The invention relates to a process A for the preparation of compounds I

their salts, tautomers, or enantiomers; by reaction of compounds I I

their salts, tautomers, or enantiomers; with compounds I II

their salts, tautomers, or enantiomers; wherein the substituents have the meaning R ¹ H, Ci-C ₂ -alkyl, or Ci-C ₂ -alkoxy-Ci-C ₂ -alkyl;

R ² H, halogen, CN, or N0 ₂ ;

Ci-Cio-alkyl, C ₂ -Cio-alkenyl, or C ₂ -Cio-alkynyl, which are unsubstituted, halogen- ated, or substituted with R ^x ;

OR ^a , SR ^a , C(Y)R ^b , C(Y)OR ^c , S(0)R ^d , S(0) ₂ R ^d , NR ^e R ^f , C(Y)NR9R ^h ;

heterocyclyl, hetaryl, C3-Cio-cycloalkyl, C3-Cio-cycloalkenyl, or phenyl, which are unsubstituted, or substituted with R ^y , or R ^x ;

R ³ H, halogen, CN, N0 ₂ ;

Ci-Cio-alkyl, C ₂ -Cio-alkenyl, or C ₂ -Cio-alkynyl, which are unsubstituted, halogen- ated, or substituted with R ^x ;

OR ^a , SR ^a , C(Y)R ^b , C(Y)OR ^c , S(0)R ^d , S(0) ₂ R ^d , NR ^e R ^f , C(Y)NR9R ^h ;

heterocyclyl, hetaryl, C3-Cio-cycloalkyl, C3-Cio-cycloalkenyl or phenyl, which are unsubstituted, or substituted with R ^y , or R ^x ;

R ^N H, CN, N0 ₂ ;

Ci-Cio-alkyl, C ₂ -Cio-alkenyl, or C ₂ -Cio-alkynyl, which are unsubstituted, halogen- ated, or substituted with R ^x ;

OR ^a , SR ^a , C(Y)R ^b , C(Y)OR ^c , S(0)R ^d , S(0) ₂ R ^d , NR ^e R ^f , C(Y)NR9R ^h , S(0) _m NR ^e R ^f , C(Y)NR'NR ^e R ^f , Ci-C ₅ -alkylen-OR ^a , Ci-C ₅ -alkylen-CN, Ci-C ₅ -alkylen-C(Y)R ^b , Ci-C ₅ -alkylen-C(Y)OR ^c , Ci-C ₅ -alkylen-NR ^e R ^f , Ci-C ₅ -alkylen-C(Y)NR ^g R ^h ,

Ci-C ₅ -alkylen-S(0) _m R ^d , Ci-C ₅ -alkylen-S(0) _m NR ^e R ^f , Ci-Cs-alkylen-NRNR ^e R ^f ; heterocyclyl, hetaryl, C3-Cio-cycloalkyl, C3-Cio-cycloalkenyl, heterocyclyl-d-Cs- alkyl, hetaryl-d-Cs-alkyl, C3-Cio-cycloalkyl-Ci-C5-alkyl, C3-Cio-cycloalkenyl-Ci- Cs-alkyl, phenyl-C-i-Cs-alkyl, or phenyl, in which groups the rings are unsubstitut- ed, or substituted with R ^y ; R ^b , R ^c independently H, Ci-C ₄ -alkyl, Ci-C ₄ -haloalkyl, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ - cycloalkylmethyl, C3-C6-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, Ci-C4-alkoxy-Ci-C4-alkyl; or

heterocyclyl, heterocyclyl-Ci-C4-alkyl, phenyl, hetaryl, phenyl-Ci-C4-alkyl, hetaryl-Ci-C4-alkyl, in which groups the ring is unsubstituted, or substituted with halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, orCi-C4- haloalkoxy;

Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkylmethyl, C3- C6-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C1-C4- alkoxy-Ci-C4-alkyl; or

heterocyclyl, heterocyclyl-Ci-C4-alkyl, phenyl, hetaryl, phenyl-Ci-C4-alkyl, and hetaryl-Ci-C4-alkyl, in which groups the ring is unsubstituted, or substituted with halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, or Ci-C4-haloalkoxy;

R ^f independently H, Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6- cycloalkylmethyl, C3-C6-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, Ci-C4-alkoxy-Ci-C4-alkyl, Ci-C4-alkylcarbonyl, Ci-C4-halo- alkylcarbonyl, Ci-C4-alkylsulfonyl, Ci-C4-haloalkylsulfonyl;

heterocyclyl, heterocyclyl-Ci-C4-alkyl, heterocyclylcarbonyl, heterocyclyl- sulfonyl, phenyl, phenylcarbonyl, phenylsulfonyl, hetaryl, hetarylcarbonyl, hetarylsulfonyl, phenyl-Ci-C4-alkyl, and hetaryl-Ci-C4-alkyl, in which groups the ring is unsubstituted, or substituted with halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, and Ci-C4-haloalkoxy; or

R ^e and R ^f are together with the nitrogen atom to which they are bound form a 5- or 6-membered, saturated, or unsaturated heterocycle, in which heter- ocycle none, or one ring member atom is replaced by O, S or N, and wherein the heterocycle is unsubstituted or substituted with halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, or Ci-C4-haloalkoxy;

R ^h independently H, Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6- halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, Ci-C4-alk- oxy-Ci-C4-alkyl;

heterocyclyl, heterocyclyl-Ci-C4-alkyl, phenyl, hetaryl, phenyl-Ci-C4-alkyl, and hetaryl-Ci-C4-alkyl, in which groups the ring is unsubstituted, or substituted with halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci-C4-alkoxy, or Ci-C4-haloalkoxy;

H, Ci-C4-alkyl, Ci-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkylmethyl, C3-C6-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, Ci- C4-alkoxy-Ci-C4-alkyl; or

phenyl, phenyl-Ci-C4-alkyl, in which groups the phenyl rings is unsubstituted, or substituted with halogen, CN, NO2, Ci-C4-alkyl, Ci-C4-haloalkyl, Ci- C4-alkoxy, or Ci-C4-haloalkoxy; R ^x CN, N0 ₂ , Ci-C ₄ -alkoxy, Ci-C ₄ -haloalkoxy, S(0) _m R ^d , S(0) _m NR ^e R ^f , C1-C10- alkylcarbonyl, Ci-C ₄ -haloalkylcarbonyl, Ci-C ₄ -alkoxycarbonyl, Ci-C ₄ -halo- alkoxycarbonyl; or

C3-C6-cycloalkyl, 5- to 7-membered heterocyclyl, 5- or 6-membered hetaryl, phenyl, C3-C6-cycloalkoxy, 3- to 6-membered heterocyclyloxy, phenoxy, which are unsubstituted, or substituted with Ry;

Ry halogen, CN, N0 ₂ , Ci-C ₄ -alkyl, Ci-C ₄ -haloalkyl, Ci-C ₄ -alkoxy, Ci-C ₄ -halo- alkoxy, S(0) _m R ^d , S(0) _m NR ^e R ^f , Ci-C ₄ -alkylcarbonyl, Ci-C ₄ -haloalkylcarbonyl, Ci-C ₄ -alkoxycarbonyl, Ci-C ₄ -haloalkoxycarbonyl, C3-C6-cycloalkyl, C3-C6- halocycloalkyl, C2-C ₄ -alkenyl, C2-C ₄ -haloalkenyl, C2-C ₄ -alkynyl, or Ci-C ₄ - alkoxy-Ci-C ₄ -alkyl;

Y O or S;

m is 0, 1 or 2; and

X halogen, N3, p-nitrophenoxy, (2,5-dioxopyrrolidin-1-yl)oxy, pentafluorophenoxy, OH, Ci-C6-alkoxy, C6-Cio-aryloxy, or C6-Cio-aryl-Ci-C6-alkoxy.

The invention further relates to compounds III in the form of their adduct salts with HCI. These compounds are highly versatile precursors for the preparation of chemicals, such as compounds in the pharmaceutical and agrochemical field. They are particularly advantageous as intermediates for the preparation of compounds I because they are directly obtained by previous production steps and can be applied a such in Process A.

Compounds III, their salts, tautomers, or enantiomers are produced in Process B by reaction of (a) compounds IVa, their salts, tautomers, or enantiomers, or (b) compounds IVb, their salts, tautomers, or enantiomers, or of a mixture of (a) and (b)

with H ₂ in the presence of a hydrogenation catalyst (cf. PCT/EP2016/060461 ).

It is known in the art that dehalogenation of certain dichloropyridazine amine compounds can be performed by a hydrogenation / dehalogenation reaction in the presence of H2 and a hydrogenation catalyst. The art suggests that this hydrogenation / dehalogenation of pyridazine amine compounds is performed in the presence of a base. In this regard, reference is made to WO 201 1/038572; Journal of Heterocyclic Chemistry, 21 (5), 1389-92; 1984; WO 2009/152325; US 4,728,355; WO 201 1/124524; WO 2010/049841 ; WO 2013/142269; US 6,258,822; and WO 2001/007436. The reason why the base is added is to avoid catalyst poisoning due to the production of HCI in the reaction. This is explained by F. Chang et al. in Bull. Korean Chem. Soc. 201 1 , 32(3), 1075, an article that relates to Pd-catalysed dehalogenations of aromatic hal- ides. It is disclosed that HCI produced from dechlorination tends to be absorbed on the activated carbon, leading to a progressive poisoning of Pd/C, and that it is efficient to add some bases for the removal of HCI. It is further disclosed that the conversions in the dechlorination reaction can be increased in the presence of a base. However, the addition of a base is disadvantageous, in particular for an industrially applicable process. First, an additional chemical substance is required for the reaction, i.e. the base, which makes the process more complex. Second, the presence of the base makes catalyst recycling difficult. In particular, when filtering off the hydrogenation catalyst after the reaction, chloride salts obtained from the reaction of the base with the HCI will additionally be filtered off, so that the filter cake comprises both, the catalyst and the chloride salt (e.g. KCI and KHCO3). A further work-up procedure is then required to isolate the catalyst again.

It was therefore an object of the present invention to provide a process for the deha- logenation of dichloropyridazine amine compounds III, which is suitable for industrial application. In particular, it is an object of the present invention to provide a process, which does not require the addition of an HCI scavenger as a further chemical substance, and which provides the advantage that the hydrogenation catalyst may be recycled after the reaction without purification. At the same time, it is of course desired to provide high yields of the process. In view of subsequent transformations of the resulting pyridazine amines, it is further desired to perform the reaction without the addition of H2O. H2O is usually detrimental to the yield of further conversions of compounds III and must be removed in an additional process step, which translates into higher production costs.

It has been discovered that the dehalogenation of dichloropyridazine amine compounds can be performed in the absence of an HCI scavenger, i.e. in the absence of a base or another chemical substance suitable for binding HCI, and that the desired product can nevertheless be obtained in high yields. The hydrogenation catalyst may simply be filtered off after the reaction and can be recycled without purification.

Processes B of the above type have been disclosed in WO2016180833. Process A is applied in the production of pesticidal compounds I that are particularly useful for combating invertebrate pests (cf. WO2010/034737, WO2010/034738, and

WO2010/1 12177). The processes for the preparation of compounds I disclosed in WO2016180833 suffer from low yields in industrial production scale, a high number of manufacturing steps, high costs, and a high amount of used chemicals, e.g. bases, and solvents. It was thus another object of the invention to provide a production process suitable for industrial manufacture of compounds I, which is easily scalable, has high yields (e.g. yields of at least 80%, preferably at least 85%, more preferably at least 90%), little waste material, few manufacturing steps, has shorter overall batch times, and is thus economically attractive.

As Process B is preferably carried out in the absence of an HCI scavenger, the produced HCI (typically 2 equivalents compared to the amount of compounds IVa and IVb) is usually at least partially still present in the crude reaction product, when the hydrogenation catalyst is removed. Due to the basic functionalities of compounds III, they are then at least partially present in the crude reaction product in form of their adduct salts with HCI. It has been discovered that it is advantageous to carry out Process A and Process B as a one-pot process without intermediate isolation of compounds III. The one-pot process has the advantages of fewer manufacturing steps, reduced costs, specifically, solid handling steps, less equipment, shorter batch times, and higher yields. It has also been discovered that the yields of the dehalogenation of dichloro- pyridazine amine compounds depend on the nature of the amino substituent. In this connection, it has been found that the reaction may advantageously be carried out with dichloropyridazine amine compounds, wherein R ¹ is CH2CH3. The objects of the invention have thus successfully been achieved by Process B, and by the subsequent reaction of compounds III with compounds II in Process A in a one-pot process as set out above and described in detail below.

Usually, (a) compounds IVa, salts, tautomers, or enantiomers thereof, or (b) compounds IVb, salts, tautomers, or enantiomers thereof, or mixtures of (a) and (b) are produced via the following reaction sequence by reaction of compounds V with POC to yield 3,4,5-trichloropyridazine, and subsequent reaction with R ¹ -NH2 either as a one- pot process (Process C); or by reaction of 3,4,5-trichloropyridazine with R ¹ -NH2, wherein optionally the 3,4,5-trichloropyridazine is produced by reaction of compounds V with POCI3 (Process D). Compounds V may in turn be produced by reaction of mucochloric acid with hydrazine (N2H4) (Process E).

Accordingly, reaction of compounds V with POCI3 and R ¹ -NH2 can be carried out via isolation of 3,4,5-trichloropyridazine, or via a one-pot reaction without the isolation of 3,4,5-trichloropyridazine.

Typically, dichloropyridazine amine compounds are prepared starting from 3,4,5-trichloropyridazine by means of a nucleophilic substitution reaction with an amine compound. For example, WO201 1/038572 describes the preparation of a mixture of 3,5- dichloro-4-pyridazineamine and 5,6-dichloro-4-pyridazineamine by reacting 3,4,5-trichloropyridazine with ammonia gas for a reaction time of 4 days. The same reaction is also described in US4,728,355, wherein the reaction is performed in a sealed tube at a temperature of 120-130 °C for five days. The reaction is performed at 125 °C for 5 hours, according to Tsukasa Kuraishi et al. (Journal of Heterocyclic Chemistry, 1964, Vol. 1 , pp. 42-47). Prior art thus suggests that either long reaction times or high temperatures are required for the nucleophilic substitution reaction, both being disadvantageous for commercial processes. Furthermore, the preparation of dichloropyridazine amine compounds by reacting 3,4,5-trichloropyridazine with an amine compound, which is different from ammonia, seems to be accompanied by further problems. WO 99/64402 discloses the reaction of 3,4,5-trichloropyridazine with 3-amino-1 -propanol as nucleophile. Although the reaction is performed in boiling CH3CH2OH, the yields are very low (only 47.7 % of the crude product), and a laborious work-up by means of crystallization is required to isolate the desired reaction products. WO2012/098387 discloses the reaction of 3,4,5-trichloropyridazine with 2-methylaminoethanol as nucleophile. Although a secondary amine, which is more nucleophilic than a primary amine is used as a nucleophile, the reaction is not quantitative, and a laborious work-up by column chromatography is required. Donna L. Romero et al. (Journal of Medicinal Chemistry, 1996, Vol. 39, No. 19, pp. 3769-3789) disclose the reaction of 3,4,5-trichloropyridazine with isopropylamine as a nucleophile. According to the information provided in the article, the reaction has to be performed in refluxing toluene, i.e. at a temperature of about 1 10 °C. Furthermore, chromatography is required for purification. Similarly,

W096/18628 discloses the same reaction, wherein 3,4,5-trichloropyridazine and isopropylamine are refluxed in toluene for three hours. Column chromatography is required afterwards to isolate the desired compound 4-isopropylamino-3,5-dichloropyri- dazine. Thus, the processes for the preparation of dichloropyridazine amines as described in the prior art are either disadvantageous in terms of the reaction conditions, the yields, and/or the work-up requirements. Furthermore, it is another disadvantage of the processes described in the art that the irritant compound 3,4,5-trichloropyridazine has to be prepared and handled as a starting material. Solid handling of 3,4,5- trichloropyridazine is particularly disadvantageous on commercial scale.

It is therefore an object of the present invention to provide a process for the preparation of dichloropyridazine amine compounds, which overcomes the disadvantages in terms of the reaction conditions, the yields, and/or the work-up requirements as evident from the prior art, or the disadvantage in terms of the use of the irritant 3,4,5-trichloropyridazine as a starting material. In this connection, it is of particular interest to provide a straightforward process, which is suitable for upscaling and provides satisfying yields, preferably yields of more than 90%. Substituents R ¹ being CH3CH2 are equally of particular interest because these can be advantageously applied in the preparation of compounds I, as described above.

The object has been achieved by a one-pot Process C for preparing (a) compounds IVa or salts, tautomers, N-oxides, or (b) compounds IVb, or salts, tautomers, or N- oxides, or (c) a mixture of (a) and (b)

by reacting compounds V with POC , and reacting the resulting crude reaction product with R ¹ -NH2, or a salt thereof

It has surprisingly been found that the process of preparing dichloropyridazine amine compounds does not necessarily have to be started from 3,4,5-trichloropyridazine. Instead, 3,4,5-trichloropyridazine may be prepared in situ in a one-pot reaction with a compound of formula V as starting material. The in situ formed 3,4,5-trichloropyridazine is then directly reacted with R ¹ -NH2 to give the desired dichloropyridazine amine compounds. This process is particularly advantageous for safety reasons, as it is not required to isolate and handle the irritant compound 3,4,5-trichloropyridazine. This makes the process more favourable for industrial applications. Furthermore, the process is more economic and suitable for upscaling. In addition, it has been found that very high yields of the dichloropyridazine amine compounds can be obtained by the above process, whereby the reaction of the in situ formed 3,4,5-trichloropyridazine with the amine compound R ¹ -NH2 does not require harsh reaction conditions. Due to the high yields, a laborious work-up can also be avoided.

Alternatively, the above object has also been achieved by Process D for preparing (a) compounds IVa or salts, tautomers, N-oxides, or (b) compounds IVb, or salts, tauto- mers, or N-oxides, or (c) a mixture of a) and (b)

by reacting 3,4,5-trichloropyridazine with an amine compound R ¹ -NH2 or a salt thereof, wherein R ¹ is CH2CH3, and wherein the process optionally further comprises the step of preparing the 3,4,5-trichloropyridazine by reacting a compound of formula V with

It has surprisingly been found that is particularly advantageous to use Ch CI-bNI-b in Process C or Process D as a nucleophile in the substitution reaction. Although prior art suggests harsh reaction conditions or at least very long reaction times for the nucleo- philic substitution reaction, it has been found that moderate reaction conditions with reaction temperatures of, e.g., not more than 100°C and reaction times of not more than 12 hours suffice to provide the desired dichloropyridazine ethylamines with high yields, and without having to perform a laborious work-up.

Combinations of embodiments are within the scope of the invention. Definitions of substituents, as well as embodiments of these definitions, are valid for the formulae of all compounds in which the respective substituent is present.

The organic moieties mentioned herein for the definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members. The prefix C _n -C _m indicates in each case the possible number of carbon atoms in the group. The term "halogen" denotes in each case F, Br, CI, or I, especially F, CI, or Br, and in particular CI. The term "alkyl" as used herein and in the alkyl moieties of al- kylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyl denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms. Examples of an alkyl group are CH3, CH3CH2, CH3CH2CH2, (CH ₃ ) ₂ CH, CH3CH2CH2CH2, CH3CH2CH(CH3), (CH ₃ ) ₂ CHCH ₂ , (CH ₃ ) ₃ C, 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-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-methyl- propyl. The term "haloalkyl" as used herein and in the haloalkyl moieties of haloalkyl- carbonyl, haloalkoxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloal- koxy and haloalkoxyalkyl, denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms. Preferred haloalkyl moieties are select- ed from Ci-C4-haloalkyl, more preferably from Ci-C ₃ -haloalkyl or Ci-C2-haloalkyl, in particular from Ci-C ₂ -fluoroalkyl such as CH ₂ F, CHF ₂ , CF ₃ , CHFCH ₃ , CH ₂ CH ₂ F, CH2CHF2, CH2CF ₃ , CF2CF ₃ , and the like. The term "alkoxy" as used herein denotes in each case a straight-chain or branched alkyl group which is bonded via an oxygen atom and has usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Examples of an alkoxy group are CH ₃ 0, CH ₃ CH20, CH ₃ CH ₂ CH ₂ 0, (CH ₃ ) ₂ CHO, CH ₃ CH2CH ₂ CH ₂ 0, CH3CH2C(CH3)0, (CH ₃ ) ₂ CHCH ₂ 0, (CH ₃ ) ₃ C, and the like. The term "alkoxyalkyl" as used herein refers to alkyl usually comprising 1 to 10, frequently 1 to 4, preferably 1 to 2 carbon atoms, wherein 1 carbon atom carries an alkoxy radical usually comprising 1 to 4, preferably 1 or 2 carbon at- oms as defined above. Examples are CH ₃ OCH ₂ , C2H5OCH2, CH ₃ OCH ₂ CH ₂ , and CH ₃ CH20CH2CH2.The term "haloalkoxy" as used herein denotes in each case a straight-chain or branched alkoxy group having from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms, in particular F-atoms. Preferred haloalkoxy moieties include Ci-C4-haloalkoxy, in particular Ci-C2-fluoroalk- oxy, such as CH ₂ FO, CHF ₂ 0, CF ₃ 0, CH ₃ CHFO, CH ₂ FCH ₂ 0, CHF ₂ CH ₂ 0, CF ₃ CH ₂ 0, CHCIFCH2O, CCIF2CH2O, CCI2FCH2O, CCI ₃ CH ₂ 0, CF ₃ CF ₂ 0 and the like. The term "alkylsulfonyl" (alkyl-S(=0)2-) as used herein refers to a straight-chain or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (= Ci- C4-alkylsulfonyl), preferably 1 to 3 carbon atoms, which is bonded via the S-atom of the sulfonyl group at any position in the alkyl group. The term "haloalkylsulfonyl" as used herein refers to an alkylsulfonyl group as mentioned above wherein the hydrogen atoms are substituted with F, CI, Br, or I. The term "alkylcarbonyl" refers to an alkyl group as defined above, which is bonded via the carbon atom of a carbonyl group (C=0) to the remainder of the molecule. The term "haloalkylcarbonyl" refers to an alkylcarbonyl group as mentioned above, wherein the hydrogen atoms are substituted with F, CI, Br, or I . The term "alkoxycarbonyl" refers to an alkylcarbonyl group as defined above, which is bonded via an oxygen atom to the remainder of the molecule. The term "haloalkoxycarbonyl" refers to an alkoxycarbonyl group as mentioned above, wherein the hydrogen atoms are substituted with F, CI, Br or I . The term "alkenyl" as used herein denotes in each case a singly unsaturated hydrocarbon radical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. vinyl, allyl (2-propen-1 -yl), 1 - propen-1 -yl, 2-propen-2-yl, methallyl (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 -methyl but-2-en-1 -yl, 2-ethylprop-2-en-

1 - yl and the like. The term "haloalkenyl" as used herein refers to an alkenyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms. The term "alkynyl" as used herein denotes in each case a singly unsaturat- ed hydrocarbon radical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. 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 the like. The term "haloalkynyl" as used herein refers to an alkynyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms. The term "cycloalkyl" as used herein and in the cycloalkyl moieties of cycloalkoxy and cycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl (CC3H4), cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cy- clononyl and cyclodecyl or cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The abbreviation "cC3H _z " means cyclopropyl to which a number of z hydrogen atoms are bound. The term "halocycloalkyl" as used herein and in the halocycloalkyl moieties of halocycloalkoxy and halocycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 C atoms or 3 to 6 C atoms, wherein at least one, e.g. 1 , 2, 3, 4, or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 1 - and 2- fluorocyclopropyl, 1 ,2-, 2,2- and 2,3-diflu- orocyclopropyl, 1 ,2,2-trifluorocyclopropyl, 2,2,3,3-tetrafluorocyclpropyl, 1 - and 2- chlorocyclopropyl, 1 ,2-, 2,2- and 2,3-dichlorocyclopropyl, 1 ,2,2-trichlorocyclopropyl, 2,2,3,3-tetrachlorocyclpropyl, 1 -,2- and 3-fluorocyclopentyl, 1 ,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1 -,2- and 3-chlorocyclopentyl, 1 ,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-di- chlorocyclopentyl and the like. The term "cycloalkoxy" refers to a cycloalkyl group as defined above, which is bonded via an oxygen atom to the remainder of the molecule. The term "cycloalkylalkyl" refers to a cycloalkyl group as defined above which is bonded via an alkyl group, such as a Ci-Cs-alkyl group or a Ci-C4-alkyl group, in particular a methyl group (= cycloalkylmethyl), to the remainder of the molecule. The term "cycloal- kenyl" as used herein and in the cycloalkenyl moieties of cycloalkenyloxy and cycloal- kenylthio denotes in each case a monocyclic singly unsaturated non-aromatic radical having usually from 3 to 10, e.g. 3, or 4 or from 5 to 10 carbon atoms, preferably from

3- to 8 carbon atoms. Exemplary cycloalkenyl groups include cyclopropenyl, cyclohep- tenyl or cyclooctenyl. The term "halocycloalkenyl" as used herein and in the halocyclo- alkenyl moieties of halocycloalkenyloxy and halocycloalkenylthio denotes in each case a monocyclic singly unsaturated non-aromatic radical having usually from 3 to 10, e.g. 3, or 4 or from 5 to 10 carbon atoms, preferably from 3- to 8 carbon atoms, wherein at least one, e.g. 1 , 2, 3, 4, or 5 of the hydrogen atoms, are replaced by halogen, in par- ticular by fluorine or chlorine. Examples are 3,3-difluorocyclopropen-1 -yl and 3,3- dichlorocyclopropen-1 -yl. The term "cycloalkenylalkyl" refers to a cycloalkenyl group as defined above which is bonded via an alkyl group, such as a Ci-Cs-alkyl group or a Ci- C ₄ -alkyl group, in particular a methyl group (= cycloalkenylmethyl), to the remainder of the molecule. The term "carbocycle" or "carbocyclyl" includes in general a 3- to 12- membered, preferably a 3- to 8-membered or a 5- to 8-membered, more preferably a 5- or 6-membered mono-cyclic, non-aromatic ring comprising 3 to 12, preferably 3 to 8 or 5 to 8, more preferably 5 or 6 carbon atoms. Preferably, the term "carbocycle" covers cycloalkyl and cycloalkenyl groups as defined above. The term "heterocycle" or "heter- ocyclyl" includes in general 3- to 12-membered, preferably 3- to 8-membered or 5- to 8- membered, more preferably 5- or 6-membered, in particular 6-membered monocyclic heterocyclic non-aromatic radicals. The heterocyclic non-aromatic radicals usually comprise 1 , 2, 3, 4, or 5, preferably 1 , 2 or 3 heteroatoms selected from N, O and S as ring members, where S-atoms as ring members may be present as S, SO or SO2. Ex- amples of 5- or 6-membered heterocyclic radicals comprise saturated or unsaturated, non-aromatic heterocyclic rings, such as oxiranyl, oxetanyl, thietanyl, thietanyl-S-oxid (S-oxothietanyl), thietanyl-S-dioxid (S-dioxothiethanyl), pyrrolidinyl, pyrrolinyl, pyrazoli- nyl, tetrahydrofuranyl, dihydrofuranyl, 1 ,3-dioxolanyl, thiolanyl, S-oxothiolanyl, S-dioxo- thiolanyl, dihydrothienyl, S-oxodihydrothienyl, S-dioxodihydrothienyl, oxazolidinyl, oxa- zolinyl, thiazolinyl, oxathiolanyl, piperidinyl, piperazinyl, pyranyl, dihydropyranyl, tetra- hydropyranyl, 1 ,3- and 1 ,4-dioxanyl, thiopyranyl, S.oxothiopyranyl, S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodihydrothiopyranyl, S-dioxodihydrothiopyranyl, tetrahydrothi- opyranyl, S-oxotetrahydrothiopyranyl, S-dioxotetrahydrothiopyranyl, morpholinyl, thio- morpholinyl, S-oxothiomorpholinyl, S-dioxothiomorpholinyl, thiazinyl and the like. Ex- amples for heterocyclic ring also comprising 1 or 2 carbonyl groups as ring members comprise pyrrolidin-2-onyl, pyrrolidin-2,5-dionyl, imidazolidin-2-onyl, oxazolidin-2-onyl, thiazolidin-2-onyl and the like. The term "hetaryl" includes monocyclic 5- or 6-membered heteroaromatic radicals comprising as ring members 1 , 2, 3, or 4 heteroatoms selected from N, O and S. Examples of 5- or 6-membered heteroaromatic radicals in- elude 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, pyr- rolyl, i.e. 2- or 3-pyrrolyl, 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 5-pyrazolyl, i.e. 1 -, 2-, 4-, or 5-imidazolyl, oxadiazolyl, e.g. 2- or 5-[1 ,3,4]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, e.g. 2- or 5-(1 ,3,4-thiadiazol)yl, 4- or 5-(1 ,2,3-thia- diazol)yl, 3- or 5-(1 ,2,4-thiadiazol)yl, triazolyl, e.g. 1 H-, 2H- or 3H-1 ,2,3-triazol-4-yl, 2H- triazol-3-yl, 1 H-, 2H-, or 4H-1 ,2,4-triazolyl and tetrazolyl, i.e. 1 H- or 2H-tetrazolyl. The term "hetaryl" also includes bicyclic 8 to 10-membered heteroaromatic radicals com- prising as ring members 1 , 2 or 3 heteroatoms selected from N, O and S, wherein a 5- or 6-membered heteroaromatic ring is fused to a phenyl ring or to a 5- or 6-membered heteroaromatic radical. Examples of a 5- or 6-membered heteroaromatic ring fused to a phenyl ring or to a 5- or 6-membered heteroaromatic radical include benzofuranyl, ben- zothienyl, indolyl, indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl, benzo- thiadiazolyl, benzoxazinyl, chinolinyl, isochinolinyl, purinyl, 1 ,8-naphthyridyl, pteridyl, pyrido[3,2-d]pyrimidyl or pyridoimidazolyl and the like. These fused hetaryl radicals may be bonded to the remainder of the molecule via any ring atom of 5- or 6-mem- bered heteroaromatic ring or via a carbon atom of the fused phenyl moiety. The term "aryl" includes mono-, bi- or tricyclic aromatic radicals having usually from 6 to 14, preferably 6, 10, or 14 carbon atoms. Exemplary aryl groups include phenyl, naphthyl and anthracenyl. Phenyl is preferred as aryl group. The terms "heterocyclyloxy", "hetaryl- oxy", and "phenoxy" refer to heterocyclyl, hetaryl, and phenyl, which are bonded via an oxygen atom to the remainder of the molecule. The terms "heterocyclylsulfonyl", "het- arylsulfonyl", and "phenylsulfonyl" refer to heterocyclyl, hetaryl, and phenyl, respectively, which are bonded via the sulfur atom of a sulfonyl group to the remainder of the molecule. The terms "heterocyclylcarbonyl", "hetarylcarbonyl", and "phenylcarbonyl" refer to heterocyclyl, hetaryl, and phenyl, respectively, which are bonded via the carbon atom of a carbonyl group (C=0) to the remainder of the molecule. The terms "hetero- cyclylalkyl" and "hetarylalkyl" refer to heterocyclyl or hetaryl, respectively, as defined above which are bonded via a Ci-Cs-alkyl group or a Ci-C4-alkyl group, in particular a methyl group (= heterocyclylmethyl or hetarylmethyl, respectively), to the remainder of the molecule. The term "phenylalkyl" refers to phenyl which is bonded via a Ci-Cs-alkyl group or a Ci-C4-alkyl group, in particular a methyl group (= arylmethyl or phenylme- thyl), to the remainder of the molecule, examples including benzyl, 1 -phenylethyl, 2- phenylethyl, etc. The terms "alkylene" refers to alkyl as defined above, which represents a linker between molecule and a substituent. The term "substituted" refers in each case to a substitution by one, or more, same or different substituents. The term "halogenated" refers to a partial, of complete substitution with halogen. The term "equivalent amount" refers to one equivalent of a substance as compared to another. Accordingly, a sub-equivalent amount means less than one equivalent of a substance as compared to another, preferably 0.05 to 0.99 equivalents, more preferably 0.1 to 0.9 equivalents, most preferably 0.1 to 0.8 equivalents, and in particular 0.2 to 0.6 equiva- lents of a substance as compared to another. In turn, an at least equivalent amount means at least one equivalent of a substance as compared to another, preferably at from 1 to 10 equivalents, more preferably from 1 to 5 equivalents, most preferably from 1 to 3 equivalents, and in particular from 1 to 2 equivalents.

The term "pyridazine amine compound(s)" refers to compounds III, i.e. pyridazine compounds with an amino group -NHR ¹ as substituent in the 4-position of the pyridazine moiety. Thus, pyridazine amine compounds according to the invention do not comprise any further substituents at the pyridazine ring. The term "dichloropyridazine amine compound(s)" covers compounds IVa or IVb, their salts, tautomers or combinations thereof, i.e. pyridazine compounds with an amino group -NHR ¹ as substituent and two chlorine substituents, wherein the substituents are present at those positions of the pyridazine moiety, which can be derived from formula IVa and IVb. The terms "compounds" and "compounds of formula" have the same meaning and are thus interchangeably. They relate to compounds that are characterized by way of the respective structural formulae. Depending on the acidity or basicity as well as the reaction conditions, the compounds of the present invention may be present in the form of salts. Such salts will typically be obtained by reacting the compound with an acid, if the compound has a basic functionality such as an amine, or by reacting the compounds with a base, if the compound has an acidic functionality such as a carboxylic acid group. Cations, which stem from a base, with which the compounds of the present invention are reacted, are e.g. alkali metal cations M _a ⁺ , alkaline earth metal cations M _ea ²⁺ or ammonium cations NR ₄ ⁺ , wherein the alkali metals are preferably sodium, potassium or lithium and the alkaline earth metal cations are preferably magnesium or calcium, and wherein the substituents R of the ammonium cation NR ₄ ⁺ are preferably independently selected from H, Ci-Cio-alkyl, phenyl and phenyl-Ci-C2-alkyl. Suitable cations are in particular the ions of the alkali metals, preferably lithium, sodium and potassium, of the alkaline earth metals, preferably calcium, magnesium and barium, and of the transition metals, preferably manganese, copper, zinc and iron, and also ammonium (NH ₄ ⁺ ) and substi- tuted ammonium in which one to four of the hydrogen atoms are replaced by Ci-C ₄ -al- kyl, Ci-C ₄ -hydroxyalkyl, Ci-C ₄ -alkoxy, Ci-C ₄ -alkoxy-Ci-C ₄ -alkyl, hydroxy-Ci-C ₄ -alkoxy- Ci-C ₄ -alkyl, phenyl or benzyl. Examples of substituted ammonium ions comprise me- thylammonium, isopropylammonium, dimethylammonium, diisopropylammonium, trime- thylammonium, tetramethylammonium, tetraethylammonium, tetrabutylammonium, 2-hydroxyethylammonium, 2-(2-hydroxyethoxy)ethylammonium, bis(2-hydroxy- ethyl)ammonium, benzyltrimethylammonium and benzl-triethylammonium, furthermore phosphonium ions, sulfonium ions, preferably tri(Ci-C ₄ -alkyl)sulfonium, and sulfoxoni- um ions, preferably tri(Ci-C ₄ -alkyl)sulfoxonium. Anions, which stem from an acid, with which the compounds of the present invention have been reacted, are e.g. chloride, bromide, fluoride, hydrogensulfate, sulfate, dihydrogenphosphate, hydrogenphosphate, phosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and the anions of Ci-C ₄ -alkanoic acids, preferably formate, acetate, propionate and butyrate. Tautomers of the compounds of the present invention include keto- enol tautomers, imine-enamine tautomers, amide-imidic acid tautomers and the like. The compounds of the present invention cover every possible tautomer. The term "N- oxide" relates to a form of the compounds of the present invention in which at least one nitrogen atom is present in oxidized form (as NO). N-oxides of the compounds of the present invention can only be obtained, if the compounds contain a nitrogen atom, which may be oxidized. N-oxides may principally be prepared by standard methods, e.g. by the method described in Journal of Organometallic Chemistry 1989, 370, 17-31. However, it is preferred according to the invention that the compounds are not present in the form of N-oxides. On the other hand, under certain reaction conditions, it cannot be avoided that N-oxides are formed at least intermediary. The term "stereoisomers" encompasses both optical isomers, such as enantiomers or diastereomers, the latter existing due to more than one centre of chirality in the molecule, as well as geometrical isomers (cis/trans isomers). Depending on the substitution pattern, the compounds of the present invention may have one or more centres of chirality, in which case they may be present as mixtures of enantiomers or diastereomers. The invention provides both the pure enantiomers or diastereomers and their mixtures. Suitable compounds of the invention also include all possible geometrical stereoisomers (cis/trans isomers) and mixtures thereof. The compounds of the invention may be in the form of solids or liquids or in gaseous form. If the compounds are present as solids, they may be amor- phous or may exist in one or more different crystalline states (polymorphs) which may have a different macroscopic properties such as stability or show different biological properties such as activities. The present invention includes both amorphous and crystalline compounds, mixtures of different crystalline states, as well as amorphous or crystalline salts thereof.

The term "one-pot", as used in "one-pot reaction", or "one-pot process", refers to a set-up in which the product of a first reaction is used as educt in a subsequent second reaction without intermediate workup, preferably as a component of a composition further comprising the solvent of the first reaction. Accordingly, the term "one-pot process" refers to a situation wherein no efforts for product isolation or purification are being made in between the reactions that are carried out in the one-pot process. The term "one-pot" may refer to a set-up in which the first and the second reaction are carried out in one reaction vessel, or to a set-up in which the reaction vessel is exchanged after the first reaction and before the second reaction. Typically, the term one-pot refers to a set-up in which the reaction vessel is exchanged after the first reaction and before the second reaction.

The term "intermediate workup", as used in the context of the term "one-pot (process)" refers to a situation, wherein no isolation of reaction products is being carried out between the reaction steps, while exchange of solvents, or the addition of acids or bases between the reaction steps may optionally be carried out.

The term "free base" refers to organic molecules, e.g. compounds (III), containing an amine group, e.g. a primary, secondary, or tertiary amine group, but which are in the form of a salt, i.e. in the form of an adduct salt with an acid, such as HCI.

Process A is usually carried out by reaction of compounds II with compounds III

in a solvent, (cf. WO2010/034737, Example 1 ). The reaction produces HX as a byproduct, wherein X has a meaning as defined for compounds II, preferably CI, in an amount of one equivalent compared to the amount of compounds I. In case X is halogen, N3, p-nitrophenoxy, (2,5-dioxopyrrolidin-1 -yl)oxy, or pentafluorophenoxy, (i.e. the produced HX is an acid) preferably halogen, or in case compounds II are used in the form of their adduct salts with HCI, Process A is carried out in the presence of a base. Compounds II, and compounds III are usually applied in equimolar amounts. However, it is also possible to apply an excess of compounds III to compounds II, e.g. a ratio of 5:1 to 1 :1 , preferably 3:1 to 1 :1 , and in particular 2:1 to 1 :1. It may also be suitable to use an excess of compound of formula II to compounds III, e.g. a ratio of 5:1 to 1 :1 , preferably 3: 1 to 1 : 1 , and in particular 2: 1 to 1 : 1. Process A is usually carried out at temperatures from -50 to 150 °C, preferably 0 to 150 °C, more preferably 0 to 120 °C, most preferably 10 to 100 °C, especially preferably 20 to 80, and in particular 20 to 50 °C. In case X is OH, d-C ₆ -alkoxy, Ce-do-aryl- oxy, or C6-Cio-aryl-Ci-C6-alkoxy, the temperature is usually from 40 to 150 °C, prefera- bly 50 to 150 °C, and most preferably from 60 to 130 °C. In case X is halogen, N ₃ , p- nitrophenoxy, (2,5-dioxopyrrolidin-1 -yl)oxy, or pentafluorophenoxy, the temperature is usually from -20 to 60 °C, preferably 10 to 50 °C, most preferably 15 to 30 °C.

Suitable solvents for Process A are water; aliphatic hydrocarbons, preferably an aliphatic C5-Ci6-hydrocarbon, more preferably a C5-Ci6-alkane, or C5-Ci6-cycloalkane, such as pentane, hexane, cyclohexane, or petrol ether; aromatic hydrocarbons, preferably an aromatic C6-Cio-hydrocarbons, such as benzene, toluene, o-, m-, and p-xylene; halogenated hydrocarbons, preferably halogenated aliphatic Ci-C6-alkanes, or halogenated aromatic C6-Cio-hydrocarbons, such as CH2CI2, CHCI3, CCU, CH2CICH2CI, CCI3CH3, CHCI2CH2CI, CCI2CCI2, or chlorobenzene; alcohols, preferably Ci-C ₄ -alco- hols and C ₂ -C ₄ -alkane diols, such as CH ₃ OH, CH3CH2OH, CH3CH2CH2OH,

CH ₃ CH(OH)CH ₃ , CH ₃ (CH ₂ ) ₃ OH, and C(CH ₃ ) ₃ OH, CH ₂ (OH)CH ₂ (OH),

CH3CH(OH)CH ₂ OH; ethers, preferably Ci-C ₆ -cycloalkyl ethers, Ci-C ₆ -alkyl-Ci-C ₆ -alkyl ethers and Ci-C6-alkyl-C6-Cio-aryl ethers, such as CH3CH2OCH2CH3,

(CH ₃ )2CHOCH(CH ₃ )2, CH ₃ OC(CH ₃ ) ₃ (MTBE), CH3OCH3 (DME), CH3OCH2CH2OCH3, dioxane, anisole, and tetrahydrofuran (THF); nitriles, preferably Ci-C6-nitriles, such as CH3CN, and CH3CH2CN; ketones, preferably Ci-C6-alkyl-Ci-C6-alkyl ketones, such as CH ₃ C(0)CH ₃ , CH ₃ C(0)CH ₂ CH ₃ , CH3CH ₂ C(0)CH ₂ CH3, and CH ₃ C(0)C(CH ₃ ) ₃ (MTBK); amides and urea derivatives, preferably dimethyl form amide (DMF), N-methyl-2- pyrrolidone (NMP), dimethyl acetamide (DMA), 1 ,3-dimethyl-2-imidazolidinone (DMI), 1 ,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (DMPU), hexamethylphosphamide (HMPA); moreover dimethyl sulfoxide (DMSO), and sulfolane. Mixtures of these solvents are also possible.

In one embodiment, the solvent is an aliphatic hydrocarbon, aromatic hydrocarbon, halogenated hydrocarbon, ether, nitrile, amide, urea derivative, DMSO, or sulfolane. In another embodiment, the solvent is an aliphatic hydrocarbon. In another embodiment, the solvent is an aliphatic C5-Ci6-hydrocarbon. In another embodiment, the solvent is an aromatic hydrocarbon. In another embodiment, the solvent is an aromatic C6-C10- hydrocarbon. In another embodiment, the solvent is benzene, toluene, 0-, m-, or p- xylene. In another embodiment, the solvent is toluene. In another embodiment, the solvent is a halogenated hydrocarbon. In another embodiment, the solvent is a halogenated aliphatic Ci-C6-alkane. In another embodiment, the solvent is CH2CI2. In another embodiment, the solvent is a halogenated aromatic C6-Cio-hydrocarbon. In another embodiment, the solvent is an ether. In another embodiment, the solvent is a Ci- C6-cycloalkyl ether. In another embodiment, the solvent is a Ci-C6-alkyl-Ci-C6-alkyl ethers. In another embodiment, the solvent is a Ci-C6-alkyl-C6-Cio-aryl ether. In another embodiment, the solvent is an alcohol, preferably a Ci-C ₄ -alcohol, more preferably CH3OH. In another embodiment, the solvent is an amide or urea derivative. In another embodiment, the solvent is DMF, NMP, DMA, DMI, DMPU, or HMPA. In another em- bodiment, the solvent is DMF. In another embodiment, the solvent is DMSO, or sul- folane. In case Process A and Process B are carried out as a one-pot process, the solvent is usually exchanged after the termination of Process A and before the start of Process B.

Suitable bases are, in general, inorganic bases, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH, and Ca(OH)2; alkali metal and alkaline earth metal oxides, such as U2O, Na20, CaO, and MgO; alkali metal and alkaline earth metal hydrides, such as LiH, NaH, KH and Cahb; alkali metal and alkaline earth metal carbonates, such as U2CO3, K2CO3 and CaCOs; alkali metal bicarbonates, such as NaHCOs; alkali and alkaline earth metal amides, such as UNH2, NaNhb, KNH2; organic bases, for example secondary amines, such as pyrrolidine; tertiary amines, such as diisopropylethylamine, (CH ₃ )3N , (CH ₃ CH ₂ )3N , ((CH ₃ )2CH) ₃ N, N-methylpiperi- dine, imidazol, and polymer bound diisopropylamine, pyridine; substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also polycyclic amides and amidines, such as 1 ,8-diazabicycloundec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO); metalorganic bases, for example alkali metal salts of secondary amines, such as alkali diisopropylamide, alkali bis(trimethylsilyl)amide, alkali tetramethylpiperi- dene; alcoholates, such as alkali methanolate, alkali ethanolate, alkali isopropanolate, alkali tert-butanolate, alkaline earth metal methanolate, alkaline earth metal ethanolate, alkaline earth metal isopropanolate, alkaline earth tert-butanolate; alkali metal alkyl, and alkali metal aryl salts, such as CH ₃ (CH ₂ )3Li, CH ₃ MgCI, (CH ₃ )3CLi, phenyl lithium. Mixtures of the aforementioned bases are also possible, preferably a mixtures of organic and inorganic bases, more preferably a mixture of alkali or earth metal carbonates and amines, more preferably a mixture of alkali carbonates and tertiary amines, e.g. a mixture of K2CO3 and (CH3CH2)3N . The ratio of the inorganic base to the organic base may be from 10:1 to 1 :10, preferably from 5:1 to 1 :5, more preferably from 2:1 to 1 :2, and in particular 1 .5:1 to 1 :1 .5.

Usually the base is an organic base, preferably a secondary amine, a tertiary amine, substituted pyridine, polycyclic amides and amidines, or a mixture thereof. In one em- bodiment, the base is a secondary amine, a tertiary amine, or a mixture thereof. In another embodiment, the base is a tertiary amine, preferably (CH3CH2)3N .

The base may be added before the start of the reaction (i.e. to compounds III before addition of compounds II), during the reaction (i.e. after having admixed compounds II to compounds III), or after the reaction.

In case Processes A and B are carried out as a one-pot process, the combined amount of base in Process A and HCI scavenger in Process B is at least equivalent to the amount of produced acid (e.g. HCI) produced in both processes, preferably one to five equivalents, in particular one to two equivalents. Accordingly, in case no HCI scavenger is applied after the removal of the hydrogenation catalyst in Process B, the amount of base in Process A is at least equivalent to the amount of acid (e.g. HCI) produced in both processes, preferably one to five equivalents, in particular one to two equivalents. In case compounds III are used in Process A in form of the free base, the amount of base added in Process A is at least equivalent to the amount of produced acid (e.g. HCI) in Process A, preferably one to five equivalents, in particular one to two equivalents.

The base may be added before, during, or after the addition of compounds II to compounds III, preferably it is added before the addition. The whole amount of the base may be added in one step, or the amount may be split and admixed to the reaction mixture at several points of time. In one embodiment, the amount of the base is split and added before the reaction, and during the reaction. In another embodiment, the amount of the base is split and added before the reaction, and after the reaction. In another embodiment, the amount of the base is split and added during the reaction, and after the reaction. In another embodiment, the amount of the base is split and added before the reaction, and during the reaction.

Typically, compounds III are used in the form of the free amine as educts for Process A. Alternatively, they may be used in the form of their salts as educts for Process A. In one embodiment compounds III are used in the form of their adduct salt with HCI. Salts of compounds III also include mixtures of compounds III and their salts. Such mixtures may have a molar ratio of compounds III to their salts from 2:1 to 1 :1000, preferably 1 :1 to 1 :1000, more preferably 1 :2 to 1 :1000, most preferably 1 :2, 5 to 1 :1000. Usually the molar ratio of compounds III to their salts is at least 1 :1 , preferably at least 1 :2, and most preferably 1 :2.5. Typical adduct salts of compounds III with HCI comprises one or two molecules of HCI per molecule of compounds III. In one embodiment, the adduct salt of compounds III with HCI comprises one molecule of HCI per molecule of compounds III. In another embodiment, the adduct salt of compounds III with HCI compris- es two molecules of HCI per molecule of compounds III.

It has surprisingly been found that it is advantageous for the reaction yield to use compounds III in the form of their free base as educts for Process A, preferably as a composition with the solvent in which they are produced in Process B.

Process B may be carried out by reaction of (a) compounds IVa, their salts, tauto- mers, or enantiomers, or (b) compounds IVb, their salts, tautomers, or enantiomers, or mixtures of (a) and (b)

with H ₂ in the presence of a hydrogenation catalyst (cf. PCT/EP2016/060461 ).

Hydrogenation catalyst relates to heterogeneous and homogeneous hydrogenation catalysts, preferably heterogeneous catalysts. It is known in the art that Pt, Pd, Rh, and Ru form highly active catalysts. Non-precious metal catalysts, such as catalysts based on nickel (such as Raney nickel and Urushibara nickel) are economical alternatives. Preferred hydrogenation catalysts include Pt, Pd, Rh, Ru, Ni, or Co on carriers such as carbon. In a preferred embodiment, the hydrogenation catalyst is Pt or Pd on a carrier, Raney nickel, or Raney cobalt, and is preferably Pt or Pd on carbon. Optionally, the catalyst may be doped with sulfur or selenium. This can enhance the selectivity of the catalyst.

In one embodiment, the hydrogenation catalyst is Pd or Pt on carbon, wherein the Pd- or Pt-content is preferably in the range of from 0.1 to 15 wt%, more preferably from 0.5 to 10 wt% based on the carbon. In another embodiment, the amount of Pd, or Pt is from 0.001 to 1 wt%, preferably from 0.01 to 0.1 wt% based on the starting material. In another embodiment, the hydrogenation catalyst is Pd on carbon, wherein the Pd- content is preferably in the range of from 0.1 to 15 wt%, more preferably from 0.5 to 10 wt% based on the carrier material. Usually, the amount of Pd is from 0.001 to 1 wt%, preferably from 0.01 to 0.1 wt% based on the starting material. In one embodiment, 10wt% Pd/C is used in amount of 0.01 to 0.1 wt% based on the amount of the starting material. In another embodiment, the hydrogenation catalyst is Pt on carbon, wherein the Pt-content is preferably of from 0.1 to 15 wt%, more preferably from 0.5 to 10 wt% based on the carrier material. Furthermore, it is particularly preferred that the amount of Pt is from 0.001 to 1 wt%, preferably from 0.01 to 0.1 % based on the starting material. It is especially preferred that 10% Pt/C is used in amount of 0.01 to 0.1 wt% based on the amount of the starting material.

In the batch-wise hydrogenation, the catalyst is preferably used in the form of a powder. In a continuous hydrogenation, the catalyst used on the carrier material carbon is Pt, or Pd. After a reaction cycle, the catalyst can be filtered off and reused without noticeable loss of activity.

The process is usually carried out in a solvent. Suitable solvents are H2O; aliphatic hydrocarbons, preferably an aliphatic C5-Ci6-hydrocarbon, more preferably a C5-C16- alkane, or C5-Ci6-cycloalkane, such as pentane, hexane, cyclohexane, or petrol ether; aromatic hydrocarbons, preferably an aromatic C6-Cio-hydrocarbons, such as benzene, toluene, 0-, m-, and p-xylene; alcohols, preferably Ci-C4-alcohols and C ₂ -C ₄ -alkane diols, such as CH ₃ OH, CH3CH2OH, CH ₃ CH ₂ CH ₂ OH, CH ₃ CH(OH)CH ₃ , CH ₃ (CH ₂ ) ₃ OH, and C(CH ₃ ) ₃ OH, CH ₂ (OH)CH ₂ (OH), CH ₃ CH(OH)CH ₂ OH; ethers, preferably Ci-C ₆ -cyc- loalkyl ethers, Ci-C6-alkyl-Ci-C6-alkyl ethers, Ci-C6-alkyl-C ₃ -C6-cycloalkyl ethers, Ci- C6-alkyl-C6-Cio-aryl ethers, and Ci-C6-polyol-Ci-C6-alky ethers, such as

CH ₃ CH ₂ OCH ₂ CH ₃ , (CH ₃ ) ₂ CHOCH(CH ₃ ) ₂ , MTBE, DME, CH ₃ OCH ₂ CH ₂ OCH ₃ ,

CH ₃ OC(CH ₃ ) ₂ CH ₂ CH ₃ , cyclopentylmethyl ether, dioxane, anisole, THF, 2-methyltetra- hydrofuran, and diethylene glycol; esters, preferably esters of aliphatic Ci-C6-alcohols with aliphatic Ci-C6-carboxylic acids, esters of aromatic C6-Cio-alcohols with aromatic C6-Cio-carboxylic acids, cyclic esters of (jo-hydroxy-Ci-C6-carboxylic acids, such as CH ₃ C(0)OCH ₂ CH ₃ , CH ₃ C(0)OCH ₃ , CH ₃ C(0)OCH ₂ CH ₂ CH ₂ CH ₃ ,

CH ₃ C(0)OCH(CH ₃ )CH ₂ CH ₃ , CH ₃ C(0)OC(CH ₃ ), CH ₃ CH ₂ CH ₂ C(0)OCH ₂ CH ₃ ,

CH ₃ CH(OH)C(0)OCH ₂ CH ₃ , CH ₃ CH(OH)C(0)OCH ₃ , CH ₃ C(0)OCH ₂ CH(CH ₃ ) ₂ ,

CH ₃ C(0)OCH(CH ₃ ) ₂ , CH ₃ CH ₂ C(0)OCH ₃ , benzyl benzoate, and γ-butyrolactone;

amides and urea derivatives, preferably DMF, NMP, DMA, DMI, DMPU, and HMPA.

Preferred solvents are protic solvents, such as H ₂ 0, Ci-C ₄ -alcohols, and C ₂ -C ₄ -alkane diols, preferably CHsOH , CH ₃ CH ₂ OH , CH ₃ CH ₂ CH ₂ OH , CH ₃ CH(OH)CH ₃ , CH ₃ (CH ₂ ) ₃ OH , and C(CH ₃ ) ₃ OH, more preferably CH ₃ OH, and CH ₃ CH ₂ OH. In one embodiment, the solvent is CH3OH. In another embodiment, the solvent CH3CH2OH. Mixtures of said solvents can also be used. Usually, the solvent is exchanged after the termination of Process B for carrying out Process A.

Usually, the applied hb-pressure is in the range of from 0.1 to 10 bar, preferably in the range of from 0.1 to 1 bar, more preferably in the range of from 0.1 to 0.5 bar. In another embodiment, the applied hb-pressure is in the range of from 1 to 10 bar, preferably 2 to 8 bar, more preferably 5 to 7 bar. Higher pressures in the range of from 0.6 bar to 10 bar, preferably 3 bar to 7 bar can be advantageous if the starting material contains impurities in an amount of more than 1 % by weight.

Usually, the reaction temperature is kept within a range of from 20 to 100 °C, preferably in the range of from 30 to 80 °C. However, as the hydrogenation reaction is exothermic, it can be required to cool the reaction mixture afterwards to keep the temperature preferably below 70 °C. A reaction temperature in the range of from 60 to 70 °C is particularly preferred.

The reaction times may vary over a broad range. Preferred reaction times are in the range of from 1 hour to 12 hours, preferably in the range of from 6 hours to 12 hours, e.g. 9 or 10 hours.

With regard to the starting materials, it is emphasized that either (a) a dichloro- pyridazine amine compound of formula IVa or a salt, tautomer, or N-oxide thereof, or (b) a dichloropyridazine amine compound of formula IVb or a salt, tautomer, or N-oxide thereof, or (c) a mixture of (a) and (b) may be used. In one embodiment, a mixture of (a) and (b) is used.

As a side product of the production of compounds III, HCI is produced. Nevertheless, the reaction is usually performed in the absence of an HCI scavenger. It has surprising- ly been found that the compounds III are obtained in higher yields, if an HCI scavenger is not present in the reaction mixture.

As used herein, the term "HCI scavenger" refers to a chemical substance, which is added to a reaction mixture to remove or de-activate HCI. HCI scavengers include bases, buffers, and precursors of ionic liquids, i.e. compounds that bind protons. It is to be understood that the term "HCI scavenger" as used herein refers to a chemical substance, which is added to the reaction mixture, and does not include the starting materials of the reaction, i.e. the compounds IVa, or IVb. As the production of compounds III is preferably carried out in the absence of an HCI scavenger, the produced HCI is then still in the reaction mixture, when the hydrogenation catalyst is removed. Due to the basic functionalities of compounds III, they are in this case present after the reaction in form of their adduct salts with HCI.

The HCI scavenger may be added after the removal of the hydrogenation catalyst, preferably without the addition of H2O. It has been found that an HCI scavenger may advantageously be used after removal of the hydrogenation catalyst, so that the HCI is bound and not set free in gaseous form. In case an HCI scavenger is added after the removal of the hydrogenation catalyst, it may be added in an at least equivalent amount compared to the amount of produced HCI in the hydrogenation reaction, or in a sub-equivalent amount compared with the produced amount of HCI in the hydrogena- tion reaction. In one embodiment, the HCI scavenger is added after the removal of the hydrogenation catalyst in an at least equivalent amount compared with the produced amount of HCI in the hydrogenation reaction, e.g. at from 1 to 10 equivalents, preferably from 1 to 5, and most preferably from 1 to 3 equivalents of the HCI scavenger com- pared to the amount of HCI produced in Process B.

In another embodiment, the HCI scavenger is added after the removal of the hydrogenation catalyst in a sub-equivalent amount compared with the amount of HCI in the reaction mixture, e.g. in a ratio of equivalents of HCI scavenger to equivalents HCI produced in Process B from 10:100 to 99:100, preferably 30:100 to 90:100, more prefera- bly from 50:100 to 70:100.

In another embodiment, an HCI scavenger is neither used during the reaction, nor after the removal of the hydrogenation catalyst in Process B. In this case - and also in case an HCI scavenger is added after removal of the hydrogenation catalyst in a sub- equivalent amount - compounds III remain in the form of their salts, usually in form of their adduct salts with HCI, and are directly used as such for Process A. Accordingly, the salts of compounds III are not converted, or not converted completely to compounds III by reaction with an HCI scavenger before Process A. Compounds III are advantageously also not isolated prior to Process A, but remain in the mother liquor, preferably in the form of their adduct salts with HCI, more preferably as a composition comprising the HCI adduct salts of compounds III in CH3OH, CH3CH2OH, or a mixture thereof.

Typical HCI scavengers are bases, buffers, precursors of ionic liquids, and combinations thereof. As described above, it is advantageous to use no HCI scavenger for production of compounds III in Process B before the hydrogenation catalyst has been re- moved.

Typical bases that may be used as HCI scavengers include alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal oxides, alkali metal and alkaline earth metal hydrides, alkali metal amides, alkali metal and alkaline earth metal carbonates, alkali metal bicarbonates, alkali metal alkyls, alkyl magnesium halides, alkali metal and alkaline earth metal alcoholates, and nitrogen containing bases including tertiary amines, pyridines, bicyclic amines, ammonia, and primary amines. Typical Buffers include aqueous and non-aqueous buffers, and are preferably non-aqueous buffers. Preferred buffers include buffers based on acetate or formate, e.g. sodium acetate or ammonium formate. Precursors of ionic liquids include imidazoles.

In one embodiment, the HCI scavenger is selected from the group consisting of bases including alkali metal and alkaline earth metal hydroxides, alkali metal and alkaline earth metal oxides, alkali metal and alkaline earth metal hydrides, alkali metal amides, alkali metal and alkaline earth metal carbonates, alkali metal bicarbonates, alkali metal alkyls, alkylmagnesium halides, alkali metal and alkaline earth metal alcoholates, nitro- gen containing bases including tertiary amines, pyridines, bicyclic amines, ammonia, and primary amines, and combinations thereof; buffers including sodium acetate and/or ammonium formate; precursors of ionic liquids including imidazoles; and combinations thereof. In another embodiment, the HCI scavenger comprises at least one base. In another embodiment, the base is selected from alkali metal and alkaline earth metal hydroxides, in particular from the group consisting of LiOH , NaOH , KOH , and Ca(OH)2. In another embodiment, the base is NaOH. In another embodiment, the base is selected from alkali metal and alkaline earth metal oxides, in particular from U2O, Na20, CaO, and MgO. In another embodiment, the base is selected from alkali metal and alkaline earth metal hydrides, in particular from LiH, NaH, KH, and CaH2. In another embodiment, the base is selected from alkali metal amides, in particular from the group consisting of L1NH2, NaNH2, and KNH2. In another embodiment, the base is selected from alkali metal and alkaline earth metal carbonates, in particular from K2CO3, U2CO3 and CaCC"3. In another embodiment, the base is selected from alkali metal bicarbonates, and is preferably NaHCC"3. In another embodiment, the base is selected from alkali metal alkyls, in particular from the group consisting of CH3L1, butyllithium, and phenyl- lithium. In another embodiment, the base is selected from alkylmagnesium halides, and is preferably CHsMgCI. In another embodiment, the base is selected from alkali metal and alkaline earth metal alcoholates, in particular from sodium methanolate, sodium ethanolate, potassium ethanolate, potassium tert-butanolate, and dimethoxymagnesi- um. In another embodiment, the base is a tertiary amine, in particular (CH3)3N,

(CH ₃ CH ₂ ) ₃ N, (CH ₃ )2CH)2(CH ₃ CH2)N, or N-methylpiperidine. In another embodiment, the base is (CH3CH2)3N. In another embodiment, the base is a pyridine including substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine. In another embodiment, the base is a bicyclic amine. In another embodiment, the base is NH3. In another embodiment, the base is a primary amine, in particular CH3CH2NH2. In another embodiment, the base is (CHsCH2)3N or NaOH.

In another preferred embodiment, the HCI scavenger comprises at least one buffer. In one embodiment, the buffer is anhydrous sodium acetate or anhydrous ammonium formate. In another preferred embodiment, the HCI scavenger comprises a precursor of an ionic liquid.

Mixtures of the aforementioned HCI scavengers are also possible, preferably a mix- tures of organic and inorganic bases, more preferably a mixture of alkali or earth metal carbonates and amines, more preferably a mixture of alkali carbonates and tertiary amines, e.g. a mixture of K2CO3 and (CHsCH2)3N. The ratio of the inorganic base to the organic base may be from 10:1 to 1 :10, preferably from 5:1 to 1 :5, more preferably from 2:1 to 1 :2, and in particular 1.5:1 to 1 :1.5.

The (a) compounds IVa, their salts, tautomers, or enantiomers, or (b) compounds IVb, their salts, tautomers, or enantiomers, or a mixture of (a) and (b) may be produced in the one-pot Process C by reaction of compounds V

with POCI3, and reacting the resulting crude reaction product with R ¹ -NH2, or a salt thereof, as outlined above. Usually, a mixture of compounds (IVa) and (IVb) is obtained. Compounds V may also be present in the form of their pyridazone tautomer. As indicated above, the one-pot production process of the dichloropyridazine amine compounds is advantageous, as the intermediary obtained 3,4,5-trichloropyridazine, which is irritating, does not have to be isolated.

Alternatively, the (a) compounds IVa, their salts, tautomers, or enantiomers, or (b) compounds IVb, their salts, tautomers, or enantiomers, or a mixture of (a) and (b) may be produced in Process D by reaction of 3,4,5-trichloropyridazine with R ¹ -NH2.

The 3,4,5-trichloropyridazine may in this case be produced in a separate production process by reaction of compounds V with POC .

The conditions for the reaction of compounds V with POCb, and for the reaction of 3,4,5-trichloropyridazine with R ¹ -NH2 given below apply to the one-pot Process C, and also to the respective steps in Process D and its preceding process for the preparation of 3,4,5-trichloropyridazine.

The conditions for the reaction of compounds V with POCI3 are usually as follows. Typically, POCI3 is used in an excess. It has been discovered that the yield of Processes C and D can be increased by increasing the molar ratio of POCI3 to compounds V in the first reaction step. The molar ratio of POCI3 to compounds V may be from 1 :1 to 20:1 , preferably from 3:1 to 15:1 , more preferably from 5:1 to 10:1. The molar ratio of POCL3 to compounds V may be at least 2:1 , preferably at least 6:1. In one embodiment, the molar ratio of POCI3 to compounds V is approximately 7:1 , e.g. from 6.5:1 to 7.5:1. In another embodiment, POCI3 is used in an amount of at least 1 .5 mol per mol of the compound of formula V. In another embodiment, POCI3 is used in an amount of from 1 .5 to 2.0 mol per mol of the compound of formula II. In another embodiment,

POCI3 is used in an amount of from 2.0 to 10 mol per mol of the compound of formula II, preferably in an amount of from 4.0 to 6.0 mol, in particular in an amount of from 4.8 to 5.2 mol per mol of the compound of formula II. In another embodiment, POCI3 is used as a solvent. Usually, the reaction is performed in the absence of a solvent differ- ent from POCI ₃ .

In case a solvent is used, suitable solvents are non-protic solvents, such as aliphatic hydrocarbons, preferably an aliphatic C5-Ci6-hydrocarbon, more preferably a C5-C16- alkane, or C5-Ci6-cycloalkane, such as pentane, hexane, cyclohexane, or petrol ether; aromatic hydrocarbons, preferably an aromatic C6-Cio-hydrocarbons, such as benzene, toluene, 0-, m-, and p-xylene; halogenated hydrocarbons, preferably halogenated aliphatic Ci-C6-alkanes, or halogenated aromatic C6-Cio-hydrocarbons, such as CH2CI2, CHCI3, CCU, CH2CICH2CI, CCI3CH3, CHCI2CH2CI, CCI2CCI2, or chlorobenzene; ethers, preferably Ci-C6-cycloalkyl ethers, Ci-C6-alkyl-Ci-C6-alkyl ethers, Ci-C6-alkyl-C3-C6- cycloalkyl ethers, Ci-C6-polyol-Ci-C6-alky ethers, and Ci-C6-alkyl-C6-Cio-aryl ethers, such as CH3CH2OCH2CH3, (CH ₃ )2CHOCH(CH ₃ )2, CH ₃ OC(CH ₃ ) ₃ (MTBE), CH3OCH3 (DME), CH3OCH2CH2OCH3, CH ₃ OC(CH3)2CH ₂ CH3, dioxane, anisole, 2-methyltetra- hydrofuran, tetrahydrofurane (THF), and diethylene glycol; nitriles, preferably C1-C6- nitriles, such as CH ₃ CN, and CH3CH2CN; ketones, preferably Ci-Ce-alkyl-Ci-Ce-alkyl ketones, such as CH ₃ C(0)CH ₃ , CH ₃ C(0)CH ₂ CH ₃ , CH3CH ₂ C(0)CH ₂ CH3, and MTBK; amides and urea derivatives, preferably DMF, NMP, DMA, DMI, DMPU; moreover DMSO, and sulfolane. Mixtures of the above solvents are also possible.

Typically, the reaction is performed in a protective gas atmosphere, e.g. under N2. The reaction temperature may be in the range of from 60 °C to 130 °C, preferably in the range of from 90 °C to 1 10 °C.

The reaction times may vary over a broad range, and are preferably in a range of from 0.5 hour to 24 hours, preferably in the range of from 0.5 hour to 5 hours, more preferably in the range of from 0.5 hour to 1.5 hours.

After the reaction, the excess POCI3 may be removed under reduced pressure. Afterwards, H2O is preferably added to the reaction mixture upon cooling so that the tem- perature preferably does not exceed 30 °C. The 3,4,5-trichloropyridazine can be isolated as a precipitate from the aqueous phase, or by transferring the 3,4,5-trichloropyridazine into an organic phase, and removing the organic solvent. Preferred organic solvents in this connection include CH2CI2, CH3CH(CH3)CH ₂ OH, CH3C(0)OCH ₂ CH3, and CH ₃ C(0)0(CH ₂ )3CH ₃ , in particular CH ₃ C(0)0(CH ₂ )3CH ₃ .

With regard to the preparation and isolation of the 3,4,5-trichloropyridazine, reference is e.g. made to WO 2013/004984, WO 2014/091368, WO 99/64402, WO 2002/100352, and Russian Journal of Applied Chemistry, Vol. 77, No.12, 2004, pp. 1997-2000.

If the one-pot reaction procedure as defined above is performed, the step of isolating the 3,4,5-trichloropyridazine can be omitted. Instead, the 3,4,5-trichloropyridazine is transferred to an organic phase and directly used in the next reaction step. The organic phase may optionally be washed with a NaOH solution in H2O (e.g. a 10 % NaOH aqueous solution) and/or H2O prior to further use.

The reaction conditions for the reaction of 3,4,5-trichloropyridazine with R ¹ -NH2 are usually as described below. In connection with the reaction, reference is also made to US 4,728,355.

Depending on the substituent R ¹ , the amine compounds R ¹ -NH2 may be in gaseous or liquid or solid form. If the amine compound R ¹ -NH2 is in gaseous form, it may either be provided as a solution or as a gas. A particularly preferred amine compound is CH3CH2NH2 as already indicated above. Suitable solvents for the amine compounds R ¹ -NH2 include protic solvents, preferably H2O, or Ci-C4-alcohols such as CH3OH, CH3CH2OH, CH3CH2CH2OH, CH ₃ CH(OH)CH ₃ , CH3CH2CH2CH2OH, and (CH ₃ ) ₃ COH, especially CH3CH2OH. In one preferred embodiment, the solvent, wherein the amine compounds R ¹ -NH2 is provided, is H2O. In one preferred embodiment, the solvent, wherein the amine compounds R ¹ -NH2 is provided, is CH3OH. Suitable concentrations of the amine compounds R ¹ -NH2 in the solvent are in the range of from 10 to 100 wt% based on the total weight of the solution, preferably in the range of from 40 to 90 wt%, more preferably 60 to 80%, most preferably 66 to 72 wt%. In a particularly preferred embodiment, the amine compound R ¹ -NH2 is CH3CH2NH2 and is provided as a solution in H2O with a concentration in the range of from 60 to 80% based on the total weight of the solution, preferably 66 to 72 wt%.

It is a surprising finding of the present invention that the presence of H2O in the reaction mixture does not negatively affect the yields of the dichloropyridazine amine com- pounds.

In another embodiment, the amine compound R ¹ -NH2 is provided in gaseous form and is introduced into the reaction mixture by bubbling it into the solvent, wherein the production of the dichloropyridazine amine compounds shall be performed, and wherein 3,4,5-trichloropyridazine may already be dissolved. In this connection, preferred sol- vents in which 3,4,5-trichloropyridazine may be added to the reaction mixture include protic solvents, preferably alcohols selected from the group consisting of CH3OH, CH3CH2OH, CH3CH2CH2OH, CH ₃ CH(OH)CH ₃ , CH ₃ (CH ₂ ) ₃ OH, and C(CH ₃ ) ₃ OH. Especially preferred is CH ₃ CH20H as solvent. Furthermore, preferred solvents, wherein the gaseous amine compound R ¹ -NH2 may be dissolved for production of dichloropyrida- zine amine compounds, generally include toluene, THF, and CH ₃ CH20H.

Usually, an excess of the amine compound R ¹ -NH2 is used compared with the amount of 3,4,5-trichloropyridazine. In one embodiment, the amine compound R ¹ -NH2 is used in an amount of from 1 .5 to 10 mol per mol of 3,4,5-trichloropyridazine, preferably in an amount of from 2.0 to 6.0 mol, in particular in an amount of from 2.0 to 3.0 mol per mol of 3,4,5-trichloropyridazine.

Suitable solvents for the reaction of 3,4,5-trichloropyridazine with R ¹ -NH2 include H2O; aliphatic hydrocarbons, preferably an aliphatic C5-Ci6-hydrocarbon, more preferably a C5-Ci6-alkane, or C5-Ci6-cycloalkane, such as pentane, hexane, cyclohexane, or petrol ether; aromatic hydrocarbons, preferably an aromatic C6-Cio-hydrocarbons, such as benzene, toluene, 0-, m-, and p-xylene; halogenated hydrocarbons, preferably halo- genated aliphatic Ci-C6-alkanes, or halogenated aromatic C6-Cio-hydrocarbons, such as CH2CI2, CHCIs, CCI4, CH2CICH2CI, CCI3CH3, CHCI2CH2CI, CCI2CCI2, or chloroben- zene; ethers, preferably Ci-C6-cycloalkyl ethers, Ci-C6-alkyl-Ci-C6-alkyl ethers, C1-C6- alkyl-C3-C6-cycloalkyl ethers, Ci-C6-polyol-Ci-C6-alky ethers, and Ci-C6-alkyl-C6-Cio- aryl ethers, such as CH3CH2OCH2CH3, (CH ₃ )2CHOCH(CH ₃ )2, MTBE, DME,

CH3OCH2CH2OCH3, CH30C(CH3)2CH ₂ CH3, dioxane, anisole, 2-methyltetrahydrofuran, THF, and diethylene glycol; alcohols, preferably Ci-C4-alcohols and C ₂ -C ₄ -alkane diols, such as CH3OH, CH3CH2OH, CH3CH2CH2OH, CH ₃ CH(OH)CH ₃ , CH ₃ (CH ₂ ) ₃ OH, and C(CH ₃ ) ₃ OH, CH ₂ (OH)CH ₂ (OH), CH ₃ CH(OH)CH ₂ OH; esters, preferably esters of alipha- tic Ci-C6-alcohols with aliphatic Ci-C6-carboxylic acids, esters of aromatic C6-Cio-alco- hols with aromatic C6-Cio-carboxylic acids, cyclic esters of (jo-hydroxy-Ci-C6-carboxylic acids, such as CH ₃ C(0)OCH ₂ CH ₃ , CH ₃ C(0)OCH ₃ , CH ₃ C(0)OCH ₂ CH ₂ CH ₂ CH ₃ ,

CH ₃ C(0)OCH(CH3)CH ₂ CH3, CH ₃ C(0)OC(CH ₃ ), CH ₃ CH2CH ₂ C(0)OCH ₂ CH ₃ ,

CH ₃ CH(OH)C(0)OCH ₂ CH ₃ , CH ₃ CH(OH)C(0)OCH ₃ , CH ₃ C(0)OCH ₂ CH(CH ₃ ) ₂ ,

CH ₃ C(0)OCH(CH ₃ ) ₂ , CH ₃ CH ₂ C(0)OCH ₃ , benzyl benzoate, and γ-butyrolactone; amides and urea derivatives, preferably DMF, NMP, DMA, DMI, and DMPU. In one embodiment, the solvent is THF, MTBE, and 2-methyltetrahydrofuran. Mixtures of said solvents can also be used. It is particularly preferred that the reaction is performed in a mixture of the solvents, in which the starting materials are provided, e.g. a mixture of H2O and CH3C(0)0(CH2)3CH3. In one embodiment, the reaction is performed in protic solvents, preferably CH ₃ OH, CH3CH2OH, CH ₃ CH ₂ CH ₂ OH, CH ₃ CH(OH)CH ₃ ,

CH ₃ (CH ₂ )30H, or C(CH ₃ )30H, especially CH3CH2OH, in particular if the amine com- pound is provided in gaseous form. In another embodiment, the reaction is performed in CH3OH. The production of the dichloropyridazine amine may be performed in this protic solvent, and, optionally, also the subsequent reaction of the dichloropyridazine amine with H2 in the presence of a hydrogenation catalyst may be directly performed afterwards in a one-pot reaction.

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

In connection with the amine compound R ¹ -NH2, especially with the amine compound R ¹ -NH2 being CH3CH2NH2, the following reaction temperatures are suitable. In one embodiment, the reaction is performed at a temperature of 100 °C or less. In another embodiment, the reaction is carried out at a temperature of 80 °C or less. In another embodiment, the reaction is carried out at a temperature of 70 °C or less. In another embodiment, the reaction is carried out at a temperature of 60 °C or less. In one embodiment, the reaction is carried out at a temperature of from 0 to 100 °C. In another embodiment, the reaction is carried out at a temperature of from 0 to 80 °C. In another embodiment, the reaction is carried out at a temperature of from 0 to 70 °C. In another embodiment, the reaction is carried out at a temperature of from 0 to 60 °C. In another embodiment, the reaction is carried out t a temperature of from 20 to 80 °C. In another embodiment, the reaction is carried out a temperature of from 20 to 70 °C. In another embodiment, the reaction is carried out at a temperature of from 20 to 60 °C. In another embodiment, the reaction is carried out at a temperature of from 35 to 60 °C.

The reaction times may range from 1 hour to 4 days. Preferably, the reaction time is in the range of from 1 hour to 24 hours, in particular from 1 hour to 12 hours. More preferably, the reaction time is in the range of from 1 hour to 5 hours, preferably from 2 hours to 4 hours.

Compounds V, their salts, and tautomers, may be prepared in Process E by reaction of mucochloric acid with N H4, or a salt thereof

The reactants are preferably provided in similar amounts, e.g. in a molar ratio of from 1 .5:1 to 1 :1.5, preferably in equimolar amounts. N2H4 is preferably provided in the form of a salt, preferably as hydrazine sulfate. Suitable solvents include protic solvents such as H2O. The reaction mixture is preferably heated to 100°C, until a precipitate forms. For further details, reference is made to US 4,728,355 (e.g. Example 5). Mucochloric acid is commercially available.

Compounds IVa, and compounds IVb, their salts, tautomers, and enantiomers are ob- tainable by a process as described in PCT/EP2016/060461. Compounds II, their salts, tautomers, and enantiomers are obtainable by a process as described in WO2010/034737. WO2010/034737 specifically discloses the preparation of compounds II (cf. Example 1 ), wherein X is CI. Compounds I, wherein X is not CI can be prepared from these acid chlorides by standard methods of organic chemistry. If individual compounds I cannot be obtained by the routes described above, they can be prepared by derivatization of other compounds I. Likewise, if individual compounds II, III, IVa, IVb, their salts, tautomers, or enantiomers are not obtained by the described routes, they can be obtained by derivatization of other compounds II, III, IVa, IVb, their salts, tautomers, or enantiomers.

The following embodiments of the substituents and variables are independently valid for all formulae containing them.

Usually, R ¹ is H, Ci-C2-alkyl, or Ci-C2-alkoxy-Ci-C2-alkyl. In one embodiment, R ¹ is CH ₃ , CH2CH3, or CH2OCH3, preferably CH2CH3.

Usually, X is halogen, N3, p-nitrophenoxy, (2,5-dioxopyrrolidin-1 -yl)oxy, pentafluoro- phenoxy, OH, Ci-C6-alkoxy, C6-Cio-aryloxy, or C6-Cio-aryl-Ci-C6-alkoxy. In one embodiment, X is OH, Ci-C6-alkoxy, C6-Cio-aryloxy, or C6-Cio-aryl-Ci-C6-alkoxy. In another embodiment, X is OH. In another embodiment, X is Ci-C6-alkoxy, C6-Cio-aryloxy, or C6- Cio-aryl-Ci-C6-alkoxy. In another embodiment, X is halogen. In another embodiment, X is CI.

In one embodiment, the substituents have the following meaning

R ² Ci-C ₄ -alkyl, or Ci-C ₄ -haloalkyl;

R ³ H;

R ^N CR ⁴ R ⁵ R ⁶ ; wherein

R ⁴ Ci-C ₄ -alkyl, which is unsubstituted, halogenated, or is substituted with 1 , or

2 R ^x , wherein R ^x is CN or C(0)NH ₂ ; or

C3-C6-cycloalkyl, which is unsubstituted, or substituted with 1 , 2, or 3 R ^y , wherein R ^y is halogen, CN, or C(0)NH ₂ ;

R ⁵ Ci-C ₄ -alkyl, which is unsubstituted, halogenated, or substituted with 1 , or 2 R ^x , wherein R ^x is CN, or C(0)NH ₂ ; or

C3-C6-cycloalkyl, which is unsubstituted, or substituted with 1 , 2 or 3 R ^y , wherein R ^y is halogen, CN or C(0)NH2; or

R ⁴ and R ⁵ together with the carbon atom to which they are attached form a 3- to

12-membered non-aromatic, saturated carbocycle, which is unsubstituted or substituted with Ri, wherein Ri is halogen, CN, or C(0)NH2;

R ⁶ H; and

X halogen, N3, p-nitrophenoxy, and pentafluorophenoxy.

In another embodiment, the substituents have the following meaning

R ² Ci-C ₄ -alkyl, or Ci-C ₄ -haloalkyl;

R ³ H;

R ^N CR ⁴ R ⁵ R ⁶ ; wherein

R ⁴ Ci-C ₄ -alkyl, which is unsubstituted, halogenated, or is substituted with 1 , or 2 R ^x , wherein R ^x is selected from CN and C(0)NH ₂ ; or

C3-C6-cycloalkyl, which is unsubstituted, or substituted with 1 , 2, or 3 R ^y , wherein R ^y is halogen, CN, or C(0)NH ₂ ;

R ⁵ Ci-C4-alkyl, which is unsubstituted, halogenated, or substituted with 1 , or 2 R ^x , wherein R ^x is CN, or C(0)NH ₂ ; or

C3-C6-cycloalkyl, which is unsubstituted, or substituted with 1 , 2 or 3 R ^y , wherein R ^y is halogen, CN or C(0)NH2; or

R ⁴ and R ⁵ together with the carbon atom to which they are attached form a 3- to 12-membered non-aromatic, saturated carbocycle, which is unsubstituted or substituted with Ri, wherein Ri is halogen, CN, or C(0)NH ₂ ;

R ⁶ H; and

X CI.

In another embodiment, R ^N is CR ⁴ R ⁵ R ⁶ , R ² is CH ³ , R ³ is H, R ⁶ is H; and wherein a) R ⁴ is CH ₃ , R ⁵ is CH ₃ ;

b) R ⁴ is CF ₃ , R ⁵ is CH ₃ ;

c) R ⁴ is CH(CH ₃ ) ₂ , R ⁵ is CH ₃ ;

d) R ⁴ is CHFCH ₃ , R ⁵ is CH ₃ ;

e) R ⁴ is 1 -CN-cC ₃ H ₄ , R ⁵ is CH ₃ ;

f) R ⁴ is 1 -C(0)NH ₂ -cC ₃ H ₄ , R ⁵ is CH ₃ ; or

g) R ⁴ and R ⁵ together are CH ₂ CH ₂ CF ₂ CH ₂ CH ₂ .

In another embodiment, R ^N is CR ⁴ R ⁵ R ⁶ , R ² is CH ³ , R ³ is H, R ⁶ is H; and wherein a) R ⁴ is CH ₃ , R ⁵ is CH ₃ ;

b) R ⁴ is CF ₃ , R ⁵ is CH ₃ ;

c) R ⁴ is CH(CH ₃ ) ₂ , R ⁵ is CH ₃ ;

d) R ⁴ is CHFCHs, R ⁵ is CH ₃ ;

e) R ⁴ is 1 -CN-cC ₃ H ₄ , R ⁵ is CH ₃ ;

f) R ⁴ is 1 -C(0)NH ₂ -cC ₃ H ₄ , R ⁵ is CH ₃ ; or

g) R ⁴ and R ⁵ together are CH ₂ CH ₂ CF ₂ CH ₂ CH ₂ ; and

X is a CI.

In one embodiment, a combination of bases as the HCI scavenger in Process B and/or as base in Process A is used. This could be a combination of inorganic and organic bases, more preferably a combination of an alkali metal or alkaline earth metal carbonate and a tertiary amine, most preferably a combination of an alkali metal carbonate and (CH ₃ CH ₂ ) ₃ N, and in particular a combination of K ₂ C0 ₃ and (CH ₃ CH ₂ ) ₃ N. In another embodiment, an inorganic base (preferably an alkali metal or alkaline earth metal carbonate, more preferably alkali metal carbonate, and in particular K ₂ C0 ₃ ) is used as HCI scavenger in Process B, and an organic base (preferably a tertiary amine, more preferably (CH ₃ CH ₂ ) ₃ N) is used as base in Process A.

In another embodiment, an inorganic base (preferably an alkali metal or alkaline earth metal hydroxide, more preferably alkali metal hydroxide, and in particular NaOH) is used as HCI scavenger in Process B, and an organic base (preferably a tertiary amine, more preferably (CH ₃ CH ₂ ) ₃ N) is used as base in Process A. In another embodiment, an inorganic base (preferably an alkali metal or alkaline earth metal hydroxide or carbonate, more preferably alkali metal hydroxide or carbonate, and in particular NaOH and K2CO3) is used as HCI scavenger in Process B, and an organic base (preferably a tertiary amine, more preferably (CHsCH2)3N) is used as base in Pro- cess A.

In another embodiment, an inorganic base (preferably an alkali metal or alkaline earth metal carbonate, more preferably alkali metal carbonate, and in particular K2CO3) is used as base in Process A, and an organic base (preferably a tertiary amine, more preferably (CHsCH2)3N) is used as HCI scavenger in Process B.

The ratio of the equivalents of inorganic to organic bases in the above embodiments may be 1 :1 . In another embodiment the ratio of equivalents of the inorganic to the organic base is at least 2:1 , preferably at least 3:1. In another embodiment the ratio of equivalents of the inorganic to the organic bases is at least 1 :2, preferably at least 1 :3. In one embodiment, Process B and Process A are subsequently carried out as one- pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein no HCI scavenger, or a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hydrogenation reaction is added after the removal of the hydrogena- tion catalyst in Process B.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A, wherein an HCI scavenger is added in an at least equivalent amount compared to the amount of produced HCI in the hydrogenation reaction after the removal of the hydrogenation catalyst in Process B.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein no HCI scavenger, or a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hydrogenation reaction is added after the removal of the hydrogenation catalyst in Process B, and wherein no HCI scavenger is present during the hydrogenation reaction in Process B.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A, wherein an HCI scavenger is added in an at least equivalent amount compared to the amount of produced HCI in the hydrogenation reaction after the removal of the hydrogenation catalyst in Process B, and wherein no HCI scavenger is present during the hydrogenation reaction in Process B.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hydrogenation reaction is added after the removal of the hydrogenation catalyst in Process B, and wherein no HCI scavenger is present during the hydrogenation reaction in Process B.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein no HCI scavenger, or a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hydrogenation reaction is added after the removal of the hydrogena- tion catalyst in Process B, wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Process B is CH3OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A, wherein an HCI scavenger is added in an at least equivalent amount compared to the amount of produced HCI in the hydrogenation reaction after the removal of the hydrogenation catalyst in Process B, wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Process B is CH3OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hydrogenation reaction is added after the removal of the hydrogenation catalyst in Process B, and wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Process B is CH3OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein no HCI scavenger, or a sub-equivalent amount of HCI scavenger compared to the pro- duced HCI in the hydrogenation reaction is added after the removal of the hydrogenation catalyst in Process B, wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Processes A and B is CH3OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A, wherein an HCI scavenger is added in an at least equivalent amount compared to the amount of produced HCI in the hydrogenation reaction after the removal of the hydrogenation catalyst in Process B, wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Processes A and B is CH3OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hy- drogenation reaction is added after the removal of the hydrogenation catalyst in Process B, and wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Processes A and B is CH3OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein no HCI scavenger, or a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hydrogenation reaction is added after the removal of the hydrogenation catalyst in Process B, wherein no HCI scavenger is present during the hydrogena- tion reaction in Process B, and wherein the solvent in Process B is CH3CH2OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A, wherein an HCI scavenger is added in an at least equivalent amount compared to the amount of produced HCI in the hydrogenation re- action after the removal of the hydrogenation catalyst in Process B, wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Process B is CH3CH2OH.

In another embodiment, Process B and Process A are subsequently carried out as one-pot processes, wherein the product of Process B, compounds III, are not isolated prior to being used in Process A and are in the form of their HCI adduct salts, wherein a sub-equivalent amount of HCI scavenger compared to the produced HCI in the hydrogenation reaction is added after the removal of the hydrogenation catalyst in Process B, and wherein no HCI scavenger is present during the hydrogenation reaction in Process B, and wherein the solvent in Process B is CH3CH2OH.

The following clauses are preferred embodiments of the production processes.

1 ) A one-pot production process comprising Processes B followed by Process A, as defined above, wherein compounds III are not isolated before being used in Process A.

2) The process of clause 1 , wherein the solvent in Process B is CH3OH,

CH3CH2OH, or a mixture thereof.

3) The process according to clause 1 or 2, wherein in the solvent in Process B is

4) The process according to clause 1 or 2, wherein in the solvent in Process B is 5) The process according to any of clauses 1 to 4, wherein the solvent in Process A is a aliphatic C5-Ci6-hydrocarbon, an aromatic C6-Cio-hydrocarbon, or a mixture thereof, preferably toluene.

6) The process according to any of clauses 1 to 3, or 5, wherein the solvent in Process A and Process B is CH3OH.

7) The process according to any of clauses 1 to 6, wherein no HCI scavenger is added in Process B before the removal of the hydrogenation catalyst.

8) The process according to any of clauses 1 to 7, wherein no HCI scavenger is added in Process B after the removal of the hydrogenation catalyst. 9) The process according to any of clauses 1 to 7, wherein an HCI scavenger is added in Process B after the removal of the hydrogenation catalyst in a sub- equivalent amount compared to the amount of produced HCI in the hydrogenation reaction.

10) The process according to any of clauses 1 to 9, wherein compounds III are used for Process A in the form of their HCI adduct salts.

1 1 ) The process according to any of clauses 1 to 6, wherein an HCI scavenger is added in Process B after the removal of the hydrogenation catalyst in an at least equivalent amount compared with the amount of produced HCI in the reaction mixture.

12) The process according to any of claims 7 to 1 1 , wherein the HCI scavenger is an organic base, preferably an amine base, in particular (CH ₃ CH ₂ ) ₃ N.

14) The process according to any of claims 7 to 1 1 , wherein the HCI scavenger is an inorganic base, preferably an alkali or alkaline earth metal carbonate, in particular K2CO3, or an alkali or alkaline earth metal hydroxide, in particular NaOH.

15) The process according to any of claims 7 to 1 1 , wherein the HCI scavenger is a mixture of an inorganic base and an organic base, preferably a mixture of an alkali or alkaline earth meatal carbonate and an amine base, in particular a mixture of (CH ₃ CH ₂ ) ₃ N and K2CO3.

16) The process according to any of clauses 1 to 15, wherein a base is added in Process A to compounds III before adding compounds II.

17) The process according to any of clauses 1 to 16, wherein a base is added in Process A during the reaction of compounds III with compounds II.

18) The process according to any of clauses 1 to 17, wherein a base is added in Pro- cess A after the reaction of compounds III with compounds II.

19) The process according to any of clauses 1 to 18, wherein the base in Process A is an amine base, preferably a tertiary amine base, and in particular (CH ₃ CH ₂ ) ₃ N.

20) The process according to any of clauses 1 to 19, wherein the base in Process A is an inorganic base, preferably an alkali or alkaline earth metal carbonate, in particular K ₂ C0 ₃ .

21 ) The process according to any of clauses 1 to 20, wherein the base in Process A is a mixture of an inorganic base and an organic base, preferably a mixture of an alkali or alkaline earth meatal carbonate and an amine base, in particular a mixture of (CH ₃ CH ₂ ) ₃ N and K ₂ C0 ₃ .

22) The process according to any of clauses 1 to 21 , wherein the combined amount of base in Process A and HCI scavenger added after the removal of the hydrogenation catalyst in Process B is at least equivalent to the amount of acid (e.g. HCI) produced in both processes.

23) The process according to any of clauses 1 to 22, wherein the amount of the base in Process A is split and added to compounds III before adding compounds II, and during the reaction of compounds III with compounds II. 24) The process according to any of clauses 1 to 23, wherein the amount of the base in Process A is split and added to compounds III before adding compounds II, and after the reaction of compounds III with compounds II.

25) The process according to any of clauses 1 to 24, wherein the amount of the base in Process A is split and added during the reaction of compounds III with compounds II, and after the reaction of compounds III with compounds II.

26) The process according to any of clauses 1 to 25, wherein X in compounds II is CI; and R ¹ in compounds III, IVa, IVb, and R ¹ -NH ₂ is CH ₂ CH ₃ .

The following examples illustrate the invention.

Examples

Characterization

The qualitative and quantitative analysis of the compounds was done by quantitative High Performance Liquid Chromatography (HPLC), which had been calibrated with pure samples of the compounds to be analyzed. Abbreviations used are: h for hour(s), min for minute(s), eq for equivalents, and Pd/C is palladium on active coal.

Preparation Example 1 : production of 3,4-dichloro-5-ethylaminopyridazine and 3,5- dichloro-4-ethylaminopyridazine

200 g of 4,5-dichloro-3-hydroxypyridazine was placed in a reactor at 20 °C under N2. 930 g of POC was added under stirring and the reaction mixture was heated to 100 °C. The reaction mixture was further stirred at 100 °C for approximately 1 h. The excess POCb was then removed via distillation. The reaction mixture was dosed into 1200 g H2O, wherein the temperature was constantly maintained at 30 °C. Butyl ace- tate (1200 g) was added and the resulting biphasic mixture was stirred for 30 min at 30 °C, upon which the phases were separated. 400 g of butyl acetate was used to wash the aqueous phase. The combined organic phases containing 3,4,5-trichloropyridazine were washed with 10% aqueous HCI and then H2O.

To the mixture of trichloropyridazine in butyl acetate was added a solution of

CH3CH2NH2 in H2O with a concentration of 70 wt% of CH3CH2NH2 based on the total weight of the solution (234 g) at 35 °C under constant stirring. The reaction was held at 45 °C for 3 h. The phases were then separated at 40 °C and the organic phase was washed once with H2O. The combined aqueous phases were once extracted with butyl acetate. The combined organic phases were concentrated by distillation (15 mbar, 35 °C). During this process, the product precipitated from solution. The mixture was cooled to 10 °C and the product was filtered off. The mother liquor was next concentrated and the crude material was recrystallized from MTBE to isolate the remainder of the product.

Preparation Example 2: One-pot synthesis in CH3CH2OH

A composition containing 39.6 g of a mixture containing 3,5-dichloro-N-ethyl-pyrid- azin-4-amine (compound IVa.1 ) and 5,6-dichloro-N-ethyl-pyridazin-4-amine (compound IVb.1 ), 135 ml. CH3CH2OH, and 5.3 g of a Pd/C catalyst (10 wt% Pd of the total mass of the catalyst) was added to a pressure reactor. Subsequently, the composition was stirred and F -gas was introduced into the pressure reactor to a final pressure of 6 bar that was maintained at 65 °C over a period of 9.5 h. The composition was then filtrated through silica gel to yield a solution of the HCI adduct of N-ethylpyridazin-4-amine (compound 111.1 ) in CH3CH2OH at a concentration of 6.6 wt% based on the total mass of the solution. To 222 g of the solution containing compound III.1 was added 18.54 g of (CH3CH2)3N in a reaction vessel at 20 to 25 °C under stirring over period of 25 min.

Subsequently, the CH3CH2OH was removed by evaporation under reduced pressure. The removed CH3CH2OH was replaced stepwise with toluene to maintain the concentration of all reactions in the solvent. The evaporation process was carried out until the amount of CH3CH2OH detectable by gas chromatography was reduced to a concentration of lower than 500 ppm. Then, 27.6 g of 1 -(1 ,2-dimethylpropyl)-5-methyl-pyrazole-4- carbonyl chloride (compound 11.1 ) in 16.4 g toluene was added dropwise to the reaction vessel at 20 to 25 °C. Finally, 27.8 g of a 50 wt% solution of (CH ₃ CH ₂ )3N in toluene was added to the reaction vessel over 20 min. The mixture was extracted with H2O. The organic phases were combined and a portion of the toluene was removed by distillation. The product 1 -(1 ,2-dimethylpropyl)-N-ethyl-5-methyl-N-pyridazin-4-yl-pyrazol e-4- carboxamide (compound 1.1 ) was crystallized from the concentrated organic phases by addition of heptane and reduction of the temperature.

Preparation Example 3: One-pot synthesis in CH3OH

A composition containing 39.6 g of a mixture containing compound IVa.1 and compound IVb.1 , 100 g CH3OH, and 5.3 g of a Pd/C catalyst (5 wt% Pd of the total mass of the catalyst) was added to a pressure reactor. Subsequently, the composition was stirred and Fb-gas was introduced into the pressure reactor to a final pressure of 6 bar that was maintained at 65 °C for 4.5 h. The composition was then stirred overnight at 4 bar Fb-gas pressure. The composition was then filtrated through silica gel to yield a solution of the HCI adduct of compound III.1 in CH3OH.

To 148.3 g of this solution containing 31.92 g of compound III.1 was added 40.4 g of (CF CFb^N in a reaction vessel at 20 to 25 °C under stirring over period of 1 h, followed by further stirring overnight.

Subsequently, the CH3OH was removed by evaporation under reduced pressure. The removed CH3OH was replaced stepwise with toluene to maintain the concentration of all reactants in the solvent. The evaporation process was carried out until the amount of CH3OH detectable by gas chromatography was reduced to a concentration of lower than 500 ppm.

Then, 30.3 g of (CF CFb^N was added to the reaction vessel at 50 °C over a period of 1 h. Subsequently, 44.92 g of compound 11.1 in 27.8 g toluene was added dropwise to the reaction vessel at 50 °C over a period of 50 min, followed by incubation of the resulting mixture overnight.

The mixture was extracted with H2O. The organic phases were combined and a por- tion of the toluene was removed by distillation. Compound 1.1 was crystallized from the concentrated organic phases by addition of heptane and reduction of the temperature. Preparation Example-4: One-pot synthesis in CH3OH

A composition containing 97.5 g of a mixture containing compounds (IVa.1 ) and compounds (IVb.1 ), 224 g CH ₃ OH and 13.2 g of a Pd/C catalyst (2 wt% Pd of the total mass of the catalyst) was added to a pressure reactor. Subsequently, the composition was stirred and hb-gas was introduced into the pressure reactor to a final pressure of 6.1 bar that was maintained at 65 °C for 6 h. The composition was then stirred overnight at 3 bar hb-gas pressure without heating. The composition was then filtrated to yield a solution of the HCI adduct of compound III.1 in CH3OH at a concentration of 16.6 wt% based on the total mass of the solution, corresponding to a yield of 94%. The solid catalyst was washed in a Buchner fun- nel.

To 453.3 g of this solution containing compound III.1 was added 24.6 g of an aqueous solution of NaOH at a concentration of 50 wt% at a temperature of 20 to 25 °C. The precipitated NaCI was filtered off.

Subsequently, CH3OH was removed by distillation. The removed CH3OH was replaced stepwise with toluene to maintain the concentration of all reactants in the solvent. The distillation process was carried until a boiling temperature of 1 10 °C was reached, marking the completion of the solvent swap from CH3OH to toluene when a total of 236.2 g of distillate had been collected.

Then, 40 g of toluene and 21 .7 g of (CH3CH2)3N were added to the distillation sump, fol- lowed by the addition of 50.8 g of compound 11.1 in 1 1 .5 g toluene over 1 h at 50 °C. After stirring over 2.75 h, 38.5 g of water and 6,4 g CH3OH were added to the reaction vessel at 50 °C, and compound 1.1 was isolated in toluene by extractive work up. The total product yield in organic and aqueous phases was 92.3% in relation of the HCI adduct of N-ethylpyridazin-4- amine measured by quantitative HPLC analytics.