KR102458689B1 - Piperidine compound and method for producing the same - Google Patents

Abstract

The present invention relates to a piperidine compound and a method for preparing the same, and piperidine can be synthesized in high yield using quinuclidine and a nitrogen nucleophile in the absence of a transition metal. In addition, it is possible to synthesize novel piperidine compounds having various substituents, which can be applied to various fields.

Description

Piperidine compound and method for preparing the same

The present invention relates to a piperidine compound and a method for preparing the same. Specifically, a piperidine derivative is synthesized in the absence of a transition metal using quinuclidine and a nitrogen nucleophile, and the synthesis is possible in one step and a high yield is achieved.

Nitrogen ring compounds are being studied by many domestic and foreign researchers because of their excellent physiological activity. Among them, piperidine derivatives are being applied as therapeutic agents for metabolic syndrome, dementia, and heart failure. Republic of Korea Patent No. 10-1498218 discloses a study result of a pentadienoyl piperidine derivative reducing body fat and blood sugar, and Korean Patent No. 10-1535954 discloses that GPR119 activity is modulated for the treatment of diabetic diseases. Piperidine derivatives that can be used are disclosed. Piperidine derivatives can be applied in various fields such as material chemistry as well as the aforementioned pharmaceutical chemistry field, and an efficient synthesis method is continuously being studied due to the importance of being applicable to various fields.

However, the conventional method for producing a piperidine derivative is synthesized in a multi-step reaction consisting of at least three steps, and there is a problem in that the reagents are expensive and the process cost is increased.

The present application relates to a piperidine compound for solving the problems of the prior art, and by synthesizing a novel piperidine compound that has not been synthesized in the prior art, it can be applied in various fields such as pharmaceutical chemistry, agricultural chemistry, and material chemistry.

In addition, a second object of the present invention is to provide a method for preparing a piperidine compound, which can be synthesized in high yield using quinuclidine and a nitrogen nucleophile in the absence of a transition metal. In particular, what was conventionally synthesized in multiple steps, can be synthesized in one step, thereby reducing process cost and time.

The piperidine compound of the present invention for achieving the above technical object provides a compound represented by the following Chemical Formula 1 or Chemical Formula 2.

[Formula 1]

[Formula 2]

In Formulas 1 and 2, R ₁ is an optionally substituted 5-membered unsaturated or aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic heterocyclic ring, and optionally substituted At least one ring selected from the group consisting of 6-membered unsaturated or aromatic heterocycles, or a polycyclic ring in which two or more rings selected from the group are fused, R ₂ and R ₃ are each independently H, which may be substituted linear or branched C ₁ -C ₂₀ alkyl, optionally substituted C ₆ -C ₂₀ aryl, or optionally substituted C ₃ -C ₂₀ ring, A ₁ is optionally substituted 5-membered unsaturated or at least one ring selected from the group consisting of an aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic heterocyclic ring and an optionally substituted 6-membered unsaturated or aromatic heterocyclic ring. Or is a polycyclic ring in which two or more rings selected from the group are fused, the hetero ring includes at least one selected from the group consisting of N, O and S, and the substitution is C ₁ -C ₆ Alkyl, C ₆ -C ₂₀ Aryl, O, S, Se, F, Cl, Br, I, and may be substituted by one selected from the group consisting of combinations thereof, but is not limited thereto.

R ₁ may be selected from the group consisting of H, methyl, butyl, turtle-butyl, methyl ether, F, Cl, benzene, pyridine, pyrrole, and combinations thereof, but is not limited thereto .

wherein R ₂ and R ₃ are each independently selected from the group consisting of H, methyl, optionally substituted benzenesulfonamide, optionally substituted imidazole, alkylamine, azide, and combinations thereof, and the substituted may be selected from the group consisting of C ₁ -C ₆ alkyl, C ₆ -C ₂₀ aryl, O, S, Se, F, Cl, Br, I, and combinations thereof, but is not limited thereto. .

Wherein A ₁ is a phthalimide that may be substituted, isoindole that may be substituted, isatin, 1H-benzo [de] isoquinoline-1,3(2H)-dione, hexahydro-1H-isoindole-1, 3(2H)-dione, optionally substituted pyrrole, optionally substituted benzenesulfonamide, carbazole, optionally substituted imidazole, piperidine, morpholine, thiomorpholine, optionally substituted triazole and these Including those selected from the group consisting of combinations of, wherein the substitution is C ₁ -C ₆ alkyl, C ₆ -C ₂₀ aryl, O, S, Se, F, Cl, Br, I and combinations thereof. It may be substituted by one selected from the group consisting of, but is not limited thereto.

The piperidine compound may be any one of the following compounds, but is not limited thereto:

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The method for preparing the piperidine compound of the present invention includes a compound represented by the following formula (3); a compound represented by the following formula (4); a compound represented by the following formula (5) or a compound represented by the following formula (6); and a synthetic reagent;

[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

In Formulas 3 to 6, R ₁ is an optionally substituted 5-membered unsaturated or aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic hetero ring, and an optionally substituted At least one ring selected from the group consisting of 6-membered unsaturated or aromatic heterocycles, or a polycyclic ring in which two or more rings selected from the group are fused, R ₂ and R ₃ are each independently H, which may be substituted linear or branched C ₁ -C ₂₀ alkyl, optionally substituted C ₆ -C ₂₀ aryl, or optionally substituted C ₃ -C ₂₀ ring, A ₁ is optionally substituted 5-membered unsaturated or at least one ring selected from the group consisting of an aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic heterocyclic ring and an optionally substituted 6-membered unsaturated or aromatic heterocyclic ring. Or is a polycyclic ring in which two or more rings selected from the group are fused, the hetero ring includes at least one selected from the group consisting of N, O and S, and the substitution is C ₁ -C ₆ Alkyl, C ₆ -C ₂₀ Aryl, O, S, Se, F, Cl, Br, I, and may be substituted by one selected from the group consisting of combinations thereof, but is not limited thereto.

The synthetic reagent comprises a material selected from the group consisting of a fluorine source, K ₂ CO ₃ , Cs ₂ CO ₃ , Na ₂ CO ₃ , Li ₂ CO ₃ , Rb ₂ CO ₃ , 18-crown-6, and combinations thereof may be, but is not limited thereto.

The fluorine source comprises a material selected from the group consisting of CsF, NaF, LiF, KF, RbF, AgF, ZnF ₂ , MgF ₂ , tetrabutylammonium fluoride, tetrabutylammonium difluorotriphenylsilicate, and combinations thereof may be, but is not limited thereto.

The reaction may be carried out under a temperature of 60 °C to 110 °C, but is not limited thereto.

The reaction may be carried out for 10 to 30 hours, but is not limited thereto.

The above-described problem solving means are merely exemplary, and should not be construed as limiting the present application. In addition to the exemplary embodiments described above, additional embodiments may exist in the drawings and detailed description.

The disclosed technology may have the following effects. However, this does not mean that a specific embodiment should include all of the following effects or only the following effects, so the scope of the disclosed technology should not be construed as being limited thereby.

According to the above-described means for solving the problems of the present application, the piperidine compound according to the present application can be applied in various fields such as medicine, chemistry, agrochemical, and material chemistry by synthesizing a novel piperidine compound that has been difficult to synthesize in the prior art.

The method for preparing the piperidine compound of the present application has the advantage of reducing the process cost and time by synthesizing in one step what was conventionally synthesized in multiple steps.

In addition, in the absence of a transition metal, a piperidine compound can be synthesized in high yield using quinuclidine and a nitrogen nucleophile.

Furthermore, various piperidine compounds can be synthesized by variously controlling the substituents. That is, the piperidine compound can be easily prepared by adjusting the substituent according to the use.

1A and 1B are diagrams illustrating a synthesis mechanism of a piperidine compound according to an embodiment of the present application.

Since the present invention can have various changes and can have various embodiments, specific embodiments are illustrated in the drawings and will be described in detail in the detailed description. However, this is not intended to limit the present invention to a specific embodiment, it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention.

In describing each figure, like reference numerals are used for like elements. The terms first, second, etc. may be used to describe various elements, but the elements should not be limited by the terms. The above terms are used only for the purpose of distinguishing one component from another.

For example, without departing from the scope of the present invention, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component. The term “and/or” includes a combination of a plurality of related listed items or any of a plurality of related listed items.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

Terms such as those defined in commonly used dictionaries should be interpreted as having meanings consistent with the meanings in the context of the related art, and should not be interpreted in an ideal or excessively formal meaning unless explicitly defined in the present application. shouldn't

Throughout this specification, when it is said that a member is positioned "on", "on", "on", "under", "under", or "under" another member, this means that a member is located on the other member. It includes not only the case where they are in contact, but also the case where another member exists between two members.

Throughout this specification, when a part "includes" a certain component, it means that other components may be further included, rather than excluding other components, unless otherwise stated.

As used herein, the terms “about,” “substantially,” and the like, to the extent used herein, are used in or close to the numerical value when the manufacturing and material tolerances inherent in the stated meaning are presented, and to aid in the understanding of the present application. It is used to prevent an unconscionable infringer from using the mentioned disclosure unfairly. Also, throughout this specification, "step to" or "step for" does not mean "step for".

Throughout this specification, the term "combination of these" included in the expression of the Markush form means one or more mixtures or combinations selected from the group consisting of the components described in the expression of the Markush form, and the components It is meant to include one or more selected from the group consisting of.

Throughout this specification, reference to “A and/or B” means “A or B”, or “A and B”.

Throughout this specification, the term "aromatic ring" refers to a C _6-30 aromatic hydrocarbon ring group, for example, phenyl, naphthyl, biphenyl, terphenyl, fluorene, phenanthrenyl, triphenylenyl, perylenyl. , chrysenyl, fluoranthenyl, benzofluorenyl, benzotriphenylenyl, benzochrysenyl, anthracenyl, stilbenyl, pyrenyl, etc. means including an aromatic ring, "aromatic heterocyclic ring" is at least one As an aromatic ring containing a hetero element, for example, pyrrolyl, pyrazinyl, pyridinyl, indolyl, isoindolyl, furyl, benzofuranyl, isobenzofuranyl, dibenzofuranyl, dibenzothiophenyl, quinolyl group, isoquinolyl, quinoxalinyl, carbazolyl, phenanthridinyl, acridinyl, phenanthrolinyl, thienyl, and pyridine ring, pyrazine ring, pyrimidine ring, pyridazine ring, triazine ring, Indole ring, quinoline ring, acridine ring, pyrrolidine ring, dioxane ring, piperidine ring, morpholine ring, piperazine ring, carbazole ring, furan ring, thiophene ring, oxazole ring, oxadia Contains an aromatic heterocyclic group formed from a azole ring, a benzoxazole ring, a thiazole ring, a thiadiazole ring, a benzothiazole ring, a triazole ring, an imidazole ring, a benzoimidazole ring, a pyran ring, and a dibenzofuran ring means to do

Throughout this specification, the term "fusion" with respect to two or more rings means that at least one pair of adjacent atoms is included in both rings.

Throughout this specification, the term “alkyl” may include linear or branched, saturated or unsaturated C ₁ -C ₆ alkyl, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl or their It may include all possible isomers, but may not be limited thereto.

Throughout the specification of the present application, the term "halogen" is a group 17 element of the periodic table, and may include, for example, F, Cl, Br, or I, but may not be limited thereto.

Hereinafter, the piperidine compound of the present application and a method for preparing the same will be described in detail with reference to embodiments, examples, and drawings. However, the present application is not limited to these embodiments and examples and drawings.

The present application relates to a piperidine compound represented by the following formula (1) or formula (2).

In Formulas 1 and 2, R ₁ is an optionally substituted 5-membered unsaturated or aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic heterocyclic ring, and optionally substituted At least one ring selected from the group consisting of 6-membered unsaturated or aromatic heterocycles, or a polycyclic ring in which two or more rings selected from the group are fused, R ₂ and R ₃ are each independently H, which may be substituted linear or branched C ₁ -C ₂₀ alkyl, optionally substituted C ₆ -C ₂₀ aryl, or optionally substituted C ₃ -C ₂₀ ring, A ₁ is optionally substituted 5-membered unsaturated or at least one ring selected from the group consisting of an aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic heterocyclic ring and an optionally substituted 6-membered unsaturated or aromatic heterocyclic ring. Or is a polycyclic ring in which two or more rings selected from the group are fused, the hetero ring includes at least one selected from the group consisting of N, O and S, and the substitution is C ₁ -C ₆ Alkyl, C ₆ -C ₂₀ Aryl, O, S, Se, F, Cl, Br, I, and may be substituted by one selected from the group consisting of combinations thereof, but is not limited thereto.

The piperidine compound of the present application can be applied in various fields such as medicine, chemistry, agrochemical, material chemistry, etc. by synthesizing a novel piperidine compound that has been difficult to synthesize in the prior art.

R ₁ may be selected from the group consisting of H, methyl, butyl, turtle-butyl, methyl ether, F, Cl, benzene, pyridine, pyrrole, and combinations thereof, but is not limited thereto .

R ₁ may be substituted or fused to the benzene ring of the skeleton of Formula 1 or 2, but is not limited thereto.

In addition, although R ₁ is represented by one, it may be two or more substituents.

wherein R ₂ and R ₃ are each independently selected from the group consisting of H, methyl, optionally substituted benzenesulfonamide, optionally substituted imidazole, alkylamine, azide, and combinations thereof, and the substituted may be selected from the group consisting of C ₁ -C ₆ alkyl, C ₆ -C ₂₀ aryl, O, S, Se, F, Cl, Br, I, and combinations thereof, but is not limited thereto. .

Wherein A ₁ is a phthalimide that may be substituted, isoindole that may be substituted, isatin, 1H-benzo [de] isoquinoline-1,3(2H)-dione, hexahydro-1H-isoindole-1, 3(2H)-dione, optionally substituted pyrrole, optionally substituted benzenesulfonamide, carbazole, optionally substituted imidazole, piperidine, morpholine, thiomorpholine, optionally substituted triazole and these Including those selected from the group consisting of combinations of, wherein the substitution is C ₁ -C ₆ alkyl, C ₆ -C ₂₀ aryl, O, S, Se, F, Cl, Br, I and combinations thereof. It may be substituted by one selected from the group consisting of, but is not limited thereto.

The piperidine compound may be any one of the following compounds, but is not limited thereto:

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More preferably, the piperidine compound may be any one selected from the group consisting of the following compounds, but is not limited thereto:

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The present application relates to a compound represented by the following formula (3); a compound represented by the following formula (4); a compound represented by the following formula (5) or a compound represented by the following formula (6); And a synthetic reagent; relates to a method for producing a piperidine compound comprising reacting in a solvent.

In Formulas 3 to 6, R ₁ is an optionally substituted 5-membered unsaturated or aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic hetero ring, and an optionally substituted At least one ring selected from the group consisting of 6-membered unsaturated or aromatic heterocycles, or a polycyclic ring in which two or more rings selected from the group are fused, R ₂ and R ₃ are each independently H, which may be substituted linear or branched C ₁ -C ₂₀ alkyl, optionally substituted C ₆ -C ₂₀ aryl, or optionally substituted C ₃ -C ₂₀ ring, A ₁ is optionally substituted 5-membered unsaturated or at least one ring selected from the group consisting of an aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic heterocyclic ring and an optionally substituted 6-membered unsaturated or aromatic heterocyclic ring. Or is a polycyclic ring in which two or more rings selected from the group are fused, the hetero ring includes at least one selected from the group consisting of N, O and S, and the substitution is C ₁ -C ₆ Alkyl, C ₆ -C ₂₀ Aryl, O, S, Se, F, Cl, Br, I, and may be substituted by one selected from the group consisting of combinations thereof, but is not limited thereto.

1A and 1B are diagrams illustrating a synthesis mechanism of a piperidine compound according to an embodiment of the present application.

Referring to FIG. 1A , the compound represented by Formula 3 and the synthetic reagent react to form an intermediate (I), which is a benzine derivative. The intermediate (I) reacts with the compound represented by the formula (4) to form the intermediate (II), which is a quaternary ammonium salt derivative. Due to the negative charge in the intermediate (II), the compound represented by the formula (5) loses hydrogen and becomes negatively charged. The negatively charged compound represented by Formula 5 reacts with the ring of the compound represented by Formula 4 to synthesize a piperidine compound (Formula 1).

Referring to FIG. 1B , the compound represented by Formula 3 reacts with the synthetic reagent to form an intermediate (I), which is a benzine derivative. The intermediate (I) reacts with the compound represented by the formula (4) to form the intermediate (II), which is a quaternary ammonium salt derivative. Due to the negative charge in the intermediate (II), the compound represented by the formula (6) loses hydrogen and becomes negatively charged. The negatively charged compound represented by Formula 6 reacts with the ring of the compound represented by Formula 4 to synthesize a piperidine compound (Formula 2).

The method for preparing the piperidine compound of the present application has the advantage of reducing the process cost and time by synthesizing in one step what was conventionally synthesized in multiple steps.

In addition, in the absence of a transition metal, a piperidine compound can be synthesized in high yield by using the compound represented by Formula 4 (quinuclidine) and a nitrogen nucleophile (compound represented by Formula 5).

Furthermore, various piperidine compounds can be synthesized by variously controlling the R ₁ , R ₂ , R ₃ and A ₁ . That is, the piperidine compound can be easily prepared by adjusting the substituent according to the use.

The synthesis reagent may include a halogen source, but is not limited thereto.

The synthetic reagent comprises a material selected from the group consisting of a fluorine source, K ₂ CO ₃ , Cs ₂ CO ₃ , Na ₂ CO ₃ , Li ₂ CO ₃ , Rb ₂ CO ₃ , 18-crown-6, and combinations thereof may be, but is not limited thereto.

The fluorine source comprises a material selected from the group consisting of CsF, NaF, LiF, KF, RbF, AgF, ZnF ₂ , MgF ₂ , tetrabutylammonium fluoride, tetrabutylammonium difluorotriphenylsilicate, and combinations thereof may be, but is not limited thereto.

The synthetic reagent may be any material capable of inducing the compound represented by Formula 3 into a benzine derivative, and is not limited to the above-described materials.

The reaction may be carried out under a temperature of 60 °C to 110 °C, but is not limited thereto.

When the reaction is carried out at a temperature of less than 60° C. or more than 110° C., the yield of synthesized piperidine may be reduced.

The reaction may be carried out for 10 to 30 hours, but is not limited thereto.

If the reaction is carried out for less than 10 hours, the reactant may not be sufficiently generated, and thus the yield may be reduced. In addition, when the reaction is carried out for more than 30 hours, by-products may increase. However, the reaction time is not particularly limited, and the reaction time may be adjusted according to the substituent of the compound to be prepared. That is, if necessary, the reaction time may be outside the above-described reaction time range.

The solvent comprises a solvent selected from the group consisting of dimethylformamide, toluene, dichloromethane, tetrahydrofuran, chlorobenzene, acetonitrile, ethanol, acetone, isopropyl alcohol, ethyl ether, and combinations thereof. may be, but is not limited thereto.

The present invention will be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present application.

1. Examples for Optimizing Reaction Conditions

First, in Scheme 1, 1 equivalent (eq) (30 mg, 0.1 mmol) of the following compound A1, 1 equivalent (eq) (11.2 mg, 0.1 mmol) of the following compound B1, 1 equivalent (eq) (14.8 mg, 0.1) mmol) of the following compound C1, 1.2 equivalents (eq) (65.3 mg, 0.12 mmol) of TBAT (tetrabutylammonium difluorotriphenylsilicate) as a synthetic reagent and 0.1 M concentration of THF (tetrahydrofuran) as a solvent in a reaction vessel, The reaction was conducted with stirring at a temperature for 18 hours to prepare a piperidine compound (Compound D1) (32 mg, 0.095 mmol, yield 95%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.83 (m, 2H), 7.72-7.70 (m, 2H), 7.24 (t, J = 8.2 Hz, 2H), 6.93 (d, J = 8.0 Hz) , 2H), 6.82 (t, J = 7.2 Hz, 1H), 3.76 (t, J = 7.2 Hz, 2H), 3.67 (d, J = 12.0 Hz, 2H), 2.68 (t, J = 11.8 Hz, 2H) ) 1.90 (d, J = 9.5 Hz, 2H), 1.67 (q, J = 6.8 Hz, 2H), 1.44-1.39 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 151.8, 134.0, 132.2, 129.1, 123.3, 119.3, 116.6, 49.9, 35.7, 35.2, 33.4, 31.9. IR : v 2921, 2853, 2811, 1704, 1598, 1502, 1454, 1064, 750, 721 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₂ N ₂ O ₂ [M] ⁺ : 334.1681. Found: 334.1679.

[Scheme 1]

A piperidine compound (Compound D1) was prepared in the same manner as in Example 1, except for reaction at a temperature of 60° C. (yield 58%).

A piperidine compound (compound D1) was prepared in the same manner as in Example 1, except that CsF as a synthesis reagent and acetonitrile as a solvent were used and the reaction was performed at a temperature of 70° C. (yield 38%).

A piperidine compound (Compound D1) was prepared in the same manner as in Example 3, except for reaction at a temperature of 90° C. (yield 62%).

A piperidine compound (Compound D1) was prepared in the same manner as in Example 3, except for reacting at a temperature of 110° C. (yield 90%).

A piperidine compound (compound D1) was prepared in the same manner as in Example 1, except that tetrabutylammonium fluoride (TBAF) was used as a synthetic reagent (yield 18%).

A piperidine compound (Compound D1) was prepared in the same manner as in Example 1, except that KF and 18-crown-6 were used as synthetic reagents (yield 74%).

A piperidine compound (Compound D1) was prepared in the same manner as in Example 1, except that K ₂ CO ₃ and 18-crown-6 were used as synthetic reagents (yield 64%).

As a result of controlling conditions such as temperature, synthetic reagents, and solvents in Examples 1 to 8, it was confirmed that the synthesis was performed in the highest yield (95%) in Example 1. Accordingly, it is intended to synthesize various piperidines by adjusting the substituents under the conditions of Example 1.

2.1 Synthesis result according to compound A

A piperidine compound (Compound D2) was prepared in the same manner as in Example 1, except that Compound A2 below was used instead of Compound A1 (yield 44%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.84 (m, 2H), 7.72-7.70 (m, 2H), 7.13 (t, J = 7.7 Hz, 1H), 6.74 (d, J = 8.5 Hz) , 2H), 6.65 (d, J = 7.5 Hz, 1H), 3.75 (t, J = 7.2 Hz, 2H), 3.65 (d, J = 12.5 Hz, 2H), 2.66 (t, J = 11.3 Hz, 2H) ), 2.30 (s, 3H), 1.89 (d, J = 9.5 Hz, 2H), 1.67 (q, J = 6.8 Hz, 2H), 1.43-1.39 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 152.0, 138.8, 134.0, 132.3, 128.9, 123.3, 120.3, 117.5, 113.8, 50.1, 35.8, 35.2, 33.5, 32.0, 21.9. IR : v 2922, 2851, 1772, 1711, 1600, 1493, 1396, 1372, 1065, 720 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₂ H ₂₄ N ₂ O ₂ [M] ⁺ : 348.1838. Found: 348.1839.

[Compound A2]

[Compound D2]

A piperidine compound (Compound D3) was prepared in the same manner as in Example 9 (yield 44%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.83 (m, 2H), 7.72-7.70 (m, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.5 Hz) , 2H), 3.75 (t, J = 7.2 Hz, 2H), 3.59 (d, J = 9.8 Hz, 2H), 2.62 (t, J = 11.5 Hz, 2H), 2.25 (s, 3H), 1.89 (d) , J = 9.0 Hz, 2H), 1.67 (q, J = 6.7 Hz, 2H), 1.46-1.42 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 149.9, 134.0, 132.3, 129.6, 128.9, 123.3, 117.0, 50.6, 35.8, 35.2, 33.4, 32.1, 20.5. IR : v 2931, 2852, 1770, 1708, 1517, 1443, 1399, 1377, 1066, 721 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₂ H ₂₄ N ₂ O ₂ [M] ⁺ : 348.1838. Found: 348.1834.

[Compound D3]

The compounds D2 and D3 are simultaneously synthesized through the method of Example 9, and the compounds D2 and D3 can be separated using column chromatography through silica. At this time, the synthesis yields of compounds D2 and D3 were 44% and 44%, respectively, and it can be seen that the total synthesis yield of piperidine prepared by the method of Example 9 was 88%.

A piperidine compound (Compound D4) was prepared in the same manner as in Example 1, except that Compound A3 below was used instead of Compound A1 (yield 55%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.86-7.84 (m, 2H), 7.72-7.70 (m, 2H), 7.18 (t, J = 8.0 Hz, 1H), 6.99 (t, J = 2.0 Hz) , 1H), 6.88 (d, J = 8.5 Hz, 1H), 6.75 (dd, J = 8.0, 2.5 Hz, 1H), 3.76 (t, J = 7.2 Hz, 2H), 3.65 (d, J = 12.0 Hz) , 2H), 2.67 (t, J = 11.5 Hz, 2H), 1.91 (d, J = 9.0 Hz, 2H), 1.67 (q, J = 6.7 Hz, 2H), 1.46-1.42 (m, 3H), 1.30 (s, 9H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 152.0, 151.9, 134.0, 132.3, 128.7, 123.3, 117.0, 114.6, 113.9, 50.5, 35.8, 35.2, 34.9, 33.4, 32.2, 31.5. IR : v 2923, 2853, 1773, 1714, 1599, 1466, 1395, 1372, 1066, 720 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₅ H ₃₀ N ₂ O ₂ [M] ⁺ : 390.2307. Found: 390.2306.

[Compound A3]

[Compound D4]

A piperidine compound (Compound D5) was prepared in the same manner as in Example 11 (yield 33%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.84 (m, 2H), 7.72-7.70 (m, 2H), 7.26 (d, J = 8.5 Hz, 2H), 6.87 (d, J = 9.0 Hz) , 2H), 3.75 (t, J = 7.5 Hz, 2H), 3.63 (d, J = 11.5 Hz, 2H), 2.64 (t, J = 11.3 Hz, 2H), 1.89 (d, J = 9.0 Hz, 2H) ), 1.67 (q, J = 6.7 Hz, 2H), 1.43-1.39 (m, 3H), 1.28 (s, 9H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 149.6, 142.1, 134.0, 132.3, 125.9, 123.3, 116.3, 50.2, 35.8, 35.2, 34.0, 33.4, 32.1, 31.5. IR : v 2925, 2854, 1770, 1709, 1518, 1464, 1399, 1372, 1062, 721 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₅ H ₃₀ N ₂ O ₂ [M] ⁺ : 390.2307. Found: 390.2306.

[Compound D5]

Compounds D4 and D5 are simultaneously synthesized through the method of Example 11, and the compounds D4 and D5 may be separated using column chromatography through silica. At this time, the synthesis yields of compounds D4 and D5 were 55% and 33%, respectively, and it can be seen that the total synthesis yield of piperidine prepared by the method of Example 11 was 88%.

A piperidine compound (Compound D6) was prepared in the same manner as in Example 1 (yield 83%), except that Compound A4 below was used instead of Compound A1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.83 (m, 2H), 7.72-7.70 (m, 2H), 7.00 (d, J = 8.0 Hz, 1H), 6.75 (d, J = 2.0 Hz) ,1H), 6.69 (dd, J = 8.0, 2.5 Hz, 1H), 3.75 (t, J = 7.2 Hz, 2H), 3.59 (d, J = 11.5 Hz, 2H), 2.62 (t, J = 11.0 Hz) , 2H), 2.22 (s, 3H), 2.17 (s, 3H), 1.89 (d, J = 9.0 Hz, 2H), 1.67 (q, J = 6.7 Hz, 2H), 1.44-1.42 (m, 3H) . ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 150.3, 137.1, 134.0, 132.3, 130.2, 127.8, 123.3, 118.8, 114.5, 50.7, 35.8, 35.2, 33.4, 32.1, 20.3, 18.9. IR : v 2922, 2854, 1772, 1712, 1612, 1505, 1396, 1372, 1065, 720 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₃ H ₂₆ N ₂ O ₂ [M] ⁺ : 362.1994. Found: 362.1996.

[Compound A4]

[Compound D6]

A piperidine compound (Compound D7) was prepared in the same manner as in Example 1, except that Compound A5 below was used instead of Compound A1 (yield 73%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.84-7.83 (m, 2H), 7.71-7.70 (m, 2H), 6.76 (d, J = 8.5 Hz, 1H), 6.58 (d, J = 2.5 Hz) ,1H), 6.45 (dd, J = 8.5, 2.5 Hz, 1H), 3.85 (s, 3H), 3.81 (s, 3H), 3.75 (t, J = 7.2 Hz, 2H), 3.50 (d, J = 12.5 Hz, 2H), 2.60 (t, J = 11.5 Hz, 2H), 1.90 (d, J = 10.5 Hz, 2H), 1.67 (q, J = 6.8 Hz, 2H), 1.48-1.40 (m, 3H) . ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 149.4, 147.1, 143.4, 134.0, 132.2, 123.3, 112.0, 108.5, 103.6, 56.3, 55.9, 51.7, 35.8, 35.2, 33.3, 32.3. IR : v 2933, 2834, 1769, 1707, 1518, 1398, 1244, 1225, 1024, 727 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₃ H ₂₆ N ₂ O ₄ [M] ⁺ : 394.1893. Found: 394.1890.

[Compound A5]

[Compound D7]

A piperidine compound (Compound D8) was prepared in the same manner as in Example 1, except that Compound A6 below was used instead of Compound A1 (yield 63%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.83 (m, 2H), 7.72-7.70 (m, 2H), 7.14 (t, J = 8.3 Hz, 1H), 6.54 (dd, J = 8.0, 2.0 Hz, 1H), 6.46 (t, J = 2.2 Hz, 1H), 6.38 (dd, J = 8.0, 2.0 Hz, 1H), 3.78 (s, 3H), 3.75 (t, J = 7.2 Hz, 2H) , 3.66 (d, J = 13.0 Hz, 2H), 2.68 (t, J = 11.8 Hz, 2H), 1.88 (d, J = 9.5 Hz, 2H), 1.66 (q, J = 7.0 Hz, 2H), 1.42 -1.38 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 160.6, 153.2, 134.0, 132.2, 129.8, 123.3, 109.4, 104.2, 102.9, 55.2, 49.8, 35.8, 35.2, 33.5, 31.9. IR : v 2923, 2835, 1771, 1710, 1600, 1495, 1396, 1169, 1062, 720 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₂ H ₂₄ N ₂ O ₃ [M] ⁺ : 364.1787. Found: 364.1785.

[Compound A6]

[Compound D8]

A piperidine compound (Compound D9) was prepared in the same manner as in Example 1 (yield 50%), except that Compound A7 below was used instead of Compound A1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.84-7.83 (m, 2H), 7.72-7.70 (m, 2H), 6.99 (q, J = 9.5 Hz, 1H), 6.69 (ddd, J = 11.6, 9.0, 3.0 Hz, 1H), 6.58-6.55 (m, 1H), 3.75 (t, J = 7.2 Hz, 2H), 3.53 (d, J = 12.5 Hz, 2H), 2.64 (t, J = 11.5 Hz, 2H), 1.90 (d, J = 9.5 Hz, 2H), 1.66 (q, J = 6.8 Hz, 2H), 1.40-1.34 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 150.5 (dd, 1C, J _CF = 243.4, 13.1 Hz), 149.0 (d, 1C, J _CF = 6.7 Hz), 144.0 (dd, 1C, J _CF ) = 237.9, 12.8 Hz), 134.0, 132.2, 123.3, 117.1 (d, 1C, J _CF = 17.1 Hz), 112.0 (d, 1C, J _CF = 1.4 Hz), 105.6 (d, 1C, J _CF = 19.8 Hz) ), 50.2, 35.7, 35.1, 33.1, 31.7. IR : v 2926, 2845, 1709, 1520, 1401, 1379, 1273, 1187, 1064, 720 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₀ F ₂ N ₂ O ₂ [M] ⁺ : 370.1493. Found: 370.1492.

[Compound A7]

[Compound D9]

A piperidine compound (Compound D10) was prepared in the same manner as in Example 1, except that Compound A8 was used instead of Compound A1 (yield 27%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.83 (m, 2H), 7.72-7.70 (m, 2H), 7.13 (t, J = 8.0 Hz, 1H), 6.86 (t, J = 2.0 Hz) , 1H), 6.78-6.74 (m, 2H), 3.75 (t, J = 7.2 Hz, 2H), 3.66 (d, J = 12.5 Hz, 2H), 2.70 (t, J = 12.0 Hz, 2H), 1.89 (d, J = 12.0 Hz, 2H), 1.66 (q, J = 7.0 Hz, 2H), 1.45-1.33 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 152.7, 134.9, 134.0, 132.1, 130.0, 123.3, 118.8, 116.1, 114.4, 49.4, 35.7, 35.1, 33.3, 31.7. IR : v 2937, 2850, 1709, 1497, 1399, 1376, 1220, 1066, 720, 667 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₁ ClN ₂ O ₂ [M] ⁺ : 368.1292. Found: 368.1292.

[Compound A8]

[Compound D10]

A piperidine compound (Compound D11) was prepared in the same manner as in Example 10 (yield 32%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.85-7.83 (m, 2H), 7.72-7.70 (m, 2H), 7.17 (d, J = 9.0 Hz, 2H), 6.83 (d, J = 9.0 Hz) , 2H), 3.75 (t, J = 7.2 Hz, 2H), 3.61 (d, J = 12.5 Hz, 2H), 2.66 (t, J = 11.8 Hz, 2H), 1.89 (d, J = 10 Hz, 2H) ), 1.66 (q, J = 6.8 Hz, 2H), 1.40-1.36 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 150.4, 134.0, 132.2, 128.9, 124.1, 123.3, 117.7, 49.9, 35.7, 35.1, 33.2, 31.8. IR : v 2923, 2851, 1711, 1593, 1396, 1372, 1220, 1064, 720, 682 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₁ ClN ₂ O ₂ [M] ⁺ : 368.1292. Found: 368.1290.

[Compound D11]

The compounds D10 and D11 are simultaneously synthesized through the method of Example 17, and the compounds D10 and D11 can be separated using column chromatography through silica. At this time, the synthesis yields of compounds D10 and D11 were 27% and 32%, respectively, and it can be seen that the total synthesis yield of piperidine prepared by the method of Example 17 was 59%.

A piperidine compound (Compound D12) was prepared in the same manner as in Example 1, except that Compound A9 was used instead of Compound A1 (yield 52%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.86-7.84 (m, 2H), 7.72-7.70 (m, 2H), 7.70 (s, 1H), 7.69 (s, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.38 (td, J = 7.5, 1.0 Hz, 1H), 7.28-7.25 (m, 2H), 7.12 (d, J = 2.5 Hz, 1H), 3.81-3.76 (m, 4H), 2.76 (t, J = 11.7 Hz, 2H), 1.95 (d, J = 9.0 Hz, 2H), 1.70 (q, J = 6.5 Hz, 2H), 1.49-1.45 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.6, 149.7, 134.8, 134.0, 132.2, 128.6, 128.4, 127.5, 126.8, 126.2, 123.3, 123.2, 120.2, 110.5, 50.3, 35.8, 35.2, 33.5, 32.0. IR : v 2929, 2853, 2814, 1708, 1597, 1463, 1404, 1068, 752, 718 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₅ H ₂₄ N ₂ O ₂ [M] ⁺ : 384.1838. Found: 384.1838.

[Compound A9]

[Compound D12]

A piperidine compound (Compound D13) was prepared in the same manner as in Example 1, except that Compound A10 was used instead of Compound A1 (yield 29%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.30 (s, 1H), 8.05 (s, 1H), 7.85-7.83 (m, 2H), 7.72-7.71 (m, 2H), 7.19-7.17 (m, 1H), 7.15-7.12 (m, 1H), 3.76 (t, J = 7.2 Hz, 2H), 3.68 (d, J = 13.0 Hz, 2H), 2.73 (t, J = 12.0 Hz, 2H), 1.92 ( d, J = 11.5 Hz, 2H), 1.67 (q, J = 7.0 Hz, 2H), 1.44-1.38 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 147.5, 140.1, 138.8, 134.0, 132.2, 123.5, 123.3, 122.8, 49.1, 35.6, 35.1, 33.2, 31.6. IR : v 2923, 2852, 2814, 1709, 1580, 1488, 1396, 1372, 1065, 720 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₀ H ₂₁ N ₃ O ₂ [M] ⁺ : 335.1634. Found: 335.1635.

[Compound A10]

[Compound D13]

A piperidine compound (Compound D14) was prepared in the same manner as in Example 13 (yield 14%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.22 (d, J = 5.0 Hz, 2H), 7.85-7.84 (m, 2H), 7.73-7.71 (m, 2H), 6.65 (d, J = 6.5 Hz, 2H), 3.89 (d, J = 13.5 Hz, 2H), 3.75 (t, J = 7.0 Hz) , 2H), 2.85 (td, J = 12.7, 2.5 Hz, 2H), 1.91 (d, J = 12.5 Hz, 2H), 1.66 (q, J = 7.0 Hz, 2H), 1.30 (qd, J = 12.3, 3.7 Hz, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.5, 155.0, 149.1, 134.1, 132.1, 123.3 108.2, 46.5, 35.5, 35.0, 33.4, 31.2. IR : v 2922, 2851, 1709, 1594, 1543, 1396, 1372, 720 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₀ H ₂₁ N ₃ O ₂ [M] ⁺ : 335.1634. Found: 335.1631.

[Compound D14]

The compounds D13 and D14 are simultaneously synthesized through the method of Example 20, and the compounds D13 and D14 can be separated using column chromatography through silica. At this time, the synthesis yields of the compounds D13 and D14 are 29% and 14%, respectively, and it can be seen that the total synthesis yield of the piperidine prepared by the method of Example 20 is 43%.

A piperidine compound (Compound D15) was prepared in the same manner as in Example 1, except that Compound A11 was used instead of Compound A1 (yield 23%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.04 (s, 1H), 7.86-7.84 (m, 2H), 7.72-7.70 (m, 2H), 7.28 (d, J = 8.5 Hz, 1H), 7.18 (s, 1H), 7.15 (t, J = 2.7 Hz, 1H), 6.99 (dd, J = 8.8, 2.3 Hz, 1H), 6.45 (t, J = 2.5 Hz, 1H), 3.77 (t, J = 7.3 Hz, 2H), 3.56 (d, J = 12.0 Hz, 2H), 2.66 (t, J = 11.0 Hz, 2H), 1.93 (d, J = 12.0 Hz, 2H), 1.69 (q, J = 7.2 Hz) , 2H), 1.55-1.47 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.6, 134.0, 132.3, 131.4, 128.4, 124.5, 123.3, 116.7, 111.4, 108.2, 102.5, 52.8, 35.9, 35.3, 33.4, 32.5. IR : v 3398, 2922, 2851, 1708, 1466, 1397, 1372, 1065, 867, 719, 530 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₃ H ₂₃ N ₃ O ₂ [M] ⁺ : 373.1790. Found: 373.1786.

[Compound A11]

[Compound D15]

A piperidine compound (Compound D16) was prepared in the same manner as in Example 15 (yield: 26%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.17 (s, 1H), 7.86-7.84 (m, 2H), 7.72-7.70 (m, 2H), 7.14 (t, J = 3.0 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.58 (d, J = 7.5 Hz, 1H), 6.55 (t, J = 2.5 Hz, 1H), 3.79 (t) , J = 7.5 Hz, 2H), 3.71 (d, J = 12.5 Hz, 2H), 2.71 (t, J = 11.0 Hz, 2H), 1.94 (d, J = 12.5 Hz, 2H), 1.73 (q, J ) = 7.2 Hz, 2H), 1.62-1.46 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.6, 146.6, 137.0, 134.0, 132.3, 123.3, 122.8, 122.5, 121.5, 106.8, 105.5, 101.5, 52.0, 35.9, 35.4, 33.9, 32.6. IR : v 3399, 2924, 2848, 2803, 1770, 1708, 1436, 1397, 1066, 745, 720, 530 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₃ H ₂₃ N ₃ O ₂ [M] ⁺ : 373.1790. Found: 373.1790.

[Compound D16]

The compounds D15 and D16 are simultaneously synthesized through the method of Example 22, and the compounds D15 and D16 can be separated using column chromatography through silica. At this time, the synthesis yields of the compounds D15 and D16 are 23% and 26%, respectively, and it can be seen that the total synthesis yield of the piperidine prepared by the method of Example 22 is 49%.

2.2. Synthesis result according to compound C

A piperidine compound (Compound D17) was prepared in the same manner as in Example 1, except that the following compound C2 was used instead of the compound C1 (yield 93%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.97 (d, J = 1.5 Hz, 1H), 7.85 (dd, J = 8.0, 1.5 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.24 (t, J = 8.2 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 3.75 (t, J = 7.5 Hz, 2H), 3.67 ( d, J = 12.0 Hz, 2H), 2.67 (t, J = 11.7 Hz, 2H), 1.89-1.87 (m, 2H), 1.66 (q, J = 6.7 Hz, 2H), 1.43-1.39 (m, 3H) ). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 167.7, 167.1, 151.9, 137.0, 133.9, 130.7, 129.1, 129.0, 126.7, 124.7, 119.4, 116.6, 50.0, 36.0, 35.1, 33.4, 32.0. IR : v 2947, 2825, 1709, 1600, 1501, 1417, 1391, 1022, 740, 694 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₁ BrN ₂ O ₂ [M] ⁺ : 412.0786. Found: 412.0785.

[Compound C2]

[Compound D17]

A piperidine compound (Compound D18) was prepared in the same manner as in Example 1 (yield 90%) except that the following compound C3 was used instead of the compound C1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.66 (d, J = 2.0 Hz, 1H), 8.63 (dd, J = 8.0, 2.0 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.24 (t, J = 7.7 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 3.81 (t, J = 7.5 Hz, 2H), 3.68 ( d, J = 12.0 Hz, 2H), 2.68 (t, J = 11.7 Hz, 2H), 1.90-1.88 (m, 2H), 1.69 (q, J = 6.7 Hz, 2H), 1.45-1.41 (m, 3H) ). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 166.3, 166.0, 151.8, 136.6, 133.6, 129.3, 129.2, 124.5, 119.5, 118.8, 116.7, 49.9, 36.5, 35.1, 33.5, 31.9. IR : v 2927, 2852, 1716, 1598, 1539, 1496, 1344, 1074, 760, 718, 690 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₁ N ₃ O ₄ [M] ⁺ : 379.1532. Found: 379.1529.

[Compound C3]

[Compound D18]

A piperidine compound (Compound D19) was prepared in the same manner as in Example 1, except that the following compound C4 was used instead of the compound C1 (yield 43%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.59 (d, J = 8.0 Hz, 1H), 7.23 (t, J = 8.0 Hz, 2H), 7.02 (d, J = 2.0 Hz, 1H), 6.93 ( d, J = 8.0 Hz, 2H), 6.83-6.80 (m, 2H), 4.33 (s, 2H), 3.69 (t, J = 7.5 Hz, 2H), 3.66 (d, J = 12.5 Hz, 2H), 2.67 (t, J = 11.5 Hz, 2H), 1.89 (d, J = 9.5 Hz, 2H), 1.64 (q, J = 6.7 Hz, 2H), 1.42-1.38 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 168.7, 168.6, 152.1, 151.9, 135.1, 129.1, 125.1, 120.9, 119.3, 118.0, 116.6, 108.6, 50.0, 35.6, 35.3, 33.4, 32.0. IR : v 3464, 3356, 2926, 1686, 1607, 1501, 1397, 1366, 1054, 749, 694 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₃ N ₃ O ₂ [M] ⁺ : 349.1790. Found: 349.1790.

[Compound C4]

[Compound D19]

A piperidine compound (Compound D20) was prepared in the same manner as in Example 1, except that the following compound C5 was used instead of the compound C1 (yield 23%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.24 (t, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.5 Hz, 1H), 3.77 ( t, J = 7.5 Hz, 2H), 3.67 (d, J = 11.5 Hz, 2H), 2.68 (t, J = 11.5 Hz, 2H), 1.89-1.87 (m, 2H), 1.67 (q, J = 6.7) Hz, 2H), 1.43-1.39 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 163.7, 151.8, 140.2, 129.7, 129.1, 127.7, 119.5, 116.6, 49.9, 36.6, 34.8, 33.3, 31.8. IR : v 2923, 2852, 1716, 1461, 1400, 1374, 1198, 1076, 738 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₁₈ Cl ₄ N ₂ O ₂ [M] ⁺ : 470.0122. Found: 470.0120.

[Compound C5]

[Compound D20]

A piperidine compound (Compound D21) was prepared in the same manner as in Example 1, except that the following compound C6 was used instead of the compound C1 (yield 72%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.06 (d, J = 7.0 Hz, 1H), 7.93 (dd, J = 7.0, 1.0 Hz, 1H), 7.87 (td, J = 7.5, 1.0 Hz, 1H) ), 7.83 (td, J = 7.4, 1.3 Hz, 1H), 7.27-7.25 (m, 2H), 7.03-6.92 (m, 2H), 6.89-6.84 (m, 1H), 3.86 (t, J = 7.2) Hz, 2H), 3.69 (d, J = 12.5 Hz, 2H), 2.73 (s, 2H), 1.92 (d, J = 10.5 Hz, 2H), 1.86 (q, J = 6.8 Hz, 2H), 1.58- 1.47 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 159.1, 151.6, 137.8, 134.8, 134.4, 129.2, 127.5, 125.2, 121.0, 119.5, 116.8, 50.0, 37.2, 34.7, 33.1, 31.6. IR : v 2923, 2852, 1730, 1597, 1495, 1457, 1334, 1298, 1181, 751 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₀ H ₂₂ N ₂ O ₃ S [M] ⁺ : 370.1351. Found: 370.1349.

[Compound C6]

[Compound D21]

A piperidine compound (Compound D22) was prepared in the same manner as in Example 1 (yield 58%), except that the following compound C7 was used instead of the compound C1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.62-7.58 (m, 2H), 7.24 (t, J = 8.0 Hz, 2H), 7.12 (t, J = 7.5 Hz, 1H), 6.93 (d, J ) = 8.5 Hz, 2H), 6.89 (d, J = 8.0 Hz, 1H), 6.83 (t, J = 7.2 Hz, 1H), 3.80 (t, J = 7.5 Hz, 2H), 3.68 (d, J = 12.5) Hz, 2H), 2.70 (t, J = 12.0 Hz, 2H), 1.90 (d, J = 11.0 Hz, 2H), 1.68 (q, J = 7.2 Hz, 2H), 1.47-1.42 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 183.6, 158.2, 151.7, 150.9, 138.4, 129.2, 125.7, 123.8, 119.6, 117.8, 116.7, 110.1, 49.9, 37.9, 33.8, 33.5, 32.0. IR : v 2923, 2852, 1737, 1611, 1495, 1469, 1355, 1094, 755, 693 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₂ N ₂ O ₂ [M] ⁺ : 334.1681. Found: 334.1678.

[Compound C7]

[Compound D22]

A piperidine compound (Compound D23) was prepared in the same manner as in Example 1, except that the following compound C8 was used instead of the compound C1 (yield 78%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.59 (d, J = 7.5 Hz, 2H), 8.20 (d, J = 7.5 Hz, 2H), 7.75 (t, J = 7.7 Hz, 2H), 7.24 ( t, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.5 Hz, 1H), 4.25 (t, J = 7.8 Hz, 2H), 3.69 (d, J = 12.5 Hz, 2H), 2.72 (t, J = 12.0 Hz, 2H), 1.95 (d, J = 12.5 Hz, 2H), 1.73 (q, J = 7.3 Hz, 2H), 1.57-1.44 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 164.2, 151.9, 134.0, 131.6, 131.2, 129.1, 128.2, 127.0, 122.7, 119.2, 116.5, 49.9, 38.4, 34.7, 34.0, 32.1. IR : v 2923, 2820, 1698, 1660, 1591, 1437, 1378, 1343, 778, 691 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₅ H ₂₄ N ₂ O ₂ [M] ⁺ : 384.1838. Found: 384.1835.

[Compound C8]

[Compound D23]

A piperidine compound (Compound D24) was prepared in the same manner as in Example 1, except that the following compound C9 was used instead of the compound C1 (yield 61%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.23 (t, J = 7.7 Hz, 2H), 6.92 (d, J = 8.5 Hz, 2H), 6.81 (t, J = 7.2 Hz, 1H), 3.66 ( d, J = 12.0 Hz, 2H), 3.54 (t, J = 7.2 Hz, 2H), 2.84 (t, J = 4.3 Hz, 2H), 2.66 (t, J = 11.3 Hz, 2H), 1.84 (d, J = 8.5 Hz, 4H), 1.75-1.72 (m, 2H), 1.54 (q, J = 6.8 Hz, 2H), 1.48-1.38 (m, 7H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 179.9, 151.9, 129.1, 119.4, 116.6, 50.0, 39.8, 36.3, 34.3, 33.7, 31.9, 23.8, 21.7. IR : v 2926, 2855, 1698, 1701, 1598, 1495, 1449, 1398, 757, 693 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₈ N ₂ O ₂ [M] ⁺ : 340.2151. Found: 340.2148.

[Compound C9]

[Compound D24]

A piperidine compound (Compound D25) was prepared in the same manner as in Example 1, except that the following compound C10 was used instead of the compound C1 (yield 91%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.24 (t, J = 8.0 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.5 Hz, 1H), 3.66 ( d, J = 12.0 Hz, 2H), 3.57 (t, J = 7.5 Hz, 2H), 2.69-2.64 (m, 6H), 1.85-1.83 (m, 2H), 1.55 (q, J = 7.0 Hz, 2H) ), 1.40-1.36 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 177.3, 151.9, 129.1, 119.4, 116.6, 49.9, 36.7, 34.3, 33.6, 31.9, 28.3. IR : v 2926, 2811, 1694, 1600, 1503, 1439, 1344, 1159, 1123, 757, 688 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₇ H ₂₂ N ₂ O ₂ [M] ⁺ : 286.1681. Found: 286.1679.

[Compound C10]

[Compound D25]

A piperidine compound (Compound D26) was prepared in the same manner as in Example 1 (yield 53%), except that the following compound C11 was used instead of the compound C1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.67 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.26-7.22 (m, 2H), 6.93 (d, J ) = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 3.65 (d, J = 12.5 Hz, 2H), 3.04 (t, J = 7.0 Hz, 2H), 2.70 (s, 3H), 2.69 (td, J = 12.1, 2.3 Hz, 2H), 2.42 (s, 3H), 1.82 (d, J = 12.5 Hz, 2H), 1.51-1.47 (m, 3H), 1.35 (qd, J = 12.0, 3.8 Hz, 2H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.8, 143.3, 134.3, 129.7, 129.1, 127.5, 119.4, 116.6, 50.0, 47.6, 34.5, 34.0, 32.8, 32.0, 21.6. IR : v 2922, 2852, 1598, 1494, 1462, 1339, 1160, 1089, 719, 549 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₈ N ₂ O ₂ S [M] ⁺ : 372.1871. Found: 372.1873.

[Compound C11]

[Compound D26]

A piperidine compound (Compound D27) was prepared in the same manner as in Example 1, except that the following compound C12 was used instead of the compound C1 (yield 74%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.76 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.25 (t, J = 8.0 Hz, 2H), 6.96 ( d, J = 5.0 Hz, 2H), 6.86 (t, J = 7.0 Hz, 1H), 4.73 (s, 1H), 3.60 (d, J = 12.0 Hz, 2H), 2.99 (q, J = 6.7 Hz, 2H), 2.65 (t, J = 11.5 Hz, 2H), 2.42 (s, 3H), 1.69 (d, J = 13.0 Hz, 2H), 1.44 (t, J = 6.5 Hz, 3H), 1.36 (s, 2H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.3, 143.6, 136.9, 129.9, 129.2, 127.2, 120.0, 117.0, 50.3, 40.7, 36.1, 32.7, 31.7, 21.7. IR : v 3280, 2922, 2847, 1598, 1495, 1324, 1158, 1120, 1093, 757 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₀ H ₂₆ N ₂ O ₂ S [M] ⁺ : 358.1715. Found: 358.1710.

[Compound C12]

[Compound D27]

A piperidine compound (Compound D28) was prepared in the same manner as in Example 1, except that the following compound C13 was used instead of the compound C1 (yield 69%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.89 (d, J = 7.5 Hz, 2H), 7.61-7.57 (m, 1H), 7.54-7.51 (m, 2H), 7.26-7.23 (m, 2H) , 6.94 (d, J = 7.0 Hz, 2H), 6.85 (t, J = 7.0 Hz, 1H), 4.75 (s, 1H), 3.61 (d, J = 12.0 Hz, 2H), 3.01 (q, J = 6.7 Hz, 2H), 2.63 (t, J = 11.8 Hz, 2H), 1.68 (d, J = 12.5 Hz, 2H), 1.44 (t, J = 5.8 Hz, 3H), 1.34 (s, 2H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.4, 139.9, 132.8, 129.3, 129.2, 127.1, 119.9, 116.8, 50.2, 40.7, 36.1, 32.7, 31.7. IR : v 3283, 3060, 2924, 2850, 2811, 1598, 1495, 1463, 1159, 1124, 1094 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₉ H ₂₄ N ₂ O ₂ S [M] ⁺ : 344.1558. Found: 344.1559.

[Compound C13]

[Compound D28]

A piperidine compound (Compound D29) was prepared in the same manner as in Example 1, except that the following compound C14 was used instead of the compound C1 (yield 46%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.89 (q, J = 4.7 Hz, 2H), 7.26 (t, J = 8.0 Hz, 2H), 7.20 (t, J = 8.5 Hz, 2H), 6.98 ( d, J = 7.0 Hz, 2H), 6.87 (t, J = 7.0 Hz, 1H), 4.70 (s, 1H), 3.62 (d, J = 12.5 Hz, 2H), 3.01 (q, J = 6.7 Hz, 2H), 2.67 (t, J = 11.8 Hz, 2H), 1.71 (d, J = 12.5 Hz, 2H), 1.47 (t, J = 6.0 Hz, 3H), 1.39 (s, 2H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 165.1 (d, 1C, J _CF = 253.1 Hz), 151.1, 136.0, 129.8 (d, 1C, J _CF = 9.0 Hz), 129.2, 120.3, 117.0, 116.4 ( d, 1C, J _CF = 22.4 Hz), 50.4, 40.8, 36.1, 32.7, 31.6. IR : v 3283, 3060, 2924, 2852, 2813, 1597, 1494, 1463, 1153, 1092 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₉ H ₂₃ FN ₂ O ₂ S [M] ⁺ : 362.1464. Found: 362.1464.

[Compound C14]

[Compound D29]

A piperidine compound (Compound D30) was prepared in the same manner as in Example 1, except that the following compound C15 was used instead of the compound C1 (yield 33%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 8.21 (d, J = 7.5 Hz, 2H), 7.58 (t, J = 7.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.37- 7.33 (m, 4H), 7.02 (d, J = 8.0 Hz, 2H), 6.95 (t, J = 7.5 Hz, 1H), 4.38 (t, J = 7.8 Hz, 2H), 3.73 (d, J = 12.5) Hz, 2H), 2.73 (t, J = 11.5 Hz, 2H), 1.93-1.86 (m, 4H), 1.58-1.49 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.8, 140.4, 129.2, 125.8, 123.1, 120.6, 119.6, 119.0, 116.7, 108.6, 50.0, 40.7, 35.4, 33.8, 32.3. IR : v 3052, 2922, 1597, 1483, 1451, 1325, 1189, 1152, 1128, 749 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₅ H ₂₆ N ₂ [M] ⁺ : 354.2096. Found: 354.2093.

[Compound C15]

[Compound D30]

A piperidine compound (Compound D31) was prepared in the same manner as in Example 1 (yield 60%), except that the following compound C16 was used instead of the compound C1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.55 (s, 1H), 7.24 (t, J = 8.0 Hz, 2H), 7.07 (s, 1H), 6.93-6.91 (m, 3H), 6.83 (t) , J = 7.2 Hz, 1H), 4.02 (t, J = 7.5 Hz, 2H), 3.66 (d, J = 12.5 Hz, 2H), 2.66 (t, J = 11.5 Hz, 2H), 1.80-1.76 (m) , 4H), 1.46-1.40 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.7, 137.0, 129.2, 129.1, 119.6, 118.8, 116.7, 49.9, 44.7, 37.7, 33.0, 31.9. IR : v 2921, 2848, 2808, 1598, 1496, 1462, 1386, 1109, 758, 693 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₆ H ₂₁ N ₃ [M] ⁺ : 255.1735. Found: 255.1736.

[Compound C16]

[Compound D31]

A piperidine compound (Compound D32) was prepared in the same manner as in Example 1, except that the following compound C17 was used instead of the compound C1 (yield 25%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 9.54 (s, 1H), 7.25-7.22 (m, 2H), 7.11-7.05 (m, 3H), 7.00 (d, J = 7.5 Hz, 1H), 6.93 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 3.96 (t, J = 7.2 Hz, 2H), 3.68 (d, J = 12.5 Hz, 2H), 2.69 (t) , J = 12.0 Hz, 2H), 1.92 (d, J = 11.0 Hz, 2H), 1.76 (q, J = 7.0 Hz, 2H), 1.55-1.43 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 155.4, 151.8, 130.3, 129.1, 128.0, 121.5, 121.4, 119.4, 116.6, 109.6, 107.8, 49.9, 38.5, 34.8, 33.4, 32.0. IR : v 3176, 3060, 2923, 2849, 1694, 1598, 1489, 1378, 1155, 754, 734, 691 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₀ H ₂₃ N ₃ O [M] ⁺ : 321.1841. Found: 321.1838.

[Compound C17]

[Compound D32]

A piperidine compound (Compound D33) was prepared in the same manner as in Example 1, except that the following compound C18 was used instead of the compound C1 (yield 27%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.24 (t, J = 7.8 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.81 (t, J = 7.2 Hz, 1H), 3.64 ( d, J = 12.5 Hz, 2H), 2.66 (t, J = 11.5 Hz, 2H), 2.43-2.40 (m, 6H), 1.78 (d, J = 9.5 Hz, 2H), 1.65 (quin, J = 5.5) Hz, 4H), 1.55-1.51 (m, 2H), 1.45-1.42 (m, 2H), 1.40-1.35 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.9, 129.1, 119.3, 116.3, 57.0, 54.6, 50.0, 34.5, 33.2, 32.3, 25.6, 24.2. IR : v 2928, 2851, 2802, 2849, 1599, 1501, 1463, 1443, 1385, 1153, 756, 691 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₈ H ₂₈ N ₂ [M] ⁺ : 272.2252. Found: 272.2249.

[Compound C18]

[Compound D33]

A piperidine compound (Compound D34) was prepared in the same manner as in Example 1 (yield 30%), except for using the following compound C19 instead of the compound C1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.24 (t, J = 8.0 Hz, 2H), 6.94 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 3.72 ( t, J = 4.5 Hz, 4H), 3.65 (d, J = 12.5 Hz, 2H), 2.68 (t, J = 12.0 Hz, 2H), 2.44 (s, 4H), 2.39 (t, J = 7.5 Hz, 2H), 1.79 (d, J = 12.5 Hz, 2H), 1.50-1.46 (m, 2H), 1.43-1.34 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.9, 129.1, 119.4, 116.6, 67.0, 56.8, 53.9, 50.1, 34.2, 33.3, 32.4. IR : v 2921, 2851, 2806, 1599, 1501, 1462, 1385, 1276, 1235, 1118 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₇ H ₂₆ N ₂ O [M] ⁺ : 274.2045. Found: 274.2042.

[Compound C19]

[Compound D34]

A piperidine compound (Compound D35) was prepared in the same manner as in Example 1, except that Compound C20 was used instead of Compound C1 (yield: 48%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.24 (t, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 3.65 ( d, J = 12.5 Hz, 2H), 2.71-2.64 (m, 10H), 2.41 (t, J = 7.8 Hz, 2H), 1.78 (d, J = 9.5 Hz, 2H), 1.48-1.44 (m, 2H) ), 1.42-1.33 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.9, 129.1, 119.4, 116.6, 57.0, 55.2, 50.1, 34.3, 33.2, 32.4, 28.1. IR : v 2919, 2849, 2805, 1599, 1598, 1500, 1462, 1385, 1280, 1223, 1127 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₇ H ₂₆ N ₂ S [M] ⁺ : 290.1817. Found: 290.1816.

[Compound C20]

[Compound D35]

A piperidine compound (Compound D36) was prepared in the same manner as in Example 1 (yield 50%), except that the following compound C21 was used instead of the compound C1. ¹ H NMR (500 MHz, CDCl ₃ ): δ 9.53 (s, 1H), 7.23 (t, J = 8.0 Hz, 2H), 6.91 (d, J = 8.5 Hz, 2H), 6.82 (t, J = 7.5) Hz, 1H), 3.65 (d, J = 12.0 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 2.70-2.65 (m, 5H), 1.86 (q, J = 7.5 Hz, 2H), 1.79 (d, J = 12.5 Hz, 2H), 1.60-1.52 (m, 1H), 1.41 (qd, J = 12.1, 3.8 Hz, 2H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.6, 129.1, 119.6, 116.6, 49.8, 47.3, 33.5, 32.9, 32.3, 31.8.

[Compound C21]

[Compound D36]

A piperidine compound (Compound D37) was prepared in the same manner as in Example 1, except that the following compound C22 was used instead of the compound C1 (yield 65%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.82 (s, 1H), 7.78 (dd, J = 8.5, 1.0 Hz, 2H), 7.43 (t, J = 7.5 Hz, 2H), 7.35 (t, J ) = 7.2 Hz, 1H), 7.24 (t, J = 7.5 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 4.54 (t, J = 7.0) Hz, 2H), 3.67 (d, J = 12.0 Hz, 2H), 2.66 (t, J = 11.5 Hz, 2H), 2.01 (q, J = 6.7 Hz, 2H), 1.86 (d, J = 9.0 Hz, 2H). 1.48-1.39 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.8, 147.6, 130.8, 130.5, 129.1, 128.9, 128.4, 125.9, 119.5, 116.6, 52.7, 49.9, 36.3, 33.1, 31.8. IR : v 2923, 2852, 2805, 1598, 1495, 1458, 1378, 977, 767, 692 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₄ N ₄ [M] ⁺ : 332.2001. Found: 332.2000.

[Compound C22]

[Compound D37]

A piperidine compound (Compound D38) was prepared in the same manner as in Example 1, except that the following compound C23 was used instead of the compound C1 (yield 26%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.84 (dd, J = 8.5, 1.0 Hz, 2H), 7.76 (s, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.34 (t, J ) = 7.5 Hz, 1H), 7.25 (t, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.84 (t, J = 7.2 Hz, 1H), 4.46 (t, J = 7.2) Hz, 2H), 3.66 (d, J = 12.5 Hz, 2H), 2.67 (t, J = 11.5 Hz, 2H), 1.93 (q, J = 6.8 Hz, 2H), 1.84 (d, J = 9.0 Hz, 2H), 1.49-1.37 (m, 3H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.7, 147.9, 130.7, 129.1, 128.9, 128.2, 125.7, 119.6, 119.4, 116.7, 49.8, 48.0, 37.0, 33.0, 31.8. IR : v 3082, 2926, 2851, 2809, 1598, 1501, 1461, 1383, 1149, 765 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₂₁ H ₂₄ N ₄ [M] ⁺ : 332.2001. Found: 332.2001.

[Compound C23]

[Compound D38]

A piperidine compound (compound D39) was prepared in the same manner as in Example 1, except that the following compound C24 was used instead of the compound C1 and the reaction temperature was carried out at 110° C. (yield 65%). ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.26 (t, J = 8.0 Hz, 2H), 6.95 (d, J = 8.5 Hz, 2H), 6.84 (t, J = 7.2 Hz, 1H), 3.68 ( d, J = 12.5 Hz, 2H), 3.36 (t, J = 6.8 Hz, 2H), 2.70 (td, J = 12.3, 2.5 Hz, 2H), 1.80 (d, J = 13.0 Hz, 2H), 1.62- 1.50 (m, 3H), 1.39 (qd, J = 12.1, 3.5 Hz, 2H). ¹³ C NMR (125 MHz, CDCl ₃ ): δ 151.8, 129.1, 119.5, 116.7, 50.0, 49.0, 35.3, 33.1, 32.0. IR : v 2924, 2847, 2808, 2094, 1598, 1495, 1462, 1386, 1245, 1188, 692 cm ^-1 ; HRMS (EI ⁺ ) calcd. for C ₁₃ H ₁₈ N ₄ [M] ⁺ : 230.1531 Found: 230.1533.

[Compound C24]

[Compound D39]

In Examples 1 and 9 to 46, piperidine compounds having various functional groups were synthesized. Through this, it can be confirmed that the synthesis method according to the present invention can be used to prepare piperidine compounds having various functional groups. In particular, in the prior art, at least three or more synthesis steps were required to synthesize the piperidine compound, but the method for preparing the piperidine compound of the present invention can synthesize the piperidine compound in one step, thereby reducing the process time. It is possible to shorten and easily achieve low cost, and at the same time improve the yield. Furthermore, the piperidine compound can be synthesized under mild reaction conditions without using expensive reagents such as transition metals.

3. Applications of Synthesis

Compound D38 was prepared by using the following Scheme 2 (click reaction) for compound D39 prepared in Example 46 (yield 98%)

[Scheme 2]

Referring to Example 47, it can be confirmed that a compound for a desired use can be easily synthesized through an additional reaction of piperidine synthesized by the method for preparing piperidine of the present application. In particular, in the case of the piperidine compound of the present application, novel piperidine compounds that have not been previously disclosed can be provided, and thus can be applied to various fields such as pharmaceuticals, pesticides, and materials.

The foregoing description of the present application is for illustration, and those of ordinary skill in the art to which the present application pertains will understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present application. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a distributed manner, and likewise components described as distributed may also be implemented in a combined form.

The scope of the present application is indicated by the following claims rather than the above detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present application.

Claims (10)

delete delete delete delete delete a compound represented by the following formula (3);
a compound represented by the following formula (4);
a compound represented by the following formula (5) or a compound represented by the following formula (6); and
A method for preparing a piperidine compound comprising reacting a synthetic reagent in a solvent:
[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

In Formulas 3 to 6,
R ₁ is any one selected from the group consisting of H, methyl, butyl, turtle-butyl, methyl ether, F, Cl, and combinations thereof,
R ₂ and R ₃ are each independently H, optionally substituted linear or branched C ₁ -C ₂₀ alkyl, optionally substituted C ₆ -C ₂₀ aryl, or optionally substituted C ₃ -C ₂₀ is a ring,
A ₁ is an optionally substituted 5-membered unsaturated or aromatic ring, an optionally substituted 6-membered unsaturated or aromatic ring, an optionally substituted 5-membered unsaturated or aromatic heterocyclic ring and an optionally substituted 6-membered unsaturated or aromatic heterocyclic ring At least one ring selected from the group consisting of rings, or a polycyclic ring in which two or more rings selected from the group are fused,
The hetero ring includes at least one selected from the group consisting of N, O and S,
The substitution is one selected from the group consisting of C ₁ -C ₆ alkyl, C ₆ -C ₂₀ aryl, O, S, Se, F, Cl, Br, I, and combinations thereof.
7. The method of claim 6,
The synthetic reagent comprises a material selected from the group consisting of a fluorine source, K ₂ CO ₃ , Cs ₂ CO ₃ , Na ₂ CO ₃ , Li ₂ CO ₃ , Rb ₂ CO ₃ , 18-crown-6, and combinations thereof A method for producing a piperidine compound.
8. The method of claim 7,
The fluorine source comprises a material selected from the group consisting of CsF, NaF, LiF, KF, RbF, AgF, ZnF ₂ , MgF ₂ , tetrabutylammonium fluoride, tetrabutylammonium difluorotriphenylsilicate, and combinations thereof The method for producing a piperidine compound.
7. The method of claim 6,
The reaction is made under a temperature of 60 ℃ to 110 ℃, the method for producing a piperidine compound.
7. The method of claim 6,
The method for producing a piperidine compound, wherein the reaction is made for 10 to 30 hours.

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