JP2003081970A - 5-pyridylmethylhydantoin and method of producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a simple, safe and inexpensive method of producing a 5-pyridylmethylhydantoin suitable as a synthetic intermediate for a 2- amino-3-(pyridyl)propionic acid. SOLUTION: The 5-pyridylmethylenehydantoin represented by general formula [1] (wherein R is H, a halogen, an alkyl, a haloalkyl, an alkoxy, a haloalkoxy, an alkylthio, an alkyl-sulfonyl or an alkoxycarbonyl; the bonding position between the pyridine ring and the hydantoin moiety is 2, 3 or 4 positions on the pyridine ring) is catalytically hydrogenated in the presence of a metal catalyst to give 5-pyridylmethyl-hidantoin represented by general formula [2] (wherein R and the bonding position between the pyridine ring and the hydantoin moiety corresponds to that in the general formula [1]).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a 5-pyridylmethylhydantoin compound useful as a raw material for producing pharmaceuticals, agricultural chemicals and the like, and a method for producing a 5-pyridylmethylenehydantoin compound which is a precursor thereof.

[0002]

2. Description of the Related Art In recent years, 2-amino-3- (pyridyl) propionic acid [β-pyridylalanine] derivatives have become increasingly important as a constituent raw material of pharmaceuticals represented by luteinizing hormone-releasing hormone antagonists (LHRH). It is an emerging compound (WO92 / 08733 publication pamphlet). In particular,
2-Amino-3- (3-pyridyl) propionic acid [β-
LHRH using (3-pyridyl) alanine as a raw material
Is attracting attention because its antiovulatory activity is about 3 times stronger than that of the 2-pyridyl derivative (US Pat. No. 4,504,414). Although many methods for synthesizing the above 2-amino-3- (pyridyl) propionic acid derivative are known, a method of hydrolyzing or microbially degrading 5-pyridylmethylenehydantoin or 5-pyridylmethylhydantoin as a raw material for production is effective. It is a synthetic method. Among them, the synthesis method using 5-pyridylmethylenehydantoin is described in, for example, Archiv der Pharmazie, 291. 436. (1958), 5
A method for directly synthesizing 2-amino-3- (pyridyl) propionic acid [β-pyridylalanine] by heating -pyridylmethylenehydantoin to 100 ° C in an aqueous ammonium sulfide solution is described. It is not a suitable method to carry out industrially. Further, regarding the synthetic method using 5-pyridylmethylhydantoin,
First, it is necessary to synthesize this compound. For example, there is a method of reducing 5-pyridylmethylenehydantoin to synthesize 5-pyridylmethylhydantoin. However, in this reduction reaction, the raw material compound is insoluble in various organic solvents, and thus far there has been a problem in reduction with hydrogen. further,
The 5-pyridylmethylenehydantoin compound, which is required in any of the synthetic methods, can be produced from inexpensive hydantoin and pyridine aldehyde, but the conventional production methods have problems such as low yield. Eg Ar
In chiv der Pharmazie, 291. 436. (1958),
Although hydantoin and pyridine-3-aldehyde are subjected to a condensation reaction in the presence of sodium hydroxide to synthesize 5- (3-pyridyl) methylenehydantoin, the yield is not satisfactory at 42%, and further, It is described that 5- (4-pyridyl) methylenehydantoin cannot be obtained by this reaction. Also, U.S. Pat.No. 2,861,079
Although the specification describes a condensation reaction of various aldehydes and hydantoin in the presence of an alkanolamine, there is no example applied to the synthesis of a 5-pyridylmethylenehydantoin compound. Therefore, 2-amino-3 has been conventionally used.
There has been a demand for the development of a new production route in the synthesis of-(pyridyl) propionic acid compounds.

[0003]

The present invention is suitable as a starting material for the production of 2-amino-3- (pyridyl) propionic acid compounds, which can be carried out simply, safely and inexpensively.
It is an object to provide a method for producing a pyridylmethylhydantoin compound. Another object of the present invention is to provide a method for producing a 5-pyridylmethylenehydantoin compound used as a precursor of the above-mentioned 5-pyridylmethylhydantoin compound in high yield.

[0004]

As a result of various investigations in view of such circumstances, the present inventor has found that the carbon-carbon double bond in the 5-pyridylmethylenehydantoin compound and its hydrogen halide salt is present in the presence of a metal catalyst. It was found below that it is easily reduced with hydrogen to give a 5-pyridylmethylhydantoin compound and a hydrogen halide salt thereof.
It was found that the -pyridylmethylenehydantoin compound can be synthesized in good yield in the reaction between an inexpensive hydantoin and a pyridine aldehyde compound by selecting the base and solvent used, and the present invention has been completed based on these findings. That is, the said subject of this invention can be achieved by the following means. (1) The following general formula [1]

[0005]

[Chemical 7]

(In the formula, R represents a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, an alkylsulfonyl group or an alkoxycarbonyl group, and a bond between the pyridine ring and the hydantoin methylene moiety. The position is 2 or 3 of the pyridine ring.
Or fourth place. ) The 5-pyridyl methylene hydantoin compound represented by the formula (4) is reduced by hydrogenation in the presence of a metal catalyst, the method for producing a 5-pyridylmethylhydantoin compound represented by the following general formula [2].

[0007]

[Chemical 8]

(In the formula, R and the bonding position between the pyridine ring and the hydantoin methyl moiety correspond to the above-mentioned general formula [1].) (2) Pyridinealdehyde compound represented by the following general formula [3] And a hydantoin represented by the following general formula [4] are reacted in the presence of a base to produce a 5-pyridylmethylenehydantoin compound represented by the following general formula [1]. ,
A method for producing a 5-pyridylmethylhydantoin compound represented by the following general formula [2], which comprises reducing by hydrogenation in the presence of a metal catalyst.

[0009]

[Chemical 9]

(In the formula, R represents a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, an alkylsulfonyl group or an alkoxycarbonyl group, and a bond between the pyridine ring and the hydantoin methylene moiety. The position is 2 or 3 of the pyridine ring.
Or fourth place. )

[0011]

[Chemical 10]

(In the formula, R and the bonding position between the pyridine ring and the hydantoin methyl moiety correspond to the above general formula [1], respectively).

[0013]

[Chemical 11]

(In the formula, the bonding positions of R and —CHO and the pyridine ring correspond to the above general formula [1], respectively).

[0015]

[Chemical 12]

(3) The method for producing a 5-pyridylmethylhydantoin compound according to item (1) or (2), wherein the 5-pyridylmethylenehydantoin compound is a hydrogen halide salt.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION In the present specification, the hydrogen halide refers to hydrogen chloride, hydrogen bromide, hydrogen iodide and the like. The halogen atom means a fluorine atom, a chlorine atom and the like. Unless otherwise specified, the alkyl group represents a linear or branched alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl etc. can be mentioned. The haloalkyl group, unless otherwise limited, is a linear or branched alkyl group having 1 to 4 carbon atoms, which is substituted with the same or different halogen atoms of 1 to 9, and includes, for example, trifluoromethyl, 2,2,2-trifluoroethyl etc. can be mentioned. A haloalkoxy group means a haloalkyl moiety as defined above,
It represents a (haloalkyl) -O- group, and examples thereof include difluoromethoxy, trifluoromethoxy, and 2,2,2-trifluoroethoxy. An alkoxy group has an alkyl moiety as defined above, (alkyl)-
It represents an O-group, and examples thereof include methoxy and ethoxy. The alkoxycarbonyl group refers to an (alkoxy) -CO- group in which the alkoxy moiety has the above meaning, and examples thereof include methoxycarbonyl and ethoxycarbonyl. The alkylthio group and the alkylsulfonyl group have the above-mentioned meanings in the alkyl moiety,
(Alkyl) -S- group, (alkyl) -SO 2 _- represents a group, such as methylthio, ethylthio, methyl sulfonyl, ethylsulfonyl, and the like.

The method for producing the 5-pyridylmethylhydantoin compound represented by the general formula [2] of the present invention will be described in more detail. R in the general formula [1] represents a group that does not directly affect the reduction reaction and the condensation reaction in the production method of the present invention, and is specifically the group of the above item (1). R is preferably a hydrogen atom or an alkyl group.
The substitution position of R on the pyridine ring can be any position other than the position at which the hydantoimethylene moiety is substituted, and is not particularly limited. The bonding position between the pyridine ring and the hydantoimethylene moiety is preferably the 3-position or 4-position of the pyridine ring, and more preferably the 3-position. In the present invention, it is preferable to use a hydrogen halide salt as the compound of the general formula [1]. This hydrogen halide salt can be obtained by reacting a 5-pyridylmethylhydantoin compound with hydrogen halide by a conventional method.
Although not particularly limited in the present invention, the hydrogen halide salt is preferably a hydrobromide salt or a hydrochloride salt, and more preferably a hydrochloride salt.

In the method for producing the compound of the general formula [2], the metal catalyst used in the reduction reaction may be one commonly used in the reduction reaction by hydrogenation, such as palladium, platinum, rhodium or Nickel etc. are mentioned. Further, these may be supported on carbon or the like, or may contain water. The amount of the metal catalyst used is not particularly limited, but is usually 0.0 with respect to the hydrogen halide salt of the 5-pyridylmethylenehydantoin compound.
It is 1 to 10 mol%, preferably 0.1 to 5 mol%.

The reduction reaction in the method for producing the compound of the general formula [2] is not particularly limited, but is carried out by reacting a hydrogen halide salt of the 5-pyridylmethylenehydantoin compound of the general formula [1], a metal catalyst and a solvent. It is sufficient to add it to a vessel and stir it in the presence of hydrogen such as hydrogen atmosphere until the reaction is completed. The hydrogen pressure is not particularly limited, but is usually 0.1 to 10 MPa, preferably 0.1 to 5 M.
Pa. The reaction temperature is not particularly limited, but is usually 0 to 100 ° C, preferably 10 to 50 ° C.
Is. The hydrogen halide salt of the compound of general formula [2] that can be produced by the above reduction reaction can be easily converted to the compound of general formula [2] by a conventional method, for example, treatment with a base. This conversion may be carried out in the reaction system as it is, or may be carried out after isolation as a salt.

In the method for producing the compound of the general formula [2], the solvent used in the reduction reaction can be appropriately selected from those capable of dissolving the starting compound to the extent necessary for the reaction, and is not particularly limited. But not, for example, water,
Alternatively, a solvent containing water and an organic solvent can be used. Examples of the organic solvent include alcohols such as methanol, ethanol, propanol, and isopropanol, ethers such as tetrahydrofuran, amides such as N, N-dimethylformamide, and a mixture thereof. In the method for producing the compound of the general formula [2], the amount of the solvent used in the reduction reaction is not particularly limited, but is preferably 1 with respect to the weight of the hydrogen halide salt of the compound represented by the general formula [1]. -20 times, more preferably 2-10 times.

Next, the method for producing the 5-pyridylmethylenehydantoin compound represented by the general formula [1] used as the precursor of the compound of the general formula [2] will be described in more detail. The method for producing the 5-pyridylmethylenehydantoin compound is represented by the general formula [2] in the present invention.
It is used as a method for producing a precursor of the compound of
Without being particularly limited, it can be generally used as a method for producing a 5-pyridylmethylenehydantoin compound. The pyridine aldehyde compound of the general formula [3] and the hydantoin of the general formula [4], which are the starting compounds in the method for producing the compound of the general formula [1], can be synthesized by a conventional method and used, or commercially available. You may use the thing. In the present invention, the preferable group of R in the general formula [3] and the substitution position on the pyridine ring are the same as those in the general formula [1].
In the same range as above, the bonding position between —CHO and the pyridine ring also corresponds to the general formula [1], and the 3-position or 4-position of the pyridine ring is preferable, and the 3-position is more preferable.

As the base used in the method for producing the compound of the general formula [1], organic bases such as alkanolamines such as monoethanolamine and diethanolamine are preferable, and in addition to these, ethylamine, n-butylamine, diethylamine and triethylamine. And the like, alkyldiamines such as ethylenediamine, and cyclic amines such as piperidine and morpholine. Examples of the inorganic bases include alkali hydroxides such as sodium hydroxide and alkali carbonates such as sodium carbonate. The amount of the base used in the method for producing the compound of the general formula [1] is not particularly limited, but is usually 0.1 to 2 mol, preferably 0.1 to 2 mol with respect to 1 mol of the pyridine aldehyde compound of the general formula [3]. It is 1 mol.

As the solvent used in the method for producing the compound of the general formula [1], a solvent that can dissolve the starting compound to an extent necessary for the reaction can be appropriately selected and is not particularly limited, but for example, , Water, or a solvent containing water and an organic solvent can be used. Examples of the organic solvent to be mixed with water are the same as the examples given as the solvent used in the method for producing the compound of the general formula [2], but alcohols are preferable, and isopropanol is more preferable. In the method for producing the compound of the general formula [1], the amount of the solvent used is not particularly limited, but is usually 1 to 20 times, preferably 2 to 10 times the weight of hydantoin.

The condensation reaction in the method for producing the compound of the general formula [1] is not particularly limited, but a pyridine aldehyde compound of the general formula [3], a hydantoin of the general formula [4], a base and a solvent are used as a reactor. In addition to the above, it can be performed by an operation such as reflux. The reaction temperature is not particularly limited, but is usually 0 to 120 ° C., preferably 2
It is 0 to 80 ° C. The compound represented by the general formula [1] thus obtained can be easily converted into its hydrogen halide salt by subsequent reaction with hydrogen halide.

The 5-pyridylmethylhydantoin compound represented by the general formula [2] which can be produced by the present invention is useful as an intermediate for pharmaceuticals, agricultural chemicals, etc. by further microbial or chemical degradation. -Amino-3- (pyridyl) propionic acid [β-pyridylalanine] compound can be easily converted. The above-mentioned microbial decomposition or chemical decomposition can be carried out by a commonly used method and is not particularly limited, for example, Agric.Biol.C.
According to the microbial degradation described in hem., 51, 721, (1987), an N-carbamoyl-3- (pyridyl) alanine compound can be obtained from the compound of the general formula [2]. This N-carbamoyl-3- (pyridyl) alanine compound is further biodegraded or chemically decomposed to give 2-amino-3-
It can be converted to a (pyridyl) propionic acid [β-pyridylalanine] compound. Further, the chemical decomposition includes hydrolysis, for example, J. Am. Chem. Soc., 70, 1451 (194
According to the chemical hydrolysis method described in 8), a 2-amino-3- (pyridyl) propionic acid [β-pyridylalanine] compound can be obtained from the compound of the general formula [2].

[0027]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited thereto.

[Production Example of 5-Pyridylmethylhydantoin Compound] Example 1 (1) Synthesis of 5- (3-pyridyl) methylhydantoin Hydrochloride 200 g of water, 40 g of methanol, 5 g of methanol in an autoclave of 500 ml.
-(3-Pyridyl) methylenehydantoin hydrochloride 22.5 g
(0.1 mol) and 10% Pd—C O.5g were added, and reduction was carried out at 45 ° C. under stirring with hydrogen pressure of 0.45 MPa. After 24 hours, Pd-C was filtered off and the filtrate was concentrated. 100 g of acetone was added to the residue, and the obtained crystals were filtered and washed with acetone to obtain 21.9 g of 5- (3-pyridyl) methylhydantoin hydrochloride (yield 96.5%, melting point 232 ° C). (2) Synthesis of 5- (3-pyridyl) methylhydantoin 5- (3-pyridyl) methylhydantoin hydrochloride 22.5 g
(0.1 mol) was dissolved in 30 g of water, and at 10 ° C, 40 g of 10% NaOH solution (O.
1 mol) was added dropwise. After stirring at 10 ° C for 1 hour, the crystals were filtered,
It was washed with 30 g of cold water to obtain 16.95 g (yield 88.7%) of 5- (3-pyridyl) methylhydantoin. The obtained compound showed the following measured values. Melting point 200 ° C. ¹ H NMR (60 MHz, DMSO-d ₆ , δ): 2.99 (d, 2H, -CH _2- ), 4.39 (t,
1H, Hydantoin-5), 7.30 (dd, 1H, Py-5), 7.61 (dd, 1H, Py-
4), 7.98 (d, 1H, Py-2), 8.48 (m, 2H, Py-6, NH), 10.51 (brs, 1
H, NH) ESIMS: m / z 192 ([M + 1] ⁺ , 100)

Example 2 (1) Synthesis of 5- (4-pyridyl) methylhydantoin Hydrochloride Instead of 5- (3-pyridyl) methylenehydantoin hydrochloride, 5- (4-pyridyl) methylenehydantoin hydrochloride
5- (4-pyridyl) methylhydantoin hydrochloride was prepared in the same manner as in (1) of Example 1 except that 22.5 g (0.1 mol) was used.
21.9 g (yield 89.4%, melting point 226 ° C.) was obtained. (2) Synthesis of 5- (4-pyridyl) methylhydantoin 5- (4-pyridyl) methylhydantoin hydrochloride 22.5 instead of 5- (3-pyridyl) methylhydantoin hydrochloride 22.5
In the same manner as in (2) of Example 1 except that g (0.1 mol) was used, 15.3 g (yield 80.3%) of 5- (4-pyridyl) methylhydantoin was obtained. The obtained compound showed the following measured values. Melting point 283 ° C ¹ H NMR (60 MHz, DMSO-d ₆ , δ): 2.97 (d, 2H, -CH _2- ), 4.43 (t,
1H, Hydantoin-5), 7.21 ~ 7.60 (m, 2H, Py-3,5), 7.98 (s, 1
H, NH), 8.52 (d, 2H, Py-2,6), 1O.57 (brs, 1H, NH) ESIMS: m / z 192 ([M + 1] ⁺ , 100)

[Production Example of Precursor of 5-Pyridylmethylhydantoin Compound] Example 3 Synthesis of 5- (3-pyridyl) methylenehydantoin 1 Hydantoin 22.5 g (0.1 mol), pyridine-3-aldehyde 22.5 g (0.1 mol) ), Sodium hydroxide 22.5 g (O.1 mol), water
A mixture of 100 g and 50 g of isopropanol was refluxed for 12 hours. After cooling to room temperature, 6 g (0.1 mol) of acetic acid was added and the product was filtered and washed with 50 g of water and 50 g of methanol. After thoroughly drying, 25 g (yield 75%) of 5- (3-pyridyl) methylenehydantoin was obtained as a pale yellow crystalline powder. The obtained compound showed the following measured values. Melting point 308 ° C ¹ H NMR (300MHz, DMSO-d ₆ , δ): 6.41 (s, 1H, -CH =), 7.41 (d
d, 1H, Py-5), 8.02 (tt, 1H, Py-4), 8.47 (dd, 1H, Py-2), 8.76
(d, 1H, Py-6), 12.03 (brs, 2H, NH) ESIMS: m / z 190 ([M + 1] ⁺ , 100) Instead of the above pyridine-3-aldehyde, equimolar amount of pyridine-2 The 5-pyridylmethylenehydantoin compounds shown in Table 1 were obtained in the same manner as above except that -aldehyde or pyridine-4-aldehyde was used. In the table, the bond position is the bond position between the pyridine ring and the hydantoin methylene moiety.

[0031]

[Table 1] Table 1

Example 4 Synthesis of 5- (3-pyridyl) methylenehydantoin 2 Hydantoin 22.5 g (0.1 mol), pyridine-3-aldehyde 22.5 g (0.1 mol), 2-aminoethanol 22.5 g (0.1 mol)
A mixture of l), 100 g of water and 50 g of isopropanol was refluxed for 5 hours. After cooling to room temperature, 6 g (0.1 mol) of acetic acid and 100 g of water were added, the product was filtered, and washed with 50 g of water and 50 g of methanol. After drying well, 5- (3-pyridyl) methylenehydantoin was obtained as a pale yellow crystalline powder, 25 g (yield 75%, melting point 308 ° C.).

Example 5 Synthesis of 5- (3-pyridyl) methylenehydantoin hydrochloride 5- (3-pyridyl) methylenehydantoin 25 g (O.1mo)
l) and 100 g of water, 22.5 g of concentrated hydrochloric acid (O.1 mol) was added, and 70
The mixture was heated at 0 ° C for 1 hour to be dissolved. Most of the water was distilled off under reduced pressure, 200 g of acetone was added to the residue, and the product was filtered.
After washing with 100 g of acetone, 30 g of 5- (3-pyridyl) methylenehydantoin hydrochloride (yield 90%, melting point 296 ° C. (decomposition))
Got Table 2 shows the same procedure as in Table 2 except that an equimolar amount of 5- (2-pyridyl) methylenehydantoin or 5- (4-pyridyl) methylenehydantoin was used instead of 5- (3-pyridyl) methylenehydantoin. Show 5-
A hydrochloride salt of the pyridyl methylene hydantoin compound was obtained.
In the table, the bond position is the bond position between the pyridine ring and the hydantoin methylene moiety.

[0034]

[Table 2] Table 2

[Production Example of 2-amino-3- (pyridyl) propionic acid [β-pyridylalanine]] Reference Example 2-Amino-3- (3-pyridyl) propionic acid [β- (3
-Pyridyl) alanine] 5- (3-pyridyl) methylhydantoin hydrochloride 22.5 g
(0.1 mol) was dissolved in 50 g of water, and 13.2 g (0.3
(3 mol) was added and the mixture was refluxed for 12 hours. After cooling to room temperature, 50 g of water and 12.3 g (0.11 mol) of concentrated sulfuric acid were added. This reaction liquid was adsorbed with an amino acid using a strongly acidic cation exchange resin (IR-120B (H)) and then eluted with 1.5 M ammonia water, and the eluate was concentrated to dryness to give 2-amino-3- ( 3-pyridyl) propionic acid [β-
(3-pyridyl) alanine] 4.1 g (melting point 252 ° C.) was obtained.

[0036]

According to the production method of the present invention, a 5-pyridylmethylhydantoin compound can be produced simply, safely and inexpensively, and is a precursor of this compound.
-Pyridyl methylene hydantoin compound can be obtained in high yield. Furthermore, according to the production method of the present invention, it is possible to produce a 5-pyridylmethylhydantoin compound in which a pyridine ring and a hydantoin methylene moiety are bonded at a desired position. Therefore, according to the production method of the present invention, a compound suitable for producing a 2-amino-3- (pyridyl) propionic acid [β-pyridylalanine] compound, which is important as a constituent raw material of a drug, particularly a compound suitable for producing a 3-pyridyl derivative thereof is preferable. It can be manufactured in yield.

Claims (3)

[Claims] 1. The following general formula [1]: (In the formula, R is a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, an alkylsulfonyl group or an alkoxycarbonyl group, and the bonding position between the pyridine ring and the hydantoin methylene moiety is The 5-pyridylmethylenehydantoin compound represented by the 2, 3 or 4 position of the pyridine ring is reduced by hydrogenation in the presence of a metal catalyst, represented by the following general formula [2]. And a method for producing a 5-pyridylmethylhydantoin compound. [Chemical 2] (In the formula, R and the bonding position between the pyridine ring and the hydantoin methyl moiety correspond to the general formula [1], respectively.) 2. A compound represented by the following general formula [1] obtained by reacting a pyridine aldehyde compound represented by the following general formula [3] with a hydantoin represented by the following general formula [4] in the presence of a base. A 5-pyridylmethylenehydantoin compound represented by the following general formula [2] characterized by producing a 5-pyridylmethylenehydantoin compound and reducing the 5-pyridylmethylenehydantoin compound by hydrogenation in the presence of a metal catalyst. Method for producing compound. [Chemical 3] (In the formula, R is a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, an alkylsulfonyl group or an alkoxycarbonyl group, and the bonding position between the pyridine ring and the hydantoin methylene moiety is It is at the 2, 3 or 4 position of the pyridine ring.) (In the formula, R and the bonding position between the pyridine ring and the hydantoin methyl moiety correspond to the above general formula [1], respectively.) (In the formula, the bonding positions of R and —CHO and the pyridine ring correspond to the above general formula [1], respectively.) 3. The method for producing a 5-pyridylmethylhydantoin compound according to claim 1 or 2, wherein the 5-pyridylmethylenehydantoin compound is a hydrogen halide salt.