Patent Application
20060217400
The present invention relates to triazolopyrimidines of the formula I
in which the index and the substituents are as defined below:
Moreover, the invention relates to processes and intermediates for preparing these compounds, to compositions comprising them and to their use for controlling phytopathogenic harmful fungi.
Triazolopyrimidines substituted in the 2-position are disclosed in EP-A 71 792, EP-A 141 317, WO 02/88126 and WO 02/88127. The compounds described in the publications mentioned are suitable for controlling harmful fungi.
However, in many cases their activity is unsatisfactory.
It is an object of the present invention to provide compounds having improve activity and/or a broader activity spectrum.
We have found that this object is achieved by the compounds defined at the outset. Furthermore, we have found processes and intermediates for their preparation, compositions comprising them and methods for controlling phytopathogenic harmful fungi using the compounds I.
The compounds of the formula I differ from those in the abovementioned publications by the substituents in the 5- and 7-positions on the triazolopyrimidine ring.
Compared to the known compounds, the compounds of the formula I have increased activity against phytopathogenic harmful fungi.
The compounds according to the invention can be obtained by different routes. Advantageously, they are obtained by reacting sulfones of the formula I′ under basic conditions with compounds of the formula II. Depending on the nature of the group R3, compounds II are either a) cyanides, hydroxides, alkoxides or amines. In these cases, the cation M in formula II is usually an ammonium, tetraalkylammonium, alkali metal or alkaline earth metal ion. In case b), where R3 is alkyl or, in particular, fluoroalkyl, M is a metal ion of valency Y, such as, for example, B, Si, Zn, Mg or Sn.
In case a), the reaction is usually carried out at temperatures from −20° C. to 120° C., preferably of from 0° C. to 25° C., in an inert organic solvent in the presence of a base. [cf. Heteroat. Chem. p. 313 (2000)].
Suitable solvents are aliphatic or aromatic hydrocarbons, such as benzene, toluene, o-, m- and p-xylene, halogenated hydrocarbons, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, ketones, alcohols and also dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferably dimethyl sulfoxide, dioxane and benzene. It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, moreover organic bases, for example tertiary amines, and also bicyclic amines. Particular preference is given to sodium hydride. The bases are generally employed in catalytic amounts; however, they can also be employed in equimolar amounts, in excess or, if appropriate, as solvents.
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of II, based on I′.
The preferred thiols of the formula I″ a can also be obtained from the sulfones I′. The reaction is carried out similarly as described above using an alkali metal sulfide or alkaline earth metal sulfide or alkali metal hydrogen sulfide or alkaline earth metal hydrogen sulfide or using hydrogen sulfide in the presence of bases. Sodium sulfide and sodium hydrogen sulfide have been found to be particularly suitable for the reaction. The free SH compounds can be obtained from the thiolate salts using acid.
In case b), the reaction can be carried out, for example, analogously to the following methods: J. Chem. Soc., Perkin Trans. 1, 1187 (1994), ibid. 2345 (1996); WO-A 99/41255; Aust. J. Chem., 43 (1990), 733; J. Org. Chem., 43 (1978), 358; J. Chem. Soc., Chem. Commun. 866 (1979); Tetrahedron Lett., 34 (1993), 8267; ibid. 33 (1992), 413. In certain cases, it may be advantageous to carry out the reaction with Pd or Ni catalysis.
Sulfones of the formula I′ are preferably obtained by oxidizing the corresponding thio compounds I″. In formula I″, the variables are as defined under formula I. These compounds are prepared under conditions disclosed in WO 02/88127. In particular hydrogen peroxide and peracids of organic carboxylic acids have been found to be suitable oxidizing agents. However, the oxidation can also be carried out using, for example, selenium dioxide.
Compounds of the formula I in which R3 is C1-C8-alkyl, C1-C4-haloalkyl, SH or C1-C6-alkylthio can advantageously be obtained by the following synthesis route:
This reaction is usually carried out at 80° C.-250° C., preferably 120° C.-180° C., without solvent or in an inert organic solvent in the presence of a base [cf. EP-A 770 615] or in the presence of acetic acid under the conditions known from Adv. Het. Chem. 57 (1993), 81ff.
Suitable solvents are aliphatic hydrocarbons, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenated hydrocarbons, ethers, nitriles, ketones, alcohols, and also N-methylpyrrolidone, dimethyl sulfoxide, dimethylformamide and dimethylacetamide. The reaction is particularly preferably carried out without solvent or in chlorobenzene, xylene, dimethyl sulfoxide, N-methylpyrrolidone. It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as 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 and also alkali metal bicarbonates, organometallic compounds, in particular alkali metal alkyls, alkylmagnesium halides and also alkali metal and alkaline earth metal alkoxides and dimethoxymagnesium, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine and N-methylpiperidine, N-methylmorpholine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to tertiary amines, such as diisopropylethylamine, tributylamine, N-methylmorpholine or N-methylpiperidine.
The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.
The starting materials are generally reaction with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of the base and the diketone IV, based on III.
The aminotriazoles of the formula III are disclosed, for example, in EP-A 71 792, EP-A 141 317, WO 02/088126 and WO 02/088127. 3-Methylthio-5-aminotriazole is also commercially available. The dicarbonyl compounds of the formula IV are disclosed in the literature or can be prepared by analogous processes (J. Am. Chem. Soc. 122 (2000), 1360; Org. Lett. 2 (2000), 1045; Synthetic Commun. 17 (1987), 393; Bull. Soc. Chim. Fr. 3 (1987), 438; Tetrahedron Lett. 30 (1989), 1373; J. Med. Chem. 35 (1992), 931; Tetrahedron 48 (1992), 6909; J. Org. Chem. 44 (1979), 4021.
A particularly interesting embodiment of the abovementioned process starts from triazoles of the formula IIIa
in which R is hydrogen, C1-C6-alkyl or unsubstituted or substituted phenyl, which are reacted with dicarbonyl compounds of the formula IV
in which n, L, R1 and R2 are as defined in claim 1, to give triazolopyrimidine sulfides of the formula I″
followed, if appropriate, by oxidation of I″ to sulfones of the formula I′. If appropriate, as discussed above, the sulfonyl radical can also be exchanged for other radicals R3.
The compounds of the formula I according to the invention in which R3 is SH can be prepared by reacting a 3-thio-5-aminotriazole of the formula III′ in which Π is hydrogen or a protective group which can be removed under acidic or, preferably, under basic conditions, such as methyl, unsubstituted or substituted phenyl, benzyl, in particular p-acetoxybenzyl [cf. Greene, Protective Groups in Organic Chemistry, J. Wiley & Sons, pp. 195-217 (1981); J. Org. Chem. 43 (1978), 1197] using appropriately substituted phenylmalonates of the formula IV
The condensation can be carried out analogously to the process described above.
3-Thio-5-aminotriazoles of the formula II are known, and some of them are commercially available. The introduction of the protective group Π into compound III′ and the removal of the protective group Π from the intermediate I# can be carried out analogously to the processes described in Greene, Protective Groups in Organic Chemistry, J. Wiley & Sons, 195-217 (1981).
A further possibility of preparing the compounds I is shown in the scheme below:
Starting with the keto esters V, the 5-alkyl-7-hydroxy-6-phenyltriazolopyrimidines VI are obtained. In formula V, R2 is C1-C4-alkyl or C1-C4-haloalkyl. Using the easily obtainable 2-phenylacetoacetates (V where R2═CH3), the 5-methyl-7-hydroxy-6-phenyltriazolopyrimidines are obtained [cf. Chem. Pharm. Bull. 9 (1961), 801]. The preparation of the starting materials V is advantageously carried out under the conditions described in EP-A 10 02 788].
The 5-alkyl-7-hydroxy-6-phenyltriazolopyrimidines obtained in this way are reacted with halogenating agents to give 7-halotriazolopyrimidines. Preference is given to using chlorinating or brominating agents such as phosphorus oxybromide, phosphorus oxychloride, thionyl chloride, thionyl bromide or sulfuryl chloride. The reaction can be carried out in the absence or in the presence of a solvent. Customary reaction temperatures are 0-150° C. or, preferably, 80-125° C. [cf. EP-A 770 615].
Using organometallic B, Zn, Mg or Sn compounds, the appropriate radical R2 can be introduced into the 7-position of the 5-alkyl-7-halo-6-phenyltriazolopyrimidines obtained in this way. In some cases, it may be advantageous to carry out the reaction under Pd or Ni catalysis. The reaction can be carried out, for example, analogously to the following methods: J. Chem. Soc., Perkin Trans. 1, 1187 (1994), ibid. 2345 (1996); WO-A 99/41255; Aust. J. Chem. 43 (1990), 733; J. Org. Chem. 43 (1978), 358; J. Chem. Soc., Chem. Commun. 866 (1979); Tetrahedron Lett. 34 (1993), 8267; ibid. 33 (1992), 413.
The compounds of the formula I according to the invention can also be obtained by reacting 5-halotriazolopyrimidines of the formula VII with substituted malonic esters of the formula VIII in which Rx is C1-C4-alkyl, allyl, phenyl or benzyl, followed by hydrolysis of the resulting ester IX and decarboxylation of the carboxylic acid IXa.
In formula VII, X is halogen, in particular chlorine or bromine. The compounds VII are known from the publications cited at the outset. In formula I′″, n, R and R1 are as defined under formula I and and RA is hydrogen or C1-C3-alkyl which may be substituted by halogen, cyano, nitro or C1-C2-alkoxy.
In a preferred embodiment of the process according to the invention, RA is hydrogen or methyl, in particular hydrogen.
The starting materials VIII are known from the literature [J. Am. Chem. Soc. 64 (1942), 2714; J. Org. Chem. 39 (1974), 2172; Helv. Chim. Acta 61 (1978), 1565], or they can be prepared according to the literature cited.
The subsequent cleavage of the ester is carried out under the generally customary conditions [cf.: Greene & Wuts, Protective Groups in Organic Synthesis, Wiley (1991), p. 224 ff: Cleavage of alkyl esters under Pd catalysis (p. 248); hydrogenolysis of benzyl esters (p. 251); cleavage of methyl or ethyl esters in the presence of lithium salts, such as LiI (p. 232), LiBr or LiCl; or under acidic or alkaline conditions]. Depending on the structural elements RA, Rn and R1, alkaline or acidic hydrolysis of the compounds IX may be advantageous. Complete or partial decarboxylation to I′″ may already occur under the conditions of the ester hydrolysis.
The decarboxylation is usually carried out at 20° C.-180° C., preferably 50° C.-120° C., in an inert solvent, if appropriate in the presence of an acid.
Suitable acids are hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, p-toluenesulfonic acid. Suitable solvents are water, aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and also dimethyl sulfoxide, dimethylformamide and dimethylacetamide; with particular preference, the reaction is carried out in hydrochloric acid or acetic acid. It is also possible to use mixtures of the solvents mentioned.
A further route to the compounds of the formula I is described in the sections below:
Starting with 3-thiomethyl-5-aminotriazole of the formula IIIa, the dihydroxytriazolopyrimidines XI are prepared using appropriately substituted phenylmalonates of the formula X in which R is alkyl, preferably C1-C6-alkyl, in particular methyl or ethyl. Analogously, starting with 3-alkyl-5-amino-substituted triazoles, it is possible to prepare the corresponding 2-alkyl-substituted dihydroxytriazolopyrimidines.
This reaction is usually carried out at 80° C.-250° C., preferably 120° C.-180° C., in the absence of a solvent or in an inert organic solvent in the presence of a base [cf. EP-A 770 615] or in the presence of acetic acid under the conditions known from Adv. Het. Chem. 57 (1993), 81ff.
Suitable solvents are aliphatic hydrocarbons, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenated hydrocarbons, ethers, nitriles, ketones, alcohols, and also N-methylpyrrolidone, dimethyl sulfoxide, dimethylformamide and dimethylacetamide. With particular preference, the reaction is carried out in the absence of a solvent or in chlorobenzene, xylene, dimethyl sulfoxide, N-methylpyrrolidone. It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in particular, organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, tributylamine and N-methylpiperidine, N-methylmorpholine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to tertiary amines such as diisopropylethylamine, tributylamine, N-methylmorpholine or N-methylpiperidine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent.
The starting materials are generally reacted with one another in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of the base and the malonate XV, based on the thiazole XIV.
3-Thiomethyl-5-aminotriazole of the formula IIIa is commercially available. Phenylmalonates of the formula X are advantageously obtained by reacting appropriately substituted bromobenzenes with dialkyl malonates under Cu(I) catalysis [cf. Chemistry Letters (1981), 367-370; EP-A 10 02 788].
The dihydroxytriazolopyrimidines of the formula XI are converted into the dihalopyrimidines of the formula XII using the conditions disclosed in WO 94/20502. The halogenating agent used is advantageously a chlorinating agent or a brominating agent, such as phosphorus oxybromide or phosphorus oxychloride, if appropriate in the presence of a solvent.
This reaction is usually carried out at 0° C.-150° C., preferably at 80° C.-120° C. [cf. EP-A 770 615].
Starting with the dihalopyrimidines of the formula XII, the substituent R1 can be introduced into the 7-position by coupling with organometallic reagents of the formula II, giving the compounds of the formula VII. In one embodiment of this process, the reaction is carried out under transition metal catalysis, such as Ni or Pd catalysis.
In formula II, M is a metal ion of valency Y, such as, for example, B, Zn, Mg or Sn. This reaction can be carried out, for example, analogously to the following methods: J. Chem. Soc., Perkin Trans. 1, 1187 (1994), ibid. 2345 (1996); WO-A 99/41255; Aust. J. Chem. 43 (1990), 733; J. Org. Chem. 43 (1978), 358; J. Chem. Soc., Chem. Commun. 866 (1979); Tetrahedron Lett. 34 (1993), 8267; ibid. 33 (1992), 413.
The reaction mixtures are worked up in a customary manner, for example by mixing with water, phase separation and, if required, chromatographic purification of the crude products. Some of the intermediates and end products are obtained in the form of colorless or slightly brownish, viscous oils, which are purified or freed from volatile components under reduced pressure and at moderately elevated temperature. If the intermediates and end products are obtained as solids, purification can also be carried out by recrystallization or digestion.
If individual compounds I cannot be obtained by the routes described above, they can be prepared by derivatization of other compounds I.
If the synthesis yields isomer mixtures, a separation is generally not necessarily required since in some cases the individual isomers can be converted into one another during the preparation for use or upon use (for example under the action of light, acids or bases). Similar conversions may also occur after use, for example in the case of the treatment of plants in the treated plant or in the harmful fungus to be controlled.
In the definitions of the symbols given in the above formulae, collective terms were used which generally represent the following substituents:
Halogen: fluorine, chlorine, bromine and iodine;
Alkyl: saturated, straight-chain or branched hydrocarbon radicals having 1 to 4, 6, 8 or 10 carbon atoms, for example C1-C6-alkyl such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 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-methylpropyl;
Haloalkyl: straight-chain or branched alkyl groups having 1 to 10 carbon atoms (as mentioned above), where all or some of the hydrogen atoms in these groups may be replaced by halogen atoms as mentioned above, for example C1-C2-haloalkyl such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl or 1,1,1-trifluoro-2-propyl;
Alkenyl: unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 4, 6, 8 or 10 carbon atoms and a double bond in any position, for example C2-C6-alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl;
Alkadienyl: unsaturated, straight-chain or branched hydrocarbon radicals having 4, 6, 8 or 10 carbon atoms and two double bonds in any position;
Haloalkenyl: unsaturated, straight-chain or branched hydrocarbon radicals having 2 to 10 carbon atoms and a double bond in any position (as mentioned above), where all or some of the hydrogen atoms in these groups may be replaced by halogen atoms as mentioned above, in particular by fluorine, chlorine and bromine;
Alkynyl: straight-chain or branched hydrocarbon groups having 2 to 4, 6, 8 or 10 carbon atoms and a triple bond in any position, for example C2-C6-alkynyl such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and 1-ethyl-1-methyl-2-propynyl;
Cycloalkyl: mono- or bicyclic, saturated hydrocarbon groups having 3 to 6 or 8 carbon ring members, for example C3-C8-cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl;
five- to ten-membered saturated, partially unsaturated or aromatic heterocycle which contains one to four heteroatoms from the group consisting of O, N and S:
The scope of the present invention includes the (R)- and (S)-isomers and the racemates of compounds of the formula I having chiral centers.
Preferred embodiments of the invention are described below.
Preference is given to triazolopyrimidines of the formula I
in which the index and the substituents are as defined below:
Triazolopyrimidines as claimed in claim 1 in which the index and the substituents are as defined below:
Triazolopyrimidines in which the index and the substituents are as defined below:
The particularly preferred embodiments of the intermediates with respect to the variables correspond to those of the radicals Ln, R1, R2 and R3 of the formula I.
With a view to the intended use of the triazolopyrimidines of the formula I, the following meanings of the substituents are particularly preferred, in each case on their own or in combination:
Preference is given to compounds I in which R1 is C3-C8-alkyl, C3-C8-alkenyl, C3-C8-alkynyl, C3-C6-cycloalkyl or C5-C6-cycloalkenyl.
Especially preferred are compounds I in which R1 is C1-C6-alkyl or C1-C6-haloalkyl.
In addition, preference is given to compounds I in which R1 is C2-C10-alkenyl or C2-C10-alkynyl.
Likewise, preference is given to compounds I in which R1 is a 5- or 6-membered saturated or aromatic heterocycle.
Moreover, particular preference is given to compounds I in which R1 is C3-C6-cycloalkyl or C5-C6-cycloalkenyl, which radicals may be substituted by C1-C4-alkyl.
Particular preference is given to compounds I in which Ra is halogen, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C1-C6-alkoximino, C2-C6-alkenyloximino, C2-C6-alkynyloximino, C3-C6-cycloalkyl or C5-C6-cycloalkenyl, where the aliphatic or alicyclic groups for their part may be partially or fully halogenated or may carry one to three groups Rb.
Especially preferred are compounds I in which Rb is halogen, cyano, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl or C1-C6-alkoxy.
Particular preference is also given to compounds I in which R2 is C1-C4-alkyl which may be substituted by halogen.
Likewise, particular preference is given to compounds I in which R2 is methyl.
In addition, particular preference is given to compounds I in which R2 is halomethyl.
If R1 and/or R2 contain haloalkyl or haloalkenyl groups having a center of chirality, preference is given to the (S)-isomers.
If R1 and/or R2 contain alkyl, alkenyl or alkynyl groups having a center of chirality, preference is given to the (R)-isomer.
Preference is given to compounds I in which R3 is cyano, C5-C8-alkyl, C1-C4-haloalkyl, hydroxy, C1-C8-alkoxy, C3-C8-alkenyl, C3-C8-alkenyloxy, C1-C8-haloalkoxy, C3-C8-haloalkenyloxy, C3-C8-cycloalkyl, N(A′)A, N(A′)-C(═O)-A or S(═O)m-A.
Preference is also given to compounds I in which R3 is halogen and in particular fluorine or chlorine.
Furthermore, preference is given to compound I in which R3 C1-C4-alkyl.
Moreover, preference is given to compounds I in which R3 is N(A′)A, N(A′)-C(═O)-A or S(═O)m-A.
Especially preferred are compounds I in which R3 is S(═O)m-A.
Especially preferred are compounds I in which R3 is SH.
Preference is given to compounds I in which at least one group L is positioned ortho to the point of attachment with the triazolopyrimidine skeleton; in particular to those compounds in which n has the value 1, 2 or 3.
Preference is given to compounds I in which Ln is halogen, methyl, cyano, ethyl, C1-haloalkyl, methoxy, —C(═O)-A, —C(═O)—O-A, —C(═O)—N(A′)A, C(A′)(═N-OA), N(A′)-C(═O)-A or S(═O)m-A, where m is 0, 1 or 2 and A, A′ independently of one another are hydrogen or C1-C4-alkyl.
Moreover, particular preference is given to compounds I in which the phenyl group substituted by Ln is the group B
in which # denotes the point of attachment with the triazolopyrimidine skeleton and
With a view to their use, special preference is given to the compounds I compiled in the tables below. Moreover, the groups mentioned in the tables for a substituent are themselves, independently of the combination in which they are mentioned, a particularly preferred embodiment of the substituents in question.
Table 1
Compounds of the formula IA in which Ln is 2-fluoro-6-chloro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 2
Compounds of the formula IA in which Ln is 2,6-difluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 3
Compounds of the formula IA in which Ln is 2,6-dichloro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 4
Compounds of the formula IA in which Ln is 2-fluoro-6-methyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 5
Compounds of the formula IA in which Ln is 2,4,6-trifluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 6
Compounds of the formula IA in which Ln is 2,6-difluoro-4-SH, R3 is SH and R1 for each compound corresponds to one row of table A
Table 7
Compounds of the formula IA in which Ln is pentafluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 8
Compounds of the formula IA in which Ln is 2-methyl-4-fluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 9
Compounds of the formula IA in which Ln is 2-trifluoromethyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 10
Compounds of the formula IA in which Ln is 2-SH-6-fluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 11
Compounds of the formula IA in which Ln is 2-chloro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 12
Compounds of the formula IA in which Ln is 2-fluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 13
Compounds of the formula IA in which Ln is 2,4-difluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 14
Compounds of the formula IA in which Ln is 2-fluoro-4-chloro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 15
Compounds of the formula IA in which Ln is 2-chloro-4-fluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 16
Compounds of the formula IA in which Ln is 2,3-difluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 17
Compounds of the formula IA in which Ln is 2,5-difluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 18
Compounds of the formula IA in which Ln is 2,3,4-trifluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 19
Compounds of the formula IA in which Ln is 2-methyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 20
Compounds of the formula IA in which Ln is 2,4-dimethyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 21
Compounds of the formula IA in which Ln is 2-methyl-4-chloro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 22
Compounds of the formula IA in which Ln is 2-fluoro-4-methyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 23
Compounds of the formula IA in which Ln is 2,6-dimethyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 24
Compounds of the formula IA in which Ln is 2,4,6-trimethyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 25
Compounds of the formula IA in which Ln is 2,6-difluoro-4-cyano, R3 is SH and R1 for each compound corresponds to one row of table A
Table 26
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 27
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methoxycarbonyl, R3 is SH and R1 for each compound corresponds to one row of table A
Table 28
Compounds of the formula IA in which Ln is 2-trifluoromethyl-4-fluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 29
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-fluoro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 30
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-chloro, R3 is SH and R1 for each compound corresponds to one row of table A
Table 31
Compounds of the formula IA in which Ln is 2-fluoro-6-chloro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 32
Compounds of the formula IA in which Ln is 2,6-difluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 33
Compounds of the formula IA in which Ln is 2,6-dichloro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 34
Compounds of the formula IA in which Ln is 2-fluoro-6-methyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 35
Compounds of the formula IA in which Ln is 2,4,6-trifluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 36
Compounds of the formula IA in which Ln is 2,6-difluoro-4-SH, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 37
Compounds of the formula IA in which Ln is pentafluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 38
Compounds of the formula IA in which Ln is 2-methyl-4-fluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 39
Compounds of the formula IA in which Ln is 2-trifluoromethyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 40
Compounds of the formula IA in which Ln is 2-methylthio-6-fluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 41
Compounds of the formula IA in which Ln is 2-chloro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 42
Compounds of the formula IA in which Ln is 2-fluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 43
Compounds of the formula IA in which Ln is 2,4-difluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 44
Compounds of the formula IA in which Ln is 2-fluoro-4-chloro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 45
Compounds of the formula IA in which Ln is 2-chloro-4-fluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 46
Compounds of the formula IA in which Ln is 2,3-difluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 47
Compounds of the formula IA in which Ln is 2,5-difluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 48
Compounds of the formula IA in which Ln is 2,3,4-trifluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 49
Compounds of the formula IA in which Ln is 2-methyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 50
Compounds of the formula IA in which Ln is 2,4-dimethyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 51
Compounds of the formula IA in which Ln is 2-methyl-4-chloro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 52
Compounds of the formula IA in which Ln is 2-fluoro-4-methyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 53
Compounds of the formula IA in which Ln is 2,6-dimethyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 54
Compounds of the formula IA in which Ln is 2,4,6-trimethyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 55
Compounds of the formula IA in which Ln is 2,6-difluoro-4-cyano, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 56
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 57
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methoxycarbonyl, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 58
Compounds of the formula IA in which Ln is 2-trifluoromethyl-4-fluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 59
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-fluoro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 60
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-chloro, R3 is methylthio and R1 for each compound corresponds to one row of table A
Table 61
Compounds of the formula IA in which Ln is 2-fluoro-6-chloro, R3 is methylsulfinyl (CH3—S(═O)—), and R1 for each compound corresponds to one row of table A
Table 62
Compounds of the formula IA in which Ln is 2,6-difluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 63
Compounds of the formula IA in which Ln is 2,6-dichloro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 64
Compounds of the formula IA in which Ln is 2-fluoro-6-methyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 65
Compounds of the formula IA in which Ln is 2,4,6-trifluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 66
Compounds of the formula IA in which Ln is 2,6-difluoro-4-SH, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 67
Compounds of the formula IA in which Ln is pentafluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 68
Compounds of the formula IA in which Ln is 2-methyl-4-fluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 69
Compounds of the formula IA in which Ln is 2-trifluoromethyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 70
Compounds of the formula IA in which Ln is 2-methylsulfenyl-6-fluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 71
Compounds of the formula IA in which Ln is 2-chloro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 72
Compounds of the formula IA in which Ln is 2-fluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 73
Compounds of the formula IA in which Ln is 2,4-difluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 74
Compounds of the formula IA in which Ln is 2-fluoro-4-chloro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 75
Compounds of the formula IA in which Ln is 2-chloro-4-fluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 76
Compounds of the formula IA in which Ln is 2,3-difluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 77
Compounds of the formula IA in which Ln is 2,5-difluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 78
Compounds of the formula IA in which Ln is 2,3,4-trifluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 79
Compounds of the formula IA in which Ln is 2-methyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 80
Compounds of the formula IA in which Ln is 2,4-dimethyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 81
Compounds of the formula IA in which Ln is 2-methyl-4-chloro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 82
Compounds of the formula IA in which Ln is 2-fluoro-4-methyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 83
Compounds of the formula IA in which Ln is 2,6-dimethyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 84
Compounds of the formula IA in which Ln is 2,4,6-trimethyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 85
Compounds of the formula IA in which Ln is 2,6-difluoro-4-cyano, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 86
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 87
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methoxycarbonyl, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 88
Compounds of the formula IA in which Ln is 2-trifluoromethyl-4-fluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 89
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-fluoro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 90
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-chloro, R3 is methylsulfinyl, and R1 for each compound corresponds to one row of table A
Table 91
Compounds of the formula IA in which Ln is 2-fluoro-6-chloro, R3 is methylsulfonyl (CH3—S(═O)2—), and R1 for each compound corresponds to one row of table A
Table 92
Compounds of the formula IA in which Ln is 2,6-difluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 93
Compounds of the formula IA in which Ln is 2,6-dichloro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 94
Compounds of the formula IA in which Ln is 2-fluoro-6-methyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 95
Compounds of the formula IA in which Ln is 2,4,6-trifluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 96
Compounds of the formula IA in which Ln is 2,6-difluoro-4-SH, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 97
Compounds of the formula IA in which Ln is pentafluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 98
Compounds of the formula IA in which Ln is 2-methyl-4-fluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 99
Compounds of the formula IA in which Ln is 2-trifluoromethyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 100
Compounds of the formula IA in which Ln is 2-methylsulfenyl-6-fluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 101
Compounds of the formula IA in which Ln is 2-chloro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 102
Compounds of the formula IA in which Ln is 2-fluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 103
Compounds of the formula IA in which Ln is 2,4-difluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 104
Compounds of the formula IA in which Ln is 2-fluoro-4-chloro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 105
Compounds of the formula IA in which Ln is 2-chloro-4-fluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 106
Compounds of the formula IA in which Ln is 2,3-difluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 107
Compounds of the formula IA in which Ln is 2,5-difluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 108
Compounds of the formula IA in which Ln is 2,3,4-trifluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 109
Compounds of the formula IA in which Ln is 2-methyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 110
Compounds of the formula IA in which Ln is 2,4-dimethyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 111
Compounds of the formula IA in which Ln is 2-methyl-4-chloro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 112
Compounds of the formula IA in which Ln is 2-fluoro-4-methyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 113
Compounds of the formula IA in which Ln is 2,6-dimethyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 114
Compounds of the formula IA in which Ln is 2,4,6-trimethyl, R3 is ethylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 115
Compounds of the formula IA in which Ln is 2,6-difluoro-4-cyano, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 116
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 117
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methoxycarbonyl, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 118
Compounds of the formula IA in which Ln is 2-trifluoromethyl-4-fluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 119
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-fluoro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 120
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-chloro, R3 is methylsulfonyl, and R1 for each compound corresponds to one row of table A
Table 121
Compounds of the formula IA in which Ln is 2-fluoro-6-chloro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 122
Compounds of the formula IA in which Ln is 2,6-difluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 123
Compounds of the formula IA in which Ln is 2,6-dichloro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 124
Compounds of the formula IA in which Ln is 2-fluoro-6-methyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 125
Compounds of the formula IA in which Ln is 2,4,6-trifluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 126
Compounds of the formula IA in which Ln is 2,6-difluoro-4-SH, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 127
Compounds of the formula IA in which Ln is pentafluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 128
Compounds of the formula IA in which Ln is 2-methyl-4-fluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 129
Compounds of the formula IA in which Ln is 2-trifluoromethyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 130
Compounds of the formula IA in which Ln is 2-methylthio-6-fluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 131
Compounds of the formula IA in which Ln is 2-chloro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 132
Compounds of the formula IA in which Ln is 2-fluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 133
Compounds of the formula IA in which Ln is 2,4-difluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 134
Compounds of the formula IA in which Ln is 2-fluoro-4-chloro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 135
Compounds of the formula IA in which Ln is 2-chloro-4-fluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 136
Compounds of the formula IA in which Ln is 2,3-difluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 137
Compounds of the formula IA in which Ln is 2,5-difluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 138
Compounds of the formula IA in which Ln is 2,3,4-trifluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 139
Compounds of the formula IA in which Ln is 2-methyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 140
Compounds of the formula IA in which Ln is 2,4-dimethyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 141
Compounds of the formula IA in which Ln is 2-methyl-4-chloro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 142
Compounds of the formula IA in which Ln is 2-fluoro-4-methyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 143
Compounds of the formula IA in which Ln is 2,6-dimethyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 144
Compounds of the formula IA in which Ln is 2,4,6-trimethyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 145
Compounds of the formula IA in which Ln is 2,6-difluoro-4-cyano, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 146
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 147
Compounds of the formula IA in which Ln is 2,6-difluoro-4-methoxycarbonyl, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 148
Compounds of the formula IA in which Ln is 2-trifluoromethyl-4-fluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 149
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-fluoro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
Table 150
Compounds of the formula IA in which Ln is 2-trifluoromethyl-5-chloro, R3 is trifluoromethyl, and R1 for each compound corresponds to one row of table A
The compounds I are suitable as fungicides. They have excellent activity against a broad spectrum of phytopathogenic fungi, in particular from the class of the Ascomycetes, Deuteromycetes, Oomycetes and Basidiomycetes. Some of them act systemically and can be employed in crop protection as foliar- and soil-acting fungicides.
They are especially important for controlling a large number of fungi in a variety of crop plants such as wheat, rye, barley, oats, rice, maize, grass, bananas, cotton, soybean, coffee, sugar cane, grapevines, fruit species, ornamentals and vegetable species such as cucumbers, beans, tomatoes, potatoes and cucurbits, and also in the seeds of these plants.
Specifically, they are suitable for controlling the following plant diseases:
The compounds I are also suitable for controlling harmful fungi such as Paecilomyces variotii in the protection of materials (for example wood, paper, paint dispersions, fibers or tissues) and in the protection of stored products.
The compounds I are employed by treating the fungi or the plants, seeds, materials or the soil to be protected against fungal attack with a fungicidally effective amount of the active compounds. The application can be carried out before or after the infection of the materials, plants or seeds by the fungi.
The fungicidal compositions generally comprise from 0.1 to 95, preferably from 0.5 to 90, % by weight of active compound.
For use in crop protection, the application rates are, depending on the kind of effect desired, from 0.01 to 2.0 kg of active compound per ha.
The treatment of seeds generally requires active compound rates of from 0.001 to 0.1 g, preferably from 0.01 to 0.05 g, per kilogram of seed.
For use in the protection of materials or stored products, the active compound application rate depends on the kind of application area and effect desired. Customary application rates in the protection of materials are, for example, from 0.001 g to 2 kg, preferably from 0.005 g to 1 kg, of active compound per cubic meter of treated material.
The compounds I can be converted into the customary formulations, e.g. solutions, emulsions, suspensions, dusts, powders, pastes and granules. The use form depends on the particular intended use; in any case, it should ensure fine and uniform distribution of the compound according to the invention.
The formulations are prepared in a known manner, e.g. by extending the active compound with solvents and/or carriers, if desired using emulsifiers and dispersants. Solvents/auxiliaries which are suitable are essentially:
Suitable surfactants which are used are the alkali metal, alkaline earth metal and ammonium salts of lignosulfonic acid, naphthalenesulfonic acid, phenolsulfonic acid, and dibutylnaphthalenesulfonic acid, alkylarylsulfonates, alkyl sulfates, alkylsulfonates, fatty alcohol sulfates, fatty acids and sulfated fatty alcohol glycol ethers, furthermore condensation products of sulfonated naphthalene and naphthalene derivatives with formaldehyde, condensation products of naphthalene or of naphthalenesulfonic acid with phenol and formaldehyde, polyoxyethylene octylphenol ethers, ethoxylated isooctylphenol, octylphenol, nonylphenol, alkylphenol polyglycol ethers, tributylphenyl polyglycol ethers, tristerylphenyl polyglycol ethers, alkylaryl polyether alcohols, alcohol and fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol ether acetal, sorbitol esters, lignosulfite waste liquors and methylcellulose are suitable.
Suitable for preparing directly sprayable solutions, emulsions, pastes or oil dispersions are petroleum fractions having medium to high boiling points, such as kerosene or diesel oil, furthermore coal-tar oils and oils of plant or animal origin, aliphatic, cyclic and aromatic hydrocarbons, for example toluene, xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes or derivatives thereof, methanol, ethanol, propanol, butanol, cyclohexanol, cyclohexanone, isophorone, strongly polar solvents, for example dimethyl sulfoxide, N-methylpyrrolidone, or water.
Powders, compositions for broadcasting and dusts can be prepared by mixing or cogrinding of the active substances with a solid carrier.
Granules, for example coated granules, impregnated granules and homogenous granules, can be prepared by binding the active compounds to solid carriers. Solid carriers are, for example, mineral earths, such as silica gels, silicates, talc, kaolin, attaclay, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground synthetic materials, fertilizers, such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas and products of plant origin, such as cereal meal, tree bark meal, wood meal and nutshell meal, cellulose powders and other solid carriers.
The formulations generally comprise from 0.01 to 95% by weight, preferably from 0.1 to 90% by weight, of the active compound. The active compounds are employed in a purity of from 90% to 100%, preferably from 95% to 100% (according to the NMR spectrum).
The following are examples of formulations:
1. Products for Dilution with Water
The active compounds can be applied as such, in the form of their formulations or in the application forms prepared therefrom, for example in the form of directly sprayable solutions, powders, suspensions or dispersions, emulsions, oil dispersions, pastes, dusts, compositions for broadcasting, or granules, by spraying, atomizing, dusting, broadcasting or watering. The application forms depend entirely on the intended uses; in any case, they should ensure very fine dispersion of the active compounds according to the invention.
Aqueous use forms can be prepared from emulsion concentrates, pastes or wettable powders (spray powders, oil dispersions) by addition of water. To prepare emulsions, pastes or oil dispersions, the substances can be homogenized in water as such or dissolved in an oil or solvent, by means of wetting agents, tackifiers, dispersants or emulsifiers. However, concentrates comprising active compound, wetting agent, tackifier, dispersant or emulsifier and possibly solvent or oil which are suitable for dilution with water can also be prepared.
The active compound concentrations in the ready-to-use preparations can be varied over a relatively wide range. In general, they are from 0.0001 to 10%, preferably from 0.01 to 1%.
It is also possible to use the active compounds with a high degree of success in the ultra-low-volume method (ULV), it being possible to apply formulations comprising more than 95% by weight of active compound or even the active compound without additives.
Oils of various types, wetting agents, adjuvants, herbicides, fungicides, other pesticides and bactericides can be added to the active compounds, if desired even immediately prior to application (tank mix). These agents can be added to the compositions according to the invention in a weight ratio of 1:10 to 10:1.
The compositions according to the invention in the use form as fungicides may also be present in combination with other active compounds, for example with herbicides, insecticides, growth regulators, fungicides or else with fertilizers. In many cases, mixing of the compounds I, or of the compositions comprising them, in the use form as fungicides with other fungicides results in a broader fungicidal spectrum of activity.
The following list of fungicides, with which the compounds according to the invention can be used in combination, is intended to illustrate the possible combinations, but not to impose any limitation:
A mixture of 45 g (0.171 mol) of dimethyl (2,4,6-trifluorophenyl)malonate, 30 g (0.162 mol) of tributylamine and 20 g (0.108 mol) of 3-amino-5-methylthio-1,2,4-triazole was stirred at 160° C. for about 6 hours, and the methanol formed was distilled off.
The reaction mixture was then cooled to 80° C., and 100 ml of 20% strength aqueous sodium hydroxide solution were added. The aqueous phase was washed with methyl t-butyl ether, and the organic phase was discarded. The aqueous phase was then acidified with dilute hydrochloric acid and diluted with water, resulting in the precipitation of a lightly colored solid. The solid was stirred overnight, filtered off with suction, washed with water and methyl t-butyl ether and dried at 50° C. under reduced pressure.
This gave 45 g (92%) of compound 1.1. as a beige solid which was used for the next reaction without further purification.
A mixture of 45 g (0.137 mol) of 2-methylthio-5,7-dihydroxy-6-(2,4,6-trifluorophenyl)-1,2,4-triazolo[1,5a]pyrimidine (example 1.1) in 200 ml of phosphorus oxychloride was heated at reflux for about 8 hours.
Excess phosphorus oxychloride was then distilled off, and the residue was taken up in methylene chloride. The organic phase was poured into water and stirred vigorously. The organic phase was separated off, extracted with NaHCO3 solution and concentrated. The residue was then purified by column chromatography using cyclohexane/ethyl acetate mixtures. This gave 42 g (84%) of the title compound 1.2. as a lightly colored solid.
1H-NMR (CDCl3, δ in ppm): 6.9 (t, 2H); 2.75 (s, 3H)
At about 70° C. bath temperature, a solution of 31 g (0.2 mol) of 2-methylbutyl bromide in 50 ml of tetrahydrofuran was added dropwise to a suspension of 4.8 g (0.2 mol) of magnesium and a catalytic amount of iodine in 50 ml of tetrahydrofuran. The mixture was then stirred at this temperature for about 30 min and subsequently cooled to room temperature.
At 10-20° C., this Grignard solution was then added to a mixture of 46 g (0.2 mol) of zinc bromide in 200 ml of tetrahydrofuran. After about 30 min, the mixture was cooled to −10° C. and a mixture of 17.4 g (0.4 mol) of lithium chloride and 18 g (0.2 mol) of copper cyanide in 100 ml of tetrahydrofuran was added. The reaction mixture was then cooled to −40° C., and 36 g (0.1 mol) of 2-methylthio-5,7-dichloro-6-(2,4,6-trifluorophenyl)-1,2,4-triazolo [1,5a]pyrimidine (example 1.2.) in 50 ml of tetrahydrofuran was added. The reaction mixture was stirred at room temperature overnight and then diluted with methyl t-butyl ether and hydrolyzed using ammonium chloride solution.
The organic phase was then separated off, and the aqueous phase was extracted three times with methylene chloride. The combined organic phases were concentrated and the residue was, together with a 12.3 mmol batch which was carried out separately, purified by column chromatography. This gave 39.5 g (88%) of the title compound 1.3. as a lightly colored solid (m.p.=92-94° C.).
1H-NMR (CDCl3, δ in ppm): 6.9 (t, 2H); 3.1 (dd, 1H); 2.7 (dd, 1H); 2.7 (s, 3H); 2.05 (m, 1H); 1.25 (m, 1H); 1.15 (m, 1H); 0.8 (t, 3H); 0.75 (d, 3H)
A mixture of 39 g (95 mmol) of 2-methylthio-5-chloro-6-(2,4,6-trifluorophenyl)-7-(2-methylbutyl)-1,2,4-triazolo-[1,5a]pyrimidine (example 1.3) and 40 g (260 mmol) of sodium dimethylmalonate was stirred at a bath temperature of 75° C. for about 3 hours.
The reaction mixture was then cooled to room temperature and methyl t-butyl ether was added, resulting in the precipitation of a yellow solid. This yellow solid was stirred with a mixture of dilute hydrochloric acid and methyl t-butyl ether, resulting in decolorization. The organic phase was then separated off, dried over magnesium sulfate and concentrated. The residue crystallized and was triturated with diisopropyl ether/hexane. This gave 34 g (72%) of the title compound 2.1. as a lightly colored solid (m.p.=126-128° C.).
1H-NMR (CDCl3, δ in ppm): 6.9 (t, 2H); 4.7 (s, 1H); 3.75 (s, 3H); 3.7 (s, 3H); 3.0 (dd, 1H); 2.7 (s, 3H); 2.7 (dd, 1H); 2.05 (m, 1H); 1.25 (m, 1H); 1.1 (m, 1H); 0.8 (t, 3H); 0.7 (d, 3H)
34 g (68 mmol) of 2-methylthio-5-(dimethylmalon-2-yl)-6-(2,4,6-trifluorophenyl)-7-(2-methylbutyl)-1,2,4-triazolo[1,5a]pyrimidine (example 2.1) in 200 ml of concentrated hydrochloric acid were heated at 90° C. for about 4 hours. The reaction mixture was then diluted with water, and the aqueous phase was extracted with methyl t-butyl ether. The combined organic phases were washed with NaHCO3 solution and water, dried and concentrated. This gave 27 g (quantitative yield) of the title compound 2.2. as a viscous material which slowly crystallized (m.p.=67-69° C.).
1H-NMR (CDCl3, δ in ppm): 6.9 (t, 2H); 3.0 (dd, 1H); 2.75 (s, 3H); 2.7 (dd, 1H); 2.4 (s, 3H); 2.05 (m, 1H); 1.3 (m, 1H); 1.15 (m, 1H); 0.8 (t, 3H); 0.75 (d, 3H)
1.6 g (7.2 mmol) of 77% strength m-chloroperbenzoic acid were added to 1.99 g (5 mmol) of 2-methylthio-5-methyl-6-(2,4,6-trifluorophenyl)-7-(2-methylbutyl)-1,2,4-triazolo[1,5a]pyrimidine (example 2.2) in 20 ml of methylene chloride, and the mixture was stirred at room temperature for about 1 hour. Another 100 mg of 77% strength m-chloroperbenzoic acid were then added, and stirring was continued for about 1 hour.
The reaction mixture was then washed with dilute aqueous sodium hydroxide solution and water and concentrated. The residue was purified by column chromatography using cyclohexane/ethyl acetate mixtures.
0.5 g (24%) of the sulfone b and 1.1 g (56%) of the sulfoxide a were obtained in this order as a lightly colored solid and a light yellow oil, respectively.
Sulfone b: (I-3)
1H-NMR (CDCl3, δ in ppm): 6.9 (t, 2H); 3.45 (s, 3H); 3.05 (dd, 1H); 2.8 (dd, 1H); 2.5 (s, 3H); 2.05 (m, 1H); 1.25 (m, 1H); 1.1 (m, 1H); 0.8 (t, 3H); 0.75 (d, 2H)
Sulfoxide a: (I-4)
1H-NMR (CDCl3, δ in ppm): 6.95 (t, 2H); 3.2 (s, 3H); 3.1 (ddd, 1H); 2.85 (ddd, 1H); 2.5 (s, 3H); 2.05 (m, 1H); 1.25 (m, 1H); 1.15 (m, 1H); 0.75 (m, 6H)
0.8 g (1.94 mmol) of 2-methylsulfonyl-5-methyl-6-(2,4,6-trifluorophenyl)-7-(2-methylbutyl)-1,2,4-triazolo[1,5a]pyrimidine (procedure 3.b) and 2 g (7.5 mmol) of tetrabutylammonium cyanide in 20 ml of acetonitrile were heated at 50° C. for about 7 hours. The reaction mixture was then diluted with water and the aqueous phase was extracted three times with methyl t-butyl ether. The combined organic phases were concentrated and the residue was purified by MPLC on silica gel RP-18 using acetonitrile/water mixtures. This gave 0.5 g (72%) of the title compound 4. as a lightly colored solid (m.p.=113-115° C.).
1H-NMR (CDCl3, δ in ppm): 6.95 (t, 2H); 3.05 (dd, 1H); 2.8 (dd, 1H); 2.5 (s, 3H); 2.0 (m, 1H); 1.3 (m, 1H); 1.15 (m, 1H); 0.8 (t, 3H); 0.75 (d, 3H)
0.83 g (2 mmol) of 2-methylsulfonyl-5-methyl-6-(2,4,6-trifluorophenyl)-7-(2-methylbutyl)-1,2,4-triazolo[1,5a]pyrimidine (example 3.b) and 0.45 g of a 30% strength sodium methoxide solution in 10 ml of acetonitrile were heated at 60° C. for about 7 hours. The reaction mixture was then diluted with water and the aqueous phase was acidified and extracted three times with methyl t-butyl ether. The combined organic phases were concentrated and the residue was purified by MPLC on silica gel RP-18 using acetonitrile/water mixtures. This gave 0.6 g (82%) of the title compound 5. as a yellow oil.
1H-NMR (CDCl3, δ in ppm): 6.9 (t, 2H); 4.2 (s, 3H); 2.95 (dd, 1H); 2.65 (dd, 1H); 2.4 (s, 3H); 2.05 (m, 1H); 1.25 (m, 1H); 1.1 (m, 1H); 0.8 (t, 3H); 0.75 (d, 3H)
The active compounds were formulated separately as a stock solution comprising 0.25% by weight of active compound in acetone or DMSO. 1% by weight of the emulsifier Uniperol® EL (wetting agent having emulsifying and dispersing action based on ethoxylated alkylphenols) was added to this solution. The stock solutions of the active compounds were diluted with water to the stated concentration.
Bell pepper seedlings of the cultivar “Neusiedler Ideal Elite”, were, after 4-5 leaves were well developed, sprayed to runoff point with an aqueous suspension having the concentration of active compound stated below. The next day, the treated plants were inoculated with a spore suspension of Botrytis cinerea which contained 1.7×106 spores/ml in a 2% strength aqueous biomalt solution. The test plants were then placed in a climatized chamber at 22-24° C. and high atmospheric humidity. After 5 days, the extent of the fungal infection on the leaves could be determined visually in %.
In this test, the plants which had been treated with 250 ppm of compound I-2, I-11 or I-12 showed an infection of ≦40%, whereas the untreated (control) plants were 90% infected by the harmful fungus.
Leaves of potted plants of the cultivar “Golden Princess” were sprayed to runoff point with an aqueous suspension having the concentration of active compound stated below. The next day, the leaves were infected with an aqueous spore suspension of Alternaria solani in 2% biomalt solution having a density of 0.17×106 spore/ml. The plants were then placed in a water-vapor saturated chamber at temperatures between 20 and 22° C. After 5 days, the blight on the untreated, but infected control plants had developed to such an extent that the infection could be determined visually in %.
In this test, the plants which had been treated with 250 ppm of the compound I-11 were <10% infected, whereas the untreated (control) plants were 80% infected.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10261189.0 | Dec 2002 | DE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP03/14374 | 12/17/2003 | WO | 3/21/2006 |
