyl group which may form a branch or a ring, and may be substituted with Z or a halogen atom; (4) a C-C4 alkyl group which may be substituted with a halogen atom Or a C-C3 alkoxy group which may be substituted with a nocturnal gen atom, an aryl group which may be substituted with a C1-C4 alkyl group which may be substituted with a halogen atom Or a cyano group, a halogen atom, or a nitro group One NR30R31 (wherein the R3 ° and R31, each independently, a hydrogen atom or optionally branched C ~ C 4 be substituted or a well and Ha port Gen atoms have an alkyl group Kadea Or an aryl group which may be substituted with a cyclic amino group formed by forming a ring with a c2 to c8 alkylene group; (5) optionally substituted with a halogen atom; C4 alkyl group, C1-C3 alkoxy group optionally substituted with a neuron atom \ Cyan group, a neuron atom, a nitro group, one NR30R31 (where R30 and R31 are Each independently a hydrogen atom, or may be branched and substituted with a halogen atom, or an alkyl group), or a C2-C8 alkylene group constitutes a ring. A cyclic amino group, which may be substituted with a heteroaryl group having an aryl moiety; (6) a C1-C4 alkyl group which may be substituted with a halogen atom, which may be substituted with a halogen atom Good Ci ~ C3 alkoxy group power, A cyano group, a nitrogen atom, a nitro group, _NR3 ° R31 (where R3 ° and R31 are each independently a hydrogen atom or a branched and halogen atom) A C1-C4 alkyl group which may be substituted) or a cyclic amino group formed by forming a ring with a C2-C8 alkylene group, or an aryl group which may be substituted with an aralkyl moiety Group; (7) C to C 4 alkyl group optionally substituted with a halogen atom, or C 1 to C 3 alkoxy group optionally substituted with a nodogen atom, a cyan group or a norogen An atom, a nitro group, or — NR30R31 (wherein R30 and R31 each independently represent a hydrogen atom, or may be branched and substituted with a halogen atom) C1 to C4 An alkyl group) or c2 to C8 alkylene A cyclic amino group which forms a ring with a group, or may be substituted with a heteroaryl moiety having a heteroaryl moiety; (8) (C1-C3 alkoxy) carbonyl group; (9) a carbamoyl group; 10) N- (C1-C4 alkyl) strong rubamoyl group; and 312 (11) N, N-di (C1-C4 alkyl) strong rubamoyl group (wherein the CC 4 alkyl groups may be the same or different from each other) are selected from the group consisting of: R42 represents a group selected from the group consisting of:

(1) a hydrogen atom;

(2) may be branched or ring-formed and may be substituted with a halogen atom;

(3) may form a branched or cyclic, and or may be substituted by halogen atom, C ₁ -C ₈ alkoxy group;

(4) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₂ -C ₂₀ alkenyl group;

(6) may be substituted by a halogen atom C i C or alkyl group, Nono Rogge optionally substituted with emissions atom C: -C ₃ alkyl in the alkoxy functionalized halogen atom may be substitution or which may be Ariru group substituted with a group, or Shiano group, or a halogen atom, or a nitro group, one NR ³⁰ R ³¹ (wherein,

R ^3G and R ³¹ are each independently a hydrogen atom or a C i to C ₄ alkyl group that may be branched and substituted with a halogen atom), or C _A cyclic amino group formed by forming a ring with a _{2 to} C ₈ alkylene group, an aryl group optionally substituted by

(7) C port Gen atoms or an optionally substituted C ~ C ₄ alkyl group, C port gain down atoms or optionally substituted Ci～C ₃ alkoxy group, or Shiano group, or a halo gen atom NR ³ ° R ³¹ (where R ³ ° and R ³¹ are each independently a hydrogen atom or a branched and halogen atom) 313 is either an optionally substituted C! -C ₄ alkyl group) force \ or C ₂ ~ c ₈ alkylene group or a cyclic amino group formed by constituting a ring, in which may be substituted, Ariru A heteroaryl group having a moiety;

(8) C port Gen atoms or an optionally substituted Ci～C ₄ alkyl group, C port gain down atoms or substituted by C ₁ optionally -C ₃ alkoxy group, or Shiano group, a halo gen atom Or a nitro group or one NR ^3t) R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom) Or a cyclic amino group comprising a ring with a C ₂ to C ₈ alkylene group, or an aryl group, having an aryl moiety;

(9) a halogen atom or an optionally substituted C i~C ₄ alkyl groups, halogen atoms or substituted by C ₁ optionally -C ₃ alkoxy group, or Shiano group, or a halo gen atom, a nitro NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted halogen atom) alkyl group is either), or cyclic amino group happens to constitute a ring C ₂ ~ C ₈ alkylene group, in which may be substituted, having Heteroariru moiety, Heteroararukiru group;

(10) (C ₁ ~C ₃ alkoxy) carbonyl group; '

(11) force rubamoyl group;

(12) N- (di-dialkyl) carbamoyl group;

(13) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group (where Ci to C ₄ alkyl groups may be the same or different from each other), and is a group selected from the group consisting of ;; And

(14) One SO ₂ R ⁴³

(Where R ⁴³ is

(i) may be branched or ring formed and In 314 down atoms may be substituted, C ₁ -C ₈ alkyl group;

(ii) may form a branched or cyclic, and z or halogen atoms may be substituted, c ₂ to c ₈ alkenyl group;

(iv) a halogen atom by Ji may E ~ Ji alkyl force substituted by, may be substituted with substituted C ₁ optionally -C ₃ alkoxy groups force ,, halogen atom in Nono androgenic atoms Ji ~. An aryl group, a cyano group, a halogen atom, a nitro group, or _NR ³⁰ R ³¹ (wherein R ³ and R ³¹ are each independently a hydrogen atom, which may be substituted with an alkyl group of Or a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group, which may be branched and may be substituted with a halogen atom. Or an aryl group optionally substituted by

(v) C ₁ -C ₄ alkyl group optionally substituted with a halogen atom, or C ₁ -C ₃ alkoxy group optionally substituted with a norogen atom, a cyano group, a halogen atom , A nitro group, or one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom) Or a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group, or a heteroaryl group having an aryl moiety, which may be substituted with:

(vi) C ₁ -C ₄ alkyl group optionally substituted by halogen atom, C i -C ₃ alkoxy group optionally substituted by nodogen atom, Cyan group \ halogen atom, nitro NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom). Is a cyclic amino group formed by forming a ring with a C _{2 to} C ₈ alkylene group, or substituted with 315 may have an aryl moiety, an aralkyl group;

(vii) It may be substituted with a halogen atom. ~ Ji or Wiarukiru group, or an optionally substituted Ci～C ₃ alkoxy group with a halogen atom, or Shiano group, or a halogen atom, or a nitro group, one NR ³ ° R ³¹ (wherein, R ³⁰ and R ³¹ Are each independently a hydrogen atom or a branched and substituted halogen atom, which is an alkyl group) a force \ or a C ₂ -C ₈ alkylene group A cyclic amino group constituting a ring with, or a heteroaralkyl group optionally substituted with a heteroaryl moiety;

(viii) (C ₁ ~C ₃ alkoxy) carbonylation Honoré group;

(ix) force rubermoyl group;

(x) N- (di-alkyl) strong rubermoyl group; or

(xi) N, N-di (Ci C alkyl) force rubamoyl group (wherein Ci to C ₄ alkyl groups may be the same or different from each other), are selected from the group consisting of:

Is)

Represents a group selected from the group consisting of and

* Indicates an asymmetric center.

9. A method for producing an optically active α-amino acid or derivative thereof, which is obtained by the method according to claim 6 or 7:

Hydrolyzing an optically active α-amino nitrile derivative represented by the following: 316

R ⁴¹ is

An alkyl group;

(2) branched or cyclic may be in the form J¾ a, and may be substituted with Z or a halogen atom, C ₂ -C ₂₀ alkenyl group;

(4) C port Gen atoms or which may be C ~ C ₄ alkyl group substituted, Nono port gain down atoms or an optionally substituted Ci Ca alkoxy groups, have been substitution at C port Gen atoms 1 to 3 alkyl groups optionally substituted with alkyl groups, cyan groups, halogen atoms, nitro groups, or NR ³ ° R ³¹ (where R ^3G and R ³¹ are each independently A hydrogen atom, or a C i Ca alkyl group that may be branched and substituted with a halogen atom), or a C _{2 to} C ₈ alkylene group to form a ring. A cyclic amino group, which may be substituted with an aryl group;

(5) C ₁ -C ₄ alkyl group optionally substituted with a halogen atom, C ₁ -C ₃ alkoxy group optionally substituted with a nocturnal gen atom, a cyano group, a halogen atom Or _NR ³⁰ R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom) a C ～〇 ₄ alkyl group in which either) force, or C ₂ ~ C ₈ or alkylene formed by constituting the ring in ¾ cyclic amino group, in which may be substituted, having Ariru moiety, Heteroariru group;

(6) or C port Gen atoms substituted by C ₁ optionally -C ₄ 7 alkyl group, C port gain down atoms or substituted by C ₁ optionally -C ₃ alkoxy group, or Shiano group, halo NR ³⁰ R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a branched and halogen atom) A Ci C alkyl group optionally substituted with 317), or a cyclic amino group formed by forming a ring with a c ₂ to c ₈ alkylene group, or having an aryl moiety optionally substituted with , Aralkyl groups;

(7) Ji may be substituted with C port Gen atoms丄~ Ji or alkyl group, C port gain down atoms or which may be substituted Ci～C ₃ alkoxy group, or Shiano group, or a halo gen atom A nitro group or — NR ³ ° R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom) Which may be an alkyl group), or a cyclic amino group comprising a ring composed of a C ₂ to C ₈ alkylene group, or may be substituted with a heteroaryl moiety having a heteroaryl moiety;

(8) (C ₁ ~C ₃ alkoxy) carbonyl group;

(9) force rubamoyl group;

(10) N- (C ₁ -C ₄ alkyl) strong rubamoyl group; and

(11) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group (where C! To C ₄ alkyl groups may be the same as or different from each other) and are selected from the group consisting of is there) ;

Represents a group selected from the group consisting of

R ⁴³

(i) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₁ -C ₈ alkyl group;

(ii) may form a branched or cyclic, and may be substituted with Z or a halogen atom, C ₂ -C ₈ alkenyl group;

(iii) may form a branched or cyclic, and or may be substituted by halogen atom, C ₂ -C ₈ alkynyl group;

(iv) optionally substituted with C port Gen atoms C i to C ₄ or an alkyl group, Ha port gain down atoms or an optionally substituted Ci Cg alkoxy group, still at Ha port Gen atoms 318 is an aryl group that may be substituted with an alkyl group, a cyan group, a halogen atom, a nitro group, or one NR ³⁰ R ³¹ (where R ^3Q and R ³¹ are independently, either a hydrogen atom, or branched Ru good C ~ C ₄ alkyl group Kadea be substituted with good and halogen atom which may have) force \ or constituting a ring C ₂ -C ₈ alkylene group A cyclic amino group, which may be substituted with an aryl group;

(v) C port Gen atoms or which may be C ~ C ₄ alkyl group substituted, may be substituted with C port gain down atoms Ci～C ₃ alkoxy or radical force \ Shiano group, Nono b Gen atoms A nitro group or one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and substituted halogen atom) A C ₁ -C ₄ alkyl group) force \ or a cyclic amino group comprising a ring with a C ₂ -C ₈ alkylene group, or substituted with a heteroaryl group having a aryl moiety;

(vi) C port Gen atoms or an optionally substituted C ~ C ₄ alkyl group, Bruno, mouth gain down atoms or an optionally substituted C Cg alkoxy group, or Shiano group, or a halo gen atom, A nitro group, or one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted halogen atom). A cyclic amino group comprising a ring with a C ₂ to C ₈ alkylene group, or an aryl group having an aryl moiety;

(Vii) a Ci C alkyl group optionally substituted with a halogen atom, a c _{1 to} c ₃ alkoxy group optionally substituted with a halogen atom, a cyan group, a nitrogen atom, a nitro group, (1) NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) Or a cyclic amino group comprising a ring with a C _{2 to} C ₈ alkylene group, or substituted with 319 may have a heteroaryl moiety, a heteroaralkyl group;

(viii) (C ₁ ~C ₃ alkoxy) carbonyl group;

(ix) force rubermoyl group;

(χ) Ν- (〇 to 〇 ₄ alkyl) force ruberamoyl. group; or

(xi) N, N—di (di-alkyl) rubamoyl group (where C ₁ -C

₄ alkyl groups may be the same or different from each other, and are groups selected from the group consisting of:

Is)

Represents a group selected from the group consisting of and

* Indicates an asymmetric center.

10. The following formula (I_1b)

A process for producing a compound represented by

The following formula (XX I I— 1 b):

(XX II-1 b)

320 is reacted in a solvent in the presence of tetramethylpiperidinemagnesium and bromine is added to form the following formula (XX III— 1 b):

Obtaining a compound represented by:

The compound represented by the formula (XX I I I—1 b) is reacted with a metal hydride in a solvent to form the following formula (XX I V—1 b):

A step of obtaining a compound represented by:

The compound represented by the formula (XX I V-1 b) is reacted with PB r ₃ in a solvent to give the following formula (XXV—lb):

(XXV- 1 b)

Obtaining a compound represented by 321;

The compound represented by the formula (XXV—l b) is dissolved in a solvent,

Let the following formula (XXV I— 1 b):

(XXV I 1 b)

Obtaining a compound represented by:

The compound represented by the formula (XXV I— lb) is converted to at least 1 represented by R ¹ — B (OH) ₂ or R ^ —B (OH) ₂ in a solvent in the presence of a palladium catalyst. The following formula (XXV II— 1 b):

(XXV II 1 1 b)

Obtaining a compound represented by:

In a solvent, the compound represented by the formula (XXV I I—l b)

Reacting with a halogenated alkyl;

Including

here,

In the formula (I _ 1 b) and the formula (XXV I I-1 b)

R ¹ and R ¹ 'are each independently 322

(i) a hydrogen atom;

(iii) a cyano group;

(iv) a nitro group;

(V) force rubermoyl group;

(vi) N- (di-alkyl) strong rubermoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a c _{1 to} c ₄ alkyl group which may be branched and may be substituted with a halogen atom);

(ix) a halogen atom;

, (xi) C ₂ -C ₆ alkenyl groups which may form branches or rings and may be substituted with halogen atoms;

Ci C ₄ alkyl group which may be branched and may be substituted with a halogen atom,

Branched even if good and ₅ alkoxy group which may be substituted with a halogen atom,

Haguchigen atom, which may be branched and substituted with haguchigen atom 323 is also good. 04 alkyl group, cyano group, one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or may be branched and substituted with a halogen atom) A good alkyl group), a nitrite group, a strong rubamoyl group, N— (dialkyl), a strong rubamoyl group, N, N—di (C ₁ -C ₄ alkyl) a strong rubamoyl group, or one NHCOR ¹⁹ (Wherein R ¹⁹ is a hydrogen atom or may be branched and may be substituted with a halogen atom, which is an alkyl group), an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted c _{1 to} c ₄ alkyl group. )

Nitro group,

Force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (C ₁ -C ₄ alkyl) carbamoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a 'C -O ₄ alkyl group which may be branched and substituted with a halogen atom), and

Halogen atom

Branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group, 324 Ci Cs ananoloxy group which may be branched and optionally substituted with a halogen atom,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, or an NR ³ ; R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) Nitto group, canolemomoyl group, N— (di-alkyl), rubamoyl group, N, N—di (C ₁ -C ₄ alkyl) rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

Nitro group,

Canoleva Moinole group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group, '

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C-alkyl group optionally branched and substituted with a halogen atom), and

Halogen atom

(XV) aryl group, where the aryl group is 325 branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group,

Branched C ₁ may be substituted in good and halogen atoms have -C ₅ alkoxy group,

Halogen atoms, branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group, Shiano group, _NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom, or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (di-alkyl) ) Carpamoyl group, N, N-di (Ci C alkyl) force rubamoyl group, or — NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) A C ₁ -C ₄ alkyl group) which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R ^3G and R ³¹ are each independently a hydrogen atom or a CC alkyl group that may be branched and substituted with a halogen atom) ,

Nitro group,

Force rubymoyl group,

N-alkyl) canolemoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

May be substituted with at least one group selected from the group consisting of 326 or 3 and 4 together, optionally substituted with O— (CH ₂ ) _p — 0— (where p is 1 or 2), an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

A halogen atom, which may be branched and optionally substituted by a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or a Ci C alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a canolevamoinole group, an N— (〇 to 〇 alkynole) force rubermoyl group, an N , N—di (dialkyl) rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) An aryl group, which may be substituted with

Ciano group,

_ _NR 30 _R 31 (wherein R 30 and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) )

Nitro group,

Force ruby moinole group,

N- (C ₁ -C ₄ alkyl) force ruberinole group,

N, N-di (. Alkyl) force rubermoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C i C alkyl group that may be branched and substituted with a halogen atom) 327), and

Halogen atom

A group selected from the group consisting of:

Formula (I— l b), Formula (XX I I-1 b), Formula (XXV I I-1 b), Formula (XX I V— l b), Formula (XXV— l b), Formula (XXV I _ l b) and Formula

(XXV I I-1 b)

R ² , R ² ′, R ³ , R ³ ′, R ⁴ , R ⁴ ′, R ⁵ , R ⁵ ′, R ⁶ , and R ⁶ ′ are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted halogen atom) Is based)

(iii) a cyano group;

(iv) Futaguchi ¾;

(V) force rubermoyl group;

(vi) N- (C ₁ -C ₄ alkyl) strong rubamoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C to C ₄ alkyl group which may be branched and substituted with a halo atom);

(ix) a halogen atom; 328

(X) it may also be substituted by branched or better and a halogen atom to form a ring Rere, alkyl C ₁ -C _6;

A halogen atom, which may be branched and optionally substituted with a halogen atom, an alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom; Or a Ci C alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N— (C ₁ -C ₄ alkyl) a strong rubermoyl group, N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or — NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) An alkyl group) which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R 31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom or an alkyl group) )

Nitro group, 329 force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a CiC alkyl group which may be branched and substituted with a halogen atom), and

Halogen atom

〇 to 〇 anoalkyl group which may be branched and may be substituted with a halogen atom,

Branched optionally substituted in well and Ha port Gen atoms optionally C i to C ₅ alkoxy group,

Halogen atoms, branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group, Shiano group, _NR ³⁰ R ³¹ (wherein, R ³⁰ Oyo Pi R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N_ (C ₁ -C ₄ Alkyl) Force rubermoyl group, N, N —Di (di 丄 ~. Alkyl) Carpamoyl group, or — NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or branched and substituted with a halogen atom) Which may be an alkyl group), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³⁰ and R 3 i are each independently hydrogen 330 atoms, or is or branched optionally substituted in well and halogen atom have not good C ₁ -C ₄ alkyl group),

Nitro group,

Force ruby moinole group,

N- (C ₁ ~C ₄ alkyl) Karupamoiru group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

A heteroalkylol group optionally substituted with at least one group selected from the group consisting of:

(XV) aryl group, where the aryl group is

A C C alkyl group which may be branched and optionally substituted with a halogen atom,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (where Pi R ³¹ R ³⁰ Oyo are each independently A hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a canolevamoyl group, N-alkynole) a force ruberamoinole group, N, N- Di (C ₁ -C ₄ alkyl) carbamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom. Which may be substituted with an aryl group, 331 cyano group,

_ _NR 30 _R 31 (wherein R 3 G and R 31 are each independently a hydrogen atom or a C 1 -C ₄ alkyl which may be branched and may be substituted with a halogen atom) )

Nitro group,

Force ruby moinole group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (dialkyl), rubamoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom, or C-optionally branched and substituted with a halogen atom. _{4 is} an alkyl group),

A halogen atom, and

-S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom Ci to C

_{4 is} an alkyl group)

May be substituted with at least one group selected from the group consisting of: O— (CH ₂ ) _m -0- (where m is 1 or 2 Which may be substituted with an aryl group;

(xvi) a heteroaryl group T, and the heteroaryl group is

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently And may be a hydrogen atom or branched and 332 be substituted with a halogen atom is either good C ₁ -C ₄ alkyl group), a nitro port group, the force Rubamoiru group, N- (C ₁ ~C ₄ alkyl) force Rubamoiru group, N, N over-di ( C ₁ -C ₄ alkyl) a strong rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom) ) An aryl group, which may be substituted with

Ciano group,

_-NR 30 _R 31 (wherein R 30 and _R 3i are each independently a hydrogen atom or an alkyl group which may be branched and may be substituted with a halogene atom) ),

Nitro group,

Force ruby moinole group,

N- (. Alkyl) Carpamoyl group,

N, N—di (dialkyl) carpamoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a ci to c ₄ alkyl group that may be branched and substituted with a halogen atom), and

Halogen atom ''

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom) • -C ₄ alkyl group);

A group selected from the group consisting of forces,

In X,> - Formula (I- 1 b) and the R ^7b '

R ^7b ′ is (i) substituted with a powerful halogen atom which may form a branch or a ring. 333 may be an alkyl group of X to J ^, X is a halogen atom,

In the formula (XX I I-1 b) and formula (XX I I I 1 b)

R ^5Q and R ^5G ′ are each independently a C i C ₂ alkyl group that may form a branch or ring and may be substituted with a halogen atom;

In the formula (XXV I— lb), formula (XXV II— lb) and the R ^7b — NH ₂ ,

The method wherein R ^7b is a C ₁ C ₃₀ alkyl group which may form a branch or a ring and may be substituted with a halogen atom. The following formula (XXV I-1 b)

Compound represented by:

here,

R ² R ² 'R ³ R ³ ' R ⁴ R ⁴ 'R ⁵ R ⁵ ' R ⁶ , and R ⁶ 'are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a CC ₄ alkyl group which may be branched and may be substituted with a halogen atom) Is) 334

(iii) a cyano group;

(iv) a nitro group;

(V) force rubermoyl group;

(vi) N- (C ₁ -C ₄ alkyl) strong rubamoyl group;

(vii) N, N-di (ju alkyl) force rubamoyl group;

(viii) —NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C to C ₄ alkyl group which may be branched and substituted with a halo atom) ■;

(ix) a halogen atom;

(X) may be branched or ringed and may be substituted with a halogen atom, a C ₁ -C ₆ alkenoquinole group;

(xi) it may also be substituted in good and halogen atoms to form a branched or cyclic Le ,, C ₂ -C _e alkenyl group;

(xii i) an aralkyl group, wherein the aryl group constituting the aralkyl group is

A halogen atom, which may be branched and may be substituted with a halogen atom. An alkyl group, a cyano group, or one NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a branched and substituted hydrogen atom; good C ₁ -C is ₄ or alkyl group), a nitro port group, the force Rubamoiru group, N- alkyl) Karupamoiru group, N, N 335

—Di (di-alkyl) force ruberamoyl group, or —NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom, or may be branched and substituted with a halogen atom) Which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R ³¹ are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom)

Nitro group, '

Force ruby moinole group,

N— (C ₁ -C ₄ alkyl) force rubamoinole group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

A C Cs alcoholecoxy group which may be branched and optionally substituted with a halogen atom,

Halogen atom, which may be branched and may be substituted with a halogen atom. Alkyl group, cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and 336 and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, or a rubamoyl group. A group, N— (di-alkyl) rubamoyl group, N, N—di (C ₁ -C ₄ alkyl) rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or branched) Or a C ₁ -C ₄ alkyl group optionally substituted with a halogen atom), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein ³ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and may be substituted with a halogen atom) is there) ,

Nitro group,

Canoleva Moinole group,

N- (Ci C alkyl) strong rubermoyl group,

N, N-di (. Alkyl) force rubermoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a c _{1 to} c ₄ alkyl group which may be branched and substituted with a halogen atom), and '

Halogen atom

(XV) aryl group, where the aryl group is

Ci Ca alkyl group which may be branched and may be substituted with a halogen atom,

Ci to C ₅ alkoxy group which may be branched and may be substituted with a halogen atom, 337 Halogen atom, which may be branched and may be substituted with a halogen atom Alkyl group, cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N— (di-alkyl) Group, N, N

—Di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom, or a Ci C alkyl group that may be branched and substituted with a halogen atom) Which may be substituted with an aryl group,.

Ciano group,

- In _NR 30 _R 31 (wherein, R ³ ° and R ³¹ are each independently a hydrogen atom, or branched c ₁ but it may also be substituted in good and halogen atom have to c ₄ alkyl )

Nitro group,

Force rubymoyl group,

N- (C i C canolequinole) canolemoyl group,

N, N—di (dialkyl), rubamoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group which may be branched and substituted with a halogen atom),

A halogen atom, and

— S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom)

4 is an alkyl group)

May be substituted with at least one group selected from the group consisting of: O- (CH ₂ ) _m -0- (where m is 1 338 or 2), an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

C atoms, C ₁ -C ₄ alkyl, Cyano, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each Independently a hydrogen atom, or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong ruberinole group, N— Alkyl) Forced rubermoyl group, N, N-di (CC alkyl) Carpamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) Which may be a Ci C alkyl group), an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein _{R 3} , and are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom),

Nitro group,

Carpamoyl group,

N- (C ₁ ~C ₄ alkyl) Karupamoiru group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C alkyl group that may be branched and substituted with a halogen atom), and 339 Halogen atom

(xvii) -S (O) _n -R ²⁰ (where n is 0 1 or 2, and R ² ° may be branched and substituted with a halogen atom C ₄ An alkyl group);

A group selected from the group consisting of and

R ^7b may form a branch or a ring, C Cg. This is an alkyl group.

2. The following formula (XXV I I-1 b)

Compound represented by:

here,

R ¹ and R ¹ 'are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a Ci C alkyl group that may be branched and may be substituted with a halogen atom) Is)

(iii) a cyano group;

(iv) Nitoguchi group; 340

(v) a carpamoyl group;

(vi) N- (C Ca alkyl) force ruberamoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(ix) a halogen atom;

(X) may form a branched or cyclic and may be substituted with a halogen atom, Arukinore group of C ₁ -C _6;

A c ₁ -c ₄ alkyl group which may be branched and optionally substituted with a halogen atom,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (where Pi R ³¹ R ³⁰ Oyo are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N— Alkyl) rubamoyl group, N, N —di (di-alkyl) rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom) 341 which is an optionally substituted C CA alkyl group), an aryl group,

Ciano group,

-NR ³⁰ R ³¹ (wherein R ^3G and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom),

Nitro group,

Force ruby moinole group,

N- (di-alkyl) force rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

An alkanoleno group optionally substituted with at least one group selected from the group consisting of:

It may be branched and may be substituted with a halogen atom

An alkyl group,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) 342 mouth group, force rubermoyl group, N_ (C ₁ -C ₄ alkyl) force ruber moyl group, N, N —di (. Alkyl) force ruber moyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom Or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

_-NR 30 _R 31 (where R ³ ° and R 31 are each independently a hydrogen atom or a branched and optionally substituted halogen atom; )

Nitoguchi,

Force rubymoyl group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N—di (dialkyl) carpamoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C i C alkyl group that may be branched and substituted with a halogen atom), and

Halogen atom

A heteroalkylenole group optionally substituted with at least one group selected from the group consisting of:

(XV) aryl group, where the aryl group is

A Cj Ca alkyl group which may be branched and optionally substituted with a halogen atom,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and 343 and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom.) Group, N— (di-alkyl) rubamoyl group, N, N—di- (dialkyl) rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or branched) A C ₁ -C ₄ alkyl group optionally substituted with a halogen atom), an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) ,

Nitro group,

Canolevamoyl group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

(xvi) a heteroaryl group, wherein the heteroaryl group is

Ci to C ₅ which may be branched and may be substituted with a halogen atom 344 alkoxy group,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom, which may be branched and may be substituted with a halogen atom, or an alkyl group), a nitrite group, a strong rubamoyl group, N— (C ₁ -C ₄ Alkyl) force rubermoyl group, N, N —di (di- to alkyl) force rubermoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom) may be substituted with may be C ₁ -C is ₄ or alkyl group), a Ariru group,

Ciano group,

Nitro group,

Force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group,, -NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or branched and may be substituted with a halogen atom) An alkyl group), and

Halogen atom

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom) ! 345

~C ₄ alkyl group);

A group selected from the group consisting of:

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) Is)

(iii) a cyano group;

(iv) a nitro group;

(V) canolevainole group;

_{(vi) N- (C 1 ~C} 4 alkyl) Karupamoiru group;

(vii) N, N-di (di-alkyl) rubamoyl group;

(viii) -NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom);

(ix) a halogen atom;

(X) a C _{1 to} C ₆ alkyl group which may form a branch or a ring and may be substituted with a no, rogen atom;

C _{1 to} C ₄ may be branched and may be substituted with a halogen atom 346 alkyl group,

_{May be} branched and may be substituted with a halogen atom.

Halogen atoms, branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group, Shiano group, _NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom, or a Ci C alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (. Group, N, N—di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) A good alkyl group) which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom) Is)

Nitro group,

Force rubymoyl group,

N- (ji-ji alkyl) rubamoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

An aralkyl group optionally substituted with at least one group selected from the group consisting of: 347

Halogen atoms, branched C ₁ may be substituted in good and halogen atoms optionally -C ₄ alkyl group, Shiano group, _NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a carbamoyl group, N- (C ₁ -C ₄ Alkyl) force rubamoyl group, N, N —di (Ci C alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) Which may be substituted with an aryl group), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R ³¹ are each independently a hydrogen atom or a CC alkyl group which may be branched and substituted with a halogen atom) ),

Nitro group,

Force rubymoyl group,

N- (ji-ji alkyl) rubamoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C i Cd alkyl group which may be branched and substituted with a halogen atom), and 348 Halogen atom

(XV) aryl group, where the aryl group is

Branched even if well and optionally substituted C ~ C ₄ alkyl group with a halogen atom,

A halogen atom, which may be branched and optionally substituted by a halogen atom, a Ci C alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently It may be a hydrogen atom, or may be branched and substituted with a halogen atom. It is an alkyl group), a nitrite group, a rubamoyl group, N— (C ₁ -C ₄ alkyl) force Rubamoyl group, N, N —dialkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom, or a Ci C alkyl group that may be branched and substituted with a halogen atom) Which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl which may be branched and may be substituted with a halogen atom) )

Nitro group,

Canolevamoyl group,

N- (Ci C alkyl) strong rubermoyl group,

N, N—di (dialkyl) carpamoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or branched 349 which is well and is optionally substituted with a halogen atom.

A halogen atom, and

-S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ²⁰ may be branched and substituted with a halogen atom C ₁ -C

_{4 is} an alkyl group)

May be substituted with at least one group selected from the group consisting of: O— (CH ₂ ) _m — O— (where m is 1 or 2 Which may be substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

A halogen atom, which may be branched and substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each Independently a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (di-alkyl) Force rubamoyl group, N, N —di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom) may be substituted with may be C ₁ -C is ₄ or alkyl group), a Ariru group,

Ciano group,

_-NR 30 _R 31 (wherein R 3 G and are each independently a hydrogen atom or may be branched and substituted with a halogen atom) c is ₄ or alkyl group),

Nitro group,

Power ruber moyl group

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (di-alkyl) alkyl rubermoyl group,

Halogen atom

Selected from the group consisting of: a heteroaryl group optionally substituted with at least one group; and

A group selected from the group consisting of and

R ^{7 B} is a C ₁ to C ₃₀ alkyl group which may form a branch or a ring and may be substituted with a halogen atom.

13. The following formula (I_2b):

A process for producing a compound represented by 351 Formula (XX II-2 b)

Is reacted in a solvent in the presence of tetramethylpiperidine magnesium, and bromine is added to form the following formula (XX III— 2 b):

Obtaining a compound represented by:

Obtaining a compound represented by:

The compound represented by the formula (XX IV-2 b) is reacted with PB r ₃ in a solvent. 352 The following formula (XXV— 2 b)

Obtaining a compound represented by:

(XXV I 1 2 b)

Obtaining a compound represented by:

The compound represented by the formula (XXV I— 2 b) is represented by R ¹ — B (OH) ₂ or R ¹ ′ — B (OH) ₂ in a solvent in the presence of a palladium catalyst. Reaction with at least one boronic acid derivative yields the following formula (XXV II— 2 b):

(XXV II 1 2 b)

Obtaining a compound represented by 353; and

Reacting the compound represented by the formula (XXV II-2b) with at least one alkyl halide represented by R ^7b′— X in a solvent;

Including

here,

In formula (I-2b) and formula (XXV I I-2b),

R ¹ and R ¹ 'are each independently

(i) a hydrogen atom;

(iii) a cyano group;

(iv) a nitro group;

(V) force rubermoyl group;

(vi) N- (.-alkyl) force rubermoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(viii) -NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom, or may be branched and substituted with a halogen atom)

An alkyl group);

(ix) a halogen atom;

(X) may be branched or ringed and may be substituted with a halogen atom; a C ₁ -C ₆ aralkyl group;

(xii) may form a branched or cyclic and may be substituted with a halogen atom, an alkynyl group of C ₂ -C _6; 354

A halogen atom, which may be branched and optionally substituted by a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, which may be branched and may be substituted with a halogen atom, or an alkyl group), a nitrite group, a strong rubamoyl group, or N_ (C ₁ -C ₄ alkyl) strong rubamoyl. A group, N, N—di (C ₁ -C ₄ alkyl) carbamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) A C ₁ -C ₄ alkyl group) which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R3 and are each independently a hydrogen atom or a branched and substituted alkyl group that is an alkyl group. ),

Nitro group,

Force rubymoyl group,

N- (C ₁ ~C ₄ alkyl) Karupamoiru group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom), and Halogen atom

It may be branched and may be substituted with a halogen atom

An alkyl group,

It may be branched and may be substituted with a halogen atom. ~ ₅ alkoxy groups,

A halogen atom, which may be branched and optionally substituted with a halogen atom, a Ci C alkyl group, a cyano group, — NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, which may be branched and may be substituted with a halogen atom, or an alkyl group), a nitrite group, a rubamoyl group, an N— (Ci C alkyl) force rubamoyl group, N, N-di (CC alkyl) Forced rubermoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom, or may be branched and substituted with a halogen atom, Ci to C ₄ alkyl) Which may be substituted with an aryl group, '

Ciano group,

_ _NR 30 _R 31 (wherein R 30 and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted halogen atom) ,

Nitro group,

Force rubymoyl group,

N— (C ₁ -C ₄ alkyl) force rubamoyl group,

N, N—di (dialkyl) carpamoyl group, 356

Halogen atom

(XV) aryl group, where the aryl group is

Branched C ₁ may be substituted in good and Ha port Gen atoms optionally -C ₄ alkyl group,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a canolevamoyl group, N— (di-alkyl) ) Force rubermoyl group, N, N —di (di- to alkyl) force rubermoyl group, or —NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom) Which may be substituted with an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R ³ ° and R 31 are each independently a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom) is there) ,

Nitro group,

Force rubymoyl group, 357

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

Or may be substituted with at least one group selected from the group consisting of: O— (CH ₂ ) _p -0- (where p is 1 or 2 Which may be substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

An alkyl group which may be branched and may be substituted with one halogen atom,

A halogen atom, which may be branched and optionally substituted by a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (C ₁ -C ₄ alkyl group) ) force Rubamoiru group, N, N over-di (C ₁ -C ₄ alkyl) Karupamoiru group or a NHCOR ¹⁹ (where,, R ¹⁹ is substituted with a hydrogen atom, or branched even if well and halogen atoms A Ci C alkyl group) which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R 31 are each independently a hydrogen atom or may be branched and substituted with a halogen atom. A C i C alkyl group),

Nitro group,

Force ruby moinole group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N—di (Ci-C ₄ alkyl) force rubermoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a C-alkyl group optionally branched and substituted with a halogen atom), and

Halogen atom

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ^2Q may be branched and substituted with a halogen atom Ci ~ A C ₄ alkyl group);

A group selected from the group consisting of:

Formula (I-2b), Formula (XXII-2b), Formula (XXIII-2b), Formula (XXIV-2b), Formula '(XXV_2b), Formula (XXVI_2_2) In Yoppi (XXV II-2 b)

R ⁸ , R ⁸ ', R ⁹ and R ⁹ ' are each independently

Is a hydrogen atom;

Is a halogen atom;

A Ci Cg alkyl group which may be substituted with a halogen atom and / or an aryl group and which may be Z or branched or ring formed; or

Optionally substituted with a halogen atom and / or an aryl group, and

Z or may form a branched or cyclic, c ₁ to c ₅ alkoxy group; der 359 and then

R ^1Q and R ^1Q 'are independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³ and R ³¹ are each independently a hydrogen atom or an alkyl group which may be branched and substituted with a halogen atom) );

(iii) a cyano group;

(iv) nitro;

(V) force rubermoyl group;

(vi) N- (C ₁ -C ₄ alkyl) strong rubamoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(ix) a halogen atom;

(xi) it may also be substituted by branched or better and Parogen atoms to form a ring Rere, alkenyl C ₂ -C _6;

C ₁ -C ₅ which may be branched and may be substituted with a haguchigen atom 360 alkoxy groups,

A halogen atom, which may be branched and optionally substituted by a halogen atom, an alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom or Or a C ₁ -C ₄ alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (C ₁ -C ₄ alkyl) a strong rubamoyl Group, N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) A good alkyl group) which may be substituted with an aryl group,

Ciano group,

_-NR 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom) Is)

Nitro group,

Force rubymoyl group,

N- (C C alkyl) strong rubermoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

(xiv) a heteroaralkyl group having a heteroaryl moiety, wherein the heteroaryl moiety is 361 Ci C alkyl group which may be branched and may be substituted with a halogen atom,

Halogen atom, which may be branched and optionally substituted with a halogen atom Ci C alkyl group, cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently hydrogen A C ₁ -C ₄ alkyl group which may be branched or substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N- (di-alkyl) Rubamoyl group, N, N —di (C ₁ -C ₄ alkyl) force rubamoyl group, or —NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom) An alkyl group) which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and may be substituted with a halogen atom) )

Nitro group,

Canoleva Moinole group,

N-alkyl) strong rubermoyl group,

N, N-di (dialkyl-dialkyl) strong rubamoyl group,

Halogen atom

Optionally substituted with at least one group selected from the group consisting of 362 teloaralkyl groups;

(XV) aryl group, where the aryl group is

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N- (C _1- C ₄ alkyl) force rubamoyl group, N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and a halogen atom) A C ₁ -C ₄ alkyl group which may be substituted with an aryl group, which may be substituted with

Ciano group,

_-NR 30 _R 31 (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom, or may be branched and substituted with a halogen atom. is there) ,

Nitro group,

Carpamoinole group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N-di (ji ~ alkyl) force ruberamoinole group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group which may be branched and substituted with a halogen atom), A halogen atom, and

-S (O) _n -R ²⁰ (wherein n is 0, 1, or 2 and R ² ° is branched and may be substituted with a halogen atom Ci C ₄ alkyl group Is)

May be substituted with at least one group selected from the group consisting of: or 0_ (CH ₂ ) _m -0- (where m is 1 or 2) Optionally substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

A C! C alkyl group which may be branched and optionally substituted with a halogen atom,

It may be branched and may be substituted with a halogen atom. ₅ alkoxy groups,

C ₁ -C ₄ alkyl group, Cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ Each independently is a hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, an N-alkyl) force Rubamoyl group, N, N —di (C ₁ -C ₄ alkyl) carbamoyl group, or —NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) The alkyl group may be substituted with an aryl group,

Ciano group,

_-NR 30 _R 31 (where R ³⁰ and R ³¹ are each independently a hydrogen atom or a Ci to C ₄ alkyl group which may be branched and substituted with a halogen atom) )

Nitro group, 364 force rubymoyl group,

N— (C C alkyl) strong rubermoyl group,

N, N—di (C CA alkyl) force rubermoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group which may be branched and substituted with a halogen atom), and

Halogen atom

Optionally substituted with at least one group selected from the group consisting of: a heteroaryl group; and

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ² ° may be branched and substituted with a halogen atom) j -C ₄ alkyl group);

A group selected from the group consisting of and

In X, - formula (I- 2 b) Oyopi said R ^7b '

R ^7b 'may be formed: (i) branched or cyclic, an alkyl group of C ₁ -C _30, X is a halogen atom,

In formula (XX I I—2 b) and formula (XX I I I—2 b),

1 ⁵ ° and 15 ^(wherein each is independently an alkyl group of C to i ₂ , which may form a branch or a ring and may be substituted with a halogen atom; And

Formula (XXV I- 2 b), the formula (XXV II- 2 b) and the R ^7b - Oite to NH _2,

R ^{7 b} is a alkyl group of the same formula, which may form a branch or a ring and may be substituted with a halogen atom.

14. The following formula (XXV I _2 b): 365

Compound represented by:

here,

R ⁸ , R ⁸ ', R ⁹ and R ⁹ ' are each independently

Is a hydrogen atom;

Is a halogen atom;

A Ci Cs alkyl group optionally substituted with a halogen atom and // or an aryl group, and optionally forming a ring or a branched or ring; or

A Ci Cs alkoxy group that may be substituted with a halogen atom and a no or aryl group, and / or may form a branch or ring;

R ^1Q and R ^{1 ()} 'are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ^3Q and R ³¹ are each independently a hydrogen atom, or may be branched and may be substituted with a halogen atom, C _{1 to} C _Is an alkyl group);

(iii) a cyano group;

(iv) a ditro group;

(V) force rubermoyl group;

(vi) N-alkyl) strong rubermoyl group; 366

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(ix) a halogen atom;

(xii) a C _{2 to} C ₆ alkynyl group which may form a branch or a ring and may be substituted with a halogen atom;

Halogen atom, which may be branched and may be substituted with a hydrogen atom C ₁ -C ₄ alkyl group, cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each Independently a hydrogen atom or a Ci C alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a carpamoyl group, N— (di-alkyl) canolemoyl A group, N, N-di (Ci Cd alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom). ○ It may be an alkyl group) or an aryl group, 367 Cyan group,

_{_NR} 30 _R 31 (wherein R 30 and R 3 i are each independently a hydrogen atom or a C ₁ -C ₄ alkyl which may be branched and may be substituted with a halogen atom) Is based)

Nitro group,

Force rubymoyl group,

N- (ji-ji alkyl) rubamoyl group,

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

O to O alkyl group which may be branched and may be substituted with a halogen atom,

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoinole group, N— (C _1- C ₄ arnolequinole) Carpamoinole group, N, N —di (Ci C alkyl) force rubermoyl group, or one NHCOR ¹⁹ (here R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

_-N R 0 _R 31 (wherein R ³ ° and R ³¹ are each independently a hydrogen atom or may be branched and substituted with a halogen atom) )

Nitro group,

Force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N-di (Ci C alkyl) force rubermoyl group,

Halogen atom

(XV) aryl group, where the aryl group is

A ₅ alkoxy group which may be branched and optionally substituted with a halogen atom, a halogen atom, a C _{1 to} C ₄ alkyl group which may be branched and optionally substituted with a halogen atom, a cyano group, (1) NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom, or a Ci to C ₄ alkyl group that may be branched and substituted with a nitrogen atom. Nito 369 mouth group, force rubamoyl group, N— (C CA alkyl) force rubamoyl group, N, N — di (dialkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom, or Which may be branched and optionally substituted by a halogen atom, which is a C! C alkyl group), an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R ^3G and R ³¹ are each independently a hydrogen atom or a branched and optionally substituted c _{1 to} c ₄ alkyl group. )

Nitro group,

Force rubymoyl group,

N— (ji-ji alkyl) canolevamoino group,

N, N—di (C ₁ -C ₄ alkyl) carbamoyl group,

A halogen atom, and

-S (O) _n -R ²⁰ (where n is 0, 1, 'or 2 and R ²⁰ may be branched and substituted with a halogen atom Ci to C

_{4 is} an alkyl group)

May be substituted with at least one group selected from the group consisting of: or O- (CH ₂ ) _m -0- (where m is 1 or 2 Which may be substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

Ci to C ₄ alkyl group which may be branched and may be substituted with a halogen atom, 370 may be branched and may be substituted with a halogen atom, a C ₁ -C ₅ anoloxy group,

A halogen atom, which may be branched and optionally substituted by a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or an alkyl group that may be branched and substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (di-alkyl) a strong rubamoyl group, N, N—di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom, Ci to C Which is a ₄ alkyl group), an aryl group,

Ciano group,

Nitro group,

Canoleva Moinole group,

N- (ji-ji alkyl) force ruberamoyl group, '

N, N—di (di-anoleyl) force rubamoyl group,

Halogen atom

(xvii) -S (O) _n -R ²⁰ (where η is 0, 1, or 2 and R ² . Is a substituted -C ₄ optionally alkyl group branched even if well and halogen atoms);

A group selected from the group consisting of and

R ^7b is a C _{1 to} C ₃₀ alkyl group which may form a branch or a ring and may be substituted with one halogen atom.

15. The following formula (XXV I I— 2 b):

Compound represented by:

here,

R ¹ and R ¹ 'are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³⁰ and R ³¹ are each independently a hydrogen atom or may be branched and substituted with a halo atom) It is an alkyl group)

(iii) a cyano group;

(iv) Ninoguchi group;

(V) force rubermoyl group;

_{(vi) N- (C 1 ~C} 4 alkyl) Karupamoiru group;

(vii) N, N-di (di-alkyl) rubamoyl group;

(viii) -NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or branched) 372 or a C ₄ to C ₄ alkyl group which may be substituted with a halogen atom);

(Ii) a halogen atom;

Ci C ₅ anorecoxy group which may be branched and may be substituted with a halogen atom,

Halogen atom, which may be branched and substituted with a halogen atom Ci C alkyl group, cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or an alkyl group that may be branched and substituted with a nitrogen atom), a nitrite group, a strong rubamoyl group, N— (C ₁ -C ₄ alkyl) carbamoyl Group, N, N

—Di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom C ₁ -C Which is a ₄ alkyl group), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³⁰ and R3i are each independently hydrogen 373 atom or an alkyl group which may be branched and substituted with a halogen atom)

Nitro group,

Force rubymoyl group,

N- (C ₁ ~C ₄ alkyl) Karupamoiru group,

N, N—di (C ₁ -C ₄ alkyl) carbamoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a c _{1 to} c ₄ alkyl group which may be branched and substituted with a halogen atom), and

Halogen atom

A _5- analkoxy group which may be branched and optionally substituted with a halogen atom,

Halogen atom, which may be branched and may be substituted with a halogen atom 〇 to 〇 Alkyl group, cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently A hydrogen atom, or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a carpamoyl group, N— (di-alkynole) force Rubamoyl group, N, N —di (Ci Ca alkyl) force rubamoyl group, or one NHCOR ¹⁹ (wherein R ¹⁹ may be a hydrogen atom, or may be branched and substituted with a halogen atom) may be substituted with ₁ -C is ₄ or alkyl group), 374 aryl group,

Ciano group,

-NR ³⁰ R ³¹ (where Shaku ³ and R ³¹ are each independently a hydrogen atom or may be branched and may be substituted with a halo atom C ₁ -C ₄ alkyl group)

Nitro group,

Force ruby moinole group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (C ₁ -C ₄ alkyl) carbamoyl group,

Halogen atom

(XV) aryl group, where the aryl group is

Ci to C ₅ anoalkoxy group which may be branched and may be substituted with a halogen atom,

A halogen atom, which may be branched and optionally substituted by a halogen atom, an alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom or Or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a rubamoinole group, N— (Ci C alkyl) a rubamoyl group, N , N —di (C ₁ -C ₄ alkyl) force rubermoyl group, or one NHCOR ¹⁹ R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group which may be branched and substituted with a halogen atom), an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³ ° and R ³¹ are each independently a hydrogen atom or an alkyl group that may be branched and substituted with a halogen atom) ,

Nitro group,

Force ruby moinole group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N—di (di-anoleyl) force rubamoyl group,

Halogen atom

May be substituted with at least one group selected from the group consisting of: O— (CH ₂ ) _p — O— (where p is 1 or 2 Which may be substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

A halogen atom, which may be branched and optionally substituted by a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently May be a hydrogen atom or branched and 376 is an alkyl group which may be substituted with a halogen atom), a nitrite group, a strong rubamoyl group, N— (dialkyl), a strong rubamoyl group, N, N—di (CC alkyl) a strong rubamoyl group, or a NHCOR ¹⁹ (wherein, either R ¹⁹ is a hydrogen atom, or may be branched substituted with Chikaratsu halogen atom is one which may C ₁ -C ₄ alkyl group) optionally substituted by Yo!

Ciano group,

Nitro group,

Force ruby moinole group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (dialkyl), rubamoyl group,

-NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a CC alkyl group that may be branched and substituted with a halogen atom), and

Halogen atom ''

(xvii) -S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ^2G may be branched and substituted with a halogen atom) ₄ alkyl group);

A group selected from the group consisting of:

R ⁸ , R ⁸ ', R ⁹ and R ⁹ ' are each independently

Is a hydrogen atom; 377 is a halogen atom;

Optionally substituted with a halogen atom and a no or aryl group, and may form a no or branched or ring. ~ Joalkyl group; or

A Ci Cs alkoxy group which may be substituted with a halogen atom opino or aryl group, and / or may form a branch or a ring;

R ^1Q and R ^lc are each independently

(i) a hydrogen atom;

(ii) -NR ³⁰ R ³¹ (wherein R ³ ° and R ³¹ are each independently a hydrogen atom, or may be branched and substituted with a halogen atom, C! ~ A C ₄ alkyl group);

(iii) a cyano group;

(iv) a nitro group;

(V) force rubermoyl group;

(vi) N- (Ci C alkyl) carbamoyl group;

(vii) N, N-di (C ₁ -C ₄ alkyl) force rubamoyl group;

(ix) a halogen atom;

(xii) may be branched or ringed and substituted with a halogen atom 378 can have, an alkynyl group of C ₂ -C _6;

Halogen atom, which may be branched and optionally substituted with a halogen atom Ci C alkyl group, cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently hydrogen atoms or branched even if well force, one which may be substituted by a halogen atom C ₁ -C ₄ is either an alkyl group), a nitro port group, the force Rubamoinore group, N- (Ji-Ji alkyl) Canolevamoyl group, N, N —di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and substituted with a halogen atom) Which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (where R ³⁰ and R ³¹ are each independently a hydrogen atom or a Ci C alkyl group that may be branched and substituted with a halogen atom) )

Nitro group,

Force rubymoyl group,

N- (C ₁ -C ₄ alkyl) force rubermoyl group,

N, N—di (dialkyl), rubamoyl group,

-NHCOR ¹⁹ (wherein R ¹⁹ is a hydrogen atom or a Ci to C ₄ alkyl group that may be branched and substituted with a halogen atom) 379), and.

Halogen atom

A halogen atom, which may be branched and optionally substituted with a halogen atom, a CC alkyl group, a cyano group, _NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently a hydrogen atom; Or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a force rubamoyl group, N— (C ₁ -C ₄ alkyl) force Rubamoyl group, N, N

—Dialkyl) a rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom) ) 'May be substituted with an aryl group,

Ciano group,

Nitro group,

Force rubymoyl group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group, 380

N, N-di (C ₁ -C ₄ alkyl) force Rubamoiru group,

Halogen atom

(XV) aryl group, where the aryl group is

An alkyl group which may be branched and may be substituted with a halogen atom;

A halogen atom, which may be branched and substituted with a halogen atom, a Ci C alkyl group, a cyano group, one NR ³⁰ R ³¹ (where R ³⁰ and R ³¹ are each independently, a hydrogen atom or is or branched even if well and an alkyl group which may be substituted by a halogen atom), a nitro port group, the force Rubamoiru group, N- (Ci~C ₄ alkyl) power Rubamoyl group, N, N —di (C ₁ -C ₄ alkyl) force rubamoyl group, or one NHCOR ¹⁹ (where R ¹⁹ may be a hydrogen atom or may be branched and substituted with a halogen atom) Which may be substituted with an aryl group,

Ciano group,

_ _NR 30 _R 31 (wherein R 30 and are each independently a hydrogen atom or a 0 to 0 alkyl group that may be branched and substituted with a halogen atom) ,

Nitro group, 381 Power rubermoyl group,

N- (C ₁ ~C ₄ alkyl) force Rubamoiru group,

N, N-di (Ci C alkyl) force rubermoyl group,

A halogen atom, and

-S (O) _n -R ²⁰ (where, n represents 0, 1 or 2, and R ^2. The Ji may be substituted with well and halogen atoms be branched-Ji ₄ alkyl, Base)

May be substituted with at least one group selected from the group consisting of: O- (CH ₂ ) _m -0- (where m is 1 or 2) optionally substituted with an aryl group;

(xvi) a heteroaryl group, wherein the heteroaryl group is

Halogen atoms, branched C ₁ -C ₄ optionally substituted at good and halogen atoms have an alkyl group, Shiano group, one NR ³⁰ R ³¹ (wherein, R ³⁰ and R ³¹ are each independently A hydrogen atom or a C ₁ -C ₄ alkyl group which may be branched and substituted with a halogen atom), a nitrite group, a strong rubermoyl group, N— (C _1- C ₄ alkyl) force rubamoyl group, N, N —di (C ₁ -C ₄ alkyl) force rubamoyl group, or —NHCOR ¹⁹ (where R ¹⁹ is a hydrogen atom or may be branched and a halogen atom) A Ci Ca alkyl group that may be substituted with 382 aryl group,

Ciano group,

Nitro group,

Canolevamoyl group,

N- (Ci C alkyl) strong rubermoyl group,

N, N-dialkyl) strong rubermoyl group,

Halogen atom

(xvii)-S (O) _n -R ²⁰ (where n is 0, 1, or 2 and R ^{2 Q} may be branched and substituted with a halogen atom) ~C ₄ alkyl group);

A group selected from the group consisting of:

R ^{7 b} is an alkyl group of 1 to 6 which may form a branch or a ring and may be substituted with a halogen atom.