JP2021035913A - N-methoxyamide compound or salt thereof, and agricultural and horticultural fungicide containing the same - Google Patents

Abstract

To provide an agricultural and horticultural fungicide manifesting a high effect of controlling a wide range of plant pathogens.SOLUTION: The invention provides a compound represented by formula (1) in the figure, where each symbol is as described in the specification, or a salt thereof.SELECTED DRAWING: None

Description

The present invention relates to N-methoxyamide compounds or salts thereof, and agricultural and horticultural fungicides containing them.

It is known that compounds having a certain phenacylamide structure are useful for controlling various pests. For example, Patent Documents 1 and 2 contain compounds having a phenacylamide structure useful as an insecticide, acaricide or nematode, and Patent Documents 3 and 4 contain a phenacylamide structure useful as a fungicide for agriculture and horticulture. The compounds to have are listed respectively. However, these documents, the compounds of the after-mentioned formula (1), i.e., compounds where a nitrogen atom of the amide having a heterocyclic group substituted with N- methoxy amide structure modified with methoxy group and R ^B is a specific example Not listed with it.

Although Patent Document 5 describes a fungicide for agricultural and horticultural use having pyrazole ring substituted with a methoxy group or an ethoxy group, mentioned formula (1) "-C (O) -C (Me) 2 - " It has no structure.

International Publication WO01 / 60783 International Publication WO 03/27059 International Publication WO2006 / 016708 International Publication WO2007 / 0697777 International Publication WO2007 / 060164

Traditionally, many agricultural and horticultural fungicides provided for controlling plant diseases are characterized in their spectrum and phytopathogen control effect. However, depending on the application situation, the effect is not sufficient for a specific plant disease, the therapeutic effect is slightly inferior to the preventive effect, the rain resistance is inferior, or the afterimage is relatively short. It may show a practically insufficient control effect against phytopathogens. Therefore, there is a demand for the creation of a fungicide for agriculture and horticulture that exhibits a high control effect against a wide range of phytopathogens regardless of the application situation.

As a result of research to solve the above-mentioned problems, the present inventors have found that the compound represented by the following formula (1) or a salt thereof exhibits an excellent control effect on various plant diseases. Obtained and completed the present invention.

That is, the present invention
Equation (1):

[In the formula, A is phenyl or pyridyl substituted with ^RA,
B is a heterocyclic group substituted with R ^B (said heterocyclic group may be further substituted with one to three R ^{B '),}
R ^A are the same or different, a halogen atom, alkyl, haloalkyl, alkenyl, alkynyl, cyclic group, nitro, or cyano or ^-L A -Y ^A, or two ^{R A} is attached, ^{Z 1} It may form a ring that may be substituted with,
R ^B is a ^{-L B} -Y B,
R B ^'is a halogen atom, an alkyl, haloalkyl, alkoxyalkyl, cycloalkyl or cyano,
L ^A is, O, S, C (= O), C (= O) O, C (= O) N (R 1), OC (= O), N (R 1), N (R 1) C (= O), N (R ¹ ) C (= O) O, C (= NR ² ), SO, SO ₂ or SO ₂ N (R ¹ ).
Y ^A is a hydrogen atom, Z ² may be substituted with alkyl, alkenyl, or Z ^{3-substituted} have been or cyclic group,
L ^B is, O, S, C (= O), C (= O) O, C (= O) N (R 3), OC (= O), N (R 3), N (R 3) C (= O), N (R ³ ) C (= O) O, C (= NR ⁴ ), SO, SO ₂ or SO ₂ N (R ³ ).
Y ^B represents a hydrogen atom, an alkyl optionally substituted by Z ^4, alkenyl, cycloalkyl, Z ⁵ substituted by optionally substituted phenyl or Z ⁵ may have a heterocyclic group,
R ¹ is a hydrogen atom or an alkyl and is
R ² is a hydrogen atom, alkyl or alkoxy,
R ³ is a hydrogen atom or alkyl
R ⁴ is hydrogen atom, alkyl or alkoxy,
Z ¹ is a halogen atom,
Z ² is a halogen atom, cyano, cycloalkyl or alkoxy,
Z ³ is a halogen atom or haloalkyl and
Z ⁴ is a halogen atom, cycloalkyl or alkoxy,
Z ⁵ is a halogen atom, alkyl, haloalkyl, cycloalkyl or alkoxy]
The compound represented by (hereinafter, also referred to as the compound of the present invention), a fungicide for agriculture and horticulture containing the compound of the present invention as an active ingredient, and the compound of the present invention are applied to plants or soil to control plant diseases. Regarding the method.

The compound of the present invention is useful as a fungicide for agriculture and horticulture because it can exhibit an excellent control effect on plant diseases and osmotic transferability as compared with similar conventional compounds.

In the present specification, the halogen atom or the halogen atom as a substituent includes each atom of fluorine, chlorine, bromine or iodine. The number of halogen atoms as substituents may be 1 or 2 or more, and in the case of 2 or more, each halogen atom may be the same or different from each other. Further, the substitution position of the halogen atom may be any position.

In the present specification, the alkyl or alkyl moiety includes, for example, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, and the like. decyl, undecyl, straight-chain or branched group of C ₁ -C _12, such as dodecyl.

In the present specification, the alkenyl or the alkenyl moiety includes, for example, vinyl, 1-propenyl, 2-propenyl, isopropenyl, 2-methyl-1-propenyl, 1-methyl-1-propenyl, 2-methyl-2-propenyl. , 1-Methyl-2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-hexenyl, 2 include straight or branched chain groups of _C 2 -C ₆ such as 3-dimethylamino-2-butenyl.

In the present specification, the alkynyl or alkynyl moiety includes, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-methyl-3-3. butynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3,3-dimethyl-1-straight or branched chain groups of _C 2 -C ₆ such as butynyl Be done.

_{As used herein, cycloalkyl or cycloalkyl moieties include C 3-} C ₁₀ groups such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, bicyclo [1,1,1] pentyl. Can be mentioned.

In the present specification, the cyclic group means a saturated or unsaturated carbocyclic group or a heterocyclic group. A carbon ring group is a cyclic group containing only a carbon atom as a ring atom, and is a cycloalkyl (for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, bicyclo [1,1,1] pentyl, etc.). _{And C 3-} C ₁₀ groups such as aryl (eg, phenyl, naphthyl, indenyl, dihydroindenyl, etc.). As the heterocyclic group, a 3- to 6-membered monocyclic heterocyclic group containing 1 to 4 atoms of at least one selected from the group consisting of O, S and N (for example, oxylanyl, tiylanyl, azetidinyl) 3-membered heterocyclic groups such as; 4-membered heterocyclic groups such as oxetanyl, thietanyl, azetidinyl; frills, tetrahydrofuryl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, dioxolanyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, imidazolyl Five-membered heterocyclic groups such as imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolydinyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl; pyranyl, pyridyl, piperidinyl, dioxanyl, oxadinyl, morpholinyl, thiazinyl, pyridadinyl, pyrimidinyl, pyrazinyl, piperazinyl A fused heterocyclic group containing 1 to 4 atoms (eg, benzofuranyl, isobenzofuranyl) containing at least 1 to 4 atoms selected from the group consisting of thiylanyl, oxatiynyl and the like) and at least one selected from the group consisting of O, S and N. , Dihydrobenzofuranyl, dihydroisobenzofuranyl, benzothienyl, isobenzothienyl, dihydrobenzothienyl, dihydroisobenzothienyl, tetrahydrobenzothienyl, indrill, isoindrill, benzoxazolyl, benzothiazolyl, indazolyl, benzimidazolyl, benzodio Xoranyl, benzodioxanyl, chromenyl, chromanyl, isochromanyl, chromonyl, chromanonyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indridinyl, quinolidinyl, imidazolidyl, naphthilidinyl, pteridinyl, dihydrobenzoxazine, Zolinonyl, dihydrobenzooxadinonyl, benzothioxanyl, etc.).

As the heterocyclic group represented by B in the formula (1), the same heterocyclic group as the heterocyclic group exemplified as the cyclic group can be used. Preferably, it is a 5- to 6-membered heterocyclic group containing 1 to 4 atoms of at least one selected from the group consisting of O, S and N, and more specifically, the following can be mentioned.
Equations (B-1) to (B-18):

[In the formula, ^{any one of R B1 to} R ^B3 , any one of R ^{B4 to} R ^B6 , any one of R ^{B7 to} R ^B9 , any one of R ^{B10 to} R ^B12 , R ^B13. any one of to R ^B15, any one of any one and ^R B19 ^{to R B20} of R B16 ^{to R B18} is ^-L B -Y ^B, the remainder, a halogen atom, alkyl, haloalkyl , alkoxyalkyl, cycloalkyl or cyano, L ^B and Y ^B are as defined above, * is 5-membered heterocyclic group represented by] represents a bonding site, and the formula (B-101) ~ formula (B-128):

[In the formula, ^{any one of R B101 to} R ^B104 , any one of R ^{B105 to} R ^B108 , any one of R ^{B109 to} R ^B111 , and any one of R ^{B112 to} R ^{B114 are-.} an L ^B -Y ^B, the remainder represents a halogen atom, an alkyl, haloalkyl, alkoxyalkyl, cycloalkyl or cyano, ^{L B} and ^{Y B} are as defined above, tables in * represents a bonding site] 6-membered heterocyclic group.

As the heterocyclic group represented by B, it may be preferable to have a substituent on the atom adjacent to the atom to which "*" is bonded.

In the formula (1), the ring two R ^A is formed by bonding a saturated or unsaturated carbocyclic or heterocyclic ring, for example, include the rings corresponding to the cyclic group exemplified above Be done. In the formula (1), the B in the embodiment in which two R ^A are combined to form a ring, may be substituted with Z ^1, benzodioxolanyl, benzodioxanyl, benzox thio Lil, Examples include dihydrobenzoxatinyl.

The salt of the compound of the formula (1) includes any agriculturally acceptable salt, and for example, an alkali metal salt such as a sodium salt and a potassium salt; an alkali such as a magnesium salt and a calcium salt. Earth metal salts; inorganic acid salts such as hydrochlorides, perchlorates, sulfates and nitrates; organic acid salts such as acetates and methanesulfonates.

The compound of the present invention includes various isomers such as optical isomers and geometric isomers, and the present invention includes both each isomer and a mixture of isomers. The compound of the present invention also includes various isomers other than those described above within the scope of common general technical knowledge in the art.

Further, depending on the type of isomers, the chemical structure may be different from the described structural formula, but those skilled in the art can sufficiently recognize that they have an isomer relationship, and thus are within the scope of the present invention. It is clear that

The compound of the present invention can be produced according to the following reactions A to F and the usual method for producing a salt, but the method for obtaining the compound of the present invention is not limited to these methods.

Reaction A
Reaction A is a method for obtaining a compound of formula (1) by methylating the compound of formula (2).

The symbols in the formula are as described above.

Reaction A can be carried out according to general methylation reaction conditions, and can usually be carried out in the presence of a methylating agent, a base and a solvent.

Examples of the methylating agent include methyl iodide, methyl bromide, dimethyl sulfate, trimethylsilyldiazomethane and the like. The methylating agent can be used in an amount of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of the formula (2).
Bases include, for example, alkali metals such as sodium and potassium; alkali metal alkoxides such as sodium methoxydo, sodium ethoxydo and potassium tertiary butoxide; carbonates such as sodium carbonate and potassium carbonate; sodium hydroxide, heavy weight. Dicarbonates such as potassium carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal hydrides such as sodium hydride and potassium hydride; such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine Amines; pyridines, pyridines such as 4-dimethylaminopyridine; organic lithium compounds such as methyllithium, n-butyllithium, lithiumdiisopropylamide and the like can be appropriately selected from one or more. The base can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (2).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; esters such as methyl acetate, ethyl acetate; methanol, ethanol, propanol, tert-butanol. Alcohols; polar aprotic solvents such as dimethylsulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile, propionitrile; ketones such as acetone, methyl ethyl ketone; water, etc. One type or two or more types can be appropriately selected from.

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

The compound of the formula (2) used in the reaction A can be produced according to the following reaction 1-1.

Reaction B
Reaction B is a method of reacting a compound of formula (3) with a compound of formula (4) to obtain a compound of formula (1).

In the formula, T is hydroxy, alkoxy, aryloxy or halogen, and the other symbols are as described above.

Reaction B can usually be carried out in the presence of a base and a solvent. The compound of the formula (4) can be used in an amount of 1 to 3, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (3).

Bases are, for example, alkali metals such as sodium, potassium; alkali metal alkoxides such as sodium methoxydo, sodium ethoxydo, potassium tertiary butoxide; carbonates such as sodium carbonate, potassium carbonate; sodium hydroxide, heavy. Dicarbonates such as potassium carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal hydrides such as sodium hydride and potassium hydride; such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine Amines; pyridines, pyridines such as 4-dimethylaminopyridine; organic lithium compounds such as methyllithium, n-butyllithium, lithiumdiisopropylamide and the like can be appropriately selected from one or more. The base can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (3).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; esters such as methyl acetate, ethyl acetate; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N- Polar aprotic solvents such as dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile and propionitrile; one or more can be appropriately selected from ketones such as acetone and methyl ethyl ketone.

Reaction B can be carried out in the presence of a dehydration condensing agent, if necessary. Examples of the dehydration condensing agent include N, N'-dicyclohexylcarbodiimide, chlorosulfonylisocyanate, N, N'-carbonyldiimidazole, trifluoroacetic anhydride and the like. The dehydration condensing agent can be used in an amount of 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (3).

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 50 ° C., and the reaction time is usually about 0.5 to 48 hours, preferably about 1 to 24 hours.

The compound of formula (3) used in Reaction B can be produced according to Reaction 1-2 or Reaction 1-3 below. The compound of the formula (4) can be produced according to the following reaction 2-1 or a known method, or a commercially available product may be used.

Reaction C
Reaction C is a method of reacting a compound of formula (5) with a compound of formula (6) to obtain a compound of formula (1).

In the formula, X is a chlorine atom, a bromine atom or an iodine atom, and other symbols are as described above.

Reaction C can usually be carried out in the presence of a base and a solvent. The compound of the formula (6) can be used in an amount of 1 to 3, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (5).

Bases include alkali metals such as sodium and potassium; alkali metal alkoxides such as sodium methoxydo, sodium ethoxydo and potassium tertiary butoxide; carbonates such as sodium carbonate and potassium carbonate; sodium hydroxide, heavy weight. Dicarbonates such as potassium carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal hydrides such as sodium hydride and potassium hydride; such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine One type or two or more types can be appropriately selected from various amines and the like. The base can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to the compound of the formula (5).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; esters such as methyl acetate, ethyl acetate; methanol, ethanol, propanol, tert-butanol. Alcohols; polar aprotic solvents such as dimethylsulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile, propionitrile; ketones such as acetone, methyl ethyl ketone; water, etc. One type or two or more types can be appropriately selected from.

The reaction temperature is usually 0 to 100 ° C., preferably 20 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 1 to 24 hours.

The compound of formula (5) used in Reaction C can be prepared according to Reaction 1-9 below. The compound of the formula (6) can be produced according to a known method, or a commercially available product may be used.

Reaction D
Reaction D is a method of converting a compound of formula (1-1) in which ^{RA is fluorine to a compound of formula (1-2) in which RA} is hydroxy using a compound of formula (7). is there.

In the formula, A ¹ is fluorine-substituted phenyl or pyridyl, A ² is hydroxy-substituted phenyl or pyridyl, and the other symbols are as described above.

Reaction D can usually be carried out in the presence of a base and a solvent. The compound of the formula (7) can be used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to 1 equivalent of the compound of the formula (1-1).

Bases are, for example, alkali metals such as sodium, potassium; alkali metal alkoxides such as sodium methoxydo, sodium ethoxydo, potassium tertiary butoxide; carbonates such as sodium carbonate, potassium carbonate; sodium hydroxide, heavy. Dicarbonates such as potassium carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal hydrides such as sodium hydride and potassium hydride; such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine Amines; pyridines, pyridines such as 4-dimethylaminopyridine; organic lithium compounds such as methyllithium, n-butyllithium, lithiumdiisopropylamide and the like can be appropriately selected from one or more. The base can be used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to the compound of formula (1-1).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; esters such as methyl acetate, ethyl acetate; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N- Polar aprotic solvents such as dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile and propionitrile; one or more can be appropriately selected from ketones such as acetone and methyl ethyl ketone.

The reaction temperature is usually 0 to 150 ° C., preferably 50 to 100 ° C., and the reaction time is usually about 1 to 24 hours, preferably about 1 to 12 hours.

Reaction E
The reaction E, using the compound or compounds of formula (9) in equation (8), a compound of formula (1-2) ^{R A} is hydroxy, ^{R A} is ^{-O-Y A1} formula ( This is a method for converting to the compound of 1-3).

Wherein, A ³ is a phenyl or pyridyl substituted with -O-Y ^A1, Y ^A1 is optionally substituted alkyl, alkenyl or Z ³ in an optionally substituted cyclic group Z ^2,
Other symbols are as described above.

Reaction E can usually be carried out in the presence of a base and a solvent. Alternatively, it can be carried out in the presence of triphenylphosphine, diethyl azodicarboxylate and a solvent according to a general Mitsunobu reaction. The compound of the formula (8) or the compound of the formula (9) can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (1-2). Triphenylphosphine can be used in an amount of 1-3 equivalents, preferably 1-1.5 equivalents, relative to 1 equivalent of the compound of formula (1-2). Diethyl azodicarboxylate can be used in an amount of 1 to 3 equivalents, preferably 1 to 1.5 equivalents, relative to 1 equivalent of the compound of the formula (1-2).

The base is, for example, an alkali metal alkoxide such as sodium methoxydo, sodium ethoxydo, potassium quaternary butoxide; a carbonate such as sodium carbonate, potassium carbonate; a bicarbonate such as sodium hydroxide, potassium hydride; Metal hydroxides such as sodium hydroxide, potassium hydroxide; metal hydrides such as sodium hydride, potassium hydride; amines such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine; pyridine, 4-dimethyl One or more are appropriately selected from pyridines such as aminopyridine. The base can be used in an amount of 1-2 equivalents, preferably 1-1.5 equivalents, relative to the compound of formula (1-2).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; esters such as methyl acetate, ethyl acetate; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N- Polar aprotic solvents such as dimethylformamide, N-methylpyrrolidone, pyridine; nitriles such as acetonitrile, propionitrile, acrylonitrile; ketones such as acetone, methyl ethyl ketone; one or more from water, etc. It can be selected as appropriate.

The reaction temperature is usually -30 to 100 ° C., preferably 0 to 50 ° C., and the reaction time is usually about 0.1 to 24 hours, preferably about 0.1 to 12 hours.

The compounds of the formulas (8) and (9) used in the reaction E can be produced according to a known method, or commercially available products may be used.

Reaction F
In the reaction F, the compound of the formula (10) or the compound of the formula (11) is used to obtain a compound ^{of the formula (1-4) in which RA} is X, and a compound of formula (1) in which ^RA is specific ^RA2. -5) This is a method for converting to a compound.

In the formula, A ⁴ is X-substituted phenyl or pyridyl, A ⁵ is ^{RA 2-} substituted ^{phenyl or pyridyl, and RA 2} is alkyl, haloalkyl, alkenyl, alkynyl, cyclic group, cyano or -L. an ^A1 -Y ^a, L ^A1 is, O, S, C (= O), C (= O) O, C (= O) N (R 1), N (R 1), SO, SO 2 or SO ₂ N (R ¹ ), M is a metal atom such as magnesium, zinc or a salt thereof, or a residue of boronic acid or an ester thereof, and other symbols are as described above.

In the reaction F, the compound of the formula (1-4) is usually added with a base in the presence of a transition metal catalyst, a solvent and an inert gas as needed, and the compound of the formula (10) or the compound of the formula (11) is added. ) Can be reacted with the compound.

The compound of the formula (10) or the compound of the formula (11) is not particularly limited as long as the reaction proceeds, and can be prepared according to a known method, or a commercially available product may be used. The compound of formula (10) or the compound of formula (11) can be used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to the compound of formula (1-4).

Examples of the transition metal catalyst include catalysts containing transition metals such as palladium, copper, rhodium, ruthenium, nickel, cobalt and molybdenum. As the transition metal catalyst, various known structures used for the cross-coupling reaction of organic halides can be used, and a transition metal catalyst containing palladium is particularly useful for this reaction. Examples of the transition metal catalyst containing palladium include palladium-carbon, palladium chloride, palladium acetate, dichlorobis (acetonitrile) palladium, bis (dibenzilidenacetone) palladium, dichlorobis (triphenylphosphine) palladium, and tetrakis (triphenylphosphine) palladium. , Dichlorobis (1,4-bis (diphenylphosphino) butane) palladium and the like. In addition, tertiary phosphine or tertiary phosphite can be used as a ligand, if necessary. Examples of the tertiary phosphine or tertiary phosphine include triphenylphosphine, phenyldimethylphosphine, tri-o-tolylphosphine, tri-p-tolylphosphine, 1,2-bis (diphenylphosphino) ethane, 1,3. Examples thereof include -bis (diphenylphosphine) propane, 1,4-bis (diphenylphosphino) butane, 1,1'-bis (diphenylphosphino) ferrocene, and triphenylphosphine. The transition metal catalyst can be used in an amount of 0.001 to 0.5 equivalents, preferably 0.05 to 0.2 equivalents, relative to the compound of formula (1-4). Further, the ligand can be used in an amount of usually 1 to 50 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the transition metal catalyst. However, depending on the reaction conditions, an amount outside this range can be used.

Bases include, for example, alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate; alkali metal alkoxides such as sodium methoxydo, sodium ethoxydo, potassium tertiary butoxide; alkali metal such as sodium hydrogen carbonate. Hydrogen carbonates; carbonates of alkaline earth metals such as calcium carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal hydrides such as sodium hydride and potassium hydride; triethylamine, diisopropylethylamine , Pyridine, 4- (N, N-dimethylamino) pyridine, organic amines such as imidazole and the like. The base can be used in an amount of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to the compound of formula (1-4).

The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliphatic hydrocarbons such as hexane and cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether and dimethoxyethane; esters such as methyl acetate and ethyl acetate; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N- Polar aprotic solvents such as dimethylformamide, N-methylpyrrolidone, pyridine; nitriles such as acetonitrile, propionitrile, acrylonitrile; ketones such as acetone, methyl ethyl ketone; methanol, ethanol, propanol, tert-butanol Such alcohols; one or more can be appropriately selected from water and the like.

As the inert gas, for example, nitrogen gas, argon gas or the like can be used.

The reaction temperature is usually −100 to 200 ° C., preferably −78 to 100 ° C., and the reaction time is usually about 0.5 to 96 hours, preferably about 1 to 48 hours.

Reaction G
Reaction G comprises reacting the compound of formula (1-6) with a (halo) alkylating agent, acylating agent or alkoxycarbonylating agent, Mitsunobu reaction or reductive alkylation to obtain the compound of formula (1-7). How to get it.

Wherein, B ¹ is a Hajime Tamaki substituted by hydroxy or amino (said heterocyclic group is, R B ^'may be further substituted with) a, B ² is substituted with -L ^B1 -Y ^B1 Hajime Tamaki (said heterocyclic group also may be further substituted with ^{R B} ') ^{is, L} B1 is O, OC (= O) or OC (= O) O, N (R 3) , N (R ³ ) C (= O), N (R ³ ) C (= O) O, where Y ^B1 is an alkyl, alkenyl or cycloalkyl optionally substituted with ^{Z 4, and other symbols.} Is as described above.

Of the reaction G, the reaction with the (halo) alkylating agent, acylating agent or alkoxycarbonylating agent can usually be carried out in the presence of a base and a solvent. The (halo) alkylating agent, acylating agent or alkoxycarbonylating agent can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (1-6).
Alternatively, the reaction G can be carried out in the presence of an aldehyde, a reducing agent, an acid and a solvent according to a general Mitsunobu reaction or a general reducing alkylation reaction.

As the base and the solvent, those mentioned in the above reaction E can be used.
Examples of the (halo) alkylating agent include alkyl halides such as methyl iodide and methyl bromide; dialkyl sulfates such as dimethyl sulfate; trimethylsilyldiazomethane; chlorodifluoromethane, sodium chlorodifluoroacetate and the like.
Examples of the acylating agent include acid chlorides such as acyl chloride; and acid anhydrides such as acetic anhydride.
Examples of the alkoxycarbonylating agent include chloroformate esters such as methyl chloroformate.

The reaction temperature is usually -30 to 100 ° C., preferably 0 to 50 ° C., and the reaction time is usually about 0.1 to 24 hours, preferably about 0.1 to 12 hours.

The Mitsunobu reaction can be carried out according to the reaction E.

As the aldehyde in the reductive alkylation, for example, formaldehyde, acetaldehyde and the like can be used. Aldehyde can be used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to 1 equivalent of the compound of formula (1-6).
As the reducing agent, for example, one kind or two or more kinds can be appropriately selected from sodium cyanoborohydride, sodium triacetoxyborohydride and the like. The reducing agent can be used in an amount of 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (1-6).
As the acid, for example, acetic acid or the like can be used. The acid can be used in an amount of 1 to 30 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of formula (1-6).
The solvent may be any solvent as long as it is inert to the reaction, for example, nitriles such as acetonitrile and propionitrile; ethers such as dioxane, tetrahydrofuran, diethyl ether and dimethoxyethane; methanol, ethanol, etc. Alcohols such as propanol and tert-butanol; one or more can be appropriately selected from water and the like.
The reaction temperature is usually 0 to 80 ° C., preferably 0 to 50 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.5 to 24 hours.

Reaction H
Reaction H is a method for obtaining a compound of formula (1-6) by reacting a compound of formula (1-8) with an acid or fluoride, or by catalytic reduction.

Wherein, ^{B 3} is ^-L B2 ^{-Y B2} Hajime Tamaki substituted by (said heterocyclic group may be further substituted with ^{R B} 'may also be) ^{a, L B2} is O or N ^{(R 3} ), Y ^B2 is alkyl, trialkylsilyl, alkoxyalkyl, arylalkyl, alkoxycarbonyl or arylalkoxycarbonyl, and other symbols are as described above.

Reaction H can usually be carried out by reacting the compound of formula (1-8) with an acid or fluoride in the presence of a solvent. Alternatively, it can be carried out by using platinum, platinum oxide, platinum black, Raney nickel, palladium, palladium carbon, rhodium, rhodium-alumina or the like as a catalyst in a hydrogen atmosphere according to general catalytic reduction.

The solvent is not particularly limited as long as the reaction proceeds, and is, for example, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene; and aliphatic hydrocarbons such as hexane, heptane, petroleum ether, ligroine and cyclohexane; Halogenized hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane; ethers such as diethyl ether, tetrahydrofuran, dioxane, esters such as methyl acetate, ethyl acetate, methanol, ethanol, propanol, One or more can be appropriately selected from alcohols such as tert-butanol, water and a mixed solvent thereof.
The acid is not particularly limited as long as the reaction proceeds, and examples thereof include Lewis acids such as boron tribromide; Bronsted acids such as hydrochloric acid and trifluoroacetic acid. The acid can be used in a ratio of 1 to 10 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of the compound of formula (1-8).
The fluoride is not particularly limited as long as the reaction proceeds, and tetra-n-butylammonium fluoride, cesium fluoride and the like can be mentioned. Fluoride can be used in a ratio of 1 to 10 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of the compound of formula (1-8).

The reaction temperature is usually -30 to 200 ° C., preferably 0 to 100 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

The methods for producing the compounds used in Reactions A to H are described below, but the method is not limited to these methods, and these compounds may be produced according to known methods, or commercially available products may be produced. You may use it.

Reaction 1-1
Reaction 1-1 is a method of reacting a compound of formula (100) with a compound of formula (4) to obtain a compound of formula (2). Further, the compound of the formula (2) can be obtained by hydrolyzing the compound of the formula (101) obtained together with the compound of the formula (2).

The symbols in the formula are as described above.

In Reaction 1-1, the reaction of the compound of formula (100) with the compound of formula (4) can usually be carried out in the presence of a base and a solvent, or, if necessary, in the presence of a dehydration condensing agent. Can be done with.
As the base, solvent and dehydration condensing agent, those mentioned in Reaction B can be used. The compound of the formula (4) can be used in an amount of 1 to 3, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (100). The base can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (100).

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 50 ° C., and the reaction time is usually about 0.5 to 48 hours, preferably about 1 to 24 hours.

In the reaction 1-1, the compound of the formula (2) can be derived by hydrolyzing the compound of the formula (101) obtained together with the compound of the formula (2).
Hydrolysis can be carried out according to general hydrolysis reaction conditions, and can usually be carried out in the presence of an acid or base and a solvent.

Examples of the acid include hydrochloric acid, sulfuric acid and the like. Examples of the base include metal hydroxides such as sodium hydroxide and potassium hydroxide. The acid or base can be used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to 1 equivalent of the compound of formula (100).
The solvent may be any solvent inert to the reaction, for example alcohols such as methanol, ethanol, propanol, tert-butanol; nitriles such as acetonitrile, propionitrile, acrylonitrile; acetone, methyl ethyl ketone. Ketones such as; one or more can be appropriately selected from water and the like.

The reaction temperature for hydrolysis is usually 0 to 100 ° C., preferably 20 to 80 ° C., and the reaction time is usually about 0.1 to 12 hours, preferably about 0.1 to 1 hour.

The compound of formula (100) used in Reaction 1-1 can be prepared according to Reaction 1-4 or Reaction 1-5 below. The compound of the formula (4) can be produced according to the following reaction 2-1 or a known method, or a commercially available product may be used.

Reaction 1-2
Reaction 1-2 is a method for obtaining a compound of formula (3) by methylating the compound of formula (100).

The symbols in the formula are as described above.

Reaction 1-2 can be carried out according to the above reaction A.

Reaction 1-3
Reaction 1-3 is a method of reacting the compound of the formula (5) with O-methylhydroxylamine hydrochloride to obtain the compound of the formula (3).

The symbols in the formula are as described above.

Reactions 1-3 can be carried out according to Reaction C. The O-methylhydroxylamine hydrochloride can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (5).

Reaction 1-4
Reaction 1-4 is a method of reducing the compound of formula (102) to obtain the compound of formula (100).

The symbols in the formula are as described above.

The reduction reaction includes, for example, catalytic reduction catalyzed by platinum oxide, Raney nickel, palladium-carbon, rhodium, etc. in a hydrogen atmosphere; from metals such as iron and zinc and acids such as hydrochloric acid, acetic acid and ammonium chloride. It can be carried out by reduction in the constructed reaction system.

Reactions 1-4 can usually be carried out in the presence of a solvent. The solvent may be any solvent as long as it is inert to the reaction, for example, aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane and cyclohexane; dioxane, tetrahydrofuran and diethyl. Ethers such as ethers, dimethoxyethane; esters such as methyl acetate and ethyl acetate; such as dimethyl sulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile, propionitrile. Polar aprotic solvent; Ketones such as acetone and methyl ethyl ketone; Alcohols such as methanol, ethanol, propanol and tert-butanol; One or more can be appropriately selected from water and the like.

The reaction temperature is usually 0 to 150 ° C., preferably 0 to 80 ° C., and the reaction time is usually about 0.5 to 96 hours, preferably about 0.5 to 48 hours.

The compound of formula (102) used in Reaction 1-4 can be produced according to Reaction 1-6 or Reaction 1-8 below.

Reaction 1-5
Reaction 1-5 is a method of reacting a compound of formula (5) with hydroxylamine hydrochloride to obtain a compound of formula (100).

The symbols in the formula are as described above.

Reaction 1-5 can be carried out according to Reaction C. Hydroxylamine hydrochloride can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (5).

The reaction temperature is usually 0 to 100 ° C., preferably 20 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 1 to 24 hours.

Reaction 1-6
Reaction 1-6 is a method of oxidizing the compound of formula (103) to obtain the compound of formula (102).

The symbols in the formula are as described above.

Oxidation reactions include, for example, oxidation in a reaction system composed of chromium acid and sulfuric acid, pyridine, and pyridinium salt; oxidation in a reaction system composed of dimethylsulfoxide and oxalyl chloride; tetrapropylammonium tetrapropylammonium and N-. Oxidation in a reaction system composed of a copolymer such as methylmorpholine-N-oxide; oxidation by des-martin periodinane; oxidation by manganese dioxide and the like.

Reactions 1-6 can usually be carried out in the presence of a solvent. The solvent may be any solvent inert to the reaction, such as aromatic hydrocarbons such as benzene, toluene, xylene; carbon tetrachloride, chloroform, dichloromethane, dichloroethane, trichloroethane, hexane, cyclohexane. Polyaliphatic hydrocarbons; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; esters such as methyl acetate and ethyl acetate; dimethylsulfoxide, sulfolanes, dimethylacetamides, N, N-dimethylformamides, N- Polar aprotic solvents such as methylpyrrolidone, pyridine, acetonitrile, propionitrile; ketones such as acetone, methyl ethyl ketone; alcohols such as methanol, ethanol, propanol, tert-butanol; one or two from water, etc. More than a species can be selected as appropriate.

The reaction temperature is usually −78 to 150 ° C., preferably −50 to 80 ° C., and the reaction time is usually about 0.5 to 96 hours, preferably about 0.5 to 48 hours.

The compound of formula (103) used in Reactions 1-6 can be prepared according to Reactions 1-7 below.

Reaction 1-7
Reaction 1-7 is a method of reacting a compound of formula (104) with 2-nitropropane to obtain a compound of formula (103).

The symbols in the formula are as described above.

Reactions 1-7 can be carried out according to a general nitroaldol reaction, and can usually be carried out in the presence of a base and, if necessary, in the presence of a solvent. 2-Nitropropane can be used in an amount of 1 to 30 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of formula (104).

Bases include, for example, alkali metals such as sodium and potassium; alkali metal alkoxides such as sodium methoxydo, sodium ethoxydo and potassium tertiary butoxide; carbonates such as sodium carbonate and potassium carbonate; sodium hydroxide, heavy weight. Dicarbonates such as potassium carbonate; metal hydroxides such as sodium hydroxide and potassium hydroxide; metal hydrides such as sodium hydride and potassium hydride; such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine Amines; amidins such as 1,8-diazabicyclo [5.4.0] undec-7-ene; tetramethylguanidine, 1,5,7-triazabicyclo [4.4.0] deca-5 -One or more can be appropriately selected from guanidines such as ene. The base can be used in an amount of 0.1 to 2 equivalents, preferably 0.1 to 1 equivalent, relative to the compound of formula (104).
The solvent may be any solvent inert to the reaction, for example alcohols such as methanol, ethanol, propanol, tert-butanol; nitriles such as acetonitrile, propionitrile, acrylonitrile; acetone, methyl ethyl ketone. Ketones such as: carbon tetrachloride, chloroform, dichloromethane, dichloroethane, trichloroethane, hexane, aliphatic hydrocarbons such as cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; dimethylsulfoxide, sulfolane, Polar aprotic solvents such as dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, and pyridine; one or more can be appropriately selected from water and the like.

The reaction temperature is usually 0 to 100 ° C., preferably 20 to 50 ° C., and the reaction time is usually about 0.1 to 168 hours, preferably about 1 to 24 hours.

The compound of formula (104) used in Reaction 1-7 can be produced according to a known method, or a commercially available product may be used.

Reaction 1-8
Reaction 1-8 is a method of nitrating the compound of the formula (5) to obtain the compound of the formula (102).

The symbols in the formula are as described above.

Reactions 1-8 can usually be carried out in the presence of a nitroating agent and a solvent.

As the nitrating agent, one or more can be appropriately selected from, for example, sodium nitrite, potassium nitrite and the like. The nitrating agent can be used in an amount of 1 to 2 equivalents, preferably 1 to 1.5 equivalents, relative to 1 equivalent of the compound of the formula (5).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, chloroform, dichloromethane, dichloroethane, trichloroethane, hexane, cyclohexane. Alibo hydrocarbons such as; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; esters such as methyl acetate, ethyl acetate; dimethylsulfoxide, sulfolanes, dimethylacetamides, N, N-dimethylformamides, Polar aprotic solvents such as N-methylpyrrolidone, pyridine, acetonitrile, propionitrile; ketones such as acetone, methyl ethyl ketone; alcohols such as methanol, ethanol, propanol, tert-butanol; one from water, etc. Alternatively, two or more types can be appropriately selected.

The reaction temperature is usually 0 to 150 ° C., preferably 20 to 50 ° C., and the reaction time is usually about 0.1 to 96 hours, preferably about 0.5 to 24 hours.

Reaction 1-9
Reaction 1-9 is a method for obtaining a compound of formula (5) by halogenating the compound of formula (105).

The symbols in the formula are as described above.

Reactions 1-9 can be carried out in the presence of a halogenating agent (eg, a chlorinating agent, a brominating agent or an iodizing agent) and a solvent, and optionally in the presence of a base. The halogenating agent can be used in an amount of 1 to 2 equivalents, preferably 1 to 1.5 equivalents, relative to 1 equivalent of the compound of the formula (105).

As the chlorinating agent, for example, one or more kinds are appropriately selected from chlorine, N-chlorosuccinimide and the like, and as the brominating agent, for example, one from bromine, N-bromosuccinimide, trimethylphenylammonium tribromid and the like. Species or two or more kinds can be appropriately selected, and as the iodizing agent, one or two or more kinds can be appropriately selected from, for example, iodine, N-iodosuccinate imide and the like.
The solvent may be any solvent inert to the reaction, for example aliphatic hydrocarbons such as carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, hexane, cyclohexane; dioxane, tetrahydrofuran, Ethers such as diethyl ether, dimethoxyethane; esters such as methyl acetate and ethyl acetate; polar aprotic such as dimethyl sulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine Solvent: One or more can be appropriately selected from organic acids such as acetic acid and propionic acid; water and the like.
Examples of the base include lithium diisopropylamide and the like. The base can be used in 1-2 equivalents, preferably 1-1.2 equivalents, relative to the compound of formula (105).
When the solvent is used in the presence of a base, one or two or more kinds of ethers such as tetrahydrofuran and diethyl ether can be appropriately selected as the solvent.
Reaction 1-9 can use an organic acid such as acetic acid or propionic acid or a Lewis acid such as aluminum chloride as a catalyst, if necessary. In addition, it can also serve as a solvent by using an excessive amount of an organic acid as a catalyst.

The reaction temperature is usually −100 to 150 ° C., preferably −78 to 110 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.5 to 24 hours. When carried out in the presence of a base, the reaction temperature is usually −100 to 0 ° C., preferably −78 to −20 ° C., and the reaction time is usually about 0.1 to 12 hours, preferably 0.5 to 6 ° C. When carried out in the presence of an acid, the reaction temperature is usually 0 to 150 ° C., preferably 20 to 110 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably 1. It takes about 24 hours.

The compound of formula (105) used in Reaction 1-9 can be prepared according to Reactions 1-10 to Reactions 1-15 below.

Reaction 1-10
Reaction 1-10 is a method for obtaining a compound of formula (105) by a Friedel-Crafts reaction of a compound of formula (106) and a compound of formula (107).

In the formula, A'is a ring corresponding to A, and other symbols are as described above.

Reaction 1-10 can be carried out according to a general Friedel-Crafts reaction, and can usually be carried out in the presence of an acid and a solvent. The compound of formula (107) can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to the compound of formula (106).
Acids include, for example, mineral acids such as hydrochloric acid and sulfuric acid; organic acids such as paratoluene sulfonic acid and trifluoromethanesulfonic acid; Lewis acids such as aluminum chloride, iron chloride, zinc chloride and boron trifluoride etherate. One type or two or more types can be appropriately selected. The acid can be used in an amount of 0.1 to 3 equivalents, preferably 1 to 2 equivalents, relative to the compound of formula (106).
The solvent may be any solvent inert to the reaction, for example nitriles such as acetonitrile, propionitrile, acrylonitrile; carbon tetrachloride, chloroform, dichloromethane, dichloroethane, trichloroethane, hexane, cyclohexane and the like. Aliphatic hydrocarbons; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; polar aprotic solvents such as dimethyl sulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine One type or two or more types can be appropriately selected from the above.

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 1 to 24 hours.

The compounds of formulas (106) and (107) used in Reactions 1-10 can be produced according to known methods, or commercially available products may be used.

Reaction 1-11
Reactions 1-11 are the first step of chlorinating or amidating the compound of formula (108) to obtain the compound of formula (109), and reacting the compound of formula (109) with the compound of formula (110). , A method comprising a second step of obtaining the compound of formula (105).

In the formula, U is a chlorine atom, dialkylamino (eg, dimethylamino, diethylamino), or N-methoxy-N-methylamino, and the other symbols are as described above.

First Step The first step can be carried out in the presence of a chlorinating agent and a solvent in the case of chlorination and in the case of amidation dialkylamine (eg, dimethylamine) or N-methoxy-N-methylamine, It can be carried out in the presence of a dehydration condensing agent, a base and a solvent.

As the chlorinating agent, one or more can be appropriately selected from, for example, thionyl chloride, oxalyl chloride, phosphorus pentachloride and the like. The chlorinating agent can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (108).
As the dehydration condensing agent, the base and the solvent, those mentioned in the reaction B can be used. The dehydration condensing agent can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (108). The base can be used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to the compound of formula (108).

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 1 to 24 hours.

Second Step The second step can usually be carried out in the presence of a solvent and, if necessary, in the presence of an inert gas. The compound of formula (110) can be used in an amount of 1-3 equivalents, preferably 1-1.5 equivalents, relative to the compound of formula (108) or formula (109).

The solvent may be any solvent as long as it is inert to the reaction, and one or more can be appropriately selected from ethers such as dioxane, tetrahydrofuran and diethyl ether. The inert gas can be appropriately selected from, for example, nitrogen gas, argon gas and the like.

The reaction temperature is usually -20 to 100 ° C., preferably 0 to 50 ° C., and the reaction time is usually about 1 to 48 hours, preferably about 1 to 20 hours.

The compounds of formulas (108) and (110) used in Reactions 1-11 can be produced according to known methods, or commercially available products may be used.

Reaction 1-12
Reaction 1-12 is a method of reacting a compound of formula (111) with a compound of formula (110) to obtain a compound of formula (105).

The symbols in the formula are as described above.

Reactions 1-12 can usually be carried out in the presence of a solvent and, if necessary, in the presence of a catalyst and an inert gas. The compound of formula (110) can be used in an amount of 1 to 3 equivalents, preferably 1 to 1.5 equivalents, relative to 1 equivalent of the compound of formula (111). The catalyst can be used in an amount of 0.001 to 1 equivalent, preferably 0.01 to 0.5 equivalent, relative to 1 equivalent of the compound of formula (111).

Examples of the catalyst include copper (I) iodide and the like.
As the solvent and the inert gas, those mentioned in the second step of Reaction 1-11 can be used.

The reaction temperature is usually -20 to 100 ° C., preferably 0 to 50 ° C., and the reaction time is usually about 1 to 48 hours, preferably about 1 to 20 hours.

The compound of formula (111) used in Reactions 1-12 can be produced according to a known method, or a commercially available product may be used.

Reaction 1-13
Reaction 1-13 is a method of reacting a compound of formula (112) with a compound of formula (113) to obtain a compound of formula (105).

In the formula, V is a bromine atom or an iodine atom, and G is a leaving group (eg, chlorine atom, halogen such as bromine atom; alkoxy such as methoxy, ethoxy; dialkylamino such as dimethylamino, diethylamino. (Aziridinyl, which may be substituted with N-methoxy-N-methylamino or alkyl, etc.), and other symbols are as described above.

Reactions 1-13 can usually be carried out in the presence of an organometallic reagent and solvent, and optionally in the presence of an inert gas. The compound of formula (113) can be used in an amount of 1 to 3 equivalents, preferably 1 to 1.5 equivalents, relative to the compound of formula (112).
As the organometallic reagent, one or more can be appropriately selected from organic lithium compounds such as methyllithium and n-butyllithium; and Grignard compounds such as isopropylmagnesium chloride. The organometallic reagent can be used in an amount of 1-2 equivalents, preferably 1-1.5 equivalents, relative to the compound of formula (112).
The solvent may be any solvent as long as it is inert to the reaction, for example, one or more from aliphatic hydrocarbons such as hexane and cyclohexane; and ethers such as dioxane, tetrahydrofuran and diethyl ether. Can be selected as appropriate.
The inert gas can be appropriately selected from, for example, nitrogen gas, argon gas and the like.

The reaction temperature is usually −100 to 50 ° C., preferably −78 to 25 ° C., and the reaction time is usually about 1 to 48 hours, preferably about 1 to 20 hours.

The compounds of formulas (112) and (113) used in Reactions 1-13 can be produced according to known methods, or commercially available products may be used.

Reaction 1-14
Reaction 1-14 is a first step of reacting a compound of formula (104) with a compound of formula (110) to obtain a compound of formula (114), and oxidizing the compound of formula (114) to form (1). A method comprising a second step of obtaining the compound of 105).

The symbols in the formula are as described above.

First Step The first step can be performed according to the second step of Reaction 1-11.

Second step The second step can be carried out according to the above reaction 1-6.

Reaction 1-15
Reactions 1-15 use the compound of formula (8) or the compound of formula (9) to obtain a compound of formula (105-1) in which ^{RA is hydroxy and RA} of −O- ^YA1 . This is a method for converting to a compound of the formula (105-2).

The symbols in the formula are as described above.

Reaction 1-15 can be carried out according to Reaction E.

Reaction 2-1
In the reaction 2-1 of the compounds of the formula (4), the compound of the formula (4-1) in which T is hydroxy is brominated or chlorinated, so that T is a bromine atom or a chlorine atom (4). -2) This is a method for obtaining the compound.

In the formula, T ¹ is a bromine atom or a chlorine atom, and other symbols are as described above.

Reaction 2-1 can usually be carried out by reacting the compound of formula (4-1) with a brominating agent or a chlorinating agent in the presence of a solvent.

The solvent is not particularly limited as long as the reaction proceeds, and is, for example, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene; and aliphatic hydrocarbons such as hexane, heptane, petroleum ether, ligroine and cyclohexane; Halogenized hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride and 1,2-dichloroethane; one or more can be appropriately selected from ethers such as diethyl ether, tetrahydrofuran and dioxane and mixed solvents thereof.
The brominating agent is not particularly limited as long as the reaction proceeds, and examples thereof include phosphorus oxybromide. The chlorinating agent is not particularly limited as long as the reaction proceeds, and examples thereof include oxalyl chloride, thionyl chloride, and phosphorus oxychloride. The brominating agent or chlorinating agent can be used in a ratio of 1 to 10 equivalents, preferably 1 to 3 equivalents, relative to 1 equivalent of the compound of the formula (4-1).

Reaction 2-1 can also be carried out by adding N, N-dimethylformamide. N, N-dimethylformamide can be used in a ratio of 0.01 to 3 equivalents, preferably 0.05 to 0.3 equivalents, relative to 1 equivalent of the compound of formula (4-1).

The reaction temperature is usually 0 to 200 ° C., preferably 0 to 100 ° C., and the reaction time is usually about 0.1 to 12 hours.

The compound of formula (4-1) can be produced according to a known method or by a method described later, or a commercially available product may be used. Known methods include, for example, International Publication No. WO1993 / 11117, US Pat. No. 5,093,347, etc., but are not limited to these, and those skilled in the art can generally describe them in various documents. Various synthetic methods and combinations thereof can be applied to the present invention.

Reaction 2-2
Reaction 2-2 is a method of reacting ^{a compound of formula (4-3) in which T 2} is alkoxy or aryloxy with an acid or base to obtain a compound of formula (4-1).

In the formula, T ² is alkoxy or aryloxy, and the other symbols are as described above.

Reaction 2-2 can usually be carried out by reacting the compound of formula (4-3) with an acid or a base in the presence of a solvent.

The acid is not particularly limited as long as the reaction proceeds, and for example, hydrochloric acid, sulfuric acid, trifluoroacetic acid, p-toluenesulfonic acid and the like can be used. The base is not particularly limited as long as the reaction proceeds. For example, alkali metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate; alkali metal bicarbonates such as sodium hydrogen carbonate; alkalis such as calcium carbonate. Earth metal carbonates; metal hydroxides such as sodium hydroxide and potassium hydroxide can be mentioned. The acid or base can be used in a ratio of 0.1 to 20 equivalents, preferably 0.1 to 10 equivalents, relative to 1 equivalent of the compound of formula (4-3).
The solvent is not particularly limited as long as the reaction proceeds, and is, for example, aromatic hydrocarbons such as benzene and toluene; aliphatic hydrocarbons such as hexane and heptane; ethers such as diethyl ether, tetrahydrofuran and dioxane; methanol. , Ethanol and other alcohols; Halogenized hydrocarbons such as chloroform, dichloroethane, carbon tetrachloride; water and a mixed solvent thereof and the like can be appropriately selected from one or more.

The reaction temperature is usually 0 to 200 ° C., preferably 0 to 100 ° C., and the reaction time is usually about 1 to 48 hours.

The compound of formula (4-3) can be produced according to a known method or by a method described later, or a commercially available product may be used. Known methods include, for example, International Publication WO2010 / 23358, Journal of the American Chemical Society, Vol. 128, pp. 5310-5311 (2006), US Pat. No. 5,093,347, US Pat. No. 5, 223, 526 and the like can be mentioned, but the present invention is not limited to these, and those skilled in the art can apply the general synthesis methods described in various documents and their appropriate combinations to the present invention.

Reaction 2-3
Reaction 2-3 is a method of reacting a compound of formula (200) with an acid or a base to obtain a compound of formula (4-1).

The symbols in the formula are as described above.

Reactions 2-3 can usually be carried out by reacting the compound of formula (200) with an acid or base in the presence of a solvent.

As the acid, base and solvent, those listed in Reaction 2-2 can be used. The acid or base can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of formula (200).

The reaction temperature is usually 0 to 200 ° C., preferably 0 to 100 ° C., and the reaction time is usually about 1 to 48 hours.

The compound of formula (200) can be produced according to a known method, or a commercially available product may be used.

Reaction 2-4
Reaction 2-4 is a method for obtaining a compound of formula (4-1) by oxidizing the compound of formula (201).

The symbols in the formula are as described above.

Reaction 2-4 can usually be carried out by reacting the compound of formula (201) with an oxidizing agent in the presence of a solvent.

The oxidizing agent is not particularly limited as long as the reaction proceeds, and examples thereof include sodium chlorite, chromium oxide, pyridinium dichromate, potassium permanganate, and the like. The oxidizing agent can be used in a ratio of 0.01 to 20 equivalents, preferably 0.1 to 10 equivalents, relative to 1 equivalent of the compound of the formula (201).
The solvent is not particularly limited as long as the reaction proceeds, and is, for example, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene; and aliphatic hydrocarbons such as hexane, heptane, petroleum ether, ligroine and cyclohexane; Halogenized hydrocarbons such as chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane; alcohols such as ethanol, methanol and butanol; one or more selected from water and mixed solvents thereof. it can.

The reaction temperature is usually −100 to 100 ° C., preferably −80 to 50 ° C., and the reaction time is usually about 1 to 48 hours.

The compound of formula (201) can be produced according to a known method, or a commercially available product may be used.

Reaction 2-5
Reaction 2-5 is a method for converting a compound of formula (202) into a compound of formula (203).

Wherein, B ⁴ is a Hajime Tamaki substituted by X (said heterocyclic group may be further substituted with R ^{B1 'may} also be) a, B ⁵ is a Hajime Tamaki substituted with Q ¹ (the heterocyclic group is R ^{B1 'may} be further substituted with), Q ¹ is an alkoxy, arylalkoxy, haloalkoxy, alkylthio, alkylamino, dialkylamino or aryl alkylamino, R ^C is a hydrogen atom , alkoxy or arylalkoxy, R ^{B1 'is} alkyl, haloalkyl, alkoxyalkyl, cycloalkyl or cyano, and the other symbols are as defined above.

Reaction 2-5 can be carried out according to Reaction F.

The compound of formula (202) can be produced according to a known method, or a commercially available product may be used.

Reaction 2-6
Reaction 2-6 is a method of converting a compound of formula (204) into a compound of formula (205).

Wherein, B ⁶ is a Hajime Tamaki substituted by R ^B and Q ² (said heterocyclic group is, R B ^'may be further substituted with) a, B ⁷ is R ^B and monofluoroalkyl or alkoxy Hajime Tamaki substituted with an alkyl (said heterocyclic group may be further substituted with R B ^'may also be) a, Q ² is an alkyl substituted with Q ^3, Q ³ is hydroxy, chlorine It is an atom, a bromine atom, an iodine atom, a nitro, an alkyl sulphonate or a fluoro sulphonate, and other symbols are as described above.

Reaction 2-6 can usually be carried out by reacting with an alkylating agent and a fluorinating agent in the presence of a base and a solvent.

The alkylating agent is not particularly limited as long as the reaction proceeds, and examples thereof include methyl iodide, alkyl halides such as methyl bromide, dialkyl sulfate such as dimethyl sulfate, and trimethylsilyldiazomethane.
The fluorinating agent is not particularly limited as long as the reaction proceeds; a fluoride salt such as cesium fluoride; a quaternary ammonium salt such as tetra-n-butylammonium fluoride; deoxidation such as crystal fluoride. Fluorinating agent and the like can be mentioned.
Bases include alkali metal alkoxides such as, for example, sodium methoxydo, sodium ethoxydo, potassium tertiary butoxide; carbonates such as sodium carbonate, potassium carbonate; bicarbonates such as sodium hydride, potassium bicarbonate; Metal hydroxides such as sodium hydroxide, potassium hydroxide; metal hydrides such as sodium hydride, potassium hydride; amines such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine; pyridine, 4-dimethyl Pyridines such as aminopyridine; one or more can be appropriately selected from organic lithium compounds such as methyllithium, n-butyllithium and lithiumdiisopropylamide. The alkylating agent, fluorinating agent or base can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of the formula (204).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; alcohols such as methanol, ethanol, propanol, tert-butanol; dimethyl sulfoxide, sulfolane, dimethylacetamide, Polar aprotic solvents such as N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile, propionitrile; one or more can be appropriately selected from water and a mixed solvent thereof.

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

The compound of formula (204) can be produced according to a known method, or a commercially available product may be used.

Reaction 2-7
Reaction 2-7 is a method for obtaining a compound of formula (207) having a fluorine atom.

Wherein, B ⁸ may be substituted with Q ^5, a Hajime Tamaki substituted with R ^B (said heterocyclic group may be further substituted with R ^{B1 '),} B ⁹ is R ^B and a heterocyclic group substituted by fluorine, Q ⁵ is a leaving group (e.g., chlorine, bromine, iodine, nitro, alkyl sulfonate or fluoro sulfonate), an amino or hydroxy, R ^D is hydrogen , Alkoxy, aryloxy, arylalkoxy, hydroxy or halogen, and other symbols are as described above.

In the reaction 2-7, when Q ⁵ is a leaving group, typically, the presence of a solvent, a compound of formula (206), by reacting it with a fluorinating agent to give a compound of formula (207) it can.
The fluorinating agent is not particularly limited as long as the reaction proceeds, and fluoride salts such as cesium fluoride; quaternary ammonium salts such as tetramethylammonium fluoride and tetra-n-butylammonium fluoride can be used. Can be mentioned. The fluorinating agent can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of the formula (206).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile , One or more can be appropriately selected from polar aprotic solvents such as propionitrile and mixed solvents thereof.
The reaction temperature is usually 0 to 200 ° C., preferably 20 to 150 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

In the reaction 2-7, when ^{Q 5} is amino, by Balz-Schiemann reaction, to give a compound of formula (207). In this case, the compound of formula (206) is usually reacted with sodium nitrite and tetrafluoroboric acid in the presence of a solvent. Sodium nitrite and tetrafluoroboric acid can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of formula (206).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile , One or more can be appropriately selected from polar aprotic solvents such as propionitrile and mixed solvents thereof.
The reaction temperature is usually 0 to 200 ° C., preferably 20 to 150 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

In the reaction 2-7, when Q ⁵ is hydroxy, to a compound of formula (206), usually in the presence of a solvent in the presence of a necessary response fluoride salt, by reacting the deoxygenated fluorinating agent The compound of formula (207) can be obtained.
The deoxidizing fluorinating agent is not particularly limited as long as the reaction proceeds, and examples thereof include phenoFluor. The oxygen scavenger fluorinating agent can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of formula (206).
Examples of the fluoride salt include potassium fluoride and cesium fluoride. The fluoride salt can be used in a ratio of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to 1 equivalent of the compound of formula (206).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile , One or more can be appropriately selected from polar aprotic solvents such as propionitrile and mixed solvents thereof.
The reaction temperature is usually 0 to 200 ° C., preferably 20 to 150 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

In Reaction 2-7, when B ⁸ is a ^{heterocyclic group not substituted with Q 5} , the electrophile fluorinating agent is usually reacted in the presence of a solvent and, if necessary, a base. A compound of formula (207) can be obtained.
The electrophilic fluorinating agent is not particularly limited as long as the reaction proceeds, and examples thereof include Selectfluor and N-fluorobenzenesulfonimide. The electrophile fluorinating agent can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of formula (206).
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; dimethylsulfoxide, sulfolane, dimethylacetamide, N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile , One or more can be appropriately selected from polar aprotic solvents such as propionitrile and mixed solvents thereof.
As the base, one or more can be appropriately selected from lithium amide compounds such as lithium diisopropylamide and lithium hexamethyldisilazide. The base can be used in a ratio of 1 to 5 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of formula (206).
The reaction temperature is usually −100 to 200 ° C., preferably −78 to 150 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

The compound of formula (206) can be produced according to a known method, or a commercially available product may be used. In addition, the compound of the formula (206) is, for example, Journal of the American Chemical Society, 139, 1452-1455 (2017), Journal of Organic Chemistry, 80, 12137. Manufactured according to the method described on page (2015), Organic Process Research & Development, Vol. 18, pp. 1041-104 (2014), etc., or a method similar thereto. You can also do it.

Reaction 2-8
Reaction 2-8 is a method of converting a compound of formula (208) into a compound of formula (209) by (halo) alkylation or cycloalkylation.

^{Wherein, B 10} is a Hajime Tamaki having NH substituted with ^{R B} (said heterocyclic group is, ^{R B} 'may be further substituted with) ^{a, B 11} is ^{R B} and (halo) alkyl or a Hajime Tamaki having a substituted N cycloalkyl (said heterocyclic group may be further substituted with R B ^'may also be), and other symbols are as defined above.

Reaction 2-8 can usually be carried out by reacting the compound of formula (208) with a (halo) alkylating agent or a cycloalkylating agent in the presence of a base and a solvent. Further, this reaction can also be carried out by reacting the compound of the formula (208) with the organometallic reagent by adding a base as necessary in the presence of the transition metal reagent and the solvent.

As the (halo) alkylating agent, those listed in Reaction G can be used.
Bases include alkali metal alkoxides such as, for example, sodium methoxydo, sodium ethoxydo, potassium tertiary butoxide; carbonates such as sodium carbonate, potassium carbonate; bicarbonates such as sodium hydride, potassium bicarbonate; Metal hydroxides such as sodium hydroxide, potassium hydroxide; metal hydrides such as sodium hydride, potassium hydride; amines such as monomethylamine, dimethylamine, triethylamine, diisopropylethylamine; pyridine, 4-dimethyl Pyridines such as aminopyridine; one or more can be appropriately selected from organic lithium compounds such as methyllithium, n-butyllithium and lithiumdiisopropylamide. The (halo) alkylating agent or base can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, relative to 1 equivalent of the compound of formula (208).
The organometallic reagent is not particularly limited as long as the reaction proceeds, and examples thereof include organoboron compounds. The organometallic reagent can be prepared according to a known method, or a commercially available product may be used. The organometallic reagent can be used in an amount of 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to the compound of formula (208).
As the transition metal reagent, various known structures used in the cross-coupling reaction can be used, and the transition metal reagent containing copper is particularly useful for this reaction. For example, copper acetate (II) and the like can be mentioned. In addition, diamine can be used as a ligand, if necessary. Examples of the diamine include N, N, N', N'-tetramethylethylenediamine, 2,2'-bipyridyl and the like. The transition metal reagent can be used in an amount of 0.1 to 5 equivalents, preferably 0.5 to 1.5 equivalents, relative to the compound of formula (208). Further, the ligand can be used in an amount of usually 1 to 10 equivalents, preferably 1 to 5 equivalents, relative to 1 equivalent of the transition metal catalyst. However, depending on the reaction conditions, an amount outside this range can be used.
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; alcohols such as methanol, ethanol, propanol, tert-butanol; dimethyl sulfoxide, sulfolane, dimethylacetamide, Polar aprotic solvents such as N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile, propionitrile; one or more can be appropriately selected from water and a mixed solvent thereof.

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

The compound of formula (208) can be produced according to a known method, or a commercially available product may be used.

Reaction 2-9
Reaction 2-9 is a method of converting a compound of formula (210) into a compound of formula (211) by (halo) alkylation, silylation, alkoxyalkylation, alkoxycarbonylation or arylalkoxycarbonylation.

^{Wherein, B 12} is ^-L B2 ^{-Y B3} Hajime Tamaki substituted by (the heterocyclic group, ^{R B} 'may be further substituted with) ^{a, Y B3} is alkyl, haloalkyl, trialkyl It is a silyl, an alkoxyalkyl, an alkoxycarbonyl or an arylalkoxycarbonyl, and other symbols are as described above.

Reaction 2-9 usually involves adding a (halo) alkylating agent, a silylating agent, an alkoxyalkylating agent, an alkoxycarbonylating agent or an arylalkoxycarbonylating agent to the compound of formula (210) in the presence of a base and a solvent. It can be done by reacting. The (halo) alkylating agent, silylating agent, alkoxyalkylating agent or base can be used in a ratio of 1 to 20 equivalents, preferably 1 to 10 equivalents, per 1 equivalent of the compound of formula (210). The alkoxycarbonylating agent or arylalkoxycarbonylating agent can be used in an amount of 1 to 3 equivalents, preferably 1 to 2 equivalents, relative to 1 equivalent of the compound of the formula (210).

As the (halo) alkylating agent, those listed in Reaction G can be used.
Examples of the silylating agent include chlorotriethylsilane and chlorotriisopropylsilane.
Examples of the alkoxyalkylating agent include chloromethyl methyl ether and the like.
Bases include alkali metal alkoxides such as, for example, sodium methoxydo, sodium ethoxydo, potassium tertiary butoxide; carbonates such as sodium carbonate, potassium carbonate; bicarbonates such as sodium hydride, potassium bicarbonate; Metal hydroxides such as sodium hydroxide, potassium hydroxide; metal hydrides such as sodium hydride, potassium hydride; amines such as monomethylamine, dimethylamine, triethylamine; pyridine, 4-dimethylaminopyridine Such pyridines; one or more can be appropriately selected from organic lithium compounds such as methyl lithium, n-butyl lithium, lithium diisopropylamide and the like.
Examples of the alkoxycarbonylating agent include di-tert-butyl dicarbonate, and examples of the arylalkoxycarbonylating agent include benzyl chloroformate.
The solvent may be any solvent inert to the reaction, for example aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene; carbon tetrachloride, methyl chloride, chloroform, dichloromethane, dichloroethane, trichloroethane, etc. Aliper hydrocarbons such as hexane, cyclohexane; ethers such as dioxane, tetrahydrofuran, diethyl ether, dimethoxyethane; alcohols such as methanol, ethanol, propanol, tert-butanol; dimethyl sulfoxide, sulfolane, dimethylacetamide, Polar aprotic solvents such as N, N-dimethylformamide, N-methylpyrrolidone, pyridine, acetonitrile, propionitrile; one or more can be appropriately selected from water and a mixed solvent thereof.

The reaction temperature is usually 0 to 100 ° C., preferably 0 to 80 ° C., and the reaction time is usually about 0.1 to 48 hours, preferably about 0.1 to 24 hours.

The compound of formula (210) can be produced according to a known method, or a commercially available product may be used.

The compound of the present invention is useful as an active ingredient of a fungicide for agriculture and horticulture that can control harmful fungi with a low dosage. When used as a bactericidal agent for agriculture and gardening, the compound of the present invention can control harmful fungi belonging to, for example, egg fungi (Oomycetes), ascomycetes (Ascomycetes), basidiomycetes, and incomplete fungi (Deuteromycetes). Among them, it is particularly effective for controlling harmful fungi belonging to ascomycetes (Ascomycetes) and incomplete fungi (Deuteromycetes).

More specific examples of the harmful fungi include, for example, the following.
As Oomycetes, potato or tomato late blight (Phytophthora infestans), Phytophthora such as tomato gray Phytophthora (Phytophthora capsici) (Phytophthora) genus; pseudotyped Perot Roh Supora as cucumber downy mildew (Pseudoperonospora cubensis) (Pseudoperonospora) genus ; grape downy mildew (Plasmopara viticol a) Purazumopara like (Plasmopara) genus; rice seedling blight (Pythium graminicola), Pythium (Pythium) genus, and the like, such as wheat brown snow molds (Pythium iwayamai) ..

As ascomycetes, Erysiphe such as wheat powdery mildew (Erysiphe graminis) (Erysiphe) genus; cucumber powdery mildew (Sphaerotheca fuliginea), Sphaerotheca (Sphaerotheca) such as strawberry powdery mildew (Sphaerotheca humuli) genus; grape udon Unshinyura such as this fungus (Uncinula necator) (Uncinula) genus; Podosufaera such as apple powdery mildew (Podosphaera leucotricha) (Podosphaera) genus; pea褐紋fungus (Mycosphaerella pinodes), apple black spot fungus (Mycosphaerella pomi), banana black Sigatoka fungus (Mycosphaerella musicola), oysters circle star deciduous fungus (Mycosphaerella nawae), Mikosufaerera (Mycosphaerella) species such as the strawberry bull's-eye fungus (Mycosphaerella fragariae); apple scab (Venturia inaequalis), pear scab (Venturia nashicola) venturi a (Venturia) genus like; barley net plaques fungi (Pyrenophora teres), Pirenohora such as barley Madaraha fungi (Pyrenophora graminea) (Pyrenophora) spp; bean Sclerotinia sclerotiorum, cucumber Sclerotinia sclerotiorum, cabbage Sclerotinia cinerea , Sclerotinia sclerotiorum , Sclerotinia sclerotiorum, Sclerotinia borealis , Sclerotinia borealis, Sclerotinia sclerotiorum, Sclerotinia sclerotiorum, Sclerotinia borealis Sclerotinia minor), alfalfa Sclerotinia sclerotiorum (Sclerotinia trifoliorum sclerotinia (Sclerotinia) like) genus; Botoriorinia (Botryolinia) genus, such as peanut small Sclerotinia cinerea (Botryolinia arachidis); rice sesame leaf spot fungus (Cochliobolus miyabeanus) Sclerotinia sclerotinia Las (Cochliobolus) genus; Didimera such as cucumber vines oryzae (Didymella bryoniae) (Didymella) genus; Gibberella (Gibberella) spp, such as Gibberella fujikuroi (Gibberella fujikuroi); grape black痘病bacteria (Elsinoe ampelina), citrus Erushinoe such as a layer or fungus (Elsinoe fawcettii) (Elsinoe) genus; citrus black spot fungus (Diaporthe citri), Diaporuse (Diaporthe) such as grapes branch膨病bacteria belonging to the genus (Diaporthe sp.); Ringomoniria fungus (Monilinia mali), Monirinia (Monilinia) genus, such as peach ash star fungus (Monilinia fructicola); Guromerera (Glomerella) such as grape evening rot fungus (Glomerella cingulata) genus, and the like.

As Basidiomycetes, Rhizoctonia such as rice sheath blight fungi (Rhizoctonia solani) (Rhizoctonia) genus; Ustilago, such as wheat loose smut pathogen (Ustilago nuda) (Ustilago) genus; Oat Crown Rust Fungus (Puccinia coronata), wheat brown rust fungus (Puccinia recondita), Pukushinia (Puccinia), such as wheat yellow rust (Puccinia striiformis) genus; Phakopsora (Phakopsora) such as soybean rust (Phakopsora pachyrhizi) genus; wheat or barley snow mold small Sclerotinia sclerotiorum (Typhula Examples include the genus Typhula, such as incarnata , Typhula ishikariensisis).

As Deuteromycetes, wheat glume blotch fungus (Septoria nodorum), Septoria (Septoria) such as wheat leaf blotch fungi (Septoria tritici) genus; grape Botrytis, citrus Botrytis cinerea, cucumber Botrytis cinerea, tomato Botrytis cinerea Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea Botrytis cinerea , Botrytis cinerea, Botrytis allii, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea, Botrytis cinerea cause leaf blight disease caused by bacteria pathogens (Botrytis squamosa, Botrytis byssoidea, Botrytis tulipae) Botrytis (Botrytis) species, such as, wheat Fusarium fungus (Fusarium graminearum), Fusarium, such as cucumber Fusarium fungus (Fusarium oxysporum) (Fusarium ) genus Pyricularia, such as rice blast fungus (Pyricularia oryzae) (Pyricularia) genus; sugar beet brown spot fungus (Cercospora beticola), Sakosupora such as oysters angle plaques fungus (Cercospora kakivola) (Cercospora) genus; cucumber anthracnose fungi ( Colletotrichum orbiculare Colletotrichum (Colletotrichum), such as a) the genus; apple leaf spot fungus (Alternaria alternata apple pathotype), pear black spot fungus (Alternaria alternata Japanese pear pathotype), potatoes summer disease or tomato Wamon fungus (Alternaria solani), cabbage or Chinese cabbage black spot fungus (Alternaria brassicae), cabbage black soot fungus (Alternaria brassicola), onion or Welsh onion black Spot fungus (Alternar Alternaria (Alternaria) genera, such as ia porri); shoe de circo Supora (Pseudocercospora) species, such as the grape brown spot fungus (Pseudocercospora vitis); wheat Memon fungus (Pseudocercosporella herpotrichoides shoe de circo spot these, such as a) (Pseudocercosporella) genus ; Homopushisu such as Momohomopushisu rot Rinko sports helium (Rhynchosporium) species such as barley scald fungi (Rhynchosporium secalis);; peach scab (Cladosporium carpophilum) Cladosporium (Cladosporium), such as the genus (Phomopsis sp.) (Phomopsis) spp; Gro Eos poly um (Gloeosporium) such as persimmon anthracnose fungi (Gloeosporium kaki) genus; Fulvia (Fulvia) such as tomato leaf mold fungus (Fulvia fulva) genus; cucumber brown spot pathogen (Corynespora cassiicola) Korinesupora (Corynespora) genus, and the like, such as.

Since the compound of the present invention can control the above-mentioned various harmful fungi, various diseases can be controlled prophylactically or therapeutically. In particular, the compound of the present invention contains various diseases that cause problems in the field of agriculture and horticultural fields, such as blast caused by Pyricularia, stupid seedling disease caused by Fuzarium, sesame leaf blight caused by Cochliobolus, and blight caused by lysoctonia; Udonko disease caused by Elysife, red mold caused by Fuzarium, rust caused by Pucsina, brown snow rot caused by Pythium, naked scab caused by Ustilago, eye print disease caused by Pseudocercosporella, leaf blight caused by Septoria Diseases of wheat such as disease or wilt; red mold caused by Fuzarium, spot disease caused by Faeospheria, rust caused by Pucsinia, soot scab caused by Setofaeria, sesame leaf blight caused by Cochliobolus, Pythium Root rot caused by bacillus, corn diseases such as smut caused by Ustilago bacterium; scab caused by bacillus bacillus, leaf burn disease caused by stagonospora, rust caused by puccinia, treetop rot caused by diberella, soot disease caused by cardariomises, Diseases of rice crops such as sugar cane diseases such as leaf blight caused by Pseudocercospora; Udonko disease caused by Eudium, rust caused by Facopsora, beetle caused by Peronosora, epidemic caused by Phytofutra, charcoal caused by Collettricum Diseases of legumes such as soybean disease, mycorrhizal disease caused by Sclerotinia, gray mold caused by Botrytis, root rot or wilt caused by Fuzarium; yellowing caused by Fuzarium, sticky disease caused by Peronospora, Diseases of Abranaceae crops such as black spot caused by Altanaria; scab caused by Bremia, epidemic caused by Phytofutra, gray mold caused by Botrytis, mycorrhizal disease caused by Sclerotinia, rust caused by Aesidium, etc. Diseases of family crops; ring-spot disease caused by Altanaria, leaf mold caused by Fulvia, plague caused by Phytophthora, gray mold caused by Botrytis, udon disease caused by Eudium, wilt disease caused by Fuzarium, and Pseudocercospora. Diseases of tomatoes such as soybean disease; diseases of eggplant family crops such as summer epidemic caused by Altanaria, epidemic caused by Phytofutra, mycorrhizal disease caused by Sclerotinia, and potato diseases such as dry rot caused by Fuzarium; Charcoal disease caused by Sphaeroteca, Udonko disease caused by Sphaeroteca, Vine blight caused by Didimela, Sticky disease caused by Pseudoperonospora, Epidemic caused by Phytofutra, Brown spot disease caused by Corinespora, Vine disease caused by Fuzarium, etc. Disease Diseases of things; powdery mildew caused by Peronospora, epidemic caused by Phytofutra, gray mold caused by Botrytis, powdery mildew caused by Sclerotinia, powdery mildew caused by Pucsinia, etc. Diseases of Seri family crops such as blight or black spot disease, gray mold caused by Botrytis, fusarium caused by Sclerotinia, powdery mildew caused by Elysife, and spot disease caused by Circospora; leaf blight caused by Botrytis, Diseases of lily family crops such as plague caused by Phytofutra, stem blight caused by homopsis; powdery mildew caused by Peronospora, powdery mildew caused by Elysife, disease caused by blight caused by Fusarium fungus; Diseases of Hirugao family crops such as vine split disease, black spot disease caused by Seratocystis, and wilt disease caused by Streptomyces; powdery mildew caused by Peronospora, epidemic caused by Phytofutra, gray mold caused by Botrytis, scleroti Diseases of Akaza family crops such as fusarium caused by near bacteria, powdery mildew caused by fusarium bacteria, brown spot disease caused by circospora bacteria; black scab caused by Elsinoe bacteria, late rot caused by collettricham bacteria, powdery mildew caused by Elysife bacteria, plasmopara Diseases of vines such as scab caused by fungi, gray mold caused by Botrytis, brown spot disease caused by Pseudosarcospora, branch swelling caused by Diaporte; powdery mildew caused by Sphaeroteca, gray mold caused by Botrytis, Strawberry diseases such as charcoal sickness caused by Glomerella and fusarium; powdery mildew caused by Monilinia, powdery mildew caused by Podosfaela, spot foliar disease caused by Altanaria, scab caused by Venturia, charcoal caused by Glomerella Powdery mildew, brown spot disease caused by Diprocarpon, powdery mildew caused by Botriosfaelia, powdery mildew caused by Chigofiara, powdery mildew caused by Groeodes, black spot caused by Micosphaerella, etc. Pear diseases such as scab, black spot caused by Altanaria, powdery mildew caused by Filactinia, epidemic caused by Fusarium, and fruit rot caused by Fusarium; Diseases of rose family crops such as peach diseases such as homopsis rot caused by Homopsis bacterium; powdery mildew caused by Diaporte bacterium, powdery mildew caused by Fusarium bacterium, Fusarium blight caused by Fusarium bacterium, etc. Diseases of family crops Diseases of Theaceae crops such as charcoal disease caused by Groeosporium, leaf fall disease caused by Circospora, powdery mildew caused by Filactinia, and soot spot disease caused by Chigofiara; It is effective in controlling plant diseases such as ring spot disease caused by Opsis, red burning disease caused by Pseudomonas, and blast disease caused by Camellia.
In addition, Fusarium head blight caused by Fusarium, charcoal disease caused by Choletotricum, Namagusa scab caused by Tyretia, bare scab caused by Ustilago, streak disease caused by Septoria sporium, and wilt disease caused by Septoria. Disease;
Corn diseases such as sesame leaf blight caused by Vipolaris, charcoal disease caused by Collettricum, and seedling blight caused by Fuzarium; red rot caused by Glomerella, black rot caused by Seratocystis, and scab caused by Sclerospora. Diseases of rice crops such as sugar cane diseases such as; purpura caused by circospora, sticky disease caused by peronospora, wilt disease caused by fuzarium, brown spot disease caused by septoria, black spot disease caused by diaporte, and cholettricum. Diseases of legumes such as charcoal disease, sleepy disease caused by Septgroium, and black spot caused by Altanaria brushcae, black spot caused by Altanaria brushcola, sticky disease caused by Peronospora, and black spot caused by Pseudomonas. Bacterial diseases, black rot caused by Zantomonas, root rot caused by Forma, and other cabbage diseases; black spots caused by Altanaria, yellowing caused by Fuzarium, and black rot caused by Zantomonas, etc. Diseases of Abrana crops such as black spot disease, black rot caused by Zantomonas bacterium, yellowing disease caused by Verticillium bacterium, etc.; Bacterial and other tomato diseases; Altanaria-induced brown spot disease, Homopsis-induced brown spot disease and other eggplant diseases; Streptomyces-induced scab, Hermintsporium-induced silver scab, Spongospora-induced powder Diseases of nasal crops such as potato diseases such as scab; Diseases of urine crops such as black spot disease caused by Altanaria, spot bacterial disease caused by Pseudomonas bacterium, brown spot bacterial disease caused by Zantomonas bacterium; Diseases of Negi family crops such as black spot disease caused by Altanaria, gray rot or mycelial rot caused by Botrytis, dry rot caused by Fuzarium, and onion disease such as sticky disease caused by Peronospora; Bacterial blight or black spot disease, spot bacterial disease caused by Zantomonas bacterium; Seri family crops such as bacterial leaf blight caused by Septoria, mycorrhizal disease caused by Sclerotinia, and bacterial leaf blight caused by Pseudomonas bacterium. It is also effective for seed-borne diseases such as scab caused by Peronospora, wilt caused by Fuzarium, and scab of spinach such as charcoal disease caused by Choletotricum.
Furthermore, it is also effective in controlling soil diseases caused by phytopathogens such as Fusarium, Pythium, Rhizoctonia, Verticillium, Plasmodiohorae, and Tierrabiopsis.

The plants that can be protected from various phytopathogenic bacteria by the present invention are not particularly limited as long as they are agriculturally useful, but for example, rice crops (rice, wheat, barley, embuck, lime tree, corn, sugar cane, etc.), beans, etc. Family crops (soybeans, green beans, azuki, etc.), Abrana family crops (cabbage, hakusai, daikon, cub, broccoli, potash flower, navana, sardine, etc.), Kiku family crops (lettuce, gobo, shungiku, etc.) Potatoes, eggplants, tomatoes, peppers, tobacco, etc.), Uri family crops (cucumber, pumpkin, melon, watermelon, etc.), Negi family crops (negi, nira, rakkyo, garlic, etc.), Seri family crops (cellly, carrot, parsley, etc.) ), Yuri family crops (lily, tulip, asparagus, etc.), Tade family (soba, etc.), Hirugao family (sweet potato, etc.), Akaza family crops (Horensou, Tensai, etc.), Vine family crops (grape, etc.), Rose family crops (Rose, strawberry, apple, pear, peach, biwa, almond, etc.), Mikan family crop (Mikan, Lemon, Orange, etc.), Kakinoki family crop (Kaki, etc.), Tsubaki family crop (Cha, etc.), Mokusei family crop (Olive) , Jasmine, etc.), Aoi family crops (Wata, Cacao, Okla, etc.), Basho family crops (Banana, etc.), Ginger family crops (Ginger, etc.), Akane family crops (Coffee tree, etc.) or Pineapple family crops (Pineapple, Ananas, etc.) Can be mentioned.

The compound of the present invention is also effective in controlling various resistant harmful fungi to drugs such as benzimidazole, strobilurin, dicarboxyimide, phenylamide, and ergosterol biosynthesis inhibitor.

Furthermore, since the compound of the present invention has excellent permeation transferability, by applying a pest control agent containing the compound of the present invention to the soil, harmful fungi in the soil can be controlled and at the same time harmful to the foliage. Fungi can also be controlled.

The compound of the present invention is usually a mixture of the compound of the present invention and various agricultural auxiliary agents, and is used as a powder, granule, granule wettable powder, wettable powder, aqueous suspension, oil suspension, aqueous solvent, emulsion. , Liquids, pastes, aerosols, microsprays, etc., but as long as it meets the objectives of the present invention, it should be in any form commonly used in the art. Can be done. Auxiliary agents used in the formulation include solid carriers such as diatomaceous soil, slaked lime, calcium carbonate, talc, white carbon, kaolin, bentonite, kaolinite and sericite mixture, clay, sodium carbonate, baking soda, grated glass, zeolite and starch. Solvents such as water, toluene, xylene, solvent naphtha, dioxane, acetone, isophorone, methylisobutylketone, chlorobenzene, cyclohexane, dimethylsulfoxide, N, N-dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, alcohol; Fatty acid salts, benzoates, alkyl sulfosuccinates, dialkyl sulfosuccinates, polycarboxylates, alkyl sulfates, alkyl sulfates, alkylaryl sulfates, alkyldiglycol ether sulfates, alcohol sulfates, alkylsulfones Acids, alkylaryl sulfonates, aryl sulfonates, lignin sulfonates, alkyl diphenyl ether disulfonates, polystyrene sulfonates, alkyl phosphates, alkylaryl phosphates, styrylaryl phosphates, polyoxy Ethethylene alkyl ether sulfate ester salt, polyoxyethylene alkylaryl ether sulfate salt, polyoxyethylene alkylaryl ether sulfate ester salt, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkylaryl phosphate ester salt, naphthalene sulfonic acid formalin condensation Anionic surfactants and spreading agents such as salts of substances; sorbitan fatty acid ester, glycerin fatty acid ester, fatty acid polyglyceride, fatty acid alcohol polyglycol ether, acetylene glycol, acetylene alcohol, oxyalkylene block polymer, polyoxyethylene Alkyl ether, polyoxyethylene alkylaryl ether, polyoxyethylene styrylaryl ether, polyoxyethylene glycol alkyl ether, polyethylene glycol, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene Nonionic surfactants and spreading agents such as hardened castor oil, polyoxypropylene fatty acid esters; olive oil, capoc oil, castor oil, shro oil, camellia oil, palm oil, sesame oil, corn oil, rice bran oil, peanut oil, Cotton seed oil, soybean oil , Vegetable oils such as rapeseed oil, linseed oil, cutting oil, liquid paraffin, and mineral oils. As long as each component of these auxiliary agents does not deviate from the object of the present invention, one kind or two or more kinds can be appropriately selected and used. In addition to the above-mentioned auxiliary agents, those known in the art can be appropriately selected and used. For example, a bulking agent, a thickener, a sedimentation inhibitor, an antifreeze agent, a dispersion stabilizer, and a phytotoxicity reduction agent. Various commonly used auxiliary agents such as agents and fungicides can also be used. The blending ratio of the compound of the present invention and various auxiliary agents is 0.001: 99.999 to 95: 5, preferably 0.005: 99.995 to 90:10. In actual use of these preparations, they can be used as they are, or diluted to a predetermined concentration with a diluent such as water, and various spreading agents (surfactant, vegetable oil, mineral oil, etc.) are added as necessary. Can be used.

The application of the compound of the present invention cannot be unequivocally defined due to differences in weather conditions, formulation form, target crop, application time, application location, type and outbreak status of harmful fungi, type and outbreak status of diseases, etc. In the case of, it can be applied at an active ingredient concentration of 0.1 to 10,000 ppm, preferably 1 to 2,000 ppm, and the appropriate amount for application is 0.1 to 50,000 g, preferably about 1 to 30,000 g of the compound of the present invention per hectare. be able to. In the case of soil treatment, generally 10 to 100,000 g, preferably 200 to 20,000 g of the compound of the present invention can be applied per hectare.

The application of various preparations of the compounds of the present invention, or dilutions thereof, is a commonly used application method, that is, spraying (for example, spraying, spraying, misting, atomizing, granulation, water surface application, etc.), soil application (for example, spraying, spraying, misting, water surface application, etc.). It can be performed by mixing (mixing, irrigation, etc.), surface application (coating, powder coating, coating, etc.), etc. It can also be applied by the so-called ultra low volume method. In this method, it is possible to contain 100% of the active ingredient.

The compound of the present invention can be mixed or used in combination with other pesticides, fertilizers, phytotoxicity reducing agents, etc., and in this case, it may exhibit more excellent effect and activity. Other pesticides include herbicides, pesticides, acaricides, nematodes, soil pesticides, fungicides, antiviral agents, attractants, antibiotics, plant hormones, plant growth regulators, etc. .. In particular, a mixed bactericidal composition in which one or more of the other bactericidal active ingredient compounds are mixed or used in combination with the compound of the present invention improves the applicable range, the timing of chemical treatment, the control activity, etc. in a preferable direction. I have something to do. The compound of the present invention and the active ingredient compound of another bactericidal agent may be prepared separately and mixed at the time of spraying, or both may be prepared and used together. The present invention also includes such a mixed bactericidal composition.

The mixing ratio of the compound of the present invention to other bactericidal active ingredient compounds depends on the weather conditions, formulation form, target crop, application time, application location, type and outbreak status of harmful fungi, type and outbreak status of diseases, etc. Although it cannot be unconditionally specified, it can be generally 1: 300 to 300: 1, preferably 1: 100 to 100: 1. The appropriate amount for application can be 0.1 to 70,000 g, preferably 1 to 30,000 g, as the total amount of the active ingredient compound per hectare. The present invention also includes a method for controlling plant diseases by applying such a mixed bactericidal composition.

In applying the compound of the present invention, other pesticides such as fungicides, insecticides, acaricides, nematodes, soil pesticides, antiviral agents, attractants, herbicides, plant growth regulators, etc. are further added. It can also be processed at the same time.

The active ingredient compound (generic name or Japanese Plant Protection Association test code) of the fungicide in the above other pesticides can be appropriately selected from the following compound group, for example. Even if there is no particular description, if various structural isomers such as salts, alkyl esters, and optical isomers are present in these compounds, they are naturally included.
Anilinopyrimidine compounds such as mepanipyrim, pyrimethanil, cyprodinil;
Triazolopyrimidine compounds such as ametoctradin;
Pyridinamine compounds such as fluazinam;
Triadimefon, bitertanol, triflumizole, etaconazole, propiconazole, penconazole, flusilazole, myclobutanil, cyproconazole (cyproconazole) cyproconazole), tebuconazole, hexaconazole, furconazole-cis, prochloraz, metconazole, epoxyconazole, tetraconazole, o Xispoconazole fumarate, prothioconazole, triadimenol, flutriafol, difenoconazole, fluquinconazole, fenbuconazole , Bromuconazole, diniconazole, tricyclazole, simeconazole, pefurazoate, ipconazole, imibenconazole, azaconazole, triticazole ), Imazalil, ipfentrifluconazole, mefentrifluconazole and other azole compounds;
Quinoxaline compounds such as quinomethionate;
Dithiocarbamate compounds such as maneb, zineb, mancozeb, polycarbamate, metiram, propineb, thiram;
Organochlorine compounds such as fthalide, chlorothalonil, quintozene;
Imidazole compounds such as benomyl, thiophanate-methyl, carbendazim, thiabendazole, fuberiazole;
Cyanoacetamide compounds such as cymoxanil;
Metalaxyl, metalaxyl-M (also known as mefenoxam), oxadixyl, offurace, benalaxyl, benalaxyl-M (also known as kiralaxyl-M, also known as kiralaxyl, kiralaxyl). )), Acyl amino acid compounds such as furalaxyl, valifenalate;
Cyprofuram, carboxin, oxycarboxin, thifluzamide, boscalid, fenhexamid, isotianil, tiadinil, pyraziflumid Anilide compounds such as;
Sulfamide compounds such as dichlofluanid;
Like cupric hydroxide, oxine copper, anhydrous copper sulfate, nonylphenol sulfonate copper, 8-hydroxyquinoline copper, dodecylbenzene sulfonate bisethylenediamine copper complex salt (II) (also known as DBEDC). Copper-based compound;
Organophosphorus compounds such as fosetyl-Al, tolclofos-Methyl, edifenphos, iprobenfos;
Phthalimide compounds such as captan, captafol, folpet;
Dicarboxyimide compounds such as procymidone, iprodione, vinclozolin;
Benzanilide compounds such as flutolanil, mepronil, benodanil;
Amide compounds such as carpropamid, diclocymet, silthiopham, fenoxanil;
Benzovindiflupyr, bixafen, fluindapyr, fluxapyroxad, furametpyr, isopyrazam, penflufen, penthiopyrad, pidiflurad Pyrazole carboxamide compounds such as pydiflumetofen, sedaxane, isoflucypram, impyrfluxam, pyrapropoyne;
Benzamide compounds such as fluopicolide, fluopyram, zoxamide, fluopimomide;
Furanilide compounds such as fenfuram;
Thiophene amide compounds such as isofetamid;
Piperazine compounds such as triforine;
Pyridine compounds such as pyrifenox, pyrisoxazole, aminopyrifen;
Pyrimidine compounds such as fenarimol, ferimzone, nuarimol;
Piperidine compounds such as fenpropidin;
Morpholine compounds such as fenpropimorph, tridemorph;
Organic tin compounds such as fentin hydroxide and fentin acetate;
Urea compounds such as peniccuron;
Carboxylic acid amide compounds such as dimethomorph, flumorph, pyrimorph, iprovalicarb, benthiavalicarb-isopropyl, mandipropamid;
Phenyl carbamate compounds such as diethofencarb;
Cyanopyrrole compounds such as fludioxonil and fenpiclonil;
Azoxystrobin, kresoxim-methyl, metomirostrobin, trifloxystrobin, picoxystrobin, oryzastrobin, dymoxystrobin (oryzastrobin) dimoxystrobin, pyraclostrobin, fluoxastrobin, Enestroburin, Pyraoxystrobin, Pyrametostrobin, coumoxystrobin, enokistrobin Strobilurin compounds such as robin (enoxastrobin), fenaminstrobin, flufenoxystrobin, triclopyricarb, mandestrobin;
Oxazole compounds such as famoxadone, oxathiapiprolin;
Thiazole carboxamide compounds such as ethaboxam;
Imidazolinone compounds such as fenamidone;
Benzene sulfonamide compounds such as flusulfamide;
Oxime ether compounds such as cyflufenamid;
Anthraquinone compounds such as dithianon;
Crotonic acid compounds such as meptyldinocap;
Antibiotics such as validamycin, kasugamycin, streptomycin, polyoxins;
Guanidine compounds such as iminoctadine and dodine;
Quinoline compounds such as tebufloquin, quinoxyfen, quinofumelin, ipflufenoquin;
Thiazolidine compounds such as flutianil;
Carbamate compounds such as propamocarb hydrochloride, pyribencarb, tolprocarb;
Tetrazole compounds such as picarbutrazox, methyltetraprole;
Sulfonamide compounds such as amisulbrom, cyazofamiid;
Allylphenylketone compounds such as metrafenone and pyriofenone;
Benzothiazole compounds such as probenazole, dichlobentiazox;
Phenylpyrazole compounds such as fenpyrazamine;
Dithiolane compounds such as isoprothiolane;
Picoline amide compounds such as fenpicoxamid, florylpicoxamid;
Sulfur compounds such as sulfur and lime sulfur;
Other compounds include pyroquilon, diclomezine, chloropicrin, dazomet, metam-sodium salt, proquinazid, spiroxamine, dipymetitrone, etc. ;
Bacillus amyloliqefaciens strain QST713, Bacillus amyloliqefaciens strain FZB24, Bacillus amyloliqefaciens strain MBI600, Bacillus amyloliqefaciens strain D747, Pseudomonas fluorescens, Bacillus subtilis Plant extract.

Among the above other pesticides, pesticides, acaricides, nematode pesticides or soil pesticides, that is, active ingredient compounds of pesticides (generic name or Japan Plant Protection Association test code) include, for example, the following. It can be appropriately selected from the compound group. Even if there is no particular description, if various structural isomers such as salts, alkyl esters, and optical isomers are present in these compounds, they are naturally included.
Profenofos, dichlorvos, fenamiphos, fenitrothion, EPN ((RS)-(O-ethyl O-4-nitrophenyl phenylphosphonothioate)), diazinon, chlorpyrifos, chlorpyrifos Methyl (chlorpyrifos-methyl), acephate, prothiofos, fosthiazate, cadusafos, disulfoton, isoxathion, isofenphos, ethion, ethion ), Quinalphos, dimethylvinphos, dimethoate, sulprofos, thiometon, vamidothion, pyraclofos, pyridaphenthion, pyridaphenthion, pirimiphos , Propaphos, phosalone, formothion, malathion, tetrachlorvinphos, chlorfenvinphos, cyanophos, trichlorfon, methidathion ), Phenthoate, oxydeprofos (also known as ESP), azinphos-methyl, fenthion, heptenophos, methoxychlor, parathion, phosphocarb, demeton -S-methyl (demeton-S-methyl), monocrotophos, metamidophos, imisia Organic phosphate compounds such as imicyafos, parathion-methyl, terbufos, phosphamidon, phosmet, phorate;
Carbaryl, propoxur, aldicarb, carbofuran, thiodicarb, methomyl, oxamyl, ethiofencarb, pyrimicarb, fenobucarb, fenobucarb Carbosulfan, benfuracarb, bendiocarb, furathiocarb, isoprocarb, metolcarb, xylylcarb, XMC (3,5-xylyl methylcarbamate), phenothiocarb Carbamate compounds such as (fenothiocarb);
Cartap, thiocyclam, thiocyclam oxalate, thiocyclam hydrochloride, bensultap, thiosultap, monosultap; also known as thiosultap- Nelystoxin derivatives such as monosodium, bisultap; also known as thiosultap-disodium, polythialan;
Organochlorine compounds such as dicofol, tetradifon, endosulfan, dienochlor, dieldrin;
Organometallic compounds such as fenbutatin oxide and cyhexatin;
Fenvalerate, permethrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, theta-cypermethrin, beta-cypermethrin Permethrin (beta-cypermethrin), deltamethrin (deltamethrin), cyhalothrin (cyhalothrin), gamma-cyhalothrin (gamma-cyhalothrin), lambda-cyhalothrin (lambda-cyhalothrin), tefluthrin (tefluthrin), kappa-tefluthrin (kappa-tefluthrin) Ethofenprox, flufenprox, cyfluthrin, beta-cyfluthrin, fenpropathrin, flucythrinate, fluvalinate, cycloprothrin (Cycloprothrin), pyrethrins, esfenvalerate, tetramethrin, resmethrin, protrifenbute, bifenthrin, kappa-bifenthrin, acrinathrin acrinathrin, allethrin, tau-fluvalinate, tralomethrin, profluthrin, metofluthrin, epsilon-metofluthrin, heptafluthrin Phenothrin, flumethrin, momfluorothrin, epsilon-momfluorothrin, silafluof en), pyrethroid compounds such as chloroprallethrin;
Diflubenzuron, chlorfluazuron, teflubenzuron, flufenoxuron, lufenuron, novaluron, triflumuron, hexaflumuron, bis Benzoylurea compounds such as (bistrifluron), noviflumuron, fluazuron;
Juvenile hormone-like compounds such as methoprene, pyriproxyfen, fenoxycarb, diofenolan;
Pyridadinone compounds such as pyridaben;
Pyrazole compounds such as fenpyroximate, fipronil, ethiprole, acetoprole, pyrafluprole, pyriprole, cyenopyrafen, flufiprole. ;
Pyrazole carboxamide compounds such as pyflubumide, tebufenpyrad, tolfenpyrad;
Pyridylpyrazole compounds such as chlorantraniliprole, cyantraniliprole, cyclaniliprole, tetraniliprole, tyclopyrazoflor;
Imidacloprid, nitenpyram, acetamiprid, thiacloprid, thiamethoxam, clothianidin, nidinotefuran, nidinotefuran, dinotefuran Noid compounds;
Hydrazine compounds such as tebufenozide, methoxyfenozide, chromafenozide, halofenozide;
Pyridine compounds such as pyridalyl and flonicamid;
Tetrolic acid compounds such as spirodiclofen, spiromesifen;
Tetramic acid compounds such as spirotetramat, spiropidion;
Strobilurin compounds such as fluacrypyrim, pyriminostrobin;
Pyrimidinamine compounds such as flufenerim, pyrimidifen;
Organic sulfur compounds such as malathion;
Urea compounds such as flufenoxuron;
Triazine compounds such as cyromazine;
Hydrazone compounds such as hydramethylnon;
Diamide compounds such as flubendiamide, broflanilide, cyhalodiamide;
Thiourea compounds such as diafenthiuron, chloromethiuron;
Form amidine compounds such as amitraz, chlordimeform, chloromebuform;
Pyridineazomethine compounds such as pymetrozine, pyrifluquinazone;
Isoxazoline compounds such as afoxolaner, fluralaner, fluxametamide, sarolaner;
Other compounds include buprofezin, hexythiazox, triazamate, chlorfenapyr, indoxacarb, acequinocyl, etoxazole, 1,3-dichloropropene. (1,3-dichloropropene), benclothiaz, bifenazate, propargite, clofentezine, metaflumizone, cyflumetofen, fenazaquin, amideflumet (amidoflumet) Sulfluramid, hydramethylnon, metaldehyde, sulfoxaflor, fluensulfone, verbutin, dicloromezotiaz, triflumezopyrim, fluhexaphon (Fluhexafon), tioxazafen, afidopyropen, flometoquin, flupyradifurone, fluazaindolizine, acynonapyr, benzpyrimoxan, benzpyrimoxan, benzpyrimoxan Compounds such as oxazosulfyl.
Moreover, the composition of this invention may be applied in combination with the following compounds.
Bacillus thuringiensis aizawai, Bacillus thuringiensis kurstaki, Bacillus thuringiensis israelensis, Bacillus thuringiensis japonensis, Bacillus thuringiensis tenebrionis or Bacillus thuringiensis crystal protein toxins, insect pathogenic viral agents, entomopathogenic fungal agents, entomopathogenic fungi Microbial pesticides;
Abamectin, emamectin benzoate, ivermectin, milbemectin, milbemycin oxime, lepimectin, spinosad, spinosad-like antibiotics And semi-synthetic antibiotics;
Natural products such as azadirachtin, rotenone, ryanodine;
Repellents like deet;
Physical control agents such as paraffin oil and mineral oil.

The preferred embodiments of the present invention are as follows. However, the present invention is not limited thereto.
[1] A compound represented by the formula (1) or a salt thereof.
[2] The compound according to the above [1], wherein B is a group represented by the formulas (B-1) to (B-18) or the formulas (B-101) to (B-128). That salt.
[3] The compound according to the above [1] or a salt thereof, wherein B is a group represented by the formulas (B-1) to (B-4).
[4] The compound according to the above [1] or a salt thereof, wherein B is a group represented by the formula (B-1) or the formula (B-2).
[5] R ^B is hydroxy, alkoxy, haloalkoxy, cycloalkylalkoxy, alkoxyalkoxy, alkenyloxy, cycloalkyl, alkylcarbonyloxy, alkoxycarbonyloxy, alkylthio, amino, alkylamino, dialkylamino; R ^B 'Is a halogen atom or an alkyl, the compound according to the above [1] to [4] or a salt thereof.
[6] ^{R B1} is a ^{-L B} -Y ^{B, R B2} is alkyl, haloalkyl or ^{cycloalkyl, R B3} is a halogen atom, a compound or a salt thereof according to the above [4].
[7] R ^B1 is hydroxy, alkoxy, haloalkoxy, cycloalkylalkoxy, alkoxyalkoxy, alkenyloxy, cycloalkyl, alkylcarbonyloxy, alkoxycarbonyloxy, alkylthio, amino, alkylamino, dialkylamino; R ^B2 The compound according to the above [4] or a salt thereof, wherein is alkyl and ^{RB3 is a halogen atom.}
[8] The compound according to the above [1] to [7] or a salt thereof, wherein ^{A is a phenyl substituted with RA.}
[9] The compound according to the above [1] to [7] or a salt thereof, wherein ^A is a phenyl substituted with the same or different 2-3 RAs.
[10] The compound according to the above [1] to [7] or a salt thereof, wherein A is phenyl in which the 2-position and / or 4-position is ^{substituted with RA.}
[11] A is the two R ^A is formed by bonding, is a good benzodioxolanyl be substituted with Z ^1, compound or salt thereof according to the above [1] to [7] ..
[12] ^{R A} is a halogen atom, alkyl, haloalkyl, or ^-L A -Y ^A, compound or salt thereof according to the above [1] to [9].

[13] A fungicide for agriculture and horticulture containing the compound according to the above [1] to [12] or a salt thereof as an active ingredient.
[14] A method for controlling plant diseases by applying the compound or salt thereof according to the above [1] to [12] to a plant or soil.

Next, examples of the present invention will be described, but the present invention is not limited thereto.

Synthesis Example 1: N- (1- (3,4-dichlorophenyl) -2-methyl-1-oxopropane-2-yl) -N-methoxy-1-methyl-3- (methylthio) -1H-pyrazol-4 -Synthesis of carboxamide (Compound No. 310) (1) Synthesis of 1- (3,4-dichlorophenyl) -2-methyl-2-nitropropane-1-ol 3,4-Dichlorobenzaldehyde (5 g) and 2-nitro To a mixture of propane (10.26 ml) was added 1,5,7-triazabicyclo [4.4.0] deca-5-ene (TBD, 1.19 g) and stirred at room temperature. After 24 hours, the reaction mixture was put into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by column chromatography (eluent: ethyl acetate / heptane) to obtain a solid target product (0.97 g).
^{1 1} H NMR (CDCl ₃ / 500MHz): δ (ppm) = 7.50 (d, J = 2.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.21 (dd, J = 8.0, 2.0 Hz, 1H), 5.28 (s, 1H), 2.73 (brs, 1H), 1.57 (s, 3H), 1.46 (s, 3H).

(2) Synthesis of 1- (3,4-dichlorophenyl) -2-methyl-2-nitropropane-1-one 1- (3,4-dichlorophenyl) -2-methyl-2-nitropropane-1-ol ( Dess-Martin peryodinane (DMP, 1.64 g) was added to a solution of 0.97 g) of dichloromethane (20 mL), and the mixture was stirred overnight at room temperature. The reaction mixture was put into water, neutralized with an aqueous sodium hydrogen carbonate solution, and the insoluble material was filtered off. The filtrate was extracted with ethyl acetate and the organic layer was washed with water. After drying over anhydrous magnesium sulfate and filtering, the mixture was concentrated under reduced pressure. The obtained residue was purified by column chromatography (eluent: ethyl acetate / heptane) to obtain an oily target product (0.78 g).
^{1 1} H NMR (CDCl _{3 /} 500MHz): δ (ppm) = 7.90 (d, J = 1.5Hz, 1H), 7.53-7.49 (m, 2H), 1.92 (s, 6H).

(3) Synthesis of 1- (3,4-dichlorophenyl) -2- (hydroxyamino) -2-methylpropane-1-one 1- (3,4-dichlorophenyl) -2-methyl-2-nitropropane-1 -Add zinc (0.95 g) in a mixed solution of tetrahydrofuran (10 mL), water (5 mL) and ethanol (5 mL) of on (0.76 g) and ammonium chloride (1.55 g) in ice water, and stir. did. After 15 minutes, the reaction mixture was filtered through Celite, the resulting filtrate was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by column chromatography (heptane: ethyl acetate) to obtain a solid target product (0.48 g).

(4) Synthesis of 1-methyl-3- (methylthio) -1H-pyrazol-4-carboxylic acid 1-methyl-3- (methylthio) -1H-pyrazol-synthesized based on US Pat. No. 5,223,526 Ethyl 4-carboxylate (2.67 g) was suspended in ethanol (8.46 g), a solution of sodium hydroxide (1.12 g) in water (13.4 g) was added, and the mixture was stirred at room temperature for 13 hours. After completion of the reaction, concentrated hydrochloric acid under ice water was added to precipitate a solid. The precipitated solid was filtered and dried to obtain a solid target product (2.15 g).
^{1 1} H NMR (CDCl _{3 /} 300MHz): δ (ppm) = 7.88 (s, 1H), 3.89 (s, 3H), 2.55 (s, 3H).

(5) N- (1- (3,4-dichlorophenyl) -2-methyl-1-oxopropan-2-yl) -N-hydroxy-1-methyl-3- (methylthio) -1H-pyrazol-4- Synthesis of Carboxamide Oxalyl chloride in a solution of 1-methyl-3- (methylthio) -1H-pyrazol-4-carboxylic acid (0.42 g) and N, N-dimethylformamide (0.02 g) in tetrahydrofuran (4.45 g). (0.34 g) was added and stirred at room temperature for 1 hour to obtain 1-methyl-3- (methylthio) -1H-pyrazole-4-carboxylic acid chloride. The obtained carboxylic acid chloride was dissolved in tetrahydrofuran (2.22 g) to prepare a tetrahydrofuran solution. Then, in a tetrahydrofuran solution (4.43 g) of 1- (3,4-dichlorophenyl) -2- (hydroxyamino) -2-methylpropane-1-one (0.25 g) and triethylamine (TEA, 0.58 g). , The prepared tetrahydrofuran solution of carboxylic acid chloride was added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate, and the organic layer was concentrated under reduced pressure. The obtained residue was washed with ethanol and solid N- (1- (3,4-dichlorophenyl) -2-methylpropan-1-oxopropan-2-yl) -1-methyl-N-((1-1-). Methyl-3- (methylthio) -1H-pyrazole-4-carbonyl) oxy) -3- (methylthio) -1H-pyrazole-4-carboxamide (0.30 g) was obtained. This was suspended in ethanol (7.12 g), a solution of sodium hydroxide (0.11 g) in water (4.62 g) was added, and the mixture was stirred at 40 ° C. for 11 hours. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure to obtain a solid target product (0.17 g).
^{1 1} H NMR (CDCl ₃ / 300MHz): δ (ppm) = 8.18 (d, J = 2.1 Hz, 1H), 7.93 (dd, J = 8.7, 2.1 Hz, 1H), 7.79 (s, 1H), 7.43 ( d, J = 8.4 Hz, 1H), 7.18 (s, 1H), 3.84 (s, 3H), 2.56 (s, 3H), 1.65 (s, 6H).

(6) N- (1- (3,4-dichlorophenyl) -2-methyl-1-oxopropan-2-yl) -N-methoxy-1-methyl-3- (methylthio) -1H-pyrazol-4- Synthesis of Carboxamide (Compound No. 310) N- (1- (3,4-dichlorophenyl) -2-methyl-1-oxopropan-2-yl) -N-hydroxy-1-methyl-3- (methylthio)- Sodium hydride (0.03 g, 60%) was added to a solution of 1H-pyrazol-4-carboxamide (0.17 g) in N, N-dimethylformamide (1.28 g) under ice water, and the mixture was stirred. After 5 minutes, a solution of methyl iodide (0.14 g) in N, N-dimethylformamide (0.34 g) was added at the same temperature, and the mixture was stirred at room temperature for 1.5 hours. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate, and the organic layer was concentrated under reduced pressure. The obtained residue was washed with a mixed solution of heptane: ethyl acetate = 1: 1 to obtain a solid target product (0.16 g, melting point: 199 to 201 ° C.).
^{1 1} H NMR (CDCl ₃ / 300MHz): δ (ppm) = 8.14 (d, J = 2.1 Hz, 1H), 7.90-7.86 (m, 2H), 7.41 (d, J = 8.4 Hz, 1H), 3.93 ( s, 3H), 3.89 (s, 3H), 2.42 (s, 3H), 1.68 (brs, 6H).

Synthesis Example 2: N- (1- (4-isopropoxyphenyl) -2-methyl-1-oxopropan-2-yl) -N, 3-dimethoxy-1-methyl-1H-pyrazole-4-carboxamide (compound) Synthesis of No. 259) (1) Synthesis of 2-bromo-1- (4-isopropoxy-2-methylphenyl) -2-methylpropan-1-one 1- (1) synthesized based on JP-A-2016-108332 To a solution of 4-isopropoxy-2-methylphenyl) -2-methylpropan-1-one (14.41 g) in tetrahydrofuran (100 mL) was added trimethylphenylammonium tribromid (28.87 g) for 5 hours at room temperature. Stirred. After completion of the reaction, the reaction mixture was filtered, and the obtained filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography (eluent: ethyl acetate / heptane) to obtain the desired product (20.4 g).

(2) Synthesis of 1- (4-isopropoxy-2-methylphenyl) -2-methyl-2-nitropropane-1-one 2-bromo-1- (4-isopropoxy-2-methylphenyl) -2 Sodium nitrite (7.6 g) was added to a solution of −methylpropane-1-one (20.4 g) in dimethyl sulfoxide (100 mL), and the mixture was stirred and reacted at room temperature for 4 hours. Dimethyl sulfoxide (40 mL) was added, and the mixture was stirred and reacted at 40 ° C. for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by column chromatography (heptane: ethyl acetate) to obtain the desired product (19.5 g).
^{1 1} H NMR (CDCl _{3 /} 300MHz): δ (ppm) = 7.31 (d, J = 8.7 Hz, 1H), 6.76 (d, J = 2.4 Hz, 1H), 6.64 (dd, J = 9.0, 2.7 Hz, 1H), 4.63-4.55 (m, 1H), 2.45 (s, 3H), 1.92 (s, 6H), 1.34 (d, J = 6.0 Hz, 6H).

(3) Synthesis of 2- (hydroxyamino) -1- (4-isopropoxy-2-methylphenyl) -2-methylpropan-1-one In the same manner as in Synthesis Example 1 (3), 1- (4) The desired product (0.5 g) was obtained from −isopropoxy-2-methylphenyl) -2-methyl-2-nitropropane-1-one (1.0 g).
^{1 1} H NMR (CDCl ₃ / 300MHz): δ (ppm) = 7.35 (d, J = 8.4 Hz, 1H), 6.73 (d, J = 2.4 Hz, 1H), 6.67 (dd, J = 8.7, 2.7 Hz, 1H), 4.60-4.52 (m, 1H), 2.38 (s, 3H), 1.36 (s, 6H), 1.32 (d, J = 6.0 Hz, 6H).

(4) Synthesis of ethyl 3-methoxy-1-methyl-1H-pyrazol-4-carboxylate Ethyl 3-hydroxy-1-methylpyrazole-4-carboxylate (10.0 g) synthesized based on JP-A-2002-348280. ), Sodium hydride (3.53 g, 60%) was added to the solution of N, N-dimethylformamide (150 mL) under ice-cooling, and the mixture was stirred. After 15 minutes, methyl iodide (16.68 g) was added at the same temperature and stirred. After 4 hours and 30 minutes, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by column chromatography (eluent: ethyl acetate / heptane) to obtain the desired product (8.42 g).
^{1 1} H NMR (CDCl _{3 /} 300MHz): δ (ppm) = 7.66 (s, 1H), 4.27 (q, J = 7.2 Hz, 2H), 3.98 (s, 3H), 3.76 (s, 3H), 1.32 ( t, J = 7.2 Hz, 3H).

(5) Synthesis of 3-methoxy-1-methyl-1H-pyrazole-4-carboxylic acid In ethyl 3-methoxy-1-methyl-1H-pyrazole-4-carboxylate (10.2 g), sodium hydroxide (2) was added. A mixed solution of .21 g) of ethanol (20 mL) and water (250 mL) was added, and the mixture was stirred at 50 ° C. for 2 hours and 45 minutes. Sodium hydroxide (0.5 g) was added and stirred at the same temperature for an additional 2 hours. After completion of the reaction, the mixture was cooled to room temperature and washed with ethyl acetate. Hydrochloric acid was added to the aqueous layer, and the precipitated crystals were collected by filtration and dried to obtain the desired product (5.88 g).
^{1 1} H NMR (DMSO-d6 / 300MHz): δ (ppm) = 11.93 (brs, 1H), 8.00 (s, 1H), 3.80 (s, 3H), 3.69 (s, 3H).

(6) N-Hydroxy-N- (1- (4-isopropoxy-2-methylphenyl) -2-methyl-1-oxopropan-2-yl) -3-methoxy-1-methyl-1H-pyrazol- Synthesis of 4-Carboxamide 3-Methoxy-1-methyl-1H-pyrazol-4-carboxylic acid (0.72 g) in a toluene (10 mL) solution with oxalyl chloride (1.39 g) and N, N-dimethylformamide (0) 0.01 g) was added, and the mixture was stirred at 90 ° C. for 1 hour. The reaction mixture was concentrated under reduced pressure to give 3-methoxy-1-methyl-1H-pyrazole-4-carboxylic acid chloride. The obtained carboxylic acid chloride was dissolved in tetrahydrofuran (10 mL) to prepare a tetrahydrofuran solution. Then, triethylamine (5.8 g) was added to a solution of 2- (hydroxyamino) -1- (4-isopropoxy-2-methylphenyl) -2-methylpropan-1-one (0.55 g) in tetrahydrofuran (20 mL). In addition, a solution of the prepared carboxylic acid chloride in tetrahydrofuran was added. The mixture was stirred at room temperature for 2 hours and 30 minutes. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. After washing with saturated brine, the organic layer was dried over sodium sulfate and concentrated under reduced pressure. The obtained residue was dissolved in ethanol (30 mL), a 2 M aqueous sodium hydroxide solution (30 mL) was added to the reaction solution, and the mixture was stirred at room temperature for 13 hours and 30 minutes. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. After washing with saturated brine, the organic layer was dried over sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by column chromatography (heptane: ethyl acetate) to obtain the desired product (0.26 g).
^{1 1} H NMR (CDCl ₃ / 300MHz): δ (ppm) = 7.84 (s, 1H), 7.80 (d, J = 8.7 Hz, 1H), 7.54 (s, 1H), 6.71 (d, J = 2.4 Hz, 1H), 6.57 (dd, J = 8.7, 2.4 Hz, 1H), 4.60-4.52 (m, 1H), 3.98 (s, 3H), 3.65 (s, 3H), 2.46 (s, 3H), 1.67 (s) , 6H), 1.31 (d, J = 6.0 Hz, 6H).

(7) N- (1- (4-isopropoxyphenyl) -2-methyl-1-oxopropan-2-yl) -N, 3-dimethoxy-1-methyl-1H-pyrazole-4-carboxamide (Compound No. .259) Synthesis N-hydroxy-N- (1- (4-isopropoxy-2-methylphenyl) -2-methyl-1-oxopropan-2-yl) -3-methoxy-1-methyl-1H- To a solution of pyrazole-4-carboxamide (0.15 g) in N, N-dimethylformamide (10 mL) was added sodium hydride (0.02 g, 60%), followed by methyl iodide (0.1 g). .. The mixture was stirred and reacted at room temperature for 30 minutes. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by column chromatography (heptane: ethyl acetate) to obtain a mixture. The obtained mixture was purified by column chromatography (heptane: ethyl acetate) using amino silica to obtain the desired product (0.146 g).
¹ H NMR (CDCl ₃ / 300MHz): δ (ppm) = 7.77 (d, J = 8.7 Hz, 1H), 7.63 (s, 1H), 6.67 (d, J = 2.4 Hz, 1H), 6.57 (dd, dd, J = 8.7, 2.4 Hz, 1H), 4.58-4.50 (m, 1H), 3.91 (s, 3H), 3.76 (s, 3H), 3.72 (s, 3H), 2.39 (s, 3H), 1.69 (brm) , 6H), 1.29 (d, J = 6.0 Hz, 6H).

Next, typical examples of the compounds of the present invention are specifically listed in Table 1. These compounds can be synthesized based on the production method, the synthesis example, and a method known in the art.
In the table, No. indicates the compound No. The numerical values shown in the physical characteristics column of Table 1 are the melting point (° C.), and the compounds described as ^{NMR show 1} H-NMR spectral data in Table 2. The abbreviations used in column B in Table 1 indicate the following substituents, respectively. Me indicates a methyl group, Et indicates an ethyl group, Pr indicates a normal propyl group, iPr indicates an isopropyl group, tBu indicates a tertiary butyl group, and Ac indicates an acetyl group.

Test Example 1: Bactericidal effect test against Zymoseptoria tritici A spore suspension of Zymoseptoria tritici is inoculated into a YBG (yeast extract, bactopeptone, glycerol) medium containing the compound of the present invention dissolved in dimethyl sulfoxide. Then, the cells were cultured at room temperature for 7 days and the degree of growth was investigated.
Compound No. 7, 55, 106, 233, 237, 245, 253, 255, 259, 288, 306, 310, 314, 321, 332, 379 suppressed the growth of wheat leaf blight fungus by 70% or more at 30 ppm.

Test Example 2: Test of bactericidal effect on Fusarium head blight of wheat A spore suspension of Fusarium graminearum of wheat was placed in a YBA (yeast extract, bactopeptone, sodium acetate) medium containing the compound of the present invention dissolved in dimethylsulfoxide. It was inoculated and cultured at room temperature for 3 days to investigate the degree of growth.
Compound No. 55, 106, 233, 237, 245, 253, 255, 259, 288, 306, 310, 314, 332, 379 suppressed the growth of Fusarium head blight at 30 ppm by 70% or more.

Test Example 3: Effect test on wheat powdery mildew Wheat is cultivated in a vinyl pot with a diameter of 6 cm, and when the leaf stage reaches 1.5 to 2.0, 10 mL of a chemical solution prepared at a predetermined concentration of the compound of the present invention is used as a spray gun. And sprayed. After the drug solution had dried (on the day of treatment), conidia of powdery mildew (Erysiphe graminis ) were sprinkled and inoculated and kept in a homeothermic chamber at 20 ° C. Seven days after inoculation, the control rate was investigated from the sporulation area.
Compound No. 106, 113, 253, and 259 suppressed the onset of wheat powdery mildew by 90% or more at 100 ppm.

Test Example 4: Effect test on Botrytis cinerea When green beans were cultivated in a plastic pot with a diameter of 15 cm and the true leaves were fully developed, 5 mL of a chemical solution prepared at a predetermined concentration of the compound of the present invention was sprayed with a spray gun. After the drug solution has dried (on the day of treatment or the next day), a paper disk having a diameter of 8 mm impregnated with a suspension of Botrytis cinerea conidia prepared in PS (potato, sucrose) medium is inoculated. It was kept in a constant temperature chamber at 20 ° C. under high humidity conditions. The control rate was investigated from the lesion length 3 days after inoculation.
Compound No. 55, 113, 233, 237, and 259 suppressed the onset of Botrytis cinerea by 90% or more at 25 ppm.

Test Example 5: Effect test on sclerotia of green bean Green bean was cultivated in a plastic pot having a diameter of 15 cm, and when the true leaves were sufficiently developed, 5 mL of a chemical solution prepared at a predetermined concentration of the compound of the present invention was sprayed with a spray gun. After the drug solution has dried (on the day of treatment or the next day), inoculate with the sclerotinia sclerotiorum (Sclerotinia sclerotiorum) flora disk (4 mm in diameter) cultivated in PSA (potato, sucrose, agar) medium facing up. However, it was kept in a constant temperature room at 20 ° C. under high humidity conditions. The control rate was investigated from the lesion length 3 days after inoculation.
Compound No. 55, 113, 237, 253, 259, 321 and 379 suppressed the onset of common bean sclerotium disease by 90% or more at 25 ppm.

Next, a formulation example of the composition of the present invention will be described, but the compounding ratio, dosage form, etc. are not limited to the described example.
Formulation Example 1
(1) 20 parts by weight of the compound of the formula (1) (2) 72 parts by weight of clay (3) Soda lignin sulfonate 8 parts by weight or more are uniformly mixed to prepare a wettable powder.
Preparation example 2
(1) Compound of formula (1) 5 parts by weight (2) Talc 95 parts by weight or more are uniformly mixed to prepare a powder.
Preparation example 3
(1) Compound of formula (1) 20 parts by weight (2) N, N'-dimethylacetamide 20 parts by weight (3) Polyoxyethylene alkyl phenyl ether 10 parts by weight (4) Xylene 50 parts by weight or more uniformly Mix and dissolve to make an emulsion.

Preparation example 4
(1) 68 parts by weight of clay (2) 2 parts by weight of sodium lignin sulfonate (3) 5 parts by weight of polyoxyethylene alkylaryl sulfate (4) Fine powder silica 25 parts by weight or more of each component and a mixture of each component of the formula (1) The compounds are mixed in a weight ratio of 4: 1 to give a wettable powder.
Formulation Example 5
(1) 50 parts by weight of the compound of the formula (1) (2) 2 parts by weight of oxylated polyalkylphenyl phosphate-triethanolamine (3) 0.2 parts by weight of silicone (4) 47.8 parts by weight or more of water Add 5 parts by weight (5) sodium polycarboxylic acid (6) 42.8 parts by weight of anhydrous sodium sulfate to the undiluted solution that has been uniformly mixed and crushed, and mix, granulate, and dry to obtain a granular wettable powder. ..
Formulation Example 6
(1) Compound of formula (1) 5 parts by weight (2) Polyoxyethylene octylphenyl ether 1 part by weight (3) Acetone ester of polyoxyethylene 0.1 parts by weight (4) Granular calcium carbonate 93.9 parts by weight ( 1) to (3) are uniformly mixed in advance, diluted with an appropriate amount of acetone, and then sprayed on (4) to remove acetone to obtain granules.

Formulation Example 7
(1) Compound of formula (1) 2.5 parts by weight (2) N-methyl-2-pyrrolidone 2.5 parts by weight (3) Soybean oil 95.0 parts by weight or more is uniformly mixed and dissolved. Use an ultra low volume formulation.
Formulation Example 8
(1) 20 parts by weight of the compound of the formula (1) (2) 2 parts by weight of oxylated polyalkylphenol phosphate-triethanolamine (3) 0.2 parts by weight of silicone (4) 0.1 parts by weight of Zansan gum (5) Ethylene glycol 5 parts by weight (6) Water 72.7 parts by weight or more is uniformly mixed and pulverized to obtain an aqueous suspending agent.

Claims (11)

Equation (1):

[In the formula, A is phenyl or pyridyl substituted with ^RA,
B is a heterocyclic group substituted with R ^B (said heterocyclic group may be further substituted with one to three R ^{B '),}
R ^A are the same or different, a halogen atom, alkyl, haloalkyl, alkenyl, alkynyl, cyclic group, nitro, or cyano or ^-L A -Y ^A, or two ^{R A} is attached, ^{Z 1} It may form a ring that may be substituted with,
R ^B is a ^{-L B} -Y B,
R B ^'is a halogen atom, an alkyl, haloalkyl, alkoxyalkyl, cycloalkyl or cyano,
L ^A is, O, S, C (= O), C (= O) O, C (= O) N (R 1), OC (= O), N (R 1), N (R 1) C (= O), N (R ¹ ) C (= O) O, C (= NR ² ), SO, SO ₂ or SO ₂ N (R ¹ ).
Y ^A is a hydrogen atom, Z ² may be substituted with alkyl, alkenyl, or Z ^{3-substituted} have been or cyclic group,
L ^B is, O, S, C (= O), C (= O) O, C (= O) N (R 3), OC (= O), N (R 3), N (R 3) C (= O), N (R ³ ) C (= O) O, C (= NR ⁴ ), SO, SO ₂ or SO ₂ N (R ³ ).
Y ^B represents a hydrogen atom, an alkyl optionally substituted by Z ^4, alkenyl, cycloalkyl, Z ⁵ substituted by optionally substituted phenyl or Z ⁵ may have a heterocyclic group,
R ¹ is a hydrogen atom or an alkyl and is
R ² is a hydrogen atom, alkyl or alkoxy,
R ³ is a hydrogen atom or alkyl
R ⁴ is hydrogen atom, alkyl or alkoxy,
Z ¹ is a halogen atom,
Z ² is a halogen atom, cyano, cycloalkyl or alkoxy,
Z ³ is a halogen atom or haloalkyl and
Z ⁴ is a halogen atom, cycloalkyl or alkoxy,
Z ⁵ is a halogen atom, alkyl, haloalkyl, cycloalkyl or alkoxy]
A compound represented by or a salt thereof. B is the formula (B-1) to the formula (B-18):

[In the formula, ^{any one of R B1 to} R ^B3 , any one of R ^{B4 to} R ^B6 , any one of R ^{B7 to} R ^B9 , any one of R ^{B10 to} R ^B12 , R ^B13. any one of to R ^B15, any one of any one and ^R B19 ^{to R B20} of R B16 ^{to R B18} is ^-L B -Y ^B, the remainder, a halogen atom, alkyl, haloalkyl , alkoxyalkyl, cycloalkyl or cyano, L ^B and Y ^B are as defined in claim 1, 5-membered heterocyclic group represented by * shows the point of attachment, and wherein (B- 101) -Formula (B-128):

[In the formula, ^{any one of R B101 to} R ^B104 , any one of R ^{B105 to} R ^B108 , any one of R ^{B109 to} R ^B111 , and any one of R ^{B112 to} R ^{B114 are-.} an L ^B -Y ^B, the remainder, a halogen atom, an alkyl, haloalkyl, alkoxyalkyl, cycloalkyl or cyano, L ^B and Y ^B are as defined in claim 1, * the binding position The compound according to claim 1 or a salt thereof, which is a heterocyclic group selected from the group consisting of 6-membered heterocyclic groups represented by [represented]. B is the formula (B-1) to the formula (B-4):

The compound according to claim 2 or a salt thereof, which is a heterocyclic group represented by [each symbol in the formula is as defined in claim 2]. B is the formula (B-1) or the formula (B-2):

The compound according to claim 2 or a salt thereof, which is a heterocyclic group represented by [each symbol in the formula is as defined in claim 2]. R ^B1 is a ^{-L B} -Y B,
^RB2 is alkyl, haloalkyl or cycloalkyl,
^RB3 is a halogen atom,
The compound according to claim 4 or a salt thereof. The compound according to claim 1, or a salt thereof, wherein A is ^{phenyl substituted with RA.} The compound according to claim 1, or a salt thereof, wherein A is phenyl in which the 2-position and / or 4-position is ^{substituted with RA.} The compound according to claim 1, or a salt thereof, wherein A is a benzodioxolanyl which may be substituted with Z ^1. R ^A is a halogen atom, an alkyl, haloalkyl or ^-L A -Y ^A, compound or salt thereof according to claim 1. A fungicide for agriculture and horticulture containing the compound according to claim 1 or a salt thereof as an active ingredient. A method for controlling plant diseases by applying the compound according to claim 1 or a salt thereof to a plant or soil.