JP2009196979A - Amide compound, and its use in controlling plant disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a compound having excellent efficacy in controlling plant diseases. <P>SOLUTION: An amide compound represented by formula (I) [in the formula, R<SP>1</SP>represents a hydrogen atom or a fluorine atom, and R<SP>2</SP>represents a straight chain 3-8C alkenyl group or a straight chain 3-8C alkynyl group] has excellent control activity against plant diseases. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an amide compound and its use for controlling plant diseases.

  Many compounds have been developed and put into practical use as active ingredients of plant disease control agents. However, these compounds may not always show sufficient control efficacy.

International Publication No. 2005/033079 Pamphlet

  The present invention provides a compound having an excellent control effect against plant diseases.

〔式中、Ｒ¹は水素原子またはフッ素原子を表し、Ｒ²は直鎖Ｃ３−Ｃ８アルケニル基または直鎖Ｃ３−Ｃ８アルキニル基を表す。〕
で示されるアミド化合物（以下、本発明化合物と記す場合もある。）が植物病害に対して優れた防除効力を有することを見出し、本発明に至った。
すなわち、本発明は以下の〔１〕〜〔１０〕のものである。
〔１〕 式（Ｉ）

〔式中、Ｒ¹は水素原子またはフッ素原子を表し、Ｒ²は直鎖Ｃ３−Ｃ８アルケニル基または直鎖Ｃ３−Ｃ８アルキニル基を表す。〕
で示されるアミド化合物。
〔２〕 Ｒ¹がフッ素原子でありである〔１〕記載のアミド化合物。
〔３〕 Ｒ¹が水素原子である〔１〕記載のアミド化合物。
〔４〕 Ｒ²が直鎖Ｃ５−Ｃ７アルケニル基である〔１〕〜〔３〕いずれか一項記載のアミド化合物。
〔５〕 Ｒ²が４−ペンテニル基、５−ヘキセニル基又は６−ヘプテニル基である〔１〕〜〔３〕いずれか一項記載のアミド化合物。
〔６〕 Ｒ²が直鎖Ｃ５−Ｃ７アルキニル基である〔１〕〜〔３〕いずれか一項記載のアミド化合物。
〔７〕 Ｒ²が４−ペンチニル基、５−ヘキシニル基又は６−ヘプチニル基である〔１〕〜〔３〕いずれか一項記載のアミド化合物。
〔８〕 〔１〕〜〔７〕いずれか一項記載のアミド化合物と担体とを含有する植物病害防除剤（以下、本発明防除剤と記す場合もある。）。
〔９〕 〔１〕〜〔７〕いずれか一項記載のアミド化合物の有効量を植物又は土壌に処理する工程を有する植物病害の防除方法（以下、本発明防除方法と記す場合もある。）。
〔１０〕 植物病害を防除するための〔１〕〜〔７〕いずれか一項記載のアミド化合物の使用。 As a result of studies to find a compound having an excellent control effect against plant diseases, the present inventors have found that the following formula (I)

[Wherein, R ¹ represents a hydrogen atom or a fluorine atom, and R ² represents a linear C3-C8 alkenyl group or a linear C3-C8 alkynyl group. ]
The present inventors have found that an amide compound represented by the formula (hereinafter sometimes referred to as the compound of the present invention) has an excellent control effect against plant diseases.
That is, the present invention includes the following [1] to [10].
[1] Formula (I)

[Wherein, R ¹ represents a hydrogen atom or a fluorine atom, and R ² represents a linear C3-C8 alkenyl group or a linear C3-C8 alkynyl group. ]
An amide compound represented by
[2] The amide compound according to [1], wherein R ¹ is a fluorine atom.
[3] The amide compound according to [1], wherein R ¹ is a hydrogen atom.
[4] The amide compound according to any one of [1] to [3], wherein R ² is a linear C5-C7 alkenyl group.
[5] The amide compound according to any one of [1] to [3], wherein R ² is a 4-pentenyl group, a 5-hexenyl group, or a 6-heptenyl group.
[6] The amide compound according to any one of [1] to [3], wherein R ² is a linear C5-C7 alkynyl group.
[7] The amide compound according to any one of [1] to [3], wherein R ² is a 4-pentynyl group, a 5-hexynyl group or a 6-heptynyl group.
[8] A plant disease control agent comprising the amide compound according to any one of [1] to [7] and a carrier (hereinafter sometimes referred to as the present control agent).
[9] A method for controlling plant diseases comprising a step of treating an effective amount of the amide compound according to any one of [1] to [7] to a plant or soil (hereinafter sometimes referred to as the present control method). .
[10] Use of the amide compound according to any one of [1] to [7] for controlling plant diseases.

  According to the present invention, plant diseases can be controlled.

In the compound of the present invention, the straight chain C3-C8 alkenyl group represented by R ² means a C3-C8 alkenyl group in which the carbon chain is not branched. The straight chain C3-C8 alkynyl group represented by R ² means a C3-C8 alkynyl group having no branching in the carbon chain.

In the compound of the present invention, the straight chain C3-C8 alkenyl group represented by R ² means a C3-C8 alkenyl group in which the carbon chain is not branched. The straight chain C3-C8 alkynyl group represented by R ² means a C3-C8 alkynyl group having no branching in the carbon chain.

Examples of the linear C3-C8 alkenyl group represented by R ² include a propenyl group, a linear butenyl group, a linear pentenyl group, a linear hexenyl group, a linear heptenyl group, and a linear octenyl group. Examples of the propenyl group include 2-propenyl group, examples of the linear butenyl group include 2-butenyl group and 3-butenyl group, and examples of the linear pentenyl group include 2-pentenyl group, 3- Examples of the linear hexenyl group include a 2-hexenyl group, a 3-hexenyl group, a 4-hexenyl group, and a 5-hexenyl group. As the linear heptenyl group, Examples thereof include 2-heptenyl group, 3-heptenyl group, 4-heptenyl group, 5-heptenyl group and 6-heptenyl group. Examples of the linear octenyl group include 2-octenyl group, 3-octenyl group and 4-octenyl group. Group, 5-octenyl group, 6-octenyl group and 7-octenyl group.

Examples of the linear C3-C8 alkynyl group represented by R ² include a propynyl group, a linear butynyl group, a linear pentynyl group, a linear hexynyl group, a linear heptynyl group, and a linear octynyl group. Examples of the propynyl group include 2-propynyl group, examples of the linear butynyl group include 2-butynyl group and 3-butynyl group, and examples of the linear pentynyl group include 2-pentynyl group, 3- Examples include a pentynyl group and a 4-pentynyl group. Examples of the linear hexynyl group include a 2-hexynyl group, a 3-hexynyl group, a 4-hexynyl group, and a 5-hexynyl group. Examples include 2-heptynyl group, 3-heptynyl group, 4-heptynyl group, 5-heptynyl group, and 6-heptynyl group. Examples of the linear octynyl group include 2-octynyl group and 3-octynyl group. Group, 4-octynyl group, 5-octynyl group, 6-octynyl group and 7-octynyl group.

Preferred examples of the linear C3-C8 alkenyl group represented by R ² include a linear pentenyl group, a linear hexenyl group, and a linear heptenyl group, and more preferred are a 4-pentenyl group, a 5-hexenyl group, and 6- A heptenyl group is mentioned.

Preferred examples of the linear C3-C8 alkynyl group represented by R ² include a linear pentynyl group, a linear hexynyl group, and a linear heptynyl group, and more preferred are a 4-pentynyl group, a 5-hexynyl group, and a 6- A heptynyl group is mentioned.

  As an aspect of this invention compound, the following are mentioned, for example.

An amide compound represented by formula (I), wherein R ¹ is a hydrogen atom, and R ² is a linear C3-C8 alkenyl group;
An amide compound represented by formula (I), wherein R ¹ is a hydrogen atom and R ² is a linear C5-C7 alkenyl group;
An amide compound in which R ¹ is a hydrogen atom and R ² is a 4-pentenyl group, a 5-hexenyl group or a 6-heptenyl group in the formula (I);
An amide compound represented by formula (I), wherein R ¹ is a fluorine atom and R ² is a linear C3-C8 alkenyl group;
An amide compound represented by formula (I), wherein R ¹ is a fluorine atom and R ² is a linear C5-C7 alkenyl group;
An amide compound in which R ¹ is a fluorine atom and R ² is a 4-pentenyl group, a 5-hexenyl group or a 6-heptenyl group in the formula (I);
An amide compound represented by formula (I), wherein R ¹ is a hydrogen atom and R ² is a linear C3-C8 alkynyl group;
An amide compound represented by formula (I), wherein R ¹ is a hydrogen atom and R ² is a linear C5-C7 alkynyl group;
An amide compound in which R ¹ is a hydrogen atom and R ² is a 4-pentynyl group, a 5-hexynyl group or a 6-heptynyl group in the formula (I);
An amide compound represented by formula (I), wherein R ¹ is a fluorine atom, and R ² is a linear C3-C8 alkynyl group;
An amide compound in which R ¹ is a fluorine atom and R ² is a linear C5-C7 alkynyl group in formula (I); and in formula (I), R ¹ is a fluorine atom and R ² is 4-pentynyl. Amide compound which is a group, 5-hexynyl group or 6-heptynyl group.

  The compound of the present invention can be produced, for example, by the following (Production Method 1), (Production Method 2) or (Production Method 3).

〔式中、Ｒ¹およびＲ²は前記と同じ意味を表す。〕
該反応は、通常溶媒の存在下で行われる。
該反応に用いられる溶媒としては、例えばテトラヒドロフラン（以下、ＴＨＦと記す。）、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル（以下、ＭＴＢＥと記す。）等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド（以下、ＤＭＦと記す。）等の酸アミド類、ジメチルスルホキシド（以下、ＤＭＳＯと記す。）等のスルホキシド類、ピリジン等の含窒素芳香族化合物類等及びこれらの混合物が挙げられる。
該反応に用いられる縮合剤としては、１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（以下、ＷＳＣと記す。）及び１，３−ジシクロヘキシルカルボジイミド等のカルボジイミド類、（ベンゾトリアゾール−１−イルオキシ）トリス（ジメチルアミノ）ホスホニウムヘキサフルオロホスフェート（以下、ＢＯＰ試薬と記す。）等が挙げられる。
該反応では化合物（ＩＩ）１モルに対して化合物（ＩＩＩ）が通常０．５〜３モルの割合、化合物（ＩＩ）１モルに対して脱水縮合剤が通常１〜５モルの割合で用いられる。
該反応の反応温度は、通常−２０℃〜１４０℃の範囲である。該反応の反応時間は通常１〜２４時間の範囲である。
反応終了後は、反応混合物に水を加えた際、固体が析出した場合は、濾過することにより本発明化合物を単離することができる。反応混合物に水を加えた際に固体が析出しない場合は、反応混合物と水との混合物を有機溶媒で抽出し、有機層を乾燥、濃縮することにより、本発明化合物を単離することができる。単離された本発明化合物をクロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 1)
The compound of the present invention can be produced by reacting compound (II), (III) or a salt thereof (for example, hydrochloride and hydrobromide) and a condensing agent.

[Wherein, R ¹ and R ² represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as tetrahydrofuran (hereinafter referred to as THF), ethylene glycol dimethyl ether, tert-butyl methyl ether (hereinafter referred to as MTBE), hexane, heptane, octane and the like. Aliphatic hydrocarbons, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, N, N-dimethylformamide (hereinafter, And acid amides such as dimethyl sulfoxide (hereinafter referred to as DMSO), nitrogen-containing aromatic compounds such as pyridine, and the like, and mixtures thereof.
Examples of the condensing agent used in the reaction include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (hereinafter referred to as WSC) and carbodiimides such as 1,3-dicyclohexylcarbodiimide, (benzotriazole- 1-yloxy) tris (dimethylamino) phosphonium hexafluorophosphate (hereinafter referred to as BOP reagent) and the like.
In the reaction, compound (III) is usually used in a proportion of 0.5 to 3 moles per mole of compound (II), and a dehydrating condensing agent is usually used in a proportion of 1 to 5 moles per mole of compound (II). .
The reaction temperature of the reaction is usually in the range of -20 ° C to 140 ° C. The reaction time is usually in the range of 1 to 24 hours.
After completion of the reaction, when water is added to the reaction mixture, if a solid is precipitated, the compound of the present invention can be isolated by filtration. When solid does not precipitate when water is added to the reaction mixture, the compound of the present invention can be isolated by extracting the mixture of the reaction mixture and water with an organic solvent, and drying and concentrating the organic layer. . The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.

〔式中、Ｒ¹およびＲ²は前記と同じ意味を表す。〕
該反応は、通常溶媒の存在下で行われる。
該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類及びこれらの混合物が挙げられる。
該反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム等のアルカリ金属炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
該反応では化合物（ＩＶ）１モルに対して化合物（ＩＩＩ）が通常０．５〜３モルの割合、化合物（ＩＶ）１モルに対して塩基が通常１〜５モルの割合で用いられる。
該反応の反応温度は通常−２０℃〜１００℃の範囲である。該反応の反応時間は通常０．１〜２４時間の範囲である。
反応終了後は、反応混合物に水を加えた際、固体が析出した場合は、濾過することにより本発明化合物を単離することができる。反応混合物に水を加えた際に固体が析出しない場合は、反応混合物と水との混合物を有機溶媒で抽出し、有機層を乾燥、濃縮することにより、本発明化合物を単離することができる。単離された本発明化合物を、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 2)
The compound of the present invention is produced by reacting compound (IV) or a hydrochloride thereof with compound (III) or a salt thereof (for example, hydrochloride and hydrobromide) in the presence of a base. can do.

[Wherein, R ¹ and R ² represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and chlorobenzene. Examples thereof include halogenated hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, and mixtures thereof.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. Can be mentioned.
In the reaction, compound (III) is usually used in a proportion of 0.5 to 3 mol per mol of compound (IV), and base is usually used in a proportion of 1 to 5 mol per mol of compound (IV).
The reaction temperature of the reaction is usually in the range of -20 ° C to 100 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, when water is added to the reaction mixture, if a solid is precipitated, the compound of the present invention can be isolated by filtration. When solid does not precipitate when water is added to the reaction mixture, the compound of the present invention can be isolated by extracting the mixture of the reaction mixture and water with an organic solvent, and drying and concentrating the organic layer. . The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.

〔式中、Ｒ¹およびＲ²は前記と同じ意味を表し、Ｌは塩素原子、臭素原子、ヨウ素原子、メタンスルホニルオキシ基、トリフルオロメタンスルホニルオキシ基又はｐ−トルエンスルホニルオキシ基を表す。〕
該反応は、通常溶媒の存在下で行われる。
該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、アセトニトリル等のニトリル類、ＤＭＦ等の酸アミド類、ＤＭＳＯ等のスルホキシド類、アセトン、メチルエチルケトン、メチルイソブチルケトン等のケトン類、水及びこれらの混合物が挙げられる。
該反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム、炭酸セシウム等のアルカリ金属炭酸塩類、水酸化ナトリウム等のアルカリ金属水酸化物類、水素化ナトリウム等のアルカリ金属水素化物類等が挙げられる。
該反応では、化合物（Ｖ）１モルに対して化合物（ＶＩ）が通常１〜１０モルの割合、化合物（Ｖ）１モルに対して塩基が通常１〜５モルの割合で用いられる。
該反応の反応温度は通常−２０℃〜１００℃の範囲である。該反応の反応時間は通常０．１〜２４時間の範囲である。
反応終了後は、反応混合物に水を加えた際、固体が析出した場合は、濾過することにより本発明化合物を単離することができる。反応混合物に水を加えた際に固体が析出しない場合は、反応混合物と水との混合物を有機溶媒で抽出し、有機層を乾燥、濃縮することにより、本発明化合物を単離することができる。単離された本発明化合物を、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 3)
The compound of the present invention can be produced by reacting compound (V) with compound (VI) in the presence of a base.

[Wherein, R ¹ and R ² represent the same meaning as described above, and L represents a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, or a p-toluenesulfonyloxy group. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, nitriles such as acetonitrile, DMF, and the like. Acid amides, sulfoxides such as DMSO, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, water, and mixtures thereof.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate, alkali metal hydroxides such as sodium hydroxide, alkali metal hydrides such as sodium hydride, and the like. .
In this reaction, compound (VI) is usually used in a proportion of 1 to 10 mol per mol of compound (V), and base is usually used in a proportion of 1 to 5 mol per mol of compound (V).
The reaction temperature of the reaction is usually in the range of -20 ° C to 100 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, when water is added to the reaction mixture, if a solid is precipitated, the compound of the present invention can be isolated by filtration. When solid does not precipitate when water is added to the reaction mixture, the compound of the present invention can be isolated by extracting the mixture of the reaction mixture and water with an organic solvent, and drying and concentrating the organic layer. . The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.

  Compound (V) can be produced, for example, by the following (Synthesis Method 1) or (Synthesis Method 2).

〔式中、Ｒ¹は前記と同じ意味を表す。〕
該反応は、通常溶媒の存在下で行われる。
該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、ＤＭＦ等の酸アミド類、ＤＭＳＯ等のスルホキシド類、ピリジン等の含窒素芳香族化合物類等及びこれらの混合物が挙げられる。
該反応に用いられる脱水縮合剤としては、ＷＳＣ及び１，３−ジシクロヘキシルカルボジイミド等のカルボジイミド類、ＢＯＰ試薬等が挙げられる。
該反応では、化合物（ＩＩ）１モルに対して化合物（ＶＩＩ）が通常０．５〜３モルの割合、化合物（ＩＩ）１モルに対して脱水縮合剤が通常１〜５モルの割合で用いられる。
該反応の反応温度は、通常−２０℃〜１４０℃の範囲である。該反応の反応時間は通常１〜２４時間の範囲である。
反応終了後は、反応混合物に水を加えた際、固体が析出した場合は、濾過することにより化合物（Ｖ）を単離することができる。反応混合物に水を加えた際に固体が析出しない場合は、反応混合物と水との混合物を有機溶媒で抽出し、有機層を乾燥、濃縮することにより、化合物（Ｖ）を単離することができる。単離された化合物（Ｖ）を、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Synthesis method 1)
Compound (V) can be produced by reacting compound (II), compound (VII) or a salt thereof (for example, hydrochloride and hydrobromide) and a condensing agent.

[Wherein R ¹ represents the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and chlorobenzene. Halogenated hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, acid amides such as DMF, sulfoxides such as DMSO, nitrogen-containing aromatic compounds such as pyridine, and mixtures thereof Can be mentioned.
Examples of the dehydrating condensing agent used in the reaction include WSC and carbodiimides such as 1,3-dicyclohexylcarbodiimide, BOP reagent and the like.
In this reaction, compound (VII) is usually used in a proportion of 0.5 to 3 mol per mol of compound (II), and a dehydration condensing agent is usually used in a proportion of 1 to 5 mol per mol of compound (II). It is done.
The reaction temperature of the reaction is usually in the range of -20 ° C to 140 ° C. The reaction time is usually in the range of 1 to 24 hours.
After completion of the reaction, when water is added to the reaction mixture, if a solid is precipitated, the compound (V) can be isolated by filtration. If solid does not precipitate when water is added to the reaction mixture, the compound (V) can be isolated by extracting the mixture of the reaction mixture and water with an organic solvent, drying and concentrating the organic layer. it can. The isolated compound (V) can be further purified by chromatography, recrystallization and the like.

〔式中、Ｒ¹は前記と同じ意味を表す。〕
該反応は、通常溶媒の存在下で行われる。
該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類及びこれらの混合物が挙げられる。
該反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム等のアルカリ金属炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
該願王では、化合物（ＩＶ）１モルに対して化合物（ＶＩＩ）が通常０．５〜１モルの割合、化合物（ＩＶ）１モルに対して塩基が通常１〜５モルの割合で用いられる。
該反応の反応温度は通常−２０℃〜１００℃の範囲である。該反応の反応時間は通常０．１〜２４時間の範囲である。
反応終了後は、反応混合物に水を加えた際、固体が析出した場合は、濾過することにより化合物（Ｖ）を単離することができる。反応混合物に水を加えた際に固体が析出しない場合は、反応混合物と水との混合物を有機溶媒で抽出し、有機層を乾燥、濃縮することにより、化合物（Ｖ）を単離することができる。単離された化合物（Ｖ）を、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Synthesis method 2)
Compound (V) is obtained by reacting compound (IV) or a hydrochloride thereof with compound (VII) or a salt thereof (for example, hydrochloride and hydrobromide) in the presence of a base. It can also be manufactured.

[Wherein R ¹ represents the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and chlorobenzene. Examples thereof include halogenated hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, and mixtures thereof.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. Can be mentioned.
In the application, the compound (VII) is usually used in a proportion of 0.5 to 1 mol per 1 mol of the compound (IV), and the base is usually used in a proportion of 1 to 5 mol per 1 mol of the compound (IV). .
The reaction temperature of the reaction is usually in the range of -20 ° C to 100 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, when water is added to the reaction mixture, if a solid is precipitated, the compound (V) can be isolated by filtration. If solid does not precipitate when water is added to the reaction mixture, the compound (V) can be isolated by extracting the mixture of the reaction mixture and water with an organic solvent, drying and concentrating the organic layer. it can. The isolated compound (V) can be further purified by chromatography, recrystallization and the like.

Specific examples of the compound of the present invention include the following compounds.
N- [2-fluoro-3- (2-propenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (2-butenyloxy) -2-fluorophenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-butenyloxy) -2-fluorophenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (2-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (3-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (4-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (2-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (3-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (4-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (5-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (2-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (3-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (4-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (5-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (6-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (2-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (3-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (4-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (4-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (6-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (7-octenyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,

N- [3- (2-propenyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (2-butenyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (3-butenyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (2-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (4-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (2-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (4-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (5-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (2-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (4-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (5-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (6-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (2-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (4-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (5-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (6-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (7-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,

N- [2-fluoro-3- (2-propynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (2-butynyloxy) -2-fluorophenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-butynyloxy) -2-fluorophenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (2-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (3-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (4-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (2-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (3-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (4-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (5-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (2-heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (3-heptynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [2-fluoro-3- (4-heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (5-heptynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [2-fluoro-3- (6-heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (2-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (3-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (4-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [2-fluoro-3- (5-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (6-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide;
N- [2-fluoro-3- (7-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,

N- [3- (2-propynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (2-butynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (3-butynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (2-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (4-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (2-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (3-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (4-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (5-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridine carboxamide,
N- [3- (2-Heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-Heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (4-Heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (5-Heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (6-Heptynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (2-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (3-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (4-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (5-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide,
N- [3- (6-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide and N- [3- (7-octynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide.

  The control agent of the present invention contains the compound of the present invention and a carrier. Examples of the carrier include a solid carrier, a liquid carrier, and a gas carrier. The control agent of the present invention is usually further added with formulation adjuvants such as surfactants, sticking agents, dispersants, stabilizers, etc., wettable powder, wettable powder, flowable powder, granules, dry flowable powder, emulsion, It is formulated into aqueous liquids, oils, smokes, aerosols, microcapsules and the like. The present control agent contains the present compound in a weight ratio of usually 0.1 to 99%, preferably 0.2 to 90%.

  Examples of the solid support include clays (for example, kaolin, diatomaceous earth, synthetic hydrous silicon oxide, wax clay, bentonite, acid clay, talc), and other inorganic minerals (for example, sericite, quartz powder, sulfur powder, activated carbon). , Calcium carbonate, hydrated silica) and the like. Examples of the liquid carrier include water, alcohols (eg, methanol, ethanol), ketones (eg, acetone, methyl ethyl ketone), aromatic hydrocarbons (eg, benzene, toluene, xylene, ethylbenzene, methylnaphthalene), fat Aliphatic or alicyclic hydrocarbons (eg, n-hexane, cyclohexanone, kerosene), esters (eg, ethyl acetate, butyl acetate), nitriles (eg, acetonitrile, isobutylronitrile), ethers (eg, dioxane) , Diisopropyl ether), acid amides (for example, dimethylformamide, dimethylacetamide), halogenated hydrocarbons (for example, dichloroethane, trichloroethylene, carbon tetrachloride) and the like.

  Surfactants include, for example, alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and their polyoxyethylene compounds, polyoxyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives. Etc.

  Other formulation adjuvants include, for example, fixing agents, dispersants, thickeners, wetting agents, extenders, antioxidants, specifically casein, gelatin, polysaccharides (eg starch, arabic gum, cellulose derivatives). , Alginic acid), lignin derivatives, bentonite, saccharides, synthetic water-soluble polymers (for example, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acids), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl- 4-methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oil, mineral oil, fatty acid or ester thereof, and the like.

  As a method of applying the present control agent for controlling plant diseases, for example, treatment to grown plants such as foliage spraying, treatment to plant cultivation areas such as soil treatment, treatment to seeds such as seed disinfection Etc.

Moreover, this invention control agent can be mixed or used together with another fungicide, insecticide, acaricide, nematicide, plant growth regulator, fertilizer or soil conditioner.
Such other fungicides include, for example, propiconazole, prothioconazole, triazimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, triflumi Azole fungicides such as sol, tetraconazole, microbutanyl, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, vitertanol, imazalyl, flutriahol; fenpropimorph, tridemorph, fenpropidin, etc. Cyclic amine bactericidal compounds: benzimidazole bactericidal compounds such as carbendazim, benomyl, thiabendazole, thiophanate methyl; procymidone; ciprodini Pyrimethanyl; Dietofencarb; Thiuram; Fluazinam; Mancozeb; Iprodione; Vinclozoline; Chlorotalonyl; Captan; Mepanipyrim; Fenpiclonyl; Fludioxonil; Xylostrobin; pyraclostrobin; dimoxystrobin; pyribencarb; spiroxamine; quinoxyphene; fenhexamide; famoxadone; fenamidone; zoxamide; ethaboxam; Metolaphenone; fluopyran; bixafen; cyflufenamide and Kinajido and the like.

  The application amount of the present control agent varies depending on weather conditions, formulation form, application time, application method, application location, target disease, target crop, etc., but per 10 ares in terms of the amount of the present compound in the present control agent, Usually 1 to 500 g, preferably 2 to 200 g. Emulsions, wettable powders, suspensions and the like are usually diluted with water and applied. In this case, the concentration of the compound of the present invention after dilution is usually 0.0005 to 2% by weight, preferably 0.005 to 1. The powder, granules and the like are usually applied as they are without dilution. In the seed treatment, the amount of the compound of the present invention in the control agent of the present invention is generally 0.001 to 100 g, preferably 0.01 to 50 g per 1 kg of seed.

  The control agent of the present invention can be used as a plant disease control agent in agricultural land such as fields, paddy fields, lawns, orchards. The control agent of the present invention can control diseases of the farmland in the farmland where the following “crop” and the like are cultivated.

Agricultural crops: corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, peanuts, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, tobacco, vegetables, solanaceous vegetables (eggplant, tomato, pepper, pepper, potato) Cucumber, pumpkin, zucchini, watermelon, melon, etc., cruciferous vegetables (radish, turnip, horseradish, kohlrabi, cabbage, cabbage, mustard, broccoli, cauliflower, etc.), asteraceae (burdock, Shungiku, artichokes, lettuce, etc.), liliaceae vegetables (leek, onion, garlic, asparagus), celeryaceae vegetables (carrot, parsley, celery, red pepper, etc.), red crustacean vegetables (spinach, chard, etc.) (Perilla, mint, basil ), Strawberry, sweet potato, yam, taro, etc.,
Bridegroom,
Foliage plant,
Fruit trees; pears (apples, pears, Japanese pears, quince, quince, etc.), nuclear fruits (peaches, plums, nectarines, ume, sweet cherry, apricots, prunes, etc.), citrus (satsuma mandarin, orange, lemon, lime, grapefruit) ), Nuts (chestnut, walnut, hazel, almond, pistachio, cashew nut, macadamia nut, etc.), berries (blueberry, cranberry, blackberry, raspberry, etc.), grape, oyster, olive, loquat, banana, coffee, Date palm, coconut palm, etc.
Trees other than fruit trees: Cha, mulberry, flowering trees, street trees (ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, redwood, fu, sycamore, zelkova, black bean, peach tree, Tsuga, rat, pine, Spruce, yew) etc.

  The above-mentioned “plant” refers to HPPD inhibitors such as isoxaflutol, ALS inhibitors such as imazetapyr and thifensulfuron methyl, EPSP synthase inhibitors such as glyphosate, glutamine synthetase inhibitors such as glufosinate, cetoxydim and the like. Also included are plants that have been imparted resistance to herbicides such as acetyl-CoA carboxylase inhibitors, PPO inhibitors such as flumioxazin, bromoxynil, dicamba, 2,4-D by classical breeding methods or genetic engineering techniques.

  Examples of “plants” that have been given resistance by classical breeding methods include rapeseed, wheat, sunflower, and rice that are resistant to imidazolinone-based ALS-inhibiting herbicides such as imazetapil under the trade name Clearfield®. Already sold. Similarly, there are soybeans that are resistant to sulfonylurea ALS-inhibiting herbicides such as thifensulfuron methyl by classical breeding methods, and are already sold under the trade name of STS soybeans. Similarly, SR corn and the like are examples of plants to which tolerance has been imparted to acetyl CoA carboxylase inhibitors such as trion oxime and aryloxyphenoxypropionic acid herbicides by classical breeding methods. Plants tolerant to acetyl CoA carboxylase inhibitors have been identified as Proceedings of the National Academy of Sciences of the United States of America (Proc. Natl. Acad. Sci. USA) 87, 7175-7179 (1990). A mutant acetyl CoA carboxylase resistant to an acetyl CoA carboxylase inhibitor has been reported in Weed Science 53, 728-746 (2005). A plant resistant to an acetyl-CoA carboxylase inhibitor can be produced by introducing a mutation into plant acetyl-CoA carboxylase or introducing a mutation associated with imparting resistance into the plant. Further, a base substitution mutation-introduced nucleic acid represented by chimera plastic technology (Gura T. 1999. Repairing the Genome's Spelling Mistakes. Science 285: 316-318.) By introducing a site-specific amino acid substitution mutation into a gene or ALS gene or the like, a plant resistant to an acetyl CoA carboxylase inhibitor or an ALS inhibitor can be produced.

  Examples of plants to which resistance has been imparted by genetic recombination techniques include glyphosate-resistant maize, soybean, cotton, rapeseed, sugar beet varieties, and are already available under trade names such as Roundup Ready (RoundupReady (registered trademark)), AgriureGT, etc. Sold. Similarly, there are corn, soybean, cotton and rapeseed varieties that are resistant to glufosinate by genetic recombination technology, and are already sold under trade names such as Liberty Link (registered trademark). Similarly, bromoxynyl-resistant cotton by gene recombination technology is already sold under the trade name BXN.

  Examples of toxins expressed in such genetically modified plants include insecticidal proteins derived from Bacillus cereus and Bacillus popirie; Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 and Cry9C derived from Bacillus thuringiensis Insecticidal proteins such as δ-endotoxin, VIP1, VIP2, VIP3 or VIP3A; nematode-derived insecticidal proteins; toxins produced by animals such as scorpion toxins, spider toxins, bee toxins or insect-specific neurotoxins; filamentous fungal toxins; plants Lectin; Agglutinin; Protease inhibitors such as trypsin inhibitor, serine protease inhibitor, patatin, cystatin, papain inhibitor; lysine, corn-RIP, abrin, ruffin, saporin, bryodin, etc. Ribosome inactivating protein (RIP); steroid metabolic enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glucosyltransferase, cholesterol oxidase; ecdysone inhibitor; HMG-CoA reductase; sodium channel, calcium channel inhibitor, etc. Ion channel inhibitors; juvenile hormone esterase; diuretic hormone receptor; stilbene synthase; bibenzyl synthase; chitinase;

  Examples of toxins expressed in such genetically modified plants include insecticidal proteins derived from Bacillus cereus and Bacillus popirie; Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 and Cry9C derived from Bacillus thuringiensis Insecticidal proteins such as δ-endotoxin, VIP1, VIP2, VIP3 or VIP3A; nematode-derived insecticidal proteins; toxins produced by animals such as scorpion toxins, spider toxins, bee toxins or insect-specific neurotoxins; filamentous fungal toxins; plants Lectin; Agglutinin; Protease inhibitors such as trypsin inhibitor, serine protease inhibitor, patatin, cystatin, papain inhibitor; lysine, corn-RIP, abrin, ruffin, saporin, bryodin, etc. Ribosome inactivating protein (RIP); steroid metabolic enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glucosyltransferase, cholesterol oxidase; ecdysone inhibitor; HMG-CoA reductase; sodium channel, calcium channel inhibitor, etc. Ion channel inhibitors; juvenile hormone esterase; diuretic hormone receptor; stilbene synthase; bibenzyl synthase; chitinase;

  Further, as toxins expressed in such a genetically modified plant, Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, Cry9C, Cry34Ab or Cry35Ab or other δ-endotoxin proteins, VIP1, VIP2, VIP3 or VIP3A, etc. Also included are insecticidal protein hybrid toxins, partially defective toxins, and modified toxins. Hybrid toxins are produced by new combinations of different domains of these proteins using recombinant techniques. As a toxin lacking a part, Cry1Ab lacking a part of the amino acid sequence is known. In the modified toxin, one or more amino acids of the natural toxin are substituted.

Examples of these toxins and recombinant plants capable of synthesizing these toxins are described in EP-A-0374753, WO93 / 07278, WO95 / 34656, EP-A-0427529, EP-A-451878, WO03 / 052073 and the like. Has been.

  Toxins contained in these recombinant plants particularly confer resistance to Coleoptera, Hemiptera pests, Diptera pests, Lepidoptera pests and nematodes.

  In addition, genetically modified plants that contain one or more insecticidal pest resistance genes and express one or more toxins are already known and some are commercially available. Examples of these transgenic plants include YieldGard® (a corn variety that expresses Cry1Ab toxin), YieldGuard Rootworm® (a corn variety that expresses Cry3Bb1 toxin), YieldGard Plus® (Cry1Ab and Cry3Bb1) Corn varieties expressing toxin), Herculex I® (corn varieties expressing phosphinotricin N-acetyltransferase (PAT) to confer resistance to Cry1Fa2 toxin and glufosinate), NuCOTN33B® ( Cotton varieties expressing Cry1Ac toxin), Bollgard I (registered trademark) (cotton varieties expressing Cry1Ac toxin), Bollgard II (registered trademark) Cotton varieties expressing Cry1Ac and Cry2Ab toxin), VIPCOT (registered trademark) (cotton varieties expressing VIP toxin), NewLeaf (registered trademark potato varieties expressing Cry3A toxin), NatureGard (registered trademark) Agurisure (registered trademark) (Trademark) GT Advantage (GA21 glyphosate resistant trait), Agurisure (registered trademark) CB Advantage (Bt11 corn borer (CB) trait), Protecta (registered trademark), and the like.

The “plant” includes those imparted with an ability to produce an anti-pathogenic substance having a selective action using a gene recombination technique.
As examples of anti-pathogenic substances, PR proteins and the like are known (PRPs, EP-A-0392225). Such anti-pathogenic substances and genetically modified plants that produce them are described in EP-A-0392225, WO95 / 33818, EP-A-0353191, and the like.

  Examples of anti-pathogenic substances expressed in such genetically modified plants include, for example, sodium channel inhibitors, calcium channel inhibitors (KP1, KP4, KP6 toxins produced by viruses, etc.). Ion channel inhibitor; stilbene synthase; bibenzyl synthase; chitinase; glucanase; PR protein; peptide antibiotics, antibiotics having heterocycles, protein factors involved in plant disease resistance (referred to as plant disease resistance gene, WO03 / 000906)) and other anti-pathogenic substances produced by microorganisms. Such anti-pathogenic substances and genetically modified plants that produce them are described in EP-A-0392225, WO95 / 33818, EP-A-0353191, and the like.

  The above “plant” includes plants imparted with useful traits such as oil component modification and amino acid content enhancing traits using genetic recombination techniques. Examples include VISTIVE (registered trademark) (low linolenic soybean with reduced linolenic content), high-lysine (high-oil) corn (corn with increased lysine or oil content), and the like.

  In addition, the above-mentioned classic herbicide traits or herbicide resistance genes, insecticidal pest resistance genes, anti-pathogenic substance production genes, oil traits modification, amino acid content enhancement traits, etc. Combined stack varieties are also included.

  Examples of plant diseases that can be controlled by the present invention include filamentous fungal diseases. Specifically, the following plant diseases can be mentioned.

Rice blast (Magnaporthe grisea), sesame leaf blight (Cochliobolus miyabeanus), blight (Rhizoctonia solani), idiot seedling (Gibberella fujikuroi);
Wheat powdery mildew (Erysiphe graminis), red mold (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivale), rust (Puccinia striiformis, P. graminis, P. recondita, P. hordei), snow Rot (Typhula sp., Micronectriella nivalis), Bare Scarf (Ustilago tritici, U. nuda), Namahusa scab (Tilletia caries), Eye ailment (Pseudocercosporella herpotrichoides), Cloud disease (Rhynchosporium secalis), Leaf blight ( Septoria tritici), blight (Leptosphaeria nodorum), net blotch (Pyrenophora teres Drechsler), blight (Gaeumannomyces graminis);
Citrus spot disease (Diaporthe citri), scab (Elsinoe fawcetti), fruit rot (Penicillium digitatum, P. italicum);
Monilinia mali, apple rot (Valsa ceratosperma), powdery mildew (Podosphaera leucotricha), spotted leaf (Alternaria alternata apple pathotype), black rot (Venturia inaequalis), anthracnose (Glomerella cingulata);
Pear black spot disease (Venturia nashicola, V. pirina), black spot disease (Alternaria alternata Japanese pear pathotype), red star disease (Gymnosporangium haraeanum);
Peach ash scab (Monilinia fructicola), black scab (Cladosporium carpophilum), Phomopsis sp. (Phomopsis sp.);

Grapes black rot (Elsinoe ampelina), late rot (Glomerella cingulata), powdery mildew (Uncinula necator), rust (Phakopsora ampelopsidis), black lot disease (Guignardia bidwellii), downy mildew (Plasmopara viticola);
Oyster anthracnose (Gloeosporium kaki), deciduous leaf disease (Cercospora kaki, Mycosphaerella nawae);
Colletotrichum lagenarium, powdery mildew (Sphaerotheca fuliginea), vine blight (Mycosphaerella melonis), vine split (Fusarium oxysporum), downy mildew (Pseudoperonospora cubensis), plague (Phytophthora sp.) Seedling blight (Pythium sp.);
Tomato ring disease (Alternaria solani), leaf mold (Cladosporium fulvum), plague (Phytophthora infestans);
Eggplant brown spot (Phomopsis vexans), powdery mildew (Erysiphe cichoracearum);
Brassicaceae vegetable black spot (Alternaria japonica), white spot (Cercosporella brassicae);
Leek rust (Puccinia allii), soybean purpura (Cercospora kikuchii), black scab (Elsinoe glycines), black spot (Diaporthe phaseolorum var. Sojae), rust (Phakopsora pachyrhizi)
Green Bean Anthracnose (Colletotrichum lindemthianum)
Groundnut black astringency (Cercospora personata), brown spot (Cercospora arachidicola), white silkworm (Sclerotium rolfsii);
Pea powdery mildew (Erysiphe pisi);
Potato summer plague (Alternaria solani), plague (Phytophthora infestans), half body wilt (Verticillium albo-atrum, V. dahliae, V. nigrescens);
Strawberry powdery mildew (Sphaerotheca humuli);
Tea net blast (Exobasidium reticulatum); white spot (Elsinoe leucospila), ring spot (Pestalotiopsis sp.), Anthracnose (Colletotrichum theae-sinensis)
Tobacco red blight (Alternaria longipes), powdery mildew (Erysiphe cichoracearum), anthracnose (Colletotrichum tabacum), downy mildew (Peronospora tabacina), plague (Phytophthora nicotianae);

Sugar beet brown spot (Cercospora beticola), leaf rot (Thanatephorus cucumeris), root rot (Thanatephorus cucumeris);
Rose scab (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa);
Chrysanthemum brown spot (Septoria chrysanthemi-indici), white rust (Puccinia horiana);
Onion white spot blight (Botrytis cinerea, B. byssoidea, B. squamosa), gray rot (Botrytis alli), sclerotia rot (Botrytis squamosa);
Various crops of gray mold (Botrytis cinerea), mycorrhizal disease (Sclerotinia sclerotiorum); radish black soot (Alternaria brassicicola);
Shiva dollar spot disease (Sclerotinia homeocarpa), Shiva brown patch disease and Rhizoctonia solani; and banana Sigatoka disease (Mycosphaerella fijiensis, Mycosphaerella musicola, Pseudocercospora musae).

  Hereinafter, although this invention is demonstrated in more detail by a manufacture example, a formulation example, a test example, etc., this invention is not limited only to these examples. In addition, a part represents a weight part.

¹H-NMR (CDCl₃) δ: 1.90-1.97 (2H, m), 2.24-2.29 (2H, m), 4.05 (2H, t, J = 6.5 Hz), 4.79 (2H, dd, J = 6.3, 1.0 Hz), 4.99-5.03 (1H, m), 5.05-5.10 (1H, m), 5.81-5.91 (1H, m), 6.89-6.95 (1H, m), 7.01-7.06 (2H, m), 7.70 (1H, dd, J = 8.8, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.5 Hz), 8.53-8.58 (3H, m), 9.05 (1H, dd, J = 4.1, 1.5 Hz). Production Example 1
To a mixture of 0.15 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.087 g of 5-bromo-1-pentene and 3 ml of DMF, 0.21 g of cesium carbonate was added. And stirred at room temperature for 12 hours. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography to give N- [2-fluoro-3- (4-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (1) and 0.15 g was obtained.
Compound (1) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.90-1.97 (2H, m), 2.24-2.29 (2H, m), 4.05 (2H, t, J = 6.5 Hz), 4.79 (2H, dd, J = 6.3, 1.0 Hz), 4.99-5.03 (1H, m), 5.05-5.10 (1H, m), 5.81-5.91 (1H, m), 6.89-6.95 (1H, m), 7.01-7.06 (2H, m), 7.70 (1H, dd, J = 8.8, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.5 Hz), 8.53-8.58 (3H, m), 9.05 (1H, dd, J = 4.1, 1.5 Hz).

¹H-NMR (CDCl₃) δ: 1.53-1.63 (2H, m), 1.81-1.88 (2H, m), 2.11-2.18 (2H, m), 4.04 (2H, t, J = 6.2 Hz), 4.79 (2H, d, J = 6.1 Hz), 4.96-5.06 (2H, m), 5.78-5.89 (1H, m), 6.90-6.94 (1H, m), 7.02-7.05 (2H, m), 7.70 (1H, dd, J = 8.0, 4.1 Hz), 8.41 (1H, d, J = 7.8 Hz), 8.52-8.58 (3H, m), 9.05 (1H, d, J = 3.7 Hz). Production Example 2
To a mixture of 0.20 g N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.14 g 6-bromo-1-hexene and 3 ml DMF, 0.26 g cesium carbonate was added. And stirred at room temperature for 12 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. This solid was washed successively with 15% aqueous sodium hydroxide, water and hexane, and dried under reduced pressure to give N- [2-fluoro-3- (5-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridine. 0.11 g of carboxamide (hereinafter referred to as the present compound (2)) was obtained.
Compound (2) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.53-1.63 (2H, m), 1.81-1.88 (2H, m), 2.11-2.18 (2H, m), 4.04 (2H, t, J = 6.2 Hz), 4.79 (2H, d, J = 6.1 Hz), 4.96-5.06 (2H, m), 5.78-5.89 (1H, m), 6.90-6.94 (1H, m), 7.02-7.05 (2H, m), 7.70 (1H , dd, J = 8.0, 4.1 Hz), 8.41 (1H, d, J = 7.8 Hz), 8.52-8.58 (3H, m), 9.05 (1H, d, J = 3.7 Hz).

¹H-NMR (CDCl₃) δ: 1.46-1.51 (4H, m), 1.81-1.87 (2H, m), 2.06-2.12 (2H, m), 4.03 (2H, t, J = 6.6 Hz), 4.79 (2H, d, J = 6.3 Hz), 4.94-5.03 (2H, m), 5.77-5.87 (1H, m), 6.88-6.94 (1H, m), 7.00-7.06 (2H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, d, J = 7.8 Hz), 8.53-8.58 (3H, m), 9.05 (1H, d, J = 3.2 Hz). Production Example 3
To a mixture of 0.17 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.13 g of 7-bromo-1-heptene and 3 ml of DMF, 0.22 g of cesium carbonate was added. And stirred at room temperature for 12 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. This solid was washed successively with 15% aqueous sodium hydroxide, water and hexane, and dried under reduced pressure to give N- [2-fluoro-3- (6-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide. (Hereinafter referred to as the present compound (3).) 0.13 g was obtained.
Compound (3) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.46-1.51 (4H, m), 1.81-1.87 (2H, m), 2.06-2.12 (2H, m), 4.03 (2H, t, J = 6.6 Hz), 4.79 (2H, d, J = 6.3 Hz), 4.94-5.03 (2H, m), 5.77-5.87 (1H, m), 6.88-6.94 (1H, m), 7.00-7.06 (2H, m), 7.70 (1H , dd, J = 8.5, 4.1 Hz), 8.41 (1H, d, J = 7.8 Hz), 8.53-8.58 (3H, m), 9.05 (1H, d, J = 3.2 Hz).

¹H-NMR (CDCl₃) δ: 1.76 (3.0H, d, J = 6.3 Hz), 4.53 (1.7H, d, J = 6.1 Hz), 4.68 (0.3H, d, J = 6.3 Hz), 4.79 (2.0H, d, J = 6.1 Hz), 5.71-5.79 (1.0H, m), 5.82-5.92 (1.0H, m), 6.89-6.95 (1.0H, m), 7.02-7.04 (2.0H, m), 7.70 (1.0H, dd, J = 8.5, 4.1 Hz), 8.40 (1.0H, d, J = 8.5 Hz), 8.52-8.57 (3.0H, m), 9.05 (1.0H, dd, J = 4.1, 1.5 Hz). Production Example 4
To a mixture of 0.17 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.10 g of 1-bromo-2-butene and 3 ml of DMF, 0.22 g of cesium carbonate was added. And stirred at room temperature for 12 hours. A 15% aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography, and N- [2-fluoro-3- (2-butenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as “N- [2-fluoro-3- (2-butenyloxy) phenyl] methyl”). This is referred to as the present compound (4).) 0.14 g was obtained.
The present compound (4)

¹ H-NMR (CDCl ₃ ) δ: 1.76 (3.0H, d, J = 6.3 Hz), 4.53 (1.7H, d, J = 6.1 Hz), 4.68 (0.3H, d, J = 6.3 Hz), 4.79 (2.0H, d, J = 6.1 Hz), 5.71-5.79 (1.0H, m), 5.82-5.92 (1.0H, m), 6.89-6.95 (1.0H, m), 7.02-7.04 (2.0H, m ), 7.70 (1.0H, dd, J = 8.5, 4.1 Hz), 8.40 (1.0H, d, J = 8.5 Hz), 8.52-8.57 (3.0H, m), 9.05 (1.0H, dd, J = 4.1 , 1.5 Hz).

¹H-NMR (CDCl₃) δ: 1.02 (3H, td, J = 7.5, 2.0 Hz), 2.07-2.19 (2H, m), 4.55 (1H, d, J = 6.1 Hz), 4.67 (1H, d, J = 4.9 Hz), 4.79 (2H, d, J = 6.3 Hz), 5.64-5.94 (2H, m), 6.91-6.95 (1H, m), 7.01-7.05 (2H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.40 (1H, dd, J = 8.5, 1.2 Hz), 8.49-8.57 (3H, m), 9.05 (1H, dd, J = 4.1, 1.5 Hz). Production Example 5
To a mixture of 0.17 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.11 g of 1-bromo-2-pentene and 3 ml of DMF was added 0.22 g of cesium carbonate. And stirred at room temperature for 12 hours. A 15% aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography to give N- [2-fluoro-3- (2-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide ( Hereinafter referred to as the present compound (5).) 0.16 g was obtained.
Compound (5) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.02 (3H, td, J = 7.5, 2.0 Hz), 2.07-2.19 (2H, m), 4.55 (1H, d, J = 6.1 Hz), 4.67 (1H, d , J = 4.9 Hz), 4.79 (2H, d, J = 6.3 Hz), 5.64-5.94 (2H, m), 6.91-6.95 (1H, m), 7.01-7.05 (2H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.40 (1H, dd, J = 8.5, 1.2 Hz), 8.49-8.57 (3H, m), 9.05 (1H, dd, J = 4.1, 1.5 Hz).

¹H-NMR (CDCl₃) δ: 1.84-1.91 (2H, m), 2.20-2.26 (2H, m), 3.97 (2H, t, J = 6.5 Hz), 4.72 (2H, d, J = 6.1 Hz), 4.96-5.00 (1H, m), 5.02-5.08 (1H, m), 5.79-5.89 (1H, m), 6.84 (1H, dd, J = 7.9, 2.3 Hz), 6.95-7.00 (2H, m), 7.28 (1H, t, J = 8.2 Hz), 7.69 (1H, dd, J = 8.5, 4.1 Hz), 8.37-8.40 (1H, m), 8.48 (1H, s), 8.56 (1H, d, J = 8.8 Hz), 8.59 (1H, d, J = 8.8 Hz), 9.05 (1H, dd, J = 4.1, 1.7 Hz). Production Example 6
To a mixture of 0.11 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 69 mg of 5-bromo-1-pentene and 2 ml of DMF, 0.20 g of cesium carbonate was added and stirred at room temperature for 12 hours. did. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography to give N- [3- (4-pentenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (6)). .12 g was obtained.
The present compound (6)

¹ H-NMR (CDCl ₃ ) δ: 1.84-1.91 (2H, m), 2.20-2.26 (2H, m), 3.97 (2H, t, J = 6.5 Hz), 4.72 (2H, d, J = 6.1 Hz ), 4.96-5.00 (1H, m), 5.02-5.08 (1H, m), 5.79-5.89 (1H, m), 6.84 (1H, dd, J = 7.9, 2.3 Hz), 6.95-7.00 (2H, m ), 7.28 (1H, t, J = 8.2 Hz), 7.69 (1H, dd, J = 8.5, 4.1 Hz), 8.37-8.40 (1H, m), 8.48 (1H, s), 8.56 (1H, d, J = 8.8 Hz), 8.59 (1H, d, J = 8.8 Hz), 9.05 (1H, dd, J = 4.1, 1.7 Hz).

¹H-NMR (CDCl₃) δ: 1.52-1.63 (2H, m), 1.75-1.83 (2H, m), 2.08-2.14 (2H, m), 3.97 (2H, t, J = 6.5 Hz), 4.72 (2H, d, J = 6.0 Hz), 4.94-5.05 (2H, m), 5.76-5.86 (1H, m), 6.84 (1H, dd, J = 8.0, 2.2 Hz), 6.95-7.00 (2H, m), 7.26-7.30 (1H, m), 7.69 (1H, dd, J = 8.7, 4.1 Hz), 8.37-8.40 (1H, m), 8.48 (1H, br s), 8.55-8.61 (2H, m), 9.05 (1H, dd, J = 4.1, 1.7 Hz). Production Example 7
To a mixture of 0.20 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.13 g of 6-bromo-1-hexene and 3 ml of DMF, 0.27 g of cesium carbonate was added, Stir for hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration. This solid was washed successively with 15% aqueous sodium hydroxide, water and hexane, dried under reduced pressure, and N-[(5-hexenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present invention). 0.11 g of compound (7) was obtained.
Compound (7) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.52-1.63 (2H, m), 1.75-1.83 (2H, m), 2.08-2.14 (2H, m), 3.97 (2H, t, J = 6.5 Hz), 4.72 (2H, d, J = 6.0 Hz), 4.94-5.05 (2H, m), 5.76-5.86 (1H, m), 6.84 (1H, dd, J = 8.0, 2.2 Hz), 6.95-7.00 (2H, m ), 7.26-7.30 (1H, m), 7.69 (1H, dd, J = 8.7, 4.1 Hz), 8.37-8.40 (1H, m), 8.48 (1H, br s), 8.55-8.61 (2H, m) , 9.05 (1H, dd, J = 4.1, 1.7 Hz).

¹H-NMR (CDCl₃) δ: 1.98 (1H, t, J = 2.7 Hz), 2.02-2.08 (2H, m), 2.45 (2H, td, J = 6.9, 2.6 Hz), 4.15 (2H, t, J = 6.1 Hz), 4.79 (2H, dd, J = 6.2, 1.1 Hz), 6.92-6.97 (1H, m), 7.03-7.05 (2H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.7 Hz), 8.53-8.58 (3H, m), 9.05 (1H, dd, J = 4.1, 1.7 Hz). Production Example 8
To a mixture of 0.20 g N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 29 mg sodium hydride (55% in oil) and 3 ml DMF, 5-chloro-1-pentyne 90 mg was added, and the mixture was stirred at 80 ° C. for 2 hours and then at 100 ° C. for 5 hours. Thereafter, the reaction mixture was cooled to around room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give N- [2-fluoro-3- (4-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (8)). ) 0.18 g was obtained.
Compound (8) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.98 (1H, t, J = 2.7 Hz), 2.02-2.08 (2H, m), 2.45 (2H, td, J = 6.9, 2.6 Hz), 4.15 (2H, t , J = 6.1 Hz), 4.79 (2H, dd, J = 6.2, 1.1 Hz), 6.92-6.97 (1H, m), 7.03-7.05 (2H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.7 Hz), 8.53-8.58 (3H, m), 9.05 (1H, dd, J = 4.1, 1.7 Hz).

¹H-NMR (CDCl₃) δ: 1.72-1.79 (2H, m), 1.93-2.00 (3H, m), 2.30 (2H, td, J = 7.0, 2.7 Hz), 4.07 (2H, t, J = 6.2 Hz), 4.79 (2H, dd, J = 6.3, 1.2 Hz), 6.90-6.94 (1H, m), 7.03-7.04 (2H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.7 Hz), 8.53-8.58 (3H, m), 9.05 (1H, dd, J = 4.1, 1.7 Hz). Production Example 9
To a mixture of 0.20 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 32 mg of sodium hydride (55% in oil) and 3 ml of DMF, 6-chloro-1-hexyne was added. 102 mg was added, and the mixture was stirred at 80 ° C. for 2 hours and then at 100 ° C. for 2 hours. The reaction mixture was then cooled to room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give N- [2-fluoro-3- (5-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (9)). 0.14 g was obtained.
The present compound (9)

¹ H-NMR (CDCl ₃ ) δ: 1.72-1.79 (2H, m), 1.93-2.00 (3H, m), 2.30 (2H, td, J = 7.0, 2.7 Hz), 4.07 (2H, t, J = 6.2 Hz), 4.79 (2H, dd, J = 6.3, 1.2 Hz), 6.90-6.94 (1H, m), 7.03-7.04 (2H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.7 Hz), 8.53-8.58 (3H, m), 9.05 (1H, dd, J = 4.1, 1.7 Hz).

¹H-NMR (CDCl₃) δ: 2.55 (1H, t, J = 2.1 Hz), 4.78-4.81 (4H, m), 7.06-7.12 (3H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, d, J = 8.5 Hz), 8.54-8.57 (3H, m), 9.05 (1H, d, J = 2.7 Hz). Production Example 10
To a mixture of 0.17 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.08 g of propargyl bromide and 3 ml of DMF was added 0.2 g of cesium carbonate, and at room temperature for 12 hours. Stir. A 15% aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography to give N- [2-fluoro-3- (2-propynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide ( Hereinafter referred to as the present compound (10).) 0.16 g was obtained.
Compound (10) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 2.55 (1H, t, J = 2.1 Hz), 4.78-4.81 (4H, m), 7.06-7.12 (3H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, d, J = 8.5 Hz), 8.54-8.57 (3H, m), 9.05 (1H, d, J = 2.7 Hz).

¹H-NMR (CDCl₃)δ: 1.12 (3H, t, J = 7.4 Hz), 2.17-2.26 (2H, m), 4.75-4.76 (2H, m), 4.79 (2H, d, J = 6.3 Hz), 7.03-7.10 (3H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.2 Hz), 8.52-8.58 (3H, m), 9.05 (1H, dd, J = 4.0, 1.6 Hz). Production Example 11
To a mixture of 0.17 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.11 g of 1-bromo-2-pentyne and 3 ml of DMF, 0.22 g of cesium carbonate was added. And stirred at room temperature for 12 hours. A 15% aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography to give N- [2-fluoro-3- (2-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide. (Hereinafter referred to as the present compound (11).) 0.26 g was obtained.
Compound (11) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.12 (3H, t, J = 7.4 Hz), 2.17-2.26 (2H, m), 4.75-4.76 (2H, m), 4.79 (2H, d, J = 6.3 Hz ), 7.03-7.10 (3H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, dd, J = 8.5, 1.2 Hz), 8.52-8.58 (3H, m), 9.05 ( (1H, dd, J = 4.0, 1.6 Hz).

¹H-NMR (CDCl₃) δ: 1.95 (1H, t, J = 2.7 Hz), 1.98-2.03 (2H, m), 2.40 (2H, td, J = 7.0, 2.7 Hz), 4.07 (2H, t, J = 6.1 Hz), 4.72 (2H, d, J = 6.1 Hz), 6.86 (1H, dd, J = 8.2, 1.8 Hz), 6.96-6.97 (1H, m), 7.00 (1H, d, J = 7.6 Hz), 7.29 (1H, t, J = 7.8 Hz), 7.69 (1H, dd, J = 8.5, 4.1 Hz), 8.37-8.40 (1H, m), 8.49 (1H, s), 8.56 (1H, dd, J = 8.8, 0.5 Hz), 8.59 (1H, d, J = 8.8 Hz), 9.05 (1H, dd, J = 4.1, 1.5 Hz). Production Example 12
To a mixture of 0.20 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 34 mg of sodium hydride (55% in oil) and 3 ml of DMF, 90 mg of 5-chloro-1-pentyne was added, The mixture was stirred at 80 ° C. for 2 hours and then at 100 ° C. for 4 hours. The reaction mixture was then cooled to room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as N- [3- (4-pentynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (12)). ) 0.21 g was obtained.
The present compound (12)

¹ H-NMR (CDCl ₃ ) δ: 1.95 (1H, t, J = 2.7 Hz), 1.98-2.03 (2H, m), 2.40 (2H, td, J = 7.0, 2.7 Hz), 4.07 (2H, t , J = 6.1 Hz), 4.72 (2H, d, J = 6.1 Hz), 6.86 (1H, dd, J = 8.2, 1.8 Hz), 6.96-6.97 (1H, m), 7.00 (1H, d, J = 7.6 Hz), 7.29 (1H, t, J = 7.8 Hz), 7.69 (1H, dd, J = 8.5, 4.1 Hz), 8.37-8.40 (1H, m), 8.49 (1H, s), 8.56 (1H, dd, J = 8.8, 0.5 Hz), 8.59 (1H, d, J = 8.8 Hz), 9.05 (1H, dd, J = 4.1, 1.5 Hz).

¹ H-NMR (CDCl₃) δ: 1.68-1.75 (2H, m), 1.87-1.94 (2H, m), 1.96 (1H, t, J = 2.7 Hz), 2.27 (2H, td, J = 7.0, 2.6 Hz), 3.99 (2H, t, J = 6.2 Hz), 4.71 (2H, d, J = 6.1 Hz), 6.84 (1H, dd, J = 7.8, 2.2 Hz), 6.95-6.96 (1H, m), 6.99 (1H, d, J = 8.3 Hz), 7.28 (1H, t, J = 8.3 Hz), 7.69 (1H, dd, J = 8.5, 4.1 Hz), 8.37-8.40 (1H, m), 8.48 (1H, s), 8.56 (1H, dd, J = 8.7, 0.6 Hz), 8.59 (1H, d, J = 8.8 Hz), 9.05 (1H, dd, J = 4.1, 1.7 Hz). Production Example 13
To a mixture of 0.20 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 34 mg of sodium hydride (55% in oil) and 3 ml of DMF, 109 mg of 6-chloro-1-hexyne was added, The mixture was stirred at 80 ° C. for 2 hours and then at 100 ° C. for 2 hours. The reaction mixture was then cooled to room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and N- [3- (5-hexynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (13)) 0 .19 g was obtained.
Compound (13) of the present invention

¹ H-NMR (CDCl ₃ ) δ: 1.68-1.75 (2H, m), 1.87-1.94 (2H, m), 1.96 (1H, t, J = 2.7 Hz), 2.27 (2H, td, J = 7.0, 2.6 Hz), 3.99 (2H, t, J = 6.2 Hz), 4.71 (2H, d, J = 6.1 Hz), 6.84 (1H, dd, J = 7.8, 2.2 Hz), 6.95-6.96 (1H, m) , 6.99 (1H, d, J = 8.3 Hz), 7.28 (1H, t, J = 8.3 Hz), 7.69 (1H, dd, J = 8.5, 4.1 Hz), 8.37-8.40 (1H, m), 8.48 ( 1H, s), 8.56 (1H, dd, J = 8.7, 0.6 Hz), 8.59 (1H, d, J = 8.8 Hz), 9.05 (1H, dd, J = 4.1, 1.7 Hz).

1H-NMR (DMSO-D6) δ: 4.60-4.66 (4H, m), 5.28 (1H, d, J = 10.5 Hz), 5.42 (1H, d, J = 17.6 Hz), 6.00-6.11 (1H, m), 6.93-6.99 (1H, m), 7.03-7.10 (2H, m), 7.91 (1H, dd, J = 8.7, 4.0 Hz), 8.39 (1H, d, J = 8.8 Hz), 8.53 (1H, d, J = 8.5 Hz), 8.62 (1H, d, J = 8.8 Hz), 9.10-9.14 (1H, m), 9.48 (1H, t, J = 5.9 Hz). Production Example 14
N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide 0.30 g, 3-chloro-1-propene 0.23 g and DMF 5 ml were mixed with potassium carbonate 0.0.42 g. And stirred at room temperature for 5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give N- [2-fluoro-3- (2-propenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (14)). 0.26 g was obtained.
The present compound (14)

1H-NMR (DMSO-D6) δ: 4.60-4.66 (4H, m), 5.28 (1H, d, J = 10.5 Hz), 5.42 (1H, d, J = 17.6 Hz), 6.00-6.11 (1H, m ), 6.93-6.99 (1H, m), 7.03-7.10 (2H, m), 7.91 (1H, dd, J = 8.7, 4.0 Hz), 8.39 (1H, d, J = 8.8 Hz), 8.53 (1H, d, J = 8.5 Hz), 8.62 (1H, d, J = 8.8 Hz), 9.10-9.14 (1H, m), 9.48 (1H, t, J = 5.9 Hz).

1H-NMR (DMSO-D6) δ: 4.52-4.53 (4H, m), 5.18-5.24 (1H, m), 5.32-5.39 (1H, m), 5.96-6.05 (1H, m), 6.80-6.85 (1H, m), 6.92-6.97 (2H, m), 7.20-7.25 (1H, m), 7.89 (1H, dd, J = 8.5, 4.1 Hz), 8.39 (1H, d, J = 8.8 Hz), 8.51 (1H, d, J = 8.5 Hz), 8.60 (1H, d, J = 8.8 Hz), 9.10 (1H, dd, J = 4.1, 1.5 Hz), 9.49 (1H, t, J = 6.2 Hz). Production Example 15
0.59 g of potassium carbonate was added to a mixture of 0.30 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.33 g of 3-chloro-1-propene and 3 ml of DMF, and 5% at room temperature. Stir for hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as N- [3- (2-propenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (15)). ) 0.27 g was obtained.
The present compound (15)

1H-NMR (DMSO-D6) δ: 4.52-4.53 (4H, m), 5.18-5.24 (1H, m), 5.32-5.39 (1H, m), 5.96-6.05 (1H, m), 6.80-6.85 ( 1H, m), 6.92-6.97 (2H, m), 7.20-7.25 (1H, m), 7.89 (1H, dd, J = 8.5, 4.1 Hz), 8.39 (1H, d, J = 8.8 Hz), 8.51 (1H, d, J = 8.5 Hz), 8.60 (1H, d, J = 8.8 Hz), 9.10 (1H, dd, J = 4.1, 1.5 Hz), 9.49 (1H, t, J = 6.2 Hz).

1H-NMR (DMSO-D6) δ: 1.34-1.41 (4H, m), 1.63-1.73 (2H, m), 1.97-2.04 (2H, m), 3.93 (2H, t, J = 6.4 Hz), 4.54 (2H, d, J = 6.3 Hz), 4.87-5.01 (2H, m), 5.70-5.83 (1H, m), 6.80 (1H, d, J = 7.5 Hz), 6.90-6.95 (2H, m), 7.23 (1H, t, J = 8.1 Hz), 7.91 (1H, dd, J = 8.6, 4.2 Hz), 8.40 (1H, d, J = 8.7 Hz), 8.52 (1H, d, J = 8.7 Hz), 8.62 (1H, d, J = 8.7 Hz), 9.09-9.13 (1H, m), 9.51 (1H, t, J = 6.4 Hz). Production Example 16
To a mixture of 0.30 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.38 g of 7-bromo-1-heptene and 3 ml of DMF, 0.70 g of cesium carbonate was added, and 5% at room temperature was added. Stir for hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and N- [3- (6-heptenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (16)). 0.33 g was obtained.
Compound (16) of the present invention

1H-NMR (DMSO-D6) δ: 1.34-1.41 (4H, m), 1.63-1.73 (2H, m), 1.97-2.04 (2H, m), 3.93 (2H, t, J = 6.4 Hz), 4.54 (2H, d, J = 6.3 Hz), 4.87-5.01 (2H, m), 5.70-5.83 (1H, m), 6.80 (1H, d, J = 7.5 Hz), 6.90-6.95 (2H, m), 7.23 (1H, t, J = 8.1 Hz), 7.91 (1H, dd, J = 8.6, 4.2 Hz), 8.40 (1H, d, J = 8.7 Hz), 8.52 (1H, d, J = 8.7 Hz), 8.62 (1H, d, J = 8.7 Hz), 9.09-9.13 (1H, m), 9.51 (1H, t, J = 6.4 Hz).

1H-NMR (DMSO-D6) δ: 1.25-1.42 (6H, m), 1.64-1.71 (2H, m), 1.95-2.02 (2H, m), 3.92 (2H, t, J = 6.5 Hz), 4.54 (2H, d, J = 6.3 Hz), 4.89-5.00 (2H, m), 5.72-5.82 (1H, m), 6.81 (1H, d, J = 8.0 Hz), 6.92-6.95 (2H, m), 7.23 (1H, t, J = 8.0 Hz), 7.90 (1H, dd, J = 8.5, 4.1 Hz), 8.40 (1H, d, J = 8.8 Hz), 8.53 (1H, d, J = 7.8 Hz), 8.62 (1H, d, J = 8.8 Hz), 9.10-9.13 (1H, m), 9.50 (1H, t, J = 6.3 Hz). Production Example 17
To a mixture of 0.30 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.41 g of 8-bromo-1-octene and 3 ml of DMF, 0.70 g of cesium carbonate was added, and 5% at room temperature was added. Stir for hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as N- [3- (7-octenyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (17)). .) 0.34 g was obtained.
The present compound (17)

1H-NMR (DMSO-D6) δ: 1.25-1.42 (6H, m), 1.64-1.71 (2H, m), 1.95-2.02 (2H, m), 3.92 (2H, t, J = 6.5 Hz), 4.54 (2H, d, J = 6.3 Hz), 4.89-5.00 (2H, m), 5.72-5.82 (1H, m), 6.81 (1H, d, J = 8.0 Hz), 6.92-6.95 (2H, m), 7.23 (1H, t, J = 8.0 Hz), 7.90 (1H, dd, J = 8.5, 4.1 Hz), 8.40 (1H, d, J = 8.8 Hz), 8.53 (1H, d, J = 7.8 Hz), 8.62 (1H, d, J = 8.8 Hz), 9.10-9.13 (1H, m), 9.50 (1H, t, J = 6.3 Hz).

1H-NMR (DMSO-D6) δ: 3.52-3.54 (1H, m), 4.55 (2H, d, J = 6.3 Hz), 4.76-4.78 (2H, m), 6.87-6.91 (1H, m), 6.97-7.01 (2H, m), 7.25-7.29 (1H, m), 7.90 (1H, dd, J = 8.5, 4.1 Hz), 8.40 (1H, d, J = 8.8 Hz), 8.53 (1H, d, J = 8.5 Hz), 8.62 (1H, d, J = 8.8 Hz), 9.10-9.13 (1H, m), 9.52 (1H, t, J = 6.3 Hz). Production Example 18
To a mixture of 0.30 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide, 0.26 g of 3-bromo-1-propyne and 3 ml of DMF, 0.30 g of potassium carbonate was added, and the mixture was stirred at room temperature. Stir for hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and described as N- [3- (2-propynyloxy) phenyl] methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as the present compound (18)). ) 0.27 g was obtained.
Compound (18) of the present invention

1H-NMR (DMSO-D6) δ: 3.52-3.54 (1H, m), 4.55 (2H, d, J = 6.3 Hz), 4.76-4.78 (2H, m), 6.87-6.91 (1H, m), 6.97 -7.01 (2H, m), 7.25-7.29 (1H, m), 7.90 (1H, dd, J = 8.5, 4.1 Hz), 8.40 (1H, d, J = 8.8 Hz), 8.53 (1H, d, J = 8.5 Hz), 8.62 (1H, d, J = 8.8 Hz), 9.10-9.13 (1H, m), 9.52 (1H, t, J = 6.3 Hz).

Next, production of an intermediate of the compound of the present invention will be shown as a reference production example.

¹H-NMR (CDCl₃) δ: 4.80 (2H, d, J = 6.6 Hz), 5.47 (1H, s), 6.94-7.04 (3H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.41 (1H, dd, J = 8.7, 1.6 Hz), 8.51 (1H, s), 8.57 (2H, s), 9.06 (1H, dd, J = 4.1, 1.7 Hz). Reference production example 1
To a mixture of 0.35 g of [1,5] naphthyridine-2-carboxylic acid, 0.46 g of 2-fluoro-3-hydroxybenzylamine hydrobromide, 0.5 ml of pyridine and 5 ml of DMF, 0.43 g of WSC was added at room temperature. Stir for 8 hours. Water was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography, so as to obtain 0.25 g of N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide.
N- (2-fluoro-3-hydroxyphenyl) methyl-2- [1,5] naphthyridine carboxamide

¹ H-NMR (CDCl ₃ ) δ: 4.80 (2H, d, J = 6.6 Hz), 5.47 (1H, s), 6.94-7.04 (3H, m), 7.70 (1H, dd, J = 8.5, 4.1 Hz ), 8.41 (1H, dd, J = 8.7, 1.6 Hz), 8.51 (1H, s), 8.57 (2H, s), 9.06 (1H, dd, J = 4.1, 1.7 Hz).

¹H-NMR (CDCl₃) δ: 4.70 (2H, d, J = 6.3 Hz), 5.19 (1H, s), 6.79 (1H, dd, J = 7.8, 2.5 Hz), 6.92 (1H, s), 6.97 (1H, d, J = 7.5 Hz), 7.25 (1H, t, J = 7.8 Hz), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.38 (1H, dd, J = 8.6, 1.6 Hz), 8.51 (1H, s), 8.55 (2H, s), 9.05 (1H, dd, J = 4.1, 1.7 Hz). Reference production example 2
A mixture of 0.42 g of 3-hydroxybenzylamine hydrochloride, 0.3 g of [1,5] naphthyridine-2-carboxylic acid, 0.43 g of WSC, 0.5 ml of pyridine and 5 ml of DMF was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography, so as to obtain 0.29 g of N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide.
N- (3-hydroxyphenyl) methyl-2- [1,5] naphthyridine carboxamide

¹ H-NMR (CDCl ₃ ) δ: 4.70 (2H, d, J = 6.3 Hz), 5.19 (1H, s), 6.79 (1H, dd, J = 7.8, 2.5 Hz), 6.92 (1H, s), 6.97 (1H, d, J = 7.5 Hz), 7.25 (1H, t, J = 7.8 Hz), 7.70 (1H, dd, J = 8.5, 4.1 Hz), 8.38 (1H, dd, J = 8.6, 1.6 Hz) ), 8.51 (1H, s), 8.55 (2H, s), 9.05 (1H, dd, J = 4.1, 1.7 Hz).

¹H-NMR (DMSO-d₆) δ: 3.89 (2H, q, J = 5.6 Hz), 6.79-6.82 (1H, m), 6.88-6.91 (2H, m), 7.18 (1H, t, J = 7.7 Hz), 8.51 (3H, s), 9.72 (1H, s). Reference production example 3
A mixture of 20 g of 3-hydroxybenzaldehyde, 200 ml of 2-propanol, 16 g of pyridine and 15 g of hydroxylamine hydrochloride was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. Water was added to the residue and extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give 26 g of 3-hydroxybenzaldehyde oxime.
A mixture of 25 g of 3-hydroxybenzaldehyde oxime and 1.3 g of 5% palladium carbon and 300 ml of ethanol was stirred at room temperature for 3 hours under a hydrogen atmosphere of about 1 atm. The reaction mixture was filtered through Celite®. The filtrate was concentrated under reduced pressure. The obtained residue, 200 ml of acetonitrile and 28 g of concentrated hydrochloric acid were mixed at 0 ° C., and the resulting solid was collected by filtration. The solid was washed with acetonitrile and dried under reduced pressure to obtain 20 g of 3-hydroxybenzylamine hydrochloride.
3-hydroxybenzylamine hydrochloride

¹ H-NMR (DMSO-d ₆ ) δ: 3.89 (2H, q, J = 5.6 Hz), 6.79-6.82 (1H, m), 6.88-6.91 (2H, m), 7.18 (1H, t, J = 7.7 Hz), 8.51 (3H, s), 9.72 (1H, s).

¹H-NMR (CDCl₃) δ: 3.00 (3H, s), 3.91 (3H, s), 5.30 (2H, s), 6.96-7.14 (3H, m). Reference production example 4
4.5 g of 2-fluoro-3-methoxybenzyl alcohol, 2.9 ml of methanesulfonyl chloride and 50 ml of THF were mixed and stirred at 0 ° C. To the mixture was added 6.0 ml of triethylamine, and the mixture was stirred at 0 ° C. for 30 minutes and then at room temperature for 2 hours. Ethyl acetate was added to the reaction mixture, followed by filtration through Celite (registered trademark). Water was added to the filtrate and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 6.9 g of (2-fluoro-3-methoxyphenyl) methylmethanesulfonate.
(2-Fluoro-3-methoxyphenyl) methylmethanesulfonate

¹ H-NMR (CDCl ₃ ) δ: 3.00 (3H, s), 3.91 (3H, s), 5.30 (2H, s), 6.96-7.14 (3H, m).

¹H-NMR (CDCl₃) δ: 3.87 (3H, s), 4.94 (2H, s), 6.86-6.90 (2H, m), 6.98-7.02 (1H, m), 7.73 (2H, dd, J = 5.4, 3.0 Hz), 7.86 (2H, dd, J = 5.4, 3.0 Hz). Reference production example 5
6.7 g of (2-fluoro-3-methoxyphenyl) methylmethanesulfonate, 5.3 g of potassium phthalimide, and 60 ml of DMF were mixed and stirred at 70 ° C. for 4 hours. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water, dilute hydrochloric acid and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was washed with hexane to obtain 5.8 g of N- (2-fluoro-3-methoxyphenyl) methylphthalimide.
N- (2-Fluoro-3-methoxyphenyl) methylphthalimide

¹ H-NMR (CDCl ₃ ) δ: 3.87 (3H, s), 4.94 (2H, s), 6.86-6.90 (2H, m), 6.98-7.02 (1H, m), 7.73 (2H, dd, J = 5.4, 3.0 Hz), 7.86 (2H, dd, J = 5.4, 3.0 Hz).

¹H-NMR (DMSO-d₆) δ: 3.85 (3H, s), 4.03 (2H, q, J = 5.3 Hz), 7.13-7.23 (3H, m), 8.60 (3H, br s). Reference production example 6
To a mixture of 7.7 g of N- (2-fluoro-3-methoxyphenyl) methylphthalimide and 30 ml of ethanol, 1.63 g of hydrazine monohydrate was added dropwise and heated to reflux for 4 hours. The reaction mixture was then cooled to room temperature. Water was added to the reaction mixture, and the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue and filtered. Ethyl acetate was added to the obtained filtrate, and 15% aqueous sodium hydroxide solution was added until the aqueous layer of the mixture reached pH 11, and the mixture was separated into two layers. Concentrated hydrochloric acid was added to the organic layer, and the mixture was concentrated under reduced pressure to obtain 4.5 g of 2-fluoro-3-methoxybenzylamine hydrochloride.
2-Fluoro-3-methoxybenzylamine hydrochloride

¹ H-NMR (DMSO-d ₆ ) δ: 3.85 (3H, s), 4.03 (2H, q, J = 5.3 Hz), 7.13-7.23 (3H, m), 8.60 (3H, br s).

¹H-NMR (CDCl₃) δ: 3.90 (3H, s), 6.96-7.00 (1H, m), 7.03-7.12 (1H, m), 7.30-7.33 (1H, m), 7.64-7.78 (1H, m), 8.39 (1H, s). Reference production example 7
To a mixed solution of 15.4 g of 2-fluoro-3-methoxybenzaldehyde, 30 ml of THF and 3 ml of water, 24 ml of pyridine was added dropwise, and hydroxylamine hydrochloride 13.8 was added under ice cooling. Stir at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure until the total volume became about half. Water was added to the mixture and extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give 16 g of 2-fluoro-3-methoxybenzaldehyde oxime.
2-Fluoro-3-methoxybenzaldehyde oxime

¹ H-NMR (CDCl ₃ ) δ: 3.90 (3H, s), 6.96-7.00 (1H, m), 7.03-7.12 (1H, m), 7.30-7.33 (1H, m), 7.64-7.78 (1H, m), 8.39 (1H, s).

Reference production example 8
To a mixed solution of 2.4 g of 10% palladium carbon, 8.3 ml of 10N hydrochloric acid and 200 ml of ethanol, 12.8 g of 2-fluoro-3-methoxybenzaldehyde oxime was added, and the mixture was stirred at room temperature for 3 hours in a hydrogen atmosphere of about 1 atm. . The reaction mixture was then filtered through Celite®. The filtrate was concentrated under reduced pressure to obtain 8.2 g of 2-fluoro-3-methoxybenzylamine hydrochloride.

¹H-NMR (CDCl₃) δ: 1.55 (2H, br s), 3.89 (3H, s), 3.90 (2H, br s), 6.86-6.91 (2H, m), 7.02-7.06 (1H, m). Reference production example 9
To a mixed solution of 10% palladium carbon 1.8 g, water 10 ml, 10N hydrochloric acid 6.5 ml and ethanol 50 ml, a mixed solution of 10 g of 2-fluoro-3-methoxybenzaldehyde and 80 ml of ethanol was added, and then 5.4 g of hydroxylamine hydrochloride Was added. Stir at room temperature for 2 hours. This mixture was stirred at room temperature for 3 hours under a hydrogen atmosphere of about 1 atm. The reaction mixture was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure. Water was added to the residue and extracted with chloroform. A 15% aqueous sodium hydroxide solution was added until the pH of the resulting aqueous layer reached 11, and the mixture was extracted with chloroform. The organic layer was dried over potassium carbonate and concentrated under reduced pressure to obtain 8.0 g of 2-fluoro-3-methoxybenzylamine.
2-Fluoro-3-methoxybenzylamine

¹ H-NMR (CDCl ₃ ) δ: 1.55 (2H, br s), 3.89 (3H, s), 3.90 (2H, br s), 6.86-6.91 (2H, m), 7.02-7.06 (1H, m) .

¹H-NMR (DMSO-d₆) δ: 4.04 (2H, q, J = 5.5 Hz), 6.90-6.94 (1H, m), 6.97-7.06 (2H, m), 8.23 (3H, br s), 10.05 (1H, br s). Reference production example 10
15 ml of 48% hydrobromic acid was added to 4 g of hydrochloride of 2-fluoro-3-methoxybenzylamine, and the mixture was heated to reflux for 5 hours. The reaction mixture was allowed to cool at around room temperature and concentrated under reduced pressure to obtain 4.0 g of 2-fluoro-3-hydroxybenzylamine hydrobromide.
2-Fluoro-3-hydroxybenzylamine hydrobromide

¹ H-NMR (DMSO-d ₆ ) δ: 4.04 (2H, q, J = 5.5 Hz), 6.90-6.94 (1H, m), 6.97-7.06 (2H, m), 8.23 (3H, br s), 10.05 (1H, br s).

¹H-NMR (CDCl₃) δ：7.53-7.57（1H, m）, 7.68-7.71 (1H, m), 8.03 (1H, d, J = 8.0 Hz), 8.57 (1H, d, J = 8.0Hz), 9.05-9.06 (2H, m). Reference production example 11
69.4 g of [1,5] naphthyridine was dissolved in 700 ml of chloroform, 120 g of m-chloroperbenzoic acid was added at room temperature, and the mixture was stirred for 2 hours. To this mixture, 12 g of m-chloroperbenzoic acid was added, and the mixture was further stirred at room temperature for 2 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 73 g of [1,5] naphthyridine N-oxide.
[1,5] Naphthyridine N-oxide

¹ H-NMR (CDCl ₃ ) δ: 7.53-7.57 (1H, m), 7.68-7.71 (1H, m), 8.03 (1H, d, J = 8.0 Hz), 8.57 (1H, d, J = 8.0 Hz ), 9.05-9.06 (2H, m).

¹H-NMR (CDCl₃) δ：7.80 (1H, dd, J = 4.0, 8.0 Hz), 7.96 (1H, d, J = 8.0 Hz), 8.49 (1H, d, J = 8.0 Hz), 8.58 (1H, d, J = 8.0 Hz), 9.14 (1H, d, J = 4.0 Hz). Reference production example 12
73 g of [1,5] naphthyridine N-oxide and 76 g of 1,8-diazabicyclo [5.4.0] -7-undecene were dissolved in 700 ml of THF, and 52 g of trimethylsilylcyanide was dissolved in ice for 1 hour. It was dripped. It returned to room temperature over about 2 hours, and stirred for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 38 g of 2-cyano [1,5] naphthyridine.
2-Cyano [1,5] naphthyridine

¹ H-NMR (CDCl ₃ ) δ: 7.80 (1H, dd, J = 4.0, 8.0 Hz), 7.96 (1H, d, J = 8.0 Hz), 8.49 (1H, d, J = 8.0 Hz), 8.58 ( 1H, d, J = 8.0 Hz), 9.14 (1H, d, J = 4.0 Hz).

¹H-NMR (DMSO-d₆) δ：7.92 (1H, dd, J = 4.0, 8.0 Hz), 8.36 (1H, d, J = 8.0 Hz), 8.60 (1H, d, J = 8.0 Hz), 8.61 (1H, d, J = 8.0 Hz), 9.14 (1H, d, J = 8.0 Hz), 13.65 (1H, br s). Reference production example 13
1.6 g of 2-cyano [1,5] naphthyridine was dissolved in 40 ml of 50% aqueous sulfuric acid solution and stirred for 4 hours under heating and reflux. The reaction mixture was ice-cooled, and 5N aqueous sodium hydroxide solution was added little by little to the reaction mixture, whereby crystals were precipitated. The crystals were collected by filtration and dried under reduced pressure to obtain 1.5 g of [1,5] naphthyridine-2-carboxylic acid.
[1,5] Naphthyridine-2-carboxylic acid

¹ H-NMR (DMSO-d ₆ ) δ: 7.92 (1H, dd, J = 4.0, 8.0 Hz), 8.36 (1H, d, J = 8.0 Hz), 8.60 (1H, d, J = 8.0 Hz), 8.61 (1H, d, J = 8.0 Hz), 9.14 (1H, d, J = 8.0 Hz), 13.65 (1H, br s).

Formulation Example 1
50 parts of any one of the compounds (1) to (18) of the present invention, 3 parts of calcium lignin sulfonate, 2 parts of magnesium lauryl sulfate and 45 parts of synthetic hydrous silicon oxide are obtained by pulverizing and mixing well to obtain a wettable powder. .

Formulation Example 2
20 parts of any one of the compounds (1) to (18) of the present invention and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, followed by a wet pulverization method. After that, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate is added thereto, and further 10 parts of propylene glycol is added and stirred and mixed to obtain a flowable preparation. Get.

Formulation Example 3
By thoroughly pulverizing and mixing 2 parts of one of the compounds (1) to (18) of the present invention, 88 parts of kaolin clay and 10 parts of talc, a powder is obtained.

Formulation Example 4
The emulsion is obtained by thoroughly mixing 5 parts of any one of the compounds (1) to (18) of the present invention, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene. .

Formulation Example 5
2 parts of any one of the present compounds (1) to (18), 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of kaolin clay are mixed well, and then water is added. Knead well and granulate dry to obtain granules.

Formulation Example 6
Mixing 10 parts of any one of the compounds (1) to (18) of the present invention, 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt and 55 parts of water, and finely pulverizing them by a wet pulverization method. To obtain a flowable formulation.

Next, test examples show that the compounds of the present invention are useful for controlling plant diseases.
The control effect is obtained by visually observing the area of the lesion on the test plant at the time of the survey, and comparing the area of the lesion on the plant treated with the compound of the present invention and the area of the lesion on the untreated plant. evaluated.

Test example 1
A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. Each of the compounds (1), (2), (4) to (17) and (18) of the present invention is made into a flowable formulation according to Formulation Example 6, and then diluted with water to a predetermined concentration (500 ppm). The foliage was sprayed so as to adhere well to the leaf surface. After spraying, the plants were air-dried, and a spore-containing PDA medium of Botrytis cinerea was placed on the cucumber leaf surface. After inoculation, the lesion area was investigated after 5 days in a humid environment at 12 ° C. As a result, the lesion area in the plant treated with the compounds (1), (2), (4) to (17) and (18) of the present invention was 30% or less of the lesion area in the untreated plant. .

Test example 2
A plastic pot was stuffed with sand loam, seeded with green beans (variety; Nagatake peas) and grown in a greenhouse for 8 days. Each of the compounds (18) of the present invention was made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed with foliage so as to adhere sufficiently to the kidney leaf surface. After spraying, the plants were air-dried, and a mycelia-containing PDA medium of sclerotia sclerotium was placed on the kidney leaf surface. After the inoculation, all kidney beans were left under high humidity only at night, and the lesion area was examined 5 days after the inoculation. As a result, the lesion area in the plant treated with the compound (18) of the present invention was 10% or less of the lesion area in the untreated plant.

Test example 3
A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. Each of the compounds (1) to (13) of the present invention was made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed on the foliage so as to adhere well to the cucumber leaf surface. After spraying, the plants were air-dried, and a mycelia-containing PDA medium of cucumber sclerotia bacterium was placed on the cucumber leaf surface. After the inoculation, the lesion area was examined after being placed at 18 ° C. under high humidity for 4 days. As a result, the lesion area in the plant which processed this invention compound (1)-(12) and (13) was 10% or less of the lesion area in an untreated plant.
Further, instead of the compound of the present invention, N- (2-methoxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as comparative compound) described in Bioorganic & Medicinal Chemistry Letters, 9, p.2583 (1999). (Indicated as (A).)
The same test was conducted using As a result, the lesion area on the plant treated with the comparative compound (A) was 76% or more of the lesion area in the untreated section.
N- (2-methoxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide is a compound represented by the following formula (A).

Test example 4
A plastic pot was filled with sand loam, sown with cucumber (Sagamihanjiro), and grown in a greenhouse for 12 days. Thereafter, a spore-containing PDA medium of Botrytis cinerea was inoculated on the cucumber leaf surface, and then each of the wettable powders of the compounds (1), (5), (8) and (13) of the present invention was added to water. Was diluted to a concentration of 200 ppm, and the spray solution was sprayed on the foliage so that the sprayed liquid adhered to the leaf surface of the cucumber. After spraying, the plants were air-dried and placed under high humidity at 12 ° C. for 2 days, and then the control effect was investigated. As a result, the lesion area of the plant which processed this invention compound (1), (5), (8) and (13) was 30% or less of the lesion area of an untreated area, respectively.
Further, N- (3-phenoxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide (hereinafter referred to as comparative compound (B)) described in International Publication No. 2005/033079 pamphlet instead of the compound of the present invention. )
The same test was conducted using As a result, the lesion area on the plant treated with the comparative compound (B) was 50% or more of the lesion area in the untreated section.
N- (3-phenoxyphenyl) methyl-2- [1,5] naphthyridinecarboxamide is a compound represented by the following formula (B).

Test Example 5
A plastic pot was filled with floor soil, rice (cultivar; Nipponbare) was sown, and grown in a greenhouse for 12 days. The present compounds (1), (2), (4), (5), (8), (10), (13) and (14) were made into flowable preparations according to Preparation Example 6 and then diluted with water. The stem and leaves were sprayed to a predetermined concentration (500 ppm) so as to adhere well to the leaf surface of the rice. After spraying, the plants were air-dried, and a pot having rice blast (Magnaporthe grisea) diseased leaves was left around the sprayed plants. All the rice plants were placed under high humidity only at night, and the lesion area was examined 5 days after the inoculation. As a result, the lesion area in the plant treated with the compounds (1), (2), (4), (5), (8), (10), (13) and (14) of the present invention was not treated. It was 30% or less of the lesion area in the plant.

Claims (10)

Formula (I)

[Wherein, R ¹ represents a hydrogen atom or a fluorine atom, and R ² represents a linear C3-C8 alkenyl group or a linear C3-C8 alkynyl group. ]
An amide compound represented by The amide compound according to claim 1, wherein R ¹ is a fluorine atom. The amide compound according to claim ¹ , wherein R ¹ is a hydrogen atom. The amide compound according to any one of claims 1 to 3, wherein R ² is a linear C5-C7 alkenyl group. The amide compound according to any one of claims 1 to 3, wherein R ² is a 4-pentenyl group, a 5-hexenyl group or a 6-heptenyl group. The amide compound according to any one of claims 1 to 3, wherein R ² is a linear C5-C7 alkynyl group. The amide compound according to any one of claims 1 to 3, wherein R ² is a 4-pentynyl group, a 5-hexynyl group or a 6-heptynyl group.   A plant disease control agent comprising the amide compound according to any one of claims 1 to 7 and a carrier.   A method for controlling plant diseases, comprising a step of treating an effective amount of the amide compound according to any one of claims 1 to 7 on a plant or soil.   Use of the amide compound according to any one of claims 1 to 7 for controlling plant diseases.