RU2043716C1 - Amide derivative and fungicide composition on its basis - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: amide derivative of the formula X₁, R₁, R₂, R₃ where

Description

 The invention relates to new condensed heterocyclic compounds or their salts, their intermediate compounds, the method for their preparation and fungicide based on them for the processing of agricultural and horticultural crops.

 Some types of amide compounds with fungicidal activity against pathogenic fungi causing various plant diseases are known. For example, the compounds disclosed in Japanese Patent Application Laid-Open No. 135364/1988, which did not pass the novelty examination, Europatent Published Application No. 61836A and UK Patent Application No. 2190375A, are active against fungi of downy mildew pathogens of grapevines and cucumbers and pathogenic mushrooms tomato and potato. However, such compounds do not have a sufficient regulatory effect and do not provide safety.

 It is necessary to create compounds that have an excellent effect for combating plant diseases, a method for their preparation and a preparation based on them to suppress plant diseases.

 Powdery mildew and other diseases of plants and fruit trees tend to occur and spread during heavy rainfall. On this basis, we need compounds that are not washed off by rain (rain resistance), have a good effect for controlling plant diseases for their treatment without damaging cultivated plants, and have low toxicity with respect to warm-blooded animals and fish.

 The inventors carried out intensive studies to solve the above problems and obtained condensed heterocyclic compounds of the general formula I and their salts, which, as it has been established, have an excellent effect for combating various types of plant diseases, especially with downy mildew along with excellent rain tolerance, while not damaging plants, and which are less toxic to warm-blooded animals and fish. These compounds can be obtained industrially.

I где Q конденсированная гетероциклическая группа, содержащая атом азота, замещенный или незамещенный в головной части мостика, Х атом водорода или группа, присоединяемая через С, О, S или N, а У группа, притягивающая электроны, или его соли.Thus, the present invention relates to a fused heterocyclic compound of the general formula
Q-CONH-CH

I where Q is a condensed heterocyclic group containing a nitrogen atom, substituted or unsubstituted at the head of the bridge, X is a hydrogen atom or a group attached via C, O, S or N, and Y is an electron attracting group or its salts.

III где Х и Y имеют указанные в формуле I значения, или с его солью.The present invention also relates to a method for producing a condensed heterocyclic compound I or its salt by reacting a compound of the general formula
Q-CO-Z II where Q has the meanings given above in formula I, and Z means a leaving group or its salts with a compound of the general formula
H ₂ N-CH

III where X and Y have the meanings indicated in formula I, or with its salt.

 In addition, the present invention relates to a fungicide for the protection of crops and horticultural crops based on a condensed heterocyclic compound of the general formula I or its salt.

R₁,

R₁,

N

N, R

R₁,

R₁,

R₂,

R₁, или

R₁
где R₁ С_1-6-алкил, галоген, С_1-4-алкокси, С_1-4-алкилтио, С_6-10-арилокси, С_6-10-арилтио, алкоксикарбонил, фенил, замещенный фенил или ароматическая гетероциклическая группа; R₂ и R₃ водород, С_1-6-алкил, галоген, нитро-, аминосульфогруппа, моно- или двузамещенный алкилсульфамоил, алкоксикарбонил, формил, цианогруппа, фенил, замещенный фенил или ароматическая гетероциклическая группа, при условии, что, когда Q₁ означает

а R₁ означает СООН₂СН₃, то либо одно из R₂ и R₁ представляет другую группу, кроме водорода, а Z означает уходящую группу, или его соль.According to yet another embodiment, the present invention provides a condensed heterocyclic carboxylic acid compound of the general formula
Q ₁ -CO-Z IV where Q ₁ means a fused heterocyclic group containing a nitrogen atom in the head of the bridge, as follows in the formulas below

R ₁

R ₁

N

N, R

R ₁

R ₁

R ₂

R ₁ , or

R ₁
where R ₁ C _1-6 alkyl, halogen, C _1-4 alkoxy, C _1-4 alkylthio, C _6-10 aryloxy, C _6-10 arylthio, alkoxycarbonyl, phenyl, substituted phenyl or an aromatic heterocyclic group ; R ₂ and R _{3 are} hydrogen, C _1-6 alkyl, halogen, nitro, amino sulfo group, mono- or disubstituted alkyl sulfamoyl, alkoxycarbonyl, formyl, cyano group, phenyl, substituted phenyl or aromatic heterocyclic group, provided that when Q ₁ means

and R ₁ means COOH ₂ CH ₃ , then either one of R ₂ and R ₁ represents a group other than hydrogen, and Z means a leaving group, or a salt thereof.

R₁, R

R₁,

R₁,

R₁, или

R₁
где R₁, R₂ и R₃ имеют указанные выше значения, или его соль, заключающийся в том, что включает взаимодействие соединения общей формулы

V где ядро

означает группу пиридина, пиридазина, пиримидина или пиразина, которая не замещена или замещена С_1-6-алкилом, галогеном, нитро-, амино-, сульфо-, моно- или диалкилсульфамоилом, алкоксикарбонилом, формилом, циано-, фенилом, замещенным фенилом или ароматической гетероциклической группой, а Z означает уходящую группу, либо его соли с соединением общей формулы
W-

-CO-R₁ VI или
W-

-NHOH VII где W атом галогена, а R₁ и R₂ имеют указанные выше значения.According to another embodiment, the present invention provides a process for preparing a compound of general formula
Q ₂ —CO — Z VIII where Q ₂ is a group of the general formula

R ₁ , R

R ₁

R ₁

R ₁ , or

R ₁
where R ₁ , R ₂ and R ₃ have the above meanings, or its salt, which consists in the fact that it includes the interaction of the compounds of General formula

V where is the core

means a group of pyridine, pyridazine, pyrimidine or pyrazine, which is unsubstituted or substituted by C _1-6 -alkyl, halogen, nitro-, amino-, sulfo-, mono- or dialkylsulfamoyl, alkoxycarbonyl, formyl, cyano-, phenyl, substituted phenyl or aromatic heterocyclic group, and Z means a leaving group, or its salts with a compound of the general formula
W-

-CO-R ₁ VI or
W-

-NHOH VII where W is a halogen atom, and R ₁ and R ₂ are as defined above.

 Compound I or a salt thereof of the present invention has a new structure characterized by the combination of a specific group, namely a fused heterocyclic group containing a nitrogen atom in the head of the bridge with a carbonyl group, which differs from the known amide compounds. The advantage of the proposed compound is that it has a good effect of inhibiting downy mildew and fungal diseases of plants, excellent water resistance, does not damage plants and is less toxic to warm-blooded animals and fish.

 A preferred embodiment of the invention.

 In formulas I and II, Q denotes a fused heterocyclic group containing a nitrogen atom in the head of the bridge, which is substituted or unsubstituted. A fused heterocyclic group containing a nitrogen atom in the head of the bridge means a fused heterocyclic group, where the atom (s) of the "head" or "tail" of the bridging bond, namely both or any of them is a non-ionized nitrogen atom. A fused heterocyclic group containing an atom in the head of the bridge, designated Q, is a group formed by the removal of one hydrogen atom bonded to a ring carbon atom in a position other than the head of the bridge of the fused heterocyclic compound represented, for example, by the general formula G or D (see Fig. 1), where a and b are a heterocyclic nucleus containing a nitrogen heteroatom that is not substituted or substituted.

 These fused heterocyclic groups may be represented, for example, by the general formula E or G (see FIG. 1).

 Preferred of them is the group represented on the left side of the specified formula.

 An N-containing heterocyclic ring represented by rings a and b means a 4-8 membered, preferably 5-6 membered heterocycle containing from one to four nitrogen atoms, which, in addition, may include from one to three oxygen atoms and / or from one to three sulfur atoms, possibly mono- or dioxidized. Such a heterocyclic ring may be further condensed with a 5-6 membered aliphatic ring (e.g. cyclopentane, cyclohexane), an aromatic ring (e.g. benzene or naphthalene), or a heterocycle (preferably a 5-6 membered heterocycle).

 Among these fused heterocyclic nuclei, groups formed by condensation of the 5- and 6-membered nuclei are preferred.

 In the above formula, the core a is preferably a 5-membered heterocycle containing one to three nitrogen atoms, and the core b is a 6-membered heterocycle containing one to two nitrogen atoms and one sulfur atom, possibly mono- or dioxide.

Kernels a and b may be substituted by 1-3 substituents (B ₁ , B ₂ , B ₃ ) having the same or different meanings, as indicated below.

In particular, the group represented by the general formula And (see Fig. 1) includes groups, for example, represented by the general formulas K (see Fig. 2), where A 'is a group forming a condensed ring at the positions [1, 2] of the imidazole ring ; A '' group forming a fused ring at the positions [1, 5] of the imidazole ring; A '''group forming a fused ring at the positions [1, 5] of the pyrazole ring; A '''' group forming a condensed ring at the positions (1, 2) of the pyrrole ring; A '''' the group forming a condensed ring at the positions (3, 4) of the triazole ring; B ₁ , B ₂ and B ₃ have the following meanings.

 Group A, A ″, A ″ ″ or A ″ ″ ″ contains from one to four, preferably from three to four carbon atoms as the atom forming the ring, and may additionally contain from one to three nitrogen, oxygen and / or sulfur (which may be present in mono- or dioxide form).

 Among these fused heterocyclic groups, groups represented by general formulas A are preferred (see FIG. 2).

 Most preferred is a group represented by general formula M (see FIG. 2).

 Examples of condensed rings represented in the form of a skeleton of the general formula (see Fig. 3) include the following: (see Fig. 4).

 Examples of condensed rings represented in the skeletons of a group of the general formula (see FIG. 5) include the following: (FIG. 6).

 Examples of condensed rings represented in the form of a skeleton of a group of the general formula (see FIG. 7) include (see FIG. 8).

 Examples of condensed rings represented in the form of a skeleton of a group of the general formula (see FIG. 9) include (see FIG. 10).

 Examples of condensed rings represented in the form of a skeleton of a group of the general formula (see FIG. 11) include (see FIG. 12).

In particular, the indicated fused heterocyclic groups include the following:
imidazo [1,2-a] pyridine, imidazo [1,2-a] pyrimidine, imidazo [1,2-c] pyrimidine, imidazo [1,2-a] pyrazine, imidazo [1,2-b] pyridazine, imidazo [1,2-b] - (1,2,4) -triazine, imidazo [2,1-a] imidazole, imidazo [1,2-b] pyrazole, imidazo [2,1-b] thiazole, imidazo [2,1-b] - (1,3,4) -thiazole, 2,3-dihydroimidazo [2,1-b] thiazole, pyrazolo [1,5-a] pyrimidine, pyrazolo [5,1-a] thiazole, pyrazolo [1,5-a] pyridine, pyrrolo [1,3-b] pyridine, imidazo [1,5-a] pyridine and (1,2,4) -triazolo [3,4-b] thiazole.

On the other hand, the group represented by the general formula H (see FIG. 13) includes groups represented, for example, by the general formulas P (see FIG. 13), where B ₁ and B ₂ each have the following meaning.

 In particular, 6H- (1,2,4) -triazolo [1,2-b] - (1,2,3,4) -tetrazyl, 1H- (1,2,4) triazolo can be given as an example [1 , 2-a] - (1,2,4) triazyl, (1,2,3) -triazolo [2,1-a] - (1,2,3) - triazinium-4, (1,2 4) -triazolo [1,2-a] pyridazinium-4 and 6H-pyrazolo [1,2-a] - (1,2,4,5) -tetrazyl.

The substituents B ₁ , B ₂ and B _{3 of} the fused heterocyclic group for Q may have the same or different meanings. Examples of these substituents include hydrogen, nitro, amino, hydroxyl, cyano, C _1-3 acyl (formyl, etc.), carbamoyl, carboxyl, alkoxycarbonyl (for example, C _1-4 alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, etc.), sulfo group, halogen (chlorine, bromine, iodine, fluorine, etc.), C _1-4 alkoxy (methoxy, ethoxy, propoxy, isopropoxy, butoxy , isobutoxy, sec-butoxy, tert-butoxy, etc.), C _6-10 aryloxy (phenoxy, etc.), C _6-10 arylcarbonyl (benzoyl, etc.), C _{6- 10} aryl (phenyl, and t. d.), C _7-10 aralkyl (benzyl, phenethyl L, etc.), C _3-7 cycloalkyl (cyclohexyl, t. d.), _C1-4 alkylthio (methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio, and t tretbutiltio. d.), C _6-10 arylthio (phenylthio, etc.), C _7-10 aralkylthio (benzylthio, etc.), mono- or dialkylsulfamoyl (e.g. mono- or di-C _1-4 -alkylsulfamoyl, for example mono- or dimethylsulfamoyl, mono- or diethylsulfamoyl, mono- or di-n-propyl-sulfamoyl), C _1-6 -alkyl (methyl, ethyl, propyl, isopropyl, pentyl, hexyl, etc.) substituted phenyl (mono-, di-, tri- or tetrahalogen substituted phenyl, e.g. 2-chloro rphenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 4-bromophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, etc. e.), mono-, di-, tri- or tetra-C _1-4 alkyl-substituted phenyl, for example 2-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 2,4-dimethylphenyl, 2, 5-dimethylphenyl, 3,4-dimethylphenyl, 2,5-diethylphenyl, 2,4,6-trimethylphenyl, etc. mono-, di-, tri- or tetra-C _1-4 alkoxy substituted phenyl, for example 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, etc. mono-, di-, tri- or tetra-C _1-4 - alkylthio substituted phenyl, for example 2-methylthiophenyl, 3,4-dimethylthiophenyl, etc. 2-chloro-4-nitrophenyl, 4-nitrophenyl, 2-methyl- 4-aminophenyl, 2-bromo-4-nitrophenyl, 2-nitro-4-methylphenyl, etc.), an aromatic heterocyclic group (a five- or six-membered heterocyclic group, for example pyridyl, furyl, thienyl, thiazolyl, etc. ) Particularly preferred is the use of B ₁ , A ₂ and B ₃ C _1-6 alkyl, phenyl or substituted phenyl as substituents.

R₁,

R₁,

N

N, R

R₁,

R₁,

R₂,

R₁, или

R₁
В качестве заместителей R₁, R₂ и R₃ используют одинаковые или разные заместители, которые имеют указанные выше значения, но любой из R₂ и R₃ означает группу кроме атома водорода, если Q₁ означает

R₂ а R₁ означает СООСН₂CH₃.Q ₁ in formula IV means a condensed heterocyclic group containing a nitrogen atom in the head of the bridge, represented by the following formulas:

R ₁

R ₁

N

N, R

R ₁

R ₁

R ₂

R ₁ , or

R ₁
As substituents R ₁ , R ₂ and R ₃ , the same or different substituents are used, which have the above meanings, but any of R ₂ and R ₃ means a group other than a hydrogen atom, if Q ₁ means

R ₂ a R ₁ means COOCH ₂ CH ₃ .

Examples of the substituent R ₁ include C _1-6 alkyl, halogen, C _1-4 alkoxy, C _1-4 alkylthio, C _6-10 aryloxy, C _6-10 arylthio, alkoxycarbonyl, phenyl, substituted phenyl or an aromatic heterocyclic group as described in the above B ₁ , B ₂ and B ₃ . Examples of the substituents R ₂ and R ₃ include hydrogen, nitro, amino, sulfo, formyl, cyano or phenyl, as well as C _1-6 -alkyl, halogen, mono- or di-alkylsulfamoyl, alkoxycarbonyl, substituted phenyl or aromatic heterocyclic groups as indicated in the above B ₁ , B ₂ and B ₃ .

Preferred substituents of R ₁ are phenyl or substituted phenyl.

Preferred Q ₁ groups are Q ′ or Q ″, which are described below.

 The symbol X in the general formula I means a hydrogen atom or a group attached through an atom of C, O, S or N. A group attached through a carbon atom may be alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl or aralkyl, or an aromatic heterocyclic group, containing a chemical bond at a carbon atom; a group attached through atom 0 may be alkoxy, aryloxy or aralkyloxy; a group attached through an S atom may be an alkylthio, arylthio or aralkylthio group; and the group attached through the N atom may be an alkylamino, arylamino or aralkylamino group, or an aromatic heterocyclic group having a chemical bond at the N atom.

 The above alkyl group or alkyl radical of haloalkyl, alkoxy, alkylthio and alkylamino groups includes a straight or branched chain group containing from one to ten carbon atoms, for example methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl , tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-octyl, n-decyl and the like.

 As the indicated alkenyl group, a group containing 2-4 carbon atoms, for example vinyl, allyl, 2-metalyl, 3-metalyl, 3-butenyl or the like, can be used.

 As a cycloalkyl group, a three to six membered group can be represented, for example cyclopropyl, cyclopentyl, cyclohexyl or the like.

 As a cycloalkenyl group, a three to four membered group can be used, for example cyclopropenyl, cyclopentenyl, cyclohexenyl or the like.

 As the aryl group and the aryl residue of the aryloxy, arylthio and arylamino groups, a group containing from six to ten carbon atoms, for example phenyl, tolyl, xylyl, naphthyl or the like, can be represented.

 As the aralkyl group or the aralkyl residue of the aralkyloxy, aralkylthio, and aralkylamino groups, there may be a group containing 7-10 carbon atoms, for example benzyl, phenethyl or the like.

,

,

и

N
В качестве ароматической гетероциклической группы, имеющей химическую связь у атома N может быть представлена пяти- или шестичленная N-содержащая группа, например

, N

,

и N

Каждая из указанных выше групп, присоединяемых через атом С, О, S или N, может дополнительно содержать от одного до четырех заместителей, например нитро-, амино-, гидроксил, циано-, карбоксил, сульфогруппу, галоген (фтор, хлор, бром и т.д.), алкоксигруппу, содержащую от одного до четырех атомов углерода (метокси, этокси, и т.д.), алкилтиогруппу, содержащую от одного до четырех атомов углерода (метилтио, этилтио и т.д.), фенилтиогруппу, бензилтиогруппу и т.п.As an aromatic heterocyclic group having a chemical bond at the C atom, a five- or six-membered aromatic heterocyclic group can be represented, for example

,

,

and

N
As an aromatic heterocyclic group having a chemical bond at the N atom, a five- or six-membered N-containing group can be represented, for example

, N

,

and N

Each of the above groups, attached through an atom of C, O, S or N, may additionally contain from one to four substituents, for example, nitro, amino, hydroxyl, cyano, carboxyl, sulfo group, halogen (fluorine, chlorine, bromine and etc.), an alkoxy group containing one to four carbon atoms (methoxy, ethoxy, etc.), an alkylthio group containing one to four carbon atoms (methylthio, ethylthio, etc.), a phenylthio group, a benzylthio group etc.

Suitable examples of X include a hydrogen atom, C _1-10 alkyl, C _2-4 alkenyl, C _1-10 alkoxy, C _1-10 alkylthio, phenyl, halogen substituted phenyl, an aromatic heterocyclic group containing a chemical bond at the atom C or N or the like. Specific examples of these groups include those that are indicated as examples for the above B ₁ , B _2, and B ₃ .

 The symbol Y in the general formula I means an electron attracting group, for example a cyano, carbamoyl, thiacarbamoyl or trichloromethyl group or the like.

I^' где Q' означает группу формулы

B

(одно из значений В₁' и В₂' представляет собой С_1-6-алкил, фенил или замещенный фенил, а другое значение представляет атом водорода), Х означает фенил, галоидзамещенный фенил или ароматическая гетероциклическую группу, имеющую химическую связь у атома С.Compounds of the present invention that are of particular interest include groups of the following formula I ':
Q′-CONH-CH

I ^' where Q' means a group of the formula

B

(one of the values of B ₁ 'and B ₂ ' represents C _1-6 -alkyl, phenyl or substituted phenyl, and the other value represents a hydrogen atom), X means phenyl, halogen-substituted phenyl or an aromatic heterocyclic group having a chemical bond at the C atom .

I^'' где Q'' означает

B

(В₁'' означает фенил или замещенный фенил, В₂'' атом водорода или С_1-6-алкил), Х фенил, фторзамещенный фенил, тиенил или фурил.Another group of compounds I of interest is a group of the following formula I ''
Q ″ -CONH-CH

I ^'' where Q '' means

B

(B ₁ ″ means phenyl or substituted phenyl, B ₂ ″ hydrogen atom or C _1-6 alkyl), X phenyl, fluoro substituted phenyl, thienyl or furyl.

The C _1-6 alkyl group and substituted phenyl group exemplified for B ₁ , B _2, and B ₃ are suitable for B ₁ ′, B ₁ ″, B ₂ ′, and B ₂ ″ of the formulas I'and I ′ '. Halogen-substituted phenyl for X may be a phenyl group substituted with 1-4 halogen atoms selected from fluorine, chlorine, bromine, etc. Ortho-, meta- or para-fluorophenyl, ortho- can be used as the fluoro-substituted phenyl group for X ″ , meta-, para-difluorophenyl or 2,4,6-trifluorophenyl. Aromatic heterocyclic groups having a chemical bond at atom C indicated above for the X symbol can be used as groups for the X 'symbol.

где n 0, 1, 2, 3 или 4, l С_1-4-алкил, С_1-4-алкокси, С_1-4-алкилтиогруппу или галоген, имеющий одинаковые или разные значения. Замещенные фенильные группы, указанные выше для В₁, В₂ и В₃ можно использовать для группы

(l)_n (n= 0). Символ Х' и

в предпочительном варианте означают 2-тиенил/ и т.д.A preferred example of the characters Q 'and Q''refers

where n is 0, 1, 2, 3 or 4, l is C _1-4 alkyl, C _1-4 alkoxy, C _1-4 alkylthio or halogen having the same or different meanings. The substituted phenyl groups indicated above for B ₁ , B ₂ and B ₃ can be used for the group

(l) _n (n = 0). X 'and

preferably 2-thienyl / etc.

 Compounds I of the present invention contain an asymmetric carbon atom, and the present invention includes in its volume each isomer due to the asymmetric carbon atom and a mixture thereof.

 As the salt of the compounds of formula I of the present invention, a salt formed by the interaction of an alkali metal or alkaline earth metal, for example sodium, magnesium, potassium, calcium, etc. can be used. with an acid group (e.g., a carboxy group, etc.) contained as a substituent, or a salt formed by the reaction of an inorganic acid, e.g., hydrochloric, phosphoric, sulfuric acid, etc. or an organic acid, for example oxalic, acetic, benzoic acid with an alkali group contained in the substituent (s) or a condensed heterocycle.

 Condensed heterocycle carboxylic acids of formulas II and IV, which are used as starting materials of the present invention, or their salts can be obtained by a method analogous to the known methods (see J. J. Org. Chem. T. 37, p. 3107, 1972; J. Org. Chem. T. 36, p. 2678, 1971; J. Org. Chem. T. 42, p. 4197, 1977; J. Med. Chem. T. 17, p. 645, 1974; J. Med. Chem. T. 20, p. 386, 1977; J. Med. Chem. T. 15, p. 982, 1972; J. Med. Chem. T. 28, p. 876, 1985; Tetrahedron Lett, t 21, p. 2195, 1980, J. Chem. Soc. Perkin Trans I, p. 1159, 1887, etc.

 In particular, some of the carboxylic acids of formula II or IV, or their salts, can be obtained, for example, by reacting an aromatic heterocyclic aminocarboxylic acid, its reactive derivative or salt with a compound of formula VI or VII.

 In particular, compound VII or its salt, which is often used among new compounds IV or their salts, can be obtained by reacting a compound of formula V or its salt with compound VI or compound VII.

V' где кольцо

имеет указанные выше значения, или ее реакционно-способным производным или ее солью;
соединение VIII или его соль может быть представлено карбоновой кислотой формулы
Q₂ COOH VIII' где Q₂ имеет указанные выше значения, или ее реакционноспособным производным, либо ее солью, соответственно.In formulas II, IV, V, and VIII, Z is a leaving group and, accordingly, a COZ group may mean —COOH or a reactive derivative thereof. Thus, compound II or a salt thereof may be represented by a carboxylic acid of the formula
Q COOH II 'where Q' has the above meanings, or its reactive derivative, or its salt;
compound V or a salt thereof may be represented by a carboxylic acid of the formula

V 'where is the ring

has the above meanings, or its reactive derivative or its salt;
Compound VIII or a salt thereof may be represented by a carboxylic acid of the formula
Q ₂ COOH VIII 'where Q ₂ has the above meanings, or its reactive derivative, or its salt, respectively.

 Examples of reactive derivatives of a carboxyl group in an aromatic heterocyclic aminocarboxylic acid and carboxylic acids II ′, IV ′, V ′ and VIII ′ include acid anhydrides, active amides, active esters or the like.

 The following are specific examples of such reactive derivatives.

 Acid anhydrides can be represented by mixed anhydrides with halogen substituted acids (for example, hydrochloric acid or hydrobromic acid), carbonic esters, aliphatic carboxylic acids (for example, acetic, trimethylacetic, valerianic, isovalerianic or trichloroacetic acids, for example, or acid), symmetric acid anhydrides.

 As active amides, there may be amides with pyrazole, imidazole, 4-substituted imidazole, dimethylpyrazole or benztriazole.

 As active esters, methyl, ethyl, methoxymethyl, propargyl, 4-nitrophenyl, 2,4-dinitrophenyl, trichlorophenyl, pentachlorophenyl or methylsulphenyl esters or other esters with 1-hydroxy-1H-2-pyrrolidone, N -hydroxysuccinimide or N-hydroxyphthalimide.

 Such reactive derivatives at the carboxyl group are selected accordingly and used depending on the type of carboxylic acid used.

 In addition, the aforementioned aromatic heterocyclic aminocarboxylic acid and carboxylic acids II ′, IV ′, V ′ and VIII ′ can be used in their free form (for example, in the form of a carboxylic acid), preferably in the presence of a condensing reagent, for example N, N'-dicyclohexylcarbodiimide , N-cyclohexyl-N'-morpholinoethylcarbodiimide, N-cyclohexyl-N '- (4-diethylaminocyclohexyl) carbodiimide or N-ethyl-N' - (3-dimethylaminopropyl) carbodiimide. In addition, the above carboxylic acids can be used in the form of salts with an alkali or alkaline earth metal.

в формуле V может быть пиридиновым, пиридазиновым, пиримидиновым или пиразиновым кольцом, которые могут быть замещены группой, упоминавшейся в R₃, Q₂, в предпочтительном варианте имеет значения Q' или Q''.The symbol W in formulas VI and VII means a halogen atom, for example chlorine, bromine or fluorine. Ring

in the formula, V may be a pyridine, pyridazine, pyrimidine or pyrazine ring, which may be substituted by the group mentioned in R ₃ , Q ₂ , preferably has the meanings Q 'or Q''.

 The specified reaction can be carried out without using a solvent or in any solvent, and if necessary in the presence of a condensing reagent, for example a base. Alcohols, for example ethanol, isopropanol, etc., can be used as suitable solvents. aromatic hydrocarbons, for example benzene, toluene, xylene, halogenated hydrocarbons, for example methylene chloride, chloroform, carbon tetrachloride, etc. ethers, for example diethyl ether, dioxane, tetrahydrofuran, dimethoxyethane, etc. ketones such as acetone, methyl ethyl ketone, etc. nitriles, e.g. acetonitrile, propionitrile, etc. amides such as dimethylformamide, dimethylacetamide, etc. esters, for example methyl acetate, ethyl acetate, butyl acetate, etc. or mixtures thereof. If necessary, you can use a mixed solvent consisting of water and an aromatic or halogenated hydrocarbon. The solvent is usually used in an amount of from 1 to 50 parts (by weight), preferably from 5 to 10 parts relative to carboxylic acids or their reactive derivatives or salts.

 The reaction can be accelerated by adding a base to the solvent. As a suitable base, tertiary amines, for example triethylamine, pyridine, 4-dimethylaminopyridine, DBU (1,8-diazabicyclo (5.4.0) -undecene-7), etc. can be used. alkali metal or alkaline earth metal hydroxide, carbonate or bicarbonate, or an alkali metal alcoholate, for example sodium carbonate, potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium alcoholate, or an organometallic salt, for example n-butyllithium. The specified base is usually used in an amount of from 1 to 5 equivalents, preferably from 1 to 3 equivalents relative to carboxylic acids, or their reactive derivatives or salts.

The compound of formula VI or VII is used in an amount of from 1.1 to 2.0 mol per 1 mol of carboxylic acid or its reactive derivative, or salt in said reaction. This reaction may be carried out at room temperature (e.g., in the range 10 ^to 30 ° C) or at elevated temperature (e.g., 30 to 100 ° ^C) to accelerate the interaction. The reaction time depends on the reaction temperature, and usually the reaction lasts from 15 minutes to 24 hours, preferably from 30 minutes to 10 hours.

 Thus, the obtained compound II or IV can be isolated and purified as a free base by a known method, for example, silica gel chromatography (silica gel P 60 manufactured by Merck and Co, Inc. using eluent solvent-chloroform, ethyl acetate, etc. ), or isolate and purify as an acid addition salt using an inorganic acid, for example hydrochloric, sulfuric, phosphoric, or organic acids such as acetic, benzenesulfonic acid, para-toluenesulfonic acid, methanesulfonic acid, citric, wines malic, oxalic, propionic, maleic, malic, malonic, fumaric, mandelic, ascorbic acids, in the traditional way using known methods, for example, concentration, concentration under reduced pressure, extraction, phase transfer, crystallization, recrystallization, or chromatography. In the case when the specified compound contains a carboxyl group as a substituent, the specified compound can be converted into a salt by reaction with an alkali or alkaline earth metal, as was shown as an example earlier in accordance with the traditional method, which can then be isolated and purified by known means.

 Condensed heterocyclic derivatives of carboxylic acids II or IV or a salt thereof obtained in accordance with the above reaction can also be converted into a nitro-substituted compound by a conventional nitration reaction or into a halogen-substituted compound using a halogenating reagent, for example, N-bromosuccinimide (NBs), N-chlorosuccinimide ( NCS) or the like.

 Amines III and their salts (salts with acids, which were mentioned above in compounds II and IV, can be obtained in a known manner.

 Compound I or its salt can usually be obtained by reacting compound II or its salt without using a solvent, or in an appropriate solvent in the presence of an appropriate base or condensing reagent. Aromatic hydrocarbons, for example benzene, toluene, xylene, halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, ethers, for example diethyl ether, dioxane, tetrahydrofuran, nitriles, for example acetonitrile, propionitrile, amides, for example dimethylformamide, can be used as a solvent. esters, for example methyl acetate, ethyl acetate, butyl acetate, or mixtures thereof. If necessary, you can use a mixture consisting of water and an aromatic or halogenated hydrocarbon.

 The solvent is usually used in a ratio of from 1 to 50 parts (by weight), preferably from 5 to 10 parts relative to compound II or its salt. This reaction can be accelerated by adding a base to the solvent. As a suitable base, tertiary amines can be used, for example triethylamine, pyridine, DBU (1,8-diazabicyclo [5.4.0] undec-7-ene), hydroxides, carbonates or bicarbonates of alkali or alkaline earth metals, or alkali metal alkoxides, for example, sodium, potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, sodium alcoholate, or an organometallic salt, for example n-butyllithium, etc. Such a base is usually used in an amount of from 1 to 20 equivalents, preferably from 2 to 5 equivalents relative to compound II or its salt. As suitable condensing agents, thionyl chloride, phosphoric acid chloride, carbonyldiimidazole, N-methyl-2-bromopyridinium iodide, dicyclohexylimide or a mixture thereof can be used. Such a condensing reagent is usually used in an amount of from 1 to 10 equivalents, preferably from 2 to 5 equivalents, relative to compound II or its salt.

In the reaction, compound II or its salt is used in an amount of from 1.1 to 1.5 mol per 1 mol of compound III or its salt. The reaction can be carried out under cooling to bringing to room temperature (in the range of from 20 ^to 30 ° C) or at elevated temperature, for example in the range from about 30 to ^about 100 C to accelerate the interaction. Although the reaction time depends on the reaction temperature, the reaction usually lasts from 15 minutes to 15 hours, and preferably from about 20 minutes to 8 hours.

 Compound I thus obtained can be isolated and purified as a free base in a known manner, for example by silica gel chromatography (silica gel 60 produced by Merck and Co. Inc. using solvent-chloroform, ethyl acetate as an eluent, or isolated and purified as an addition salt acids using inorganic acid, for example hydrochloric, sulfuric, phosphoric acids, etc. or an organic acid, for example, acetic benzenesulfonic acid, para-toluenesulfonic acid, methanesulfonic acid, citric, tartaric , oxalic, propionic, maleic, malic, malonic, fumaric, mandelic, ascorbic acids, in the traditional way.In the case when the specified compound contains a carboxyl group, or similar as a substituent, this compound can be converted into a salt using alkaline or alkaline earth metal, which can then be isolated and purified by well-known methods.

 The obtained compounds of formula I of the present invention have an excellent effect, preventing and regulating various types of plant diseases caused by pathogenic fungi, especially downy mildew of vegetable crops, for example cucumbers, Chinese cabbage, onions, legumes and fruit trees, for example, vine, citrus, apple trees, rot of tomato, potato, eggplant, green pepper, pumpkin. In addition, the proposed compounds of formula I and their salts retain a stable fungicidal effect for a significantly longer period of time after applying them to plants (prolonged effect), while their fungicidal activity is reduced to a lesser extent due to insignificant washing off by rain after spraying (rain tolerance) ) Thus, the proposed compounds I or their salts exhibit a sufficient effect even in rainy times, when downy mildew often occurs, or a disease accompanied by rotting plants. In addition, the proposed compounds I and their salts have safety and better ability as an agricultural fungicide, since the aftereffect on plants is low along with their low toxicity to fish.

 The proposed compounds of formula I or their salts can be used as a fungicide in the traditional form of agricultural pesticides. In particular, depending on the intended purpose, in the preferred embodiment, one, two or more types of the proposed compounds I can be used in the form of an emulsifiable concentrate, an oily preparation, a spray solution, a wettable powder, a powder, granules, ointments, which can be formulated with an appropriate carrier or carriers in a conventional manner, for example, by dissolving or dispersing them in a liquid carrier, mixing with a suitable solid carrier or adsorption on a solid carrier. If necessary, an emulsifier, a suspending agent, a spray, a wetting agent, a moisturizing agent, a binder, a stabilizer, etc. can be added to the above preparations, which can be obtained by any conventional method.

 The preferred consumption of compound I of the present invention or its salt for the entire fungicidal composition is from about 1 to 80 wt. for emulsifiable concentrate or wettable powder, from about 0.1 to 10 wt. for the preparation in the form of oil or powder and from about 5 to 50 wt. for granules, although the concentration of the active component may vary depending on the intended purpose. Emulsifiable concentrates, wettable powders, etc. Before use, dilute and fill (for example, up to 100-5000 times) with water or the like to the required degree. and then they are sprayed.

 As a suitable liquid carrier (solvent), you can use, for example, water, alcohols (methanol, ethanol, n-propanol, isopropyl alcohol, ethylene glycol), ethers (dioxane, tetrahydrofuran, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, monomethyl glycol) , ketones (acetone, methyl ethyl ketone), aliphatic hydrocarbons (kerosene, lighting oil, fuel oil, engine oil), aromatic hydrocarbons (benzene, toluene, xylene, solvent naphtha, methylnaphthalene), halogenated hydrocarbons (x Oristà chloride, chloroform, carbon tetrachloride), acid amides (dimethylformamide, dimethylacetamide), esters (ethyl acetate, butyl acetate, glycerin ester of fatty acid), nitriles (acetonitrile, propionitrile), or the like These liquid carriers can be used either individually or as an arbitrary mixture thereof.

 As a suitable base for the ointment, for example, polyethylene glycol, pectin, esters of polyhydric alcohols of higher fatty acids, for example glycerol monostearate, cellulose derivatives, for example methyl cellulose, sodium alginate, bentonite, higher alcohols, polyhydric alcohols, for example glycerin, petroleum jelly, white petroleum jelly, liquid paraffin, lard, various types of vegetable oils, lanolin, dehydrated lanolin, solid lubricant, resins, etc. These bases can be used either individually or as an arbitrary mixture thereof, or in combination with a surfactant, given below as an example.

As the surfactant used as necessary, as an emulsifier, atomizer, a wetting agent, a dispersant and so. G. May be used non-ionic or anionic surfactants, for example soaps, polioksialkilarilovye esters (e.g. Nonal ^®, manufactured by Jakemoto Gushi KK Japan) alkyl sulfates (e.g. Emal 10 Emal 40 ^® , manufactured by Kao-Atlas KK Japan), alkyl sulfonates (e.g. Neogen ^® , Neogen T ^® , manufactured by Dai-ichi Kojyo Seiyaku KK Japan), Neopleck ^® , manufactured by Kao-Atlas KK Japan, ethers n glycols (e.g., Nonipol 85 ^®, Nonipol 100 ^®, Nonipol 160 ^®, manufactured by Sanyo Kasli Japan K.K.), polyhydric alcohol esters (e.g. Tween 20 ^®, Tween 80 ^®, manufactured by Kao-Atlas K.K., Japan ) or the like

 The fungicide of the invention can be applied at any time, starting from seed treatment, seedlings (seedlings) to harvest. The proposed fungicide can be used to prevent an outbreak of plant disease during the preliminary application of the drug, as well as for the treatment of plant disease by introducing it after the appearance of the disease by a well-known method.

 The amount of compound I of the present invention or a salt thereof used as an agricultural pesticide may vary depending on conditions, for example, the stage of development of the plant and the place of growing of the plant into which the pesticide is introduced, the type of plant disease, the outbreak, the time and method of applying the fungicide etc. Compound I or a salt thereof is usually used in an amount of from about 3 to 300 g, preferably from about 10 to 100 g, per 10 ar. The concentration of the active ingredient introduced is preferably from 10 to 1000 ppm. The fungicide is usually applied by direct scattering, dusting or watering it directly on the plant or by spraying the seeds. The amount, concentration and method of application can be changed if desired to ensure reliable and efficient use of the fungicide.

 The proposed fungicide, if necessary, can be used in any combination with other types of fungicides (for example, a fungicide based on an organochlorine compound, a fungicide based on an organophosphorus compound, a fungicide based on an organic sulfur compound, a benzimidazole type fungicide, a copper-containing fungicide, a phenolic fungicide, a triazole type fungicide, a fungicide pyrimidine type, acrylic acid type fungicide, sulfenamide type fungicide, amino acid type fungicide, antibiotic fungicide, etc. e.), insecticides (e.g. natural insecticide, carbamate type insecticide, organophosphate insecticide, phytotoxin type insecticide, synthetic pyrethroid, etc.), acaricidamine, nematicides, herbicides, plant hormones, plant growth regulators, stabilizers synergists, attractants, repellents, perfumes, pigments, fertilizers, plant nutrients, various amino acids, low or high molecular weight phosphoric acids or the like . To obtain a synergistic effect, metal salts (e.g., copper chloride, copper sulfate, etc.) can also be added.

 The proposed compounds I and their salts have an excellent protective or prophylactic effect against downy mildew and the disease of vegetable crops and fruit trees caused by pathogenic fungi. These compounds or their salts are not washed off, have excellent resistance to rain and, on this basis, demonstrate excellent protective and prophylactic effects especially in the rainy season. Compounds I or their salts reduce the spread of the disease of vegetable crops and fruit trees and can be used as the preferred fungicide, without causing any significant harm to the crop.

 And with the rst and n and e 1. Protection against a disease of tomatoes.

(концентрация 0,02 мас.). После этого полученную смесь разводят водой до заданной концентрации активного ингредиента. К указанному раствору прибавляют смачивающий агент, D yno

производимый фирмой Takeda Chemical Industries, LTD, содержащий 20% (мас./мас) нонилфениловый эфир полиоксиэтилена и 12% лингинсульфоната кальция в количестве 0,05% (мас./мас), конечная концентрация с получением разбрызгивающего раствора. Этот раствор распыляют на рассаду помидоров (растения примерно четырехнедельного возраста) до стекания раствора каплями. После высыхания растений на воздухе осуществляют инокуляцию суспензией, содержащей зооспорангии возбудителя болезни томата (концентрация примерно 10⁵/мд) путем ее разбрызгивания. После инокуляции растения выдерживают во влажном помещении при 17^оС в течение 5 дн. После этого оценивают степень поражения заболеванием растения. Показатель защиты приведен в соответствии со следующими коэффициентами:
Показатель защиты 3; площадь поражения 0-5%
Показатель защиты 2; площадь поражения 6-15%
Показатель защиты 1; площадь поражения 16-30%
Показатель защиты 0; площадь поражения 31% или более.The compound of the invention is dissolved in dimethylformamide (concentration of 1 wt.), Then xylene (concentration of 0.2 wt.) And tween 20 are added to the resulting solution.

(concentration of 0.02 wt.). After that, the resulting mixture was diluted with water to a predetermined concentration of the active ingredient. A wetting agent, D yno, is added to the indicated solution.

manufactured by Takeda Chemical Industries, LTD, containing 20% (w / w) polyoxyethylene nonylphenyl ether and 12% calcium linginsulfonate in an amount of 0.05% (w / w), final concentration to obtain a spray solution. This solution is sprayed on tomato seedlings (plants of about four weeks of age) until the solution drips. After the plants have dried in air, the suspension is inoculated with a suspension containing zoosporangia of the tomato pathogen (concentration of about 10 ⁵ / ppm) by spraying it. After inoculation, the plants are kept in a humid environment at 17 ^{° C} for 5 days. After that, the degree of damage to the plant disease is evaluated. The protection index is given in accordance with the following ratios:
Protection rate 3; lesion area 0-5%
Protection rate 2; lesion area 6-15%
Protection rate 1; lesion area 16-30%
Protection score 0; lesion area 31% or more.

 The results are presented in table. 1.

 And with the test 2. Protection against false powdery mildew of cucumbers.

According to the method described in test 1, a spray solution is prepared containing the compound of the invention at a given concentration, which is sprayed onto young seedlings (about three weeks old) of cucumbers before dripping with drops of said solution. After the plants are dried in air, a suspension containing the zoosporangia of the causative agent of powdery mildew of cucumbers (concentration of about 10 ⁵ / ml) is inoculated by spraying. After inoculation, the plants are kept in a humid room for 6 days. After that, the area of damage to the plant by the disease is estimated, while the protection index is presented in accordance with the following coefficients:
Protection rate 3; lesion area 0-5%
Protection rate 2; lesion area 6-15%
Protection rate 1; lesion area 16-30%
Protection score 0; lesion area of 31% or more.

 The results are shown in table. 2.

 And with a stance 3. Protection of the vine from downy mildew.

According to the method described in test 1, a spray solution containing the compound of the invention at a given concentration is obtained, which is then sprayed onto young grape seedlings (approximately six weeks old) until the solution drops down. After air drying, a suspension containing zoosporangia of the causative agent of downy mildew of grapes (concentration of about 105 / ml) is inoculated by spraying. After inoculation, the plants are kept in a humid environment at 18 ^{° C} for 10 days. After that, assess the degree of damage to the plant, while the protection index is determined based on the following factors:
Protection rate 3; lesion area 0-5%
Protection rate 2; lesion area 6-15%
Protection rate 1; lesion area 16-30%
Protection score 0; lesion area of 31% or more.

 The results are presented in table. 3.

 In the table. 1-3 numbers in the column of the test compound mean the number of the compound obtained in the following examples in the description.

 From the above test results, it can be seen that compounds I of the present invention and their salts have an excellent effect for protecting against downy mildew and preventing the disease of vegetable crops and fruit trees.

The invention is explained in more detail in the examples below, however, it should not be limited to these examples. Elution during column chromatography was performed under thin layer chromatography (TLC). TLC was performed using Kesel gel 60F 254 (Art. 5715) manufactured by Merck and Co. as a TLC plate, a similar solvent used as an eluent for column chromatography, which was used as a developing solvent and a UV detector as a detection means. A silica gel 60 (70-230 mesh Art. 7734) manufactured by Merck and Co. was used as silica gel filling the column. By the NMR spectrum is meant the NMR ( ¹ H NMR), and tetramethylsilane was used as the internal and external standard. The NMR spectrum was measured with a Varian bM 390 type spectrometer (90 Hz) unless otherwise specified. Each value is given in ppm. The numerical value in parentheses indicates the mixing speed by volume of each of the solvents used in the solvent mixture as eluent.

Each of the abbreviations used in the following examples and tables has the following meanings:
S singlet, d doublet, m multiplet, t triplet, br wide, I coupling constant, НZ ГЦ, CD Cl ₃ heavy chloroform, DMSOd6 heavy dimethyl sulfoxide; (except output): wt./wt.

Under the room temperature has a temperature in the range of from 15 to 25 ° ^C.

 PRI me R 1. Synthesis of methyl ester of imidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-1).

47% solution of hydrogen bromide (2.5 mL, 14.4 mmol) was added to dietoksibrometanu (2.0 mL, 13.2 mmol) and the resulting mixture was stirred ^at 50 ° C for 2 hours. The reaction mixture was cooled to room temperature and ethanol (7.0 ml) and sodium bicarbonate (1.0 g, 11.9 mmol) were added thereto. The mixture is stirred and the precipitate formed is filtered off. 2-aminonicotinic acid methyl ester (1.0 g, 6.6 mmol), sodium bicarbonate (2.0 g, 13.8 mmol) and ethanol (7.0 ml) were added to the obtained filtrate, and the resulting mixture was heated to reflux. refrigerator for 4 hours. The reaction mixture was cooled to room temperature and saturated aqueous sodium bicarbonate was added to it. The resulting mixture was extracted with dichloromethane (100 ml x 3), the resulting extract was washed with water, dried over anhydrous magnesium sulfate MgSO ₄ and evaporated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: chloroform, followed by a 9: 1 mixture of chloroform and methanol), and the target compound (0.6 g, 55% yield) was obtained as yellow crystals, mp. 67-69 ^about S.

PRI me R 2. Synthesis of methyl ester of 2-methylimidazole [1,2-a] pyridine-8-carboxylic acid (compound 1-3)
Bromoacetone (6.5 g, 42.7 mmol) and 2-aminonicotinic acid methyl ester (4.8 g, 31.5 mmol) are added to ethanol (50 ml) and the resulting mixture is refluxed for 17 hours. the mixture was cooled to room temperature, the solvent was distilled off under reduced pressure. Saturated aqueous sodium bicarbonate solution (50 ml) was added to the residue, and the resulting mixture was extracted with chloroform (100 ml x 3). The extract was washed with water, dried on MgSO ₄ and evaporated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: chloroform, followed by a 9: 1 mixture of chloroform and methanol). Get the target compound (4.0 g, yield 85%) as an oily substance.

 PRI me R 3. Synthesis of 2-phenyl-imidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester bromide hydrate (compound 1-25).

Phenacyl bromide (11.0 g, 55.3 mmol) and 2-aminonicotinic acid ethyl ester (8.68 g, 52.2 mmol) are added to methyl ethyl ketone (100 ml) and the resulting mixture is refluxed for 5.5 hours. The reaction mixture was kept at room temperature overnight and after collecting the precipitated crystals by filtration, the target compound (16.3 g, yield 89.96%) was obtained in the form of crystals, mp. 174-176 ^about S.

PRI me R 4. Synthesis of methyl ester of 3-chloro-2-methylimidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-15)
2-methylimidazo [1,2-a] pyridine-8-carboxylic acid methyl ester (5.3 g, 27.9 mmol) was dissolved in chloroform (30 ml), and N-chlorosuccinimide (3.7 g) was added to the resulting solution. , 27.9 mmol) by reacting at room temperature for 40 minutes Then, a 10% aqueous sodium bicarbonate solution (80 ml) was added to the reaction mixture, and the resulting mixture was stirred for 30 minutes. The organic layer was separated from the reaction mixture, and the aqueous layer was extracted with chloroform (10 ml x3). The extracts are combined, washed with water, dried over MgSO ₄ and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: chloroform), whereby the target compound (3.6 g, yield 57%) was obtained as an oily substance.

 PRI me R 5. Synthesis of methyl ester of 3-dimethylaminomethyl-2-methylimidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-17).

To acetonitrile (10 ml) was added 37% formaldehyde (0.3 ml) and acetic acid, and 50% aqueous dimethylamine (0.3 ml) was slowly added to the mixture with stirring at 0 ° ^C. Then to the reaction mixture was added methyl 2-methylimidazo [1,2-a] pyridine-8-carboxylic acid and reaction was continued at ⁵⁰ ° C for 2 hours and then at room temperature for 2.5 hours. The reaction mixture was evaporated under reduced pressure and then neutralized with saturated aqueous NaHCO ₃ . The resulting solution was extracted with dichloromethane, the extract was washed with water, dried over anhydrous sodium sulfate, and after evaporation under reduced pressure, the desired compound was obtained (0.48 g, yield 52%), mp. 123-124 ^about S.

 PRI me R 6. Synthesis of 2-methylimidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-4).

 2-methylimidazo [1,2-a] pyridine-8-carboxylic acid methyl ester (4.0 g, 21 mmol) was dissolved in a mixture of ethanol (45 ml) and water (20 ml), and then sodium hydroxide was added. (2.5 g, 63 mmol). The resulting mixture was refluxed for 30 minutes. The reaction mixture was cooled to room temperature and then evaporated under reduced pressure. Water was added to the concentrate, then the mixture was adjusted to pH 4 by adding concentrated hydrochloric acid. Precipitated crystals were collected by filtration, whereby the desired compound (2.3 g, 64% yield) was obtained.

 PRI me R 7. Synthesis of 2-phenylimidazo [1,2-a] -pyridine-8-carboxylic acid (compound 1-26).

2-Phenylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester bromide (8.4 g, 24.2 mmol) was added to a 20% aqueous solution of NaOH (200 ml) and ethanol (100 ml), after which the resulting mixture was refluxed for 1 hour. The reaction mixture was cooled to room temperature and the alcohol was distilled off under reduced pressure. The residue was adjusted to pH 4 by the addition of concentrated hydrochloric acid. Precipitated crystals were collected by filtration, whereby the desired compound (56.7 g, yield 98.4%) was obtained in the form of crystals, mp. 226 ^about With
PRI me R 8. Synthesis of 2-chloromethylimidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-90).

2-Chloromethylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (8.4 g, 24.2 mmol) was added to concentrated hydrochloric acid (100 ml), and the resulting mixture was refluxed for 5 hours. The reaction mixture was cooled to room temperature and the pH was adjusted to 4 with the introduction of a saturated aqueous solution of sodium bicarbonate. The precipitated crystals were collected by filtration to yield the target compound (56.7 g, yield 98.4%) as crystals, mp. 250 ^about C (decomp.).

 PRI me R 9. Synthesis of 3-nitro-2- (4-nitrophenyl) -imidazo [1,2-a] pyridine-3-carboxylic acid (compound 1-96).

2-Phenylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (2.9 g, 10 mmol) was dissolved in a concentrated solution of sulfuric acid (5 ml), after which 70% nitric acid was slowly added to the resulting solution. acid (1.3 mL) at 10 ^C. After complete addition the mixture was stirred at room temperature for 30 min, then poured into ice-water and the pH adjusted to 7 by adding 20% NaOH. Precipitated crystals were collected by filtration, which were ethyl ester of the title compound (3.6 g, 99.2% yield). A solution of these crystals in concentrated hydrochloric acid (35 ml) was refluxed for 1.5 hours, after which it was cooled to room temperature. After filtering the precipitated crystals and drying, the title compound (2.9 g, 87.3% yield), m.p.> 300 ° ^C.

 PRI me R 10. Synthesis of 3-nitroimidazo [1,2-a] pyridine-8-carboxylic acid (compound N 1-125).

2-Ethoxycarbonylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (3.8 g, 14.5 mmol) was dissolved in concentrated sulfuric acid (10 ml), and 70% nitric acid was gradually added to the resulting solution. acid (1.5 mL) at 10 ^C. The resulting mixture was stirred at room temperature for 30 min, then poured into ice water and adjusted to pH 7 by introducing 20% sodium hydroxide. After filtering the precipitated crystals, 2-ethoxycarbonyl-3-nitroimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (2.4 g, yield 53.8%) is obtained in the form of crystals, mp. 139-140 ^about C. A solution of these crystals in concentrated hydrochloric acid (35 ml) is refluxed for 1.5 hours and then cooled to room temperature. The precipitated crystals were collected by filtration and, after drying, the desired compound was obtained (1.2 g, yield 74.3%), mp. 300 ^about .

 PRI me R 11. Synthesis of ethyl ester of 3-formyl-2-phenylimidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-119).

To a solution containing 2-phenylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester bromide hydrate (14.7 g, 4 mmol) in dimethylformamide (8 ml) was added dropwise phosphoric acid chloride (2 ml), keeping the reaction temperature below 15 ^C. The reaction was then carried out at room temperature for 30 minutes and further 2 hours at 70 ^C. After completion of the reaction, the reaction mixture was cooled, poured into ice water, and the pH adjusted to 7 with the introduction of 20% caustic soda. The precipitated crystals were collected by filtration, and after recrystallization from ethanol, the target compound (1.0 g, 85.5% yield) was obtained as colorless crystals, mp. 139 ^about S.

 Example 12 Synthesis of 3-cyano-2-phenylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (compound 1-121).

2-Phenylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester bromide (1.96 g, 5.35 mmol) and triethylamine (0.55 g, 5.44 mmol) are added to acetonitrile (20 ml) . Then, to the resulting solution was added dropwise a solution of chlorosulfonyl isocyanate (SlSO ₂ NCO) (0,8 ml, 9.19 mmol) in acetonitrile (5 ml) at an internal reaction temperature of 0 to 20 ^C. The mixture was then allowed to stand at room temperature for 1 h. At the end of the reaction, the mixture was concentrated under reduced pressure. The resulting concentrate, to which water was added, was then extracted with dichloromethane, the extract was washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform) to obtain the target compound (1.06 g, yield 67.9%) as crystals, mp 87-89 ^about S.

 PRI me R 13. Synthesis of ethyl ester of 2-ethoxycarbonylimidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-123).

A mixture consisting of ethyl bromopyruvic acid ethyl ester (2.3 g, 10.2 mmol) and 2-aminonicotinic acid ethyl ester (1.7 g, 10 mmol) in methyl ethyl ketone (17 ml) is boiled for 5 hours. After completion of the reaction the mixture was cooled to room temperature and distilled off under reduced pressure to remove the solvent. The residue, to which saturated aqueous sodium bicarbonate was added (50 ml, was extracted with chloroform. The extract was washed with water, dried over MgSO ₄ and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent, ethyl acetate) to obtain the target compound (0, 7 g, yield 26.7%) as crystals, mp 97 ° ^C.

 Example 14. Synthesis of 2-methyl-3-sulfoimidazo [1,2-a] imidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (compound 1-127).

To a solution containing 2-methylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (1.2 g, 5.9 mmol) in chloroform (15 ml) was added chlorosulfonic acid (0.6 ml). The mixture was refluxed for 3 hours and then evaporated under reduced pressure. Precipitation crystals are collected by filtration, washed with a sufficient amount of water, and after drying, the desired compound (1.2 g, yield 71.4%) is obtained in the form of crystals, mp. 247-250 ^{° C} (dec.).

 Example 15 Synthesis of 2-methyl-3-N-methylsulfamoylimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (compound 1-129).

2-Methyl-3-sulfoimidazo [1,2-a] pyridine-8-carboxylic acid ethyl ester (1.7 g) and tri-n-propylamine (2.6 g) were added to acetonitrile (17 ml). Then to the mixture was added phosphorous oxychloride (1.1 ml), maintaining the internal reaction temperature between 50-60 ^C. The mixture was kept at the same temperature for 1 hour. After completion of the reaction, the mixture was evaporated under reduced pressure , and water is added to the residue. The precipitated crystals were collected by filtration, washed with water, and after drying, ethyl 2-methyl-3-chlorosulfonylimidazo [1,2-a] pyridine-8-carboxylic acid (1.2 g, 66.3%) was obtained in the form of crystals, i.e. pl. 182-183 ^about S.

The resulting crystals (1.2 g) was dissolved in acetonitrile (12 ml) and the resulting solution was added dropwise 40% aqueous solution of methylamine (0.75 g) in acetonitrile (3 ml) at an internal reaction temperature of 0 to 10 ^C. Then, the resulting mixture was kept at room temperature for 1 hour. After completion of the reaction, the mixture was evaporated under reduced pressure. The concentrate to which water was added was adjusted to pH 7 by introducing dilute hydrochloric acid. The precipitated crystals were collected by filtration, washed with water, and after drying, the desired compound (1.1 g, yield 93.2%) was obtained in the form of crystals, mp. 184-185 ^about S.

 PRI me R 16. Synthesis of 2-chlorimidazo [1,2-a] pyridine-8-carboxylic acid (compound 1-135).

A mixture composed of diethyl bromo malonate (26 ml) and ethyl 2-aminonicotinic acid (13.3 g) were reacted at 80-90 ^{° C} for 6 hours under a nitrogen atmosphere. After completion of the reaction, the mixture was cooled to room temperature and acetone (100 ml) was added to it. Precipitated crystals were collected by filtration to give 3,8-diethoxycarbonyl-2-hydroxyimidazo [1,2-a] pyridine bromide (9.98 g, 34.8% yield).

A mixture of the crystals (6.6 g) in phosphorus oxychloride (30 mL) were reacted at 160 ^{° C} for 2 hours in an autoclave. After the reaction, an excess of phosphoric acid chloride is distilled off under reduced pressure. Ethanol was added to the residue, and the resulting mixture was evaporated under reduced pressure. The concentrate was purified by silica gel column chromatography (eluent: chloroform) to obtain 2-chloro-3,8-diethoxycarbonylimidazo [1,2-a] pyridine (compound 1-133) (2.2 g, yield 40.3%) as crystals, mp 105-106 ^about S.

The resulting crystals (0.9 g) were dissolved in ethanol (10 ml), and 10% sodium hydroxide (5 ml) was added to the resulting solution. The mixture was kept at room temperature for 1 h, and then brought to pH 4 by the addition of concentrated hydrochloric acid. The precipitated crystals were collected by filtration, washed with water, and after drying, 2-chlorimidazo [1,2-a] pyridin-3,8-dicarboxylic acid (0.73 g, 100% yield) was obtained as crystals, t pl. 210-212 ^{° C} (dec.). Then, a mixture of the obtained crystals (0.73 g) in concentrated hydrochloric acid (5 ml) was refluxed for 2 hours. The reaction solution was adjusted to pH 4 by adding saturated aqueous sodium bicarbonate solution to form crystals of the target compound (0.5 g, yield 83.9%), mp. 237 ^about S.

 Example 17 Synthesis of α- (imidazo [1,2-a] pyridin-8-ylcarbonylamino) - (2-furyl) acetonitrile (compound 2-1).

α- (2-Furyl) -α-aminoacetonitrile (0.7 g, 5.5 mmol) is dissolved in acetonitrile (20 ml) and imidazo [1,2-a] pyridine-8-carbonic acid chloride is added to the resulting solution with stirring acid (1.0 g, 5.5 mmol). The resulting mixture was reacted at room temperature for 2 hours. After completion of the reaction, the solvent was distilled off from the reaction mixture under reduced pressure. Water (20 ml), saturated aqueous sodium bicarbonate (50 ml) and chloroform (50 ml) were added to the residue, and the resulting mixture was stirred. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane, 2: 1). Get the target compound (0.16 g, yield 11%) in the form of crystals, so pl. 149-151 ^about S.

 PRI me R 18. Synthesis of α- (imidazo [1,2-a] pyridin-5-ylcarbonylamino (2-furyl) acetonitrile (compound 2-134).

 α- (2-Furyl) -α-aminoacetonitrile (0.7 g, 5.5 mmol) was dissolved in acetonitrile (20 ml) and imidazo [1,2-a] pyridine-5-carboxylic acid chloride was added to the resulting solution ( 1.0 g, 5.5 mmol). The resulting mixture was reacted at room temperature for 2 hours. After completion of the reaction, the solvent was removed from the reaction mixture. Water (20 ml), saturated aqueous sodium bicarbonate (50 ml) and chloroform (50 ml) were added to the residue, and the resulting mixture was stirred. The organic layer was separated, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by silica gel column chromatography (eluent: methanol / chloroform, 1: 9) to obtain the target compound (0.9 g, yield 64%) as an amorphous solid.

 Example 19. Synthesis of α- (2-phenylimidazo [1,2-a] pyridin-8-ylcarbonylamino) - (2-furyl) acetonitrile (compound 2-24).

2-Phenyl-imidazo [1,2-a] pyridine-8-carboxylic acid (1.5 g, 5.5 mmol) is added to dry tetrahydrofuran (100 ml), and then carbonyldiimidazole (1 5 g, 5.5 mmol) with stirring at room temperature in a nitrogen atmosphere. The mixture was stirred at room temperature for 8 hours, and then α- (2-furyl) - α-aminoacetonitrile (0.7 g, 5.5 mmol) was added and the reaction was carried out at room temperature for 5 hours. The solvent was removed from the reaction mixtures under reduced pressure, water (20 ml) and ethyl acetate (50 ml) were added to the resulting residue, followed by stirring. The organic layer was separated, dried over anhydrous magnesium sulfate, and then evaporated. The concentrate was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane, 1: 1) to obtain the target compound (0.9 g, 64% yield) as crystals, mp 197-199 ^about S.

 Example 20. Synthesis of α- (3-chloro-imidazo [1,2-a] pyridin-8-ylcarbonylamino) - (2-furyl) acetonitrile (compound 2-10).

3-Chlorimidazo [1,2-a] pyridine-3-carboxylic acid (1.8 g, 9.2 mmol) was added to thionyl chloride (20 ml) and the resulting mixture was refluxed for 30 minutes with stirring, then evaporated under reduced pressure. The resulting crude acid chloride and α- (2-furyl) - α-aminoacetonitrile (1.1 g, 8.5 mmol) were added to acetonitrile (50 ml) and the reaction was carried out at room temperature for 1 h with stirring. The solvent was removed from the reaction mixture under reduced pressure. Then, water (20 ml), saturated aqueous sodium bicarbonate (50 ml) and chloroform were added to the residue, and then stirred. The organic layer was separated, dried over anhydrous magnesium sulfate, and then evaporated. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane, 1: 2), and the target compound (0.6 g, yield 22%) was obtained in the form of crystals, m.p. 142-143 ^about S.

 Example 21. Synthesis of α- (2-phenylimidazo [1,2-a] pyridin-8-ylcarbonylamino) - (3-chlorophenyl) acetonitrile (compound 2-35).

2-Phenylimidazo [1,2-a] pyridine-8-carboxylic acid (1.0 g, 4.2 mmol), α- (3-chlorophenyl) aminoacetonitrile (0.77 g, 4.5 mmol) and NaHCO ₃ (1.1 g, 13.1 mmol) was added to acetonitride (10 ml). Phosphoric acid chloride (0.7 ml, 7.51 mmol dissolved in 5 ml of acetonitrile) is slowly added to the resulting mixture with stirring, while cooling with ice. The resulting mixture was kept at room temperature for 10 hours, the solvent was removed from the reaction mixture under reduced pressure, then water (50 ml) was added to the residue, and the mixture was adjusted to pH 7 with saturated aqueous sodium bicarbonate. The mixture was then extracted with a solvent mixture of dichloromethane / ethyl acetate (10: 1), (100 ml × 2). The resulting extract was dried over anhydrous magnesium sulfate and evaporated. Acetonitrile (5 ml) was added to the residue, and the precipitated crystals were collected by filtration. The result is the target compound (0.44 g, yield 27.2%) in the form of crystals, so pl. 210-211 ^about S.

 Example 22. Synthesis of α- (3-dimethylaminoethyl-2-phenylimidazo [1,2-a] pyridin-8-incarbonylamino (3-fluorophenyl) acetonitrile (compound 2-79).

37% formaldehyde (0.3 ml) and acetic acid (0.4 ml) were added to acetonitrile (10 ml), after which a 50% aqueous solution of dimethylamine (0.3 ml) was slowly added to the resulting mixture at 0 ^o With stirring. To the mixture was added α- (2-phenylimidazo [1,2-a] pyridin-8-ylcarbonylamino) - (3-fluorophenyl) acetonitrile (1.0 g, 2.7 mmol) and the mixture was stirred ^at 50 ° C for 2 hours, and then another 2.5 hours at room temperature. After this, the reaction mixture was evaporated under reduced pressure, the residue was neutralized with a saturated aqueous solution of NaHCO ₃ . The solution was extracted with dichloromethane, and the extract was washed with water, dried over anhydrous sodium sulfate, followed by evaporation under reduced pressure. The resulting concentrate was purified by silica gel column chromatography (eluent: chloroform to give the title compound (0.47 g, yield 40.8%) as crystals, m.p. 123-124 ° ^C.

 EXAMPLE 23. Synthesis of α- (3-methylsulfinylmethylimidazo [1,2-a] pyridin-8-ylcarbonylamino) - (2-furyl) acetonitrile (compound 2-122).

α- (2-Methylthiomethylmidazo [1,2-a] pyridin-8-ylcarbonylamino) - (2-furyl) acetonitrile (0.33 g, 1 mmol) is added to chloroform (10 ml), after which said mixture is added m-chloroperbenzoic acid (0.25 g, 1.1 mmol) at 5 ^C. The mixture was then stirred at room temperature for 2.5 hours and then the reaction mixture was treated with saturated aqueous sodium bicarbonate. The chloroform layer was separated, washed with water, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The concentrate was purified by column chromatography, or on silica gel (eluent: ethyl acetate) to obtain the target compound (0.1 g, yield 30.3%) as crystals, mp 214-216 ^about S.

 Example 24. Synthesis of α- (2-trifluoromethylimidazo [1,2-a] pyridin-8-ylcarbonylamino) - (3-fluorophenyl) acetamide (compound 2-169).

A mixture consisting of α- (2-trifluoromethylimidazo [1,2-a] pyridin-8-ylcarbonylamino) - (3-fluorophenyl) acetonitrile (1.26 g) and chlorosulfonic acid (0.5 ml) in chloroform (13 ml) was refluxed for 1.5 hours. The reaction solution was concentrated under reduced pressure and water was added to the residue. The precipitated crystals were collected by filtration and, after recrystallization from ethanol, the target compound (0.45 g, yield 34.1%) was obtained in the form of crystals, mp. 118-120 ^about S.

 The compounds of formula II obtained by similar methods described in examples 1-16 are shown in table. 4, their melting points and NMR analysis data in table. 5.

 The compounds of formula I obtained by similar methods described in examples 17-24 are shown in table. 6, their melting points and NMR analysis data in table. 7.

) 5
Состав 2
Смачиваемые порошки, приготовленные смешиванием и измельчением следующих компонентов, мас. Соединение 2-24 50 Диатомовая земля 44 Полиоксиэтиленалкил- ариловый эфир 6 Нонипол 85

)
Состав 3.Composition 1. Emulsifiable concentrates prepared by mixing the following components, wt. Compound 2-2 20 Xylene 75 Polyoxyethylene alkyl aryl ether (Nonipol 85

) 5
Composition 2
Wettable powders prepared by mixing and grinding the following components, wt. Compound 2-24 50 Diatomaceous earth 44 Polyoxyethylene alkyl aryl ether 6 Nonipol 85

)
Composition 3.

 Powders prepared by mixing the following mixture, wt. Compound 2-27 3 Clay 40 Talc 57

Claims (1)

1. A fungicidal composition comprising the active ingredients one derivative and target additives, characterized in that, in order to enhance fungicidal activity, it contains as a amide derivative a compound of the general formula

where X is furyl, methylfuryl, thienyl, phenyl, which may be substituted once by halogen, methyl, methoxy, trifluoromethyl, double-halogen, methylthienyl, methylpyrrolyl, pyridyl, benzyl, methyl;
R ₁ hydrogen, thienyl, phenoxy, naphthyl, C ₁ C ₆ -alkyl, trifluoromethyl, methyl, substituted by chlorine, methoxy, methylthio, methylsulfonyl, phenoxy, phenylthio; phenyl optionally substituted once with C ₁ -C ₃ -alkyl, C ₁ -C ₃ -alkoxy, halogen, nitro, dimethylamino, phenyl, sulfo, hydroxy, phenyl, twice substituted with the same or different groups selected from C ₁ C ₄ -alkyl, methoxy , halogen, nitro, methylthio, methylsulphenyl, methylsulphonyl, tetramethylphenyl, phenylthio, cyclohexyl; thiazolyl;
R ₂ hydrogen, halogen, amino, phenyl, formyl, nitro, cyano, sulfo, methyl, which may be substituted by dimethylamino, morpholino, sulfo, SO ₂ NHCH ₃ , N = CHC ₆ H ₅ ;
R ₃ hydrogen, methyl,
or its salts, such as hydrochloride or oxalate, in the following ingredients, wt. Active ingredient 3-50
Target Supplements Else
2. The amide derivative of the General formula

where X is furyl, thienyl, methylfuryl, phenyl, which may be substituted once by halogen, methylthienyl and methylpyrrolyl, pyridyl, benzyl, methyl;
R ₁ hydrogen, thienyl phenoxy, naphthyl C ₁ C ₄ -alkyl, trifluoromethyl, substituted with chlorine, methoxy, methylthio, methylsulphenyl, phenoxy, phenylthio, phenyl, possibly once substituted with C ₁ C ₃ -alkyl, C ₁ - C ₃ -alkoxy, halogen, nitro, dimethylamino, phenyl, sulfohydroxy, phenyl doubly substituted with the same or different groups selected from C ₁ -C ₄ alkyl, methoxy, halogen, nitro, methylthio, methylsulphenyl, methylsulphonyl, tetramethylphenyl, phenylthio, cyclohexyl, thiazol;
R ₂ hydrogen, halogen, amino, phenyl, formyl, nitro, cyano, sulfo, methyl, which may be substituted by dimethylamino, morpholino, sulfo, SO ₂ NHCH, N CHC ₆ H ₅ ;
R ₃ hydrogen, methyl,
or its salts, such as hydrochloride or oxalate.

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