JPH05202046A - Pyrimidopteridine derivative and its production - Google Patents

Abstract

PURPOSE:To obtain a new pyrimidopteridine derivative useful as an intermediate for agricultural chemicals and medicines, dyes, perfumes, oxidizing agents, etc., a monomer for high polymers or a fluorescent pigment, etc. CONSTITUTION:A compound of formula I (R<1> is alkyl, alkenyl, alkynyl, aryl or heterocyclic group which may have a substituent group, respectively; R<3> is H or alkyl, alkenyl or alkynyl which may have a substituent group, respectively, with the proviso that R<1> and R<3> are not simultaneously methyl). A compound of formula II (r<2> is alkyl, alkenyl or alkynyl which may have a substituent group, respectively; X is NH or O) is hydrolyzed in the presence of a mineral acid to give the compound of formula I wherein R<3> is H, which is as necessary made to react with a compound of the formula r<3>Z (r<3> is same as r<2>; Z is halogen) to provide the compound of formula I wherein R<3> is a group except for H.

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. Among them, for example, introduction of a hydroxyl group or a carbonyl group by oxidation with electron transfer such as pyrimido [5,4-g] pteridine N-oxide [(chemical formula 8)] [Chem. Pharm. B
all. 1991 , 39 (1), 195-198] and induction of aldehydes with decarboxylation of substituted acetic acid [J. Chem. Soc. Chem. Commu
n. 1989 , (22) 1780-2, Chem. Ph
arm. Bull. 1989 , 37 (12) 3239-.
42] A compound having a function has been found.

[0003]

[Chemical 8] However, most of these are pyrimido [5,4-g] pteridine-type derivatives, and as the pyrimido [4,5-g] pteridine-type derivatives of the present invention, compounds in which all the substituents are methyl groups [( Chemical formula 9)] is only known (J. Am. Chem. Soc., 1955 ,
77 (8), 2243-2248, J. Chem. So
c. D 1969 , (23), 1426, Chem. P
harm. Bull. 1971 , 19 (5), 1060
-2, J. Hetrocycl. Chem. 1973 ,
10 (6), 993-6).

[0004]

[Chemical 9]

[0005]

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

[0006]

The present inventors have previously found 3,6-diamino-2,5-pyrazinedicarbonitrile. (Japanese Patent Application No. 2-59935) As a result of extensive studies using this compound 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]

[Chemical 10] [In the formula, R ¹ is an alkyl group which may have a substituent, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, and an aryl group which may have a substituent. Or a heterocyclic group which may have a substituent, R ³ represents a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an alkynyl which may have a substituent. (In the formula [I], R ¹ and R ³ are both methyl groups). ] It is a compound represented by these, and its manufacturing method.

A method for producing the compound of the present invention will be described. (1) conversion 11

[Chemical 11] r ² represents an alkyl group which may have a substituent, an alkenyl group which may have a substituent or an alkynyl group which may have a substituent, and R ¹ and X have the same meanings as described above. ..
The compound represented by the general formula [II] can be obtained by heating under reflux using a mineral acid (for example, hydrochloric acid or sulfuric acid) or a mixed solvent of an inorganic acid and an alcohol.

(2) Conversion 12

[Chemical formula 12] R ¹ has the same meaning as described above. It can be obtained by treatment with 1-30% hydrogen peroxide in 5-30 wt% ammonia water. At this time, the reaction temperature is 0 to 60 ° C,
It is preferable to carry out at room temperature to 40 ° C.

(3) Conversion 13

[Chemical 13] r ³ represents an alkyl group which may have a substituent, an alkenyl group which may have a substituent or an alkynyl group which may have a substituent, and Z represents a halogen atom. Obtained by carrying out a reaction in a suitable solvent such as dimethylformamide (DMF) using a suitable halogenated compound in an amount of at least 2 times the molar amount of the general formula [I-1] and potassium carbonate or sodium hydride as a base. be able to. In this case, the reaction temperature is -50 ° C to 40 ° C, preferably -20 ° C to room temperature in the case of hydride such as sodium hydride,
In the case of hydroxide such as sodium hydroxide, -20 ℃ ~ 4
It is desirable to carry out at 0 ° C, preferably 0 ° C to room temperature, and in the case of potassium carbonate, 80 ° C to 200 ° C, preferably 140 ° C to 160 ° C.

The production of the starting compound for the compound of the present invention is described in "Pyrimidopteridine Derivatives and Production Method Thereof" filed on the same day by the same applicant. For example, when X = NH in the general formula [II], 3,6-diamino-2,
It can be synthesized from 5-pyrazine dicarbonitrile as shown in Chemical formula 14.

[Chemical 14] After the completion of the reaction, the target product can be obtained by performing a usual post-treatment. The synthesized compound has NMR, I
It was identified by R, MASS, etc.

[0012]

【Example】

 Example 1 (Compound No. 3)

[Chemical 15] In the general formula [II], X is NH, R ¹ is an n-propyl group, r ²
A suspension of a compound (0.84 g, 2.0 mmol) in which 1 is an ethyl group in 1-propanol (40 ml) and 16% sulfuric acid (40 ml) was heated under reflux for 3 days. After allowing to cool, the precipitate was filtered off and water (5 ml x 1), saturated aqueous sodium hydrogen carbonate (5 ml x 1), water (5 ml
ml × 2) and then washed with acetone (3 ml × 1). After drying under reduced pressure, 0.58 g of the desired product of yellow crystals was obtained. Yield 85
%, 457 ° C (endothermic peak) ^{* * The} terms with endothermic and exothermic peaks are DSL.
Is the measured value. (The same applies to the following examples and tables)

Example 2 (Compound No. 4)

[Chemical 16] 20% of the compound (0.39 g, 1.0 mmol) in the general formula [II] where X is oxygen, R ¹ is an n-butyl group, and r ² is hydrogen.
6% aqueous hydrogen peroxide was added to a suspension of aqueous ammonia at room temperature. After 2 days, the precipitate was filtered off and washed with water then acetone. After drying under reduced pressure, 0.09 g of the desired product of yellow crystals was obtained. Yield 25%, 452 ° C (endothermic peak)

Example 3 (Compound No. 9)

[Chemical 17] A compound of the general formula [II] in which X is NH, R ¹ is a phenyl group, and r ² is an ethyl group (0.200 g, 0.41 mmol).
A 30% sulfuric acid (20 ml) solution of was heated under reflux for 30 hours.
After cooling, the precipitate was filtered off and water (3 ml x 2), saturated aqueous sodium hydrogen carbonate (3 ml x 1), water (3 ml x 2) and then acetone (2 ml x 2).
Washed in 1). After drying under reduced pressure, the target substance of yellow powder 0.1
12 g was obtained. Yield 68%, 496 ° C (endothermic peak)

Example 4 (Compound No. 12)

[Chemical 18] In a nitrogen atmosphere, in the general formula [I], R ¹ is an n-butyl group, R is
Compound in which ³ is hydrogen (0.180 g, 0.50 mmol)
Of DMF (10 ml) was ice-cooled, and oily sodium hydride (containing 60%) (0.12 g, 3 mmol) was added.
After 5 minutes iodoethane (0.25 ml, 3 mmol) was added and after 5 minutes it was brought to room temperature. After reacting for another 20 minutes, the mixture was poured into ice water (40 ml) and extracted with ethyl acetate (60 ml × 3). The extract was washed with saturated brine (60 ml × 2), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Column chromatography using silica gel as a carrier (eluent: benzene-ethyl acetate 5: 1) was performed to obtain the desired product of yellow crystals 0.05.
3 g was obtained. Yield 26%, mp196-197 ° C

Example 5 (Compound No. 13)

[Chemical 19] In a nitrogen atmosphere, in the general formula [I], R ¹ is an n-butyl group, R is
Compound in which ³ is a hydrogen atom (2.16 g, 6.0 mmol)
To a suspension of DMF (80 ml) in 10 mL of potassium carbonate (6.63
g, 48.0 mmol) and 1-iodobutane (3.41 ml,
30.0 mmol) was added and the mixture was heated under reflux for 2 hours (bath temperature,
About 160 ° C). After cooling, it was filtered to remove potassium carbonate. The filtrate was concentrated under reduced pressure, 80 ml of water was added, and the mixture was extracted with ethyl acetate (80 ml × 2) and dichloromethane (80 ml × 1). The organic layers were combined and washed with water (80 ml × 1) and saturated saline solution (80 ml × 1). The extract was dried over magnesium sulfate and concentrated under reduced pressure. Purification was performed by column chromatography using silica gel as a simple substance (eluent: dichloromethane-ethyl acetate 20: 1) to obtain 2.09 g of the desired product as yellow crystals. Yield 73%, mp 153 to 154 ° C Table 1 shows typical examples of the compounds, including the compounds of the above Examples.

[0017]

[Table 1]

[0018]

The compounds of the present invention are agricultural chemicals, dyes, fragrances,
It is useful as an intermediate raw material such as an oxidizing agent, a polymer monomer, or a fluorescent dye.

Claims (4)

[Claims] 1. A compound represented by the general formula [I]: [In the formula, R ¹ is an alkyl group which may have a substituent, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, and an aryl group which may have a substituent. Or a heterocyclic group which may have a substituent, R ³ represents a hydrogen atom, an alkyl group which may have a substituent, an alkenyl group which may have a substituent, or an alkynyl which may have a substituent. A group is shown (provided that R ¹ and R ³ are both methyl groups). ] The compound represented by. 2. A compound represented by the general formula [II]: (In the formula, R ¹ has the same meaning as described above, and r ² is an alkyl group which may have a substituent, an alkenyl group which may have a substituent or an alkynyl group which may have a substituent. To
X represents NH or an oxygen atom. ) The compound represented by the formula (1) is hydrolyzed in the presence of a mineral acid. (Wherein R ¹ has the same meaning as described above). 3. A compound represented by the general formula [III]: (In the formula, R ¹ has the same meaning as described above.) Ammonia aqueous suspension of the compound represented by the formula [I-1] (Wherein R ¹ has the same meaning as described above). 4. A compound represented by the general formula [I-1]: (Wherein R ¹ has the same meaning as described above), in the presence of a base, a compound represented by the general formula r ³ Z (in the formula, r ³ is an alkyl group which may have a substituent, a substituent) A alkenyl group which may have a group or an alkynyl group which may have a substituent, and Z represents a halogen atom.) Is reacted with a compound represented by the general formula [I-2 ] [Chemical 7] (Wherein R ¹ and r ³ have the same meanings as described above).