JP2000239261A - Triazolone derivative, its use and intermediate for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound having excellent plant disease injury controlling efficacy, therefore useful as an agricultural/horticultural germicide in the field, paddy field, orchard, tea garden, pasture, etc. SOLUTION: This new compound is a compound of formula I [R1 is a (substituted) 1-10C alkyl or the like; R2 is a 1-6C alkyl or the like; R3 is a 1-6C alkoxy or the like; T, U and V are each CR4, CH, N or CR5; W is CR6 or N (R4 to R6 are each H, a halogen, 1-6C alkyl or the like)], e.g. 5-methoxy-2- methyl-4-(2-methyl-5-phenylbenzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one. The compound of formula I is obtained, for example, when R3 is a 1-6C alkoxy, 1-6C alkylthio, cyano, F, Br or I, by reaction between a chlorotriazolone compound of formula II and a compound of the formula R34-M (R34 is a 1-6C alkoxy, cyano, F, Br or the like; M is an alkali metal) (e.g. potassium fluoride) pref. at -20 to 200 deg.C for 1-100 h.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a triazolone derivative, its use and an intermediate for its production.

[0002]

SUMMARY OF THE INVENTION An object of the present invention is to provide a compound having an excellent plant disease controlling effect.

[0003]

Means for Solving the Problems The present inventors have made intensive studies.
As a result, the triazolone derivative represented by the following general formula [I]
Found that the conductor has excellent plant disease control effect,
The present invention has been reached. That is, the present invention provides a compound represented by the general formula [I]:[Wherein, R¹Is an optionally substituted C1-C10 al
Kill group, optionally substituted C2-C10 alkenyl
Group, an optionally substituted C2-C10 alkynyl group,
Halogen atom (chlorine, bromine, iodine or
Nitrogen atom), nitro group, cyano group, may be substituted
C3 to C10 cycloalkyl groups, which may be substituted
C4 to C20 cycloalkylalkyl groups, substituted
An optionally substituted C5-C10 cycloalkenyl group,
C6-C20 cycloalkenylalkyl which may be
Group, an optionally substituted C6-C10 aryl group,
An optionally substituted C7-C20 arylalkyl group,
An optionally substituted C1-C9 heteroaryl group,
Optionally substituted C2-C19 heteroarylalkyl
Group, A¹-L¹-Group, A¹-ON = CA^Two-Group, A¹-O
N = C (Me) CH_TwoON = CA^Two-Group, A¹C (A^Two) =
NOCH_Two-Group, A¹SC (A^Two) = N-group, A¹C (=
S) NH— group, A¹SC (= S) NH- group, A¹SC (S
A^Two) = N-group, A¹-ON = C (CN)-group, A¹-O
N = C (Me) CH_TwoON = C (CN) -group or A¹C
(CN) = NOCH_Two-Group ｛where L¹Is an oxygen atom, a sulfur atom, a carbonyl group,
-OCH_Two-Group, -SCH _Two— Group, —C (＝ O) O— group,
—OC (＝ O) — group, —C (＝ O) OCH_Two-Group, -N
An H-group or a C1-C6 alkylimino group,
¹And A^TwoAre the same or different and may be substituted
C1-C10 alkyl group, optionally substituted C2-
C10 alkenyl group, optionally substituted C2-C1
0 alkynyl group, optionally substituted C3-C10
A cycloalkyl group, an optionally substituted C4 to C20
Chloroalkylalkyl group, optionally substituted C5-
C10 cycloalkenyl group, optionally substituted C6
~ C20 cycloalkenylalkyl group, substituted
C6 to C10 aryl group, which may be substituted
C7-C20 arylalkyl group, hydrogen atom, substituted
An optionally substituted C1-C9 heteroaryl group or substituted
An optionally substituted C2-C19 heteroarylalkyl group
Represents ｝, R^TwoIs a hydrogen atom or C1-C
6 represents an alkyl group;^ThreeIs C1-C6 alkoxy
Group, C1-C6 alkylthio group, cyano group, halogen atom
, Vinyl, ethynyl, cyclopropyl or C
1-C6 alkyl group, one of T, U and V
Is CR^FourA CH group or a nitrogen atom
And the other one is CR^FiveGroup or nitrogen atom
And W is CR⁶Represents a group or a nitrogen atom. Poko
Where R^Four, R^FiveAnd R⁶Are the same or different,
, Halogen atom, C1-C6 alkyl group, C1-C6
Alkoxy group, C1-C6 haloalkyl group, C1-C6
Haloalkoxy group, cyano group, nitro group, C2-C6
Alkoxycarbonyl group, C1-C6 alkylthio group or
Represents a C1 to C6 haloalkylthio group. ｝]
Triazolone derivative (hereinafter, referred to as the compound of the present invention)
And an agricultural and horticultural fungicide containing it as an active ingredient.
Offer. The present invention also produces (part of) the compounds of the present invention.
A general formula [II-1] which is an intermediate useful for[Wherein, R³¹Is a C1-C6 alkyl group (e.g., methyl
Group, ethyl group, etc.). The alkoxytri represented by
Azolone compound, general formula [III-1][Wherein, R¹⁴Is a group in which two are bonded at the terminal to form an ethylene group or
Is a trimethylene group (each of which is one or more methyl groups)
Or a phenyl group).
If -C (CH_Three)_Two-C (CH_Three)_Two-,-CH_TwoCH_Two-,-CH_TwoCH_TwoCH_Two-,-CH_Two-C
(CH_Three)_Two-CH_Two-,-CH (Ph) -CH_Two-CH (Ph)-etc.) or
C1-C6 alkyl group (for example, methyl group, ethyl group,
Isopropyl group) or a hydrogen atom;^Two, R^Three,
V, U, T and W have the same meaning as described above. ]
Boron compound and general formula [IV][Wherein, R¹, R^Two, R^Three, V, U, T and W are as described above.
Represent the same meaning. The triazolone compound represented by
provide.

[0004]

BEST MODE FOR CARRYING OUT THE INVENTION In the present invention, R ¹ , A ¹ and A
The C1~C10 alkyl group in an optionally substituted C1~C10 alkyl group represented by ^2, for example a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a 1-methylpropyl group, pentyl Group, 1-methylbutyl group, 1-ethylbutyl group, 2-
Methylbutyl group, 3-methylbutyl group, 2,2-dimethylpropyl group, 1,2-dimethylpropyl group, 1,1-
Dimethylpropyl group, a hexyl group, 1-methylpentyl group, 1-ethylpentyl group, 3,3-dimethylbutyl group, heptyl group, 3,7-dimethyl octyl group and the like, R ^1, A ¹ and A ² Examples of the C2 to C10 alkenyl group in the optionally substituted C2 to C10 alkenyl group include a vinyl group, an allyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, Butenyl group, 2-pentenyl group, 3-methyl-
2-butenyl group and the like, as the C2~C10 alkynyl group in R ^1, A optionally substituted C2~C10 alkynyl group represented by ¹ and A ^2, for example, ethynyl group, propargyl group, 1-methyl -2-propynyl group, 2-butynyl group and the like. Examples of the halogen atom represented by R ¹ , A ¹ and A ² include a chlorine atom, a bromine atom,
Iodine atom or fluorine atom; R ¹ , A ¹ and A
The C3~C10 cycloalkyl group in substituted C3~C10 may cycloalkyl group represented by ^2, for example, a cyclopropyl group, a cyclopentyl group, a cyclohexyl group, and in R ^1, A ¹ and A ² Examples of the C4 to C20 cycloalkylalkyl group in the optionally substituted C4 to C20 cycloalkylalkyl group include a cyclopropylmethyl group, a cyclopentylmethyl group, a 2-cyclopentylethyl group, a cyclohexylmethyl group, and the like. the C5~C10 cycloalkenyl group in R ^1, A optionally substituted C5~C10 cycloalkenyl group represented by ¹ and A ^2, for example, cyclopentenyl group, cyclohexenyl group and the like, R ^1, A it may be substituted represented by ¹ and A ² C6~ C20 The C6~C20 cycloalkenylalkyl group in cycloalkenylalkyl group, for example, cyclopenten-1-ylmethyl group, a cyclohexene-1-ylmethyl group and the like, optionally substituted represented by R ^1, A ¹ and A ² Examples of the C6 to C10 aryl group in the C6 to C10 aryl group include a phenyl group, an α-naphthyl group, and a β-naphthyl group, and are substituted by R ¹ , A ¹ and A ^2. C7 to C20 in an optionally substituted C7 to C20 arylalkyl group
Examples of the arylalkyl group include a phenylmethyl group, a 2-phenylethyl group, a 3-phenylpropyl group,
A 4-phenylbutyl group, an α-naphthylmethyl group, a β-naphthylmethyl group and the like, and a C1 to C9 heteroaryl in the optionally substituted C1 to C9 heteroaryl group represented by R ¹ , A ¹ and A ^2. Examples of the aryl group include a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group,
-Pyrimidinyl group, 4-pyrimidinyl group, 5-pyrimidinyl group, 2-pyrazinyl group, 3-pyridazinyl group, 4-
Pyridazinyl group, 2-thienyl group, 3-thienyl group, 2
-Furyl group, 3-furyl group, pyrrol-1-yl group, pyrrol-2-yl group, pyrrol-3-yl group, 1-pyrazolyl group, 3-pyrazolyl group, 4-pyrazolyl group, 2-thiazolyl group, 4-thiazolyl group, 5-thiazolyl group, 3
-Isothiazolyl group, 4-isothiazolyl group, 5-isothiazolyl group, 2-oxazolyl group, 4-oxazolyl group, 5-oxazolyl group, 3-isoxazolyl group, 4
-Isoxazolyl group, 5-isoxazolyl group, 1-
Imidazolyl group, 2-imidazolyl group, 4-imidazolyl group, 5-imidazolyl group, 1- (1,2,4-triazolyl) group, 3- (1,2,4-triazolyl) group, 4
-(1,2,4-triazolyl) group, 2-benzothienyl group, 3-benzothienyl group, benzothiazole-2-
Examples of the C2-C19 heteroarylalkyl group in the optionally substituted C2-C19 heteroarylalkyl group represented by R ¹ , A ¹ and A ² include 2-yl group and 2-quinolinyl group. Pyridylmethyl group, 4-pyridylmethyl group, 2-pyrimidinylmethyl group, 4-pyrimidinylmethyl group, 3-pyrazolylmethyl group, 2-thiazolylmethyl group, 2-imidazolylmethyl group, 3- (1,2,4-triazolyl) Methyl group, 2-
Quinolinylmethyl group and the like;

[0005] An optionally substituted C1-C10 alkyl group, an optionally substituted C2-C10 alkenyl group, an optionally substituted C2-C10 alkynyl group represented by R ¹ , A ¹ and A ² , An optionally substituted C3
To C10 cycloalkyl group, optionally substituted C4
-C20 cycloalkylalkyl group, optionally substituted C5-C10 cycloalkenyl group, optionally substituted C6-C20 cycloalkenylalkyl group, optionally substituted C6-C10 aryl group, substituted Examples of the substituent in the optionally substituted C7 to C20 arylalkyl group, the optionally substituted C1 to C9 heteroaryl group or the optionally substituted C2 to C19 heteroarylalkyl group include a halogen atom [a chlorine atom, a bromine Atom, fluorine atom, etc.], C1-C10 alkyl group [for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, 1-methylpropyl group, pentyl group, 1-methylbutyl group, 1-ethylbutyl group A 2-methylbutyl group, a 3-methylbutyl group,
2,2-dimethylpropyl group, 1,2-dimethylpropyl group, 1,1-dimethylpropyl group, hexyl group, 1-
A methylpentyl group, a 1-ethylpentyl group, a 3,3-dimethylbutyl group, a heptyl group, a 3,7-dimethyloctyl group, etc.], a C3-C20 trialkylsilyl group [eg, a trimethylsilyl group, a triethylsilyl group, etc.] C1
To C10 haloalkyl group [for example, trifluoromethyl group, 2,2,2-trifluoroethyl group, 1,1,2,2
2-tetrafluoroethyl group etc.), C3-C10 cycloalkyl group [eg cyclopropyl group, cyclopentyl group, cyclohexyl group etc.], C1-C10 alkoxy group [eg methoxy group, ethoxy group, n-propoxy group,
Isopropoxy group, n-butoxy group, sec-butoxy group, isobutoxy group, n-pentyloxy group, etc.], C1
To C10 haloalkoxy group [for example, trifluoromethoxy group, difluoromethoxy group, bromodifluoromethoxy group, chlorodifluoromethoxy group, fluoromethoxy group, 2,2,2-trifluoroethoxy group, 1,1,1
2,2-tetrafluoroethoxy group etc.], C1 to C10
Alkylthio group (for example, methylthio group, ethylthio group,
n-propylthio group, n-butylthio group, isobutylthio group, sec-butylthio group, n-pentylthio group, n
-Hexylthio group etc.), C1-C10 haloalkylthio group [for example, trifluoromethylthio group, difluoromethylthio group, bromodifluoromethylthio group, chlorodifluoromethylthio group, fluoromethylthio group, 2,2,
2-trifluoroethylthio group, 1,1,2,2-tetrafluoroethylthio group, etc.], C2-C10 alkoxycarbonyl group [methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, isopropoxycarbonyl group, n-butoxycarbonyl group, isobutoxycarbonyl group, sec-butoxycarbonyl group, n-
Pentyloxycarbonyl group, n-hexyloxycarbonyl group, etc.], phenyl group, phenoxy group, benzyloxy group, phenoxymethyl group, C1-C9 heteroaryl group, (C1-C9 heteroaryl) methyloxy group,
(C1-C9 heteroaryl) oxymethyl group, C1-
C9 heteroaryloxy group wherein the phenyl group,
Each of a phenoxy group, a benzyloxy group, a phenoxymethyl group, a C1-C9 heteroaryl group, a (C1-C9 heteroaryl) methyloxy group, a (C1-C9 heteroaryl) oxymethyl group and a C1-C9 heteroaryloxy group , A halogen atom (such as a chlorine atom),
C1-C6 alkyl group (for example, methyl group, ethyl group, etc.), C1-C6 alkoxy group (for example, methoxy group,
Ethoxy group), a trifluoromethyl group and a cyano group. Further, the C1-C9 heteroaryl group, (C1-
The C1-C9 heteroaryl group in the (C9 heteroaryl) methyloxy group, the (C1-C9 heteroaryl) oxymethyl group and the C1-C9 heteroaryloxy group includes, for example, a 2-pyridyl group, a 3-pyridyl group,
-Pyridyl group, 2-pyrimidinyl group, 4-pyrimidinyl group, 5-pyrimidinyl group, 2-pyrazinyl group, 3-pyridazinyl group, 4-pyridazinyl group, 2-thienyl group, 3
-Thienyl group, 2-furyl group, 3-furyl group, pyrrol-1-yl group, pyrrol-2-yl group, pyrrol-3-yl group, 1-pyrazolyl group, 3-pyrazolyl group, 4-pyrazolyl group, 2-thiazolyl group, 4-thiazolyl group, 5-
Thiazolyl group, 3-isothiazolyl group, 4-isothiazolyl group, 5-isothiazolyl group, 2-oxazolyl group,
4-oxazolyl group, 5-oxazolyl group, 3-isoxazolyl group, 4-isoxazolyl group, 5-isoxazolyl group, 1-imidazolyl group, 2-imidazolyl group, 4-imidazolyl group, 5-imidazolyl group, 1-
(1,2,4-triazolyl) group, 3- (1,2,4-
Triazolyl) group, 4- (1,2,4-triazolyl)
Group, 2-benzothienyl group, 3-benzothienyl group, benzothiazol-2-yl group, 2-quinolinyl group and the like. ｝, A methylenedioxy group, a difluoromethylenedioxy group (where each of the methylenedioxy group and the difluoromethylenedioxy group substitutes for two adjacent carbon atoms on the aryl group), a hydroxyl group, a cyano group And a nitro group.

Examples of the C1-C6 alkyl group represented by R ² and R ³¹ include a methyl group and an ethyl group.
The C1~C6 alkoxy group represented by R ^3, for example, methoxy, ethoxy and the like, as the C1~C6 alkylthio group represented by R ^3, for example, methylthio group, ethylthio group and the like, R ³ in the halogen atom represented, for example, chlorine atom, bromine atom, iodine atom and a fluorine atom and the like, C1～C represented by R ³
The 6 alkyl group such as methyl group, an ethyl group, and the halogen atom represented by R ^4, R ⁵ and R ^6, for example, a chlorine atom, a bromine atom and a fluorine atom and the like, R ^4, Examples of the C1-C6 alkyl group represented by R ⁵ and R ⁶ include a methyl group and an ethyl group. Examples of the C1-C6 alkoxy group represented by R ⁴ , R ⁵ and R ⁶ include a methoxy group, C1 to C6 haloalkyl groups represented by R ⁴ , R ⁵ and R ⁶ include, for example, trifluoromethyl group; and C ¹ to C ⁶ halo alkyl groups represented by R ⁴ , R ⁵ and R ^6. Examples of the alkoxy group include a trifluoromethoxy group, a difluoromethoxy group, a bromodifluoromethoxy group, a chlorodifluoromethoxy group, a fluoromethoxy group,
Examples thereof include a 2-trifluoroethoxy group and a 1,1,2,2-tetrafluoroethoxy group. Examples of the C2 to C6 alkoxycarbonyl group represented by R ⁴ , R ⁵ and R ⁶ include a methoxycarbonyl group and an ethoxycarbonyl group. And the C1 to C6 alkylthio groups represented by R ⁴ , R ⁵ and R ⁶ include, for example, a methylthio group, an ethylthio group and the like, and C ¹ to C ^{6 represented} by R ⁴ , R ⁵ and R ^6.
Examples of haloalkylthio groups include trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetra Specific examples of the 6-membered aromatic ring containing T, U, V and W include a benzene ring, a pyridine ring and a pyrimidine ring.

The compounds of the present invention may have (E) and (Z) isomers based on a C ＝ N bond and / or a C ＝ C bond, each of which and a mixture thereof are included in the present invention. . (As used herein, the terms (E) and (Z) are used to denote Kahn-, a widely used geometric isomer.
It is defined by the Ingold-Prelog rule. )

Among the compounds of the present invention, R ¹ is preferably a phenyl group which may be substituted, R ² is preferably a hydrogen atom, and R ² is a hydrogen atom. Examples of ³ include a methoxy group. Among the compounds of the present invention, as the 6-membered aromatic ring moiety containing T, U, V and W which are preferable in view of the plant disease controlling effect, T is a CMe group, U is a CH group, V is a CH group, and W is And a ring that is a CH group. Among the compounds of the present invention, as an example of a more preferred compound in terms of plant disease control effect,
5-methoxy-2-methyl-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,
4-triazol-3-one [the present compound 6] 4- {5- (3,3-dimethyl-1-butynyl) -2-
Methylbenzyl} -5-methoxy-2-methyl-2,4
-Dihydro-3H-1,2,4-triazol-3-one [the present compound 526].

The compound of the present invention is described, for example, in the following (Production method A)
To (Production method E) and (Production method G). Also, depending on the content of R ^1, it can also be introduced or build the desired R ¹ to the end (for example, (Process F)). In these production methods, a protecting group can be used if necessary to protect the functional group from the reaction.

(Production method A): Production method of the compound of the present invention wherein R ³ is a C1 to C6 alkoxy group, a C1 to C6 alkylthio group, a cyano group, a fluorine atom, a bromine atom or an iodine atom, general formula [I-1] [Wherein, R ¹ , R ² , T, U, V and W represent the same meaning as described above. A chlorotriazolone compound represented by the general formula [V]: [Wherein, R ³⁴ is a C1-C6 alkoxy group, a C1-C6 alkylthio group, a cyano group, a fluorine atom, a bromine atom, an iodine atom, and M is an alkali metal (eg, sodium,
Potassium, lithium, cesium, etc.). A method of reacting with the compound represented by the formula Specific examples of the compound represented by the general formula [V] include sodium methoxide, sodium ethoxide, sodium thiomethoxide, sodium thioethoxide, sodium hydrocyanate, potassium hydrocyanate,
Potassium fluoride, sodium bromide and the like. The reaction temperature of the reaction is usually in the range of -20 to 200 ° C, and the reaction time is usually in the range of 1 to 100 hours. The amount of the reagent used for the reaction is usually 1 to 100 mol of the compound represented by the general formula [V] to 1 mol of the chlorotriazolone compound represented by the general formula [I-1]. The reaction is usually carried out using a solvent.
Ethers such as 4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethyl ether, t-butyl methyl ether, and aliphatics such as n-hexane, heptane, ligroin, petroleum ether Hydrocarbons, aromatic hydrocarbons such as toluene and xylene, alcohols such as methanol and ethanol, N, N-dimethylformamide,
Examples thereof include N, N-dimethylacetamide, dimethylsulfoxide, water, and the like, and mixtures thereof. After completion of the reaction, the reaction mixture is subjected to post-treatment operations such as extraction with an organic solvent and concentration to isolate the target compound. The compound can be purified by recrystallization, chromatography or the like. The chlorotriazolone compound represented by the general formula [I-1] can be produced, for example, by the following method (Production Method B).

(Production method B): Production method of the compound of the present invention wherein R ³ is a chlorine atom. General formula [VI] [Wherein, R ¹ , R ² , T, U, V and W represent the same meaning as described above. And a reaction of triphosgene [bis (trichloromethyl) carbonate], diphosgene (trichloromethyl chloroformate) or phosgene. The reaction temperature of the reaction is usually -20.
To 150 ° C, and the reaction time is usually in the range of 1 to 100 hours. The amount of the reagent used for the reaction is usually 1 mol of triphosgene, diphosgene or phosgene per 1 mol of the semicarbazide compound represented by the general formula [VI].
１００100 mol. The reaction is carried out using a solvent as necessary. Examples of such a solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, and t-butyl methyl ether. , N-hexane, heptane, ligroin, aliphatic hydrocarbons such as petroleum ether, aromatic hydrocarbons such as toluene and xylene, methylene chloride, chloroform, dichloroethane, carbon tetrachloride, and halogenation such as monochlorobenzene Examples thereof include hydrocarbons and the like, and mixtures thereof. After completion of the reaction, the reaction mixture is subjected to post-treatment operations such as extraction with an organic solvent and concentration to isolate the target compound. The compound can be purified by recrystallization, chromatography or the like. The semicarbazide compound represented by the general formula [VI]
For example, it can be produced by a method according to the following scheme 1.

Embedded image [Wherein, R ¹ , R ² , T, U, V, and W represent the same meaning as described above, R ²¹ represents a C1-C4 alkyl group (eg, a methyl group, an ethyl group, etc.), and M ¹ represents silver L represents a leaving group such as a chlorine atom, a bromine atom, an iodine atom, a p-toluenesulfonyloxy group, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, DIBAH represents diisobutylaluminum hydride, and BuLi Represents butyllithium, and DMF represents N,
Represents N-dimethylformamide. The reaction for producing a compound represented by the general formula [VII] by reacting a compound represented by the general formula [XII] with diphosgene or phosgene is described in, for example, J. Org. Chem. 61, 3883-3884 (1996). Can be performed according to the method described in (1).

(Production method C) General formula [IV] [Wherein, R ¹ , R ² , R ³ , T, U, V and W represent the same meaning as described above. And a triazolone compound represented by the general formula [XV] [Wherein L ² is a chlorine atom, a bromine atom, an iodine atom, a p-toluenesulfonyloxy group, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, an OSO ₂
Represents a leaving group such as OCH ₃ . ] The method of reacting with a methylating agent represented by the formula: The reaction is usually performed in the presence of a base, and examples of the base used include sodium hydride,
Sodium hydroxide, potassium hydroxide, sodium carbonate,
And inorganic bases such as potassium carbonate. The reaction temperature of the reaction is usually in the range of -20 to 150 ° C, and the reaction time is usually in the range of 1 to 100 hours. The amount of the reagent to be subjected to the reaction is such that the methylating agent represented by the general formula [IV] is usually in a ratio of 1 to 5 mol, and the base is usually 1 to 1 mol per mol of the triazolone compound represented by the general formula [IV]. 10 moles. The reaction is carried out using a solvent as necessary. Examples of such a solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, and t-butyl methyl ether. , N-hexane, heptane,
Aliphatic hydrocarbons such as ligroin and petroleum ether, aromatic hydrocarbons such as toluene and xylene, and organics such as pyridine, triethylamine, N-methylaniline, N, N-dimethylaniline and N, N-diethylaniline Bases,
Nitriles such as acetonitrile and isobutyronitrile,
N, N-dimethylformamide, dimethylsulfoxide, water and the like or a mixture thereof are mentioned. After completion of the reaction, the reaction mixture is subjected to post-treatment operations such as extraction with an organic solvent and concentration to isolate the target compound. The compound can be purified by recrystallization, chromatography or the like. The triazolone compound represented by the general formula [IV] can be produced, for example, by a method according to the following scheme 2.

Embedded image Wherein R ¹ , R ² , R ³ , T, U, V, W and L have the same meaning as described above. The reaction is usually performed in the presence of a base (eg, sodium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc.). The compound represented by the general formula [XVI] is described in, for example, JP-A-8-325244,
J. Chem. Soc. Perkin I, 2644-2646 (1973), Chem. Ber. 10
2,755-766 (1969), known compounds described in Chem. Ber. 98, 3025-3033 (1965), etc., or can be produced according to the methods described therein, or It can be prepared from the compounds described. In the triazolone compound represented by the general formula [IV], R ³ is C
What is a 1-C6 alkyl group or a cyclopropyl group,
It can also be produced by a method according to the following Scheme 3.

Embedded image [Wherein, R ³³ represents a C1-C6 alkyl group (eg, a methyl group, an ethyl group, etc.) or a cyclopropyl group;
R ¹ , R ² , T, U, V and W have the same meaning as described above. Examples of the base include an aqueous solution of potassium hydroxide. ]

(Production method D) General formula [II] Wherein R ³ has the same meaning as described above. (Including an alkoxytriazolone compound represented by the general formula [II-1]) represented by the general formula [II-1] and a compound represented by the general formula [VIII] in Scheme 1. The reaction is usually performed in the presence of a base, and examples of the base used include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium hydride, pyridine, 2-picoline, 4-picoline, Organic bases such as 4-dimethylaminopyridine, quinoline, triethylamine, ethyldiisopropylamine, N, N-dimethylaniline, N, N-diethylaniline, and the like, and mixtures thereof. The reaction temperature of the reaction is usually in the range of -20 to 150 ° C, and the reaction time is usually in the range of 1 to 100 hours. The amount of the reagent used for the reaction is such that the compound represented by the general formula [VIII] is usually 0.5 to 2 mol per 1 mol of the triazolone represented by the general formula [II], and the base is usually 0.5 to 2 mol. ４4 mol. The reaction is carried out using a solvent as necessary. As such a solvent, it is needless to say that the solvent is properly used depending on the base to be used. Ethers such as dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as n-hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as toluene and xylene; pyridine; triethylamine , N-methylaniline, N, N-dimethylaniline, N, N-diethylaniline and other organic bases, acetonitrile, isobutyronitrile and other nitriles, N, N
-Dimethylformamide, dimethylsulfoxide, water and the like or a mixture thereof. After completion of the reaction, the reaction mixture is subjected to post-treatment operations such as extraction with an organic solvent and concentration to isolate the target compound. The compound can be purified by recrystallization, chromatography or the like. Triazolones represented by the general formula [II] are described, for example, in Chem.
r.102,755-766 (1969), Chem.Ber.98,3025-3033 (1965)
Or can be prepared according to the method described therein or according to the method described in JP-A-8-325244, or can be prepared from the compound described therein. can do. For example, the alkoxytriazolone compound represented by the general formula [II-1] can be produced, for example, according to the following scheme 4.

Embedded image [Wherein, X ¹ represents a bromine atom or a chlorine atom, R ³¹ represents the same meaning as described above, and R ³² represents a C1-C6 alkyl group (eg, a methyl group, an ethyl group, etc.). That is, the alkoxytriazolone compound represented by the general formula [II-1] can be obtained by converting the isosemicarbazide compound represented by the general formula [XXIII] or a tautomeric compound thereof, usually from 20 to
Cyclization at 150 ° C. in the presence of a sodium alkoxide (eg, sodium methoxide, sodium ethoxide, etc.) generally represented by the general formula [XXIV], followed by treatment with an acid (eg, hydrochloric acid, etc.) Can be. The isosemicarbazide compound represented by the general formula [XXIII] can be obtained by converting a dialkyl iminocarbonate represented by the general formula [XXII] and a carbazate derivative represented by the general formula [XIX] at a temperature of usually −20 to 120 ° C. Catalysts (eg, hydrochloric, sulfuric, phosphoric, carbonic, acetic, propionic,
Protonic acid such as pivalic acid and methanesulfonic acid). The dialkyl iminocarbonate represented by the general formula [XXII] is, for example, a cyanogen halide (cyan bromide or cyanogen chloride) represented by the general formula [XX] and a sodium alkoxide represented by the general formula [XXIV] (eg, sodium methoxy). , Sodium ethoxide, etc.) with usually -20 to 50
After reacting at ° C., it can be produced by treating with an acid (for example, hydrochloric acid or the like). The carbazate derivative represented by the general formula [XIX] is represented by the general formula [XVIII]
Can be produced usually by reacting an alkyl chlorocarbonate represented by with methylhydrazine at -20 to 50 ° C. in the presence of a deoxidizing agent, if necessary.

(Production method E): Production method of the compound of the present invention wherein R ³ is a C1-C6 alkyl group or a cyclopropyl group. General formula [XXV] [Wherein, R ¹ , R ² , R ³³ , T, U, V and W represent the same meaning as described above. Cyclization and dehydration of the compound represented by the formula The reaction is usually performed in the presence of a base, and examples of the base used include inorganic bases such as potassium hydroxide and sodium hydroxide. The reaction temperature of the reaction is usually-
The reaction time is usually from 1 to 10 ° C.
The range is 0 hours. The amount of the reagent used for the reaction is usually 1 to 10 mol of the base per 1 mol of the compound represented by the general formula [XXV]. The reaction is carried out using a solvent, if necessary, such as water, 1,4
-Dioxane, tetrahydrofuran, ethylene glyco-
Ethers such as dimethyl ether, diethylene glycol dimethyl ether and t-butyl methyl ether; n
-Aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as toluene and xylene; and mixtures thereof. After completion of the reaction, the reaction solution is acidified if necessary, and then subjected to post-treatment operations such as extraction with an organic solvent and concentration to isolate the target compound. The compound can be purified by recrystallization, chromatography or the like. General formula [XX
The compound represented by V] can be produced, for example, by a method according to the following scheme 5.

Embedded image [Wherein, R ¹ , R ² , R ³¹ , T, U, V and W represent the same meaning as described above. ]

(Production Method F) For example, the following (F-1) to (F-6) can be mentioned. (F-1) A method according to the following scheme:

Embedded image[Where X^TwoRepresents a bromine atom or an iodine atom;^Two, R
^Three, T, U, V and W have the same meaning as described above. General formula
Represented by AC≡C in [XXVI] and the general formula [I-3]
Is a C2-C10 alkynyl which may be substituted.
Represents a group having a triple bond at the terminal, and A represents
Represents an optionally substituted C2 to C10 al
Examples of the substituent in the quinyl group include the compounds of the present invention described above.
Substituent R ¹Optionally substituted C2 to C2
The same substituents as those in the 10 alkynyl group are exemplified.
You. The reaction is performed, for example, using an aprotic polar solvent (for example, acetic acid).
In nitrile, N, N-dimethylformamide, etc.)
Groups {eg, tertiary amines (triethylamine, diisopropane
Propyl ethylamine, etc.), secondary amine (diethylamine
Etc.) Primary amines (butylamine etc.) etc. and catalysts
(For example, palladium (II) acetate, tetrakis (tri
Phenylphosphine) palladium (0), bis- (g
Riphenylphosphine) palladium (II) dichlora
Id (PdCl_Two(PPh_Three)_Two) And other palladium catalysts
Copper (I) iodide and triphenylphosphine as required
Etc.) (more specifically, for example, international
Exam in patent application WO 98/03464 published specification
ple1, Tetrahedron Lett., 1975, 4467
According to the method described in Synthesis, 1980, 627
Do it. )be able to.

(F-2) A method according to the following scheme 7.

Embedded image [In the formula, X represents a bromine atom, an iodine atom, a chlorine atom or a trifluoromethanesulfonyloxy group, and Z represents B (O
R ¹⁴ ) ₂ groups or SnR ¹⁵ ₃ groups, wherein R ¹⁵ is
4 represents an alkyl group (for example, a methyl group, an ethyl group, a butyl group, etc.), and A ³ represents an optionally substituted C 6 -C 10
An aryl group or an optionally substituted C1~C9 heteroaryl ^{group, R 2, R 3, R} 14, T, U, V and W are as defined above. The reaction temperature is usually in the range of 20 to 120 ° C., the reaction time is usually in the range of 1 to 24 hours, and the molar ratio of the compound represented by the general formula [XXVII] is represented by the general formula [I-2]. Usually in the range of 0.8 to 5 for the compound to be prepared. The molar ratio of the catalyst used in the reaction is usually in the range of 0.001 to 0.1 with respect to the compound represented by the general formula [I-2]. Examples of the catalyst include palladium (II) acetate, tetrakis (triphenylphosphine) palladium (0),
{1,1′-bis (diphenylphosphino) ferrocene} dichloropalladium (II) methylene chloride complex, tris (dibenzylideneacetone)-(chloroform)-
Palladium catalysts such as dipalladium (0) [Pd ₂ (dba) ₃ CHCl ₃ ] and bis- (triphenylphosphine) palladium (II) dichloride. The reaction may be carried out with a base if necessary (eg, sodium acetate, potassium acetate,
Inorganic bases such as potassium carbonate, cesium carbonate, tripotassium phosphate, and sodium bicarbonate), phase transfer catalysts (for example, quaternary ammonium salts such as tetrabutylammonium bromide and benzyltriethylammonium bromide), ligands (for example, tri-t-butylphosphine and the like) Can also be performed in the presence of Further, in the compound represented by the general formula [XXVII], Z is if a SnR ¹⁵ ₃ group, copper oxide as a co-catalyst (II), can also be used silver (I) oxide and the like.
The reaction is usually performed in a solvent. Examples of the solvent include methanol, ethanol, propanol and butanol.
Alcohol solvents such as toluene and isopropanol; ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butylmethyl ether; and aliphatic solvents such as n-hexane and n-heptane. Examples thereof include a hydrocarbon solvent, an aromatic hydrocarbon solvent such as toluene, a nitrile solvent such as acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide, water, and the like, and a mixture thereof. The reaction is more specifically, for example,
J. Org, Chem. , 1997, 62, 7170-
7173 [in water in the presence of tetrabutylammonium bromide, a base (eg, an inorganic base such as potassium carbonate) and a catalyst (eg, palladium (II) acetate, etc.)], International Patent Application WO 96/35669. In a mixed solvent of water and dimethoxyethane, a base (eg, an inorganic base such as sodium bicarbonate) and a catalyst (eg, Pd (PPh ₃ ) ₄
And the like). Org. Chem. , 1
995, 60, 7508-7510, Ange
Int. Ed. 1998, 37 (24), 3387-3388, Angew. Chem. Int. Ed. Eng
l. , 1986, 25, 508-524. After completion of the reaction, the reaction solution is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration to obtain a target compound. If necessary, it can be purified by recrystallization, chromatography or the like. General formula [XXVI
The compound of the formula (I) may be a commercially available compound, or may be produced, for example, by the method shown in the following Scheme 8.

Embedded image 中 In the formula, A ³ , X and Z represent the same meaning as described above. ｝ The reaction is carried out, for example, in a solvent (eg, diethyl ether, tetrahydrofuran, etc.) with a compound represented by the general formula [XXVIII] and a metal (eg, magnesium, lithium, etc.) or an organic lithium reagent (eg, t-butyl lithium, n
-Butyl lithium, lithium diisopropylamide, etc.)
A Grignard reagent or an organolithium compound obtained by reacting the compound with a boric acid ester (eg, trimethyl borate, triethyl borate, triisopropyl borate, etc.) and, if necessary, hydrolyzing the compound (more specifically, Include, for example, Organometallics, 1983, 2, 1316; Li
ebigsAnn., 1996, 1037; 4th edition Experimental Chemistry Course 24, Organic Synthesis VI, p.80, Maruzen; Am. Chem. Soc. , 19
58, 80, 4291-4293. ) Or a solvent (dimethylsulfoxide, N, N-
A base (eg, an inorganic base such as potassium acetate) and a catalyst (eg, ｛1, dimethylformamide).
The compound represented by the general formula [XXVIII] is reacted with bis (pinacolato) diboron in the presence of 1'-bis (diphenylphosphino) ferrocene {dichloropalladium (II) methylene chloride complex and the like. (More specifically, for example, J. Or.
g. Chem. , 1995, 60, 7508-7510.
And in accordance with the method described in ) And, (catalyst (e.g. in toluene, etc.), tetrakis (triphenylphosphine) solvent compound represented by the general formula [XXVIII] in the presence of a palladium (0) etc.) and R ¹⁵ ₃ SnSnR ¹⁵ ₃ (e.g. , Bu ₃ SnSnBu _3, etc. (more specifically, for example, Chem. Letters, 1
981, 829-830. ) And the like. After completion of the reaction, the reaction solution is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration to obtain a target compound. If necessary, the target compound can be isolated by purification by recrystallization, distillation, chromatography or the like.

(F-3) A method according to the following scheme 9.

Embedded image [Wherein, A ¹¹ represents A ¹ other than a hydrogen atom, and A ¹ , A ² ,
R ² , R ³ , L, T, U, V and W have the same meaning as described above. Among the compounds represented by the general formula [I-5], those wherein A ² is a methyl group are described, for example, in J. Org. Chem., 1992, 57, 1481-148.
According to the method described in 6, the compound represented by the general formula [I-2] and butyl vinyl ether are reacted in the presence of a palladium catalyst, a phosphine ligand and a base, followed by acid hydrolysis.

(F-4) A production method according to the following scheme 10.

Embedded image [Wherein A ¹ , A ² , R ² , R ³ , L, T, U, V and W represent the same meaning as described above. ]

(F-5) A production method according to the following scheme 11.

Embedded image [Wherein, X ² , R ² , R ³ , T, U, V and W represent the same meaning as described above. The reaction is described, for example, in Synlett, 1994, 371-3.
72 can be carried out.

(F-6) A method according to the following scheme:

Embedded image Wherein A ³ , X, Z, R ² , R ³ , T, U, V and W have the same meaning as described above. The reaction temperature is usually in the range of 20 to 120 ° C., the reaction time is usually in the range of 1 to 24 hours, and the molar ratio of the compound represented by the general formula [XXX] is the compound represented by the general formula [III]. Is usually in the range of 1 to 5. The molar ratio of the catalyst used in the reaction is usually in the range of 0.001 to 0.1 with respect to the compound represented by the general formula [III]. Examples of the catalyst include palladium (II) acetate, tetrakis (triphenylphosphine) palladium (0),
{1,1′-bis (diphenylphosphino) ferrocene} dichloropalladium (II) methylene chloride complex, tris (dibenzylideneacetone)-(chloroform)-
Palladium catalysts such as dipalladium (0) [Pd ₂ (dba) ₃ CHCl ₃ ] and bis- (triphenylphosphine) palladium (II) dichloride. The reaction may be carried out with a base if necessary (eg, sodium acetate, potassium acetate,
Inorganic bases such as potassium carbonate, cesium carbonate, tripotassium phosphate, and sodium bicarbonate), phase transfer catalysts (for example, quaternary ammonium salts such as tetrabutylammonium bromide and benzyltriethylammonium bromide), ligands (for example, tri-t-butylphosphine and the like) Can also be performed in the presence of Further, in the compound represented by the general formula [XXX], Z is if a SnR ¹⁵ ₃ group, copper oxide as a co-catalyst (II), can also be used silver (I) oxide and the like.
The reaction is usually performed in a solvent. Examples of the solvent include methanol, ethanol, propanol and butanol.
Alcohol solvents such as toluene and isopropanol; ether solvents such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butylmethyl ether; and aliphatic solvents such as n-hexane and n-heptane. Examples thereof include a hydrocarbon solvent, an aromatic hydrocarbon solvent such as toluene, a nitrile solvent such as acetonitrile, N, N-dimethylformamide, dimethyl sulfoxide, water, and the like, and a mixture thereof. The reaction is more specifically, for example,
J. Org, Chem. , 1997, 62, 7170-
7173 (in water in the presence of tetrabutylammonium bromide, a base (for example, an inorganic base such as potassium carbonate) and a catalyst (for example, palladium acetate and the like)), and the specification of International Patent Application WO 96/35669. (For example, Pd (PPh ₃ ) _{4 and the} like) in a mixed solvent of water and dimethoxyethane in a mixed solvent of water and dimethoxyethane.
Carried out in the presence of). Org. Chem. , 199
5, 60, 7508-7510, Angew.
Int. Ed. 1998, 37 (24), 3387-3388, or the method described in Angew. Chem. Int. Ed. Engl. , 1
986, 25, 508-524. After completion of the reaction, the reaction solution is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration to obtain a target compound. If necessary, the target compound can be isolated by purification by recrystallization, distillation, chromatography or the like. The compound represented by the general formula [III] can be produced, for example, by a method represented by the following scheme 13.

Embedded image [Wherein, X, Z, R ² , R ³ , T, U, V and W represent the same meaning as described above. In the reaction of Scheme 13, the reaction temperature is usually in the range of 20 to 100 ° C., the reaction time is usually in the range of 1 to 24 hours, and the molar ratio of [XXIX] to [I-2] is usually 1 to 5 range. The reaction is carried out, for example, in a solvent (dimethylsulfoxide, N, N-dimethylformamide, etc.) in a base (for example, an inorganic base such as potassium acetate) and a catalyst (for example, 1,1, '-bis (diphenylphosphino)). In the presence of ferrocene (dichloropalladium (II) methylene chloride complex), the compound represented by the general formula [I-
2] with bis (pinacolato) diboron or the like (more specifically, for example, as described in
Org. Chem. , 1995, 60, 7508-75.
Performed according to the method described in No. 10. ) And the solvent (catalyst (e.g. with toluene, etc.) in, tetrakis (triphenylphosphine) compound represented by the general formula in the presence of a palladium (0), etc.) [I-2] and R ¹⁵ ₃ SnSnR ¹⁵ ₃ (For example, Bu ₃ SnSnBu ₃ etc.) (more specifically, for example, Chem. Letters, 1
981, 829-830. ) And the like. Further, those wherein Z is B (OR ¹⁴ ) ₂ and R ¹⁴ is C1-C6 alkyl in [III] are represented by the general formula [I-2] in a solvent (for example, diethyl ether, tetrahydrofuran, etc.). Grignard reagent or organolithium compound obtained by reacting a compound to be reacted with a metal (eg, magnesium, lithium, etc.) or an organolithium reagent (eg, t-butyllithium, n-butyllithium, lithium diisopropylamide, etc.) and boric acid Birds (C1-C6
Alkyl) ester (eg, trimethyl borate, triethyl borate, triisopropyl borate, etc.) and, if necessary, hydrolysis (for example, Organometallics, 1983, 2, 1316; Liebigs Ann) ., 199
6, 1037; 4th edition Experimental Chemistry Course 24, Organic Synthesis VI, p. 80, Maruzen; Am. Chem. Soc. , 1958, 80,
This is performed according to the method described in No. 4291-4293. ) Can be manufactured. After completion of the reaction, the reaction solution is subjected to ordinary post-treatments such as extraction with an organic solvent and concentration to obtain a target compound. If necessary, it can be purified by recrystallization, chromatography or the like.

(Production Method G) A production method according to the following Scheme 14.

Embedded image [Wherein, TMS represents a trimethylsilyl group;
R ¹ , R ² , T, U, V and W represent the same meaning as described above. From the compound represented by the general formula [XXXII] to the general formula [I-15]
Examples of the dehydrating agent for producing the compound represented by are acetic anhydride and the like. Examples of the reducing agent for producing the compound represented by the general formula [I-16] from the compound represented by the general formula [I-17] include Lindlar catalyst / H _{2 and the} like. As a strong base for producing the compound represented by the general formula [I-17] from the compound represented by the general formula [XXXIII], for example, butyllithium and the like can be mentioned. As a catalyst for producing the compound represented by the general formula [I-19] from the compound represented by the general formula [I-18], for example, palladium (II) acetate, tetrakis (triphenylphosphine) palladium (0 ), Bis- (triphenylphosphine) palladium (II) dichloride (PdCl ₂
Palladium catalysts such as (PPh ₃ ) ₂ ) and, if necessary, copper (I) iodide and triphenylphosphine. The formyl compound represented by the general formula [XXXI] in Scheme 14 can be produced, for example, according to Scheme 15 below.

Embedded image [Wherein A ³ , L ¹ , X, Y, R ⁶ , R ⁷ and R ⁸ represent the same meaning as described above. From the compound represented by the general formula [XXXVIII]
Examples of the base for producing the compound represented by I] include an aqueous potassium hydroxide solution. Examples of the methylating agent for producing the compound represented by the general formula [XXXVII] from the compound represented by the general formula [XXXVI] include methyl iodide-potassium carbonate. General formula [XX
An oxidizing agent for producing the compound represented by the general formula [XXXI] from the compound represented by the formula [XVII] includes, for example, manganese dioxide.

When the compound of the present invention is used as an active ingredient of an agricultural and horticultural fungicide, it may be used as it is without adding any other components, but it is usually used as a solid carrier, a liquid carrier, a surfactant, and other pharmaceutical preparations. Mix with adjuvants, emulsions, wettable powders,
It is formulated into suspensions, powders, granules, etc. and used. In these preparations, the compound of the present invention as an active ingredient is usually added in a weight ratio.
It contains 0.1-90%. Examples of the solid carrier used in the preparation include, for example, kaolin clay, attapulgite clay, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, corn cob powder, walnut shell powder, urea, Examples of the liquid carrier include fine powders or granular materials such as ammonium sulfate and synthetic hydrous silicon oxide. Examples of the liquid carrier include aromatic hydrocarbons such as xylene and methylnaphthalene, and alcohols such as isopropanol, ethylene glycol and cellosolve. And ketones such as acetone, cyclohexanone and isophorone, vegetable oils such as soybean oil and cottonseed oil, dimethyl sulfoxide, acetonitrile, water and the like. Examples of the surfactant include anions such as alkyl sulfate, alkyl (aryl) sulfonate, dialkyl sulfosuccinate, polyoxyethylene alkyl aryl ether phosphate, and naphthalenesulfonic acid formalin condensate. Examples of the surfactant include nonionic surfactants such as surfactants, polyoxyethylene alkyl ethers, polyoxyethylene alkyl polyoxypropylene block copolymers, and sorbitan fatty acid esters. Pharmaceutical adjuvants include, for example, lignin sulfonate, alginate, polyvinyl alcohol-
, Gum arabic, CMC (carboxymethylcellulo-
), PAP (acidic isopropyl phosphate) and the like. Specific examples of the application method of the compound of the present invention include foliage application, soil treatment, seed disinfection, and the like, and can be used in any application method usually used by those skilled in the art.

When the compound of the present invention is used as an active ingredient in agricultural and horticultural fungicides, the application rate of the active ingredient depends on the type of target plant (crop etc.), the type of target disease, the degree of occurrence of disease,
Although it may vary depending on the form of formulation, application method, application time, weather conditions, etc., it is usually 0.01 to 50 g, preferably 0.05 to 10 g per arc. When the emulsion, wettable powder, suspending agent, etc. are diluted with water and applied, the application concentration is
0.0001 to 3%, preferably 0.0005 to 1%, and dusts, granules and the like are applied without any dilution.

The compound of the present invention can be used as a fungicide for agricultural and horticultural use in fields, paddy fields, orchards, tea fields, pastures, lawns, and the like. It can also be expected to increase the bactericidal efficacy. Other agricultural and horticultural fungicides that can be mixed include, for example, propiconazo-
, Triadimenol, prochloraz, penconazo
, Tebuconazole, flusilazole, diniconazole
, Bromconazole, epoxyconazole, difenoconazole, cyproconazole, metconazole, triflumizole, tetraconazole, microbutanyl,
Azol-based germicidal compounds such as fenbuconazole, hexaconazole, fluquinconazole, triticonazole, bitertanol, imazalil, and flutriaphor;
Cyclic amine fungicides such as fenpropimorph, tridemorph and fenpropidine, benzimidazole fungicides such as carbendazim, benomyl, thiabendazole, thiophanate-methyl, etc., procymidone, cyprodinil, pyrimethanil, dietofencarb, thiuram, fluazinam , Mancozeb, iprodione, vinclozolin, chlorothalonil, captan, mepanipyrim, fenpiclonil, fludioxonil, diclofluanid, folpet, kresoxime methyl, azoxystrobin, N-methyl-α-methoxyimino-2-
[(2,5-dimethylphenoxy) methyl] phenylacetamide, spiroxamine, quinoxyfen, fenhexamide, famoxadone, phenamidone (RP-4
07213), iprovaricarb and the like.

The compound of the present invention can be mixed with or used in combination with other agricultural and horticultural insecticides, acaricides, nematicides, herbicides, plant growth regulators, and fertilizers. Examples of such insecticides and / or miticides and / or nematicides include fenitrothion [O, O-dimethyl O- (3-methyl-4-nitrophenyl) phosphorothioate] and phenythion [O, O- Dimethyl O- (3-methyl-4-
(Methylthio) phenyl) phosphorothioate], diazinone [O, O-diethyl O-2-isopropyl-
6-methylpyrimidin-4-yl phosphorothioe-
G), chlorpyrifos [O, O-diethyl O-3,
5,6-trichloro-2-pyridyl phosphorothioe-
Acetoate [O, S-dimethylacetylphosphoramide thioate], methidathion [S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3] -Ylmethyl O, O-dimethyl phosphorodithioate], disulfotone [O, O-diethyl S
-2-ethylthioethyl phosphorothioate], DDV
P [2,2-dichlorovinyldimethylphosphate],
Sulfophophos [O-ethyl O-4- (methylthio) phenyl S-propyl phosphorodithioate], cyanophos [O-4-cyanophenyl O, O-dimethyl phosphorothioate], dioxabenzophos [2 -Methoxy-4H-1,3,2-benzodioxaphosphinin-2
-Sulfide], dimethoate [O, O-dimethyl S
-(N-methylcarbamoylmethyl) dithiophospho-
G), phentoate [ethyl 2-dimethoxyphosphinothioylthio (phenyl) acetate], malathion [diethyl (dimethoxyphosphinothioylthio) succinate], trichlorfon [dimethyl 2,2,2
-Trichloro-1-hydroxyethylphosphonate],
Azinphosmethyl [S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl
O, O-dimethyl phosphorodithioate], monocrotophos [dimethyl (E) -1-methyl-2- (methylcarbamoyl) vinyl phosphate], ethion [O, O,
O ', O'-tetraethyl S, S'-methylenebis (phosphorodithioate)], phosthiazetate [N-
Organic phosphorus compounds such as (O-methyl-S-sec-butyl) phosphorylthiazolidine-2-one], BPMC [2
-Sec-butylphenylmethylcarbamate], benfracarb [ethyl N- (2,3-dihydro-2,2-
Dimethylbenzofuran-7-yloxycarbonyl (methyl) aminothio] -N-isopropyl-β-alaninate], propoxur [2-isopropoxyphenyl
N-methyl carbamate], carbosulfan [2, 3
-Dihydro-2,2-dimethyl-7-benzo [b] furanyl N-dibutylaminothio-N-methylcarbamoyl
), Carbaryl [1-naphthyl N-methylcarbamate], mesomyl [S-methyl-N-[(methylcarbamoyl) oxy] thioacetimidate], ethiophenecarb [2- (ethylthiomethyl) phenylmethylcarbamate Bamate], aldicarb [2-methyl-2- (methylthio) propionaldehyde O-methylcarbamoyloxime], oxamyl [N, N-dimethyl-2-methylcarbamoyloxyimino-2- (methylthio) acetamide], phenothiocarb [ Carbamate-based compounds such as S-4-phenoxybutyl-N, N-dimethylthiocarbamate and ethofenprox [2- (4-ethoxyphenyl) -2-methylpropyl-3-phenoxybenzyl ether- Ter], fenvalerate [(RS) -α
-Cyano-3-phenoxybenzyl (RS) -2-
(4-chlorophenyl) -3-methylbutyrate], esfenvalerate [(S) -α-cyano-3-phenoxybenzyl (S) -2- (4-chlorophenyl)-
3-methylbutyrate], fenpropatrin [(R
S) -α-Cyano-3-phenoxybenzyl 2,2
3,3-tetramethylcyclopropanecarboxyle
G), cypermethrin [(RS) -α-cyano-3-phenoxybenzyl (1RS, 3RS) -3- (2,2
-Dichlorovinyl) -2,2-dimethylcyclopropanecarboxylate], permethrin [3-phenoxybenzyl (1RS, 3RS) -3- (2,2-dichlorovinyl) -2,2-methylcyclopropanecarboxylate −
G], cyhalothrin [(RS) -α-cyano-3-phenoxybenzyl (Z)-(1RS, 3RS) -3-
(2-chloro-3,3,3-trifluoropropenyl)
-2,2-dimethylcyclopropanecarboxyle-
G), deltamethrin [(S) -α-cyano-m-phenoxybenzyl (1R, 3R) -3- (2,2-dibromovinyl) -2,2-dimethylcyclopropanecarboxylate], cycloprothrin [(RS) -α-cyano-3-phenoxybenzyl (RS) -2,2-dichloro-1- (4-ethoxyphenyl) cyclopropanecarboxylate], fluvalinate [α-cyano-3-
Phenoxybenzyl N- (2-chloro-α, α, α-
Trifluoro-p-tolyl) -D-barynate], bifensulin [2-methylbiphenyl-3-ylmethyl]
(Z)-(1RS) -cis-3- (2-chloro-3,
3,3-trifluoroprop-1-enyl) -2,2-
Dimethylcyclopropanecarboxylate], acrinasulin [(1R- {1α (S *), 3α (Z)}]-
2,2-dimethyl-3- [3-oxo-3- (2,2,
2-trifluoro-1- (trifluoromethyl) ethoxy-1-propenyl] cyclopropanecarboxylic acid cyano (3-phenoxyphenol) methyl ester)], 2-
Methyl-2- (4-bromodifluoromethoxyphenyl) propyl (3-phenoxybenzyl) ether, tralomethrin [(S) -α-cyano-3-phenoxybenzyl (1R) -cis-3- (1,2, Pyrethroid compounds such as 2,2-tetrabromoethyl) -2,2-dimethylcyclopropanecarboxylate and silafluorene [[4-ethoxyphenyl (3- (4-fluoro-3-phenoxyphenyl) propyl) dimethylsilane]; Thiadiazine derivatives such as buprofezin (2-t-butylimino-3-isopropyl-5-phenyl-1,3,5-triadiadinan-4-one), nitroimidazolidine derivatives, cartap (S, S '-(2-dimethylamino) Trimethylene) bis (thiocarbamate)],
Thiocyclam [N, N-dimethyl-1,2,3-trithian-5-ylamine], bensultap [S, S'-
2-dimethylaminotrimethylene di (benzenethiosulfonate)], N-cyano-N'-methyl-N '-(6-chloro-3-pyridylmethyl) acetamidine and the like. N-cyanoamidine derivative, endosulfan [6,7,8,9,10,10-
Hexachloro-1,5,5a, 6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin oxide], gamma-BHC (1,2,
3,4,5,6-hexachlorocyclo n-hexane],
Chlorinated hydrocarbon compounds such as 1,1-bis (chlorophenyl) -2,2,2-trichloroethanol, chlorofluazurone [1- (3,5-dichloro-4- (3-chloro-5- Trifluoromethylpyridin-2-yloxy)
Phenyl) -3- (2,6-difluorobenzoyl) urea], teflubenzuron [1- (3,5-dichloro-
2,4-difluorophenyl) -3- (2,6-difluorobenzoyl) urea], flufenoxuron [1-
Benzoylphenylurea-based compounds such as (4- (2-chloro-4-trifluoromethylphenoxy) -2-fluorophenyl) -3- (2,6-difluorobenzoyl) urea], amitraz [N, N '[( Methylimino)
Dimethylidin] di-2,4-xylysine], chlordimeform [N '-(4-chloro-2-methylphenyl)-
N, N-dimethylmetanimidamide], thiourea derivatives such as diafenthiuron [N- (2,6-diisopropyl-4-phenoxyphenyl) -N′-t-butylcarbodiimide], phenylpyrazones -Based compound, tebufenozide [Nt-butyl-N '
-(4-ethylbenzoyl) -3,5-dimethylbenzohydrazide], 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl-5-trifluoromethylpyrrol-3-carbonitrile, bromopropyl [Isopropyl 4,4'-dibromobenzylate], tetradiphone [4-chlorophenyl 2,4,5-trichlorophenyl sulfone], quinomethionate [S, S-6
-Methylquinoxaline-2,3-diyldithiocarbonate], propargate [2- (4-t-butylphenoxy) cyclohexylprop-2-yl sulfite], fenbutatin oxide [bis [tris (2
-Methyl-2-phenylpropyl) tin] oxide], hexthiazox [(4RS, 5RS) -5-
(4-chlorophenyl) -N-chlorohexyl-4-methyl-2-oxo-1,3-thiazolidine-3-carboxamide], clofentezine [3,6-bis (2-chlorophenyl) -1,2,4 , 5-tetrazine, pyridathioben [2-t-butyl-5- (4-t-butylbenzylthio) -4-chloropyridazin-3 (2H) -one], fenpyroximate [t-butyl (E) -4-
[(1,3-dimethyl-5-phenoxypyrazole-4)
-Yl) methyleneaminooxymethyl] benzoe-
G), tebufenpyrad [N-4-t-butylbenzyl) -4-chloro-3-ethyl-1-methyl-5-pyrazolcarboxamide], polynactin complex [tetranactin, dinactin, trinactin], milbemectin, avermectin , Iva-mectin, azadirachtin [AZAD], pyrimidifen [5-chloro-
N- [2- {4- (2-ethoxyethyl) -2,3-dimethylphenoxy} ethyl] -6-ethylpyrimidine-
4-amine, pymetrozine [2,3,4,5-tetrahydro-3-oxo-4-[(pyridin-3-yl) -methyleneamino] -6-methyl-1,2,4-triazine and the like. .

The plant diseases which can be controlled by the compounds of the present invention include, for example, the following diseases. Rice blast (Pyricularia oryzae), sesame leaf blight (Cochliobolus miyabeanus), sheath blight (Rhizoc)
tonia solani, wheat powdery mildew (Erysiphe grami)
nis), Fusarium head blight (Gibberella zeae), Rust (Puccinia
striiformis, P. graminis, P. recondita, P. horde
i), snow rot (Typhula sp., Micronectriella nivalis),
Nude smut (Ustilago tritici, U. nuda), black smut (Tilletia caries), eye spot (Pseudocercosporella)
herpotrichoides), scald (Rhynchosporium secalis)
, Leaf blight (Septoria tritici), Fusarium wilt (Leptosphaer)
ia nodorum), citrus black spot (Diaporthe citr)
i), scab (Elsinoe fawcetti), fruit rot (Peni
cillium digitatum, P. italicum), Monilia disease of apples (Sclerotinia mali), Rot rot (Valsa mali), Powdery mildew (Podosphaera leucotricha), Spot leaf rot (Al
ternaria mali), scab (Venturia inaequalis), pear scab (Venturia nashicola, V. pirina), black spot (Alternaria kikuchiana), red scab (Gymnosporangium)
haraeanum), peach scab (Sclerotinia cinerea), scab (Cladosporium carpophilum), phomopsis rot (Phomopsis sp.), grape scab (Elsinoe ampe)
lina), late rot (Glomerella cingulata), powdery mildew (Uncinula necator), rust (Phakopsora ampelopsi)
dis), black lot disease (Guignardia bidwellii), downy mildew (Plasmopara viticola), oyster anthracnose (Gloeospo
rium kaki), deciduous disease (Cercospora kaki, Mycosphaerell
a nawae), Anthracnose of cucumber (Colletotrichum lagenariu)
m), powdery mildew (Sphaerotheca fuliginea), vine blight
(Mycosphaerella melonis), vine disease (Fusarium oxy
sporum), downy mildew (Pseudoperonospora cubensis), plague (Phytophthora sp.), seedling blight (Pythium sp.), tomato ring spot (Alternaria solani), leaf mold (Clados)
porium fulvum), plague (Phytophthora infestans), eggplant brown spot (Phomopsis vexans), powdery mildew (Erysip)
he cichoracearum), black spot of cruciferous vegetables (Altern
aria japonica), vitiligo (Cercosporella brassicae),
Leek rust (Puccinia allii), soybean purpura (Ce)
rcospora kikuchii), black rot (Elsinoe glycines),
Black spot (Diaporthe phaseolorum var. Sojae), kidney anthracnose (Colletotrichum lindemthianum), peanut black spot (Cercospora personata), brown spot (Cerco
spora arachidicola), pea powdery mildew (Erysiph)
e pisi), potato summer blight (Alternaria solani),
Plague (Phytophthora infestans), strawberry powdery mildew (Sphaerotheca humuli), tea net blast (Exobasidiu)
m reticulatum), white scab (Elsinoe leucospila), tobacco scab (Alternaria longipes), powdery mildew (Erys)
iphe cichoracearum), anthracnose (Colletotrichum tabac)
um), downy mildew (Peronospora tabacina), plague (Phytop
hthora nicotianae), brown spot of sugar beet (Cercospora b
eticola), rose scab (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa), chrysanthemum yellow rot (Septori)
a chrysanthemi-indici), white rust (Puccinia horia)
na), gray mold on various crops (Botrytis cinerea),
Sclerotinia sclerotiorum, etc.

[0027]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Production Examples, Preparation Examples, Test Examples, and the like, but the present invention is not limited to only these examples. First, a production example of the compound of the present invention (a production example of a triazolone compound represented by the general formula [IV] of an intermediate compound: Reference Production Examples 4, 5, 6, and 10)
11, 12, 13, 16, 17, and 18).
The numbers of the compounds of the present invention are the compound numbers described in Tables 1 to 23 below.

Production Example 1 5-chloro-2-methyl-4- (3-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 2 of the present invention; 300 mg (1.0 mmol) in 10 ml of anhydrous methanol
And 0.85 g (4.4 mmol) of sodium methoxide (28% methanol solution) was added thereto, followed by heating under reflux for 3.5 hours. After allowing to cool to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue is subjected to silica gel preparative thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 1)
To give 5-methoxy-2-methyl-4- (3-phenylbenzyl) -2,4-dihydro-3H-1,2,4-
0.24 g of triazol-3-one (Compound 1 of the present invention)
(0.81 mmol) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.6 (9H, m), 4.76 (2H, s), 3.95 (3H, s), 3.38
(3H, s)

Production Example 2 To a solution of 2.75 g (9.28 mmol) of triphosgene in 15 ml of methylene chloride was added 1,1-dimethyl-4- (3-phenylbenzyl) semicarbazide (see Reference Production Example 1 below) under ice-cooling. A solution of 1.25 g (4.64 mmol) in 10 ml of methylene chloride was added dropwise. The reaction vessel was removed from the ice-cooled bath, heated to reflux for 4 hours after reaching room temperature. After allowing to cool to room temperature, the reaction mixture was poured into about 5% aqueous sodium bicarbonate (100 ml) and stirred for 1 hour. The organic layer was washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 5: 1).
Then eluted 3: 1) to give 5-chloro-2-methyl-4- (3-phenylbenzyl) -2,4-dihydro-.
0.59 g (2.0 mmol) of 3H-1,2,4-triazol-3-one (the present compound 2) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.6 (9H, m), 4.91 (2H, s), 3.47 (3H, s)

Reference Production Example 1 (1) 22.84 g (95.0 mm) of 3-bromobiphenyl
ol) in n-butyllithium (1.64m
ol / liter, n-hexane solution) 61 ml (99.8 mmol) was added. After stirring at the same temperature for 1 hour, 36.55 g (0.50 mol) of N, N-dimethylformamide was added dropwise, and the mixture was stirred overnight while gradually returning to room temperature. 400 ml of about 5% aqueous hydrochloric acid was added to the reaction solution, and the mixture was stirred at room temperature for 2 hours. The mixture was extracted with t-butyl methyl ether, and the organic layer was washed with about 5% aqueous sodium bicarbonate and water, dried, and concentrated. The residue was subjected to silica gel column chromatography (n-hexane, then
n-hexane: ethyl acetate = 15: 1).
13.95 g (76.56 mmol) of 3-phenylbenzaldehyde were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 10.09 (1 H, s), 7.3-8.1 (9 H, m) (2) 5.47 g of 3-phenylbenzaldehyde (30 m
mol) was dissolved in 50 ml of anhydrous methanol and 50 ml of anhydrous tetrahydrofuran, 1.34 g (32 mmol) of sodium borohydride was added little by little under ice cooling, and the mixture was further stirred for 1 hour under ice cooling. The reaction solution was added to 400 ml of about 5% aqueous ammonium chloride, extracted with t-butyl methyl ether, and the organic layer was dried and concentrated to obtain 5.57 g (30 mmol) of 3-phenylbenzyl alcohol. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.7 (9H, m), 4.75 (2H, brd), 1.75 (1H, br)
t) (3) 5.57 g of 3-phenylbenzyl alcohol (3
(0 mmol) dissolved in n-hexane, 4.06 g (13.5 mmol) of phosphorus tribromide was added dropwise under ice cooling. The reaction vessel was removed from the ice bath and stirred at room temperature for an additional 3.5 hours. Ice water and t-butyl methyl ether were added to the reaction solution, stirred for 30 minutes, and then separated. 2 organic layers
After washing with water, drying and concentration, 6.62 g (26.8 mmol) of 3-phenylbenzyl bromide was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.65 (9H, m), 4.56 (2H, s) (4) 2.47 g of 3-phenylbenzylbromide (10 m
mol) was dissolved in 30 ml of anhydrous tetrahydrofuran, and 1.99 g (13 mmol) of silver cyanate was added thereto, followed by heating under reflux for 2 hours. The reaction solution was filtered, and the filtrate was concentrated to obtain 2.56 g of crude 3-phenylbenzyl isocyanate. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25-7.65 (9H, m), 4.56 (2H, s) 2.56 g of this crude 3-phenylbenzyl isocyanate
Was dissolved in 8 ml of toluene, and under ice-cooling, 0.78 g (13 mmol) of N, N-dimethylhydrazine was added dropwise, and the reaction vessel was removed from the ice-cooled bath, and further stirred for 1.5 hours. The reaction solution was concentrated, and the residue was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 1: 1, then 1: 2) to give 1,1-dimethyl-4- (3-phenylbenzyl) semicarbazide 1 .40 g (5.20
mmol). ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (9H, m), 6.45 (1H, br), 5.10 (1H, br),
4.53 (2H, d), 2.51 (6H, s)

Production Example 3 5-chloro-2-methyl-4- {3- (1- (benzyloxyimino) ethyl) benzyl} -2,4-dihydro-3H-1,2,4-triazole-3- ON (the present compound 249: produced in Production Example 4 described later) 193 mg
(0.52 mmol) was dissolved in 10 ml of anhydrous methanol, and sodium methoxide (28% methanol solution) was added thereto.
0.20 g (1.0 mmol) was added, and the mixture was heated under reflux for 3 hours. Further, 0.20 g (1.0 mmol) of sodium methoxide (28% methanol solution) was added, and the mixture was heated under reflux for 3 hours. After allowing to cool to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue was subjected to silica gel preparative thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 1) to give 5-methoxy-2-methyl-4- {3- (1- (benzyloxyimino) ethyl). Benzyl {-2,4-dihydro-3H-
1,2,4-triazol-3-one (Compound 2 of the present invention)
39) 141 mg (0.385 mmol) were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (9H, m), 5.24 (2H, s), 4.71 (2H, s), 3.9
2 (3H, s), 3.37 (3H, s), 2.25 (3H, s)

Production Example 4 To a solution of 0.96 g (3.24 mmol) of triphosgene in 10 ml of anhydrous methylene chloride was added 1,1-dimethyl-4- {3- (1- (benzyloxyimino) ethyl) under ice-cooling. ) A solution prepared by dissolving 0.55 g (1.62 mmol) of benzyl @ semicarbazide (produced in Reference Production Example 2 described later) in 15 ml of anhydrous methylene chloride was added dropwise. The reaction vessel was removed from the ice-cooled bath, heated to reflux for 4 hours after reaching room temperature.
After cooling to room temperature, the reaction solution was poured into about 5% aqueous sodium bicarbonate (40 ml) and stirred for 0.5 hour. The organic layer was washed with water, dried and concentrated. The residue was subjected to silica gel preparative thin-layer chromatography (developed with n-hexane: ethyl acetate = 3: 2) to give 5-chloro-2-methyl-4- {3- (1- (benzyloxyimino) ethyl). Benzyl} -2,4-dihydro-3H-1,2,4-triazol-3-one
0.27 g (0.74 mmol) of (the present compound 249) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (9H, m), 5.24 (2H, s), 4.86 (2H, s), 3.4
6 (3H, s), 2.25 (3H, s)

Reference Production Example 2 (1) 14.52 g of 3-acetylbenzonitrile (0.
10 mol) was suspended in 100 ml of methanol.
17.56 g of benzylhydroxylamine hydrochloride
(0.11 mol), and 9.49 g of pyridine was added thereto.
(0.12 mol) was added dropwise. After stirring at room temperature for 2.5 hours, most of the methanol was distilled off. Ethyl acetate was added to the residue, twice with about 5% aqueous hydrochloric acid, once with about 5% aqueous sodium bicarbonate,
The extract was washed successively with water once, dried, concentrated, and crude 3- (1
-(Benzyloxyimino) ethyl) benzonitrile 2
4.15 g (95.0 mmol) were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25-8.0 (9H, m), 5.25 (2H, s), 2.26 (3H, s) Crude 3- (1- (benzyloxyimino) ethyl) To a solution of 24.15 g (95.0 mmol) of benzonitrile in 1 L of anhydrous toluene was added 77.3 ml (116 mmol) of diisobutylaluminum hydride (1.5 mol / toluene solution) at -70 ° C or lower under a nitrogen atmosphere, and gradually added. The mixture was stirred overnight while returning to room temperature. About 20% aqueous ammonium chloride 20
After adding 0 ml and stirring at room temperature for 0.5 hour, 400 ml of about 5% aqueous sulfuric acid was added under ice-cooling, stirred at the same temperature for 0.5 hour, and further stirred at room temperature for 6 hours. Separate and separate the aqueous layer
Extracted with -butyl methyl ether, the organic layers were combined, washed twice with water, dried and concentrated. The residue was subjected to silica gel column chromatography (n-hexane: toluene = 1: 1).
1 then 1: 2), 18.26 g of 3- (1- (benzyloxyimino) ethyl) benzaldehyde
(72.1 mmol) were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 10.04 (1H, s), 7.25-8.15 (9H, m), 5.27 (2H, s), 2.
31 (3H, s) (2) A solution of 9.92 g (39.17 mmol) of 3- (1- (benzyloxyimino) ethyl) benzaldehyde dissolved in 70 ml of anhydrous methanol and 70 ml of anhydrous tetrahydrofuran was hydrogenated under ice-cooling. Sodium boron 1.
81 g (43 mmol) was added little by little, and further cooled under ice-cooling.
Stirred for hours. Under ice cooling, further 0.30 g of sodium borohydride was added, and the mixture was stirred under ice cooling for 2 hours. The reaction mixture was added to about 5% aqueous ammonium chloride (500 ml) and extracted with t-butyl methyl ether. The organic layer was dried, concentrated, and 9.64 g of 3- (1- (benzyloxyimino) ethyl) benzyl alcohol. (37.8 mmol) were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25-7.7 (9H, m), 5.25 (2H, s), 4.73 (2H, brd),
2.28 (3H, s), 1.72 (1H, brt) (3) A solution of 2.55 g (10 mmol) of 3- (1- (benzyloxyimino) ethyl) benzyl alcohol in 20 ml of anhydrous diethyl ether was added under ice-cooling. Then, 1.35 g (4.5 mmol) of phosphorus tribromide was added dropwise. The reaction vessel was removed from the ice bath and stirred at room temperature for another 6 hours. Ice water and diethyl ether were added to the reaction solution, stirred for 30 minutes, and then separated. The organic layer was washed successively with about 5% aqueous sodium bicarbonate and water, dried and concentrated, and 2.78 g of 3- (1- (benzyloxyimino) ethyl) benzyl bromide.
(8.74 mmol) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25-7.70 (9H, m), 5.25 (2H, s), 4.51 (2H, s), 2.
27 (3H, s) (4) Dissolve 2.78 g (8.74 mmol) of 3- (1- (benzyloxyimino) ethyl) benzyl bromide in 30 ml of anhydrous tetrahydrofuran.
74 g (11.4 mmol) was added, and the mixture was heated under reflux for 3 hours.
Further, 1.74 g (11.4 mmol) of silver cyanate was added,
The mixture was heated under reflux for 2 hours. Furthermore, 1.74 g of silver cyanate (1
(1.4 mmol), and the mixture was heated under reflux for 2 hours. The reaction solution was filtered, and the filtrate was concentrated to obtain 2.75 g of crude 3- (1- (benzyloxyimino) ethyl) benzyl isocyanate. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (9H, m), 5.23 (2H, s), 4.51 (2H, s), 2.
27 (2H, s) N, N-dimethylhydrazine 0.53 was added to a solution of 2.75 g of crude 3- (1- (benzyloxyimino) ethyl) benzyl isocyanate in 13 ml of anhydrous toluene under ice-cooling.
g (8.74 mmol) in 5 ml of anhydrous toluene was added dropwise, and the reaction vessel was removed from the ice-cooled bath.
Stirred for hours. The reaction solution was concentrated, and the residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate =
1: 1 then 1: 2) to give 1,1-dimethyl-
0.55 g (1.62 mmol) of 4- {3- (1- (benzyloxyimino) ethyl) benzyl} semicarbazide was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25-7.6 (9H, m), 6.4 (1H, br), 5.24 (2H, s), 5.05
(1H, br), 4.45 (2H, d), 2.49 (6H, s), 2.26 (3H, s)

Production Example 5 5-chloro-2-methyl-4- {3- (1- (benzyloxyimino) ethyl) benzyl} -2,4-dihydro-3H-1,2,4-triazole-3- Instead of on, 5-chloro-2-methyl-4- {3- (1- (benzyloxyimino) ethyl) -6-methylbenzyl}-
2,4-dihydro-3H-1,2,4-triazole-
Using 3-one (the present compound 349: produced in Production Example 6 described below), the operation according to Production Example 3 was carried out to give 5-methoxy-2-methyl-4- {3- (1- (benzyloxyimino). ) Ethyl) -6-methylbenzyl {-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 314).

Production Example 6 In place of 1,1-dimethyl-4- {3- (1- (benzyloxyimino) ethyl) benzyl} semicarbazide,
Using 1,1-dimethyl-4- {3- (1- (benzyloxyimino) ethyl-6-methyl) benzyl} semicarbazide (manufactured in Reference Production Example 3 described later), the same operation as in Production Example 4 was performed. , 5-chloro-2-methyl-4- {3-
(1- (benzyloxyimino) ethyl-6-methyl)
Benzyl} -2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 349 of the present invention) is obtained.

Reference Production Example 3 (1) Using 3-acetyl-6-methylbenzonitrile instead of 3-acetylbenzonitrile, the same procedure as in (1) of Reference Production Example 2 was carried out to give crude 3- Via (1- (benzyloxyimino) ethyl) -6-methylbenzonitrile, 3- (1- (benzyloxyimino) ethyl)
This gives -6-methylbenzaldehyde. (2) Instead of 3- (1- (benzyloxyimino) ethyl) benzaldehyde, 3- (1- (benzyloxyimino) ethyl) -6-methylbenzaldehyde was used according to (2) of Reference Production Example 2. Operation, and
(1- (benzyloxyimino) ethyl) -6-methylbenzyl alcohol is obtained. (3) Instead of 3- (1- (benzyloxyimino) ethyl) benzyl alcohol, 3- (1- (benzyloxyimino) ethyl) -6-methylbenzyl alcohol was used, and (3) of Reference Production Example 2 was used. Perform the operation according to
(1- (benzyloxyimino) ethyl) -6-methylbenzylbromide is obtained. (4) Instead of 3- (1- (benzyloxyimino) ethyl) benzylbromide, 3- (1- (benzyloxyimino) ethyl) -6-methylbenzylbromide was used instead of (4) of Reference Production Example 2. )) And the crude 3-
Via (1- (benzyloxyimino) ethyl) -6-methylbenzylisocyanate, 1,1-dimethyl-4-isocyanate
{3- (1- (benzyloxyimino) ethyl) -6
Methylbenzyl} semicarbazide is obtained.

Production Example 7 5-methoxy-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (referred to in Reference Production Example 4 below) Production) 443m
g (1.5 mmol) and 234 mg of methyl iodide (1.6
5 mmol) was dissolved in 5 ml of anhydrous N, N-dimethylformamide, and 66 mg (1.65 mmol) of sodium hydride (60% oil dispersion) was added thereto under ice-cooling. After the vigorous bubbling subsided, the reaction vessel was removed from the ice bath and stirred at room temperature for 2 hours. Water was added to the reaction solution, and the mixture was extracted with a mixed solvent of t-butyl methyl ether and ethyl acetate. The organic layer was washed twice with water, dried and concentrated. Acetonitrile and n-hexane were added to the residue, liquid separation was performed, and the acetonitrile layer was concentrated to give 5-methoxy-2-methyl-4- (2-methyl-5-phenylbenzyl) -2,4.
0.45 g of -dihydro-3H-1,2,4-triazol-3-one (compound 6 of the present invention) was obtained as a viscous oil (crystallized on standing at room temperature). ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2-7.6 (8H, m), 4.78 (2H, s), 3.93 (3H, s), 3.39
(3H, s), 2.44 (3H, s)

Reference Production Example 4 (1) 7.51 g of methyl 2-methylbenzoate was stirred into 50 g of dry powder of Na-X type zeolite (Zeolam type F-9, manufactured by Tosoh Corporation; 100 mesh or less).
(50.0 mmol) was added dropwise. To this, 3.9 ml (75 mmol) of bromine was added dropwise at 45 to 50 ° C, and the mixture was stirred at 80 ° C for 1 hour.
Potassium carbonate (5.5 g) was added to water (50 ml) and methanol
(250 ml), stirred at room temperature for 10 minutes, filtered, and the remaining zeolite powder was washed with warm aqueous methanol (10%, 250 ml). The filtrate and washings were combined and concentrated, the residue was diluted with ethyl acetate, washed twice with water, dried and concentrated. Residue (2.98
g) was subjected to silica gel column chromatography (eluted with n-hexane: toluene = 10: 1, then 5: 1, then 3: 1) to give 1.97 g of methyl 5-bromo-2-methylbenzoate (8. 60 mmol) were obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.04 (1H, d), 7.52 (1H, dd), 7.12 (1H, d), 3.90 (3
H, s), 2.54 (3H, s) (2) 1.19 g (9.46 mmol) of phenylboronic acid, methyl 5
1.97 g of bromo-2-methylbenzoate (8.6
0 mmol), 4 mg (0.017 mmol) of palladium (II) acetate, 2.97 g (21.5 mmol) of potassium carbonate and 2.77 g (8.6 mmol) of tetrabutylammonium bromide were suspended in 20 ml of water, and the mixture was vigorously stirred under a nitrogen stream. The mixture was stirred at 70 ° C. for 1 hour under a nitrogen atmosphere. Water was added to the reaction mixture, and the mixture was extracted with t-butyl methyl ether. The organic layer was dried and concentrated. The residue (1.9 g) was subjected to silica gel column chromatography (n
-Hexane: ethyl acetate = 30: 1), and methyl 5-phenyl-2-methylbenzoate (1.65 g) was obtained.
(7.29 mmol) was obtained as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.16 (1H, d), 7.3-7.7 (7H, m), 3.92 (3H, s), 2.64
(3H, s) (3) Lithium aluminum hydride 0.20 g (5.2
1.65 g (7.29 mmol) of methyl 5-phenyl-2-methylbenzoate was added to a suspension of 7 mmol) in 50 ml of anhydrous diethyl ether while cooling with ice under a nitrogen atmosphere.
A solution of l) dissolved in 20 ml of anhydrous diethyl ether was added dropwise. After gradually returning to room temperature, the mixture was stirred at room temperature for 1 hour. 0.20 g of lithium aluminum hydride (5.27 g)
mmol) and stirred for an additional hour. 0.20 g (5.27 mmol) of lithium aluminum hydride was added, and the mixture was further stirred for 1 hour. Hydrous sodium sulfate (prepared from 20 g of anhydrous sodium sulfate and 1.5 ml of water) was added, and the mixture was filtered.
The filtrate was concentrated. The residue (1.43 g) was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 10:
(Eluted with 1: 1 then 3: 1) to give 1.33 g (6.71 mmol) of 5-phenyl-2-methylbenzyl alcohol as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (8H, m), 4.78 (2H, d), 2.40 (3H, s),
1.62 (1H, t) (4) 1.33 g (6.71 mmol) of 5-phenyl-2-methylbenzyl alcohol was added to anhydrous diethyl ether 3
0.91 g of phosphorus tribromide was added to the solution dissolved in 0 ml under ice-cooling.
(3.02 mmol) was added dropwise. After further stirring for 3 hours under ice cooling, ice water and t-butyl methyl ether were added to the reaction solution, and the mixture was stirred for 30 minutes and then separated. The organic layer was washed successively with about 5% aqueous sodium bicarbonate and water, dried, concentrated and concentrated to 5-phenyl-2-methylbenzylbromide 1.4.
2 g (5.44 mmol) were obtained as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (8H, m), 4.58 (2H, s), 2.46 (2H, s) (5) 5-methoxy-2,4- Dihydro-3H-1,
2,4-triazol-3-one (the compound is described in J. Chem. S
It is a known compound described in oc.Perkin I, 2645 (1973), and was produced according to the method described in the literature. In the literature, the compound is named 3-methoxy-1,2,4-triazol-5 (4H) -one. ) 62
6 mg (5.44 mmol) was dissolved in 7 ml of anhydrous acetonitrile, and 0.79 g (5.71 mmol) of potassium carbonate was added thereto.
Was added. At 55 ° C., a solution prepared by dissolving 1.42 g (5.44 mmol) of 5-phenyl-2-methylbenzyl bromide in 20 ml of anhydrous acetonitrile was added dropwise. After stirring at the same temperature for 5 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. T-Butyl methyl ether was added to the obtained solid residue (1.51 g), and the solid was washed, cooled with ice, collected by filtration, dried, and dried to give 5-methoxy-4- (2-methyl-5-methyl-5-methyl-5-methyl-5-methyl-5-methyl-5-methyl-5-methyl-5-methyl-5-methyl-5-methoxy-4- (2-methyl-5-5
Phenylbenzyl) -2,4-dihydro-3H-1,
0.72 g of 2,4-triazol-3-one (2.44
mmol) as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.22 (1H, brs), 7.2-7.6 (8H, m), 4.80 (2H, s), 3.
94 (3H, s), 2.44 (3H, s)

Production Example 8 0.19 g (1.18 mmol) of 4-chlorophenylboronic acid
l), 4- (3-bromobenzyl) -5-methoxy-2-
Methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 296 of the present invention: Production Example 9 described later)
0.32 g (1.07 mmol), palladium acetate
(II) 1 mg (0.004 mmol), potassium carbonate 0.37 g
(2.68 mmol) and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 2 ml of water, stirred vigorously under a nitrogen stream, and then stirred at 75 ° C. for 1 hour under a nitrogen atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried and concentrated. Residue (0.39
g) on silica gel thin layer chromatography (toluene:
4-ethyl 3- (4-
0.32 g of (chlorophenyl) benzyl} -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 21) was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.6 (7H, m), 4.76 (2H, s), 3.95 (3H, s), 3.37
(3H, s)

Production Example 9 4- (3-bromobenzyl) -5-methoxy-2,4-
1.70 g of dihydro-3H-1,2,4-triazol-3-one (produced in Reference Production Example 5 described below) (5.98 mm
ol) and 1.02 g (7.18 mmol) of methyl iodide were dissolved in 20 ml of anhydrous N, N-dimethylformamide, and the solution was cooled with ice.
To this was added 287 mg (7.18 mmol) of sodium hydride (60% oil dispersion). After the vigorous bubbling subsided, the reaction vessel was removed from the ice bath and stirred at room temperature for 3 hours. Water was added to the reaction solution, and the mixture was extracted with a mixed solvent of t-butyl methyl ether and ethyl acetate. The organic layer was washed twice with water, dried and concentrated. Acetonitrile and n-hexane were added to the residue, liquid separation was performed, and the acetonitrile layer was concentrated to give 4- (3-bromobenzyl) -5-.
Methoxy-2-methyl-2,4-dihydro-3H-1,
2,4-triazol-3-one (Compound 29 of the present invention)
6) 1.64 g (5.50 mmol) were obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15-7.5 (4H, m), 4.66 (2H, s), 3.95 (3H, s), 3.38
(3H, s)

Reference Production Example 5 5-methoxy-2,4-dihydro-3H-1,2,4-
2.30 g (20 mmol) of triazol-3-one was dissolved in 20 ml of anhydrous acetonitrile, and 2.90 g of potassium carbonate (21 m
mol) was added. At 55 ° C., 5.00 g (20 mmol) of 3-bromobenzyl bromide was added to 20 ml of anhydrous acetonitrile.
The solution dissolved in was added dropwise. After stirring at the same temperature for 6 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. An equal mixture of t-butyl methyl ether and n-hexane was added to the obtained solid residue (5.2 g), and the solid was washed and then cooled with ice.
It was collected by filtration and dried. Further, t-butyl methyl ether was added to the obtained solid residue, and the solid was washed, cooled with ice, collected by filtration, dried and dried to give 4- (3-bromobenzyl) -5-methoxy-2,4-. 1.70 g (5.98 mmol) of dihydro-3H-1,2,4-triazol-3-one was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.52 (1H, brs), 7.15-7.5 (4H, m), 4.67 (2H, s),
3.96 (3H, s)

Production Example 10 5-methoxy-4- (3-phenoxybenzyl) -2,
4-dihydro-3H-1,2,4-triazole-3-
On (produced in Reference Production Example 6 described below), 0.27 g (0.91 mmol) and 0.15 g (1.09 mmol) of methyl iodide were dissolved in 3 ml of anhydrous N, N-dimethylformamide. % Oil dispersion) (44 mg, 1.09 mmol) was added. After the vigorous bubbling subsided, the reaction vessel was removed from the ice bath and stirred at room temperature for 7 hours. Water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was washed twice with water, dried and concentrated. Acetonitrile and n-hexane were added to the residue, liquids were separated, and the acetonitrile layer was concentrated to give 5-
0.26 g of methoxy-2-methyl-4- (3-phenoxybenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 176) was obtained as a viscous oil. . ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 6.85-7.4 (9H, m), 4.67 (2H, s), 3.91 (3H, s), 3.37
(3H, s)

Reference Production Example 6 5-methoxy-2,4-dihydro-3H-1,2,4-
575 mg (5 mmol) of triazol-3-one was dissolved in 7 ml of anhydrous acetonitrile, and 726 mg of potassium carbonate (5.25 mm
ol). At 55 ° C., a solution of 1.32 g (5 mmol) of 3-phenoxybenzyl bromide in 9 ml of anhydrous acetonitrile was added dropwise thereto. After stirring at the same temperature for 5.5 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. An equal mixture of t-butyl methyl ether and n-hexane was added to the obtained solid residue (1.36 g), and the solid precipitated was cooled, washed with ice, cooled with ice, collected by filtration and dried to obtain a residue. Was. This was recrystallized from t-butyl methyl ether to give 5-methoxy-4.
-(3-phenoxybenzyl) -2,4-dihydro-3
0.27 g of H-1,2,4-triazol-3-one was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.25 (1H, brs), 6.9-7.4 (9H, m), 4.68 (2H, s), 3.
93 (3H, s)

Production Example 11 5-chloro-2-methyl-4- {1- (3-phenylphenyl) ethyl} -2,4-dihydro-3H-1,2,2
314 mg (1.0 mmol) of 4-triazol-3-one (the present compound 12: produced in Production Example 12 described below) was dissolved in 10 ml of anhydrous methanol, and 0.85 g of sodium methoxide (28% methanol solution) (4%) was added. .4 mmol)
Was added and heated under reflux for 4 hours. Further, 0.85 g (4.4 mmol) of sodium methoxide (28% methanol solution)
l) was added and the mixture was heated under reflux for 5.5 hours. After cooling to room temperature, water was added, and the mixture was extracted with t-butyl methyl ether.
The organic layer was washed with water, dried and concentrated. Residue (0.25g)
Was subjected to silica gel preparative thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 1) to give 5-methoxy-2-methyl-4- {1- (3-phenylphenyl) ethyl} -2, 0.21 g of 4-dihydro-3H-1,2,4-triazol-3-one (the present compound 11) was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.65 (9H, m), 5.38 (1H, q), 3.90 (3H, s), 3.35
(3H, s), 1.86 (3H, d)

Production Example 12 To a solution of 4.33 g (14.6 mmol) of triphosgene in 15 ml of methylene chloride was added 1,1-dimethyl-4- {1- (3-phenylphenyl) ethyl} semicarbazide under ice-cooling. 2.07 g (produced in Reference Production Example 7 described below)
A solution of (7.30 mmol) in 20 ml of methylene chloride was added dropwise. The reaction vessel was removed from the ice-cooled bath, heated to reflux for 4 hours after reaching room temperature. After cooling to room temperature,
The reaction solution was poured into about 5% aqueous sodium bicarbonate (150 ml) and stirred for 1 hour. The organic layer was washed with water, dried and concentrated. Left behind
(1.93 g) was purified by silica gel column chromatography (n-
Hexane: ethyl acetate = 10: 1 then eluted with 5: 1 then 3: 1) to give 5-chloro-2-methyl-4-.
{1- (3-phenylphenyl) ethyl} -2,4-dihydro-3H-1,2,4-triazol-3-one
418 mg (1.33 mmol) of (the present compound 12) was obtained as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.65 (9H, m), 5.52 (1H, q), 3.44 (3H, s), 1.97
(3H, d)

Reference Production Example 7 (1) Phenylboronic acid 6.71 g (55 mmol), 3-bromoacetophenone 9.95 g (50 mmol), palladium acetate 30 mg (0.13 g)
mmol), 17.28 g (125 mmol) of potassium carbonate and 16.12 g (50 mmol) of tetrabutylammonium bromide were suspended in 55 ml of water, and the mixture was vigorously stirred under a nitrogen stream.
The mixture was stirred at 70 ° C. for 1 hour and 15 minutes. Water was added to the reaction mixture, and the mixture was extracted with t-butyl methyl ether. The organic layer was dried and concentrated. The residue (10.23 g) was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 7: 1).
To give 9.82 g of 3-acetylbiphenyl as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.20 (1 H, t), 7.95 (1 H, dt), 7.81 (1 H, dt), 7.3-7.6
5 (6H, m), 2.66 (3H, s) (2) To a solution of 9.82 g (50 mmol) of 3-acetylbiphenyl in 80 ml of anhydrous methanol and 80 ml of anhydrous tetrahydrofuran, sodium borohydride was added under ice-cooling.
36 g (80 mmol) was added little by little, and the mixture was further stirred for 1 hour. The reaction solution was added to about 5% of an aqueous solution of ammonium chloride (600 ml) and extracted with t-butyl methyl ether. The organic layer was dried and then concentrated to obtain 9.86 g (49.7 mmol) of 3- (1-hydroxyethyl) biphenyl as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.65 (9H, m), 4.98 (1H, q), 1.85 (1H, br), 1.
55 (3H, d) (3) 3.97 g of 3- (1-hydroxyethyl) biphenyl
To a solution of (20 mmol) in 60 ml of anhydrous diethyl ether, 2.70 g (9.0 mmol) of phosphorus tribromide was added dropwise under ice cooling, and the mixture was further stirred under ice cooling for 3 hours. Ice water and t-butyl methyl ether were added to the reaction solution, stirred for 30 minutes, and then separated. The organic layer was washed successively with about 5% aqueous sodium bicarbonate and water, dried and concentrated to obtain 3.73 g (14.28 mmol) of 3- (1-bromoethyl) biphenyl as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.7 (9H, m), 5.28 (1H, q), 2.10 (3H, d) (4) 3- (1-bromoethyl) biphenyl 2.61g (10mm
ol) was dissolved in 30 ml of anhydrous tetrahydrofuran, and 1.99 g (13 mmol) of silver cyanate was added thereto, followed by heating under reflux for 2 hours. The reaction solution was filtered and the filtrate was concentrated to give 1- (3-
2.29 g of phenylphenyl) ethyl isocyanate were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25-7.65 (9H, m), 4.85 (1H, q), 1.65 (3H, d) (5) 1- (3-phenylphenyl) 0.78 g (13 mmol) of N, N-dimethylhydrazine was added to a solution of 2.29 g of ethyl isocyanate dissolved in 8 ml of toluene under ice-cooling.
Was dropped, the reaction vessel was removed from the ice-cooled bath, and the mixture was further stirred for 1.5 hours. The reaction solution was concentrated, and the residue (2.89 g) was subjected to silica gel column chromatography (n-hexane:
(Eluted with ethyl acetate = 2: 1 then 1: 1 then 1: 2)
And 2.29 g (8.08) of 1,1-dimethyl-4- {1- (3-phenylphenyl) ethyl} semicarbazide.
mmol) as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3-7.65 (9H, m), 6.38 (1H, brd), 5.10 (1H, m),
4.98 (1H, br s), 2.51 (6H, s), 1.55 (3H, d)

Production Example 13 Crude 4- {3- (bromomethyl) benzyl} -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
5 mg of -triazol-3-one (the present compound 62: produced in Production Example 14 described below) and 3 mg (0.016 mmol) of 3- (trifluoromethyl) acetophenone oxime were treated with anhydrous N, N-
Dissolve in 0.5 ml of dimethylformamide and add 1m of sodium hydride (60% oil dispersion) under ice-cooling
g (0.025 mmol) was added. The reaction vessel was removed from the ice bath and stirred at room temperature for 2 hours. Ice water is added to the reaction solution and t
-Extracted with butyl methyl ether. The organic layer was washed twice with water, dried and concentrated. The residue was subjected to silica gel thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 1) to give 5-methoxy-2-methyl-4- {3-.
2 mg of [[α-methyl- (3-trifluoromethyl) benzylidene] aminooxymethyl] benzyl} -2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 477) were obtained. Was. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.89 (1H, s), 7.84 (1H, d), 7.61 (1H, d), 7.48 (1H,
t), 7.25-7.4 (4H, m), 5.24 (2H, s), 4.71 (2H, s), 3.91 (3H,
s), 3.36 (3H, s), 2.29 (3H, s)

Production Example 14 4- {3- (hydroxymethyl) benzyl} -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,2
A solution of 50 mg (0.20 mmol) of 4-triazol-3-one (the present compound 476, prepared in Production Example 15 described below) dissolved in 5 ml of anhydrous diethyl ether was added with 30 m of phosphorus tribromide under ice-cooling.
A solution of g (0.1 mmol) in 5 ml of anhydrous diethyl ether was added dropwise, and the mixture was further stirred under ice cooling for 2.5 hours. Ice water and t-butyl methyl ether were added to the reaction solution, stirred for 30 minutes, and then separated. The organic layer was washed successively with about 5% aqueous sodium bicarbonate and water (twice), dried, concentrated, and
{3- (bromomethyl) benzyl} -5-methoxy-2
5 mg of -methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 62) were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2-7.4 (4H, m), 4.69 (2H, s), 4.47 (2H, s), 3.95
(3H, s), 3.37 (3H, s)

Production Example 15 Crude 4- (3-formylbenzyl) -5-methoxy-2-
Methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 55 of the present invention: Production Example 16 described later)
To a solution of 0.16 g in 3 ml of anhydrous methanol and 3 ml of anhydrous tetrahydrofuran was added 32 mg (0.75 mmol) of sodium borohydride little by little under ice-cooling, and the mixture was further stirred for 1 hour while cooling with ice. The reaction solution was added to 15 ml of about 5% aqueous ammonium chloride, extracted with t-butyl methyl ether, and the organic layer was dried. The residue (0.10 g) was subjected to silica gel thin layer chromatography (developed with ethyl acetate) to give 4- {3- (hydroxymethyl) benzyl} -5-
Methoxy-2-methyl-2,4-dihydro-3H-1,
2,4-triazol-3-one (the present compound 476)
50 mg (0.20 mmol) were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2-7.4 (4H, m), 4.67 (2H, s), 4.65 (2H, s), 3.93
(3H, s), 3.34 (3H, s), 2.70 (1H, br s)

Production Example 16 4- (3-formylbenzyl) -5-methoxy-2,4
-Dihydro-3H-1,2,4-triazol-3-one (prepared in Reference Production Example 8 described later) 0.35 g (1.50 m
mol) and 0.23 g (1.65 mmol) of methyl iodide
Dissolve it in 5 ml of N, N-dimethylformamide and add sodium hydride (60% oil dispersion) 6 under ice-cooling.
6 mg (1.65 mmol) were added. After the vigorous bubbling subsided, the reaction vessel was removed from the ice bath and stirred for an additional 3 hours. Water was added to the reaction solution, and the mixture was extracted with a mixed solvent of t-butyl methyl ether and ethyl acetate. The organic layer was washed twice with water, dried and concentrated. Acetonitrile and n-hexane were added to the residue, liquids were separated, and the acetonitrile layer was concentrated. The residue (0.25 g) was subjected to silica gel thin layer chromatography (developed with ethyl acetate: toluene = 2: 1) to give crude 4- (3-formylbenzyl) -5-methoxy-2-methyl-2,4-. Dihydro-3H-1,2,4-
Triazol-3-one (Compound 55) 0.16
g was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 10.01 (1 H, s), 7.83 (1 H, s), 7.83 (1 H, d), 7.63 (1
H, d), 7.51 (1H, t), 4.78 (2H, s), 3.95 (3H, s), 3.39 (3H, s)

Reference Production Example 8 5.00 g of 3- (bromomethyl) benzonitrile (2
5.5 mmol) in a solution of 50 ml of anhydrous toluene,
37.9 ml of diisobutylaluminum hydride (0.95 mol / l n-hexane solution) while cooling with ice under a nitrogen atmosphere.
(36 mmol) was added dropwise, and the mixture was further stirred for 1 hour under ice cooling. After adding 80 ml of chloroform to the reaction solution under ice-cooling, 200 ml of about 10% hydrochloric acid aqueous solution was added under ice-cooling, followed by stirring at room temperature for 1 hour. The organic layer was separated, washed with water, dried and concentrated. The solid residue (4.90 g) was washed with n-hexane, cooled, collected by filtration, and dried to obtain 4.27 g of crude 3- (bromomethyl) benzaldehyde as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 10.02 (1H, s), 7.91 (1H, s), 7.83 (1H, d), 7.66 (1
H, d), 7.53 (1H, t), 4.54 (2H, s) 5-methoxy-2,4-dihydro-3H-1,2,4-
0.92 g (8.0 mmol) of triazol-3-one was dissolved in 15 ml of anhydrous acetonitrile, and 1.16 g (8.4%) of potassium carbonate was added thereto.
mmol). The crude 3
A solution obtained by dissolving 1.59 g of-(bromomethyl) benzaldehyde in 30 ml of anhydrous acetonitrile was added dropwise. After stirring at the same temperature for 6 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated.
The residue (1.31 g) was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 1: 1, then 1: 2) to give 4- (3-formylbenzyl) -5-methoxy-2,4-dihydro 0.35 g (1.50 mmol) of -3H-1,2,4-triazol-3-one was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 10.01 (1H, s), 8.63 (1H, brs), 7.83 (1H, s), 7.83
(1H, d), 7.63 (1H, d), 7.52 (1H, t), 4.79 (2H, s), 3.97 (3H, s)

Production Example 17 In place of 5-methoxy-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one, 4- {5 Production using-(4-chlorophenyl) -2-methylbenzyl} -5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one (produced in Reference Production Example 9 described later). By following the same procedure as in Example 7, 4- {5- (4-chlorophenyl) -2-methylbenzyl} -5-methoxy-2-methyl-2,4-
Dihydro-3H-1,2,4-triazol-3-one (the present compound 46) is obtained.

Reference Production Example 9 The procedure of Reference Production Example 4 (2) was carried out using 4-chlorophenylboronic acid in place of phenylboronic acid.
This gives methyl 5- (4-chlorophenyl) -2-methylbenzoate. Next, the same operation as in (3) of Reference Production Example 4 was performed using methyl 5- (4-chlorophenyl) -2-methylbenzoate instead of methyl 5-phenyl 2-methylbenzoate to obtain 5- (4- (Chlorophenyl) -2-methylbenzyl alcohol is obtained. Next, 5- (4-chlorophenyl) -2-methylbenzyl alcohol was used in place of 5-phenyl-2-methylbenzyl alcohol, and the same procedure as in (4) of Reference Production Example 4 was carried out to obtain 5- (4 -Chlorophenyl) -2-methylbenzylbromide is obtained. Next, instead of 5-phenyl-2-methylbenzylbromide, 5- (4-chlorophenyl) -2-methylbenzylbromide was used, and the same operation as in (5) of Reference Production Example 4 was performed to obtain 4- {5 -(4-chlorophenyl) -2-methylbenzyl} -5-methoxy-2,
4-dihydro-3H-1,2,4-triazole-3-
Get on.

Production Example 18 Instead of 5-methoxy-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one, 5-methoxy- Using 4- {2-methyl-5- (4-methylphenyl) benzyl} -2,4-dihydro-3H-1,2,4-triazol-3-one (prepared in Reference Production Example 10 described later), The same operation as in Production Example 7 was performed, and 5-methoxy-2-methyl-4- {2
-Methyl-5- (4-methylphenyl) benzyl} -2,4
-Dihydro-3H-1,2,4-triazol-3-one (the present compound 49) is obtained.

Reference Production Example 10 The same operation as in Reference Production Example 4 (2) was carried out using 4-methylphenylboronic acid instead of phenylboronic acid.
This gives methyl 2-methyl-5- (4-methylphenyl) benzoate. Then, instead of methyl 5-phenyl 2-methylbenzoate, methyl 2-methyl-5-
Using (4-methylphenyl) benzoate, the procedure according to (3) of Reference Production Example 4 was performed to give 2-methyl-5-
(4-Methylphenyl) benzyl alcohol is obtained. Next, 2-methyl-5- (4-methylphenyl) benzyl alcohol was used in place of 5-phenyl-2-methylbenzyl alcohol, and the same procedure as in (4) of Reference Production Example 4 was carried out to give 2-methyl-5- (4-methylphenyl) benzyl alcohol. -5- (4-methylphenyl)
Obtain benzyl bromide. Then, 5-phenyl-2-
Instead of methylbenzylbromide, 2-methyl-5-
Using (4-methylphenyl) benzyl bromide, the same procedure as in (5) of Reference Production Example 4 was performed to give 5-methoxy-
4- {2-methyl-5- (4-methylphenyl) benzyl}-
2,4-dihydro-3H-1,2,4-triazole-
To obtain 3-one.

Production Example 19 1.19 g (9.46 mmol) of phenylboronic acid, 4- (5
-Bromo-2-methylbenzyl) -5-methoxy-2-
Methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 299 of the present invention: Production Example 2 described below)
2.68 g (8.6 mmol), palladium acetate
(II) 4 mg (0.017 mmol), potassium carbonate 2.97 g
(21.5 mmol) and 2.77 g (8.6 mmol) of tetrabutylammonium bromide were suspended in 20 ml of water, and vigorously stirred under a nitrogen stream.
Stirred for hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried, and concentrated. The residue (2.84 g) was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 2: 1, then 1: 1,
Then eluted at 1: 2) to give 5-methoxy-2-methyl-4- (2-methyl-5-phenylbenzyl) -2,
4-dihydro-3H-1,2,4-triazole-3-
2.47 g of ON (compound 6 of the present invention) is a viscous oil (crystallized by adding n-hexane and triturating).
As obtained. ¹ H-NMR (CDCl ₃ , TMS) spectrum data was consistent with the data described in Production Example 7.

Production Example 20 4- (5-bromo-2-methylbenzyl) -5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one (manufactured in Reference Production Example 11 described later) ) 11.96g
(40.12 mmol) and 6.83 (48.14 mmol) of methyl iodide were dissolved in 100 ml of anhydrous N, N-dimethylformamide, and the solution was cooled with ice.
To this, 1.93 g (48.14 mmol) of sodium hydride (60% oil dispersion) was added. After the vigorous bubbling subsided, the reaction vessel was removed from the ice bath and stirred at room temperature for 3 hours. The reaction solution was added to ice water (500 ml) and extracted with ethyl acetate (300 ml). The organic layer was washed with water and then with a saturated saline solution, dried and concentrated. Cold n-hexane was added to the solid residue, and the solid was sufficiently washed, collected by filtration, dried, and dried.
-(5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-
11.6 g of triazol-3-one (the present compound 299)
Was obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.32 (1H, dd), 7.27 (1H, d), 7.03 (1H, d), 4.67 (2
H, s), 3.94 (3H, s), 3.40 (3H, s), 2.34 (3H, s)

Reference Production Example 11 (1) 37.5 g of methyl 2-methylbenzoate (0.2 g of dry powder of Na-X type zeolite) (0.2 g of zeolam type F-9, manufactured by Tosoh Corporation; 100 mesh or less) were stirred.
5 mol) was added dropwise. 60.0 g (0.3754 mol) of bromine was added dropwise thereto, and the mixture was stirred at 80 to 85 ° C for 1 hour. The reaction mixture was ice-cooled, a solution of potassium carbonate (20 g) dissolved in water (250 ml) was added thereto, and 1 liter of methanol was further added. The mixture was stirred at room temperature and filtered. Concentrate the filtrate to about 100 ml,
Water and ethyl acetate were added to carry out liquid separation, and the organic layer was washed with water and then concentrated to obtain 20 g of a residue. On the other hand, the zeolite powder remaining after filtration was washed twice with 1.1 liter of 90% methanol water, the washing solution was concentrated to about 100 ml, water and ethyl acetate were added, liquid separation was performed, and the organic layer was washed with water and then concentrated. , Left 1
7 g were obtained. These residues (37 g) are combined and distilled (about 6 g).
A 0mm Vigreux type rectification column is used. bp 80-95 ° C / 0.6
mmHg) to obtain 17.0 g of methyl 5-bromo-2-methylbenzoate as crystals. ¹ H-NMR (CDCl ₃ ,
TMS) spectral data was consistent with the data described in Reference Production Example 4 (1). (2) 4.2 g (0.1094 mol) of lithium aluminum hydride
Was suspended in 250 ml of anhydrous diethyl ether, and a solution of 33.4 g (0.1458 mol) of methyl 5-bromo-2-methylbenzoate dissolved in 50 ml of anhydrous diethyl ether was added thereto at room temperature while cooling with ice under a nitrogen atmosphere. It was added dropwise over 30 minutes. After stirring at room temperature for 2 hours, about 10 ml of ethyl acetate was added dropwise, and about 50 ml of tetrahydrofuran was further added. This was added to 200 ml of 10% aqueous sulfuric acid and ice, and the mixture was separated. The organic layer was washed sequentially with water, saturated aqueous sodium hydrogen carbonate and saturated saline, dried, and concentrated. The residue (28.7 g) was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 1).
0: 1 then 5: 1)) to give 5-bromo-2-
24.36 g of methylbenzyl alcohol were obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.51 (1H, d), 7.30 (1 H, dd), 7.02 (1 H, d), 4.63 (2
H, d), 2.22 (3H, s), 2.07 (1H, t) (3) 5-bromo-2-methylbenzyl alcohol 24.4
g (0.1214 mol) in 200 ml of anhydrous diethyl ether, 16.4 g (0.06067 mol) of phosphorus tribromide was added dropwise over 30 minutes under ice-cooling. After further stirring under ice-cooling for 3 hours, the reaction solution was added to ice water (500 ml) and separated. The organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate and saturated brine, dried and concentrated to give 29.07 g of 5-bromo-2-methylbenzylbromide as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.44 (1H, d), 7.33 (1 H, dd), 7.05 (1 H, d), 4.43 (2
H, s), 2.35 (3H, s) (4) 5-methoxy-2,4-dihydro-3H-1,
12.7 g (0.1102 mol) of 2,4-triazol-3-one
Was dissolved in 150 ml of anhydrous acetonitrile, and 16.0 g (0.1158 mol) of potassium carbonate was added thereto. A solution of 29.1 g (0.1102 mol) of 5-bromo-2-methylbenzyl bromide in 200 ml of anhydrous acetonitrile was added dropwise thereto. After stirring at 55 ° C to 60 ° C for 5 hours, the reaction solution was cooled with ice water (about 1
l) and extracted with ethyl acetate (500 ml). The organic layer was washed with water, dried and concentrated. After adding cold t-butyl methyl ether to the obtained semi-solid residue and washing the solid,
The solid was collected by filtration and dried to obtain a solid residue (15.9 g). This was recrystallized from a mixed solvent of toluene and ethyl acetate to give 4-
(5-bromo-2-methylbenzyl) -5-methoxy-
2,4-dihydro-3H-1,2,4-triazole-
11.96 g of 3-one were obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.80 (1H, brs), 7.31 (1H, dd), 7.27 (1H, d), 7.06
(1H, d), 4.70 (2H, s), 3.96 (3H, s), 2.35 (3H, s)

Production Example 21 0.19 g (1.18 mmol) of 4-chlorophenylboronic acid
l), 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,
2,4-triazol-3-one (the present compound 29
9: produced in Production Example 20) 0.34 g (1.07 mmol),
1 mg (0.004 mmol) of palladium (II) acetate, 0.37 g (2.68 mmol) of potassium carbonate and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water, and vigorously stirred under a nitrogen stream. Thereafter, the mixture was stirred at 75 ° C. (bath temperature) for 1 hour under a nitrogen atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried and concentrated. The residue (0.41 g) was subjected to silica gel thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 2) to give 4- {5- (4-chlorophenyl) -2-.
Methylbenzyl} -5-methoxy-2-methyl-2,4
0.37 g of -dihydro-3H-1,2,4-triazol-3-one (the present compound 46) was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2-7.65 (7H, m), 4.77 (2H, s), 3.93 (3H, s), 3.39
(3H, s), 2.44 (3H, s)

Production Example 22 In place of 0.19 g of 4-chlorophenylboronic acid, 4-
Production Example 21 using 0.16 g of methylphenylboronic acid
The same procedure was followed to give 5-methoxy-2-methyl-4-.
{5- (4-methylphenyl) -2-methylbenzyl}
0.36 g of -2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 49) was obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15 to 7.45 (7H, m), 4.77 (2H, s), 3.92 (3H, s), 3.3
9 (3H, s), 2.43 (3H, s), 2.38 (3H, s)

Production Example 23 4-Chlorophenylboronic acid was replaced with 0.19 g of 4-chlorophenylboronic acid
Production Example 2 using 0.18 g of methoxyphenylboronic acid
The operation according to 1 was performed to obtain 5-methoxy-4- {5- (4
0.32 g of -methoxyphenyl) -2-methylbenzyl {-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 478) was obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 6.85-7.5 (7H, m), 4.76 (2H, s), 3.92 (3H, s), 3.84
(3H, s), 3.39 (3H, s), 2.42 (3H, s)

Production Example 24 In place of 0.19 g of 4-chlorophenylboronic acid, 4-
Production Example 2 using 0.17 g of fluorophenylboronic acid
The operation according to 1 was performed to obtain 4- {5- (4-fluorophenyl) -2-methylbenzyl} -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazole- 0.32 g of 3-one (the present compound 480) was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.0-7.55 (7H, m), 4.77 (2H, s), 3.93 (3H, s), 3.39
(3H, s), 2.43 (3H, s)

Production Example 25 3-chlorophenylboronic acid was replaced with 0.19 g of 3-chlorophenylboronic acid
Production Example 21 using 0.19 g of chlorophenylboronic acid
The procedure was followed to give 4- {5- (3-chlorophenyl) -2-methylbenzyl} -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazole-3-. 0.32 g of ON (the present compound 47) was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15 to 7.55 (7H, m), 4.77 (2H, s), 3.94 (3H, s), 3.3
9 (3H, s), 2.44 (3H, s)

Production Example 26 2-Chlorophenylboronic acid was replaced with 0.19 g of 2-chlorophenylboronic acid.
Production Example 21 using 0.19 g of chlorophenylboronic acid
The procedure was followed to give 4- {5- (2-chlorophenyl) -2-methylbenzyl} -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazole-3-. 0.29 g of ON (the present compound 48) was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15-7.5 (7H, m), 4.77 (2H, s), 3.92 (3H, s), 3.38
(3H, s), 2.47 (3H, s)

Production Example 27 0.15 g (0.92 mmol) of 4-chlorophenylboronic acid
l), 4- (5-bromo-2-chlorobenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,
2,4-triazol-3-one (Compound 50 of the present invention)
1: 0.28 g (produced in Production Example 28 described below) (0.84 mmo
l), 1 mg (0.004 mmol) of palladium (II) acetate, 0.29 g (2.1 mmol) of potassium carbonate and 0.27 g (0.84 mmol) of tetrabutylammonium bromide in 5 ml of water.
And stirred vigorously under a nitrogen stream, followed by stirring at 75 ° C. (bath temperature) for 1 hour under a nitrogen atmosphere. After adding water to the reaction mixture and extracting with ethyl acetate, drying the organic layer,
Concentrated. The residue (0.32 g) was subjected to silica gel thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 2) to give 4- {2-chloro-5- (4-chlorophenyl) benzyl} -5-methoxy. -2-methyl-2,4
0.23 g of -dihydro-3H-1,2,4-triazol-3-one (the present compound 19) was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2-7.5 (7H, m), 4.90 (2H, s), 3.94 (3H, s), 3.41
(3H, s)

Production Example 28 4- (5-bromo-2-chlorobenzyl) -5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one (prepared in Reference Production Example 12 described later) ) 0.75g
(2.35 mmol) and 0.40 g (2.82 mmol) of methyl iodide were dissolved in 8 ml of anhydrous N, N-dimethylformamide, and sodium hydride (60% oil dispersion) was added thereto under ice-cooling.
113 mg (2.82 mmol) were added. After the vigorous bubbling subsided, the reaction vessel was removed from the ice bath and stirred at room temperature for 2 hours. Ice water was added to the reaction solution, and the mixture was extracted with a mixed solvent of t-butyl methyl ether and ethyl acetate. Organic layer with water 2
It was washed twice, dried and concentrated. N-hexane was added to the solid residue (0.80 g), and the solid was sufficiently washed, cooled, collected by filtration,
Dry to give 4- (5-bromo-2-chlorobenzyl)-
5-methoxy-2-methyl-2,4-dihydro-3H-
1,2,4-triazol-3-one (the present compound 5
01) 0.65 g was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2-7.4 (3H, m), 4.81 (2H, s), 3.94 (3H, s), 3.42
(3H, s)

Reference Production Example 12 (1) Under a nitrogen atmosphere while cooling with ice, 5-bromo-2-
To a solution of 6.20 g (25 mmol) of chlorobenzoic acid dissolved in 10 ml of anhydrous tetrahydrofuran was added borane-tetrahydrofuran complex (1.0 M solution in tetrahydrofuran).
3.3 ml was added slowly over 15 minutes. After stirring for 2 hours under ice cooling, the mixture was stirred at room temperature for 17 hours. Water 8 while cooling on ice
After dropwise adding ml, 6 g of potassium carbonate was added little by little. Water and t-butyl methyl ether were added for liquid separation. The aqueous layer was further extracted twice with t-butyl methyl ether, and the organic layers were combined, dried and concentrated. N-Hexane was added to the residue (4.34 g), and the precipitated crystals were cooled, collected in a furnace and dried to give 5-bromo-2-chlorobenzyl alcohol 2.08 g.
Was obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.66 (1H, d), 7.37 (1 H, dd), 7.21 (1 H, d), 4.76 (2
H, s), 1.97 (1H, brs) (2) 5-bromo-2-chlorobenzyl alcohol 2.08
1.27 g (4.23 mmol) of phosphorus tribromide was added dropwise to a solution of g (9.39 mol) in 30 ml of anhydrous diethyl ether under ice-cooling. After further stirring for 3 hours under ice cooling, the mixture was stirred at room temperature for 1.5 hours. Ice water and then t-butyl methyl ether were added to the reaction solution, stirred for 30 minutes, and then separated. The organic layer was washed successively with about 5% aqueous sodium bicarbonate and water, dried,
Concentrated. The solid residue (1.99 g) was subjected to silica gel column chromatography (eluted with n-hexane) to give 1.88 g of 5-bromo-2-chlorobenzylbromide as flocculent crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.58 (1H, d), 7.38 (1 H, dd), 7.25 (1 H, d), 4.51 (2
H, s) (3) 5-methoxy-2,4-dihydro-3H-1,
0.91 g (7.93 mmol) of 2,4-triazol-3-one was dissolved in 8 ml of anhydrous acetonitrile, and potassium carbonate was added thereto.
0.96 g (6.94 mmol) was added. At 55 ° C., a solution of 1.88 g (6.61 mmol) of 5-bromo-2-chlorobenzyl bromide dissolved in 20 ml of anhydrous acetonitrile was added dropwise thereto. 55
After stirring at 5 ° C. for 5 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated.
Cold t-butyl methyl ether was added to the obtained solid residue (1.90 g), and the solid was washed well, collected by filtration and dried to give 4-
(5-bromo-2-chlorobenzyl) -5-methoxy-
2,4-dihydro-3H-1,2,4-triazole-
0.75 g of 3-one was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.36 (1H, brs), 7.2 to 7.5 (3H, m), 4.83 (2H, s),
3.96 (3H, s)

Production Example 29 0.17 g (1.35 mmol) of 9-phenylboronic acid, 4- (5
-Bromo-2-chlorobenzyl) -5-methoxy-2-
0.36 g (1.07 mmol) of methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 501: produced in Production Example 28), palladium acetate (I
I) 1 mg (0.004 mmol), potassium carbonate 0.37 g
(2.68 mmol) and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water, and the mixture was vigorously stirred under a nitrogen stream, followed by stirring at 75 ° C. (bath temperature) for 1 hour under a nitrogen atmosphere. . Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried and concentrated. The residue (0.40 g) was subjected to silica gel thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 2),
4- (2-chloro-5-phenylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,
4-triazol-3-one (Compound 487 of the present invention)
28 g were obtained as a viscous oil which crystallized on standing at room temperature. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2-7.6 (8H, m), 4.90 (2H, s), 3.91 (3H, s), 3.39
(3H, s)

Production Example 30 111 mg of 3-phenylbenzyl bromide (0.45 mm
ol) and 5-methoxy-2-methyl-2,4-dihydro-
3H-1,2,4-triazol-3-one 77.4 m
g (0.60 mmol) (produced in Intermediate Production Example 1 described below)
Was dissolved in 2 ml of N, N-dimethylformamide, followed by purging with nitrogen. 24.0m quickly under ice cooling
After adding g (0.60 mmol) of sodium hydride, the mixture was stirred for 1 hour and further stirred at room temperature overnight. T-Butyl methyl ether was added to the reaction mixture, washed with water, dried, and concentrated. The residue was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 2: 1 then 1:
Eluted with 1) to give 5-methoxy-2-methyl-4-
(3-phenylbenzyl) -2,4-dihydro-3H-
Thus, 51 mg (0.17 mmol) of 1,2,4-triazol-3-one (the present compound 1) was obtained. ¹ H-NMR
(CDCl3, TMS) spectrum data was consistent with the data described in Production Example 1. The by-product (n-hexane:
(Eluted with ethyl acetate = 2: 1) as 5-methoxy-2-
Methyl-3- (3-phenylbenzyloxy) -1,
53 mg (0.18 mmol) of 2,4-triazole were obtained. ¹ H-NMR (CDCl3, TMS) δ (ppm): 7.36-7.65 (9H, m), 5.44 (2
H, s), 3.91 (3H, s), 3.50 (3H, s)

Production Example 31 In place of 111 mg of 3-phenylbenzyl bromide, 2
Using 118 mg of -methyl-5-phenylbenzylbromide, the same procedure as in Production Example 30 was carried out to give 5-methoxy-
2-Methyl-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 6 of the present invention) is obtained.

Production Example 32 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 62
4 mg (2.0 mmol), 1.00 g (7.1 mmol) of triethylsilylacetylene, PdCl ₂ (PP
h ₃ ) ₂ 59 mg (0.084 mmol), copper (I) iodide
32 mg (0.17 mmol), 90 mg (0.34 mmol) of triphenylphosphine and 1.5 g of triethylamine were added to 8 ml of acetonitrile, and the mixture was refluxed for 4 hours under a nitrogen atmosphere. After cooling to room temperature, the mixture was diluted with t-butyl methyl ether, washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (n-
Hexane: ethyl acetate = 3: 1).
{5- (2-triethylsilyl) ethynyl-2-methylbenzyl} -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 459 of the present invention) 0.68 g (1.83 mmol) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.30 (1 H, dd, J = 8.2 Hz),
7.23 (1H, s), 7.09 (1H, d, J = 8H)
z), 4.67 (2H, s), 3.92 (3H, s),
3.40 (3H, s), 2.39 (3H, s), 1.0
4 (9H, t, J = 8 Hz), 0.67 (6H, q, J
= 8Hz)

Production Example 33 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 62
4 mg (2.0 mmol), t-butylacetylene
50 g (18.3 mmol), PdCl ₂ (PPh ₃ ) ₂
67 mg (0.095 mmol), copper (I) iodide 33 m
g (0.17 mmol), triphenylphosphine 10
6 mg (0.40 mmol) and triethylamine 1.
5 g was added to 8 ml of acetonitrile, and the mixture was stirred at room temperature for 31 hours under a nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate, washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 6: 1) to give 4- {5- (3,3-dimethyl-1-butynyl) -2-methylbenzyl} -5-methoxy -2-methyl-2,4-dihydro-3H-1,
2,4-triazol-3-one (Compound 52 of the present invention)
6) 0.21 g (0.66 mmol) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.20 (1 H, dd, J = 8.2 Hz),
7.14 (1H, d, J = 2 Hz), 7.06 (1H, d, J = 2 Hz)
d, J = 8 Hz), 4.66 (2H, s), 3.92
(3H, s), 3.40 (3H, s), 2.37 (3
H, s), 1.30 (9H, s)

Production Example 34 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 62
4 mg (2.0 mmol), 3- (trimethylsilyl)
-1-propyne 700 mg (6.3 mmol), PdC
63 mg (0.095 mmol) of l ₂ (PPh ₃ ) ₂ , 32 mg (0.17 mmol) of copper (I) iodide, 104 mg (0.40 mmol) of triphenylphosphine and 1.0 g of triethylamine were added to 6 ml of acetonitrile,
The mixture was stirred at 80 ° C. for 9 hours under a nitrogen atmosphere. After cooling to room temperature, the mixture was diluted with t-butyl methyl ether, washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 2: 1) to give 4- {5- (3-trimethylsilyl-1-).
Propynyl) -2-methylbenzyl} -5-methoxy-
2-Methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 527) 0.30
g (0.68 mmol) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.18 (1 H, dd, J = 8.2 Hz),
7.12 (1H, s), 7.05 (1H, d, J = 8H)
z), 4.66 (2H, s), 3.92 (3H, s),
3.39 (3H, s), 2.37 (3H, s), 1.6
7 (2H, s), 0.15 (9H, s)

Production Example 35 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 4.56
g (14.6 mmol) was dissolved in 30 ml of N, N-dimethylformamide, and 4.20 g (16 mmol) of thallium (I) acetate was added thereto.
l), butyl vinyl ether 9.34 ml (72.6 mmol),
1,3-bis (diphenylphosphino) propane 604mg
(3.64 mmol), 160 mg of palladium (II) acetate (0.72
mmol) and 2.44 ml (17.5 mmol) of triethylamine
Was added and the mixture was stirred at 90 ° C. for 8 hours under a nitrogen atmosphere.
After cooling to room temperature, dilute hydrochloric acid (prepared by mixing concentrated hydrochloric acid 21 ml and water 130 ml) was added, and the mixture was stirred for 30 minutes. The solution was filtered with cotton, the residue was washed with chloroform, and the filtrate was separated. After the aqueous layer was extracted with chloroform, the organic layers were combined, washed with water (twice), dried, and concentrated. An equal mixture of t-butyl methyl ether and hexane was added to the residue, and the mixture was stirred for a while at room temperature. 2.58 g of -2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 73) was obtained as a pale yellow powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.75 to 7.85 (2H, m), 7.25 (1H, d), 4.75
(2H, s), 3.94 (3H, s), 3.39 (3H, s),
2.56 (3H, s), 2.47 (3H, s)

Production Example 36 4- (5-acetyl-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,2
4-triazol-3-one (Compound 73 of the present invention) 275 m
g was dissolved in 4 ml of methanol, and 134 mg (1.2 mmol) of propoxyamine hydrochloride and 95 mg (1.2 mmol) of pyridine were added thereto, followed by stirring at room temperature for 8 hours. After most of the methanol was distilled off, ethyl acetate was added to the residue, and diluted hydrochloric acid,
Washing was sequentially performed with dilute aqueous sodium bicarbonate and water. The organic layer was dried and then concentrated. The residue (0.31 g) was subjected to silica gel preparative thin-layer chromatography (n-hexane: ethyl acetate = 1: 1).
And developed with 5-methoxy-2-methyl-4- {2
0.27 g of -methyl-5- (1-propoxyimino) ethyl @ benzyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 303) was obtained as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.45-7.5 (2H, m), 7.14 (1H, d), 4.73 (2
H, s), 4.13 (2H, t), 3.92 (3H, s), 3.38 (3H,
s), 2.41 (3H, s), 2.19 (3H, s), 1.75 (2H,
m), 0.97 (3H, t)

Production Example 37 4- (5-acetyl-2-methylbenzyl) -5-methoate
Xy-2-methyl-2,4-dihydro-3H-1,2,2
4-triazol-3-one (Compound 73 of the present invention) 275 m
g in 4 ml of methanol.
192 mg (1.2 mmol) and 95 mg (1.2 mmol) of pyridine were added.
Then, the mixture was stirred at room temperature for 2 hours. Silica reaction solution
Gel preparative thin-layer chromatography (n-hexane: acetic acid
Ethyl = 4: 3) to give 4- {5- (1-benzyl)
(Ruoximino) ethyl-2-methyl @ benzyl-5-
Methoxy-2-methyl-2,4-dihydro-3H-1,
2,4-triazol-3-one (Compound 31 of the present invention)
4) 0.27 g was obtained as an oil. ¹ H-NMR (CDCl_Three, TMS) δ (ppm): 7.25 to 7.5 (7H, m), 7.12 (1H, d), 5.21
(2H, s), 4.71 (2H, s), 3.88 (3H, s), 3.37 (3
H, s), 2.40 (3H, s), 2.21 (3H, s)

Production Example 38 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 524 m
g (1.68 mmol), 534 mg of trimethylsilylacetylene
(5.22 mmol), 19 mg of palladium (II) acetate (0.085
mmol), 37 mg (0.14 mmol) of triphenylphosphine and 1.5 ml of triethylamine were added to 2 ml of toluene, and the mixture was stirred under a nitrogen atmosphere at a bath temperature of 80 to 90 ° C. for 3 hours. After cooling to room temperature, the mixture was filtered and the residue was washed with toluene. The filtrate was concentrated, and the residue (0.79 g) was subjected to silica gel preparative thin layer chromatography (developed with hexane: ethyl acetate = 1: 2) to give 4- {5- (2-trimethylsilyl) ethynyl-
2-methylbenzyl} -5-methoxy-2-methyl-
2,4-dihydro-3H-1,2,4-triazole-
0.28 g of 3-one (the present compound 457) (as the impurity, the starting compound 4- (5-bromo-2-methylbenzyl)-
5-methoxy-2-methyl-2,4-dihydro-3H-
1,2,4-triazol-3-one). ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2 to 7.35 (2H, m), 7.08 (1H, d), 4.67 (2H,
s), 3.92 (3H, s), 3.40 (3H, s), 2.38 (3
H, s), 0.24 (9H, s)

Production Example 39 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 0.44
g (1.4 mmol) was dissolved in 8 ml of N, N-dimethylformamide, and 30 mg (0.042 mmol) of PdCl ₂ (PPh ₃ ) ₂ was dissolved.
l) and 0.12 g (1.4 mmol) of copper (II) oxide powder were added, followed by stirring at 80 ° C. for 30 minutes under a nitrogen atmosphere. 0.48 g (2.0 mmol) of trimethyl (2-pyridyl) tin
Was dissolved in 4 ml of N, N-dimethylformamide, and the mixture was stirred at 80 ° C. for 3 hours under a nitrogen atmosphere. After cooling to room temperature, the mixture was poured into ice water and ethyl acetate was added. After cotton filtration, the filtrate was separated, and the organic layer was washed twice with water, dried and concentrated. The residue (0.43 g) was subjected to silica gel preparative thin layer chromatography (developed with ethyl acetate) to give 5-methoxy-2-methyl-4- {2-methyl-5- (2-pyridyl) benzyl} -2, 4-dihydro-3H-1,2,2
4-triazol-3-one (Compound 152)
18 g were obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.65 (1H, m), 7.8 to 7.9 (2H, m), 7.6 to 7.75
(2H, m), 7.15 to 7.3 (2H, m), 4.79 (2H, m), 3.91
(3H, s), 3.39 (3H, s), 2.45 (3H, s)

Production Example 40 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 1.80
g (5.77 mmol), 4-chlorobenzonitrile 0.89 g
(5.77 mmol), 75 mg (0.577 mmol) of anhydrous nickel (II) chloride
And 0.31 g (1.15 mmol) of triphenylphosphine were dissolved in 6 ml of pyridine and heated to 80 ° C. under a nitrogen atmosphere. 0.79 g (12.1 mmol) of zinc powder was added thereto, and the mixture was stirred at 80 ° C. for 5 hours under a nitrogen atmosphere. After cooling to room temperature, the mixture was poured into a mixture of dilute aqueous hydrochloric acid (prepared by mixing 72 ml of water and 8 ml of concentrated hydrochloric acid) and ice, and ethyl acetate was added. After filtration through cotton, the layers were separated, and the organic layer was washed successively with aqueous sodium hydrogen carbonate and water, dried, and concentrated. The residue (2.17 g) was subjected to silica gel column chromatography (n-hexane: ethyl acetate = 2:
1 then 1: 1 to elute impurities; then 1: 2 to elute the desired product) to give 4- {5- (4-cyanophenyl) -2-
Methylbenzyl} -5-methoxy-2-methyl-2,4
0.65 g of -dihydro-3H-1,2,4-triazol-3-one (the present compound 489) was obtained as crystals. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.6 to 7.75 (4H, m), 7.4 to 7.45 (2H, m),
7.28 (1H, d), 4.78 (2H, s), 3.94 (3H, s),
3.39 (3H, s), 2.46 (3H, s)

Production Example 41 4- (5-bromo-2-fluorobenzyl) -5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one (referred to in Reference Production Example 13 below) Production) 3.33g
(11.0 mmol) and 1.88 g (13.2 mmol) of methyl iodide were dissolved in 30 ml of N, N-dimethylformamide, and 0.53 g of sodium hydride (60% oil dispersion) was added thereto under ice-cooling.
3.2 mmol) was added in small portions. After the vigorous foaming subsided, the ice-cooled bath was removed and the mixture was stirred at room temperature for 3 hours. Ice water was added to the reaction solution, and the mixture was extracted with a mixed solvent of ethyl acetate and t-butyl methyl ether. The organic layer was washed with water (twice),
After drying, it was concentrated. Add n-hexane to the solid residue, stir for a while, cool, then collect the solid in a furnace,
4- (5-bromo-2-fluorobenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,
4-triazol-3-one (the present compound 528) 2.
77 g was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.35 to 7.45 (2H, m), 6.95 (1H, t), 4.75
(2H, s), 3.95 (3H, s), 3.39 (3H, s)

Reference Production Example 13 (1) 9.45 g of 5-bromo-2-fluorotoluene (50 m
mol) was dissolved in 100 ml of carbon tetrachloride, and 9.08 g (50 mmol) of N-bromosuccinimide and 1,1 ′
-Azobis (cyclohexane-1-carbonitrile)
26 g (1 mmol) was added, and the mixture was heated under reflux for 5 hours. After cooling to room temperature, the mixture was filtered and the filtrate was concentrated to obtain 13.54 g of crude 5-bromo-2-fluorobenzyl bromide as a liquid. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.35-7.6 (2H, m), 6.96 (1H, t), 4.44
(2H, s) (2) 5-methoxy-2,4-dihydro-3H-1,
5.75 g (50 mmol) of 2,4-triazol-3-one was dissolved in 30 ml of acetonitrile, and 6.21 g (45%) of potassium carbonate was added thereto.
mmol) was added. To this, 13.54 g of crude 5-bromo-2-fluorobenzyl bromide was added at 55 ° C. in 50 ml of acetonitrile.
The solution dissolved in was added dropwise. After stirring at 55 ° C. for 2.5 hours, 5-methoxy-2,4-dihydro-3H-1,2,2,5.
1.15 g of 4-triazol-3-one and potassium carbonate
1.24 g was added, and the mixture was further stirred at 55 ° C. for 3 hours. Water was added to the reaction solution, which was extracted with a mixed solvent of ethyl acetate and t-butyl methyl ether. Wash the organic layer with water,
After drying, it was concentrated. To the semi-solid residue (13.37 g) was added an equal mixture of t-butyl methyl ether and n-hexane, and the mixture was stirred for a while, cooled, and the solid was collected in a furnace.
3.64 g of 4- (5-bromo-2-fluorobenzyl) -5-methoxy-2,4-dihydro-3H-1,2,4-triazol-3-one was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.26 (1 H, br), 7.35 to 7.45 (2 H, m), 6.9
4 (1H, t), 4.76 (2H, s), 3.96 (3H, s)

Production Example 42 0.17 g (1.35 mmol) of phenylboronic acid, 4- (5-bromo-
2-fluorobenzyl) -5-methoxy-2-methyl-
2,4-dihydro-3H-1,2,4-triazole-
338 mg (1.07 mmol) of 3-one (the present compound 528), 1 mg (0.004 mmol) of palladium (II) acetate, 0.37 g of potassium carbonate
(2.68 mmol) and tetrabutylammonium bromide.
34 g (1.07 mmol) was suspended in 5 ml of water, and the mixture was vigorously stirred under a nitrogen stream, and then stirred under a nitrogen atmosphere at a bath temperature of 75 ° C. for 1 hour. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried and then concentrated. Residue (0.35
g) was subjected to silica gel preparative thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 2) to give 4- (2-
Fluoro-5-phenylbenzyl) -5-methoxy-2
0.27 g of -methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 529) was obtained as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.3 to 7.55 (7H, m), 7.11 (1H, t), 4.84 (2
H, s), 3.94 (3H, s), 3.37 (3H, s)

Production Example 43 4,4,5,5-Tetramethyl-2- {3- (4-pyrimidinyl) phenyl} -1,3,2-dioxoborolane (prepared in Reference Production Example 14 described later) 195 mg (0.691) mmol), 4
-(5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-
200 mg (0.692 mmol) of triazol-3-one (the present compound 299: produced in Production Example 20), 734 mg (3.46 mmol) of tripotassium phosphate hydrate,
{1,1′-bis (diphenylphosphino) ferrocene} dichloropalladium (II) methylene chloride complex 28
mg (0.03 mmol), palladium (II) acetate 7
mg (0.03 mmol) and 3 ml of ethylene glycol dimethyl ether, followed by stirring at 83 ° C. for 4 hours. After the mixture was cooled to room temperature, saturated saline was added thereto, and the mixture was extracted with ethyl acetate. After drying the organic layer,
Concentrated. Preparative thin-layer chromatography of the residue on silica gel (developed with ethyl acetate: isopropanol = 12: 1)
To give 5-methoxy-2-methyl-4- {2-methyl-5- [3- (4-pyrimidinyl) phenyl] benzyl} -2,4-dihydro-3H-1,2,4-triazole- 102 mg of 3-one (the present compound 534) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 9.28 (1 H, d, J = 1.3 Hz),
8.80 (1H, d, J = 5.4 Hz), 8.28 (1
H, t, J = 1.8 Hz), 8.02 to 8.05 (1
H, m), 7.77 (1H, dd, J = 5.4 Hz, J
= 1.5 Hz), 7.67 to 7.70 (1H, m),
7.48 to 7.60 (3H, m), 7.29 (1H,
m), 4.80 (2H, s), 3.95 (3H, s),
3.39 (3H, s), 2.47 (3H, s)

Reference Production Example 14 (1) 9.0 g (59.9 m) of 3-bromoacetophenone
mol), 17.1 g (118 mmol) of N, N ′, N ″ -methylidenetrisformamide, 0.57 g (3.0 mmol) of p-toluenesulfonic acid and 27 g of formamide were stirred at 160 ° C. for 2 hours. After cooling to room temperature, pour into 5% aqueous sodium hydroxide
After adjusting the pH to 4 with a solution of hydrochloric acid, the mixture was extracted with ethyl acetate. The organic layer was washed successively with a saturated aqueous ammonium chloride solution and a saturated saline solution, dried, and concentrated. The obtained solid residue was recrystallized from ethanol: water = 1: 2 to give 4-
2.49 g of (3-bromophenyl) pyrimidine were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 9.29 (1 H, d, J = 0.9 Hz),
8.81 (1H, d, J = 5.4 Hz), 8.28 (1
H, t, J = 1.7 Hz), 8.01 (1H, d, J =
7.8 Hz), 7.71 (1H, dd, J = 5.1,
1.2 Hz), 7.7 (1H, dd), 7.40 (1
(H, t, J = 7.8 Hz) (2) 4- (3-bromophenyl) pyrimidine 0.70
g (6.31 mmol), bis (pinacolato) diboron 0.91 g (3.9 mmol), {1,1′-bis (diphenylphosphino) ferrocene} dichloropalladium (II) methylene chloride complex 0.121 g (0.1
49 mmol), potassium acetate 0.88 g (9.0 mm
ol) and dimethyl sulfoxide (2 ml) were mixed and stirred at 80 ° C. for 4 hours. After cooling the mixture to room temperature, water was added and this was extracted with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried, and concentrated. The residue was subjected to silica gel column chromatography (n
-Elution with a mixed solvent of hexane and ethyl acetate)
520 mg of 4,4,5,5-tetramethyl-2- {3- (4-pyrimidinyl) phenyl} -1,3,2-dioxoborolane was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 9.3 (1H, s), 8.8 (1H, d),
8.5 (1H, s), 8.2 (1H, d), 8.0 (1
H, d), 7.8 (1H, d), 7.5 (1H, t),
1.37 (12H, s)

Production Example 44 5-Methoxy-2-methyl-4- {2-methyl-5
(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl) benzyl} -2,4-dihydro-3H-1,2,4-triazol-3-one (intermediate described below) 300 mg (manufactured in Production Example 2)
l), 173 mg of 2-bromopyrimidine (1.09 mm
ol), 890 mg of tripotassium phosphate hydrate (4.19 m
mol), {1,1'-bis (diphenylphosphino) ferrocene} dichloropalladium (II) methylene chloride complex 34 mg (0.042 mmol), palladium (II) acetate 9 mg (0.04 mmol) and ethylene glycol dimethyl ether After mixing 4ml, 83 ℃
For 4 hours. After cooling the mixture to room temperature, celite and ethyl acetate were added, the mixture was filtered, and the filtrate was concentrated. The residue is separated by silica gel preparative thin-layer chromatography (isopropyl alcohol: ethyl acetate = 1: 99).
To give 5-methoxy-2-methyl-4- {2-methyl-5- (2-pyrimidinyl) benzyl} -2,4-dihydro-3H-1,2,4-triazol-3-one (this Inventive compound 166) (109 mg) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 8.77 (2H, dd, J = 4.9 Hz, J
= 0.8 Hz), 8.24 to 8.29 (2H, m),
7.14 to 7.31 (2H, m), 4.81 (2H,
s), 3.92 (3H, s), 3.40 (3H, s),
2.47 (3H, s)

Production Example 4 2.00 g (8.77 mm) of 3- (benzyloxy) phenylboronic acid
ol), 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,
2,4-triazol-3-one (Compound 29 of the present invention)
9) 2.49 g (7.97 mmol), 8.4 mg (0.037 palladium (II) acetate)
mmol), 2.75 g (19.9 mmol) of potassium carbonate and 2.60 g (8.07 mmol) of tetrabutylammonium bromide were suspended in 18.5 ml of water, stirred vigorously under a nitrogen stream, and then stirred at 70 ° C. for 1 hour under a nitrogen atmosphere. did. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with brine, dried and concentrated. The residue (3.68 g) was subjected to silica gel column chromatography (developed with hexane: ethyl acetate = 1: 2) to give 4- {5- (3-benzyloxy) phenyl-2-methyl} benzyl-5-methoxy-2. -Methyl-2,4-dihydro-3H-1,2,4-
2.93 g of triazol-3-one (the present compound 530)
Was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.1 to 7.5 (11H, m), 6.95 (1H, m), 5.11 (2H,
s), 4.77 (2H, s), 3.92 (3H, s), 3.39 (3H, s), 2.44
(3H, s)

Production Example 46 0.23 g (1.16 mmol) of 3-phenylphenylboronic acid, 4-
(5-bromo-2-methylbenzyl) -5-methoxy-
0.34 g of 2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 299) (1.
09 mmol), 2.3 mg (0.01 mmol) of palladium (II) acetate, 0.37 g (2.68 mmol) of potassium carbonate and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water, and the mixture was vigorously stirred under a nitrogen stream. 1 at 70 ° C under nitrogen atmosphere
Stirred for hours. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with brine, dried and concentrated. The residue (0.48 g) was subjected to silica gel preparative thin-layer chromatography (developed with hexane: ethyl acetate = 1: 2),
5-methoxy-2-methyl-4- {2-methyl-5
0.32 g of (3-phenyl) phenyl} benzyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 531) was obtained as a viscous oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2 to 7.8 (12H, m), 4.79 (2H, s), 3.93
(3H, s), 3.39 (3H, s), 2.46 (3H, s)

Production Example 47 0.24 g (1.16 mmol) of 3,4-dichlorophenylboronic acid, 4
-(5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-
0.34 g of triazol-3-one (the present compound 299)
(1.09 mmol), 3.9 mg (0.016 mmol) of palladium (II) acetate, 0.37 g (2.68 mmol) of potassium carbonate and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water,
After vigorous stirring under a nitrogen stream, 70 ° C under a nitrogen atmosphere
For 1 hour. Water was added to the reaction mixture and extracted with chloroform. The organic layer was washed with saline and dried,
Concentrated. The residue (0.84 g) was subjected to silica gel preparative thin-layer chromatography (developed with chloroform: ethyl acetate = 1: 2) to give 4- {5- (3,4-dichlorophenyl).
-2-methyl {benzyl-5-methoxy-2-methyl-
2,4-dihydro-3H-1,2,4-triazole-
0.27 g of 3-one (the present compound 45) was obtained as a solid. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.60 (1 H, d), 7.48 (1 H, d), 7.3 to 7.4 (3 H, m),
7.24 (1H, d), 4.77 (2H, s), 3.94 (3H, s), 3.40 (3H,
s), 2.45 (3H, s)

Production Example 48 0.18 g (1.14 mmol) of 3,5-difluorophenylboronic acid,
4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 0.34
g (1.09 mmol), palladium (II) acetate 7.1 mg (0.029 mmol),
0.37 g (2.68 mmol) of potassium carbonate and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water, and the mixture was vigorously stirred under a nitrogen stream.
Stirred at 0 ° C. for 1 hour. Water was added to the reaction mixture, which was extracted with chloroform. The organic layer was washed with brine, dried and concentrated. The residue (0.78 g) was subjected to silica gel preparative thin layer chromatography (developed with chloroform: ethyl acetate = 1: 2) to give 4- {5- (3,5-difluorophenyl) -2-methyl} benzyl-5. -Methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 532) 0.25
g was obtained as a white powder. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.2 to 7.45 (3H, m), 6.95 to 7.10 (2H,
m), 6.77 (1H, tt), 4.77 (2H, s), 3.94 (3H, s), 3.
40 (3H, s), 2.45 (3H, s)

Production Example 49 0.16 g (1.16 mmol) of 2-fluorophenylboronic acid, 4- (5
-Bromo-2-methylbenzyl) -5-methoxy-2-
Methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 299) 0.34 g (1.09 mm
ol), 4.7 mg (0.014 mmol) of palladium (II) acetate, 0.37 g (2.68 mmol) of potassium carbonate and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water, and the mixture was vigorously stirred under a nitrogen stream. The mixture was stirred at 70 ° C. for 1 hour under a nitrogen atmosphere. Water was added to the reaction mixture and extracted with chloroform. The organic layer was washed with brine, dried and concentrated. The residue (1.34 g) was subjected to silica gel preparative thin-layer chromatography (developed with chloroform: ethyl acetate = 1: 2) to give 4- {5- (2-fluorophenyl) -2-methyl}.
0.26 g of benzyl-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 533) was obtained as an oil. ¹ H-NM
R (CDCl ₃ , TMS) δ (ppm): 7.05 to 7.45 (7H, m), 4.77 (2H, s), 3.93
(3H, s), 3.39 (3H, s), 2.45 (3H, s)

Production Example 50 0.16 g (1.16 mmol) of 3-fluorophenylboronic acid, 4- (5
-Bromo-2-methylbenzyl) -5-methoxy-2-
Methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 299) 0.34 g (1.09 mm
ol), 7.1 mg (0.022 mmol) of palladium (II) acetate, 0.37 g (2.68 mmol) of potassium carbonate and 0.34 g (1.07 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water, and the mixture was vigorously stirred under a nitrogen stream. The mixture was stirred at 70 ° C. for 1 hour under a nitrogen atmosphere. Water was added to the reaction mixture, which was extracted with chloroform. The organic layer was washed with brine, dried and concentrated. The residue (0.83 g) was subjected to silica gel preparative thin-layer chromatography (developed with chloroform: ethyl acetate = 1: 2) to give 4- {5- (3-fluorophenyl) -2.
-Methyl @ benzyl-5-methoxy-2-methyl-2,
4-dihydro-3H-1,2,4-triazole-3-
0.29 g of ON (the present compound 28) was obtained as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15 to 7.45 (6H, m), 6.95 to 7.1 (1H,
m), 4.78 (2H, s), 3.94 (3H, s), 3.40 (3H, s), 2.4
5 (3H, s)

Production Example 51 3-methylphenylboronic acid 0.20 g (1.2 mmol), 4- (5-
Bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 299) 0.34 g (1.09 mmol)
l), palladium (II) acetate 4 mg (0.022 mmol), potassium carbonate
0.37 g (2.7 mmol) and 0.35 g (1.09 mmol) of tetrabutylammonium bromide were suspended in 5 ml of water, and were suspended under a stream of nitrogen.
After vigorous stirring, the mixture was stirred at 70 ° C. for 2 hours under a nitrogen atmosphere. A saline solution was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with brine, dried and concentrated. The residue (0.94 g) was subjected to silica gel preparative thin layer chromatography (developed with chloroform: ethyl acetate = 2: 1) to give 4- {5- (3-methylphenyl) -2-methyl}.
0.33 g of benzyl-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 50) was obtained as an oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.1 to 7.45 (7H, m), 4.79 (2H, s), 3.92
(3H, s), 3.39 (3H, s), 2.44 (3H, s), 2.41 (3H, s)

Production Example 52 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 43
7 mg (1.4 mmol), benzylacetylene 325
_{mg (2.8mmol), PdCl 2 (} PPh 3) 2 41
mg (0.058 mmol), copper (I) iodide 33 mg
(0.17 mmol), 82 m of triphenylphosphine
g (0.31 mmol) and triethylamine 0.80
g was heated and refluxed in 4 ml of acetonitrile under a nitrogen atmosphere for 9 hours. After cooling to room temperature, the mixture was diluted with t-butyl methyl ether, washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 2: 1) to give 4- {5-
(3-phenyl-1-propynyl) -2-methylbenzyl} -5-methoxy-2-methyl-2,4-dihydro-
0.25 g of 3H-1,2,4-triazol-3-one (the present compound 535) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15-7.45 (7H, m), 7.09
(1H, d, J = 8 Hz), 4.68 (2H, s),
3.92 (3H, s), 3.40 (3H, s), 2.3
8 (3H, s)

Production Example 53 To a solution of 9.24 g (31.1 mmol) of triphosgene in 50 ml of methylene chloride was added 1,1-dimethyl-4- (2-methyl-5-phenylbenzyl) semicarbazide (described below) under ice-cooling. 4.41 g (produced in Reference Production Example 15) (1
A solution of 5.6 mmol) in 35 ml of methylene chloride was added dropwise. The reaction vessel was removed from the ice-cooled bath, allowed to come to room temperature, and heated under reflux for 6 hours. After allowing to cool to room temperature, the reaction solution was poured into about 5% aqueous sodium bicarbonate (300 ml) and stirred for 1 hour.
This was separated, the organic layer was washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (n-
Hexane: ethyl acetate = 2: 1, then developed at 1: 1), and 5-chloro-2-methyl-4 having a melting point of 115.7 ° C.
2.01 g (6.4 mmol) of-(2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 7) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.55 (8H, m), 4.92 (2H, s), 3.49 (3H, s), 2.4
4 (3H, s)

Reference Production Example 15 (1) 2-Methyl-5-phenylbenzylbromide
83 g (30 mmol) was dissolved in 90 ml of anhydrous tetrahydrofuran, and 5.84 g (39 mmol) of silver cyanate was added thereto, followed by heating under reflux for 2 hours. The reaction solution was filtered, and the filtrate was concentrated to obtain 7.11 g of crude 2-methyl-5-phenylbenzyl isocyanate. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (8H, m), 4.53 (2H, s), 2.37 (3H, s) (2) This crude 2-methyl-5 To a suspension obtained by adding 7.11 g of phenylbenzyl isocyanate to 24 ml of toluene, 2.10 g of N, N-dimethylhydrazine (3.
5 mmol), and the reaction vessel was removed from the ice bath.
The mixture was further stirred at room temperature for 2 hours. The reaction solution was concentrated, and the solid residue was recrystallized from ethanol to give 1,1-dimethyl-4.
4.41 g (15.6 mmol) of-(2-methyl-5-phenylbenzyl) semicarbazide was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.65 (8H, m), 6.27 (1H, br), 5.22 (1H, br),
4.48 (2H, d), 2.49 (6H, s), 2.38 (3H, s)

Production Example 54 5-chloro-2-methyl-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4
-Triazol-3-one (Compound 7 of the present invention) 500 m
g (1.59 mmol) was dissolved in 5 ml of N, N-dimethylacetamide, and 1.0 ml of sodium thiomethoxide (15% aqueous solution) was added thereto, followed by stirring at 80 ° C. for 4.5 hours. Water was added to the reaction solution, which was extracted with t-butyl methyl ether. The organic layer was washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 2: 1, then 1: 1).
5-methylthio-2-methyl-4-p with a melting point of 95.6 ° C.
0.32 g (0.98 mmol) of (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (the present compound 8) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.25 to 7.60 (8H, m), 4.86 (2H, s), 3.49 (3H, s), 2.4
2 (3H, s), 2.41 (3H, s)

Production Example 55 5-Methyl-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (refer to Reference Production Example 16 described later). Production) 0.8
6 g (3.08 mmol) and 1.31 g of methyl iodide (9.
24 mmol) was dissolved in 20 ml of anhydrous N, N-dimethylformamide, and under ice cooling, 0.37 g (9.24 mmol) of sodium hydride (60% oil dispersion) was added thereto. After the severe foaming subsided, the reaction vessel was removed from the ice-cooled bath and stirred at room temperature for 1 hour. After ice cooling again, 5
A 200% aqueous hydrochloric acid solution (200 ml) was added, and the mixture was extracted with t-butyl methyl ether. The organic layer was washed with water, 5% aqueous sodium bicarbonate and then with saturated saline, dried, and concentrated. The residue was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 1: 1, and then with ethyl acetate) to give 2,5-dimethyl-4- (2- (2-methyl-2-methyl-4- (2-ethyl) -2-phenyl-2- (2-methyl) -2-phenyl-2- (2-methyl) -2-phenyl-2- (2-methyl-2-methyl) -2-propane)
Methyl-5-phenylbenzyl) -2,4-dihydro-
0.73 g (2.50 mmol) of 3H-1,2,4-triazol-3-one (Compound 10 of the present invention) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.10-7.55 (8H, m), 4.87 (2H, s), 3.47 (3H, s), 2.3
8 (3H, s), 2.05 (3H, s)

Reference Production Example 16 (1) 0.82 g of acetohydrazide was added to a solution of 2.47 g (11.1 mmol) of crude 2-methyl-5-phenylbenzyl isocyanate in 50 ml of tetrahydrofuran.
(11.1 mmol) was added and the mixture was heated under reflux for 1 hour. After allowing to cool to room temperature, the reaction solution was concentrated, the residue was recrystallized from ethanol, and 0.93 g of 1-acetyl-4- (2-methyl-5-phenylbenzyl) semicarbazide (3.13)
mmol). ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.95 (1H, br), 7.15-7.60 (8H, m), 5.17 (2H, br),
4.48 (2H, d), 2.28 (3H, s), 1.90 (3H, s) (2) 0.87 g (2.92 mmol) of 1-acetyl-4- (2-methyl-5-phenylbenzyl) semicarbazide
Is added to 10 ml of a 2% aqueous potassium hydroxide solution,
Stirred for hours. After cooling to room temperature, the reaction solution was extracted with ethyl acetate, and the organic layer was washed with water, dried and concentrated. The residue was subjected to silica gel column chromatography (eluted with ethyl acetate) to give 5-methyl-4- (2-methyl-5-
Phenylbenzyl) -2,4-dihydro-3H-1,
0.87 g (3.11 m) of 2,4-triazol-3-one
mol). ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 9.38 (1H, br), 7.1 to 7.55 (8H, m), 4.88 (2H, s), 2.
38 (3H, s), 2.06 (3H, s)

Production Example 56 5-methoxy-4- {1- (2-methyl-5-phenyl) phenylethyl} -2,4-dihydro-3H-1,
2,4-triazol-3-one (Reference Production Example 17 described later)
0.36 g (1.17 mmol) and 0.22 ml (3.50 mmol) of methyl iodide were dissolved in 10 ml of anhydrous N, N-dimethylformamide.
0.14 g (3.50 mmo of 0% oil dispersion)
l) was added. After the severe foaming subsided, the reaction vessel was removed from the ice-cooled bath and stirred at room temperature for 1 hour. After ice-cooling again, 200 ml of a 5% hydrochloric acid aqueous solution was added, and this was extracted with t-butyl methyl ether. The organic layer was washed with water, 5% aqueous sodium bicarbonate and then with saturated saline, dried, and concentrated. The residue was subjected to silica gel preparative thin-layer chromatography (developed with n-hexane: ethyl acetate = 2: 1),
5-methoxy-2-methyl-4- {1- (2-methyl-
5-phenyl) phenylethyl {-2,4-dihydro-
0.22 g (0.69 mmol) of 3H-1,2,4-triazol-3-one (the present compound 537) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15 to 7.85 (8H, m), 5.53 (1H, q), 3.89 (3H, s), 3.3
5 (3H, s), 2.40 (3H, s), 1.82 (3H, d)

Reference Production Example 17 (1) Anhydrous diethyl ether 5 was added to 600 mg of magnesium.
ml was poured and a catalytic amount of iodine was added. After stirring until the iodine color disappeared, 1.40 ml (22.4 mmol) of methyl iodide was obtained.
Was added dropwise. After the addition, the mixture was further stirred for 30 minutes. Then, the mixture was cooled to 0 ° C., and 4.00 g (20.4 mmol) of 2-methyl-5-phenylbenzaldehyde was slowly added dropwise. After stirring for an additional hour, a saturated aqueous ammonium chloride solution was added. The reaction vessel was removed from the ice-cooled bath, allowed to come to room temperature, and extracted with t-butyl methyl ether. The organic layer was washed with saturated saline, dried and concentrated to obtain 4.33 g (20.38 mmol) of 1- (2-methyl-5-phenyl) phenylethanol. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15 to 7.80 (8H, m), 5.19 (1H, q), 2.38 (3H, s), 1.77
(1H, br), 1.52 (3H, d) (2) A solution of 4.33 g (20.38 mmol) of 1- (2-methyl-5-phenyl) phenylethanol in anhydrous diethyl ether was added under ice-cooling. Phosphorus tribromide 2.21
g (8.15 mmol) were added dropwise. The reaction vessel was removed from the ice bath and stirred at room temperature for another 9 hours. Ice water was added to the reaction solution, and the mixture was separated. The organic layer was washed twice with 5% aqueous sodium bicarbonate, dried and concentrated, and 4.98 g of 1- (2-methyl-5-phenyl) phenylbromoethane ( 18.1mmo
l) got. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.20-7.80 (8H, m), 5.48 (1H, q), 2.48 (3H, s), 2.1
4 (3H, d) (3) 5-methoxy-2,4-dihydro-3H-1,
0.99 g (8.63) of 2,4-triazol-3-one
mol) and anhydrous acetonitrile (22 ml) were added with 0.99 g (7.20 mol) of potassium carbonate and stirred for 10 minutes. To this suspension, 1.98 g (7.19 mol) of 1- (2-methyl-5-phenyl) phenylbromoethane was added, and the mixture was stirred at 50 ° C. for 7 hours. After allowing the reaction solution to cool to room temperature, 200 ml of water was added, and the mixture was extracted three times with 70 ml of t-butyl methyl ether. The organic layers are combined, washed with water,
After drying, it was concentrated. The residue was subjected to silica gel column chromatography (eluted with n-hexane: ethyl acetate = 2: 1, then 1: 1) to give 5-methoxy-4- {1-
(2-methyl-5-phenyl) phenylethyl {-2,
4-dihydro-3H-1,2,4-triazole-3-
0.36 g (1.17 mmol) of on was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 9.15 (1H, br), 7.10-7.90 (8H, m), 5.54 (1H, q), 3.
88 (3H, s), 2.40 (3H, s), 1.83 (3H, d)

Production Example 57 5-Cyclopropyl-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-1,2,4-triazol-3-one (Reference Production Example 18 described later) Manufacturing)
0.29 g (0.96 mmol) and 0.15 g methyl iodide
(1.05 mmol) in anhydrous N, N-dimethylformamide 10
Dissolve in ice-cold solution and add sodium hydride (60%
0.06 g (1.43 mmol) of oil dispersion was added. After the severe foaming subsided, the reaction vessel was removed from the ice-cooled bath and stirred at room temperature for 1 hour. After cooling again with ice, 70 ml of a 5% hydrochloric acid aqueous solution was added, and the mixture was extracted with t-butyl methyl ether. The organic layer was washed with water, 5% aqueous sodium bicarbonate and then with saturated saline, dried, and concentrated. The residue was subjected to silica gel preparative thin layer chromatography (developed with n-hexane: ethyl acetate = 1: 2) to give a melting point of 102.4 ° C.
5-cyclopropyl-2-methyl-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H-
1,2,4-triazol-3-one (Compound 5 of the present invention)
38) 0.25 g (0.78 mmol) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.15-7.55 (8H, m), 4.98 (2H, s), 3.45 (3H, s), 2.4
0 (3H, s), 1.42 (1H, m), 0.75-0.9 (4H, m)

Reference Production Example 18 (1) To a suspension obtained by adding 3.11 g of crude 2-methyl-5-phenylbenzyl isocyanate to 24 ml of toluene, 1.27 g of cyclopropylcarbonylhydrazide (12.
7 mmol) and stirred at 60 ° C. for 1.5 hours. After cooling to room temperature, the reaction solution was concentrated, and the residue was recrystallized from ethanol to give 1-cyclopropylcarbonyl-4- (2-methyl-5-phenylbenzyl) having a melting point of 147.0 ° C.
1.86 g (5.75 mmol) of semicarbazide were obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 9.21 (1H, br), 8.03 (1H, br), 7.05-7.60 (8H, m),
6.16 (1H, br), 4.24 (2H, d), 2.19 (3H, s), 1.14 (1H, m), 0.73
(2H, br), 0.57 (2H, m) (2) 1.67 g of 1-cyclopropylcarbonyl-4- (2-methyl-5-phenylbenzyl) semicarbazide
(5.16 mmol) was added to 20 ml of a 2% aqueous potassium hydroxide solution and stirred at 90 ° C. for 7 hours. After cooling to room temperature, the reaction solution was extracted with ethyl acetate, the organic layer was washed with water, dried and concentrated. The residue is subjected to silica gel column chromatography (n-hexane: ethyl acetate = 1: 1).
Eluting with), 5-cyclopropyl-4- (2-methyl-5-phenylbenzyl) -2,4-dihydro-3H
0.64 g of -1,2,4-triazol-3-one
(2.09 mmol) was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 9.20 (1H, br), 7.15-7.55 (8H, m), 4.98 (2H, s), 2.
40 (3H, s), 1.42 (1H, m), 0.86 (2H, m), 0.78 (2H, m)

Next, a production example of the alkoxytriazolone compound represented by the general formula [II-1] will be described. Intermediate Production Example 1 20.0 ml (210 mmol) of ethyl chlorocarbonate was added to a solution of 19.3 g (420 mmol) of methylhydrazine in 80 ml of tetrahydrofuran under ice-cooling under a nitrogen atmosphere.
It was added dropwise over 0 minutes. After stirring at room temperature for 2 hours, insolubles were removed by filtration, and the filtrate was concentrated under reduced pressure to obtain 21.7 g of crude N-ethoxycarbonyl-N-methylhydrazine as a colorless oil. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.28 (3H, t, J = 7.5 Hz), 3.11
(3H, s), 4.1 (2H, br), 4.17 (2H, q, J = 7.5
Hz) 9.49 g (90 mmol) of cyanogen bromide in methanol (6 m
1) 18.4 ml of sodium methoxide (28% methanol solution) (90 mm
ol) was added dropwise and stirred overnight. After neutralization with concentrated hydrochloric acid, insolubles were removed by filtration, and the filtrate was ice-cooled. The crude N-ethoxycarbonyl-N-methylhydrazine 1
A solution of 0.6 g of methanol (8 ml) was added. After adding 1.2 ml of concentrated hydrochloric acid, the mixture was stirred at room temperature for 21 hours. Sodium methoxide (28% methanol solution) 1
8.4 ml (90 mmol) was added, and the mixture was stirred at 60 ° C. for 10 hours. Thereafter, the reaction mixture was concentrated under reduced pressure, water was added to the residue, acidified with concentrated hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated. The residue (colorless powder) is washed with t-butyl methyl ether,
5-methoxy-2-methyl-2,4-dihydro-3H-
1.24 g of 1,2,4-triazol-3-one (9.
6 mmol). ¹ H-NMR (DMSO-D6) δ (ppm): 3.17 (3H, s), 3.82 (3H, s), 11.3
8 (1H, br-s)

Next, a production example of the boron compound represented by the general formula [III-1] will be described. Intermediate Production Example 2 4- (5-bromo-2-methylbenzyl) -5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4
-Triazol-3-one (the present compound 299) 3.
00g (10.4 mmol), 3.16 g (12.4 mmol) of bis (pinacolato) diboron, {1,1′-
Bis (diphenylphosphino) ferrocene / dichloropalladium (II) methylene chloride complex 0.42 g (0.
51 mmol), 3.05 g (31.1 m) of potassium acetate
mol) and dimethyl sulfoxide (75 ml), and the mixture was stirred at 80 ° C for 8 hours. The mixture was cooled to room temperature, ethyl acetate and celite were added and filtered.
The filtrate was washed sequentially with water and saturated saline, dried, and
Concentrated. The residue was subjected to neutral alumina column chromatography (eluted with a mixed solvent of hexane and ethyl acetate),
5-methoxy-2-methyl-4- {2-methyl-5
(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl) benzyl} -2,4-dihydro-3H-1,2,4-triazol-3-one 1.76
g was obtained. ¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.61 to 7.64 (2H, m), 7.16
(1H, d, J = 7.5 Hz), 4.72 (2H,
s), 3.90 (3H, s), 3.39 (3H, s),
2.41 (3H, s), 1.32 (12H, s)

Next, examples of the compound of the present invention are shown in Tables 1 to 23 together with the compound numbers. A compound represented by the formula:

[0106]

[Table 1]

[0107]

[Table 2]

[0108]

[Table 3]

[0109]

[Table 4]

[0110]

[Table 5]

[0111]

[Table 6]

[0112]

[Table 7]

[0113]

[Table 8]

[0114]

[Table 9]

[0115]

[Table 10]

[0116]

[Table 11]

[0117]

[Table 12]

[0118]

[Table 13]

[0119]

[Table 14]

[0120]

[Table 15]

[0121]

[Table 16]

[0122]

[Table 17]

[0123]

[Table 18]

[0124]

[Table 19]

[0125]

[Table 20]

[0126]

[Table 21]

[0127]

[Table 22]

[0128]

[Table 23]

In the above table, Me is a methyl group, Et is an ethyl group, Pr is a propyl group, Bu is a butyl group, Pent is a pentyl group, Hex is a hexyl group, and Ph is a phenyl group. , Py is a pyridyl group, Bn
Represents a benzyl group. Further, n- represents normal-,
i- represents iso-, sec- represents secondary-, t- represents tertiary-, and c- represents cyclo-.

Next, formulation examples will be shown. Parts represent parts by weight, and the compounds of the present invention are indicated by the compound numbers shown in Tables 1 to 21 above. Formulation Example 1 50 parts of each of the present compounds 1 to 575, 3 parts of calcium ligninsulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic hydrous silicon oxide are thoroughly pulverized and mixed to obtain each wettable powder. Formulation Example 2 25 parts of each of the present compounds 1 to 575, 3 parts of polyoxyethylene sorbitan monooleate, 3 parts of CMC and 69 parts of water are mixed, and wet-pulverized until the particle size of the active ingredient becomes 5 μm or less. Thereby, each suspension is obtained. Formulation Example 3 2 parts each of Compounds 1 to 575 of the present invention, Kaolin Cre-8
By crushing and mixing 8 parts and 10 parts of talc well,
Obtain each powder. Formulation Example 4 Emulsions are obtained by thoroughly mixing 20 parts of each of the present compounds 1 to 575, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 60 parts of xylene. Formulation Example 5 Two parts of each of Compounds 1 to 575 of the present invention, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay are thoroughly pulverized and mixed,
After adding water and kneading well, the mixture is granulated and dried to obtain each granule. Formulation Example 6 20 parts of each of the compounds 1 to 575 of the present invention and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and finely pulverized with a sand grinder (particle size of 3 μm or less). ) After that, in this, xanthan gum 0.
Add 40 parts of an aqueous solution containing 05 parts and 0.1 part of aluminum magnesium silicate, and further add 10 parts of propylene glycol, and stir and mix to obtain a 20% suspension in water.

Next, Test Examples show that the compounds of the present invention are useful as fungicides for agricultural and horticultural use. In addition, this invention compound is shown by the compound number of Table 1-Table 23. The control effect of the compound of the present invention was evaluated by visually observing the area of the lesion on the test plant at the time of the investigation, and comparing the area of the lesion in the untreated section with the area of the lesion in the section treated with the compound of the present invention. did.

Test Example 1: Rice Blast Control Test (Preventive Effect) A plastic pot was filled with sandy loam, and rice (Nipponbare) was sown and grown in a greenhouse for 20 days. Thereafter, the compounds of the present invention 1, 2, 6, 7, 8, 10, 19, 21, 28, 4
5, 46, 47, 48, 49, 50, 152, 176,
296, 299, 303, 314, 457, 459, 4
78, 480, 487, 489, 526, 527, 52
9, 530, 531, 532, 533, 534 and 5
After preparing 35 as a wettable powder according to Formulation Example 1, each was diluted with water to a predetermined concentration (500 ppm) and sprayed with foliage so as to sufficiently adhere to the rice leaf surface. After spraying, the plants were air-dried and sprayed with a suspension of the blast fungus. 28 ° C after inoculation,
After 6 days in humid conditions, the control effect was investigated. As a result, the lesion area on the plant in the treated section of the compound of the present invention was 10% or less of the lesion area in the untreated section.

Test Example 2: Wheat powdery mildew control test (therapeutic effect) A plastic pot was filled with sandy loam,
No. 2) and grown in a greenhouse for 10 days. The wheat seedlings, which had developed the second leaf, were sprinkled with wheat powdery mildew spores and inoculated. After inoculation, they were placed in a greenhouse at 23 ° C. for 2 days.
Compounds of the invention 1, 6, 7, 19, 21, 28, 45, 4
6, 47, 49, 50, 152, 176, 314, 45
7, 459, 480, 487, 489, 529, 53
After suspensions 0, 531, 532 and 533 were prepared according to Formulation Example 2, each was diluted with water to a predetermined concentration (500 ppm), and sufficiently diluted on the leaves of wheat inoculated with powdery mildew. The foliage was sprayed so as to adhere. After spraying, it was further placed under lighting for 7 days, and the control effect was investigated. as a result,
The lesion area on the plant in the treated section of the compound of the present invention was 10% or less of the lesion area in the untreated section.

Test Example 3: Wheat Rust Control Test (Preventive Effect) A plastic pot was filled with sandy loam, and wheat (Agriculture and Forestry 73)
No. 2) and grown in a greenhouse for 10 days. Compounds of the present invention 1, 6, 7, 8, 10, 21, 28, 45, 46, 4
7, 48, 49, 50, 152, 176, 299, 31
4, 457, 478, 480, 526, 529, 53
After preparing 0, 531, 532, 533 and 535 as emulsions according to Formulation Example 4, each of them was diluted with water to a predetermined concentration (500 pp).
m), and it was sprayed with foliage so as to sufficiently adhere to the wheat leaf surface. After spraying, the plants were air-dried and inoculated with wheat rust spores. Initially after inoculation, under 23 ° C, dark and humid
After one day and then six days under light, the control effect was investigated. As a result, the lesion area on the plant in the treated section of the compound of the present invention was 10% or less of the lesion area in the untreated section.

Test Example 4: Wheat wilt control test (preventive effect) A plastic pot was filled with sandy loam, and wheat (agriculture and forestry 73
No. 2) and grown in a greenhouse for 10 days. Compounds of the present invention 1, 2, 6, 7, 8, 10, 11, 21, 28, 4
5, 46, 47, 48, 49, 50, 152, 176,
239, 299, 303, 314, 457, 478, 4
80, 489, 526, 529, 530, 531, 53
After preparing 3, 534 and 535 as emulsions according to Formulation Example 4, each was diluted with water to a predetermined concentration (500 ppm).
The foliage was sprayed so as to sufficiently adhere to the wheat leaf surface. After spraying, the plants were air-dried and spray-inoculated with a spore suspension of wheat wilt. After the inoculation, they were first placed in a dark and humid environment at 15 ° C. for 4 days, and then placed under illumination for 7 days. As a result, the lesion area on the plant in the treated section of the compound of the present invention was 10% or less of the lesion area in the untreated section.

Test Example 5 Control Test for Wheat Eye Spot Disease (Preventive Effect) Sand loam was packed in a plastic pot, and wheat (Agriculture and Forestry 73)
No.) and sowed in a greenhouse for 10 days. Compounds of the invention 1, 6, 7, 10, 21, 28, 45, 46, 4
7, 49, 50, 152, 176, 239, 303, 3
14, 457, 480, 489, 526, 529, 53
After preparing 0, 531, 532, 533 and 535 as emulsions according to Formulation Example 4, each of them was diluted with water to a predetermined concentration (500 pp).
m), and it was sprayed with foliage so as to sufficiently adhere to the wheat leaf surface. After spraying, the plants were air-dried and inoculated with a PDA containing spores of wheat eye spot disease fungus. 15 ℃ at the beginning after inoculation,
After 7 days in dark and humid, and 4 days in the light,
The control effect was investigated. As a result, the area of the lesion on the plant in the group treated with the compound of the present invention was 10% or less of the area of the lesion in the untreated group.

Test Example 6: Test for Control Effect of Grape Downy Mildew (Preventive Effect) A plastic pot was filled with sandy loam and grape (berry)
A) were sown and grown in a greenhouse for 40 days. Compounds of the present invention 6, 7, 8, 10, 19, 21, 28, 45, 46,
47, 48, 49, 50, 303, 457, 459, 4
78, 480, 487, 489, 526, 527, 52
8, 529, 530, 531, 532, 533, 534
And 535 were made into suspensions in accordance with Formulation Example 2, and then each was diluted with water to a predetermined concentration (200 ppm) and sprayed with foliage so as to sufficiently adhere to the vine leaf surface. After spraying, the plants were air-dried and spray-inoculated with a zoosporangial suspension of grape downy mildew. After the inoculation, they were first placed in a humid environment at 23 ° C. for 1 day, and further placed in a greenhouse for 6 days. As a result, the lesion area on the plant in the treated section of the compound of the present invention was 10% or less of the lesion area in the untreated section.

Test Example 7: Cucumber gray mold control effect test (preventive effect) A plastic pot was filled with sandy loam, cucumber (Sagamihanjiro) was sowed, and grown in a greenhouse for 12 days. Compounds of the Invention 6, 19, 21, 28, 46, 47, 48, 49, 5
0, 314, 457, 478, 480, 487, 526
And 533 were prepared as wettable powders according to Formulation Example 1, and then each was diluted with water to a predetermined concentration (500 ppm).
The foliage was sprayed so as to sufficiently adhere to the cucumber leaf surface.
After spraying, air-dry the plant and contain the mycelium of cucumber gray mold fungus
PDA medium was placed on cucumber leaves. After inoculation, the plants were placed in a humid environment at 10 ° C. for 4 days, and the control effect was examined. As a result, the lesion area on the plant in the treated section of the compound of the present invention was 10% or less of the lesion area in the untreated section.

Test Example 8 Test for Controlling Effect of Cucumber Powdery Mildew (Preventive Effect) A plastic pot was filled with sandy loam, cucumber (Sagami Hanjiro) was sowed, and grown in a greenhouse for 12 days. Compounds 6, 7, 10, 21, 28, 45, 46, 47, and 4 of the present invention
9, 50, 152, 457, 478, 480, 489,
After preparing 526, 527, 529, 530, 531, 532 and 533 as suspension agents according to Formulation Example 2, each was diluted with water to a predetermined concentration (200 ppm), and sufficiently adhered to the cucumber leaf surface. Foliage was sprayed as if to do. After spraying, the plants were air-dried and inoculated with spores of cucumber powdery mildew. After 12 days at 23 ° C after inoculation, the control effect was investigated. As a result, the lesion area on the plant in the treated section of the compound of the present invention was 10% or less of the lesion area in the untreated section.

[0140]

INDUSTRIAL APPLICABILITY The compound of the present invention has excellent plant disease controlling effect.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Hiroshi Sakaguchi 4-2-1 Takashi, Takarazuka-shi, Hyogo Sumitomo Chemical Science Co., Ltd. (72) Tomohiro Araki 4-2-1 Takashi Takarazuka-shi, Hyogo Sumitomo Kagaku Kogyo Co., Ltd. F term (reference) 4C063 AA01 BB06 BB08 CC41 CC52 CC62 CC92 CC94 DD04 DD12 DD14 DD22 DD29 DD41 EE03 4H011 AA01 BB09 BC01 BC07 BC18 BC19 BC20 DA02 DA15 DA16 DC04 DC06 DD03 DE15 DH03

Claims (21)

[Claims] 1. A compound of the general formula [I][Wherein, R¹Is an optionally substituted C1-C10 al
Kill group, optionally substituted C2-C10 alkenyl
Group, an optionally substituted C2-C10 alkynyl group,
Halogen atom, nitro group, cyano group, even if substituted
Good C3-C10 cycloalkyl group, even if substituted
Good C4-C20 cycloalkylalkyl groups, substituted
An optionally substituted C5-C10 cycloalkenyl group, substituted
C6-C20 cycloalkenylalkyl which may be optionally
Group, an optionally substituted C6-C10 aryl group,
An optionally substituted C7-C20 arylalkyl group,
An optionally substituted C1-C9 heteroaryl group,
Optionally substituted C2-C19 heteroarylalkyl
Group, A¹-L¹-Group, A¹-ON = CA^Two-Group, A¹-O
N = C (Me) CH_TwoON = CA^Two-Group, A¹C (A^Two) =
NOCH_Two-Group, A¹SC (A^Two) = N-group, A¹C (=
S) NH— group, A¹SC (= S) NH- group, A¹SC (S
A^Two) = N-group, A¹-ON = C (CN)-group, A¹-O
N = C (Me) CH_TwoON = C (CN) -group or A¹C
(CN) = NOCH_Two-Group ｛where L¹Is an oxygen atom, a sulfur atom, a carbonyl group,
-OCH_Two-Group, -SCH _Two— Group, —C (＝ O) O— group,
—OC (＝ O) — group, —C (＝ O) OCH_Two-Group, -N
An H-group or a C1-C6 alkylimino group,
¹And A^TwoAre the same or different, are hydrogen atoms, are substituted
An optionally substituted C1-C10 alkyl group, optionally substituted
Good C2-C10 alkenyl group, which may be substituted
C2-C10 alkynyl group, optionally substituted C3
To C10 cycloalkyl group, optionally substituted C4
~ C20 cycloalkylalkyl group, even when substituted
Good C5-C10 cycloalkenyl group, substituted
C6 to C20 cycloalkenylalkyl group, substituted
An optionally substituted C6-C10 aryl group,
An optionally substituted C7-C20 arylalkyl group,
An optionally substituted C1-C9 heteroaryl group or substituted
An optionally substituted C2-C19 heteroarylalkyl group
Represents ｝, R^TwoIs a hydrogen atom or C1-C
6 represents an alkyl group;^ThreeIs C1-C6 alkoxy
Group, C1-C6 alkylthio group, cyano group, halogen atom
, Vinyl, ethynyl, cyclopropyl or C
1-C6 alkyl group, one of T, U and V
Is CR^FourA CH group or a nitrogen atom
And the other one is CR^FiveGroup or nitrogen atom
And W is CR⁶Represents a group or a nitrogen atom. Poko
Where R^Four, R^FiveAnd R⁶Are the same or different,
, Halogen atom, C1-C6 alkyl group, C1-C6
Alkoxy group, C1-C6 haloalkyl group, C1-C6
Haloalkoxy group, cyano group, nitro group, C2-C6
Alkoxycarbonyl group, C1-C6 alkylthio group or
Represents a C1 to C6 haloalkylthio group. ｝]
Triazolone derivatives. 2. In the above general formula [I], R ³ is C1 to C
The triazolone derivative according to claim 1, which is a 6 alkoxy group, a C1 to C6 alkylthio group, a cyano group, a halogen atom or a C1 to C6 alkyl group. 3. An optionally substituted C1 to C10 alkyl group or an optionally substituted C2 to C10 alkenyl group in R ¹ , A ¹ and A ² of the triazolone derivative represented by the above general formula [I]. An optionally substituted C2-C10 alkynyl group, an optionally substituted C2
3-C10 cycloalkyl group, optionally substituted C
4-C20 cycloalkylalkyl group, optionally substituted C5-C10 cycloalkenyl group, optionally substituted C6-C20 cycloalkenylalkyl group, optionally substituted C1-C9 heteroaryl group, substituted Each of the optionally substituted C2 to C19 heteroarylalkyl groups is the same or different and is one or more groups selected from the following group a, and optionally substituted C6 to C10 aryl groups, C7 that may be
3. The triazolone derivative according to claim 1, wherein the substituents in the C20 arylalkyl group are the same or different and are at least one group selected from the group consisting of the following groups a and b. 4. group a [halogen atom, C1-C10 alkyl group, C3-C2
0 trialkylsilyl group, C1-C10 haloalkyl group, C3-C10 cycloalkyl group, C1-C10 alkoxy group, C1-C10 haloalkoxy group, C1-C1
0 alkylthio group, C1-C10 haloalkylthio group,
C2-C10 alkoxycarbonyl group, phenyl group, phenoxy group, benzyloxy group, phenoxymethyl group,
C1-C9 heteroaryl group, (C1-C9 heteroaryl) methyloxy group, (C1-C9 heteroaryl)
Oxymethyl group, C1-C9 heteroaryloxy group (the phenyl group, phenoxy group, benzyloxy group, phenoxymethyl group, C1-C9 heteroaryl group, (C
1-C9 heteroaryl) methyloxy group, (C1-C
9 heteroaryl) oxymethyl group and each of the C1 to C9 heteroaryloxy groups are a halogen atom, a C1 to C9 heteroaryloxy group.
It may be substituted with one or more groups selected from the group consisting of a C6 alkyl group, a C1-C6 alkoxy group, a trifluoromethyl group and a cyano group. ), Hydroxyl group, cyano group and nitro group] Group b [methylenedioxy group and difluoromethylenedioxy group (each of the methylenedioxy group and difluoromethylenedioxy group is bonded to two adjacent carbon atoms in the aryl moiety) Yes.)] 4. An optionally substituted C1 to C10 alkyl group or an optionally substituted C2 to C10 alkenyl group in R ¹ , A ¹ and A ² in the triazolone derivative represented by the above general formula [I]. An optionally substituted C2-C10 alkynyl group, an optionally substituted C2
3-C10 cycloalkyl group, optionally substituted C
4-C20 cycloalkylalkyl group, optionally substituted C5-C10 cycloalkenyl group, optionally substituted C6-C20 cycloalkenylalkyl group, optionally substituted C1-C9 heteroaryl group, substituted Each of the optionally substituted C2-C19 heteroarylalkyl groups is the same or different and is at least one group selected from the following group c, and optionally substituted C6-C10 aryl groups, C7 that may be
3. The triazolone derivative according to claim 1, wherein the substituents in the C20 arylalkyl group are the same or different and are at least one group selected from the group consisting of the following groups c and b. 4. Group c [halogen atom, C1-C10 alkyl group, C3-C2
0 trialkylsilyl group, C1-C10 haloalkyl group, C3-C10 cycloalkyl group, C1-C10 alkoxy group, C1-C10 haloalkoxy group, C1-C1
0 alkylthio group, C1-C10 haloalkylthio group,
C2-C10 alkoxycarbonyl group, phenyl group, phenoxy group, benzyloxy group, pyridin-2-yloxy group (wherein each of the phenyl group, phenoxy group, benzyloxy group and pyridin-2-yloxy group is a halogen atom, C1 -C6 alkyl group, C1-C6
It may be substituted with one or more groups selected from the group consisting of an alkoxy group, a trifluoromethyl group and a cyano group. ), Hydroxyl group, cyano group and nitro group] Group b [methylenedioxy group and difluoromethylenedioxy group (each of the methylenedioxy group and difluoromethylenedioxy group is bonded to two adjacent carbon atoms in the aryl moiety) Yes.)] 5. In the general formula [I], R ³ is a methoxy group, methylthio group, cyano group, halogen atom, vinyl group, ethynyl group, cyclopropyl group, ethyl group or methyl group. The triazolone derivative according to any one of the above. 6. The triazolone derivative according to claim 1, wherein in the general formula [I], R ³ is a methoxy group, a methylthio group, a cyano group, a halogen atom, an ethyl group or a methyl group. 7. The triazolone derivative according to claim 1, wherein in the general formula [I], R ³ is a methoxy group. 8. In the general formula [I], T, U and V
Of which is a CR ⁴ group, another is a CH group, and the other is a CR ⁵ group, and W is a CR ⁶ group (R ⁴ , R ⁵ and R ⁶ are the same as those described above). The triazolone derivative according to any one of claims 1 to 7, which represents a meaning. 9. The triazolone derivative represented by the above general formula [I], wherein R ⁴ , R ⁵ and R ⁶ are the same or different and are a hydrogen atom, a halogen atom or a methyl group. 3. The triazolone derivative according to item 1. 10. In the above general formula [I], U, V and W are CH groups and T is a CR ⁴ group (R ⁴ has the same meaning as described above). 3. The triazolone derivative according to item 1. 11. The triazolone derivative according to claim 10, wherein R ⁴ is a methyl group. 12. In the above general formula [I], R ¹ is a phenyl group which may be substituted;
9 heteroaryl groups, optionally substituted C2 to C1
A alkynyl group or an A ¹ -ON = CA ² -group (A ¹ and A ² represent the same meaning as described above).
The triazolone derivative according to any one of the above. 13. In the above general formula [I], R ¹ may be a phenyl group which may be substituted;
9 heteroaryl groups, optionally substituted C2 to C1
The triazolone derivative according to claim 11, which is a 0 alkynyl group or an A ¹ -ON = C (Me)-group. 14. The triazolone derivative according to claim 1, wherein in the general formula [I], R ² is a hydrogen atom or a methyl group. 15. The triazolone derivative according to claim 1, wherein in the general formula [I], R ² is a hydrogen atom. 16. A fungicide for agricultural and horticultural use, comprising the triazolone derivative according to claim 1 as an active ingredient. 17. A compound of the general formula [II-1] [In the formula, R ³¹ represents a C1 to C6 alkyl group. An alkoxytriazolone compound represented by the formula: 18. The alkoxytriazolone compound according to claim 17, wherein in the general formula [II-1], R ³¹ is a methyl group. 19. A compound of the general formula [III-1] [Wherein, R ¹⁴ represents a C1-C6 alkyl group or a hydrogen atom, or two R ¹⁴ represent an ethylene group or a trimethylene group (the ethylene group and the trimethylene group are
It may be substituted with two or more methyl groups or phenyl groups. ) And R ² , R ³ , V, U, T and W have the same meaning as described above. ] The boron compound shown by these. 20. The boron compound according to claim 19, wherein in the general formula [III-1], two R ¹⁴ are —CMe ₂ —CMe ₂ — groups. 21. The general formula [IV] [Wherein, R ¹ , R ² , R ³ , V, U, T and W represent the same meaning as described above. A triazolone compound represented by the formula: