Fluorine-containing pyrimidone compound and method for producing same

Abstract

Provided is a fluorine-containing pyrimidone compound represented by general formula (1). (In general formula (1), R1 and R2 each independently represent a hydrogen atom, a cyano group, or a hydrocarbon group having 1 to 12 carbon atoms, wherein: at least one -CH2- moiety in the hydrocarbon group may be substituted by -O-, -S-, -NH-, -CO-, -SO-, or -SO2-; at least one -CH= moiety in the hydrocarbon group may be substituted by -N=; a halogen atom, a cyano group, a nitro group, or a -NRARB group may be further bonded to the hydrocarbon group; RA and RB each independently represent a hydrogen atom, or an alkyl group having 1 to 4 carbon atoms; an option in which both R1 and R2 represent a methyl group is excluded, or alternatively, R1 and R2 are bound to each other to form a divalent hydrocarbon group having 2 to 24 carbon atoms; at least one -CH2- moiety in the divalent hydrocarbon group may be substituted by -O-, -S-, -NH-, -CO-, -SO-, or -SO2-; at least one -CH= moiety in the divalent hydrocarbon group may be substituted by -N=; and a halogen atom, a cyano group, a nitro group, or a -NRARB group may be further bound to the divalent hydrocarbon group.)

Description

Fluorine-containing pyrimidone compounds and methods for producing the same

[0001] The present invention relates to a fluorine-containing pyrimidone compound and a method for producing the same.

[0002] The pyrimidone ring can be considered a substructure of the four major nucleic acid bases, excluding adenine. Therefore, compounds with a pyrimidone ring structure are important in life activities and are attracting attention as drug targets. Specific examples of pharmaceuticals with a pyrimidone ring structure include the anti-cancer drug 5-fluorouracil and the antiviral drug acyclovir. Compounds with a pyrimidone ring structure are also widely used in the agricultural field. Such examples include the herbicide bromacil and the fungicide etirimol. There is interest in introducing heteroatom substituents to the pyrimidone ring structure in the hope of further improving pharmacological activity. For example, Patent Document 1 discloses a method for producing a compound in which a dimethylamino group is introduced at the 2-position and a trifluoromethyl group at the 5-position of the pyrimidone ring.

[0003] In the manufacturing method disclosed in Patent Document 1, chloroform is used as the solvent during the reaction. Furthermore, in the same document, dichloromethane is also used as the solvent during the synthesis of a similar compound. Both of these substances are highly toxic and have a significant environmental impact, and are therefore designated as Class II specified chemical substances under the Industrial Safety and Health Act and as Class I designated chemical substances under the PRTR Act. For these reasons, such manufacturing methods are avoided, and the synthesis of derivatives or similar compounds has not been considered at all.

[0004] Japanese Unexamined Patent Publication No. 63-216877

[0005] Compounds having a specific group containing a nitrogen atom at the 2-position of the pyrimidone ring and a trifluoromethyl group at the 5-position are useful not only in the fields of medicine and agriculture but also in the field of organic electronic materials. However, as described above, the reported examples of such compounds and their production methods are extremely limited. Therefore, providing a novel compound having a specific group at the 2-position of the pyrimidone ring and a trifluoromethyl group at the 5-position, and a novel production method thereof, is highly valuable in itself. In addition, while such compounds can be useful by themselves, they have high structural expandability due to having multiple substituents and can also be expected to be useful intermediates for obtaining further compounds.

[0006] The present invention provides a novel fluorine-containing pyrimidone compound and a method for producing the same.

[0007] The gist of the present invention is as follows. [1] A fluorine-containing pyrimidone compound represented by the following general formula (1).

[0008]

[0009] (In general formula (1), R １ and R ２ each independently represent a hydrogen atom, a cyano group, or a hydrocarbon group having 1 to 12 carbon atoms. Here, one or more of the -CH ２ - may be replaced by -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ -, one or more of the -CH= may be replaced by -N=, and the hydrocarbon group may further have a halogen atom, a cyano group, a nitro group, or a -NR Ａ R Ｂ group bonded thereto. Here, R Ａ and R Ｂ each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, provided that R １ and R ２ are not simultaneously methyl groups, or; R １ and R ２ together represent a divalent hydrocarbon group having 2 to 24 carbon atoms. Here, the divalent hydrocarbon group is -CH２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the divalent hydrocarbon group may have one or more -CH= replaced by -N=, and the divalent hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ (The groups may be further bonded.)

[0010] [2] A method for producing a fluorine-containing pyrimidone compound represented by the following general formula (1), comprising the step of reacting a guanidine compound represented by the following general formula (2) or a salt thereof with a fluorine-containing compound represented by the following general formula (3) or (4).

[0011]

[0012]

[0013]

[0014] (In general formulas (1) to (4), R １ and R ２ Each of these independently represents a hydrogen atom, a cyano group, or a hydrocarbon group having 1 to 12 carbon atoms, where the hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the hydrocarbon group may have one or more -CH= replaced by -N=, and the hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ Further groups may be bonded, where R Ａ and R Ｂ Each is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, or; R １ and R ２ Together, these represent a divalent hydrocarbon group having 2 to 24 carbon atoms, where the divalent hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２- may be replaced by -N=, and the divalent hydrocarbon group may have one or more -CH= replaced by -N=, and the divalent hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ The group may be further bonded; R ３ (This represents a hydrocarbon group with 1 to 12 carbon atoms.)

[0015] [3] A method for producing [2], comprising the step of reacting a guanidine compound represented by general formula (2) or a salt thereof with a fluorine-containing compound represented by general formula (3).

[0016] [4] A method for producing [2], comprising the step of reacting a guanidine compound represented by general formula (2) or a salt thereof with a fluorine-containing compound represented by general formula (4).

[0017] According to the present invention, novel fluorine-containing pyrimidone compounds and methods for producing the same can be provided.

[0018] [Fluorine-containing pyrimidone compounds] The fluorine-containing pyrimidone compounds of the present invention are represented by the following general formula (1).

[0019]

[0020] (In general formula (1), R １ and R ２ Each of these independently represents a hydrogen atom, a cyano group, or a hydrocarbon group having 1 to 12 carbon atoms, where the hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the hydrocarbon group may have one or more -CH= replaced by -N=, and the hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ Further groups may be bonded, where R Ａ and R Ｂ Each is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, however, R １ and R ２ It cannot be a methyl group at the same time, or; R １and R ２ Together, these represent a divalent hydrocarbon group having 2 to 24 carbon atoms, where the divalent hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the divalent hydrocarbon group may have one or more -CH= replaced by -N=, and the divalent hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ (The groups may be further bonded.)

[0021] The fluorine-containing pyrimidone compound of the present invention can be produced by the novel method described below. The fluorine-containing pyrimidone compound of the present invention has an amino group at the 2-position of the pyrimidone ring, a trifluoromethyl group at the 5-position, and a fluoro group at the 6-position. This novel compound is not only useful in the pharmaceutical and agrochemical fields, but also promising in the field of organic electronic materials. Furthermore, because it has numerous substituents and high structural expandability, it can be used as an intermediate for obtaining various useful compounds. Therefore, the fluorine-containing pyrimidone compound of the present invention will make a significant contribution to industry.

[0022] R １ and R ２ The hydrocarbon groups having 1 to 12 carbon atoms that each of these independently represents are not particularly limited as long as they are hydrocarbon groups consisting of carbon atoms and hydrogen atoms having 1 to 12 carbon atoms, and include linear hydrocarbon groups, aromatic hydrocarbon groups, alicyclic hydrocarbon groups, etc. The linear hydrocarbon group is not particularly limited as long as the total number of carbon atoms is 1 to 12, and may be a straight-chain hydrocarbon group or a branched-chain hydrocarbon group. The aromatic hydrocarbon group is not particularly limited as long as the total number of carbon atoms is 6 to 12, and may be an aromatic hydrocarbon group with substituents or an aromatic hydrocarbon group without substituents. In this case, substituents are R １ , R ２The hydrocarbon substituents may be such that the total number of carbon atoms falls within the range of 6 to 12. Furthermore, the aromatic hydrocarbon group may have a condensed polycyclic structure. The alicyclic hydrocarbon group is not particularly limited as long as the total number of carbon atoms is between 3 and 12, and may be an alicyclic hydrocarbon group with substituents or an alicyclic hydrocarbon group without substituents. In this case, substituents refer to R １ , R ２ The hydrocarbon substituents may be such that the total number of carbon atoms falls within the range of 3 to 12. Furthermore, the alicyclic hydrocarbon group may have a cross-linked ring structure. The hydrocarbon group having 1 to 12 carbon atoms may be an aralkyl group such as a benzyl group.

[0023] The above hydrocarbon group may contain a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ Further groups may be bonded. The hydrocarbon group may have one or more of these halogen atoms or groups bonded to it. Examples of halogen atoms that may be bonded to the hydrocarbon group include at least one selected from the group consisting of fluorine, chlorine, bromine, and iodine atoms. The hydrocarbon group may be substituted with, for example, 1 to 9 halogen atoms, 1 to 6 halogen atoms, or 1 to 3 halogen atoms. The hydrocarbon group may also have -NR Ａ R Ｂ When a group is bonded, R Ａ and R Ｂ Each of these is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Ａ and R Ｂ Each is preferably independently a hydrogen atom or a methyl group. Furthermore, a cyano group or -NR Ａ R Ｂ Carbon atoms that may be included in the group are not counted in the carbon number of the hydrocarbon group mentioned above.

[0024] R １ and R ２ It is impossible for both to be a methyl group at the same time. １ and R ２ Unless R is also a methyl group, １ R may be a methyl group,２ It may be a methyl group.

[0025] R １ and R ２ Examples of chain-like hydrocarbon groups that each of these groups independently represents include alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl groups; alkenyl groups such as ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, and dodecenyl groups; and alkynyl groups such as ethinyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octinyl, noninyl, desynyl, undecynyl, and dodecynyl groups.

[0026] R １ and R ２ Examples of aromatic hydrocarbon groups that can be independently represented by each include phenyl, benzyl, tolyl, and naphthyl groups. The tolyl group may be any of o-tolyl, m-tolyl, or p-tolyl groups.

[0027] R １ and R ２ The alicyclic hydrocarbon groups that each of these independently represents include saturated or unsaturated cyclic hydrocarbon groups. Examples of cyclic hydrocarbon groups include cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, adamantyl, and norbornyl groups.

[0028] R １ and R ２ The groups that each of these independently represents are preferably chain hydrocarbon groups or aromatic hydrocarbon groups, more preferably chain hydrocarbon groups or aromatic hydrocarbon groups having 1 to 8 carbon atoms, and even more preferably alkyl groups or aromatic hydrocarbon groups having 1 to 8 carbon atoms. In particular, R １ and R ２The groups that each of these groups independently represents are more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, phenyl, or benzyl groups; particularly preferably methyl, ethyl, n-propyl, isopropyl, isobutyl, s-butyl, t-butyl, or benzyl groups; and most preferably methyl, ethyl, isopropyl, or benzyl groups.

[0029] The above hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ It may be replaced by -, and one or more -CH= may be replaced by -N=. In this case, the replaced -O-, -S-, -CO-, -SO-, -SO ２ - and -N= are counted as one carbon atom in the carbon number of the hydrocarbon group. Preferably, -O- and -S- are not adjacent to other -O- or -S-.

[0030] The above hydrocarbon group is, for example, adjacent to -CH ２ One of the hyphens is replaced with -O-, and the other is replaced with -CO-, -SO-, or -SO ２ -By being managed, -OCO-, -COO-, -OSO-, -SOO-, -OSO ２ -, or -SO ２ It may have at least one substructure selected from O-. The hydrocarbon group is, for example, a methyl group (-CH ３ ) -CH ２ The - portion may be replaced with -O- or -S-, thereby giving the compound a hydroxyl group (-OH) or a thiol group (-SH).

[0031] The above hydrocarbon group constitutes the cyclic skeleton -CH ２- Or -CH=, one or more of which may be replaced by -O-, -S-, -NH-, or -N=, may have a heterocyclic structure. The hydrocarbon group may have a heteroaryl group or a heteroarylene group. The hydrocarbon group may have a polycyclic structure in which two or more rings are condensed.

[0032] R １ and R ２ may each independently have a structure represented by -R Ｃ -X-R Ｄ Here, R Ｃ represents a single bond or a divalent alkylene group, alkenylene group, arylene group, heteroarylene group, aralkylen group, or heteroaralkylen group having x carbon atoms (x is an integer of 1 or more) to which a halogen atom may be bonded; R Ｄ represents a hydrogen atom or an alkyl group, alkenyl group, aryl group, heteroaryl group, aralkyl group, or heteroaralkyl group having y carbon atoms (y is an integer of 1 or more) to which a halogen atom may be bonded; X represents O, S, NH, CO, SO, SO ２ , COO, SOO, or SO ２ O, and x + y does not exceed 12.

[0033] R Ｃ When represents a divalent alkylene group, alkenylene group, arylene group, heteroarylene group, aralkylen group, or heteroaralkylen group having x carbon atoms (x is an integer of 1 or more) to which a halogen atom may be bonded, its carbon number may be within the range of 1 to 12, may be within the range of 1 to 8, may be within the range of 1 to 5, or may be within the range of 1 to 3. Here, an arylene group is a divalent group obtained by removing two hydrogen atoms from an aromatic compound excluding an aromatic heterocyclic compound. A heteroarylene group is a divalent group obtained by removing two hydrogen atoms from an aromatic heterocyclic compound. An aralkylen group is a divalent group formed by bonding an alkylene group and an arylene group. A heteroaralkylen group is a divalent group formed by bonding an alkylene group and a heteroarylene group.

[0034] RＤ When represents an alkyl group, alkenyl group, aryl group, heteroaryl group, aralkyl group, or heteroaralkyl group having y carbon atoms (y being an integer of 1 or more) to which a halogen atom may be bonded, the number of carbon atoms may be in the range of 1 to 12, 1 to 8, 1 to 5, or 1 to 3. Here, an aryl group is a monovalent group obtained by removing one hydrogen atom from an aromatic compound, excluding aromatic heterocyclic compounds. A heteroaryl group is a monovalent group obtained by removing one hydrogen atom from an aromatic heterocyclic compound. An aralkyl group is a monovalent group formed by the bonding of an alkylene group and an aryl group. A heteroaralkyl group is a monovalent group formed by the bonding of an alkylene group and a heteroaryl group.

[0035] R １ and R ２ These may be the same group or different groups. For example, R １ and R ２ Both may be a hydrogen atom, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a pentyl group, a hexyl group, a phenyl group, or a benzyl group. Also, R １ is a methyl group, R ２ R may be an ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, hexyl group, phenyl group, or benzyl group. Furthermore, R １ is an ethyl group, R ２ R may be an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a pentyl group, a hexyl group, a phenyl group, or a benzyl group. In one embodiment, R １ and R ２ One of them may be a hydrogen atom, and the other may be a cyano group or a hydrocarbon group having 1 to 12 carbon atoms as described above. １ and R ２ The combinations are not limited to those mentioned above.

[0036] R １ and R２ These may together represent a divalent hydrocarbon group with 2 to 24 carbon atoms. In that case, R １ and R ２ The adjacent nitrogen atom and the carbon atom form a ring. The number of carbon atoms in the above divalent hydrocarbon group is preferably 3 to 12, preferably 4 to 10, and more preferably 4 to 6. １ and R ２ The group formed by the bonding of these elements may be a divalent saturated hydrocarbon group or a divalent linear alkylene group. １ and R ２ The group formed by the bonding of these elements may be, for example, a propylene group, a butylene group, a pentylene group, a hexylene group, a heptylene group, or an octylene group.

[0037] The above divalent hydrocarbon group may contain a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ Further groups may be bonded. The above divalent hydrocarbon group may have one or more of these halogen atoms or groups bonded to it. Examples of halogen atoms that may be bonded to the above divalent hydrocarbon group include at least one selected from the group consisting of fluorine, chlorine, bromine, and iodine atoms. The above divalent hydrocarbon group may be substituted with, for example, 1 to 9 halogen atoms, 1 to 6 halogen atoms, or 1 to 3 halogen atoms. The above divalent hydrocarbon group may have -NR Ａ R Ｂ When a group is bonded, R Ａ and R Ｂ Each of these is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Ａ and R Ｂ Each is preferably independently a hydrogen atom or a methyl group. Furthermore, a cyano group or -NR Ａ R Ｂ Carbon atoms that may be included in the group are not counted in the carbon number of the divalent hydrocarbon group mentioned above.

[0038] The above divalent hydrocarbon group is -CH２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ It may be replaced by -, and one or more -CH= may be replaced by -N=. In this case, the replaced -O-, -S-, -CO-, -SO-, -SO ２ - and -N= are counted as one carbon atom in the carbon number of the divalent hydrocarbon group. Preferably, -O- and -S- are not adjacent to other -O- or -S- groups.

[0039] The above divalent hydrocarbon group is, for example, adjacent to -CH ２ One of the hyphens is replaced with -O-, and the other is replaced with -CO-, -SO-, or -SO ２ -By being managed, -OCO-, -COO-, -OSO-, -SOO-, -OSO ２ -, or -SO ２ It may have at least one substructure selected from O-. The above divalent hydrocarbon group is, for example, a methyl group (-CH ３ ) -CH ２ The - portion may be replaced with -O- or -S-, thereby giving the compound a hydroxyl group (-OH) or a thiol group (-SH).

[0040] The above divalent hydrocarbon group constitutes the cyclic skeleton -CH ２ The divalent hydrocarbon group may have a heterocyclic structure by replacing one or more of the - or -CH= groups with -O-, -S-, -NH-, or -N=. The divalent hydrocarbon group may have a heteroaryl group or a heteroarylene group. The divalent hydrocarbon group may have a polycyclic structure in which two or more rings are fused together.

[0041] Examples of fluorine-containing pyrimidone compounds of the present invention are listed below, but the present invention is not limited to these.

[0042]

[0043]

[0044] (Applications) The fluorine-containing pyrimidone compounds having an amino group of the present invention are useful in the fields of pharmaceuticals, agrochemicals, and organic electronic materials, and can also be used as intermediates for obtaining further useful compounds. The fluorine-containing pyrimidone compounds having an amino group of the present invention may also be used in the form of salts. Examples of salts in this case include hydrochloride, hydroiodide, hydrobromide, acetate, and sulfate.

[0045] Applications of the amino group-containing fluorine pyrimidone compounds or derivatives of the present invention in the field of agrochemicals include, for example, use as a fungal control agent, an arthropod control agent, and a herbicide. For example, the amino group-containing fluorine pyrimidone compounds of the present invention can be used as a fungal control agent for various cultivated plants such as wheat, rye, barley, oats, rice, corn, pasture grass, bananas, cotton, soybeans, coffee plants, sugarcane, grapevines, fruit trees, and ornamental plants; vegetables such as cucumbers, beans, tomatoes, potatoes, and melons; and numerous fungi that infest the seeds of these plants.

[0046] The fluorine-containing pyrimidone compounds or derivatives having an amino group of the present invention are suitable for controlling the following plant diseases caused by harmful fungi, for example: rice blast (Primularia oryzae), sesame leaf spot (Cochliobolus miyabeanus), sheath blight (Rizoctonia solani), etc.; wheat powdery mildew (Erysiphe graminis), Fusarium head blight (Gibberella zeae), (red) rust (Puccinia striiformis, P. graminis, P. recondita, P. hordei), snow mold (Typhula sp., Micronectriella) Examples include: nivaris, smut (Ustilago tritici, U. nuda), smut (Tilletia caries), eye spot disease (Pseudocercosporella herpotrichoide), cloudy spot disease (Rhynchosporium secalis), leaf blight (Septoria tritici), rot (Leptosphaeria nodorum), reticulated spot disease (Pyrenophora teres), and leopard spot disease (Helminthosporium zonatum Ikata); black spot disease of citrus fruits (Diaporthe citri), scab (Elsinoe) Fawcetti, fruit rot (Penicillium digitatum, P. italicum), brown rot (Phytophora citrophora, P. nicotianae), black spot (Phyllostictina citricarpa), canker (Xanthomonas citri), etc.Apple diseases such as Monilinia mali, Valsa mali, powdery mildew (Podosphaera leucotricha), Alternaria mali, black spot (Venturia inaequalis), black spot (Mycospherella pomi), anthracnose (Colletotrichum acutatum), ring spot (Botryosphaeria berengeriana), cedar-apple rust (Gymnosporangium yamadae), and gray mold (Monilinia fructicola); and pear black spot (Venturia nashicola). V. pirina), black spot disease (Alternaria kikuchiana), cedar-apple rust (Gymnosporangium hareanum), gray mold (Monilinia fructicola), etc.; peach gray mold (Monilinia fructicola), black spot disease (Cladosporium caepophilum), Phomopsis rot (Phomopsis sp.), etc.; grape black rot (Elinoe ampelina), late blight (Colletotrichum acutatum), powdery mildew (Uncinula necaator), rust (Phakopsora) Examples include: Ampelopsidis, black rot (Guignardia bidwellii), downy mildew (Plasmopara viticola), gray mold (Monilinia fructigena), black spot (Cladosporium viticolum), gray mold (Botrytis cinerea), etc.; anthracnose of persimmons (Gloeosporium kaki), leaf spot (Cercospora kaki, Mycoshaerella nawae); anthracnose of cucurbits (Colletotrichum lagenarium), powdery mildew (Sphaerotheca fuliginea, Examples include Oidiopsis taurica, Didymella bryoniae, Fusarium oxysporum, downy mildew (Pseudoperonospora cubensis), blight (Phytophthora sp.), and Pythium sp.;Tomato ring spot disease (Alternaria solani), leaf mold (Cadosporium fluvum), late blight (Phytophora infestans), stem rot (Fusarium solani), etc.; Eggplant brown spot disease (Phomopsis vexans), powdery mildew (Erysiphe cichoraceaum), etc.; Brassicaceae black spot disease (Alternaria japonica), white spot disease (Cercosporella brassicae), soft rot (Erwinia carotovora), etc.; Leek rust disease (Puccinia allii), etc.; Soybean purple spot disease (Cercospora) Examples of diseases include: kikuchii, black rot (Elsinoe gycyneses), black spot (Diaporthe phaseolorum var. sojae); anthracnose of green beans (Colletotrichum lindemthianum); black spot of peanuts (Cercospora personata), brown spot (Cercospora arachidicola); powdery mildew of peas (Erysiphe pisi); late blight of potatoes (Alternaria solani), late blight (Phytophora infestans), leaf blight (Rhizoctonia) (solani), etc.; powdery mildew of strawberries (Sphaerrotheca humuli), etc.; net-like blight of tea plants (Exobasidium reticulatum), white spot disease (Elsinoe leucospila), etc.; cedar-apple rust of tobacco plants (Alternaria longipes), powdery mildew (Erysiphe cichoraceaum), anthracnose (Colletotrichum tabacum), downy mildew (Peronospora tabacina), late blight (Phytophora nicotianae), wildfire (Pseudomonus syringae), etc.; brown spot disease of sugar beets (Cercospora Examples include beticola, seedling blight (Aphanomyces cochliodes), rose black spot (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa), etc.Chrysanthemum brown spot disease (Septoria chrysanthemi-indici), white rust disease (Puccinia horiana), etc.; gray mold (Botrytis cinerea), sclerotinia rot (Sclerotinia sclerotiorum), etc. in various crops.

[0047] When actually applying the harmful fungal control agent, the amino group-containing fluorine pyrimidone compound or its derivative of the present invention may be used in its pure form without adding other components, or it may be used in any form that a general pesticide can take, namely solid formulations such as granules, powders, broad-area sprays, or powdered products; or liquid formulations such as wettable powders, emulsions, aqueous solutions, solutions, pastes, oil dispersions, dispersion formulations, emulsion formulations, oils, aerosols, sprays, or flowable formulations. The application form will depend on the specific purpose, but in each case, it is preferable that the amino group-containing fluorine pyrimidone compound or its salt of the present invention is finely and uniformly dispersed.

[0048] A fungal control agent may be prepared, for example, by applying the amino group-containing fluorine pyrimidone compound or a derivative thereof of the present invention to a solvent and / or on a solid carrier, using auxiliary agents such as emulsifiers and dispersants as needed.

[0049] [Method for producing fluorine-containing pyrimidone compounds] The following describes in detail a method for producing fluorine-containing pyrimidone compounds represented by the following general formula (1), which includes a step of reacting a guanidine compound represented by the following general formula (2) or a salt thereof with a fluorine-containing compound represented by the following general formula (3) or (4).

[0050]

[0051]

[0052]

[0053] (In general formulas (1) to (4), R １ and R ２ Each of these independently represents a hydrogen atom, a cyano group, or a hydrocarbon group having 1 to 12 carbon atoms, where the hydrocarbon group is -CH ２One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the hydrocarbon group may have one or more -CH= replaced by -N=, and the hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ Further groups may be bonded, where R Ａ and R Ｂ Each is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, or; R １ and R ２ Together, these represent a divalent hydrocarbon group having 2 to 24 carbon atoms, where the divalent hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the divalent hydrocarbon group may have one or more -CH= replaced by -N=, and the divalent hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ The group may be further bonded; R ３ (This represents a hydrocarbon group with 1 to 12 carbon atoms.)

[0054] According to this method, by having the above steps, it is possible to produce a fluorine-containing pyrimidone compound represented by general formula (1) without using chlorine-based solvents that have a high environmental impact, such as chloroform or dichloromethane.

[0055] In one embodiment, a guanidine compound represented by general formula (2) or a salt thereof is reacted with a fluorine-containing compound represented by general formula (3). In another embodiment, a guanidine compound represented by general formula (2) or a salt thereof is reacted with a fluorine-containing compound represented by general formula (4).

[0056] In one embodiment, a guanidine compound represented by general formula (2) or a salt thereof, and a fluorine-containing compound represented by general formula (3) or (4) are introduced as raw materials. In this specification, "introducing a compound as a raw material" means introducing or adding the compound itself into the system. Therefore, it should be noted that in a particular embodiment in which a compound is introduced as a raw material, there are no embodiments in which the compound is not introduced or added into the system, but is generated only by a chemical reaction in the system.

[0057] R １ , R ２ and R ３ The hydrocarbon groups having 1 to 12 carbon atoms that each of these independently represents are not particularly limited as long as they are hydrocarbon groups consisting of carbon atoms and hydrogen atoms having 1 to 12 carbon atoms, and include linear hydrocarbon groups, aromatic hydrocarbon groups, alicyclic hydrocarbon groups, etc. The linear hydrocarbon group is not particularly limited as long as the total number of carbon atoms is 1 to 12, and may be a straight-chain hydrocarbon group or a branched-chain hydrocarbon group. The aromatic hydrocarbon group is not particularly limited as long as the total number of carbon atoms is 6 to 12, and may be an aromatic hydrocarbon group with substituents or an aromatic hydrocarbon group without substituents. In this case, substituents are R １ , R ２ , R ３ The hydrocarbon substituents may be such that the total number of carbon atoms falls within the range of 6 to 12. Furthermore, the aromatic hydrocarbon group may have a condensed polycyclic structure. The alicyclic hydrocarbon group is not particularly limited as long as the total number of carbon atoms is between 3 and 12, and may be an alicyclic hydrocarbon group with substituents or an alicyclic hydrocarbon group without substituents. In this case, substituents refer to R １ , R ２ , R ３ The hydrocarbon substituents may be such that the total number of carbon atoms falls within the range of 3 to 12. Furthermore, the alicyclic hydrocarbon group may have a cross-linked ring structure. The hydrocarbon group having 1 to 12 carbon atoms may be an aralkyl group such as a benzyl group.

[0058] The above hydrocarbon group may contain a halogen atom, a cyano group, a nitro group, or -NR Ａ RＢ Further groups may be bonded. The hydrocarbon group may have one or more of these halogen atoms or groups bonded to it. Examples of halogen atoms that may be bonded to the hydrocarbon group include at least one selected from the group consisting of fluorine, chlorine, bromine, and iodine atoms. The hydrocarbon group may be substituted with, for example, 1 to 9 halogen atoms, 1 to 6 halogen atoms, or 1 to 3 halogen atoms. The hydrocarbon group may also have -NR Ａ R Ｂ When a group is bonded, R Ａ and R Ｂ Each of these is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Ａ and R Ｂ Each is preferably independently a hydrogen atom or a methyl group. Furthermore, a cyano group or -NR Ａ R Ｂ Carbon atoms that may be included in the group are not counted in the carbon number of the hydrocarbon group mentioned above.

[0059] In this method, R １ and R ２ It should be noted that there is no restriction that it must not be a methyl group at the same time. １ and R ２ Both may be methyl groups.

[0060] R １ , R ２ and R ３Examples of chain-like hydrocarbon groups that each of these groups independently represents include alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl groups; alkenyl groups such as ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, and dodecenyl groups; and alkynyl groups such as ethinyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octinyl, noninyl, desynyl, undecynyl, and dodecynyl groups.

[0061] R １ , R ２ and R ３ Examples of aromatic hydrocarbon groups that can be independently represented by each include phenyl, benzyl, tolyl, and naphthyl groups. The tolyl group may be any of o-tolyl, m-tolyl, or p-tolyl groups.

[0062] R １ , R ２ and R ３ The alicyclic hydrocarbon groups that each of these independently represents include saturated or unsaturated cyclic hydrocarbon groups. Examples of cyclic hydrocarbon groups include cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, adamantyl, and norbornyl groups.

[0063] R １ , R ２ and R ３ The groups that each of these independently represents are preferably chain hydrocarbon groups or aromatic hydrocarbon groups, more preferably chain hydrocarbon groups or aromatic hydrocarbon groups having 1 to 8 carbon atoms, and even more preferably alkyl groups or aromatic hydrocarbon groups having 1 to 8 carbon atoms. In particular, R １ and R ２The groups that each of these independently represents are more preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl, phenyl, or benzyl groups, particularly preferably methyl, ethyl, n-propyl, isopropyl, isobutyl, s-butyl, t-butyl, or benzyl groups, and most preferably methyl, ethyl, isopropyl, or benzyl groups. ３ More preferably, the group is a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, hexyl group, or benzyl group; particularly preferably, a methyl group, ethyl group, n-propyl group, isopropyl group, isobutyl group, s-butyl group, or t-butyl group; and most preferably, a methyl group or an ethyl group.

[0064] The above hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ It may be replaced by -, and one or more -CH= may be replaced by -N=. In this case, the replaced -O-, -S-, -CO-, -SO-, -SO ２ - and -N= are counted as one carbon atom in the carbon number of the hydrocarbon group. Preferably, -O- and -S- are not adjacent to other -O- or -S-.

[0065] The above hydrocarbon group is, for example, adjacent to -CH ２ One of the hyphens is replaced with -O-, and the other is replaced with -CO-, -SO-, or -SO ２ -By being managed, -OCO-, -COO-, -OSO-, -SOO-, -OSO ２ -, or -SO ２ It may have at least one substructure selected from O-. The hydrocarbon group is, for example, a methyl group (-CH ３ ) -CH ２ The - portion may be replaced with -O- or -S-, thereby giving the compound a hydroxyl group (-OH) or a thiol group (-SH).

[0066] The above hydrocarbon group constitutes the cyclic skeleton -CH ２ The hydrocarbon group may have a heterocyclic structure by replacing one or more of the - or -CH= groups with -O-, -S-, -NH-, or -N=. The hydrocarbon group may have a heteroaryl group or a heteroarylene group. The hydrocarbon group may have a polycyclic structure in which two or more rings are fused together.

[0067] R １ and R ２ Each of these is independently of -R Ｃ -X-R Ｄ It may have a structure represented by R. Ｃ R represents a single bond or a divalent alkylene group, alkenylene group, arylene group, heteroarylene group, aralkylene group, or heteroaralkylene group with x carbon atoms (where x is an integer of 1 or more) that may have a halogen atom bonded to it; Ｄ represents a hydrogen atom, or an alkyl, alkenyl, aryl, heteroaryl, aralkyl, or heteroaralkyl group having y carbon atoms (where y is an integer of 1 or more) that may have a halogen atom bonded to it; X is O, S, NH, CO, SO, SO ２ COO, SOO, or SO ２ It represents O, and x + y does not exceed 12.

[0068] R ＣWhen x represents a divalent alkylene group, alkenylene group, arylene group, heteroarylene group, aralkylene group, or heteroaralkylene group having x carbon atoms (where x is an integer of 1 or more) to which halogen atoms may be bonded, the number of carbon atoms may be in the range of 1 to 12, in the range of 1 to 8, in the range of 1 to 5, or in the range of 1 to 3. Here, an arylene group is a divalent group obtained by removing two hydrogen atoms from aromatic compounds, excluding aromatic heterocyclic compounds. A heteroaralkylene group is a divalent group obtained by removing two hydrogen atoms from aromatic heterocyclic compounds. An aralkylene group is a divalent group formed by the bonding of an alkylene group and an arylene group. A heteroaralkylene group is a divalent group formed by the bonding of an alkylene group and a heteroarylene group.

[0069] R Ｄ When represents an alkyl group, alkenyl group, aryl group, heteroaryl group, aralkyl group, or heteroaralkyl group having y carbon atoms (y being an integer of 1 or more) to which a halogen atom may be bonded, the number of carbon atoms may be in the range of 1 to 12, 1 to 8, 1 to 5, or 1 to 3. Here, an aryl group is a monovalent group obtained by removing one hydrogen atom from an aromatic compound, excluding aromatic heterocyclic compounds. A heteroaryl group is a monovalent group obtained by removing one hydrogen atom from an aromatic heterocyclic compound. An aralkyl group is a monovalent group formed by the bonding of an alkylene group and an aryl group. A heteroaralkyl group is a monovalent group formed by the bonding of an alkylene group and a heteroaryl group.

[0070] R １ and R ２ These may be the same group or different groups. For example, R １ and R ２ Both may be a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a pentyl group, a hexyl group, a phenyl group, or a benzyl group. Also, R １ is a methyl group, R ２R may be an ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, hexyl group, phenyl group, or benzyl group. Furthermore, R １ is an ethyl group, R ２ R may be an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a pentyl group, a hexyl group, a phenyl group, or a benzyl group. In one embodiment, R １ and R ２ One of them may be a hydrogen atom, and the other may be a cyano group or a hydrocarbon group having 1 to 12 carbon atoms as described above. １ and R ２ The combinations are not limited to those mentioned above.

[0071] R １ and R ２ These may together represent a divalent hydrocarbon group with 2 to 24 carbon atoms. In that case, R １ and R ２ The adjacent nitrogen atom and the carbon atom form a ring. The number of carbon atoms in the above divalent hydrocarbon group is preferably 3 to 12, preferably 4 to 10, and more preferably 4 to 6. １ and R ２ The group formed by the bonding of these elements may be a divalent saturated hydrocarbon group or a divalent linear alkylene group. １ and R ２ The group formed by the bonding of these elements may be, for example, a propylene group, a butylene group, a pentylene group, a hexylene group, a heptylene group, or an octylene group.

[0072] The above divalent hydrocarbon group may contain a halogen atom, a cyano group, a nitro group, or -NR Ａ R ＢFurther groups may be bonded. The above divalent hydrocarbon group may have one or more of these halogen atoms or groups bonded to it. Examples of halogen atoms that may be bonded to the above divalent hydrocarbon group include at least one selected from the group consisting of fluorine, chlorine, bromine, and iodine atoms. The above divalent hydrocarbon group may be substituted with, for example, 1 to 9 halogen atoms, 1 to 6 halogen atoms, or 1 to 3 halogen atoms. The above divalent hydrocarbon group may have -NR Ａ R Ｂ When a group is bonded, R Ａ and R Ｂ Each of these is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Ａ and R Ｂ Each is preferably independently a hydrogen atom or a methyl group. Furthermore, a cyano group or -NR Ａ R Ｂ Carbon atoms that may be included in the group are not counted in the carbon number of the divalent hydrocarbon group mentioned above.

[0073] The above divalent hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ It may be replaced by -, and one or more -CH= may be replaced by -N=. In this case, the replaced -O-, -S-, -CO-, -SO-, -SO ２ - and -N= are counted as one carbon atom in the carbon number of the divalent hydrocarbon group. Preferably, -O- and -S- are not adjacent to other -O- or -S- groups.

[0074] The above divalent hydrocarbon group is, for example, adjacent to -CH ２ One of the hyphens is replaced with -O-, and the other is replaced with -CO-, -SO-, or -SO ２ -By being managed, -OCO-, -COO-, -OSO-, -SOO-, -OSO ２ -, or -SO ２It may have at least one substructure selected from O-. The above divalent hydrocarbon group is, for example, a methyl group (-CH ３ ) -CH ２ The - portion may be replaced with -O- or -S-, thereby giving the compound a hydroxyl group (-OH) or a thiol group (-SH).

[0075] The above divalent hydrocarbon group constitutes the cyclic skeleton -CH ２ The divalent hydrocarbon group may have a heterocyclic structure by replacing one or more of the - or -CH= groups with -O-, -S-, -NH-, or -N=. The divalent hydrocarbon group may have a heteroaryl group or a heteroarylene group. The divalent hydrocarbon group may have a polycyclic structure in which two or more rings are fused together.

[0076] The compounds represented by general formulas (2) to (4) may be commercially available or manufactured by known methods. The compound represented by general formula (2) may be used as a salt. Examples of salts in this case include hydrochloride, hydroiodide, hydrobromide, acetate, and sulfate.

[0077] In this method, the reaction may be carried out in the presence of an organic solvent. Examples of organic solvents that can be used include ethers such as tetrahydrofuran, diethyl ether, diisopropyl ether, dioxane, monoglyme, diglyme, triglyme, and tetraglyme; aliphatic hydrocarbons such as hexane, heptane, octane, and isooctane; aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene; nitriles such as acetonitrile; and aprotic polar solvents such as dimethylformamide, dimethylacetamide, methylpyrrolidone, dimethylethylene urea, tetramethylurea, dimethyl sulfoxide, and sulfolane. Mixed solvents of these may also be used. The reaction may be carried out using a two-phase solution of water and an organic solvent. It is preferable to carry out the reaction without using chlorine-based solvents such as chloroform or dichloromethane.

[0078] In this method, the reaction may be carried out in the presence of a basic substance. Examples of basic substances that can be used include alkali metal / alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, magnesium hydroxide, and barium hydroxide; alkali metal / alkaline earth metal carbonates such as sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate; metal hydrides such as sodium hydride, potassium hydride, and calcium hydride; tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine, diazabicycloundecene, 7-methyl-1,5,7-triazabicyclo[4.4.0]deca-5-ene, 2-tert-butyl-1,1,3,3-tetramethylguanidine, and N,N-dimethylaniline; and phosphazene bases such as P1-t-Bu, P2-t-Bu, P3-t-Bu, and P4-t-Bu.

[0079] The reaction temperature in this method is preferably -20°C or higher and below the boiling point of the organic solvent, more preferably 0 to 50°C, and even more preferably 10 to 30°C. The reaction time in this method is preferably 0.5 to 48 hours, more preferably 1 to 36 hours, and even more preferably 10 to 30 hours.

[0080] Although some embodiments of the present invention have been described above, the present invention is not limited to the above embodiments and includes all aspects included in the concept and claims of the present invention, and can be modified in various ways within the scope of the present invention.

[0081] The present invention will be described in more detail below with reference to examples, but the present invention is not limited in any way by these examples.

[0082] (Example 1) [Preparation of 2-dimethylamino-6-fluoro-5-trifluoromethyl-4-pyrimidone] To a two-phase solution of 100 g of water and 100 g of diisopropyl ether, under ice water cooling, 1.0 g (3.7 mmol) of 1,1-dimethylguanidine sulfate and 1.5 g (7.3 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate were added. Subsequently, 4.4 ml (22 mmol) of 5 M aqueous sodium hydroxide solution was added dropwise, ensuring that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After stirring at room temperature for 24 hours, 1 M hydrochloric acid was added until the contents became neutral, and the organic phase was recovered. The organic phase was dehydrated with anhydrous sodium sulfate, the solvent was removed by vacuum distillation, the residue was dissolved in ethyl acetate, and the compound was purified by silica gel column in a hexane:ethyl acetate = 7:3 mixed solvent to obtain 0.5 g of the following compound. The isolation yield was 31%.

[0083]

[0084] The analysis results were as follows: Mass spectrum (APCI, m / z): 225 ([M] ＋ )

[0085] (Example 2) [Preparation of 2-diethylamino-6-fluoro-5-trifluoromethyl-4-pyrimidone] Under ice water cooling, 1.0 g (8.7 mmol) of 1,1-diethylguanidine and 1.1 g (8.7 mmol) of diisopropylethylamine were added to 100 g of MeCN. Subsequently, 1.7 g (8.7 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)propenoate was added dropwise, ensuring that the internal temperature did not exceed 10°C, and the mixture was heated to room temperature. After stirring at room temperature for 16 hours, the solvent was removed by vacuum distillation, the residue was dissolved in ethyl acetate, and the compound was purified by silica gel column in a hexane:ethyl acetate = 7:3 mixed solvent to obtain 0.2 g of the following compound. The isolation yield was 9%.

[0086]

[0087] The analysis results were as follows: Mass spectrum (APCI, m / z): 253 ([M] ＋ )

[0088] (Example 3) [Preparation of (6-fluoro-5-trifluoromethyl-4-pyrimidon-2-yl)carbamate-1,1-dimethylethyl ester] To a mixed solution of 50 g THF and 50 g MeCN under ice water cooling, 1.4 g (8.7 mmol) of 1-(t-butoxycarbonyl)guanidine and 1.1 g (8.7 mmol) of diisopropylethylamine were added. Subsequently, 1.7 g (8.7 mmol) of methyl 3,3-difluoro-2-(trifluoromethyl)propenoate was added dropwise, ensuring that the internal temperature did not exceed 10°C, and the temperature was raised to room temperature. After stirring at room temperature for 16 hours, the solvent was removed by vacuum distillation, the residue was dissolved in ethyl acetate, and the compound was purified by silica gel column in a hexane:ethyl acetate = 7:3 mixed solvent to obtain 0.3 g of the following compound. The isolation yield was 11%.

[0089]

[0090] The analysis results were as follows: Mass spectrum (APCI, m / z): 297 ([M] ＋ ) １ H-NMR (400MHz, CDCl ３ ) δppm: 1.55 (s, 9H)

[0091] (Example 4) [Preparation of 2-(3,5-dimethyl-1H-pyrazole-1-yl)-6-fluoro-5-trifluoromethyl-4(3H)-pyrimidone] 1.1 g (5.3 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate and 1.1 g (5.2 mmol) of 3,5-dimethylpyrazole-1-carboxyamidine nitrate were added to a two-phase solution of 25 ml of water and 25 ml of diisopropyl ether. The mixture was cooled to 0°C, 4.6 ml (23.0 mmol) of 5 M aqueous sodium hydroxide solution was added dropwise, and the mixture was heated to room temperature. After stirring at room temperature for 44 hours, the mixture was extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate. The solvent was removed by vacuum distillation, the residue was dissolved in ethyl acetate, and 0.2 g of the following compound was obtained by silica gel column purification. The isolation yield was 15%.

[0092]

[0093] The analysis results were as follows: Mass spectrum (APCI, m / z): 276 ([M] ＋ ) 1H-NMR (400MHz, CDCl ３ ) δppm: 10.60 (br, 1H), 6.12 (s, 1H), 2.66 (s, 3H), 2.27 (s, 3H)

[0094] (Example 5) [Preparation of 2-(ethylmethylamino)-6-fluoro-5-trifluoromethyl-4(3H)-pyrimidone] 1.1 g (5.3 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate and 0.6 g (5.8 mmol) of N-ethyl-N-methylguanidine were added to a two-phase solution of 26 ml of water and 26 ml of diisopropyl ether. The mixture was cooled to 0°C, 4.7 ml (23.5 mmol) of 5 M aqueous sodium hydroxide solution was added dropwise, and the mixture was heated to room temperature. After stirring at room temperature for 27 hours, 1 M hydrochloric acid was added until the contents became neutral, and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate. The solvent was removed by vacuum distillation, the residue was dissolved in ethyl acetate, and the following compounds were obtained in trace amounts by silica gel column purification.

[0095]

[0096] The analysis results were as follows: Mass spectrum (APCI, m / z): 238 ([M-H] － )

[0097] (Example 6) [Preparation of 6-fluoro-2-(4-morpholinyl)-5-trifluoromethyl-4(3H)-pyrimidone] 1.0 g (4.8 mmol) of methyl 3,3,3-trifluoro-2-(trifluoromethyl)propanoate and 1.0 g (4.9 mmol) of morpholin-4-carboxyimidamide bromide were added to a two-phase solution of 30 ml of water and 30 ml of diisopropyl ether. The mixture was cooled to 0°C, 4.3 ml (21.5 mmol) of 5 M aqueous sodium hydroxide solution was added dropwise, and the mixture was heated to room temperature. After stirring at room temperature for 24.1 hours, 1 M hydrochloric acid was added until the contents became neutral, and the mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, the residue was dissolved in ethyl acetate, and silica gel column purification was performed to obtain 12 mg of the crude product of the following compound.

[0098]

[0099] The analysis results were as follows: Mass spectrum (APCI, m / z): 368 ([M+H] ＋ )

[0100] From the above, it can be seen that the novel fluorine-containing pyrimidone compound of the present invention can be produced.

[0101] The fluorine-containing pyrimidone compounds and their production methods of the present invention are suitably applicable in the fields of pharmaceuticals, agrochemicals, and organic electronic materials. Furthermore, because the fluorine-containing pyrimidone compounds of the present invention have numerous substituents and high structural expandability, they can also be used as intermediates for various useful compounds.

Claims

1. A fluorine-containing pyrimidone compound represented by the following general formula (1). (In general formula (1), R １ and R ２ each independently represent a hydrogen atom, a cyano group, or a hydrocarbon group having 1 to 12 carbon atoms. Here, in the hydrocarbon group, one or more of -CH ２ - may be replaced by -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ -. The hydrocarbon group may have one or more of -CH= replaced by -N=. The hydrocarbon group may further have a halogen atom, a cyano group, a nitro group, or a -NR Ａ R Ｂ group attached thereto. Here, R Ａ and R Ｂ are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, provided that R １ and R ２ are not simultaneously methyl groups, or; R １ and R ２ together represent a divalent hydrocarbon group having 2 to 24 carbon atoms. Here, in the divalent hydrocarbon group, one or more of -CH ２ - may be replaced by -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ -. The divalent hydrocarbon group may have one or more of -CH= replaced by -N=. The divalent hydrocarbon group may further have a halogen atom, a cyano group, a nitro group, or a -NR Ａ R Ｂ group attached thereto.) 2. A method for producing a fluorine-containing pyrimidone compound represented by the following general formula (1), comprising the step of reacting a guanidine compound represented by the following general formula (2) or a salt thereof with a fluorine-containing compound represented by the following general formula (3) or (4). (In general formulas (1) to (4), R １ and R ２ Each of these independently represents a hydrogen atom, a cyano group, or a hydrocarbon group having 1 to 12 carbon atoms, where the hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the hydrocarbon group may have one or more -CH= replaced by -N=, and the hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ Further groups may be bonded, where R Ａ and R Ｂ Each is independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, or; R １ and R ２ Together, these represent a divalent hydrocarbon group having 2 to 24 carbon atoms, where the divalent hydrocarbon group is -CH ２ One or more hyphens are -O-, -S-, -NH-, -CO-, -SO-, or -SO ２ - may be replaced by -N=, and the divalent hydrocarbon group may have one or more -CH= replaced by -N=, and the divalent hydrocarbon group may have a halogen atom, a cyano group, a nitro group, or -NR Ａ R Ｂ The group may be further bonded; R ３ (This represents a hydrocarbon group with 1 to 12 carbon atoms.) 3. The manufacturing method according to claim 2, comprising the step of reacting a guanidine compound represented by general formula (2) or a salt thereof with a fluorine-containing compound represented by general formula (3).

4. The manufacturing method according to claim 2, comprising the step of reacting a guanidine compound represented by general formula (2) or a salt thereof with a fluorine-containing compound represented by general formula (4).

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