DE2306001A1 - COCCIDIOSTATIC COMPOUNDS - Google Patents

Description

The present invention relates to new pyrimidine derivatives substituted by heterocyclic pension, which are useful for prevention and cure coccidiosis. The new connections allow if you never eat poultry or administered to other animals, an effective control of coccidiosis.

Coccidiosis is a common and widespread disease of poultry, which see through several species of protozoan, ! Parasites of the genus Eimeria, such as E. tenella, E. necatrix, E. acervulina, E. maxima, E. hagani and E. brunetti. E. tenella is the causative agent of a serious and often life-threatening infection in the appendix (C η e cum) of chickens. The symptoms of this infection are profuse bleeding, a build-up of blood in the appendix and an appearance of blood in the feces. E. necatrix and certain other species attack the small intestine of the chicken and cause what is known as "intestinal coccidiosis"

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known disease, related species of coccidia (Coccidia), such as E. melagridis and E; adenoid.es, .are the pathogens of the Fok- ' cidiosis in turkeys. The "serious forms of coccidiae lead, if left untreated, to poultry poor weight gain, decreased feed conversion and high mortality. Eliminating or combating coccidiosis is therefore extremely important for the poultry industry. ■

It has now been found that certain pyrimidine derivatives are highly effective against the protozoa responsible for coccidiosis, including those against conventional coccidiostats have resistant protozoa. It is an object of the present invention to provide such compounds to deliver. Another object of the invention is to provide a process for making such derivatives. One Further. The object of the invention is to provide animal feed and feed additives and to provide water-soluble compositions containing these pyrimidine derivatives.

According to the invention it has been found that 5 ~ M3thyl- (heterocyclic) -;? - -lower-a.lkyl-4-amino pyrimide in compounds, including those compounds in which the heterocyclic substituent is in turn substituted by at least one methyl group, is a very effective one Ensure prevention and treatment of coccidiosis. The compounds are of particular value in curing and combating diseases caused by various "resistant" strains of Eimeria. The term "resist ent" is applied to the strains of parasites which cannot be controlled by some commercially available coccidiostats. These parasites are apparently identical to known species, but are considered to be varieties as regards their sensitivity compared to the commercial coccidia. To you? New compounds of the present invention are not only effective coccidiostats against various species, but also allow one or more of the "resistant" species to be controlled.

_ »2 -

The compounds according to the invention have the general Formula I.

(D

in which R * denotes an alkyl radical with 1 to 3 carbon atoms, a perfluoroalkyl radical with 1 to 3 carbon atoms, a 1,1-difluorate group or a 7 , 7 , 2-T ri fluorine H. thy I group, X represents an anion and b and c denote such integers that the positive charge of b Tföl of the cation by c mol of the. Anion X is neutralized. The imprint "Perfluorn.lkylrent" means a completely fluorinated alkyl prop, for example a pentafluoroethyl, n-He-ptafluoropropyl or trifluoromethyl prop. Apart from these backs R ¹ , which correspond to the "precautionary embodiments according to the invention, other substituents can be preceded, such as the methoxymothy" or cyclopropyl methyl group or other known groups. In the general formula T, -F (^ denotes the radical of a bicyclic heterocyclic base with one of the formulas A to G

(Λ)

OH-

V ^

OH-

(D)

.NO

(E)

Τ> ίν ΛΤ ^

OH.

(F)

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OH

U)

where R represents a hydrogen atom or a methyl group and the dotted line indicates that only one of the c> 6-methyl groups may be present in the ring.

As will be explained in more detail below, the inventive antikokzldi-behen connections by implementing a ? -R '.-- 4-amino-5-haiogenmethylpyrimidine or a 2-R'-4-amino- -5-alkoxymethylpyrimidines with the bioyelic heterocyclic Base made.

It can be seen that if R represents a hydrogen stream in the compounds of the formulas D and E (both are pyrrolopyridines), these compounds can occur in the corresponding deprotonized tertiary base forms of the formulas T) * or, Έ * :

OH-

This can vary depending on the Ρττ value of the physiological medium Shift equilibrium in favor of either the quaternary form or the tertiary base form. However, both forms can be used separately identify in the laboratory.

It can also be seen that other positional isomers and homologs of the aforementioned compounds can be easily prepared and have coccidiostatic activity. In particular, can in the bicyclic ring systems described, up to two methyl substituents be present, one of which is in Qir position to the connecting nitrogen atom and the other in in any other available position, as long as it is not the other position, there are

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Adhesive connections of this kind are n'nne according to the For my Ap, A ^ and 13 «:

Finally, it can be seen that all compounds with the aforementioned structural formulas can easily be prepared, isolated and used in the form of the quaternary halide hydrohalides, where the halide can be chloride or bromide. As mentioned, there is an exception for. the compounds of the formulas D * and E ^f . Furthermore, when "R 'is a pentafluomethyl group in any of the compounds, the quaternary halide is most easily formed, although the use of an excess of hydrogen halide during isolation can also isolate the halide hydrohalide.

Among the compounds according to the invention, those are preferred in which the nitrogen-containing heterocyclic base thieno—. ? / ?, ^3-r c7py idin (Formula A), thieno / 3, - c7pyridin (Formula B), or furo / 3,2-c7pyridin (Formula Π) is:

OH-

(A)

H484 2.30800.1,

(B)

The dotted line indicates that the methyl group cannot be in, i or the "two positions or in neither of these positions, but not in both positions at the same time. The particularly preferred compounds of the aforementioned group include 6- / t4-amino-2 -äthy.l-5-pyrimidinyl) -methyl7-7- -methylthieno / 2, vol / pyridinium chloride hydrochloride, 6 - / ^ 4- ATnino -? - pentafluoroethyl-5-pyrimidinyl) -methy3 _< 7-7-methylthieno - / 5,3-c / pyridinium ,. 6- / C4-amino-2-ethyl-5-pyrimidinyl) - methyl / - 2, 7-dimethylthieno / ?, .3-cZpyridiniumchlorid hydrochloride, 6- / X 4-Amino -? - ethyl-5-pyrimidinyl) -ττ ^ ethyl7-5-methylthieno-. / ?, 3-c7pyridiniumbromid ~ hydrobromide, 5- / C4-amino-2-ethyl ~ 5- -pyrimidinyl) -methyl7- 4-methylthieno ^, 2-c7pyridiniumchlorid- hydrochloride, 5- / Ϊ 4-amino-2-isopropyl-5-pyrimidine? / ^I l) -inethyl7- -6-methylthieno / 3,2-q7pyridiniumbromid-h? / 'drobromide, 5- / T4-amino -2-pentaf (luoroethyl-5-pyrimidinyl) -methyüy-4-methylthiRno ^,? -q / pyridinium bromide, 5- / X 4-amino-2-ethyl-5-p yrimidinyl) -methyl / -4-methylfurano / ^, 2-c / pyridiniumbroinid-hydrobromide, 5- $ 4-amino--2 * -ethyl-5-pyrimidinyl) -methyl7-6-methy] furano / 3.2 -o7pyrid chloride hydrochloride and 5 ~ / Γ4-amino-2-1 ', 1'-difluoroethyl-5-

-hyiiro chlo rid.

A further preferred group are those compounds in which the nitrogen-containing heteronjrcniRohe B.af3e 1H ^r -pyrrolo / 2,3-n7pyridine (formula T)) or 1H-pyrrolo / 3,2-c / pyridine (formula E) or whose

14 484 2308001

tertiary base forms described above are:

OH ₁ +

OH Γ

; QÜ

(TS)

Wp dotted line indicates that the methyl group is in can be in one of the two positions or in neither of these positions, but not in both positions at the same time; 'R is a hydrogen atom or nine M eth: rl group.

Specific examples of suitable compounds within these preferred class are 6 - / (4-amino-P-ethyl-! 5-pyrimidin.yi) -

-T-methyl-IH'-pyrrolo / ?, 3-i7pyri.d inium bromide-hydrobromide, -amino-2-propyl-5-pyrimidinyl) -methyl7-1,7-dimathyl-1H- -pyrrolo / ?, 3- c7py ^r idiniumbromid hydrobromide, S-Jl Ί-amino -? - methyl-5-pyrimidinyl) -methyl ^ - ^ - methyl-IH-pyrrolq / ^ !, 3-o7pyridiniumnhlorid hydrochloride, 6 - / \ 4-amino -? - pentafluoroethyl-5-pyrimidine? / - l) -methyl7-5-methyl-6H-pyrrolo / T ^> , 3-c7pyridine, 5- JX4-amino-P-ethyl-5-pyrimidinyl) -methy ] L7-4-ynethyl-1H-pyrrolo / '3,2-c ^ - pyridiniurachlorid-hydrochloride and 6 - / (4-amino-2-ethyl-5-pyrimidinyl) -methyl / -7-methyl-6H-pyrrolo / 2,3-c7 pyridine.

A third larger preferred class of compounds are those in which the nitrogenous heterocyclic base is Tmidazo- 31 2-a / pyridine (Formula F) or imidazo / i, 5-a / pyridine (Formula G) »

00

The dotted line indicates that the methyl group is in. either of the two positions, but not in both at the same time Positions can be located. It should be noted that the

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14 484 2308001

Compounds according to the formula P the presence only one or no methyl group is preferred.

Specific examples of compounds within the foregoing preferred class sin ^ 1- ^ 4-amino-2-ethyl-5-pyrimidiny1) -Trmthyl7- -imidazo / l, P-a / pyridiniumchlorid-hydro chloride, 1 -, / jf 4-amino-2-

bromide hydrobromide, 2- / T4-amino-2-ethyl-5-pyrimidinyl) - -3-methylimidazo / i, 5-a7pyriäiniuTnbromid-h7 / drobromid and. 2- / T4- -Amino-P-ethyl-5-pyriTrjidinyl) -methyl / -1 -methylimidazo / ϊ, 5-a7pyridiniumchlorid-hydro chloride.

The salt is present in all of the aforementioned preferred compounds expediently in the Ohlorid-hydrochloridform. The bromide hydrobromide is also valuable. In these preferred compounds, X represents bromide or chloride. The quaternary anion can can also be any inorganic anion, for example an iodide, nitrate, sulfate or phosphate ion, or the anion of an organic acid, such as citric, tartaric, vinegar, Stea.rin, amber, benzoin, phthalic, phenoxyacetic, embon, Abietic or 2-naphthalenesulfonic acid. It can also be that Anion of a polymer act as a polyphosphate or Polystyrene sulfonate ion. The type of anion is -not decisive; any anion can be used as long as it does not cause intolerable toxicity to the poultry.

To produce the connection classes described here you can several procedures can be used. In general, the appropriately substituted pyrimidine is condensed (then referred to as "the pyrimidine") and the methylated nitrogen-containing bicyclic Ba.se (hereinafter referred to as "the bicyclic Base ") by bringing the two components to reaction in a solvent system. The starting materials, i.e., the pyrimidine and the bicyclic base, are either known compounds or can easily be derived from conventional ones Process are produced.

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14 484

A) Acid test method

In the preferred process, the suitable 5-hydroymethylpyrimidine, which has been converted to the ester of a strong acid, is used in the TTT etching with the bicyclic base. The "ester of a strong acid" is understood here to mean the enter in the 5-position of the pyriraidine, which is formed by esterification of the hydroxymethyl group with a strong inorganic acid, such as a hydrogen halide acid. Then? -T? * - 4 -.- Amino-5-halomethylpyrimidine dihydrohalide, in which halogen is then bromine or chlorine and H ^{1 has} the meaning given above, is, for example, reacted directly with the bicyclic base.

A test of the organic solvents which are inert under the reaction conditions according to a modified method, for example acetonitrile or a N / TT-di-lower-alkylalkanolamide, such as dimethylformamide, can be used in the reaction medium. The reaction temperature is not critical; the process is preferably carried out at about room temperature. After a short time, the product, which usually represents the quaternary salt, crystallizes out and is isolated by conventional methods, such as by filtration or centrifugation. The procedure can be represented as follows:

(II)

(I)

cX b

where R ^{1 is} an alkyl or perfluoroalkyl radical with 1 to 1 carbon atoms or a 1,1 ^ -difluoroethyl or?,?,? - trifluoroethyl group, X »is a halogen anion, such as a chlorine or bromine ion, X, b and c the above stated

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14 484

have clear and -TJ ^ represents the remainder of the bicyclic base, as defined above. ■

Although the 5-Haloganmethylpyrimidinen in general the greatest advantages are achieved in a reaction with nitrogen-containing heterocyclic Bane ^ the quatemization can be done with other esters de-s 2-R ^v - ^ - Amino ^ -hydroxymethylpyrimidins. The esters of organic sulfonic and sulfonic acids are suitable, such as methyl sulfinate or p-toliolsilfona-to. Han can carry out the reaction in such a way that the special salt desired for the treatment of coccidiosis is obtained directly. According to a modified method, the quaternary salt obtained from the synthetic reaction medium can advantageously be converted into another salt using conventional methods «

B) Ktherq splitting procedures

Another method involves taking part in the implementation the bicyclic base ^ -R'-4 "amino-5-methyletherpyrimidine in Presence of an excess of hydrohalic acid, wherein that halogen is gold or bromine.

Can this process be represented as follows?

.HX »

(III)

(T)

where R ^{9 is} a alkyl or perfluoroalkyl radical with 1 to 3 carbon atoms or r sine 1,1-difluoroethyl or 2,2,2-trifluoroethyl group , "R @ in @ n alkyl or ? Aralkylreat with less than

Π represents carbon atoms, X ^{f is} a halogen, such as a chlorine or bromine ion, and -T ₁ O has the meaning given above. '-

Daa is the pyrimidine derivative used (general formula TTI) the hydrohalide of? -R'-4-amino-5-hydrocarbonoxymethylpyrimidine. The hydrocarbon or hydrocarbyl radical (R "in formula III), which forms part of the ether substituent in the 5-position, can be an alkyl or aralkyl radical; it is preferably a group with fewer than 9 carbon atoms. Of the

ρ.

The radical R ″ can thus represent a lower alkyl radical, for example a methyl, ethyl, propyl, inopropyl, tert-butyl, Amyl or benzyl group. Pyrimidines with a methoxymethyl or isopropoxymethyl group are preferred. "These connections are known; , icne connections which are not specifically described are easily prepared by the methods used for the known, similar compounds; see e.g. J.A.C.S. 59 (1947), page 105? or US Patents 3,161 or? 350-65.

The bicyclic base used is also in the form of the Hydrohalides. These Pyrimidinylmethylather are with the bicyclic base (as defined above) under the reaction conditions explained below. for implementation brought.

An excess of the bicyclinic base is used over the pyrimidine a. Satisfactory results are obtained when one. 1.5 to 10 Hols of base are used per mole of pyrimidine.

As can be seen from the aforementioned reaction topic, the Process described here by the hydrochloride of the binvical Base is a pyrimidyl methyl ether of the general formula ITT split, forming the desired quaternary salt. Although the two reaction components are in the form of the Hydrochloride can mix and carry out the reaction in the manner described below, it is also possible that

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Pyrimidine and the bicyclic base in the form of the free bases to be introduced into the reaction mixture and the salts in situ by adding hydrogen chloride to the reaction mixture, to deliver.

A feature of the present process is that the cleavage of the P-Lower-a] kyl-4-amino-5-'h3 ^r drocarbonoxyjnethylpyriinidins is performed with the hydrochloride of the bicyclic base in the presence of a hydrogen halide excess, of an excess ie those hydrohalic quantitative which is necessary to convert the total amount of the pyrimidine and bicyolic base present to their hydrohalodene. The excess of acid over the amount required for salt formation is 7.5 to $ 100.

The process is carried out at atmospheric pressure and at elevated temperatures, ie from about 110 to 200.degree. It can be seen that the optimal reaction time depends to a large extent on the temperature used. Satisfactory green results are already achieved within 5 to 10 minutes at higher temperatures, while 10 to 12 hours or more are required at lower temperatures. When the process is carried out within the preferred temperature range, the quaternary salt turns out to be in high yield in about 1 to 8 hours. The reaction mixture is thermogenic in some stages of the process, so that the degree of mixing can play a role in large-scale systems. The optimal reaction time increases with a decrease in the stirring efficiency ρ.

The present process is carried out in an organic solvent medium. Numerous aromatic and aliphatic solvents can be used; specific examples of these are toluene, xylene, sec-butylbenzene, tetrahalorethane, tetrachlorethylene and the chlorinated bromoles. It is advisable to use a solvent with a boiling point close to the desired reaction temperature so that the process can be carried out under reflux. The solvent should of course have a boiling point of at least 110 ⁰ C, so that the

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above-mentioned temperature conditions are maintained. In addition, the solvent should not be miscible with Wn ^ Rer no, since achieving optimal yields of undesired reaction byproducts, such as lower alkenols and / or water, are to be constantly removed from the site of the reaction. To the distance Several methods are suitable for low-boiling by-products, for example the continuous distillation of the organic solvent and its replacement with fresh solvent, distillation or refluxing through a steam-cooled condenser which removes the low-boiling material can be drawn off, but the organic solvent returns to 'the reaction vessel, or the use of commercially available mechanical separators. ,

The reaction product is obtained at the end of the reaction period expediently by cooling the reaction medium and separating the essentially pure pesticide from the organic Solvent. The product becomes from the remaining reaction solvent by washing with suitable solvents such as acetonitrile, isopropanol or ether, freed. If this procedure is carried out under the reaction conditions described above, the desired products are obtained in yields above $ 80 of theory. Reach tn many cases the yields a · value of $ 90 of theory.

C) Other procedures

Further variations of the two above can be used Apply procedure.

For example, one can use either 5-hyirocarbonoxymethylpyrimidine or the 5-hydrochloride methylpyrimidine hydrohalide with an excess of the hydrohalide of the bicyolic "Baso" in the absence of a T, ösnnr; smittp1 s to implement by the components are refluxed for 0 minutes to 10 hours an elevated temperature, preferably from 1 ^ 0 to ?? 0 ° C, if necessary cooks under pressure. The hydrohalides can, if desired, be prepared in situ by first preparing the

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U 484 '' - - '4H

Pyrimidine, and the bicyclic base in a low boiling solvent enters and hydrogen halide gas Mndurchführt the! Solvent _f "at a temperature below .100 ⁰ G evaporates, and then heated to the Rea.ktionstemperatur. The product can in each case by dissolving the Reaktionspro & uktgemisches in a Solvent _p such as ethanol or propanol, and subsequent recirculation can be obtained using the usual methods »

Another modified method uses the reaction between the 5-hydroxymethylpyrimidine-hydroha.logenidr, which was preferably obtained in situ by reacting the 5-hydroxymethyl-4-arnino- = 2-R ⁹ -pyrimidine, with the hydrohalide of the -bicyclic base in an organic solvent g "Never. Benzolj, toluene or xylene, with a p ^ -value of 3 Ms 6j 5. Wan adds additional '.aqueous acid if this is necessary »The reaction is carried out at an elevated temperature such as from 160 to 170 ° C» The difficulty with this abgewandelten- method is _s that the Tiösiangsiaittelsystem and water könnenj evaporate from the reaction mixture, the water is separated from the solvent and the solvent is recycled in order to prevent the ionization of the vorlis-Tid enes hydrohalic acid and thereby the corrosive nature of the System to reduce "

According to another modification of the? S.etzt method is a 5-Hyrlrorymetlriyl .-- 4 "= a.mino ~? I = R ⁰ --pyriTriidin with the bicyclic base is _s prepared by Reaktionsraedium first, the 5-hydroxymethyl pyrimidine or in a ßir / in the form of a Mixtures of thionyl chloride and a WjN dialkylfornamide and a.nachlisBsnd. the Mcyclisohs base adds ₀ "The latter can either be the free base or its hydroha.logenid bandθ1ώ _ε The reaction medium is prepared from stoichiometric proportions of both components. This medium is kept at low during the pyrimidinsuga.be temperature s, d = h _o of about -5 to 1O ⁰ O ₀ subsequently, the mixture is heated and · adds the bass. _o wax of the base addition to holding the Reaktionrsge- · miscli 1 Ma 2 "hours under reflux, then it cools and isolate the product. · "■

45Γ

With the bicyclic bane see also ι in: 5- (Tri-lower- -al kyl. ammonium) -methyl-4-amino -? - R '-pyrimidine halides, in particular the chlorides, as well as 5- (tri-lower alkylphosphonium) - -Tethyl-4-amino-P-R · -pyrimidine halides, especially the Chlorides. Another analogous method uses the reaction between the tetrachloride zinc compiler of a 1- (2-R * -4- -A.minopyriTnidin-5-yl) methyl base with ammonia.

Another modification consists in the fact that a 5-Halogpmmethyl-4-aTnino-2-R'-p? / Rimidine with the. bicyclic base in dimethyl sulfoxide within 30 minutes to 3 hours at temperatures from 40 to 135 C - "optionally in the presence of one A.lkalihalogenides, as converted by potassium bromide, subsequently the »reaction mixture with an aryl sulfone Mure, such as p-toluenesulfonic acid, added, the mixture then refluxed for a few minutes and then cooled, and finally the product isolated. This method is the Sriureester method described above very similar, of course, and can also be viewed as a modification of that procedure.

Other obvious modifications of the aforementioned processes can be found. Similar TCond en sat ions are described in detail in the literature. Of course, any method can be used for the preparation of the new compounds of the invention, although this is not described in more detail here, but it is already possible was applied to similar reaction components.

When using the compounds according to the invention for treatment and coccidiosis prevention are pre-fed. these to the poultry with advantage in fo-nn a component of the animal feed, though the compounds can also be dissolved or suspended in drinking water Form can administer. According to the invention there are provided new compositions in which the above compounds described as an anti-coccidic agent are included. Within such compositions, the quaternary salts are thoroughly in an inert carrier or Diluent dispersed or thoroughly with such

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Carrier or diluent mixed * An inert carrier is to be understood as a carrier which is not reactive towards the quaternary salt and which can be administered to the animals without danger. The carrier or the diluent is preferably a material that is a constituent part of the animal feed from the outset or is added to it as a component .

Compositions preferred according to the invention are the feed additives which contain relatively high amounts of active ingredient and which can be incorporated into the poultry feed either directly or after prior dilution or mixing. Examples of carriers or diluents which are suitable for such compositions are solid, orally ingestible carriers such as dried stillage or spent grains, corn meal, citrus meal, fermentation residues, ground oyster shells, Attapulgus- tone, fine wheat bran, soluble Melassebestandteile, corn cob meal, edible vegetable matter, "toasted" liberated from shells soy flour, Sun ₁ ^-] The quaternary salts are thoroughly dispersed in the solid inert carrier, for example by rubbing, stirring, grinding or centrifuging, or mixed in this way with the carrier of the carrier / Active ingredient / quantity ratio, compositions with any desired concentration can be prepared. Mixtures with an active ingredient content of about 1 to about 40 wt .- $, preferably from about 2 to 25 wt .- #, are particularly suitable as an additive for poultry feed. Compositions containing from about 5 to 15% by weight of the coccidiostat provide excellent results. The active compound or the active ingredient is generally uniformly dispersed in the diluent or mixed with them; in some cases the active ingredient can be adsorbed onto the carrier. The optimal concentration of the coccidiostatilnxms in the aforementioned feed additives depends to a certain extent on the particular compound used. Since e * is an advantage for the feed manufacturer, per ton of the finished feed material

-16.- '

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To use about 0.45 "kr. O pound) feed additive, the preferred concentration of any coccidiostat according to the invention in a feed additive depends in part on the proportion of active substance desired for the finished feed material.

In addition to its sole use in feed mixtures, the novel compounds of the invention may have been used moh? Combined with nnde- ren known Kokzidiostatikn. In the latter case, the development of coccidiostatic activity is guaranteed to its full extent, ie even against resistant strains. Specific examples of other coccidio-antibiotics, which we naturally offer for a combination, are Amprolium £ \ - ( 4-Amino -? - propylpyrimidinyl - 5-methyl) -i) t-pico-Iiniumchlorid-hydrochlorid7, Ethopabate, Nicarbaz .in (1: 1 molar complex of 4,4'-T) initrocarbanilide and 4,6-T) imethyl -? - pyrimidinol), Rohbenzidene, SulfacMnoxalin ^? - (4 ^f -Aminoben5? olnulfonamido) -quinoxali ^, Pyrimethamine [2 , 4-Dimethylamino - 5- (p - chlorophenyl) -6-eth? / Lpyrimidin7f Alklomide, Sulfanitran, Clopidol, Nitromide, Zoalene (2-Methyl-3,5-Dinitrobenzamid), Roxaraone, Areanilic acid, Enquinolate , T) ecoquin8i; e, Nonennin, Nitrophenide (3,3 ^f -DinitrodiphenyldiPulfid), Furazolidon / N- (5'- ^{Nitro-? R} - -furfuryliden) -3-amino -? - oxazolidon /, Nihprdrazone, Nitrofurazon (5 ? -Nitrofursn- ~ ^{a3.dehydRemiei:} rbn 7, on), "Di me thai ium and Clothiamine!.

Examples of typical feed additives that are one in one Divergent, inert carriers diverged quaternary pyridinium salts included, piind:

^ (poundπ)

-7-methyl thieno / i *, Vc7pvridiniumnh1 ori d ~

hydrochloride?, 7 (6)

Weiaen standard feed meal 4?, 6 (94)

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14 484 2305001

^ f (pounds)

-4-methyltliieno / 3, .P-c / pyriiium chloride-

-hydrochloride 4.5 (10)

dried Oetyfn.deschlempe 40.8 (90)

-hydro 0Ϊ1Χ0 rid 9.1 (? 0)

C-cereal germ flour H _? 6 (30)

Grain Meat? 2.7 (5.0)

These and similar Futterraittel2; usM.tse is one characterized forth _p durehmieeht that the product with the carrier or the carriers uniformly _o .- "" ·..

Dienes dilution "The imagining described PuttermittelziuRätsie ^ before they EIBT dam veri an animal feed ¹ ₉ generally diluted further, for example with HaiRtnehl or soy flour. Serves the uniform distribution ρ of the substance in the finished lining material? Facilitate .u. The finished feed material has a G-elia.lt of fats _s EiweiPBtoffen ₉ carbohydrates "Mineralstoffenj vitamins and other nutrients on"

The amount of drug required to combat poultry coke idiosis will of course vary to a certain extent depending on the particular compound (s) used. The compounds of general formula I allow for administration in doses von'weniger as etwn 0 _s 05 fiew /.-$ the feed material .a wirksawe Disease-tHbekampfiing "By means of the invention preferred Vnrbindungen, .DH the 6- / I4- Amino- -P-nieaer-alkyl-5-pyrimidinyl) -methyV-thieno / ?, λ-c / pyridinium- or the €> - / { 4-amino - =? - niader ^> -alkyl-5-pyrimidinyl) - methyl7- -thieno / 'Bj ^' - cJ'pyr'idiniuraBalge _s are good prophylactinche results obtained _g if these compounds in Donen from about 0.01 to about 0 _? 05 Sewo- / »of the entire handicapped fodder

■ "'- 18 -

Λ AA Λ I i 4 4 es

administered. The best results are achieved when the poultry feed has the preferred salt content of about 0.001 to _: 0.025% by weight. If one wants to use the salts as therapeutic agents, one applies the higher proportions within relatively short periods of time. To treat coccidiosis that has already broken out, it is therefore advantageous to use concentrations of around 0.0? Use up to 0.05% by weight of the putter material. T ⁵ Is it is advisable to use the lowest proportions that guarantee a fully adequate control of coccidiosis, in order to eliminate as far as possible any risk of side reactions "which could occur when the compounds are fed for a longer period of time.

Many of the aforementioned quaternary salts are not tolerated in poultry Administer with advantage with their drinking water. This method of treatment is often used in therapy of the compounds according to the invention applied because of coccidiosis infested poultry versus solid feed material has a lower capacity than healthy animals. You can add the water-soluble quaternary salts directly to the drinking water incorporate. You can also prepare water-soluble powders, in which the coccidiostatic agent intimately with a suitable carrier, such as glucose or cane sugar, is mixed. These powders are then added to the poultry drinking water as needed added. Such water-soluble powders can contain any desired concentration of the coccidiostat. Good Preparations with an active ingredient content of 1 to? 5 # are suitable

The examples illustrate the invention without, however, restricting it. Examples A to E relate to the starting compounds which are used to prepare the compounds according to the invention can be used.

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309834/1162

Example A.

2-Pentafluoroethyl- _ι 4- _ι amino-5-hydroxymethylpyrimidine 2-pentafluoroethyl-4-aTnino- [5-hydroxyin (3thylpyrimidine (A) can be prepared starting from pentafluoropropionamidine, as described by Barone et al. In J. of Ori ;. Chem. 24 (1959), page 199. If one uses heptafluorobutyramidine, trifluoroacetamidine, .3,3, .Vtrifluorpropionamidine or 2,2-difluoropropion < ^c imidine in the process of Barone, 2-n- Heptafluoropropyl-4-amino-5-hydroxymethylpyrimidine, 2-trifluoromethyl- -4-araino-5-hydrox; p ^ thylpyrimidine, 2- (2, 2, 2-trifluoroethyl) -4- -a.mino-5-hydroxymethylpyrimidine or 2- (1,1-difluoroethyl) -4- -a-thino-5-hydroxymethylpyrimidine.

B e i s ρ i e 1 _i B.

2-P ent af luoroethyl - 4-a.mino - 5 -br omme thylpy r imid in-hydr ο bromide Dissolve 5. g of 2-pentafluoroethyl-4-aτnino-5-hydroxymethylpyrimidine in 30 ml of a 30 to 32 percent , p; en Hydrogen bromide solution in acetic acid. The resulting mixture is heated for 6 hours at 65 ⁰ G and then cooled it to room temperature. A precipitate forms, which is poured into 100 ml of ether, filtered off, washed thoroughly with fresh ether and air-dried. The pyrimidine hydrobromide (6.6 g; yield 86 fo) is obtained in the form of a colorless, solid substance with a melting point of 167 ° to 169 ° C. (decomposition). '

• Example C

Perfluoroalkylamidines

Pentafluoropropionamidine is prepared as follows: 80 g of commercially available pentafluoropropionitrile are condensed in an I-Lite ^ r flask immersed in a dry ice / acetone condenser and in a dry ice / acetone bath. The flask is charged with about 250 ml of liquid ammonia, the cooling body is removed and the (Roman) is allowed to reflux for 1 hour. The ammonia is then allowed to draw in. The amidine remains in the form of a colorless, crystalline, solid substance. (75.2 g; yield. 84 f) of melting point 48 to 50 ^° C.

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309834/1162

The other perfluoroalkylamidines can be made by hand in the same way Perfluoroalkyl nitriles are produced.

Example T) .3 »3 r 3-Tt ifluorpropionamidi n

a) A solution of 76.3 g kept ^{at 0 0 O is added}

3,3,? -TT "i'fluoropropionitrile / manufactured as written by AI Shchekotikhim et al., Zh. V ^ en. K" him. Ohshohest., 13 (1968), page 358 / in 35.4 g of anhydrous ethanol with 8.1 g of water-free hydrogen chloride. The reaction mixture can be kept at ⁰ ° C. for 4 days and then crosslinked with 500 ml of ether. The reaction mixture is then cooled down to about −50 °. The crystalline 3,3,3-T ¹ rifluoropropionimidoethyl ester ~ -hydrochloride formed is filtered off and washed with ether.

b) 88.7 g of 3,3,3-trifluoropropionimidoethyl ester hydrochloride are carried with stirring in a solution of? 0 g ammonia in? 00 ml ethanol. After 3 hours at room temperature, it is filtered the reaction mixture and then concentrated in vacuo to a thick one Syrup one. Fan adds an equal volume fraction of acetone and filters the resulting precipitate from 3,3,3-trifluoropropionamidine hydrochloride away. The pIter residue is washed with ether. The material obtained is then treated with an equimolar amount of sodium ethylate in ethanol. Receives one the free amidine.

"Example E

• ?. _t P-Dif J. uorpropionamidine

a) 116 r, pyruvic acid ethyl ester are placed in a 1-liter hydrogenation vessel made of corrosion-resistant steel. "The vessel is cooled to -78 ⁰ C, evacuated to a pressure of 1 mm and purged three times with nitrogen. Then, 3? 5 Γ, sulfur tetrafluoride knito in the distilled evacuated vessel. The vessel is then sealed and 10 hours 90 ⁰ C heated. it is allowed to deduct the gaseous Roaktionskomponenten and pour the liquid in 50 g of sodium fluoride in 1? 5 ml ether a. it is washed with ether then the vessel

309834/1 1

and distilled the combined ether lungs through a column at atmospheric pressure. The ethyl - 2-difluoropropionate is ?, illation by Vakuumde st in the form of a colorless liquid of boiling point 45 isolated (50 mm) up to 5O ⁰ G.. .

b) Dissolve 18 g of ethyl -., 2-difluoropropionate in 70 ml of ethanol and churn the solution to 0 O. The reaction mixture is then saturated with ammonia and left to stand at ⁰ ° C. overnight. The insoluble substances are then filtered off from the mixture. After the ethanol has been evaporated off in vacuo, 2,2-difluoropropionamide remains in the form of a colorless, crystalline, solid substance of m.p. 65 to 66 ⁰ O.

c) Place a mixture of 100 n; P,? .- Difluoropropiona.mid tind 200 g of phosphorus pentoxide in a distillation flask, which with one cooler and one in a dry ice / acetone bath cooled template is equipped. Han gradually dips the flask in an oil bath kept at 200 ° 0. While screaming th of the reaction, the 2,2-difluoropropionitrile formed distills from the reaction mixture. The crude nitrile is then distilled at atmospheric pressure.

d) The P ₅ P-difluoropropionamidine 2,2-difluoropropionitrile is then prepared using the method described for pentafluoropropionamidine »

6- / t4-Amno-P- ethyl-5-pyrimidlny

17.8 g of 4rAmino-2-ethyl-5-pyrimidiny! Methylbromide- hydrobromide and ö _? 94 g 7 ™ methylthieno / ?, 3-o / pyridine in 5Q ml of dry acetonitrile Wasner _o Reaktionsgemiseh is mechanically stirred overnight at room temperature ₀ is isolated colorless ^ precipitated and washed with ether ,, After !! "crystallization-a. un metha.no l / acetone one obtains 16.5. S (. Yield 61 _S 5 ^) of a substance of m.p. 249 Ms 25O ⁰ C (decomposition), which as. 6 - / ^ 4-Amino- -2- & thyl-5-pyrimidinyl) -methyl7-7 ™ methylthieno ^ 2,3-

_ 22 1 =

Ji

bromld-hydrobromide is identified.

The bromide hydrobromide is dissolved in 50 ml of concentrated hydrochloric acid and then precipitated with 1.5 liters of acetone. This procedure is repeated four times. Finally, 7.85 g (60% yield) of a colorless, crystalline, solid substance are obtained from Pp. 249 to 25O ⁰ C (decomposition), which as 6- / Ϊ4- -Amino-2-ethyl-5-ryri.Tnidinyl) -methylJ ^ -T-methy ^ thieno / 2,3-c / pyridiniumchlorid hydrochloride is identified.

The compounds 6 ~ / X 4-amino-2-ethyl-5-pyrimidinyl) -methyl7-5- -methylthieno / 2, Bc / pyridiniunchlorid-hydrochloride and 6- / Ϊ4- -amino ^ -methyl ^ -pyrimidinyl) -meth ? rl7-thieno / P, 3-c / pyridinium chloride hydrochloride can ^ emn.B the aforementioned reaction are prepared, with 4-amino-P-ethyl-5-p: yrimidinyl meth? / lbromide hydrobromide with 5 -Methylthieno- / 2,3-q7pyridine or 4-amino-? - methyl-5-pyrimidinylmethylbromide- hydrobromide with thieno / 2,3-o7pyridine is used.

Ex iel?

/ 2, ₁ 3- c ^ pyridiniümbrοmid-hydrο bromid

891 mg of 2-ethyl-4-amino-5-bromomethylpyrimidine-hyd: rx) -bromide are dissolved in 5 ml of dimethylformamide and 1.95 E ?, 7-dimethylthieno / j?, 3-Q7ry ^ idin are added. A precipitate forms immediately, which is isolated, washed out with dimethylformamide and discarded. The filtrates are stirred overnight at room temperature and diluted with ether. The grayish precipitate is separated off and treated with ether. The solid obtained is dissolved in methanol and hydrogen bromide gas is passed into the mixture. The colorless product is isolated and discharged Methanol / isopropanol crystallized in. 70 mg of product are obtained, ie diniumbromid hydrobromide, mp 15-216 ⁰ C. (decomposition);.? yield 20 i>.

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309834/1182

Bod s r \ i R

-P-pent afluorethyl-5-jyrimidinyl) -mc

, 4-amino-2-pentaf luor-

ethyl - 5-P77 "rimidin7; l) -methyl

Ttan suspended 967 mg of 4-A'mino -? - pentafluoroethyl-5-Tnet'hyl'broTnpyriTnidin-hydroViromid in 1? ml of acetonitrile and 160 mg (2.75 mmol) of propylene oxide are added to dissolve the solid substance. Then 373 mg of 7-methylthieno / P, 3-c / pyridine are added and the homogeneous reaction is stirred for the weekend. "The formed, colorless precipitate is diluted with ether · isolated and umlrristailisiert from isopropanol Fan obtained 530 mg (yield 46.5 fo) of product, mp 215-216 ⁰ C, which as 6 -... / (4-amino- ? -pentafluoroethyl-5-pyrimidinyl) -methyl7-7-methylthieno- £ 2,3-o7pyridiniumbromid is identified.

The aforementioned product will then be more concentrated aqueous hydrobromic acid yellow st. The solution is with one sufficient to precipitate the bromide hydrobromide Amount of acetone added.

f}> , > 2-c ^ yridiniumchlp rId-hydrp chloride

82.5 g of 4-amino-.2-ethereal-5-P7 / "rimidin, ylmethylbromide hydrobromide are suspended in 1 liter of anhydrous acetonitrile. 82.5 g of 4-methylthieno / 3,2-cj? pyridine is added and the reaction mixture is stirred for 2 days at room temperature. The resulting colorless precipitate is isolated, washed with ether and recrystallized from methanol / isopropanol. 69.5 g of a colorless, solid substance with a melting point of 218.5 to 220 ^° C. (decomposition) are obtained. After further recrystallization from methanol / T sopropanol, this yields 52.1 g (42% today) of a product of .Fp. 229-230 ⁰ C (decomposition), which is identified as 5- / t4-amino-2-ethyl-5-pyrimidinyl) -methylJ7_4-methylthieno / 3,2-c7pyridiniumbromid hydrobromide.

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309834/1162

The abovementioned "Rromide" is then dissolved in 130 ml of concentrated HCl and precipitated with acetone. This procedure is carried out five times. Fan finally receives 33 g (yield 33 #) of 5- ^ T4-amino -? - ethyl-5-pyrimidine , vl) -methyV ^r - -4-methylthieno / 3,2-o7pyridiniuTnchlorid-hydrochloride from m.p. ?? 9 to -30 ° C (decomposition).

The other compounds produced according to the present invention are shown in the table. The condensation process described above for Examples 1 to 4 is used. In each case, the 5-B "mermethylpyrimidine and the bicyclic base are condensed in an inert solvent in approximately equimolar proportions at room temperature (about 25 ° C.). The term" base type "in the table relates to the formulas A, B ₁ C, D, E, F and G, which have been explained in more detail above.

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example

Link?:

Base type yield, fo melting point, ⁰ C

O CO OO

6- / J 4-A * "ino-2-ethyl-5-pyridinyl) -methyV-7-methylpyrrolo / 2,3-Q / pyridine

1 - / t 4-amino-2-ethyl-5-T) yrimidinyl) r -methy ^ -imidazo / i, 2-a7pyridiniumbromid-

12th

13th

1- / T4-amino-2-ethyl-5-pyrimidinyl) -

-mefhyl7-3-neth.yliinida.zo / i,? -g7pyridiniuinbroTnid-hydro "bra raid

47

55.

192-194 (decomposition)

278-280 (decomposition)

^ 10-312 (decomposition)

2- / X 4-Anino ~ 2-ethyl-5-pyrimidinyl) -

-Tneth3r3 _i 7-3-TnefhyliTnidazo / 1,5-a / pyridinium bromide-liydrobromide

52.

266-267 (decomposition)

B e χ π ρ i_ e 1 16 6- / 1 4-amino-2-ethyl-5-pyrimidinyl) -, 3- ^ pyridiniumchi. orid-hydronhlorid '

"One puts 50 g of 2-eth7 /: l-4-a.mino-5-methorymethylpyrimidine, 50 g of 7-methylthieno / 2,3-c7pyridine and 500 ml of xylene in a 2-section equipped with a condenser, stirrer, thermometer and gas inlet tube In this mixture, hydrogen chloride gas is passed over a period of 30 minutes at a rate sufficient to use 0.2 mole of HCl per mole of pyrimidine. it is to replace the gas inlet pipe da.nn with a distillation head and the mixture heated for 2 hours under reflux (138 ⁰ O). During this period, we replace the a.bdestillierten volume fraction of the liquid by fresh xylene. it adds an additional 25 g of 7-methyl thieno / ?, added 3-c7pyridin and boil the mixture for 40 minutes under reflux. at the end of the reflux period, the reaction mixture is cooled to 65 ⁰ C a "b, and the xylene decanted the residue with 50 ml of acetonitrile. The resulting mixture is stirred at room temperature for about 12 hours and filtered. The solid 6 - / ^ 4-amino-2-ethyl-5-pyrimidinyl) -methylj ^ -methylthieno / ¹ ?, 3-c7pyridiniumchlorid- hydrochloride is washed. The product has a melting point of 249 "to 25O ⁰ G (decomposition).

The reaction described above can also be carried out using chlorobenzene instead of xylene as a solvent the second addition of 7-methylthieno / 2,3-c7pyridine is carried out is omitted. The same product is obtained, i.e. 6- / I4-amino -? - ethyl-5-pyrimidinyl) -methyl7-7- -methylthieno / ^, 3-c7pyridiniumchlorid-hydro chloride.

Example . 17 6- / t4-amino-2- eth 77; 1.-5 -pvrimidinyl

-pyrrolo / fr, 3-c / pyridinium broth and 6- / T 4-amino-2-ethyl- -5-pyrimidinyl) -methyl7-7- methyl l-6H-pyrrolo /? ₁ 3-C ^ PyT ¹ JdJn One carries 420 mg of diisopolyethylamine in a solution of 1 g

- 28 -

30983A / 1162

of pyrimidinylmethyl bromide hydrobromide (I) and 0.44 g of pyrrolopyridine (II) in 6 ml of dimethyl formamide. . The mixture is stirred 16 hours at room temperature "in an embroidery stof fatmosphäre the Umsetzungsprodukti partially crystallizes sun from the mixture; the complete deposition are employed ether added Nnch filtration and air drying, one obtains 1,6 <* crude product, which one. . Dissolve in chloroform / 25 # methanol (approx. 5 ml) for cleaning. The Ρττ value of the solution is adjusted to approx. 8 by adding a few drops of aqueous concentrated ammonia. H in Chi ^ ro form /? 5 methanol omnographed. Pure 6 - / (4-amino- -? - ethyl-5-pyrimidine: A) -meth7 / V'-7-methylpyridinium bromide (0.63 g) with a melting point of? "* 5 am

"00 mg of the aforementioned quaternary" Rromidn are dissolved in? Ml of methanol, the solution is adjusted to a value of 8 with 1 η aqueous LiOH and the product is allowed to crystallize out of the solution. 100 mg of 6- £ ( 4-Amino-? - ethyl-5-pyrimidinyl) -methylJ-T-methyl-6H-pyrrol6 / ^, 3-q7 ~

pyridine of m.p. 19? to 194 C. ⁿ

By adding 1 mole of hydrohalic acid to the base conversely, the quaternary halide is obtained again.

The addition of excess halohydric acid to one of the two compounds obtained provides the quaternary halide hydrohalide.

/ nc)

Claims (1)

.1. Compounds of the general formula I T ?. in the Ή. ".- an alkyl or perfluoroalkyl radical with 1 to 3 carbon atoms or a 1" 1-Difluoroäthyl- or P ^ jP-Trifluoroäth ^ rl ^ group, X is a chlorine or bromine ion, b and c such integers mean that the positive bond of b Fo.l of the cation is neutralized, i.e. c Hol the anion X , and -N j is a residue of one of the formulas A to 6 (B) GH. .Tf-R t id ΛΑ & / 1- 1 Θ means, wherein H represents a hydrogen atom or a methyl group and the dotted line indicates that
the methyl group or a hydrogen atom may be present, with the proviso that at least one al-methyl group is present, but not both of these groups are present, 2. Compounds according to claim 1, characterized in that R ^{1 is} an alkyl radical having 1 to 3 carbon atoms. 3. Compounds according to claim 2, characterized in that R * is an Ä'thylgruppe. 4. Compounds according to claim 3, characterized in that -lO is a radical of the formula A, B or C. 5. Compounds according to claim 4, characterized in that -N _- ) is a radical of the formula A. 6. Compounds according to claim 5, characterized in that -NJ is a radical of the formula A ^ CH, . ■ ^<A i> is. 7. Compounds according to claim 4, characterized in that vJ is a radical of the formula int. 8. Compounds according to claim 4, characterized in that O is a radical of the formula Cj - 31 - 309834/1162 14 484 is. 9. Compounds according to claim 3, characterized in that a radical of the formula D or E is. 10. Compounds according to claim 9, characterized in that f is a radical of the formula D. 11. Compounds according to claim 10, characterized in that -N) is a radical of the formula D. (D ₁ ) is. 12. Compounds according to claim 11, characterized in that i, when R is hydrogen, the deprotonated Formula D., ' having. 13 · Connections according to claim 3, characterized in that -lO a remainder of the. Formula is F or G. 14. Compounds according to claim 13, characterized in that -N J is a radical of the formula G. - 32 - 309834/1162 15. Compounds according to claim 14, characterized in that a residue of the formula G. 1
OH. (G ₁ ) int. 16. Compounds according to claim 1, characterized in that R ^{f is} a perfluoroalkyl radical having 1 to 3 carbon atoms. 17. Compounds according to claim 16, characterized in that R * is a Pentafluorftthylgruppe. 18. Compounds according to claim 17, characterized in that is a radical of the formula A ₁ . 19. Process for the preparation of the compounds of the general formula Ia NH * »IT ⁰ VO (Ia) in which R ^f denotes an alkyl or perfluoroalkyl radical with 1 to 3 carbon atoms or a 1,1-difluoroethyl or?,?,? - -trifluoroethyl group, b and c represent such integers that the positive charge of b moles of the cation is neutralized by ο mol of the chlorine ion, and -NJ the remainder of a bicyclic base with a.v of the formulas A to G 'J 1 KJ 484 2305001 (β) (σ) -w ^ r (ρ) , 1 L Λ ' ^η 3 means, where R represents a hydrogen atom or a methyl group and the dotted line indicates that the methyl group or a hydrogen atom can be present, with the proviso that at least one ot-methyl group is present, but not both of these groups are present, characterized in that, that the acid ester of 2 -R'-4-amino-5-hydroxymethylpyrimidine, the acid being a hydrohalic acid (halogen »bromine or chlorine), is reacted with the bicyelic base and the reaction product is obtained. ³ 20, method according to claim 19, characterized in that one either the base is used in excess or the reaction is carried out in an inert organic solvent. 21. The method according to claim 20, characterized in that R ^{1 is} an ethyl group and -N ~ y, a radical of the formula Aj represents, and that the quaternary halide hydrohalogenide, wherein Halide is bromide or chloride - 34 - 309834/1162 2 ?. Method of making the? quaternary halides
or of the quaternary halide hydrohalide, where
Halide, chloride or bromide, of the compounds of the general formula I cX
b (D in which R ^{1 is} an alkyl or perfluoroalkyl radical with 1 to
3 carbon atoms or a 1,1-Mfluoroäthyl- or 2,2,2- -Trifluoroäthylgruppe, X is a chlorine or bromine ion, b and c such integers that the positive Tiadung of b mol of the cation by c mol of the Anion X is neutralized, and -τθ the remainder of a bicyclic base with one of the formulas A to G CH.
+ (B) (C) -N ' CH (D) Joo- (E) (F) TJH. CH. (G) 309834/1162 where R represents a hydrogen atom or a methyl group and the dotted line indicates that the methyl group or a hydrogen atom may be present, with the proviso that at least one J , -Methyl group is present, but not both of these groups. are, characterized in that a 2-R * ^ -amino ^ -hydrocarbonoxymethylpyrimidine hydrochloride, where "hydrocarbon" means an alkyl or aralkyl radical with less than 9 carbon atoms, with the Hydrochlorid.der bicyclischen Bane in proportions such as that 1.5 to 10 moles of base per mole of pyrimidine are used, reacts in the additional presence of Hydrogen Hydrogen acid and wins the reaction product, 23 · The method of claim 22, characterized in that one carries out the reaction in a water-immiscible organic solvent having a boiling point of ViO to 20O ⁰ C. "'· ■ ·. 24. The method according to claim 23, characterized in that the Solvent is xylene, 25. The method according to claim 24, characterized in that the Reaction pressure is atmospheric pressure and the temperature is the reflux temperature of xylene are. ■ 26. Process according to Claim 25, characterized in that the hydrochloric acid is in an approximately 10 to 75 percent excess over that for the formation of the hydrochlorides of pyrimidine and. the required proportion of the base is present. 27 · The method according to claim 26, characterized in that Substances with a boiling point below the reflux temperature of xylene are continuously removed from the reaction medium removed. 28. Process according to claim 27, characterized in that R ¹ denotes an ethyl group and -τθ denotes a radical of the formula A ^ - 36 - 309834/1162 2308001 . ■ * (A ₁ ) represents. ? 9 · Poultry feed composition, contained as an admixture an anti-coccidic effective amount of a compound of the general formula I. cX " (D in which R ¹ is an alkyl or perfluoroalkyl group having 1 to 3 carbon atoms or a 1,1-Oifluoräthyl- or 2, PjiMPrifluorathylgruppe, X represents a chlorine or Broraion, b and c are integers such that the positive charge of b Mol des Nations duroh ο Mol of the anion X is neutralized, and -N ) a residue of one of the formulas A to G (A) N) ⁵ p (O) - 37 - 30983A / 1162 denotes, where R is a hydrogen atom or a methyl group and the dotted line indicates that the methyl group or a hydrogen atom is present with the proviso that at least one (X-M ethyl group is present, but not both of these groups are present. 30. Composition according to claim PQ, characterized in that that it contains a second coccidiostat, the Weight ratio of the compound of the general formula I to this second coccidiostat is 1: 1 to 1:10. 31 Composition according to Claim 30, characterized in that that the second coccidioate amprolium / ΐ- (4-amino-2- -propylpyrimidinyl - ^ - methyl ^ -picoliniumchlorid-hydrochloridy ' is.