JPH0641134A - Pyrimidopteridine derivative and its production - Google Patents

Abstract

PURPOSE:To provide the novel pyrimidopteridine derivative useful as an intermediate raw material for agricultural chemicals, medicines, pigments, dyestuffs, etc., or as a fluorescent pigment, and capable of being simply synthesized. CONSTITUTION:The compound of formula I (R<1>-R<3> are each, H, an alkyl, alkenyl, alkinyl, cycloalkyl, aryl, heterocyclic, or R<2> and R<3> form a ring together; R<4>, R<5> are each H, an alkyl, alkenyl, alkinyl, cycloalkyl, or R<3> and R<4> form a single bond), e.g. a compound of formula II. A compound of formula III in the compound of formula I is obtained by reacting 3,6-diamino-2,5- pyradinecarbonitrile with a compound of formula R<1>NH2 and further with a compound of formula R<2>COR<3>. A compound of formula V which is one of the compound of formula I is obtained by oxidizing a compound of formula IV which is one of the compound of formula I. A compound of formula VI (r<4> is an alkyl, alkenyl, etc.,) which is one of the compound of formula I is also obtained by reacting the compound of formula II with a compound of formula r<4>X (X is a halogen).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel pyrimidopteridine derivative and a method for producing the same.

[0002]

2. Description of the Related Art Pyrimidopteridine derivatives have been known for a long time and there are many reports. However, most of them relate to pyrimido [5,4-g] pteridine derivatives and pyrimido [1,2,3-ij] pteridine derivatives, which are structural isomers, and pyrimido [4,5-g]
Since there are few reports on pteridine derivatives and the raw materials are limited, only a few kinds of compounds have been synthesized. They are, for example, tetramethylpyrimides [4,5-, formed by self-condensation of uracil derivatives.
g] Synthesis of pteridine tetron derivative [Chem. Be
r. , 86, 845-50 (1953), J. Am. C
hem. Soc. , 76, 2798-2800 (195
4), J. Chem. Soc. D, 1969, (2
3), 1426, Chem. Pharm. Bull. ，
1971, 19 (5), 1060-2] [(chemical formula 9)],
Tetrahydroxypyrimides formed by condensation of alloxan and piperidine derivatives or self-condensation of uric acid [4,5
-G] Synthesis of pteridine derivative [J. Am. Chem.
Soc. , 76, 1874-6 (1954), Che
m. Ber. , 92, 2468-77 (1959)]
Synthesis of tetraaminopyrimido [4,5-g] pteridine derivative produced by self-condensation of [(Chemical Formula 10)] or tetraaminopyrimidine [J. Am. Chem. So
c. , 77, 2243-8 (1955)] [(Chemical formula 1
1)] Examples are available.

[0003]

[Chemical 9]

[0004]

[Chemical 10]

[0005]

[Chemical 11]

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel pyrimidopteridine derivative which can be easily synthesized.

[0007]

The present inventors have previously found 3,6-diamino-2,5-pyrazinedicarbonitrile [II] (Japanese Patent Application No. 2-59935). As a result of extensive studies using this compound [II] as a starting material, it was found that the compound of the present invention can be easily synthesized.

That is, the present invention has the general formula [I] (wherein
R ¹ , R ² and R ³ are the same or different and each is a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, Represents a cycloalkyl group which may have a substituent, an aryl group which may have a substituent or a heterocyclic group which may have a substituent, and R ² and R ³ together form a ring. You may form. R ⁴ and R ⁵ are the same or different and each is a hydrogen atom,
R ³ represents an alkyl group which may have a substituent, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent or a cycloalkyl group which may have a substituent, and R ³ And R ⁴ may together form a single bond. ) And a method for producing the same.

When the alkyl group, alkenyl group, alkynyl group or cycloalkyl group in R ¹ , R ² , R ³ , R ⁴ and R ⁵ has a substituent, the substituent may have a substituent. Aryl group such as phenyl group, cyano group,
Examples thereof include a nitro group, an alkoxy group, an aryloxy group, an alkylthio group, an arylthio group and a halogen atom. When the aryl group or heterocyclic group in R ¹ , R ² or R ³ has a substituent, examples of the substituent include an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryloxy group, a nitro group and a cyano group. , Amino group, halogen atom, alkylthio group, arylthio group,
Examples thereof include an alkoxycarbonyl group, and those possible among these groups may further have a substituent. The number of substituents and the bonding position thereof are arbitrary, and when a plurality of substituents are bonded, they may be the same or different from each other. The method for producing the compound of the present invention will be described. (1)

[Chemical 12] R ¹ , R ² and R ³ have the same meanings as described above. A compound represented by the general formula [III] R ¹ NH ₂ is used in an amount of at least 2 times the molar amount of the compound [II], and the reaction is carried out in a suitable solvent at 0 ° C. to 80 ° C., preferably room temperature to 60 ° C. Gives an intermediate [VII]. This [VII] is isolated or used as it is without isolation, and then the compound of the general formula [I]
V] R ² COR ³ can be obtained by using the compound represented by 2 times or more moles in an appropriate solvent or without solvent at room temperature to 160 ° C., preferably 40 ° C. to 120 ° C. As the solvent, dimethylformamide (DMF), dimethylacetamide (DMAC), dimethylsulfoxide (DMS) in any reaction.
O), tetrahydrofuran (THF), and polar solvents such as dimethoxyethane (DME), which are used alone or as a mixed solvent.

(2)

[Chemical 13] R ¹ and R ² have the same meanings as described above. Compound [I-
2] can be obtained by carrying out the reaction in the presence of air, oxygen or a suitable oxidizing agent in a suitable solvent at -20 ° C to 200 ° C, preferably 0 ° C to 150 ° C. As the solvent, those listed in (1) are used, and alcohols such as methanol and ethanol, ethers such as dioxane, hydrocarbons such as benzene and toluene, and halogen solvents such as dichloromethane are used. Examples of the oxidizing agent include inorganic and organic peroxides such as hydrogen peroxide and peracetic acid, metal salts having oxygen such as manganese oxide, permanganate, chromic acid and dichromate, and halogens such as bromine. Further, organic oxidants such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and tetrachlorobenzoquinones are used.

(3)

[Chemical 14] R ¹ , R ² , R ³ , r ⁴ and X have the same meanings as described above. To the compound [I-1], a halogenated compound represented by the general formula [V] r ⁴ X is used in an amount of 4 times by mole or more and a suitable base by 4 times or more moles, and in a suitable solvent, from −50 ° C. to 200 ° C.
It can be obtained by reacting at a temperature of ℃, preferably from -20 ℃ to 150 ℃. As the solvent, those mentioned in (1) are used, and as the base, carbonates such as sodium carbonate and potassium carbonate, hydroxides such as sodium hydroxide and potassium hydroxide, metals such as sodium hydride and potassium hydride. Organic bases such as hydrides, alkoxides such as sodium methoxide and potassium t-butoxide, or amines such as DBU are used.

(4)

[Chemical 15] R ¹ , R ² , R ⁵ and Y have the same meanings as described above. With respect to the compound [I-3], the halogenated compound represented by the general formula [VI] R ⁵ Y is used in an amount of at least 2 times the mole of a suitable base and at least 2 times the mole of a suitable base, and in a suitable solvent at −50 ° C. to 200 ° C. It can be obtained by reacting at a temperature of ℃, preferably from -20 ℃ to 150 ℃. The solvent described in (1) is used, and the base used in (3) is used. After the completion of the reaction, the desired product can be obtained by performing a usual post-treatment. The synthesized compounds are NMR, IR and MASS
Etc. were identified.

[0013]

EXAMPLES The present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited to these examples.

Example 1 (Compound No. 1)

[Chemical 16] 3,6-diamino-2,5-pyrazinedicarbonitrile [II] 1.28 g (8.0 mmol) anhydrous DMF
(20 ml) 10.5 ml of n-hexylamine in the solution
(79 mmol) was added, and the mixture was stirred at room temperature for 54 hours. 100 ml of saline was added, and extraction was performed with 150 ml of ethyl acetate. Concentration under reduced pressure gave yellowish brown crystals. Then, 100 ml of acetone was added and the mixture was heated under reflux for 1 hour. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (developing solvent; hexane-ethyl acetate 1.5: 1) to obtain 1.49 g (3.4 mmol) of the desired product. Yield 43%, mp148-149.5 ° C

Example 2 (Compound No. 2)

[Chemical 17] Compound [II] 1.28 g (8.0 mmol) of anhydrous D
To the MF (20 ml) solution, 6.3% (65 mmol) of a 40% methylamine methanol solution was added, and the mixture was stirred at room temperature for 6 days. Excess methylamine was distilled off under reduced pressure, and 10 ml (96 mmol) of cyclohexanone was added to about 10
Heated at 0 ° C. for 30 minutes. After concentration under reduced pressure, 20 ml of dichloromethane was added and stirred, and the crystals were collected by filtration to obtain 0.42 g of the desired product as orange crystals. The filtrate was concentrated under reduced pressure, 10 ml of dichloromethane was added again, and the mixture was stirred. The crystals were collected again by filtration to obtain 0.54 g of the desired product as orange crystals. The filtrate was concentrated under reduced pressure and then purified by silica gel column chromatography (developing solvent; benzene-ethyl acetate 1: 1) to obtain 0.34 g of the desired product as orange crystals. 1.30 g (3.4 mmol) in total
I got the object. Yield 43%, 264 ° C (endothermic peak)
^{* * For} items with an endothermic or exothermic peak, see D
It is the value measured by SC.

Example 3 (Compound No. 5)

[Chemical 18] 0.18 g (0.51 mm) of a compound [I-1] in which R ¹ is a methyl group and R ² and R ³ are tetramethylene groups.
ol) and 0.4 ml of iodomethane (98%, 6.2 mm)
ol) in DMF (3 ml) was ice-cooled, and 0.26 g (96%, 6.2 mmol) of sodium hydroxide powder was added and reacted. After 3 hours, add 10 ml of water and add 30 more water.
ml was added and the mixture was extracted with dichloromethane. The organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the product was isolated by preparative liquid chromatography (GPC column, developing solvent; chloroform) to give 0.10 g (0.26 g) of the desired product.
mmol) obtained. Yield 51%, mp189-191 ° C

Example 4 (Compound No. 7)

[Chemical 19] Compound [II] 1.29 g (8.1 mmol) anhydrous DM
6.6 ml of n-propylamine in F (20 ml) solution
(80 ml) was added, and the mixture was stirred at room temperature for 6 days. Excess n-propylamine was distilled off under reduced pressure to give benzaldehyde 1
0 ml (25 mmol) was added, and it heated at about 100 degreeC for 1 hour. After distilling off the solvent, etc. under reduced pressure, 50 ml of ethyl acetate
Was added, and the mixture was stirred well and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate 2: 1) to give the desired product as orange crystals in an amount of 0.
29 g were obtained. Yield 8%, 152 ° C. (endothermic peak) Including the compounds of the above examples, Table-1 and Table-2 show typical examples of the compounds. Table 3 shows their fluorescence characteristics.

[0018]

[Table 1]

[0019]

[Table 2]

[0020]

[Table 3]

[0021]

INDUSTRIAL APPLICABILITY The compounds of the present invention are useful as intermediate raw materials for agricultural medicine, pigments and dyes, fluorescent dyes and the like.

Claims (5)

[Claims] 1. A compound represented by the general formula [I]: (In the formula, R ¹ , R ² and R ³ are the same or different and each is a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or a substituent which may have a substituent. A alkynyl group, a cycloalkyl group which may have a substituent, an aryl group which may have a substituent or a heterocyclic group which may have a substituent, and R ² and R ³ are taken together. R ⁴ and R ⁵ are the same or different and each is a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or a substituent. An alkynyl group which may be present or a cycloalkyl group which may have a substituent, and R ³ and R ⁴ may be taken together to form a single bond). 2. 3,6-Diamino-2,5-pyrazinedicarbonitrile [II] and the general formula [III] R ¹ NH ₂ [III] (wherein R ¹ has the same meaning as described above). ) And then reacting with a compound represented by the general formula [IV] R ² COR ³ [IV] (in the formula, R ² and R ³ have the same meanings as described above). A general formula [I
-1] [Chemical formula 2] (In the formula, R ¹ , R ² and R ³ have the same meanings as described above.) A method for producing a compound represented by the formula. 3. A compound represented by the general formula [I-2]: (In the formula, R ¹ and R ² have the same meanings as described above.) A compound represented by the general formula [I-
3] [Chemical 4] (In the formula, R ¹ and R ² have the same meanings as described above.) A process for producing a compound represented by the formula. 4. A compound [I-1]: (In the formula, R ¹ , R ² and R ³ have the same meanings as described above.) And the general formula [V] r ⁴ X [V] (wherein, r ⁴ has a substituent. Represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, or an optionally substituted cycloalkyl group, and X represents a halogen atom. ), A compound represented by the general formula [I-4]: (In the formula, R ¹ , R ² , R ³ and r ⁴ have the same meanings as described above.) 5. A compound [I-3]: (In the formula, R ¹ and R ² have the same meaning as described above.) And the general formula [VI] R ⁵ Y [VI] (In the formula, R ⁵ is an alkyl group which may have a substituent or a substituent. An alkenyl group which may have a substituent, an alkynyl group which may have a substituent, or a cycloalkyl group which may have a substituent, and Y represents a halogen atom). General formula [I-5] characterized by reacting in the presence of a base (In the formula, R ¹ , R ² and R ⁵ have the same meanings as described above.) A method for producing a compound represented by the formula.