UA124228C2 - Process for preparing 4-amino-pyridazines - Google Patents

Abstract

The present invention relates to a process for preparing a pyridazine amine compound of formula V, and to processes for preparing dichloropyridazine amine compounds of formula IVa, IVb, or mixtures thereof. Furthermore, the present invention relates to the novel dichloropyridazine amine compounds of formula lVa, IVb, ormixturcs thereof, wherein the amino group is an ethylamino group.

Description

Description

The present invention relates to a method of obtaining a pyridazine amine compound of the formula M according to the following sequence of reactions: c) and M stage (PI si Z M si on () On (V C (0) stage (10 (PD 1. ROSIz stage (11) k'-MNo 2. B'-MNo

SI 1 M

M vm TM

CI in CI. same AM M vm syh

S (Ma) S ma

N N

SI v'-M i- -- 6 - --:-- "y v-Mm z M i si s M stage (17) OM

SI (Ma) C (m) (M

In the above scheme and the following ones, stage (I) represents the transformation of mucochloric acid I into the compound of formula II, stage (I) represents the transformation of the compound of formula II into the trichloropyridazine compound of formula IS, stage (II) represents the transformation of the trichloropyridazine compound of formula PI into a mixture dichloropyridazinamine compounds of the formula

It and IM, and stage (IM) represents the transformation of a mixture of compounds of the formula IMa and IMb into a pyridazine compound of the formula U. It should be noted that stages (II) and (I) can also be carried out by the reaction in one vessel, which is indicated by references at stage (I) and (IP) in the above scheme.

The resulting pyridazine-amine compounds of the formula M can be reacted with compounds of the formula MI, obtaining compounds of the formula MI! according to the following reaction scheme, 2 o 2 o M k-th | n; sah muh o Lkfrosml V

TSI m vch -M, - uidinuchnnia vm - still with M M v3 stage (R M muscle (U (MI) (MI)

Further, this reaction stage is denoted as stage (M).

Pyridazinamine compounds, especially pyridazineamine compounds with an amino group in the 4-position of the pyridazine component, are multipurpose intermediates for the preparation of products of fine organic synthesis derived from pyridazines, such as compounds in the field of pharmaceuticals and agrochemicals. For example, pyridazinamine compounds are at the center of the search for drugs that are, for example, suitable for the treatment of disease

Alzheimer's, depression, hypotonia and anxiety. In addition, pyridazinamine compounds are multipurpose intermediates for the preparation of pesticides with a pyridazine component, such as 4-pyrazole-M-pyridazineamide compounds, which are known to be particularly useful against invertebrate pests (see M/O 2009/027393,

MO 2010/034737, UMO 2010/034738, and UMO 2010/112177).

For certain applications, pyridazineamine compounds that do not contain any substituents other than the amino substituent are preferred, especially pyridazineamine compounds that are not additionally substituted with halogen substituents, such as chlorine. However, chlorine substituents are often present in pyridazineamine compounds, as a typical starting material for the preparation of these compounds by a nucleophilic substitution reaction with an amine compound, which is 3,4,5-trichloropyridazine.

In view of the above, there is a need for an efficient dehalogenation method by which dichloropyridazinamine compounds can be converted to pyridazineamine compounds. In particular, there is a need for a method that provides improved yields. Taking into account the subsequent transformations of the obtained pyridazineamines, it is additionally desirable to carry out the reaction without adding water.

It is known in the art that the dehalogenation of certain dichloropyridazinamine compounds can be carried out by a hydrogenation/dehalogenation reaction in the presence of hydrogen and a hydrogenation catalyst. In this field of technology, it is assumed that this hydrogenation / dehalogenation of pyridazinamine compounds is carried out in the presence of a base. (Regarding this, reference should be made to UMO 2011/038572; Chdoigppai oi Neiegosusiis Spetivigu, 21(5), 1389-92; 1984;

MO 2009/152325; 05 4,728,355; MO 2011/124524; MO 2010/049841; MO 2013/142269;

O56,258,822; and MO 2001/007436). For example, UMO 2011/038572 describes the dehalogenation of a mixture of 3,5-dichloro-4-pyridazinamine and 5,6-dichloro-4-pyridazinamine by reacting the mixture with hydrogen in the presence of a hydrogenation catalyst (Ra/cS) and a base (sodium hydroxide).

The reason for the addition of the base is to avoid a decrease in the activity of the catalyst due to the production of NSI in the reaction. This is explained by RE. Spapa and others. in (Vy. Kogeap Spet. os. 2011, 32(3), 1075), an article dealing with the Ra-catalyzed dehalogenation of aromatic halides.

It has been described that HCI produced during dechlorination tends to adsorb on activated carbon, leading to progressive Ra/C poisoning, and that it is effective to add some bases to remove HCI. It has also been described that the conversion in dechlorination reactions can be increased in the presence of a base.

However, the addition of a base is disadvantageous, especially for an industrial method. First, the reaction requires an additional chemical substance, that is, a base, which makes the process more complex. Secondly, the presence of a base complicates the recycling of the catalyst.

Especially, when filtering the hydrogenation catalyst from the reaction, the chloride salts obtained during the reaction of the base with NSI must be additionally filtered, thus the sediment on the filter

Zo contains both components, a catalyst and a chloride salt (for example, Ksi and KHSO3). After that, an additional treatment procedure is required to re-separate the catalyst.

Thus, the task of this invention is to provide a method of dehalogenation of dichloropyridazinamine compounds, which is suitable for industrial use.

In particular, the object of the present invention is to provide a method for which there is no need to add a base as an additional chemical substance, and which provides the advantage that the hydrogenation catalyst can be reused after the reaction without purification.

At the same time, it is undoubtedly desirable to provide high yields of the method.

The above-mentioned problem is solved using method A, as described further in this application and in independent clause 1 and in the clauses of the claims, which directly or indirectly depend on it.

In the first aspect, thus, the present invention relates to a method, hereinafter referred to as method A, for the preparation of a pyridazinamine compound of formula M or its salt, tautomer or M-oxide 1n

SHII M SU which includes the reaction stage of (a) a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide, or (b) a dichloropyridazinamine compound of the formula IMB or its salt, tautomer or M-oxide, or (c) a mixture (a ) and (6) . Nn

S an kA ah

SHII II

Si aha) so U) with hydrogen in the presence of a hydrogenation catalyst, where

B' represents H, C1-C8-alkyl, or C1-C8-alkyl-C1-C8-alkyl.

It should be noted that the reaction stage underlying method A corresponds to stage (IM) in the reaction scheme presented above.

The inventors of the present invention have unexpectedly discovered that the dehalogenation of dichloropyridazinamine compounds can be carried out in the absence of a NCI neutralizer, i.e. in the absence of a base or other chemical substance suitable for the binding of HeI, and that, nevertheless, the desired product can be obtained in high yield. The hydrogenation catalyst can be easily filtered after the reaction and can be reused without purification.

It has also been found that the NSI neutralizer can be advantageously used after the hydrogenation catalyst has been removed, so that the hydrogen chloride is bound and will not be released in gaseous form.

If the NSI catalyst is used after removal of the hydrogenation catalyst, it has been found to be advantageous when the NSI catalyst is provided without water, as this facilitates processing.

In addition, the inventors of this invention unexpectedly discovered that the yields of dehalogenation of dichloropyridazinamine compounds depend on the nature of the amino substituent. In this regard, it was unexpectedly found that the reaction can be advantageously carried out with dichloropyridazinamine compounds in which the amino group is an ethylamino group.

Also, dichloropyridazinamine compounds are multi-purpose intermediate compounds for obtaining products of fine organic synthesis, pyridazine derivatives, such as compounds in the field of pharmaceuticals and agrochemistry. In particular, chlorine substituents provide the possibility of additional derivatization of the pyridazine component, for example, the introduction of additional amino groups by means of a nucleophilic substitution reaction. Therefore, many different compounds are available from dichloropyridazineamine compounds, because not only the amino group can react, for example, with an activated carboxylic acid derivative, but also the chlorine substituents can be replaced by other substituents.

Thus, there is also a need for an efficient method of preparing dichloropyridazinamine compounds.

In addition, there is a need to provide dichloropyridazinamine compounds in which the amino group is an ethylamino group because these compounds or mixtures thereof are of great interest

Zo as intermediate compounds for the preparation of pesticides and medicines.

Typically, dichloropyridazineamine compounds are prepared using 3,4,5-trichloropyridazine as starting compounds by a nucleophilic substitution reaction with an amino compound.

For example, MO 2011/038572 describes the preparation of a mixture of 3,5-dichloro-4-pyridazinamine and 5,6-dichloro-4-pyridazinamine by reacting 3,4,5-trichloropyridazine with gaseous ammonia during a reaction time of 4 days. A similar reaction is also described in 05 4,728,355, where the reaction is carried out in a sealed tube at a temperature of 120-130 C for five days. The reaction is carried out at 125"C for 5 hours, according to T5yKaza KygaivNpi and others.

Negegosusiis Spetivigu, 1964, volume 1, p. 42-47).

The above-described reaction conditions for this reaction already indicate that it is believed in the art that either long reaction times or high temperatures are necessary for the nucleophilic substitution reaction, both of which are unfavorable for industrial processes.

In addition, as can be seen, the preparation of dichloropyridazineamine compounds by the reaction of 3,4,5-trichloropyridazine with an amino compound, which is different from ammonia, is accompanied by additional problems.

UMO 99/64402 describes the reaction of 3,4,5-trichloropyridazine with 3-amino-1-propanol as a nucleophile. Although the reaction is carried out in boiling ethanol, the yields are extremely low (only 47.7 96 of crude product) and a laborious work-up by crystallization is required to isolate the desired reaction products.

UMO 2012/098387 describes the reaction of 3,4,5-trichloropyridazine with 2-methylaminoethanol as a nucleophile. Although the nucleophile uses a secondary amine, which is more nucleophilic than the primary amine, the reaction is not quantitative and requires routine workup by column chromatography. Roppa Y. Kotego and others. (Choigpa! oi Meaisipa! Spetivigu, 1996, Vol. 39, Mo. 19, pp. 3769-3789) described the reaction of 3,4,5-trichloropyridazine with isopropylamine as a nucleophile. According to the information presented in the article, the reaction can be carried out in dephlegmated toluene, that is, at a temperature of approximately 110 "C. In addition, chromatography is necessary for purification.

Similarly, UMO 96/18628 described an identical reaction where 3,4,5-trichloropyridazine and isopropylamine were heated in a reflux flask in toluene for hours. Subsequently, column chromatography is required to isolate the desired compound 4-isopropylamino-3,5-60 dichloropyridazine.

Thus, methods of preparing dichloropyridazinamines as described in the prior art are either disadvantageous in terms of reaction conditions, yields, and/or processing requirements.

In addition, another disadvantage of the methods described in the prior art is the fact that the irritant compound 3,4,5-trichloropyridazine must be prepared and processed as a starting compound. Solid processing of 3,4,5-trichloropyridazine is extremely unfavorable on an industrial scale.

Thus, the task of this invention is to provide a method for obtaining dichloropyridazineamine compounds, which overcomes the shortcomings regarding the reaction conditions, yields and/or processing requirements, which are obvious from the known state of the art, or the drawbacks regarding the use of the irritant substance 3,4,5-trichloropyridazine as a starting component .

In this connection, it is of great interest to provide a simple process which is suitable for industrial implementation and provides satisfactory yields, preferably yields greater than 90 95.

The above-mentioned problem is solved using method B, as described further in this application and in independent clause 12 and in the clauses of the claims, which directly or indirectly depend on it.

Thus, in a second aspect, the present invention relates to a method, hereinafter referred to as method B, for the preparation of (a) a dichloropyridazinamine compound of formula IMa or its salt, tautomer or M-oxide, or (b) a dichloropyridazinamine compound of formula IM or its salt, tautomer or

M-oxide, or (c) a mixture of (a) and (B) 1 N

Si ak K-M a

SCHI SCHI vi-k xx YAM si same M

СИ (Ма) со (а УВ) by a reaction in one vessel of the stage, which includes the interaction of the compound of the formula ІІ with К

CI si z M on z ROS", and the interaction of the obtained crude reaction product with the amino compound K!-MN" or its salt, where VE! is H, C1-C8-alkyl, or C1-C8-alkoxy-C1-C2-alkyl.

It should be noted that the reaction in one vessel, which is the basis of method B, corresponds to stages (I) Ж(I) in the sequence of reactions presented above.

Unexpectedly, it was discovered that in the method of obtaining dichloropyridazinamine compounds no

It is mandatory to use 3,4,5-trichloropyridazine as the starting compound. Alternatively, 3,4,5-trichloropyridazine can be prepared by 5y in a one-pot reaction with a compound of formula II as starting material. After that, the formed ip 5yi 3,4,5-trichloropyridazine is directly reacted with an amine compound, obtaining the desired dichloropyridazineamine compounds.

This method is extremely favorable for safety purposes, as there is no need to isolate and process the irritant compound 3,4,5-trichloropyridazine. This makes the method more favorable for industrial application. In addition, the method is more economical and suitable for implementation on a larger scale.

In addition, it was found that extremely high yields of dichloropyridazineamine compounds can be obtained using the above-described method, as a result of which harsh reaction conditions are not necessary for the reaction of the formed 5y 3,4,5-trichloropyridazine with an amine compound. Due to high yields, complex processing can also be avoided.

The above-mentioned problem is also solved by method C, as described further in this application and in independent clause 13 and clauses that directly or indirectly depend on it.

Therefore, in a third aspect, the present invention relates to a method, hereinafter referred to as method C, for the preparation of (a) a dichloropyridazinamine compound of formula IMa or its salt, tautomer or M-oxide, or (b) a dichloropyridazinamine compound of formula IM or its salt, tautomer or

M-oxide, or (c) a mixture of (a) and (B)

sit in! M

M M

SHHI SHHI) hi with M vm si

Si Ua) in ah" which includes the stage of interaction of the trichloropyridazine compound of the formula PI

Si a

These are M

SI si (Shu with the amino compound K!-MH" or its salt, where E! represents СНеСнН3З, and where the method optionally additionally includes the stage of obtaining a trichloropyridazine compound of the formula

SI House

ШЧХ

СІ с (Shu by the reaction of the compound of the formula ІІ с ах

These f

Si (o on (p) with ROSI).

It should be noted that the reaction stage underlying method C is covered by stage (I) in the sequence of reactions presented above. Optionally, stage (II) of the above-described sequence of reactions is also carried out.

It was unexpectedly found that the method of obtaining dichloropyridazinamine compounds is extremely favorable if ethylamine is used as a nucleophile in a nucleophilic substitution reaction. Although the prior art provides for severe reaction conditions or at least long reaction times for nucleophilic substitution reactions, the inventors of the present invention have found that moderate reaction conditions with reaction temperatures of, for example, no more than 100 "C and reaction times, are not more than 12 hours, sufficient to provide the desired dichloropyridazineethylamines in high yields, and without labor-intensive workup.

In a fourth aspect, the present invention relates to a dichloropyridazinamine compound of the formula

It or its salts, tautomer or M-oxide; si a

SHI with M vA-m

N s de VE! is СНеСнНз; or dichloropyridazinamine compound of formula IM or its salt, tautomer or M-oxide, ncl k-M a

Shchi with M

SI som) where VE" is SNSN".

In addition, the present invention relates to a mixture of a dichloropyridazinamine compound of the formula MA or its salt, tautomer or M-oxide and a dichloropyridazineamine compound of the formula IMB or its salt, tautomer or M-oxide, as defined above.

As already indicated above, these compounds are extremely versatile precursors for the production of chemicals such as pharmaceutical and agrochemical compounds. Also, they can be advantageously used in the hydrogenation / dehalogenation process, as described in this application.

In a fifth aspect, the present invention relates to a method for the preparation of a compound of the formula III" or its stereoisomer, salt, tautomer or M-oxide

In Khy M or

Bo мя озК в в (UP), which includes the stage of interaction of the pyridazineamine compound of the formula U or its salt, tautomer or M-oxide

CI with a compound of formula MI" or its stereoisomer, salt, tautomer or M-oxide in: o) em n-- 1 br de

B' is СНеСН»;»; and where

B2 represents CH", Bz represents H, BE" represents CH3, B? represents CH33 and 2? represents H; or 82 represents CH", Az represents H, KE" represents CEz, B" represents is CH3 and 5 is H; or

Bg represents CH»z, Az represents H, K7 represents CH(CH3)»g, B5 represents CH3 and E represents H; or

B represents CH", Az represents H, EC? is SNESN", But is CH3 and Be is H; or

B: represents CHbz, Ez represents H, KE" represents 1-CM-cSzNaya, B? represents SnHz and 5 represents H; or

IN? represents SnH3, Az represents H, B" represents 1-C(O)MH"-cSzNae, B? represents

CH3 and E5 is H; or

IN? represents SiH3, Hz represents H, B" and B? together represent

СНг.СнНгСЕсСНнесН;», and 29 is H; goes

X' is a leaving group, which is preferably selected from halogen, Mz,

From p-nitrophenoxy, and pentafluorophenoxy, and especially preferably is chlorine.

This method is hereinafter referred to as method Y. It should be noted that the reaction stage underlying method Y is covered by stage (M) in the reaction sequence presented above.

The method demonstrates that pyridazinamine compounds, which can be obtained using the hydrogenation / dehalogenation method as described in this application, are important intermediate compounds for the preparation of 4-pyrazole-M-pyridazinamide compounds, which are pesticides, for example, suitable for the control of invertebrate pests.

It should be understood that methods A, B, C, and O, as defined above, may optionally additionally include additional reaction stages of the sequence of reactions indicated above.

For example, method A may optionally additionally include stage (II) and optionally also stage (II), where stages (II) and (I) can be carried out separately or together as stages (II) and (I) in the reaction in one vessel. Additionally, method A may optionally further include step (I). In addition, it is understood that method A may optionally additionally include stage (M).

Method B may optionally additionally include stage (I) and/or stage (IM). Additionally, stage (M) may optionally be performed after stage (IM).

Method C may optionally additionally include stage (I) and/or stage (IM). Additionally, stage (M) may optionally be performed after stage (IM). b

Method Y may optionally additionally include one or more preliminary stages (IM), "I), "II) or (I), as indicated in the sequence of reactions presented above.

It is understood that the reaction stages of the above reaction sequences, which are preferably covered by methods A, B, C, or 0, can be carried out separately, that is, with the release of intermediate compounds, or without the release of intermediate compounds. In particular, it is preferable that certain successive stages are carried out by reactions in one vessel, as, for example, in the case of stages (1)-A (PV).

In addition, it should be emphasized that each reaction stage can be carried out on an industrial scale. Preferably, the reagents are also converted well and only minor deviations in yields are observed.

In connection with the above aspects of this invention, the following definitions are given. "Compounds according to the present invention" or "compounds according to the invention", that is, compounds of the formulas I, PI, PP, Ma, IMB, M, MI, and MI (as well as MI" and MIU), as defined in this application, include compound (i), as well as their salts, tautomers or M-oxides, if the formation of these derivatives is possible; and, if chirality centers are present, which may be the case for compounds Mi and MII, as well as compounds MI" and

MI", as well as their stereoisomers.

As used in this application, the term "pyridazinamine compound(s)" refers to compounds of formula B, i.e. pyridazine compounds with an amino group -MNEA' as a substituent in the 4th position of the pyridazine component. Thus, the pyridazine amine compounds according to the invention do not contain any additional substituents on the pyridazine ring.

As used in this application, the term "dichloropyridazineamine compound(s)" covers compounds of formula IMa or MB or a combination thereof, i.e., pyridazine compounds with an amino group -

ME! as a substituent and two chlorine substituents, where the substituents are present in those positions of the pyridazine component, which originates from the formula IMa and Mb.

As used herein, the term "trichloropyridazineamine compound(s)" preferably refers to compounds of formula I, i.e., 3,4,5-trichloropyridazine.

Depending on the acidity or alkalinity, as well as the conditions of the reactions, the compounds according to the present invention can be presented in salt form. Such salts are typically prepared by reacting the compound with an acid if the compound has a basic functional group such as an amine, or by

From the reaction of compounds with a base, if the compound has an acidic functional group, such as a carboxylic acid group.

The base-derived cations with which the compounds of the present invention react are, for example, alkali metal cations Ma, alkaline earth metal cations Mea?, or ammonium cations MK, where the alkali metals are preferably sodium, potassium or lithium and cations of alkaline earth metals are mainly magnesium or calcium, and where the substituents E are ammonium cation MK." preferably independently chosen from H,

C1-C10-alkyl, phenyl and phenyl-C1-C1-alkyl. Suitable cations are especially ions of alkali metals, preferably lithium, sodium and potassium, alkaline earth metals, preferably calcium, magnesium and barium, and transition metals, preferably manganese, copper, zinc and iron, and also ammonium (MH) and substituted ammonium. , in which from one to four hydrogen atoms are replaced by C1-C4-alkyl, C1-C2-hydroxyalkyl, C:-C1-alkyl, C:1-C4-alkyl-C1-C4-alkyl, hydroxy-C1- C4- alkoxy-C1-C4--alkyl, phenyl or benzyl. Examples of substituted ammonium ions include methylammonium, isopropylammonium, dimethylammonium, diisopropylammonium, trimethylammonium, tetramethylammonium, tetraethylammonium, tetrabutylammonium, 2-hydroxyethylammonium, 2-(2-hydroxyethoxy)ethylammonium, bis(2-hydroxyethylammonium, benzyltrimethylammonium, and benzyltriethylammonium), in addition to phosphonium, sulfonium ions, preferably tri(C1-C4-alkyl)sulfonium, and sulfoxonium ions, preferably tri(C1-C4-alkyl)usulfoxonium.

Anions derived from the acid with which the compounds of this invention react are, for example, chloride, bromide, fluoride, acid sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and C-C4 anions of monobasic carboxylic acids, mainly formate, acetate, propionate and butyrate.

Tautomers of the compounds according to the present invention include keto-enol tautomers, imine-enamine tautomers, amide-imido acid tautomers, and others. The compounds of the present invention encompass every possible tautomer.

The term "M-oxide" refers to the form of compounds according to the present invention in which at least one nitrogen atom is present in an oxidized form (in the form of MO). M-oxides of the compounds according to the present invention can be obtained if the compounds contain a nitrogen atom that can be oxidized.

M-oxides can preferably be prepared using standard methods, for example 60 using the method described in doshgpa! oi Ogdapoteiai s SPpetivigu 1989, 370, 17-31. But,

preferably according to the invention, if the compounds are not present in the form of M-oxides. On the other hand, under certain reaction conditions, it is impossible to avoid the formation of M-oxides at least at an intermediate stage.

The term "stereoisomers" includes both optical isomers such as enantiomers or diastereomers, the latter existing due to the presence of more than one center of chirality in the molecule, as well as geometric isomers (cis/trans isomers). Depending on the nature of the substitution, the compounds according to the present invention may have one or more centers of chirality, in which case they may be present as mixtures of enantiomers or diastereomers. The invention provides both pure enantiomers or diastereomers and their mixtures. Suitable compounds according to the invention also include all possible geometric stereoisomers (cis/grans isomers) and mixtures thereof.

The compounds of the invention may be in solid or liquid form or in gaseous form. If the compounds are present as solids, they may be amorphous or may exist as one or more different crystalline states (polymorphs), which may have different macroscopic properties, such as stability, or exhibit different biological properties, such as activity. This invention includes both amorphous and crystalline compounds, mixtures of different crystalline states, as well as their amorphous or crystalline salts.

The organic components specified above in the definitions of variables are - similar to the term halogen - collective terms for individual lists of representatives of individual groups. The prefix Сп-Ст indicates in each case the possible number of carbon atoms in the group.

The term "halogen" means in each case fluorine, bromine, chlorine or iodine, especially fluorine, chlorine or bromine.

The term "alkyl" as used herein and in the alkyl components alkylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyl means in each case a straight or branched alkyl group, usually having from 1 to 10 carbon atoms, often from 1 to b carbon atoms, preferably from 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms. Examples of the alkyl group are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2, 2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-

Co) dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2- trimethylpropyl, 1-ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl.

The term "haloalkyl" as used herein and in the haloalkyl components of haloalkylcarbonyl, haloalkoxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkyl, and haloalkylalkyl means in each case a straight or branched alkyl group, usually having from 1 to 10 carbon atoms, often from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, where the hydrogen atoms of this group are partially or completely replaced by halogen atoms. The best haloalkyl components are selected from

C1-C4-haloalkyl, more preferably from C1i-C3-haloalkyl or C1-C0-haloalkyl, especially from C1-C2-fluoroalkyl, such as fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl , 2,2,2-trifluoroethyl, pentafluoroethyl, and others.

The term "Alkoxy" as used in this application means in each case a straight or branched alkyl group which is bound by an oxygen atom and usually has from 1 to 10 carbon atoms, often from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms. Examples of the alkoxy group are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert-butyloxy, and others.

The term "alkoxyalkyl" as used in this application refers to an alkyl usually containing from 1 to 10, often from 1 to 4, preferably from 1 to 2 carbon atoms, where 1 carbon atom carries an alkoxy radical, usually containing from 1 to 4, preferably 1 or 2 carbon atoms as defined above. Examples are CH3OCH, CH»-OC»H5, 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.

The term "haloalkyl", as used in this application, means in each case a straight or branched oxy group having from 1 to 10 carbon atoms, often from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, where the hydrogen atoms of this groups partially or completely replaced by halogen atoms, especially fluorine atoms. Preferred haloalkoxy moieties include C1-C1-haloalkoxy, especially C1-C0-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2- chloro-2-fluoroethoxy, 2-chloro-2,2-difluoro-ethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and others.

The term "alkylsulfonyl" (alkyl-5(-0)2-), as used in this application, refers to a straight or branched saturated alkyl group having from 1 to 10 carbon atoms,

preferably from 1 to 4 carbon atoms (- C1-C4-alkylsulfonyl), preferably from 1 to 3 carbon atoms, which is connected with the sulfur atom of the sulfonyl group in any position in the alkyl group.

The term "haloalkylsulfonyl" as used herein refers to an alkylsulfonyl group as defined above, wherein the hydrogen atoms are partially or fully substituted with fluorine, chlorine, bromine, and/or iodine.

The term "alkylcarbonyl" refers to an alkyl group, as defined above, which is linked via the carbon atom of the carbonyl group (C-O) to another part of the molecule.

The term "haloalkylcarbonyl" refers to an alkylcarbonyl group, as defined above, where the hydrogen atoms are partially or completely replaced by fluorine, chlorine, bromine and/or iodine.

"Alkoxycarbonyl" refers to an alkylcarbonyl group, as defined above, which is linked by an oxygen atom to another part of the molecule.

The term "haloalkylcarbonyl" refers to an alkyloxycarbonyl group, as defined above, wherein the hydrogen atoms are partially or fully substituted with fluorine, chlorine, bromine, and/or iodine.

The term "alkenyl", as used in this application, means in each case a monounsaturated hydrocarbon radical having usually from 2 to 10, often from 2 to 6, preferably from 2 to 4 carbon atoms, for example, vinyl, allyl (2- propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, metalyl (2-methylprop-2-en-1-yl), 2-buten-1-yl, 3-buten- 1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl, 2-ethylprop-2-en-1- Yiil and others.

The term "haloalkenyl", as used in this application, refers to an alkenyl group as defined above, where the hydrogen atoms are partially or completely replaced by halogen atoms.

The term "alkynyl", as used in this application, means in each case a monounsaturated hydrocarbon radical having usually from 2 to 10, often from 2 to 6, preferably from 2 to 4 carbon atoms, for example, ethynyl, propargyl (2- propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl, 3-butyn-1-yl, 1-pentyn-1- yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1-methylbut-2-yn-1-yl, 1-ethylprop-2-yn-1-yl and others.

The term "haloalkynyl", as used in this application, refers to an alkynyl group as defined above, where the hydrogen atoms are partially or completely replaced by halogen atoms.

The term "cycloalkyl", as used in this application, and in cycloalkyl components

By cycloalkyl and cycloalkylthio, means in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The term "halocycloalkyl" as used herein, and in the halocycloalkyl components halocycloalkyl and halocycloalkylthio, means in each case a monocyclic cycloaliphatic radical having typically from 3 to 10 carbon atoms or from 3 to 6 carbon atoms, wherein at least one, e.g. 1, 2, 3, 4 or 5 hydrogen atoms replaced by halogen, especially fluorine or chlorine. Examples are 1- and 2-fluorocyclopropyl, 1,2-, 2,2- and 2,3-difluorocyclopropyl, 1,2,2-trifluorocyclopropyl, 2,2,3,3-tetrafluorocyclopropyl, 1- and lower 2-chlorocyclopropyl, 1,2-, 2,2- and 2,3-dichlorocyclopropyl, 1,2,2-trichlorocyclopropyl, 2,2,3,3-tetrachlorocyclopropyl, 1-,2- and 3-fluorocyclopentyl, 1,2-, 2 ,2-, 2,3-, 3,3-, 34-, 2,5-difluorocyclopentyl, 1-,2- and 3-chlorocyclopentyl, 1,2-, 2,2-, 2,3-, 3, 3-, C,4-, 2,5-dichlorocyclopentyl and others.

The term "cycloalkyl" refers to a cycloalkyl group, as defined above, which is linked by an oxygen atom to another part of the molecule.

The term "cycloalkylalkyl" refers to a cycloalkyl group, as defined above, which is linked by an alkyl group, such as a C1-C4 alkyl group or a C1-C4 alkyl group, especially a methyl group (-cycloalkylmethyl), to another part of the molecule.

The term "cycloalkenyl", as used herein and in the cycloalkenyl compounds cycloalkenyloxy and cycloalkenylthio, means in each case a monocyclic monounsaturated non-aromatic radical having usually from 3 to 10, for example 3, or 4 or from 5 to 10 carbon atoms , preferably from 3 to 8 carbon atoms. Examples of cycloalkenyl groups include cyclopropenyl, cycloheptenyl or cyclooctenyl.

The term "halocycloalkenyl" as used herein, and in the halocycloalkenyl compounds halocycloalkenyloxy and halocycloalkenylthio, means in each case a monocyclic monounsaturated non-aromatic radical having typically from 3 to 10, for example 3 or 4 or from 5 to 10 carbon atoms , preferably from 3 to 8 carbon atoms, where at least one, for example, 1, 2, 3, 4 or 5 hydrogen atoms are replaced by halogen, especially fluorine or chlorine. Examples are 3,3-difluorocyclopropen-1-yl and 3,3-dichlorocyclopropen-1-yl. for The term "cycloalkenylalkyl" refers to a cycloalkenyl group, as defined above, which is linked by means of an alkyl group, such as a C1-C5 alkyl group or a C1-C- alkyl group, especially a methyl group (- cycloalkenylmethyl), to another moiety molecules.

The term "carbocycle" or "carbocyclyl" generally includes a 3-x-12-membered, preferably 3-x-8-membered or 5-x-1-membered, more preferably 5-x-6-membered monocyclic, non-aromatic ring, containing from C to 12, preferably from C to 8 or from 5 to 8, more preferably 5 or 6 carbon atoms. Preferably, the term "carbocycle" includes cycloalkyl and cycloalkenyl groups as defined above.

The term "heterocycle" or "heterocyclyl" includes in general 3-x-12-cyclic, preferably 3-x-8-cyclic or 5-ty-8-cyclic, more preferably 5-ty-b-tycylation, especially b-ty membered monocyclic heterocyclic non-aromatic radicals. Heterocyclic non-aromatic radicals usually include 1, 2, 3, 4, or 5, preferably 1, 2, or 3 heteroatoms selected from M, O, and 5 as ring members, where the 5-atoms as ring members may be represented as 5, ZO, or

ZO. Examples of 5- and b-membered heterocyclic radicals include saturated or unsaturated, non-aromatic heterocyclic rings such as oxyranyl, oxetanyl, thietanyl, thietanyl-5-oxide (5-oxothietanyl), thietanyl-5-dioxide (5-dioxothietanyl), pyrrolidinyl, pyrrolinyl, pyrazolinyl, tetrahydrofuranyl, dihydrofuranyl, 1,3-dioxolanyl, thiolanyl, 5-oxothiolanyl, 5-dioxothiolanyl, dihydrothienyl, 5-oxodihydrothienyl, 5-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thiazolinyl, oxathiolanyl, piperyl, pyranyl, pyranyl dihydropyranil, tetrahydropyranil, 1,3- and 1,4-dioxanil, thiopyranil, Z-oxothiopyranil, z-dioxothiopyranil, dihydrothiopyranil,

Z-oxodihydrothiopyranyl, z-dioxodihydrothiopyranyl, tetrahydrothiopyranyl,

Z-oxotetrahydrothiopyranyl, z-dioxotetrahydrothiopyranyl, morpholinyl, thiomorpholinyl,

C-oxothiomorpholinyl, 5-dioxothiomorpholinyl, thiazinyl and others. Examples for a heterocyclic ring also containing 1 or 2 carbonyl groups as ring members include pyrrolidin-2-onyl, pyrrolidin-2,5-dionyl, imidazolidin-2-onyl, oxazolidin-2-onyl, thiazolidin-2-onyl, and others

The term "hetaryl" includes monocyclic 5- to 6-membered heteroaromatic radicals containing as ring members 1, 2, 3, or 4 heteroatoms selected from M, O, and 5. Examples of 5- to 6-membered heteroaromatic radicals include pyridyl, i.e. 2-, 3-, or 4-pyridyl, pyrimidinyl, i.e. 2-, 4-, or 5-pyrimidinyl, pyrazinyl, pyridazinyl, i.e. 3- or 4-pyridazinyl, thienyl, i.e. 2- or 3- thienyl, furyl, i.e. 2- or 3-furyl, pyrrolyl, i.e. 2- or 3-pyrrolyl,

Co) oxazolyl, i.e. 2-, 3-, or 5-oxazolyl, isoxazolyl, i.e. 3-, 4-, or 5-isoxazolyl, thiazolyl, i.e. 2-, 3-, or 5-thiazolyl, isothiazolyl, i.e. 3-, 4 -, or 5-isothiazolyl, pyrazolyl, i.e. 1-, 3-, 4-, or 5B-pyrazolyl, i.e. 1-, 2-, 4-, or b5-imidazolyl, oxadiazolyl, e.g. 2- or 5-

P1,3,oxadiazolyl, 4- or 5-(1,2,3-oxadiazol)yl, 3- or 5-(1,2,4-oxadiazol)yl, 2- or 5-(1,3,4- thiadiazol)yl, thiadiazolyl, for example, 2- or 5-(1,3,4-thiadiazol)yl, 4- or 5-(1,2,3-thiadiazol)yl, 3- or 5-(1,2, 4-thiadiazolyl, triazolyl, for example 1H-, 2H- or 3H-1,2,3-triazol-4-yl, 2H-triazol-3-yl, 1H-, 2H-, or 4H-1,2 ,4-triazolyl and tetrazolyl, i.e. 1H- or 2H-tetrazolyl. The term "hetaryl" also includes bicyclic 8- to 10-membered heteroaromatic radicals containing as ring members 1, 2 or C heteroatoms selected from M, O and 5, where the 5- to b-membered heteroaromatic ring is conjugated with a phenyl ring or with a 5-membered heteroaromatic radical. Examples of a 5-b6-membered heteroaromatic ring conjugated to a phenyl ring or a 5-b6-membered heteroaromatic radical include benzofuranyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, quinolinyl, isoquinolinyl, purinyl, 1,8-naphthyridyl, pteridyl, pyridoyiZ3,2-4|Ipyrimidyl or pyridoimidazolyl and others. These conjugated heteryl radicals can be linked to the rest of the molecule by any ring atom of a 5-ti-b6-membered heteroaromatic ring or by a carbon atom of a conjugated phenyl component.

The term "aryl" includes mono-, bi-, or tricyclic aromatic radicals having usually from 6 to 14, preferably 6, 10, or 14 carbon atoms. Examples of aryl groups include phenyl, naphthyl and anthracenyl. Phenyl is preferred as the aryl group.

The terms "heterocyclyloxy," "hetaryloxy," and "phenoxy" refer to heterocyclyl, hetaryl, and phenyl, which are linked by an oxygen atom to another part of the molecule.

The terms "heterocyclylsulfonyl," "hetarylsulfonyl," and "phenylsulfonyl" refer to heterocyclyl, hetaryl, and phenyl, respectively, which are linked via the sulfur atom of the sulfonyl group to the rest of the molecule.

The terms "heterocyclylcarbonyl," "hetarylcarbonyl," and "phenylcarbonyl" refer to heterocyclyl, hetaryl, and phenyl, respectively, which are linked via a carbon atom of the carbonyl group (C-O) to the rest of the molecule.

The terms "heterocyclylalkyl" and "hetarylalkyl" refer to heterocyclyl or hetaryl, 60 respectively, as defined above, which are linked by means of a C 1 -C 6 -alkyl group or a C 1 -C 4 -

of an alkyl group, especially a methyl group (- heterocyclylmethyl or hetarylmethyl, respectively), with the rest of the molecule.

The term "phenylalkyl" refers to phenyl which is linked by means of a C1-C5 alkyl group or a C1-C4 alkyl group, especially a methyl group (- arylmethyl or phenylmethyl), to another part of the molecule, examples include benzyl, 1-phenylethyl, 2-phenylethyl, etc.

The terms "alkylene" refer to alkyl as defined above, which is a linker between a molecule and a substituent.

The best embodiments of the invention relating to methods A, B, C, and O according to the invention are described further in this application.

In general, the reaction stages carried out in methods A, B, C, and O, as described in more detail later in this application, are carried out in reaction vessels generally accepted for such reactions, the reactions are carried out in a continuous, semi-continuous or batch manner.

In general, the predominant reactions will be carried out at atmospheric pressure. However, the reactions can also be carried out under reduced pressure.

The temperatures and duration of the reactions may vary within a wide range known to a skilled person in the art for similar reactions. Temperatures often depend on the reflux temperature of the solvents. Other reactions are preferably carried out at room temperature, that is, at about 25 "C, or when cooled on ice, that is, at about 0 "C. Completion of the reaction can be monitored by methods known to one skilled in the art, such as thin layer chromatography or

TOP.

Unless otherwise specified, the molar ratios of the reactants used in the reactions range from 0.2:1 to 1:0.2, preferably from 0.571 to 1:0.5, more preferably from 0.8: 1 to 1:0.8. Preferably, equimolar amounts are used.

Unless specifically stated otherwise, the reactants may in principle be contacted with each other in any desired sequence.

One skilled in the art knows that if the reactants or reagents are sensitive to moisture, then the reaction should be carried out under an atmosphere of protective gases, such as nitrogen, and dehydrated solvents should be used.

One skilled in the art will also know the best way to handle the reaction mixture after the reaction is complete.

The following are the preferred embodiments relating to method A according to the invention.

It is understood that the preferred embodiments indicated above and those to be illustrated below for method A according to the invention are preferred individually or in combination with each other.

As already indicated above, the present invention relates in the first aspect to method A for obtaining a pyridazineamine compound of the formula M or its salt, tautomer or M-oxide 'H

Kk-mM Do

SHI

In Mu) which includes the reaction stage of (a) a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide, or (5) a dichloropyridazinamine compound of the formula IMB or its salt, tautomer or M-oxide, or (c) a mixture of (a) and (B) 1 n

SI sa k-M ah

TSI TSI vmzi M and M

SI (Ia) with (mM) with hydrogen in the presence of a hydrogenation catalyst, where

B' represents H, C1-C8-alkyl, or C1-C8-alkyl-Ci-C8-alkyl.

The reaction stage underlying the A method corresponds to stage (IM) in the sequence of reactions presented above.

The reaction stage (RI) can be carried out only in the presence of a hydrogenation catalyst.

As used in this application, the term "hydrogenation catalyst" encompasses heterogeneous and homogeneous hydrogenation catalysts, but preferably refers to heterogeneous catalysts.

It is known in the art that platinum, palladium, rhodium and ruthenium form extremely active catalysts. Base metal catalysts such as nickel-based catalysts (such as Raney nickel and Ogy5piragh nickel) are economical alternatives. The best hydrogenation catalysts according to the invention are presented later in this description.

As a byproduct of the reaction stage (RI), hydrogen chloride is formed.

Despite this, in the best embodiment of method A, the reaction is carried out in the absence of a neutralizer NS. Unexpectedly, it was found that compounds of formula M are obtained in higher yields if the NCI neutralizer is not present in the reaction mixture.

As used in this application, the term "neutralizer NS!" refers to a chemical added to a reaction mixture to remove or deactivate hydrogen chloride (HCH). Preferred NSI neutralizers include bases, buffers, and ionic liquid precursors, which are further defined below. Of particular interest is the ability of the NOSI neutralizer to bind protons. The best NSI neutralizers are presented below.

Preferably, it is meant that the term "NS neutralizer", as used in this application, refers to a chemical substance that is added to the reaction mixture, and which does not include the starting substances of the reactions, that is, the compounds of the formula (IMa) or (IMB).

Therefore, it is better if the reaction stage (IM) is carried out in the absence of any chemical substance that is additionally added, which acts as a neutralizer of NOSI.

Since the reaction stage (RI) is preferably carried out in the absence of the NSI neutralizer, the formed NSI is still in the reaction mixture when the hydrogenation catalyst is removed.

Thus, in another preferred embodiment of method A, the NCI neutralizer is added after removing the hydrogenation catalyst. Preferably, the NSI neutralizer is provided without water. It has been found advantageous to maintain the reaction product, i.e., the compound of formula M, without water to avoid loss of the compounds in the aqueous phase, allowing for easier workup, and to avoid the need to dry the compound prior to further reactions.

The neutralizer, NSI, which is preferably added only after the removal of the hydrogenation catalyst, can preferably be selected from bases, buffers, precursors of ionic liquids, and combinations thereof.

Bases include hydroxides of alkali metals and alkaline earth metals, oxides of alkali metals and alkaline earth metals, hydrides of alkali metals and alkaline earth metals, amides of alkali metals, carbonates of alkali metals and alkaline earth metals, bicarbonates of alkali metals, alkyls of alkali metals, alkylmagnesium halides, alkali metal and alkaline earth metal alcoholates, and nitrogen-containing bases, including tertiary amines, pyridines, bicyclic amines, ammonia, and primary amines.

Buffers include aqueous and non-aqueous buffers, and are preferably non-aqueous buffers. Preferred buffers include acetate- or formate-based buffers, such as sodium acetate or ammonium formate.

Precursors of ionic liquids include imidazoles.

In a preferred embodiment of method A according to the present invention, the NOSI neutralizer is selected from the group that includes bases, including hydroxides of alkali metals and alkaline earth metals, oxides of alkali metals and alkaline earth metals, hydrides of alkali metals and alkaline earth metals, amides alkali metals, alkali metal and alkaline earth metal carbonates, alkali metal bicarbonates, alkali metal alkyls, alkylmagnesium halides, alkali metal and alkaline earth metal alcoholates, nitrogen-containing bases, including tertiary amines, pyridines, bicyclic amines, ammonia, and primary amines and their combinations; buffers including sodium acetate and/or ammonium formate; precursors of ionic liquids, including imidazoles; and their combinations.

In one preferred embodiment, the NSI neutralizer contains at least one base.

In one particularly preferred embodiment, the base is selected from the hydroxides of alkali metals and alkaline earth metals, especially from the group that includes lithium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide.

In another particularly preferred embodiment, the base is selected from alkali metal oxides and alkaline earth metal oxides, especially from the group including lithium oxide, sodium oxide, calcium oxide, and magnesium oxide.

In another particularly preferred embodiment, the base is selected from alkali metal hydrides and alkaline earth metal hydrides, especially from the group including lithium hydride, sodium hydride, potassium hydride, and calcium hydride.

In another particularly preferred embodiment, the base is selected from alkali metal amides, especially from the group including lithium amide, sodium amide, and potassium amide.

In another particularly preferred embodiment, the base is selected from alkali metal carbonates and alkaline earth metal carbonates, especially from the group consisting of lithium carbonate and calcium carbonate.

In another particularly preferred embodiment, the base is selected from bicarbonates of alkali metals, and is preferably sodium bicarbonate.

In another particularly preferred embodiment, the base is selected from alkali metal alkyls, especially from the group that includes methyllithium, butyllithium, and phenyllithium.

In another particularly preferred embodiment, the base is selected from alkylmagnesium halides, and is preferably methylmagnesium chloride.

In another particularly preferred embodiment, the base is selected from alkali metal and alkaline earth metal alcoholates, especially from the group consisting of sodium methanolate, sodium ethanolate, potassium ethanolate, potassium tert-butanolate, and dimethoxymagnesium.

In another particularly preferred embodiment, the base is a tertiary amine, especially trimethylamine, triethylamine, isopropylethylamine, or M-methylpiperidine.

In another particularly preferred embodiment, the base is pyridine, including substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine.

In another particularly preferred embodiment, the base is a bicyclic amine.

In another particularly preferred embodiment, the base is ammonia.

In another particularly preferred embodiment, the base is a primary amine, especially ethylamine.

In the most preferred embodiment of method A according to the invention, the CARRIER neutralizer is potassium hydroxide or any of the above-defined carbonates.

The bases may be used in any equimolar amounts, in excess, or, if appropriate, as solvents.

In another preferred embodiment, the NSI neutralizer contains at least one buffer.

In a particularly preferred embodiment, the buffer is anhydrous sodium acetate or anhydrous ammonium formate.

In another preferred embodiment, the NSI neutralizer contains an ionic liquid precursor.

In a particularly preferred embodiment, the precursor of the ionic liquid is an imidazole compound that forms an ionic liquid after interaction with NSI, which is set free in the hydrogenation/dehalogenation reaction. After that, the non-polar organic phase containing the desired pyridazine amine compound can be easily separated from the newly formed ionic liquid.

As already indicated above, any hydrogenation catalysts known in the art can be used for the reaction step (IM), especially heterogeneous hydrogenation catalysts.

Preferred hydrogenation catalysts include platinum, palladium, rhodium, ruthenium, nickel, or cobalt on supports such as coal.

In a preferred embodiment of method A according to the present invention, the hydrogenation catalyst is selected from the group consisting of platinum or palladium on a base, Raney nickel, and Raney cobalt, and is preferably platinum or palladium on carbon.

Optionally, the catalyst can be doped with sulfur or selenium. This can increase the selectivity of the catalyst.

In a particularly preferred embodiment, the hydrogenation catalyst is preferably palladium or platinum on carbon, wherein the content of palladium or platinum preferably ranges from 0.1 to 1595 by weight, more preferably from 0.5 to 1095 by weight based on the carrier material.

In another particularly preferred embodiment, the amount of palladium or platinum used is from 0.001 to 1 95 by weight, preferably from 0.01 to 0.1 95 by weight, based on the starting material.

In one particularly preferred embodiment, the hydrogenation catalyst is palladium on carbon, wherein the palladium content preferably ranges from 0.1 to 15 95 by weight, more preferably from 0.5 to 1095 by weight based on the carrier material. In addition, it is particularly preferred that the amount of palladium used in the reaction stage (IM) is from 0.001 to 1 95 by weight, preferably from 0.01 to 0.1 95 by weight based on the starting material. More preferably, 10 95 Ra/C is used in an amount of 0.01 to 0.1 95 by weight based on the weight of the starting material.

In another particularly preferred embodiment, the hydrogenation catalyst is platinum on carbon, wherein the platinum content is preferably from 0.1 to 15 95 by weight, more preferably from 0.5 to 10 95 by weight, based on the carrier material. In addition, it is particularly preferred that the amount of platinum used in the reaction stage (IM) is from 0.001 to 1, preferably from 0.01 to 0.1 95 by weight based on the starting material. More preferably, 10 95

RUS is used in an amount from 0.01 to 0.1 95 by weight based on the weight of the starting substance.

In batch hydrogenation, the catalyst is preferably used in powder form. In continuous hydrogenation, the catalyst used on the carbon carrier material is platinum or palladium.

After the reaction cycle, the catalyst can be filtered and reused without noticeable loss of activity.

With regard to the starting substances in the reaction stage (IM), it should be noted that one can use either (a) a dichloropyridazine compound of the formula IMa or its salt, tautomer or M-oxide, or (B) a dichloropyridazinamine compound of the formula IMBr or its salt, tautomer or M- oxide, or (c) a mixture of (a) and (5).

In the best embodiment of method A, a mixture of (a) and (B) is used.

Deputy K! in the compounds of the formulas IMa, IM, and M are preferably selected from the group that includes CH33,

СНесСнН;», and СНгОСсН».».

In the best embodiment of method A, K! in the compounds of the formulas IMa, IMBO, and M is

SnesnN

In a particularly preferred embodiment of method A, a mixture of (a) and (B) is used. It is selected in the compounds of the formulas IMa, IMb, and M from the group that includes CH3, СНеCH»3, and CH3OCH», and is preferably CH3CH3 .

Mild reactive are better for the reaction stage (IM).

In a preferred embodiment, the applied hydrogen pressure is in the range from 0.1 to 10 bar, preferably in the range from 0.1 to 1 bar, more preferably in the range from 0.1 to 0.5 bar. Elevated pressures in the range of 0.6 bar to 10 bar, preferably 1 bar to 5 bar, may be advantageous if the starting material contains impurities in amounts greater than 2 95 by weight or more than 5 95 by weight.

In the best embodiment, the reaction temperature is maintained in the range from 20 to 100 "C, preferably in the range from 20 to 65 "C. It is preferable that the reaction mixture is heated to a temperature of 30 to 40 "C after the high-pressure reactor, where the reaction is preferably carried out, is filled with hydrogen. However, since the hydrogenation reaction is exothermic, it may be necessary to subsequently cool the reaction mixture to maintain a temperature preferably below 60 "WITH. The reaction temperature in the range from 50 to 60 "С is especially preferable.

Reaction time can vary in a very wide range. The preferred reaction time is in the range of 1 hour to 12 hours, preferably in the range of 3 hours to 6 hours, e.g. 4

Ko) or 5 hours.

Suitable solvents include water and aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether; aromatic hydrocarbons such as toluene, o-, m- and p-xylene; halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene; alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol; С2о-С.--alkanediols, such as ethylene glycol or propylene glycol; alkanol ethers such as diethylene glycol; esters of carboxylic acids, such as ethyl acetate; M-methylpyrrolidone; dimethylformamide; and ethers, including open-chain ethers and cyclic ethers, especially diethyl ether, methyl tert-butyl ether (MTBE), 2-methoxy-2-methylbutane, cyclopentyl methyl ether, 1,4-dioxane, tetrahydrofuran, and 2-methyltetrahydrofuran, especially tetrahydrofuran, MTBE, and 2-methyltetrahydrofuran. Mixtures of the specified solvents can also be used.

Preferred solvents are protic solvents, preferably alcohols selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol.

In a preferred embodiment, the solvent is a C1-C4 alcohol, especially ethanol.

As can be seen above, method A may not only include the reaction stage (IM), but also other reaction stages of the reaction sequence described above.

In particular, method A may optionally additionally include stage (II) and optionally also stage (II), where stages (II) and (II) can be carried out separately or jointly as stages (II) and (I) in the reaction in one vessel. Additionally, method A may optionally further include step (I). In addition, it is understood that method A may optionally additionally include stage (M).

In one embodiment of method A, the method additionally includes reaction stages (1) - (PP), i.e. the stage of obtaining (a) a dichloropyridazinamine compound of the formula Ma or its salt, tautomer or M-oxide, or (b) a dichloropyridazinamine compound of the formula IMB or its salt, tautomer or M-oxide, or (c) a mixture of (a) and (B)

v'-M s sh a

ШЧЧЧЧШ with M with them in the si

Si (Ma) Si (mV) by reaction in one vessel of the stage, which includes the interaction of the compound of the formula

S an

TSI from M

SI on (I) with ROS", and the interaction of the resulting crude reaction product with the amino compound K!-MN" or its salt, where VE! is H, C1-C8-alkyl, or C1-C8-alkoxy-C1-C2-alkyl.

As indicated above, the one-pot reaction is advantageous because the intermediate trichloropyridazine compound of formula I, which is an irritant, does not need to be isolated.

It is meant that (a) or (B) or a mixture of (a) and (5) can be obtained at stages (II) and (PI).

In the best embodiment, a mixture of (a) and (B) is obtained.

Deputy K! in the compounds of the formulas IMa and IMb, and the amine compound K'-MHg is preferably selected from the group that includes CH3, СНеCH», and CHg2ОСН.

In the best embodiment, KE! in the compounds of the formulas IMa and MB, and the amine compound B'-MH»g is СНоСН».

In a particularly preferred embodiment, a mixture of (a) and (B) and E' in the compounds of the formulas are obtained

Ma and IMB, and the amine compound K'"-MH" is selected from the group that includes CH3, CH3CH3, and CHg2OCH3, and is preferably CH3CH3.

It is intended that the compound of formula II may also be present in the form of its pyridazone tautomer.

Reaction conditions for stages (II) and (111), which are carried out sequentially in a reaction in one vessel, as defined above, without isolation of the obtained intermediate compound of formula I, are defined in more detail below.

In an alternative embodiment of method A, the method additionally includes a reaction stage (I), i.e. a stage of obtaining (a) a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide, or (b) a dichloropyridazinamine compound of the formula IMB or its salt, a tautomer or M-oxide, or (c) a mixture of (a) and (6)

To you and MM

SCHI SCHI same M fY,: vm si

SI (Ia) and m by the reaction of the trichloropyridazine compound of formula PI

SI ZK

SHI

M sy Z zo sy (a with the amino compound K!-MH" or its salt, where VE! represents H, C-Cg-alkyl, or C-Cg- alkoxy-Ci-C2-alkyl, and where the method is optional additionally includes the reaction stage (I), i.e. the stage of obtaining the trichloropyridazine compound of the formula PI si a

AND

M sy so (PP) by the reaction of the compound of the formula ІІ

Si ah

These are from M on (PU from RUSSIA).

According to this embodiment, the compound of formula PS is isolated, which can be done, for example, by precipitation.

It is meant that (a) or (B) or a mixture of (a) and (5) can be obtained in stages (PP).

In the best embodiment, a mixture of (a) and (B) is obtained.

Deputy KE! in the compounds of formulas IMa and IMBb, and the amine compound B'-MHg is preferably selected from the group that includes CH3, СНеCH»в, and CHgОСН».

In the best embodiment, K' in the compounds of the formulas IMa and Mr, and the amine compound K'!-MH»g is СНоСН».

In a particularly preferred embodiment, a mixture of (a) and (B) is obtained, and KE" in the compounds of the formulas

YMa and IMb, and the amine compound K'-MNe is selected from the group that includes CH3, CH»CH», and CHg2OCH», and is preferably CHgCH3.

As indicated above, it is intended that the compound of formula IH may also be present in the form of its pyridazole tautomer.

Reaction conditions for stages (II) and (II), which also apply to the situation in which stages are carried out in the form of stages (II) - (PI) in a reaction in one vessel, are defined further in this application.

The reaction conditions for stage (II) are preferably as follows.

In a preferred embodiment of reaction step (II), ROS is used in excess.

In another preferred embodiment, ROSis is used in an amount of at least 1.5 mol per mol of the compound of formula II.

In one particularly preferred embodiment, ROCIis is used in an amount of from 1.5 to 2.0 mol per mol of the compound of formula II.

In another particularly preferred embodiment, ROS is used in an amount of more than 2.0 to 10 mol per mol of the compound of formula II, preferably in an amount of 4.0 to 6.0 mol, especially in an amount of 4.8 to 5.2 mol per mol of the compound of formula HER.

In yet another particularly preferred embodiment, ROCIz is used as a solvent for reaction step (1).

It is preferable that the reaction stage (II) is carried out in the absence of a solvent.

In addition, it is preferable that the reaction is carried out in an atmosphere of a protective gas, for example, in an atmosphere of nitrogen.

The reaction temperature can be in the range from 60 "C to 130 "C, preferably in the range from 100 "C to 125 "C.

The reaction time can vary in a very wide range, and is preferably in the range from 1 hour to 24 hours, preferably in the range from 17 hours to 5 hours, more preferably in the range from 1 hour to 2 hours.

After the reaction, the excess ROS can be removed under reduced pressure. After that, water is preferably added to the reaction mixture while cooling in such a way that the temperature preferably does not exceed 30 °C.

The trichloropyridazine compound of formula I can be isolated as a precipitate from the aqueous phase, or by transferring the compound of formula I to the organic phase and removing the organic solvent.

Preferred organic solvents in this regard include dichloromethane, |iso-butanol, ethyl acetate, and butyl acetate, especially butyl acetate. (Regarding the preparation and isolation of the trichloropyridazine compound of formula I, you can refer, for example, to MUO 2013/004984, M/O 2014/091368, MO 99/64402,

MO 2002/100352, and Kizviap ChShoshigpai! of Ariied Spitivig, vol. 77, Mo. 12, 2004, p. 1997-2000).

If the one-pot reaction procedure is carried out as defined above, then the step of isolating the trichloropyridazine compound of formula IS can be omitted. Instead, trichloropyridazine is transferred to the organic phase and used directly in the next reaction step.

Preferred organic solvents in this regard include dichloromethane, |iso-butanol, ethyl acetate, and butyl acetate, especially butyl acetate.

The organic phase can optionally be washed with a solution of sodium hydroxide in water (for example, a 10 95 aqueous solution of MAOH) and/or water before further use.

The reaction conditions for stage (III) are mainly as follows.

Depending on the substituent K', the amine compound K"-MNe can be in gaseous or liquid or solid form. If the amine compound K'-MNe is in gaseous form, then it can be provided either in the form of a solution or in the form of a gas.

Especially preferably, the amine compound is ethylamine, as already indicated above.

Suitable solvents include protic solvents, preferably water or C1-Ca alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, especially ethanol.

In one preferred embodiment, the solvent providing the amine compound K'-

MN" represents water. Suitable concentrations are in the range from 10 to 100 wt. 95 based on the total weight of the solution, preferably in the range from 40 to 90 wt. 95, more preferably from 60 to 80 95, most preferably from 66 to 72 wt. About.

In a particularly preferred embodiment, the amine compound K'-MNeo is ethylamine and is provided as a solution in water at a concentration in the range of 60 to 80 95 based on the total weight of the solution, preferably from 66 to 72 wt. 95.

It is an unexpected discovery according to the present invention that the presence of water in the reaction mixture does not adversely affect the yields of reaction step (11).

In another preferred embodiment, the amine compound Б'-МНо is provided in gaseous form and introduced into the reaction mixture by bubbling it in the solvent, where the reaction stage (II) will be carried out, and where the trichloropyridazine compound of the formula PS can already be dissolved. In this regard, preferred solvents include protic solvents, preferably alcohols selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol. Ethanol is a particularly good solvent. In addition, preferred solvents in which the gaseous amine compound K"-MH" can be dissolved for the reaction stage (PI) generally include toluene, TNE, and ethanol.

It is better to use an excess of the amine compound K'-MNe".

In the best embodiment, the amine compound K'-MH" is used in an amount from 1.5 to 10 mol per mol of the compound of formula I, preferably in an amount from 2.0 to 6.0 mol, especially in an amount from 2.0 to 3 .0 mol per mol of compound of formula PI.

Suitable solvents for the reaction include water and aliphatic hydrocarbons such as pentane, hexane, cyclohexane and petroleum ether; aromatic hydrocarbons such as toluene, o-, m- and p-xylene;

Halogenated hydrocarbons such as methylene chloride, chloroform and chlorobenzene; alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol; С2о-С.--alkanediols, such as ethylene glycol or propylene glycol; alkanol ethers such as diethylene glycol; esters of carboxylic acids, such as ethyl acetate; M-methylpyrrolidone; dimethylformamide; and ethers, including open-chain ethers and cyclic ethers, especially diethyl ether, methyl tert-butyl ether (MTBE), 2-methoxy-2-methylbutane, cyclopentyl methyl ether, 1,4-dioxane, tetrahydrofuran, and 2-methyltetrahydrofuran, especially tetrahydrofuran, MTBE, and 2-methyltetrahydrofuran. Mixtures of the specified solvents can also be used.

It is particularly preferable that the reaction is carried out in a mixture of solvents in which the starting materials are provided, for example, a mixture of water and butyl acetate.

Alternatively, it is particularly preferred that the reaction is carried out in protic solvents, preferably alcohols selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, especially ethanol, especially if the amine compound is provided in gaseous form. After that, the reaction stage (II) will be carried out in this protic solvent, and, optionally, also the reaction stage (IM) can be directly carried out later in a one-pot reaction, optionally using an excess of an amine compound as a carrier neutralizer.

The reaction can be carried out at temperatures in the range from 0 "C to 140 "C, preferably in the range from 25 "C to 60 "C, more preferably in the range from 30 "C to 50 "C.

BO With regard to the amine compound K'-MH as defined in this application, especially to the amine compound K'"-MH", which is ethylamine, the following reaction temperatures are particularly preferable.

In one embodiment, the reaction stage (II) is carried out at a temperature of 100 "C or less.

In another embodiment, the reaction stage (II) is carried out at a temperature of 80 °C or less.

In another embodiment, the reaction stage (I) is carried out at a temperature of 70 "C or less.

In another embodiment, the reaction stage (II) is carried out at a temperature of 60 "C or less. In one embodiment, the reaction stage (II) is carried out at a temperature from 0 "C to

100 76.

In another embodiment, the reaction stage (III) is carried out at a temperature from 0 "С to 80 s.

In another embodiment, the reaction stage (I) is carried out at a temperature from 0 "C to 7076.

In another embodiment, the reaction stage (I) is carried out at a temperature from 0 "С to 60 s.

In the best embodiment, the reaction stage (III) is carried out at a temperature from 20 C to 80 "C.

In another preferred embodiment, the reaction stage (II) is carried out at a temperature from 20 C to 70 76.

In another preferred embodiment, the reaction stage (III) is carried out at a temperature from 20 "C to 60 "C.

In a particularly preferred embodiment, the reaction stage (II) is carried out at a temperature from 25 "C to 60 "C.

Reaction time will vary widely, for example, in the range from 1 hour to 4 days.

Preferably, the reaction time is in the range from 1 hour to 24 hours, especially from 1 hour to 12 hours. More preferably, the reaction time is in the range from 1 hour to 5 hours, preferably from 3 hours to 4 hours. (Regarding the reaction step (PI), reference may also be made to 05 4,728,355).

As indicated above, method A may optionally additionally include step (I) to provide a compound of formula II.

In one embodiment of method A, the method additionally includes stages (II) and (PI), either carried out separately or as a reaction in one vessel, as well as stage (I), i.e., the method additionally includes the stage of obtaining a compound of the formula YII with ac

THESE

M

WITH

Finn! (II) by the reaction of mucochloric acid I 16)

SI about

SI on (a) with hydrazine or its salt.

The reaction conditions for stage (II) are mainly as follows.

The reactants are preferably provided in similar amounts, for example, in a molar ratio of 1.5:1 to 1:1.5, preferably in equimolar amounts.

Hydrazine is preferably provided in salt form, preferably as hydrazine sulfate.

Suitable solvents include protic solvents such as water.

The reaction mixture is preferably heated to 100 "C, until the formation of a precipitate. (For further details, reference is given to 5 4,728,355).

As already indicated above, method A may optionally additionally include stage (M).

In one embodiment of method A, the method additionally includes stage (M), i.e., the method additionally includes the stage of converting the pyridazineamine compound of formula M or its salt, tautomer, or M-oxide into the compound of formula MI or its stereoisomer, salt, tautomer, or M-oxide M se vm ry

MOtdz (MI) by the reaction of a pyridazineamine compound of formula U or its salt, tautomer or M-oxide n 1.

Kk co

SHI f (U)

with a compound of formula MI or its stereoisomer, salt, tautomer or M-oxide

geo o pe '

M Z (where VE! represents H, Ci-C8-alkyl, or Ci-C8-alkyl-Ci-C2-alkyl, follows

B2 is H, halogen, CM, MO", C:-C0-alkyl, C2-C0-alkenyl, or C2-C0-alkynyl, where at least C of the latter radicals may be unsubstituted, may be partially or fully halogenated, or may carry 1, 2 or Z of the same or different substitutes EX, or

Onva, 5Ba, C(U)Be, C(MKOHNg, 5(0)NU, 5(0)289, MAV, C(U)MAV", heterocyclyl, hetaryl, C3-C10-cycloalkyl, C3-C10-cycloalkenyl or phenyl, where the last five specified radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents selected from radicals KU and Ex;

BZ is H, halogen, CM, MO", C1-C0-alkyl, C2-Shio-alkenyl, or C2-Shio-alkynyl, where at least C of the latter radicals may be unsubstituted, may be partially or fully halogenated, or may bear 1, 2 or From the same or different substitutes Ex, or

Ova, 5Na, C(U)Be, C(MONBe, B(O)NU, 5(0)289, MAV, C(U)MAV", heterocyclyl, hetaryl, C3-C10-cycloalkyl, C3-C10-cycloalkenyl or phenyl, where the last five specified radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents selected from radicals KU and Ex;

A" represents H, CM, MO", C1-C0-alkyl, C2-C0-alkenyl, or C2-C:o-alkynyl, where the last three indicated radicals may be unsubstituted, may be partially or fully halogenated, or may bear 1, 2 or From the same or different substitutes Kh, or

Ovag, Ba, S(U)Ve, S(MOvVe, (0), (0289, MAVeV S(M)MAeV", B(O)ptMAeV!, S(M)MAMAeVI,

C-C5-alkylene-ONEa, C-Cv-alkylene-SM, C1-Cv-alkylene-C(M)AB", C1-Cv-alkylene-C(M)ONBe, C1-Cv-alkylene-MAeVI, C1 -Cv-alkylene-C(U)MAeV", C1-Cv-alkylene-5(O)tNeU, C1-Cv-alkylene-5(O)tMVeV, Сch-

C5-alkylene-MV'MVegVI, heterocyclyl, hetaryl, C3-C0-cycloalkyl, C3-C0-cycloalkenyl, heterocyclyl-C1-C8-alkyl, hetaryl-C1-C8-alkyl, C3-Cio-cycloalkyl-C1-C8- alkyl, C3-Co-cycloalkenyl-Ci-C5-alkyl, phenyl-Ci-Cv-alkyl, or phenyl, where the rings of the last ten indicated radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents CU;

From and where

Ba, B, Be are each, independently of each other, selected from H, C1-C6-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkylmethyl, C3-C6-halocycloalkyl, C2-C4- alkenyl,

C2-C4-haloalkenyl, C2-Ca-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, heterocyclyl, heterocyclyl-C1-

C-alkyl, phenyl, hetaryl, phenyl-Ci-C4-alkyl, and hetaryl-Ci-C4-alkyl, where the ring in the last six indicated radicals may be unsubstituted or may carry 1, 2, 3, 4, or 5 substituents , which, independently of each other, are selected from halogen, SM, MO", C1-Cα-alkyl, C-C--haloalkyl,

Ci-C--Alkoxy, and C--C--halo-Alkoxy;

BZ is selected from Ci-Ca-alkyl, Ci-C4-haloalkyl, C3-Cv-cycloalkyl, C3-Cv-cycloalkylmethyl,

C3-C4-halocycloalkyl, C0-C4-alkenyl, C0-C4-haloalkenyl, C2-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, heterocyclyl, heterocyclyl-C1-C4-alkyl, phenyl, hetaryl , phenyl-C1-C--alkyl, and hetaryl-C1-C--alkyl, where the ring in the last six indicated radicals can be unsubstituted or can carry 1, 2, 3, 4, or 5 substituents, which, regardless of one of one, chosen from halogen,

CM, MO", C-C-alkyl, C-C-haloalkyl, C-C-alkoxy, and C-C-haloalkyl;

Wow, V! each, independently of each other, is selected from H, C1i-Cα-alkyl, C1-C4-haloalkyl, C3-

Ce-cycloalkyl, C3-C8-cycloalkylmethyl, C3-C8-halocycloalkyl, C0-C0-alkenyl, /C2-C4-haloalkenyl, C0-C0-alkynyl, C10-C10-alkoxy-C10-C10-alkyl, Si -Ca-alkylcarbonyl, /-Ci-C4- haloalkylcarbonyl, C1-C4-alkylsulfonyl, C1-C4-haloalkylsulfonyl, heterocyclyl, heterocyclyl-C1-C-alkyl, heterocyclylcarbonyl, heterocyclylsulfonyl, phenyl, phenylcarbonyl, phenylsulfonyl, hetaryl, hetarylcarbonyl, hetarylsulfonyl , phenyl-C-

C.4-alkyl, and hetaryl-Ci-C4-alkyl, where the ring in the last twelve indicated radicals may be unsubstituted or may bear 1, 2, 3, 4, or 5 substituents, which, independently of each other, are selected from halogen , SM, MO", C--Cα-alkyl, C-C"-haloalkyl, C--Cα-alkyl, and C-C4-haloalkyl; or

Ve and V! together with the nitrogen atom to which they are bound, form a 5 - b-membered, saturated or unsaturated heterocycle, which can carry an additional heteroatom selected from O, 5 and M as a ring atom and where the heterocycle can be unsubstituted or can bear 1, 2, 3, 4, or substituents, which, independently of each other, are selected from halogen, CM, MO", C1-Ca-alkyl, C1-

C4-haloalkyl, C1-C1-alkoxy, and C1-C-haloalkyl;

Be, B" are each, independently of each other, selected from H, C1-Cα-alkyl, C1-Cα-haloalkyl,

C3-C8-cycloalkyl, C3-C8-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, 5 0 C1-64-alkoxy-C1-C4-alkyl, heterocyclyl, heterocyclyl- C-C"-alkyl, phenyl, hetaryl, phenyl-

C1-C4-alkyl, and hetaryl-C1-C--alkyl, where the ring in the last six specified radicals can be unsubstituted or can carry 1, 2, 3, 4, or 5 substituents, which, independently of each other, are selected from halogen, SM, MO", C--Cα-alkyl, C--Cα-haloalkyl, C--Cα-alkyl, and C-C4-haloalkyl;

B is selected from H, C-Cα-alkyl, C-Cα-haloalkyl, C3-C6-cycloalkyl, /C3-Cv-cycloalkylmethyl, C3-Cv-halocycloalkyl, C2-C--alkenyl, C2-C4-haloalkenyl, C2 -Ca4-alkynyl,

C-C4-Alkoxy-C1-C.-alkyl, phenyl, and phenyl-Ci-C4-alkyl, where the phenyl ring in the last two indicated radicals may be unsubstituted or may bear 1, 2, 3, 4, or 5 substituents, which, independently of each other, are selected from halogen, SM, MO", C1-Cα-alkyl, C1-C. haloalkyl, C1-

Ca4-Alkoxy, and Ci-C--halo-Alkoxy;

Ah is selected from CM, MO», C1-C6-Alkoxy, C1-C6-halo-Alkoxy, Z(O)tNAYA, 5(O)ptMAeV, C1-C6-alkylcarbonyl, C1-C4-haloalkylcarbonyl, C1-C4-haloalkylcarbonyl, C1-C4-haloalkylcarbonyl , C1-C4-haloalkoxycarbonyl,

C3-Cv-cycloalkyl, 5-th-7-membered heterocyclyl, 5-th-b-membered hetaryl, phenyl, C3-Cv-cycloalkyl, 3-x-b-thyl-membered heterocyclyloxy, and phenoxy, where the last 7 indicated radicals can be unsubstituted or may carry 1, 2, 3, 4, or 5 KU radicals;

VU is chosen from halogen, CM, MO, C1-Cα-alkyl, C-C4-haloalkyl, C1-Cα-alkoxy, C1-Cα4- haloalkoxy, 5(O)tNYA, 5(O)tMAeV, Si -C.-alkylcarbonyl, C.sub.-C.-haloalkylcarbonyl, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.3-C.sub.-haloalkylcarbonyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.-halocycloalkyl, C.sub.2-C.sub.4-alkenyl, C.sub.4-C.sub.4-haloalkenyl , Co-Ca-alkynyl, and C-C-Alkoxy-C1-Ca4-alkyl; and where

U represents O or 5; and t is 0, 1 or 2; goes

X' is a leaving group, which is preferably selected from halogen, Mz,

From p-nitrophenoxy, and pentafluorophenoxy.

In a preferred embodiment,

B' is СНеСнНз;

IN? represents C1-C--alkyl, which may be unsubstituted, or may be partially or fully halogenated;

ВZ is H; and

A" represents the group -СВ"В5Не where

A" is selected from C-C4-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may carry 1 or 2 identical or different substituents KX, where Ex is selected from CM and C(C)MH", and

C3-C8-cycloalkyl, which may be unsubstituted or may bear 1, 2, or C of the same or different substituents RU, where KU is selected from halogen, SM and С(О)МН"; and

AND? is selected from C-C4-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may carry 1 or 2 identical or different substituents Xx, where Ex is selected from CM and C(C)MH", and

C3-C8-cycloalkyl, which may be unsubstituted or may bear 1, 2 or C of the same or different substituents KU, where KU is chosen from halogen, SM and C(IS)MN"; or

B" and 2", together with the carbon atom to which they are attached, form a 3- to 12-membered non-aromatic, saturated carbocycle, which can be partially or completely substituted by K), where

E) choose from halogen, CM, and С(О)МН"; and

IN? is H; and

X' is a leaving group that is preferably selected from halogen, Mz, p-nitrophenoxy, and pentafluorophenoxy, and is particularly preferably chlorine.

In a better embodiment of the invention, EM is -SV" ANU, and

B' is СНеСН;»; and

B represents CH", Bz represents H, EC" represents CH3, B? represents CH3 and EC? represents 60 is H; or

82 represents CH", Az represents H, KE" represents CE3, B" represents CH3 and 5 represents H; or

B: represents SnH»z, Az represents H, K" represents CH(CH3z)2, B? represents CH3 and E represents H; or

B2 is CH»z, Bz is H, B" is SNESCH", Bo is CH3 and 25 is H; or

B: represents CHbz, Bz represents H, KE" represents 1-CM-cSzNae, B? represents CHbz and 5 represents H; or

IN? represents CH3, Az represents H, K" represents 1-С(О)МН»-сСзНе, B» represents

SnH3 and K9 is H; or

Vg represents SiHz, Hz represents H, MK" and KK? together represent

СНгСнНгСЕсСНнесН;», and 29 is H; and

X' is a leaving group that is preferably selected from halogen, Mz, p-nitrophenoxy, and pentafluorophenoxy, and is particularly preferably chlorine.

Regarding reaction conditions for stage (M), reference can be made to UMO 2009/027393 and

MO 2010/034737.

In the following, the best implementation options relating to method B according to the invention are presented. It is understood that the preferred embodiments indicated above and those illustrated below for method B according to the invention are preferred individually or in combination with each other.

As already indicated above, the present invention relates to the second aspect of method B for obtaining (a) a dichloropyridazinamine compound of the formula Ma or its salt, tautomer or M-oxide, or (B) a dichloropyridazinamine compound of the formula IMOB or its salt, tautomer or M-oxide, or ( c) mixture of (a) and (B) 1 n

SI To kA-M ah

SHHI SHHI in-m with M s with M

SI (Iua) with MU by reaction in one vessel of the stage, which includes the interaction of the compound of the formula ІІ

Si sakh

These are the same M on (PZ from ROS", i

From the interaction of the resulting crude reaction product with the amino compound K!-MH" or its salt, where VE! is H, C1-C8-alkyl, or C1-C8-alkoxy-C1-C2-alkyl.

The reaction stage underlying method B corresponds to stages (II) of (1) in the sequence of reactions presented above.

As indicated above, the one-pot reaction is advantageous because the intermediate trichloropyridazine compound of formula I, which is an irritant, does not need to be isolated.

As indicated above, it is intended that the compound of formula II may also be present in the form of its pyridazone tautomer.

It is meant that (a) or (B) or a mixture of (a) and (B) can be obtained at stages (II) and (PP).

In the best embodiment, a mixture of (a) and (B) is obtained.

Deputy K! in the compounds of the formulas IMa and IMb, and the amine compound K'-MHg is preferably selected from the group that includes CH3, СНеCH»в, and CHgОСН».

In the best embodiment, K' in the compounds of the formulas IMa and Mr, and the amine compound K'!-MH»g is СНеCH».

In a particularly preferred embodiment, a mixture of (a) and (B) and E'" is obtained in the compounds of the formulas

Ma and IMB, and the amine compound K'"-MH" is selected from the group that includes CH3, CH3CH3, and CHg2OCH3, and is preferably CH3CH3.

Reaction conditions for stages (II) and (111), which are carried out sequentially in a reaction in one vessel, as defined above, without isolation of the obtained intermediate compound of formula I, have already been described above.

BO In the best embodiment of method B, the method additionally includes stage (I), i.e. the stage of obtaining the compound of the formula

THESE

M so on (1) by the reaction of mucochloric acid (I) 16) si o

Si on () with hydrazine or its salt.

The reaction conditions for this reaction stage (I) have already been described above.

In another preferred embodiment of method B, the method additionally includes a step (IM), i.e. a step of converting (a) a dichloropyridazine compound of the formula Ma or its salt, tautomer or M-oxide, or (b) a dichloropyridazine compound of the formula IMB or its salt, a tautomer or M-oxide, or (c) a mixture of (a) and (b) into a pyridazinamine compound of the formula M or its salt, tautomer or M-oxide 1 n

SHI same AM (U by reaction of (a) dichloropyridazinamine compound of formula IMa or its salt, tautomer or

M-oxide, or (b) a dichloropyridazinamine compound of the formula IMB or its salt, tautomer or M-oxide, or (c) a mixture of (a) and (B)

And in-K she M M

WHAT ARE THESE?

M M

V'-k iv: you are with

SI (IMa) with aUum with hydrogen in the presence of a hydrogenation catalyst, where E" has the meaning as defined above; and where the method optionally additionally includes step (M), i.e. the step of converting the pyridazineamine compound of formula M or its salt, tautomer or M -oxide into the compound of the formula

MI or its stereoisomer, salt, tautomer or M-oxide p OM vm y

M in Kk (U) by the reaction of a pyridazinamine compound of the formula U or its salt, tautomer or M-oxide

In M nF.

SHI with a compound of the formula MI or its stereoisomer, salt, tautomer or M-oxide p: (o)

Sheh! -er

M. Z

(M where K! has the meaning as defined above, and where B, VU, VM, and X' have the values as defined above.

The best implementation options and reaction conditions for reaction stages (IM) and (M) have already been described above in relation to method A.

In the following, better implementation options relating to method C according to the invention are presented. It is understood that the preferred embodiments indicated above and those to be illustrated below for method C according to the invention are preferred individually or in combination with each other.

As already indicated above, the present invention relates in the third aspect to method C for the preparation of (a) a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide, or (B) a dichloropyridazinamine compound of the formula IMB or its salt, tautomer or M-oxide, or (c) mixtures of (a) and (b)

YOU

Si a Doc

SHI P s M zh M vm si

SI (IMa) with M) which includes the stage of interaction of the trichloropyridazine compound of the formula PI

SI ah

WHAT'S WITH THEM

SI si (that with the amino compound K'-MH" or its salt, where VE" represents СНоСН»5, and where the method optionally additionally includes the stage of obtaining the trichloropyridazine compound of the formula

Si a

The same M

SI and 5 s (Pp) by reaction of the compound of the formula ІІ

Count it

THESE. phys

SI on (1) from RUSSIA".

The reaction stage underlying method C includes stage (II) in the sequence of reactions presented above, and optionally additionally stage (II) as a separate stage.

It was unexpectedly discovered that extremely high yields can be obtained in the reaction stage (IP) if ethylamine is used as the amine compound K'-MH". In addition, time-consuming processing is not necessary.

As indicated above, it is intended that the compound of formula IH may also be present in the form of its pyridazole tautomer.

It is understood that (a) or (B) or a mixture of (a) and (B) can be obtained in step (10).

In the best embodiment, a mixture of (a) and (B) is obtained.

Reaction conditions for stages (II) and (PI), which are carried out separately according to method C, have already been described above.

Ko) In the best embodiment of the method C, the method additionally includes stage (I), i.e. the stage of obtaining the compound of the formula ІІ (93) ac

TSI z i M (o on (I) by the reaction of mucochloric acid (I)

at

SI about

Si on (I) with hydrazine or its salt.

The reaction conditions for this reaction stage (I) have already been described above.

In another preferred embodiment of method C, the method additionally includes a stage (IM), i.e. a stage of conversion of (a) a dichloropyridazinamine compound of formula IMa or its salt, tautomer or M-oxide, or (b) a dichloropyridazinamine compound of formula IMB or its salt, tautomer or M-oxide, or (c) a mixture of (a) and (5) into a pyridazinamine compound of formula U or its salt, tautomer or M-oxide 1 N k so

SHI with M (U) by the reaction of (a) a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or

M-oxide, or (b) a dichloropyridazinamine compound of the formula IMB or its salt, tautomer or M-oxide, or (c) a mixture of (a) and (B) 1 n

Si ah KA-M a

SHI SHI SHI

M j M vm si

SI (Iua) coaM" with hydrogen in the presence of a hydrogenation catalyst, where K' has the value as defined above; and where the method optionally additionally includes step (M), i.e. the step of converting a pyridazineamine compound of formula M or its salt, tautomer or M-oxide into a compound of formula

MI or its stereoisomer, salt, tautomer or M-oxide

She M zim -M you

MO (MI) by the reaction of a pyridazinamine compound of formula B or its salt, tautomer or M-oxide

V'-M

IF

SHI with M (U) with a compound of the formula MI or its stereoisomer, salt, tautomer or M-oxide

Ge (in) -E x! es de K! has the meaning as defined above, and where B, VU, VM, and X' have the values as defined above.

The best implementation options and reaction conditions for reaction stages (IM) and (M) have already been described above in relation to method A.

In the following, better implementation options relating to method Y according to the invention are presented. It is meant that the best options for implementation, indicated above and those that will be

3 and 3 illustrated below for method O according to the invention are preferred individually or in combination with each other.

As already indicated above, the present invention relates in a further aspect to the method of preparation of the compound of the formula MI! or its stereoisomer, salt, tautomer or M-oxide from M

Che: M byu, which includes the stage of interaction of the pyridazineamine compound of the formula U or its salt, tautomer or M-oxide in M nF

SHI

5 with a compound of formula MI" or its stereoisomer, salt, tautomer or M-oxide p2 IF) in 1 with Xx 5 where

B' is СНеСН»;»; and where

B2 represents CH", Bz represents H, BE" represents CH3, B? represents CH33 and 2? represents H; or 82 represents CH", Az represents H, KE" represents CEz, B" represents is CH3 and 5 is H; or

Bg2 represents SnH»z, Az represents H, K" represents CH(CH3z)2, B? represents CH3 and E represents H; or

B represents CH", Hz represents H, KE? represents SNESN", B" represents CH3 and 5 represents H; or

B: represents CHbz, Bz represents H, KE" represents 1-CM-cSzNae, B? represents CHbz and 5 represents H; or

B: represents CH", Az represents H, K" represents 1-С(О)МН»г-сСзНае, В? represents

CH3 and E5 is H; or

IN? represents SiH3, Hz represents H, B" and B? together represent

СНг.СнНгСЕсСНнесН;», and 29 is H; goes

X' is a leaving group that is preferably selected from halogen, Mz, p-nitrophenoxy, and pentafluorophenoxy, and is particularly preferably chlorine.

The reaction stage underlying method Y is covered by stage (M) of the above-described sequence of reactions.

In a preferred embodiment, the method further includes a step (IM) of a sequence of reactions.

In a better embodiment of the invention, the method additionally includes stage (I) and

Not necessarily also stage (II), where stages (I) and (I) can be carried out separately by isolating the compound of formula II, or together in a reaction in one vessel.

In an even more preferred embodiment, the method further comprises step (1).

Further details for stages (I), (1), (PI), and (IM) have already been described above.

As already indicated above, the present invention relates in another aspect to the dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide; si ek

SHI

M vm i

SI (Ma) de VE! is СНеСнНз; or dichloropyridazinamine compound of formula IM or its salt, tautomer or M-oxide,

1 N kA-M an

Shchi si hi M

SI (M) where B! is СНоСН".

In a further aspect, the present invention relates to a mixture of a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide and a dichloropyridazinamine compound of the formula

IMB or its salt, tautomer or M-oxide, as defined above, i.e. where K' is in each case CH2CH»».

These compounds are valuable starting materials for obtaining 4-ethylaminopyridazine, which itself, for example, can be transformed into pesticidally active 4-pyrazole-M-pyridazineamide compounds of the formula MI.

Typically, a mixture of a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide and a dichloropyridazinamine compound of the formula IMB or its salt, tautomer or M-oxide, as defined above, i.e. where K! is in each case CH2CH3, can be obtained using methods B or C, as described in this application. The mixtures can be separated into components (a) a dichloropyridazinamine compound of formula IMa or a salt, tautomer, or M-oxide thereof and (B) a dichloropyridazinamine compound of formula IMB or a salt, tautomer, or M-oxide thereof using separation techniques known to those skilled in the art technical field, for example, by means of column chromatography. However, separation of the two components is not required to obtain the pyridazinamine compound of formula M because both components are suitable starting materials for the dehalogenation/hydrogenation reaction.

In the mixture, the components (a) dichloropyridazinamine compound of formula IMa or its salt, tautomer or M-oxide and (b) dichloropyridazinamine compound of formula IMB or its salt, tautomer or M-oxide can be present in any ratio, preferably in weight ratios in the range from 100:1 to 1:100, preferably 10:1 to 1:10, more preferably 5:1 to 1:5, most preferably 2:1 to 1:22, especially preferably 1:1.

Examples

I. Characteristics

Characterized by combined high-performance liquid chromatography / mass spectrometry (HPLC/MS), by NMR or by their melting points.

TOP: Adiepi Ekhiepa 1.8 micron C18 4.6x100 mm; mobile phase: A: water 0.1 95 NzPOx;

Zo B: acetonitrile (Mesp) w0.1 95 NzRO»x; gradient: 5-9595 A for 10 minutes; 0-10 minutes is 5:95 A:B then gradient from 10-10.1 minutes to 95:5 A:B flow: 1.2 ml/min for 10 minutes at 60 "C. min HER 7777777 A 777717 17717171 11717111 Flow | Pressure (bar): С 2861117 Г1111115111117171717171717117195.... | ..Ю.7.12 2 YushЩ| 400 "H-NMR: Signals were characterized by chemical shift (frequency per million) relative to tetramethylsilane, by their multiplicity and their integral ( relative number of represented hydrogen atoms). The following abbreviations are used to characterize the multiplicity of signals: t - multiplet, d - quartet, i - triplet, a - doublet, and 5 - singlet.

Abbreviations used are: h. for hour(s), min for minute(s) and room temperature for 20-25 76.

II. Production examples 1. Preparation of a mixture of 3,4-dichloro-5-ethylaminopyridazine and 3,5-dichloro-4-ethylaminopyridazine using a procedure in one vessel, using 4,5-dichloro-3-hydroxypyridazine as a starting material: 200 g 4, 5-dichloro-3-hydroxypyridazine was placed in a reactor at 20 °C under M atmosphere, and Osiz (930 g, 5 equiv) was added to P and the reaction mixture was heated to 100 °C. The reaction mixture was further stirred for 1 hour until complete conversion was achieved. Excess ROS was removed by distillation. The reaction mixture was dosed in 1200 g of HO, controlling the temperature at 30 "C. Butyl acetate (1200 g) was added and the two-phase mixture was stirred for 30 minutes at 30 "C and then the phases were separated. Another portion of butyl acetate (400 g) was used to wash the aqueous phase. The combined organic phases were washed with 10 95 NOSI and then H2O.

A solution of ethylamine in water at a concentration of 70 wt was added to a mixture of trichloropyridazine in butyl acetate. 96 ethylamine based on the total weight of the solution (234 g, 3 equiv) at 35 C.

The reaction was maintained at 45 °C for 3 hours (or until the conversion was complete).

The phases were separated at 40 "C and the organic phase was washed once with NgO. The combined aqueous phases were extracted once with butyl acetate. The butyl acetate from the combined organic phases was distilled off (15 mbar, 35 "C) to concentrate the reaction mixture. During this process, the product was precipitated from the solution. The reaction mixture was cooled to 10 °C and the product was filtered off. The mother liquor was then concentrated and the crude material was recrystallized from MTBE to isolate the product residue. 2. Preparation of 4-ethylaminopyridazine: b00 g (3.09 mol) of a mixture of 3,4-dichloro-5- ethylaminopyridazine and 3,5-dichloro-4-ethylaminopyridazine were dissolved in EP (3.5 liters). 15 g (0.01 mol) of 10,965 Pa/C were added and the reactor was purged with nitrogen under pressure. The pressure in the high-pressure reactor was increased to 0 ,2 bar using Neo and heated to 35"C. Since the reaction is exothermic, the temperature was controlled at 55°C for 4 hours. After that, the pressure was reduced and the reactor was purged with Me. The reaction mixture was filtered at room temperature to remove the catalyst. The catalyst can be reused in the next batch without purification.

In the second reactor, a mixture of K2СО3 (1 kg) and 1 liter of Ею was prepared. The reaction mixture was dosed into the potassium carbonate solution for 60 minutes and the temperature was controlled at 20-25,760.

The reaction mixture was further stirred for 3 hours. The salts obtained in the method were filtered. A portion of the solvent from the reaction mixture was distilled off and MTBE was added to precipitate pure ethylaminopyridazine (354 g, purity 91 95, yield 85 9b).

Claims (9)

FORMULA OF THE INVENTION 1. The method of obtaining a pyridazinamine compound of the formula M or its salt, tautomer or M-oxide is also M (M which includes the stage of interaction of (a) a dichloropyridazinamine compound of the formula IMa or its salt, tautomer or M-oxide, or (5) a dichloropyridazinamine compound formula IMB or its salt, tautomer or M-oxide, or (c) a mixture of (a) and (B) with hydrogen in the presence of a hydrogenation catalyst, where the method additionally includes the step of obtaining (a) a dichloropyridazineamine compound of formula IMa or its salt, tautomer or M-oxide, or (5) a dichloropyridazinamine compound of formula IM or its salt, tautomer or M-oxide, or (c ) mixture of (a) and (B) by reaction in one vessel, which includes stages: interaction of the compound of the formula ІІІІІІІІІІІІ! » or its salt, where the stage of isolation of the trichlorpyridazine compound of the formula PI is omitted, and where trichlorpyridazine p transferred to the organic phase and directly used in the next reaction stage; and where B' represents H, C1-C2-alkyl, or C1-C2-alkoxy-C1-C2-alkyl. 2. The method according to claim 1, where the reaction is carried out in the absence of the NS neutralizer. 3. The method according to claim 1 or 2, where the NSI neutralizer is added after removing the hydrogenation catalyst, where the NSI neutralizer is preferably provided without water. 4. The method according to any one of claims 1-3, where the NSI neutralizer is selected from the group that includes bases, including hydroxides of alkali metals and alkaline earth metals, oxides of alkali metals and alkaline earth metals, hydrides of alkali metals and alkaline earth metals, alkali amides metals, alkali metal and alkaline earth metal carbonates, alkali metal bicarbonates, alkali metal alkyls, alkylmagnesium halides, alkali metal and alkaline earth metal alcoholates, nitrogen-containing bases, including tertiary amines, pyridines, bicyclic amines, ammonia, and primary amines; and their combinations; buffers including sodium acetate and/or ammonium formate; precursors of ionic liquids, including imidazoles; and their combinations. 5. The method according to any one of claims 1-4, where the hydrogenation catalyst is selected from the group that includes platinum or palladium on the basis, Raney nickel and Raney cobalt, and is preferably platinum or palladium on carbon. 6. The method according to any of claims 1-5, where KE! is СНеСН»в. 7. The method according to any one of claims 1-6, where the method additionally includes the stage of obtaining the compound of the formula II Sv KO k (1) by the reaction of mucochloric acid (I) with se iy Ma? Kai Yuk () with hydrazine or its salt. 8. The method according to any one of claims 1-7, where the method additionally includes the step of converting a pyridazineamine compound of the formula M or its salt, tautomer or M-oxide into a compound of the formula MI or its stereoisomer, salt, tautomer or M-oxide: m is za M aso -y Kk ich (MI) Zo by reacting a pyridazinamine compound of the formula B or its salt, tautomer or M-oxide B veve t bi os (M) with a compound of the formula MI or its stereoisomer, salt, tautomer or M -oksidom ek reve i hi I » ve sche I EK ; (M) where E! has the values specified in claim 1 or 6, and where Bg is H, halogen, CM, MO", C.1-C:to-alkyl, C.sub.2-C:to-alkenyl or C.2-C:io-alkynyl, where at least Of the last mentioned radicals may be unsubstituted, may be partially or fully halogenated, or may carry 1, 2, or C of the same or different substituents ЕХ, or Ова, 582, С(У)Ае, С(МОВе, 5Б(О)НУ, 5 (0)289, MAeV, C(U)MAeV", heterocyclyl, hetaryl, C3-C0-cycloalkyl, C3-C0-cycloalkenyl or phenyl, where the last five specified radicals can be unsubstituted or can carry 1, 2, 3 , 4 or 5 identical or different substituents selected from KU and Ex radicals; BZ represents H, halogen, CM, MO", C-C0-alkyl, C2-C0-alkenyl or C2-C0-alkynyl, where at least C of the latter the indicated radicals may be unsubstituted, may be partially or fully halogenated, or may carry 1, 2, or C of the same or different substituents ЭХ, or Оваг, 582, С(У)В?, С(КОВе, 5(0)НУ, 5( 0)289, MAeVi, C(U)MAoV", heterocyclyl, hetaryl, C3-C0-cycloalkyl, C3-Cio-cycloalkenyl or f enyl, where the last five indicated radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different substituents selected from radicals KU and Ex; VAM is H, CM, MO", C1-C0-alkyl, C1-C0-alkenyl, or C2-C0-alkynyl, where the last three indicated radicals may be unsubstituted, may be partially or fully halogenated, or may bear 1, 2, or Of the same or different substitutes Kh, or Ov, 58a, С(У)В, С(СМОВУ, Б(О)ВУ, 5(0)289, MAV, С(М)МАУА", Б(О)пМвеВ!, C(M)MV'MAeVI, C5-C5-alkylene-ONE, C-C5-alkylene-CM, C-Cv-alkylene-C(M)Be, C1-Cv-alkylene-C(H)ONBe, C- C1-C1-alkylene-MAV, 0 C1-C1-alkylene-C(U)MAUV", /C1-C5-alkylene-5(O)tAYA, C1-C1-alkylene-5(O)pMAeV, 0 C1-Cv- alkylene-MV'MVA2VI, heterocyclyl, hetaryl, C3-Cio-cycloalkyl, C3-Cio-cycloalkenyl, heterocyclyl-Ci-Cv-alkyl, hetaryl-Ci-Cv5-alkyl, C3-C10-cycloalkyl-C1-Cv-alkyl, C3-Sthio-dichloroalkenyl-C-i-Cv-alkyl, phenyl-Ci-Cv-alkyl or phenyl, where the rings of the last ten indicated radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 identical or different KU substituents ; and where Be, He, Be are each, independently of each other, selected from H, C1-Cα-alkyl, C-C--haloalkyl, Zo C3-Cv-cyclo alkyl, C3-C6-cycloalkylmethyl, C3-C6-halocycloalkyl, C2-C1-alkenyl, C2-C4-haloalkenyl, C2-C6-alkynyl, C1i-C--alkyl-Ci--C--alkyl, heterocyclyl, heterocyclyl -C1-Ca4- alkyl, phenyl, hetaryl, phenyl-C1-Ca-alkyl and hetaryl-C1-C.-alkyl, where the ring in the last six indicated radicals can be unsubstituted or can carry 1, 2, 3, 4 or 5 substituents, which, independently of each other, are selected from halogen, CM, MO", C-C-alkyl, C-C--haloalkyl, C1- C.4-Alkoxy and C-C--halo-Alkoxy; VU is selected from C-C-alkyl, C-C-haloalkyl, C3-Ce-cycloalkyl, C3-Ce-cycloalkylmethyl, C3-S5-halocycloalkyl, C2-C.-alkenyl, C2-C.--haloalkenyl, C2 -C--alkynyl, C1-C-alkoxy-C1-C4-alkyl, heterocyclyl, heterocyclyl-C1-C4-alkyl, phenyl, hetaryl, phenyl-C1-C4-alkyl and hetaryl-C1-C4-alkyl, where the ring in the six last indicated radicals may be unsubstituted or may bear 1, 2, 3, 4 or 5 substituents, which, independently of each other, are selected from halogen, CM, MO", Ci-C.-alkyl, Ci-C4- -haloalkyl, C1-C--alkoxy and C1--C--haloalkoxy; Wow, V! each, independently of each other, is selected from H, C1-Cα-alkyl, C1-C-haloalkyl, C3-C8-cycloalkyl, C3-C8-cycloalkylmethyl, C3-C8-halocycloalkyl, C3-C8-alkenyl, C2 -C4- haloalkenyl, C2-Cα-alkynyl, C-C--Alkoxy-Ci--C--Alkyl, C-C.-Alkylcarbonyl, /C-C4- haloalkylcarbonyl, C-C-Alkylsulfonyl, C1-C .-haloalkylsulfonyl, heterocyclyl, heterocyclyl-C1-C4-alkyl, heterocyclylcarbonyl, heterocyclylsulfonyl, phenyl, phenylcarbonyl, phenylsulfonyl, hetaryl, hetarylcarbonyl, hetarylsulfonyl, phenyl-C- C.-alkyl and hetaryl-Ci-C.-alkyl, where the ring in the last twelve specified radicals may be unsubstituted or may carry 1, 2, 3, 4 or 5 substituents, which, independently of each other, BO are selected from halogen, SM, MO», C-Cg-alkyl, C-i-C--haloalkyl, C-C--alkoxy and C-C-haloalkyl; or Ve i 2! together with the nitrogen atom to which they are bound, form a 5-6 membered, saturated or unsaturated heterocycle, which may carry an additional heteroatom selected from O, 51 M as a ring atom, and where the heterocycle may be unsubstituted or may carry 1, 2, 3, 4 or 5 substituents, which, independently of each other, are selected from halogen, CM, MO", C1-Cα-alkyl, C1i-Cα-haloalkyl, C-C-Alkoxy and C--C- - haloalkoxy; Бе, А" are each, independently of each other, selected from H, C-Cα4-alkyl, C-C--haloalkyl, C3-Cv-cycloalkyl, C3-Cv-halocycloalkyl, Cg-Cα-alkenyl, Cg-C4- -haloalkenyl, C2-C6-alkynyl, C1-C1- alkoxy-C1-C6-alkyl, heterocyclyl, heterocyclyl-C1-C6-alkyl, phenyl, hetaryl, phenyl-C1-C6-alkyl, and hetaryl-C6- C--alkyl, where the ring in the last six indicated radicals can be unsubstituted or can carry 1, 2, 3, 4 or 5 substituents, which, independently of each other, are selected from halogen, CM, MO", Ci-Cg-alkyl , C-i-C--haloalkyl, C-C-- alkoxy, and C-C--haloalkyl; B' is selected from H, C:-C-alkyl, C-C--haloalkyl, C3-C6-cycloalkyl, C3 -C6-cycloalkylmethyl, C3-C6-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C1-C-alkoxy-C1-C4-alkyl, phenyl and phenyl-C1-C4 -alkyl, where the phenyl ring in the last two indicated radicals can be unsubstituted or can carry 1, 2, 3, 4 or 5 substituents, which, independently of each other, are selected from halogen, CM, MO", Ci-Ca-alkyl, Si-S--g haloalkyl, C1-C1-alkoxy and C1-C1-haloalkoxy; Ah is selected from CM, MO», C-C-Alkoxy, C-C-halo-Alkoxy, 5(O)tNYA, 5(O)tpMAeVi, C1-C0-alkylcarbonyl, C1-C4-haloalkylcarbonyl, C-C-Alkoxycarbonyl . may be unsubstituted or may carry 1, 2, 3, 4 or 5 KU radicals; VU is chosen from halogen, SM, MO", C.1-Cα-alkyl, C-C--haloalkyl, C-C-alkoxy, C1-C4- haloalkoxy, 5(O)tAU, 5(O)tptMAeVi, C1 -C.-alkylcarbonyl, C1-C.-haloalkylcarbonyl, C1-C4- alkoxycarbonyl, C-C4-haloalkylcarbonyl, C3-C8-cycloalkyl, C3-C8-halocycloalkyl, C2-C4-alkenyl, Co-C4-haloalkenyl , Co-Ca-alkynyl and Ci-C-Alkoxy-C1-C4-alkyl; goes U represents O or 5; and t is 0, 1 or 2; and X' represent a leaving group preferably selected from halogen, Mz, p-nitrophenoxy, and pentafluorophenoxy. 9. Method of registration 8, where Co) B' represents СНеСнНз; B2 is C1-C6-alkyl, which may be unsubstituted or may be partially or fully halogenated; ВZ is H; and where A" represents the group -CV"B5He where B" is selected from C-C4-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may carry 1 or 2 identical or different substituents Ex, where Ex is selected from CM Her C(O)MH2O, and C3-C6-cycloalkyl, which may be unsubstituted or may bear 1, 2 or C of the same or different substituents KU, where KU is selected from halogen, CM and C(O)MH"; and B ? is selected from C-C4-alkyl, which may be unsubstituted, may be partially or fully halogenated, or may carry 1 or 2 identical or different Kx substituents, where EX is selected from CM and C(O)MH", and C3-Sve -cycloalkyl, which may be unsubstituted or may bear 1, 2 or C of the same or different KU substituents, where KU is chosen from halogen, SM and C(O)MH"; or B? and Co together with the carbon atom to which they are attached , form a 3-12-membered non-aromatic, saturated carbocycle, which can be partially or fully substituted by BC), where E) is selected from halogen, CM, and C(O)MH"; and A is H; and X' is a leaving group which is preferably selected from halogen, Mz, p-nitrophenoxy and pentafluorophenoxy, and is particularly preferably chlorine.