JP2007008864A - Pyrazolopyrimidine derivative and germicide for use in agriculture and gardening - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pyrazolopyrimidine derivative having excellent activity as a germicide for use in agriculture and gardening. <P>SOLUTION: The pyrazolopyrimidine derivative is represented by the following formula: (wherein, R<SP>1</SP>indicates a branched 4-6C alkyl group; and R<SP>2</SP>indicates a halogen) and used as a germicide for use in agriculture and gardening. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a novel pyrazolopyrimidine derivative, the use of a pyrazolopyrimidine derivative as a fungicide, a production method thereof, and a novel intermediate.

  It is already known that certain pyrazolopyrimidine derivatives exhibit an action as a fungicide (see, for example, Patent Documents 1 to 4).

In addition, it is already known that certain pyrazolopyrimidine derivatives exhibit an action as an angiotensin II receptor antagonist (see, for example, Patent Document 5), and are reported to be used as photographic light-sensitive materials. (For example, refer to Patent Document 6).
PCT International Publication No. 05/851 Pamphlet German Patent No. 10223917 German Patent No. 3130633 German Patent No. 3338292 JP 7-504177A JP 63-199347 A

  However, conventional derivatives have not been sufficiently satisfactory in terms of the effect and / or safety as a fungicide.

  The inventors of the present invention have intensively studied to create a novel compound having a better effect as a fungicide and higher safety. As a result, the present inventors have found a novel pyrazolopyrimidine derivative represented by the following formula (I) having excellent biological activity.

式中、
Ｒ^１はＣ_４−６分岐鎖状アルキルを示し、そして
Ｒ^２はハロゲンを示す。

Where
R ¹ represents C _4-6 branched alkyl and R ² represents halogen.

  The compound represented by the formula (I) of the present invention can be synthesized, for example, by the following (a):

Production method (a) :
formula

式中、
Ｒ^３はＣ_１−４アルキルを示し、
Ｒ^１及びＲ^２は前記と同義である、
で表される化合物を加水分解する方法。

Where
R ³ represents C _1-4 alkyl;
R ¹ and R ² are as defined above,
The method of hydrolyzing the compound represented by these.

  The pyrazolopyrimidine derivative of the formula (I) provided by the present invention exhibits a strong bactericidal action.

In this specification,
Halogen represents fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.

Examples of “C _4-6 branched alkyl” include sec-butyl, 1,2-dimethylpropyl, neopentyl, 1,2,2-trimethylpropyl, and the like.

“C _1-4 alkyl” may be linear or branched, for example, methyl, ethyl, n-propyl, isopropyl, (n-, iso-, sec- or tert-) butyl, and the like. It can be illustrated.

In the compound of the formula (I), preferably
R ¹ represents sec-butyl, 1,2-dimethylpropyl, neopentyl or 1,2,2-trimethylpropyl, and R ² represents fluorine or chlorine.

In the compound of the formula (I), particularly preferably
R ¹ represents 1,2-dimethylpropyl or 1,2,2-trimethylpropyl, and R ² represents fluorine or chlorine.

In the compound of the formula (I), when the group R ¹ has an asymmetric carbon, it includes an enantiomer (R / S configuration).

  The production method (a) is, for example, 5-chloro-7- (1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester Is hydrolyzed using, for example, an aqueous potassium hydroxide solution, it is represented by the following reaction formula.

前記製法（ａ）において原料として用いられる式（ＩＩ）の化合物は、従来の文献に未記載の新規化合物であり、例えば、ＰＣＴ国際公開ＷＯ０３／０９７９８パンフレット等に記載される方法に準じて、式

The compound of the formula (II) used as a raw material in the production method (a) is a novel compound not described in the conventional literature. For example, according to the method described in PCT International Publication WO 03/09798 pamphlet,

式中、
Ｒ^２及びＲ^３前記と同義である、
で表される化合物を式
Ｒ^１−ＮＨ_２ （ＩＶ）
Ｒ^１は前記と同義である、
で表される化合物と反応させることにより容易に製造することができる。

Where
R ² and R ³ are as defined above,
A compound represented by the formula: R ¹ —NH ₂ (IV)
R ¹ is as defined above,
It can manufacture easily by making it react with the compound represented by these.

  The compound of the above formula (III) is a novel compound that has not been described in the conventional literature. For example, according to the method described in PCT International Publication WO 03/09798 pamphlet,

式中、
Ｒ^２及びＲ^３前記と同義である、
で表される化合物をハロゲン化剤、例えば、オキシ塩化リンと反応させることにより容易に製造することができる。

Where
R ² and R ³ are as defined above,
Can be easily produced by reacting a compound represented by the formula with a halogenating agent such as phosphorus oxychloride.

  The compound of the above formula (V) is a novel compound that has not been described in the conventional literature. For example, according to the method described in JP-A-2002-249492,

式中、
Ｒ^２及びＲ^３前記と同義である、
で表される化合物を式

Where
R ² and R ³ are as defined above,
A compound represented by the formula

式中、
Ｒ^３前記と同義である、
で表される化合物と反応させることにより容易に製造することができる。

Where
R ³ is as defined above,
It can manufacture easily by making it react with the compound represented by these.

  A part of the compound of the above formula (VI) is a novel compound which has not been described in the conventional literature. For example, JP-A-11-228500, Journal of Medicinal Chemistry, Vol. 45, no. 7, p. In accordance with the method described in 3639-3648 (2002) etc.

式中、
Ｒ^３は前記と同義である、
で表される化合物を式

Where
R ³ is as defined above,
A compound represented by the formula

式中、
Ｘはハロゲンを示し、
Ｒ^２は前記と同義である、
で表される化合物と反応させることにより容易に製造することができる。

Where
X represents halogen,
R ² is as defined above,
It can manufacture easily by making it react with the compound represented by these.

The compound of the above formula (VIII) is a compound known per se, and examples thereof include diethyl malonate, dimethyl malonate and the like as typical examples.
The compound of the above formula (IX) is a compound known per se. For example, 3-fluorobenzyl bromide, 3-chlorobenzyl bromide and the like can be exemplified as typical examples.

  The compound of formula (VII), which is a raw material for producing the compound of formula (V), is a compound known per se, and examples thereof include ethyl 3-amino-4-pyrazolecarboxylate.

As typical examples of the compound of the formula (II) used as a starting material in the production method (a), the following can be exemplified.
7-sec-butylamino-5-chloro-6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
7-sec-butylamino-5-chloro-6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid methyl ester,
5-chloro-7- (1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid propyl ester,
5-chloro-7- (1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid butyl ester,
5-chloro-7- (1,2-dimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (2,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (2,2-dimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2,2-trimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2,2-trimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester and the like.

As typical examples of the compound of formula (III) used as a raw material in the production of the compound of formula (II), the following can be exemplified.
5,7-dichloro-6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5,7-dichloro-6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester and the like.

In the production of the compound of formula (II), the compound of formula (IV) used as a raw material is a compound known per se, and typical examples thereof include the following.
sec-butylamine,
(R) -sec-butylamine,
(S) -sec-butylamine,
Neopentylamine,
3-methyl-2-butylamine,
(R) -3-methyl-2-butylamine,
(S) -3-methyl-2-butylamine,
3,3-dimethyl-2-butylamine,
(R) -3,3-dimethyl-2-butylamine,
(S) -3,3-dimethyl-2-butylamine and the like.

As representative examples of the compound of formula (V) used as a raw material in the production of the compound of formula (III), the following can be exemplified.
6- (3-fluorobenzyl) -5,7-dihydroxypyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
6- (3-chlorobenzyl) -5,7-dihydroxypyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester and the like.

As typical examples of the compound of the formula (VI) used as a raw material in the production of the compound of the formula (V), the following can be exemplified.
Diethyl (3-fluorobenzyl) malonate,
Diethyl (3-chlorobenzyl) malonate and the like.

  In preparing the compound of the formula (III), starting from the compounds of the formula (VI) and the formula (VII), the reaction of the compound of the formula (V) is continuously performed without purifying the compound of the formula (III). Compounds can also be obtained.

  As described above, in the process for producing the compound of the formula (I) of the present invention, the compounds of the formulas (II), (III) and (V) are novel compounds not described in the documents before the filing date of the present application. The compounds are collectively represented by the following formula (X).

式中、
Ｒ^２及びＲ^３は前記と同義を示し、
Ｒ^４はヒドロキシ又は塩素原子を示し、そして
Ｑはヒドロキシ、塩素原子又は基
−ＮＨ−Ｒ^１
を示し、ここでＲ^１は前記と同義を示し、
但し、Ｒ^４がヒドロキシを示す場合、Ｑはヒドロキシを示し、
Ｒ^４が塩素原子を示す場合、Ｑは塩素原子又は基
−ＮＨ−Ｒ^１
を示す。

Where
R ² and R ³ are as defined above,
R ⁴ represents a hydroxy or chlorine atom, and Q represents a hydroxy, chlorine atom or group —NH—R ¹
Where R ¹ is as defined above,
Provided that when R ⁴ represents hydroxy, Q represents hydroxy;
When R ⁴ represents a chlorine atom, Q is a chlorine atom or a group —NH—R ¹
Indicates.

Reaction of the said manufacturing method (a) can be implemented in a suitable diluent, As an example of the diluent used in that case,
water;
Ethers such as ethyl ether, methyl ethyl ether, isopropyl ether, butyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF), diethylene glycol dimethyl ether (DGM) and the like;
Alcohols such as methanol, ethanol, isopropanol, butanol, ethylene glycol and the like can be mentioned.

  The production method (a) can be carried out in the presence of an acid binder, and as such an acid binder, hydrides, hydroxides, carbonates and bicarbonates of alkali metals and alkaline earth metals as inorganic bases can be used. Examples of the salt include sodium hydride, lithium hydride, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide.

The production method (a) can be carried out within a substantially wide temperature range.
Generally, it can be carried out between about -78 to about 200 ° C, preferably between about -20 and about 140 ° C. The reaction is preferably carried out under normal pressure, but can be operated under pressure or reduced pressure.

  In carrying out the production method (a), for example, by reacting 1 mol of the compound of formula (II) in the presence of 1.0 to 10 mol of potassium hydroxide in a diluent such as dioxane-water. The target compound (I) can be obtained.

  The active compounds of the formula (I) according to the invention exhibit a strong fungicidal action and can in fact be used to control unwanted phytopathogenic fungi.

  The active compounds of the formula (I) according to the invention are generally used as fungicides (Plasmodiophoromycetes), Oomycetes, Zygomycetes, Ascomycetes, Basidiomycetes (Basidiomycetes) It can be used against various plant diseases caused by Basidiomycetes and Deuteromycetes.

According to the invention, the active compound of formula (I) is in particular:
Cucumber gray mold ( Botrytis cinerea ),
It shows excellent control effect against rice blast ( Pyricularia oryzae ). In addition, the present invention includes compounds showing an excellent control effect against rice mold fungus ( Fusarium graminearum ).

  The active compound of the formula (I) according to the present invention exhibits good compatibility with the plant at the concentration of the active compound necessary for controlling phytopathogenic fungi. Chemical treatment, chemical treatment of rootstocks and seeds, and soil treatment are possible.

  The active compounds of the formula (I) according to the invention can furthermore be used in the protection of various materials and raw materials to protect them against unwanted infection and destruction by microorganisms.

  In the present specification, “materials, raw materials” are understood to mean inanimate materials that have been widely produced for their use.

  Examples of various materials and materials that can be protected by the active compound of the present invention against changes or destruction caused by invasion of microorganisms include, for example, adhesives, sizes (glue), paper and cardboard, woven fabric, leather, wood, Paints and synthetic paints, cooling lubricants, heat exchange fluids and all other materials that can be infected and destroyed by microorganisms, particularly preferably wood.

  The area of materials, materials to be protected includes parts of the manufacturing plant, for example cooling water circuits that can be harmed by the growth of microorganisms.

  Examples of microorganisms that cause deterioration or change of materials and raw materials include bacteria, fungi, yeasts, algae, and slime organisms.

  The active compounds of the formula (I) according to the invention are preferably against fungi, in particular mold, fungi that discolor or destroy wood (Basidiomycetes), and slime organisms and algae Shows the effect.

For example, microorganisms belonging to the following genera can be cited:
Alternaria, such as Alternaria tenuis, Aspergillus, such as Aspergillus niger, Chaetomium, such as Chaetomium globosum, Idake Coniophora, such as Coniophora puetana, Lentinus, such as Lentinus tigrinus, Penicillium, such as Penicillium glaucum, Penicillium porus,・ Polyporus versicolor, Aureobasidium, such as Aureobasidium pullulans, Sclerophoma, such as Sclerophoma pityoph ila), Trichoderma, such as Trichoderma viride, Escherichia, such as Escherichia coli, Pseudomonas, such as Pseudomonas aeruginosa, Staphylococcus (Staphylococcus), for example Staphylococcus aureus.

  Moreover, the compound of the formula (I) of the present invention has low toxicity to warm-blooded animals and can be used safely.

  The active compound of the formula (I) of the present invention can be formulated into a usual preparation form when used as an agricultural chemical or the like. Examples of the dosage form include liquids, wettable powders, emulsions, suspensions, powders, foams, pastes, tablets, granules, aerosols, active compound infiltration-natural and synthetic, microcapsules, seed coatings. , ULV [cold mist, warm mist] and the like.

  These preparations can be produced in a manner known per se. For example, the active compound is prepared by mixing with a developing agent, i.e. a liquid diluent, solid diluent or carrier, and optionally with a surfactant, i.e. emulsifier and / or dispersant and / or foam former. be able to.

  Liquid diluents or carriers generally include aromatic hydrocarbons (eg, xylene, toluene, alkylnaphthalene, etc.), chlorinated aromatic or chlorinated aliphatic hydrocarbons (eg, chlorobenzenes, ethylene chlorides, Methylene chloride etc.), aliphatic hydrocarbons [eg cyclohexane etc., paraffins (eg mineral oil fraction etc.)], alcohols (eg butanol, glycol etc.) and their ethers, esters etc., ketones (eg Acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), strong solvents (for example, dimethylformamide, dimethyl sulfoxide, etc.), and water. When water is used as the developing agent, for example, an organic solvent can be used as an auxiliary solvent.

  Examples of the solid diluent include ground natural minerals (for example, kaolin, clay, talc, chalk, quartz, attapul guide, montmorillonite, diatomaceous earth, etc.), ground synthetic minerals (for example, highly dispersed silicic acid, alumina, silicates, etc.) Can be mentioned.

  Solid carriers for granules include, for example, crushed and fractionated rocks (eg calcite, marble, pumice, gabbro, dolomite, etc.), synthetic grains of inorganic and organic powders, organic substances (eg sawdust) , Coconuts, corn cobs, tobacco stems, etc.).

  Examples of the emulsifier and / or foaming agent include nonionic and anionic emulsifiers [for example, polyoxyethylene fatty acid ester, polyoxyethylene fatty acid alcohol ether (for example, alkylaryl polyglycol ether, alkyl sulfonate, alkyl sulfate, Aryl sulfonates, etc.)], albumin hydrolysis products, and the like.

  Examples of the dispersant include lignin sulfite waste liquid, methylcellulose and the like.

  The sticking agent can also be used in preparations (powder, granules, emulsions). Examples of the sticking agent that can be used in this case include carboxymethyl cellulose, natural and synthetic polymers (eg, gum arabic, polyvinyl alcohol, polyvinyl). Acetate).

  A colorant can also be used. Examples of the colorant include inorganic pigments (for example, iron oxide, titanium oxide, Prussian blue, etc.), alizarin dyes, organic dyes such as azo dyes or metal phthalocyanine dyes, and iron, manganese. And trace elements such as boron, copper, cobalt, molybdenum, zinc and salts of these metals.

  The formulations in general contain the active compounds of the formula (I) according to the invention in a proportion in the range from 0.1 to 95% by weight, preferably from 0.5 to 90% by weight.

  The active compounds of the formula (I) according to the invention can be used in the above formulations or in various use forms, for example in other known active compounds such as fungicides (fungisides, bacteriides), insecticides, acaricides, nematocides. , Herbicides, avian repellents, growth regulators, fertilizers and / or soil conditioners.

  When the active compound of the formula (I) of the present invention is actually used, it is used directly as it is or in the form of a preparation for spraying, an emulsion, a suspension, a powder, a tablet, a paste, a micro-cuff cell, a granule, etc. Or in a use form prepared by further dilution. The active compound is then applied in the usual way, for example, watering, dipping, spraying, atomizing, misting, irrigation, suspension formation, application, dusting, dusting, dressing, wet dressing, wet coating, pasty It can be applied by a method such as coating or robe coating.

  In the treatment of each part of the plant body, the concentration of the active compound in the actual use form can vary within a substantial range, but is generally 0.0001 to 1% by weight, preferably 0.001. It can be in the range of -0.5 wt%.

  In seed treatment, the active compound can be used in a proportion of generally 0.001 to 50 g, preferably 0.01 to 10 g, per 1 kg of seed.

  In the soil treatment, it is possible to use an active compound having a concentration in the range of generally 0.00001 to 0.1% by weight, particularly 0.0001 to 0.02% by weight, based on the point of action.

  Next, although the specific example shows the manufacture and use of the compound of this invention by the following example, this invention should not be limited only to these.

<Examples of compound production>
Synthesis example 1

５−クロロ−７−（１，２−ジメチルプロピルアミノ）−６−（３−フルオロベンジル）−ピラゾロ［１，５−ａ］ピリミジン−３−カルボン酸エチルエステル（２４１ｍｇ、０．５６ｍｍｏｌ）をジオキサン（２０ｍｌ）に溶解し、水（１０ｍｌ）及び水酸化カリウム（１３０ｍｇ）を加え、９０℃で２時間３０分攪拌した。反応終了後、減圧下濃縮し、氷水を加え、濃塩酸で酸性化し、沈殿を瀘別し、水、次いでｎ−ヘキサンで洗浄後、デシケーターで乾燥し、５−クロロ−７−（１，２−ジメチルプロピルアミノ）−６−（３−フルオロベンジル）−ピラゾロ［１，５−ａ］ピリミジン−３−カルボン酸（２００ｍｇ）を得た。
ｍｐ １９１−１９４℃

5-Chloro-7- (1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester (241 mg, 0.56 mmol) was added to dioxane. (20 ml), water (10 ml) and potassium hydroxide (130 mg) were added, and the mixture was stirred at 90 ° C. for 2 hours 30 minutes. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, ice water was added, acidified with concentrated hydrochloric acid, the precipitate was filtered off, washed with water and then with n-hexane, dried in a desiccator, and 5-chloro-7- (1,2 -Dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid (200 mg) was obtained.
mp 191-194 ° C

  The compounds obtained in the same manner as in Synthesis Example 1 are shown in Table 1 together with the compounds synthesized in Synthesis Example 1.

Reference Example 1 (Manufacture of raw materials)

３−フルオロベンジルブロミド（５０ｇ、０．２６ｍｏｌ）、ジエチルマロネート（３２０ｍｌ、２．１ｍｏｌ）および炭酸カリウム（８０ｇ、０．５８ｍｏｌ）をアセトン（３００ｍｌ）に縣濁し７５℃で６時間攪拌した。反応終了後、沈殿物を濾過、アセトン洗浄した。減圧下、溶媒、過剰のマロン酸ジエチルを除去し、残渣をシリカゲルカラムクロマトグラフィー（溶出溶媒： ｎ−ヘキサン：酢酸エチル＝２０：１）にて精製し、ジエチル（３−フルオロベンジル）マロネート（６２ｇ）を得た。
そのまま精製することなく、次の反応に用いた。

3-Fluorobenzyl bromide (50 g, 0.26 mol), diethyl malonate (320 ml, 2.1 mol) and potassium carbonate (80 g, 0.58 mol) were suspended in acetone (300 ml) and stirred at 75 ° C. for 6 hours. After completion of the reaction, the precipitate was filtered and washed with acetone. Under reduced pressure, the solvent and excess diethyl malonate were removed, and the residue was purified by silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 20: 1) to give diethyl (3-fluorobenzyl) malonate (62 g). )
The product was used in the next reaction without purification.

Synthesis Example 2 (Production of Intermediate)

ジエチル（３−フルオロベンジル）マロネート（１６．１ｇ、６０ｍｍｏｌ）、３−アミノ−４−ピラゾールカルボン酸エチル（９．６ｇ、６０ｍｍｏｌ）及びトリブチルアミン（２９ｍｌ、１２０ｍｍｏｌ）の混合物を、１９０℃にて１３時間加熱攪拌した。反応混合物を冷却し、水を加えた。氷冷下、濃塩酸で酸性化し、沈殿を瀘別し、水、次いでｎ−ヘキサンで洗浄後、デシケーターで乾燥し、６−（３−フルオロベンジル）−５，７−ジヒドロキシピラゾロ［１，５−ａ］ピリミジン−３−カルボン酸エチルエステル（２７．７ｇ）を得た。
そのまま精製することなく、次の反応に用いた。

A mixture of diethyl (3-fluorobenzyl) malonate (16.1 g, 60 mmol), ethyl 3-amino-4-pyrazolecarboxylate (9.6 g, 60 mmol) and tributylamine (29 ml, 120 mmol) was prepared at Stir for hours. The reaction mixture was cooled and water was added. Acidified with concentrated hydrochloric acid under ice-cooling, the precipitate was filtered off, washed with water and then with n-hexane, dried with a desiccator, and 6- (3-fluorobenzyl) -5,7-dihydroxypyrazolo [1, 5-a] pyrimidine-3-carboxylic acid ethyl ester (27.7 g) was obtained.
The product was used in the next reaction without purification.

Synthesis Example 3 (Production of Intermediate)

６−（３−フルオロベンジル）−５，７−ジヒドロキシピラゾロ［１，５−ａ］ピリミジン−３−カルボン酸エチルエステル（２７．７ｇ）にＮ，Ｎ−ジメチルアニリン（１５ｍｌ）、オキシ塩化リン（１００ｍｌ）を加え９時間加熱還流した。反応終了後、減圧下、過剰のオキシ塩化リンを除去し、氷水を加え、酢酸エチルで抽出した。酢酸エチル層を無水硫酸マグネシウムで乾燥し、シリカゲルを詰めたグラスフィルターにて酢酸エチルを用いて濾過した。瀘液を減圧下濃縮し得られた粗製生成物をジオキサンに溶解し、氷水を加え、生成した沈殿を瀘別し、水で洗浄後、デシケーターで乾燥し、５，７−ジクロロ−６−（３−フルオロベンジル）−ピラゾロ［１，５−ａ］ピリミジン−３−カルボン酸エチルエステル（１６．３ｇ）を得た。
ｍｐ １１２−１１５℃。

6- (3-Fluorobenzyl) -5,7-dihydroxypyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester (27.7 g) and N, N-dimethylaniline (15 ml), phosphorus oxychloride (100 ml) was added and heated to reflux for 9 hours. After completion of the reaction, excess phosphorus oxychloride was removed under reduced pressure, ice water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, and filtered through a glass filter packed with silica gel using ethyl acetate. The crude product obtained by concentrating the filtrate under reduced pressure was dissolved in dioxane, ice water was added, the formed precipitate was filtered off, washed with water, dried in a desiccator, and 5,7-dichloro-6- ( 3-Fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester (16.3 g) was obtained.
mp 112-115 ° C.

Synthesis Example 4 (Production of Intermediate)

５，７−ジクロロ−６−（３−フルオロベンジル）−ピラゾロ［１，５−ａ］ピリミジン−３−カルボン酸エチルエステル（６８ｍｇ、１．０ｍｍｏｌ）をテトラヒドロフラン（２０ｍｌ）に溶解し、次いで１，２−ジメチルプロピルアミン（１２０μｌ、１．０ｍｍｏｌ）およびトリエチルアミン（４２０μｌ、３．０ｍｍｏｌ）を加え、室温で４時間攪拌した。反応終了後、沈殿物を除去し、濾液を減圧下濃縮し、残渣をシリカゲルカラムクロマトグラフィー（溶出溶媒： ｎ−ヘキサン：酢酸エチル＝９：１）にて精製し、５−クロロ−７−（１，２−ジメチルプロピルアミノ）−６−（３−フルオロベンジル）−ピラゾロ［１，５−ａ］ピリミジン−３−カルボン酸エチルエステル（３５２ｍｇ）を得た。
ｍｐ ９０−９３℃。

5,7-Dichloro-6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester (68 mg, 1.0 mmol) was dissolved in tetrahydrofuran (20 ml) and then 1, 2-Dimethylpropylamine (120 μl, 1.0 mmol) and triethylamine (420 μl, 3.0 mmol) were added, and the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the precipitate was removed, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: n-hexane: ethyl acetate = 9: 1) to give 5-chloro-7- ( 1,2-Dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester (352 mg) was obtained.
mp 90-93 ° C.

Representative examples of the compounds of formulas (II), (III) and (V) obtained in the same manner as in Synthesis Examples 2 to 4 are shown below.
7-sec-butylamino-5-chloro-6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
7- (R) -sec-butylamino-5-chloro-6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
7- (S) -sec-butylamino-5-chloro-6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
7-sec-butylamino-5-chloro-6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
7- (R) -sec-butylamino-5-chloro-6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
7- (S) -sec-butylamino-5-chloro-6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7-((R) -1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7-((S) -1,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2-dimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7-((R) -1,2-dimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7-((S) -1,2-dimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (2,2-dimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (2,2-dimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2,2-trimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7-((R) -1,2,2-trimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7-((S) -1,2,2-trimethylpropylamino) -6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7- (1,2,2-trimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-chloro-7-((R) -1,2,2-trimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5-Chloro-7-((S) -1,2,2-trimethylpropylamino) -6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester.
5,7-dichloro-6- (3-fluorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
5,7-Dichloro-6- (3-chlorobenzyl) -pyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester.
6- (3-fluorobenzyl) -5,7-dihydroxypyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester,
6- (3-Chlorobenzyl) -5,7-dihydroxypyrazolo [1,5-a] pyrimidine-3-carboxylic acid ethyl ester.

<Biological test example>
Test Example 1 : Preparation of test compound for foliage spraying efficacy test against cucumber gray mold Active compound: 5 parts by weight Organic solvent: Acetone 142.5 parts by weight Emulsifier: Polyoxyethylene alkyl phenyl ether 7.5 parts by weight The above active compound Acetone and emulsifier are mixed, diluted with water to a predetermined concentration, and used for the test.

Test Method Cucumber (variety: Sagamihanjiro) was cultivated in a plastic pot having a diameter of 4 cm, and 6 ml of a predetermined concentration diluted solution of an active compound prepared in advance was sprayed on small seedlings that reached the cotyledon. One day after spraying, a suspension of artificially cultured gray mold spores ( Botrytis cinerea ) mixed with agar gel (2 × 10 ⁴ spores / ml gel) is inoculated on the cotyledon as an inoculum, and inoculated in a wet box And kept at 20 ° C. for infection and disease. Four days after the inoculation, the morbidity per cotyledon was evaluated according to the following criteria, and the control value (%) was further determined. The phytotoxicity was also investigated at the same time. This test is the average of the results from 2 wards and 4 leaves.

The morbidity evaluation and control value calculation methods are as follows.
Disease severity Rate of lesion area (%)
0 0
0.5 Less than 2 1 Less than 2 to 5 2 Less than 5 to 10 3 Less than 10 to 20 4 Less than 20 to 40 5 40 or more

Control value (%) = (1- {morbidity of treated area ÷ morbidity of untreated area}) × 100

Test results As representative examples, compounds Nos. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and 20 are drugs. A control value of 100% was exhibited at the concentration (500 ppm). In the compound of the present invention, no phytotoxicity was observed.

Test Example 2 : Stem and foliage spraying efficacy test for rice blast Test method Rice (cultivar: Koshihikari) was cultivated in a plastic pot with a diameter of 4 cm and prepared in the same manner as in Test Example 1 from 1.5 to 2 leaves. 6 ml of a predetermined concentration dilution of the active compound was sprayed per 3 pots. One day after the spraying, an artificially cultured spore suspension of rice blast fungus ( Pyricularia oryzae ) was spray-inoculated (once) and kept at 25 ° C. and 100% relative humidity for infection. Seven days after the inoculation, the morbidity per pot was classified and the control value (%) was determined. The phytotoxicity was also investigated at the same time. This test is the average of the results of 3 pots in 1 district.

The morbidity evaluation and control value calculation methods are as follows.
Disease severity Rate of lesion area (%)
0 0
0.5 Less than 2 1 Less than 2-5 2 Less than 5-10 3 Less than 10-20 4 Less than 20-40 5 40 or more

Control value (%) = (1- {morbidity of treated area ÷ morbidity of untreated area}) × 100

Test Results As representative examples, the compounds of Compound Nos. 11, 13, 14, 15 and 17 exhibited a control value of 100% at the drug concentration (500 ppm). In the compound of the present invention, no phytotoxicity was observed.

Formulation Example 1 (Granule)
Water (25 parts) was added to a mixture of the present compound No. 15 (10 parts), bentonite (montmorillonite) (30 parts), talc (talc) (58 parts) and lignin sulfonate (2 parts) and well hatched. Then, it is granulated to 10 to 40 mesh with an extrusion granulator and dried at 40 to 50 ° C. to give granules.

Formulation Example 2 (Granule)
After putting clay mineral grains (95 parts) having a particle size distribution in 0.2-2 mm into a rotary mixer, and spraying the compound No. 13 (5 parts) of the present invention together with a liquid diluent under rotation, the mixture is uniformly moistened. Dry at 40-50 ° C. to give granules.

Formulation Example 3 (Emulsion)
The compound No. 7 (30 parts) of the present invention, xylene (55 parts), polyoxyethylene alkylphenyl ether (8 parts) and calcium alkylbenzenesulfonate (7 parts) are mixed and stirred to obtain an emulsion.

Formulation Example 4 (Wetting agent)
Compound No. 14 (15 parts) of the present invention, mixture of white carbon (hydrous amorphous silicon oxide fine powder) and powder clay (1: 5) (80 parts), sodium alkylbenzenesulfonate (2 parts) and alkylnaphthalenesulfonic acid Sodium formalin polymer (3 parts) is mixed with powder to obtain a wettable powder.

Formulation Example 5 (Hydrated Granules)
Compound No. 11 (20 parts) of the present invention, sodium lignin sulfonate (30 parts), bentonite (15 parts) and calcined diatomaceous earth powder (35 parts) were added well, water was added, and the mixture was extruded through a 0.3 mm screen. Dry into hydrated granules.

  The novel pyrazolopyrimidine derivatives of the present invention have excellent properties as agricultural and horticultural fungicides, as is apparent from the above biological test examples.

Claims (5)

formula

Where
R ¹ represents C _4-6 branched alkyl, and R ² represents halogen,
A pyrazolopyrimidine derivative represented by: R ¹ represents sec-butyl, 1,2-dimethylpropyl, neopentyl or 1,2,2-trimethylpropyl, and R ² represents fluorine or chlorine.
The compound represented by Claim 1. R ¹ represents 1,2-dimethylpropyl or 1,2,2-trimethylpropyl, and R ² represents fluorine or chlorine,
The compound represented by Claim 1.   An agricultural and horticultural fungicide containing the compound according to any one of claims 1 to 3 as an active ingredient. formula

Where
R ² represents halogen,
R ³ represents C _1-4 alkyl;
R ⁴ represents a hydroxy or chlorine atom, and Q represents a hydroxy, chlorine atom or group —NH—R ¹
Wherein R ¹ represents C _4-6 branched alkyl,
Provided that when R ⁴ represents hydroxy, Q represents hydroxy;
When R ⁴ represents a chlorine atom, Q is a chlorine atom or a group —NH—R ¹
Showing,
A pyrazolopyrimidine derivative represented by: