4-(3-aminobenzoyl)-5-cyclopropylisoxazoles effective as herbicides

专利摘要:

公开号:AU2009228599A1
申请号:U2009228599
申请日:2009-03-19
公开日:2009-10-01
发明作者:Hartmut Ahrens；Jan Dittgen；Dieter Feucht；Ines Heinemann；Martin Jeffrey Hills；Heinz Kehne；Stefan Lehr；Christopher Hugh Rosinger；Andreas Van Almsick
申请人:Bayer CropScience AG；
IPC主号:C07D261-08

专利说明:
WO 2009/118125 PCT/EP2009/002029 Description 4-(3-Aminobenzoyl)-5-cyclopropylisoxazoles effective as herbicides 5 The invention relates to the technical field of the herbicides, in particular to that of the herbicides for the selective control of broad-leafed leaves and grass weeds in crops of useful plants. 0 It has already been disclosed in various publications that certain benzoylisoxazoles have herbicidal properties. Thus, EP 0 418 175, EP 0 527 036 and WO 97/30037 describe benzoylisoxazoles which are substituted on the phenyl ring by a variety of radicals. 5 However, the compounds known from these publications frequently do not display a sufficient herbicidal activity. It is therefore an object of the present invention to provide herbicidally active compounds whose herbicidal properties are improved over those of the compounds known from the prior art. 0 It has now been found that certain 4-benzoylisoxazoles which have a cyclopropyl group attached in the 5-position and whose phenyl ring has an amino or amidine group attached in the 3-position are especially suitable as herbicides. The present invention relates to 4 -(3-aminobenzoyl)-5-cyclopropylisoxazoles of the 5 formula (1) or their salts i x N z Y in which WO 2009/118125 PCT/EP2009/002029 2 A is NR 1
R
2 or N=CR 3
NR
4
R
5 ,
R
1 and R 2 independently of one another are hydrogen, (C-C 6 )-alkyl, (C-C4) alkoxy-(CI-C 6 )-alkyl, (C 2
-C
6 )-alkenyl, (C2-C 6 )-alkynyl, (C 3
-C
6 )-cycloalkyl or (C 3
-C
6
)
5 cycloalkyl-(C-C 6 )-alkyl, where the six abovementioned radicals are substituted by m halogen atoms,
R
3 , R 4 and R 5 independently of one another are hydrogen, (C-C)-alkyl or (C3-C 6 )-cycloalkyl, where the three last-mentioned radicals are substituted by m 0 halogen atoms, X and Y independently of one another are hydrogen, (CI-C 6 )-alkyl, (Cr1C4) alkoxy, (CI-C4)-alkoxy-(C-C 6 )-alky, (C2-Ce)-alkenyl, (C 2
-C
6 )-alkynyl, (C 3
-C
6
)
cycloalkyl, (C3-C6)-cycloalkyl-(0 1
-C
6 )-alkyl, (CI-C6)-haloalkyl, halogen, (C-C4-alkyl 5 S(O)n, (C3-Cs)-cycloalkyl-S(O),, nitro or cyano, Z is hydrogen or C0 2 R,
R
6 is (C-C 6 )-alkyl or (C3-C 6 )-cycloalkyl, 0 m is 0,1, 2, 3, 4 or 5, n is 0, 1 or 2. 5 In formula (I) and all formula given below, alkyl radicals which have more than two carbon atoms may be straight-chain or branched. Alkyl radicals are, for example, methyl, ethyl, n- or i-propyl, n-, i-, t- or 2-butyl, pentyls, hexyls, such as n-hexyl, i-hexyl and 1,3-dimethylbutyl. Halogen is fluorine, chlorine, bromine or iodine. ) If a group is polysubstituted by radicals, this is to be understood as meaning that this group is substituted by one or more of the abovementioned radicals which are identical or different.
WO 2009/118125 PCT/EP2009/002029 3 Depending on the nature and linkage of the substituents, the compounds of the formula (1) may be present in the form of stereoisomers. If, for example, one or more asymmetric carbon atoms are present, enantiomers and diastereomers may occur. Equally, stereoisomers occur when n is 1 (sulfoxides). Stereoisomers can be 5 obtained from the mixtures generated in the course of the preparation by customary separation methods, for example by chromatographic separation methods. Equally, stereoisomers can be prepared selectively using stereoselective reactions and employing optically active starting materials and/or adjuvants. The invention also relates to all stereoisomers and their mixtures which are comprised by the formula 0 (1), but are not specifically defined. Preferred compounds of the formula (1) are those in which A is NR 1
R
2 or N=CR 3
NR
4
R
5 , 5 RW and R 2 independently of one another are hydrogen, (C1-Ce)-alkyl, (C 1
-C
4
)
alkoxy-(C-C 6 )-alkyl, (C 2
-C
6 )-alkenyl, (C 3
-C
6 )-cycloalkyl or (C3-Cs)-cycloalkyl-(C 1 -Ce) alkyl, 0 R3, R 4 , R 5 independently of one another are hydrogen or (C-C 6 )-alkyl, X and Y independently of one another are methyl, methoxy, trifluoromethyl, chlorine, bromine, fluorine or methylsulfonyl, 5 Z is hydrogen or CO 2 R,
R
6 is methyl or ethyl. Especially preferred compounds of the formula (I) are those in which A is NR'R 2 or N=CR 3
NR
4
R
5
,
WO 2009/118125 PCT/EP2009/002029 4
R
1 and R 2 independently of one another are hydrogen, methyl, ethyl, propyl, methoxyethyl, ethoxyethyl or methoxypropyl,
R
3 , R4, R 5 independently of one another are hydrogen or methyl, 5 X and Y independently of one another are methyl, methoxy, trifluoromethyl, chlorine, bromine, fluorine or methylsulfonyl, Z is hydrogen or C0 2 R, 0
R
6 is methyl or ethyl. Unless otherwise defined, the substituents and symbols in all the formulae mentioned hereinbelow have the same meaning as described in formula (I). 5 For example, compounds according to the invention in which Z is hydrogen can be prepared by the method specified in Scheme 1 and known from EP 0 418 175 Al by reacting a compound of the formula (II) with a salt of hydroxylamine, such as hydroxylamine hydrochloride, in a suitable solvent such as ethanol or acetonitrile, if 0 appropriate with catalysis of a base such as triethylamine, at a temperature of from room temperature up to the temperature of the boiling point of the solvent. In formula (II), L is a group such as ethoxy or dimethylamino. Scheme 1 0 0 X 0 x AA N NEt 3 N A + HO-NH 2 x HCI N-t- 0 O L z Y N z (II) (I) 5 Compounds of the formula (II) can be prepared for example by the method specified in Scheme 2 and in J. Heterocyclic Chem., 1976, 13, 973 by reacting the dione (Ill) WO 2009/118125 PCT/EP2009/002029 5 with, for example, triethyl orthoformate with acid catalysis. Scheme 2 0 0 X 0 0 X A + (EtO) 3 CH Ac 2 O A Y L Y (Ill) (II) The preparation of compounds of the formula (1ll) is known to the skilled worker in 5 principle and can be effected for example with trisubstituted benzoic acids of the formula (IV) or their derivatives such as acid chloride or ester. For example, such benzoic acids of the formula (IV) can be prepared by the methods described in WO 98/42678. 0 X HO Y 0 (IV) Compounds according to the invention in which Z is hydrogen or C0 2
R
6 can be prepared for example by the method specified in Scheme 3 and known from WO 97/30037 by reacting a compound of the formula (Ila) with hydroxylamine or a salt thereof in a suitable solvent such as ethanol or acetonitrile, if appropriate with 5 catalysis of a base such as triethylamine, at a temperature of from room temperature up to the temperature of the boiling point of the solvent.
WO 2009/118125 PCT/EP2009/002029 6 Scheme 3 0 0 X 0 x A A NEt 3 + HO-NH2 x HCI -N-t 0 HN zY N z Y (Ila) (I) Compounds according to the invention in which Z is C0 2
R
6 can also be prepared for example by the method specified in Scheme 4 and known from WO 98/5153 by 5 reacting a compound of the formula (Ill) with a 2-chloro-2-hydroxyiminoacetic ester of the formula (V). Scheme 4 o o x NOH 0 X A N OA + 1 6 c l CO
R
6 02RN (lil) (V)() 0 Compounds of the formulae (11) and (Ila) in which X, Y, A and Z are defined as for formula (I) and L is defined as mentioned above are novel and also subject matter of the present application. Collections of compounds of the formula (1) and/or their salts which can be 5 synthetized in accordance with the abovementioned reactions can also be prepared in a parallelized manner, which can be effected manually or in a partly or fully automated manner. Here, it is possible for example to automate the procedure of the reaction, the work-up or the purification of the products or intermediates. In total, this is understood as meaning the procedure as described for example by D. Tiebes in 0 Combinatorial Chemistry - Synthesis, Analysis, Screening (Editor Gonther Jung), Wiley 1999, on pages I to 34.
WO 2009/118125 PCT/EP2009/002029 7 A series of commercially available apparatuses can be used for the parallelized reaction procedure and work-up, for example Calpyso reaction blocks from Barnstead International, Dubuque, Iowa 52004-0797, USA, or reaction stations from 5 Radleys, Shirehill, Saffron Walden, Essex, CB 11 3AZ, England or MultiPROBE Automated Workstations from Perkin Elmar, Waltham, Massachusetts 02451, USA. Chromatographic apparatuses, for example from ISCO, Inc., 4700 Superior Street, Lincoln, NE 68504, USA, are available, inter alia, for the parallelized purification of compounds of the formula (1) and their salts or of intermediates generated in the 0 course of the preparation. The apparatuses listed lead to a modular procedure in which the individual passes are automated, but manual operations must be carried out between the passes. This can be circumvened by the use of partly or fully integrated automation systems, 5 where the relevant automation modules are operated by, for example, robots. Such automation systems can be obtained for example from Caliper, Hopkinton, MA 01748, USA. The performance of individual, or a plurality of, synthesis steps can be aided by the 0 use of polymer-supported reagents/scavenger resins. The specialist literature describes a series of experimental protocols, for example in ChemFiles, Vol. 4, No. 1, Polymer-Supported Scavengers and Reagents for Solution-Phase Synthesis (Sigma-Aldrich). 5 Besides the methods described herein, the preparation of compounds of the formula (I) and their salts can be effected fully or in part by solid-phase-supported methods. For this purpose, individual intermediates, or all intermediates, of the synthesis or of a synthesis adapted to the relevant procedure are bound to a synthesis resin. Solid phase-supported synthesis methods are described sufficiently in the specialist 0 literature, for example Barry A. Bunin in "The Combinatorial Index", Academic Press, 1998 and Combinatorial Chemistry - Synthesis, Analysis, Screening (Editor G~nther Jung), Wiley, 1999. The use of solid-phase-supported synthesis methods permits a WO 2009/118125 PCT/EP2009/002029 8 series of protocols known from the literature, which, again, can be carried out manually or in an automated manner. For example, the reactions can be carried out by means of IRORI technology in microreactors from Nexus Biosystems, 12140 Community Road, Poway, CA92064, USA. 5 Carrying out individual or a plurality of synthesis steps, both on a solid and in the liquid phase, can be aided by the use of microwave technology. A series of experimental protocols are described in the specialist literature, for example in Microwaves in Organic and Medicinal Chemistry (Editors C. 0. Kappe and 10 A. Stadler), Wiley, 2005. The preparation in accordance with the processes described herein generates compounds of the formula (I) and their salts in the form of substance collections, which are referred to as libraries. The present invention also relates to libraries which 5 comprise at least two compounds of the formula (1) and their salts. The compounds of the formula (1) according to the invention (and/or their salts), hereinbelow together referred to as "compounds according to the invention", have an outstanding herbicidal activity against a broad spectrum of economically important 0 monocotyledonous and dicotyledonous annual harmful plants. The active substances also act efficiently on perennial harmful plants which produce shoots from rhizomes, woodstocks or other perennial organs and which are difficult to control. 5 The present invention therefore also relates to a method of controlling undesired plants or for regulating the growth of plants, preferably in crops of plants, where one or more compound(s) according to the invention is/are applied to the plants (for example harmful plants such as monocotyledonous or dicotyledonous weeds or undesired crop plants), to the seeds (for example grains, seeds or vegetative O propagules such as tubers or shoot parts with buds) or to the area on which the plants grow (for example the area under cultivation). In this context, the compounds according to the invention can be applied for example pre-planting (if appropriate WO 2009/118125 PCT/EP2009/002029 9 also by incorporation into the soil), pre-emergence or post-emergence. Examples of individual representatives of the monocotyledonous and dicotyledonous weed flora which can be controlled by the compounds according to the invention shall be mentioned, without the mention being intended as a limitation to certain species. 5 Monocotyledonous harmful plants of the genera: Aegilops, Agropyron, Agrostis, Alopecurus, Apera, Avena, Brachiaria, Bromus, Cenchrus, Commelina, Cynodon, Cyperus, Dactyloctenium, Digitaria, Echinochloa, Eleocharis, Eleusine, Eragrostis, Eriochloa, Festuca, Fimbristylis, Heteranthera, Imperata, Ischaemum, Leptochloa, 0 Lolium, Monochoria, Panicum, Paspalum, Phalaris, Phleum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, Sorghum. Dicotyledonous weeds of the genera: Abutilon, Amaranthus, Ambrosia, Anoda, Anthemis, Aphanes, Artemisia, Atriplex, Bellis, Bidens, Capsella, Carduus, Cassia, 5 Centaurea, Chenopodium, Cirsium, Convolvulus, Datura, Desmodium, Emex, Erysimum, Euphorbia, Galeopsis, Galinsoga, Galium, Hibiscus, lpomoea, Kochia, Lamium, Lepidium, Lindernia, Matricaria, Mentha, Mercurialis, Mullugo, Myosotis, Papaver, Pharbitis, Plantago, Polygonum, Portulaca, Ranunculus, Raphanus, Rorippa, Rotala, Rumex, Salsola, Senecio, Sesbania, Sida, Sinapis, Solanum, o Sonchus, Sphenoclea, Stellaria, Taraxacum, Thlaspi, Trifolium, Urtica, Veronica, Viola, Xanthium. If the compounds according to the invention are applied to the soil surface before germination, either the emergence of the weed seedlings is prevented completely or 5 the weeds grow until they have reached the cotyledon stage, but then stop their growth and, finally, die completely after three to four weeks have elapsed. When the active substances are applied post-emergence to the green plant parts, growth stops after the treatment, and the harmful plants remain in the growth stage 0 of the time of application or die fully after a certain period of time, so that competition by weeds, which is harmful to the crop plants, is thus eliminated at an early point in time and in a sustained manner.
WO 2009/118125 PCT/EP2009/002029 10 Although the compounds according to the invention display an outstanding herbicidal activity against monocotyledonous and dicotyledonous weeds, crop plants of economically important crops, for example dicotyledonous crops of the genera Arachis, Beta, Brassica, Cucumis, Cucurbita, Helianthus, Daucus, Glycine, 5 Gossypium, Ipomoea, Lactuca, Linum, Lycopersicon, Nicotiana, Phaseolus, Pisum, Solanum, Vicia, or monocotyledonous crops of the genera Allium, Ananas, Asparagus, Avena, Hordeum, Oryza, Panicum, Saccharum, Secale, Sorghum, Triticale, Triticum, Zea, in particular Zea and Triticum, are damaged only to an insignificant extent, or not at all, depending on the structure of the respective 0 compound according to the invention and its application rate. This is why the present compounds are highly suitable for the selective control of undesired plant growth in plant crops such as agriculturally useful plants or ornamentals. Moreover, the compounds according to the invention (depending on their respective 5 structure and the application rate applied) have outstanding growth-regulatory properties in crop plants. They engage in the plant metabolism in a regulatory fashion and can therefore be employed for the influencing, in a targeted manner, of plant constituents and for facilitating harvesting, such as, for example, by triggering desiccation and stunted growth. Moreover, they are also suitable for generally 0 controlling and inhibiting undesired vegetative growth without destroying the plants in the process. Inhibiting the vegetative growth plays an important role in many monocotyledonous and dicotyledonous crops since for example lodging can be reduced, or prevented completely, hereby. 5 Owing to their herbicidal and plant-growth-regulatory properties, the active substances can also be employed for controlling harmful plants and crops of genetically modified plants or plants which have been modified by conventional mutagenesis. As a rule, the transgenic plants are distinguished by especially advantageous properties, for example by resistances to certain pesticides, mainly 0 certain herbicides, resistances to plant diseases or causative organisms of plant diseases, such as certain insects or microorganisms such as fungi, bacteria or viruses. Other special properties relate for example to the harvested material with WO 2009/118125 PCT/EP20091002029 11 regard to quantity, quality, storability, composition and specific constituents. Thus, transgenic plants with an increased starch content or a modified starch quality or those with a different fatty acid composition of the harvested material are known. 5 As regards transgenic crops, the use of the compounds according to the invention in economically important transgenic crops of useful plants and ornamentals, for example of cereals such as wheat, barley, rye, oats, sorghum and millet, rice and maize or else crops of sugar beet, cotton, soybean, oil seed rape, potato, tomato, peas and other vegetables is preferred. It is preferred to employ the compounds 0 according to the invention as herbicides in crops of useful plants which are resistant, or have been made resistant by recombinant means, to the phytotoxic effects of the herbicides. It is preferred to use the compounds according to the invention or their salts in 5 economically important transgenic crops of useful plants and ornamentals, for example of cereals such as wheat, barley, rye, oats, sorghum and millet, rice, cassava and maize or else crops of sugar beet, cotton, soybean, oil seed rape, potato, tomato, peas and other vegetables. It is preferred to employ the compounds according to the invention as herbicides in crops of useful plants which are resistant, 0 or have been made resistant by recombinant means, to the phytotoxic effects of the herbicides. Conventional ways of generating novel plants which, in comparison with existing plants, have modified properties are, for example, traditional breeding methods and 5 the generation of mutants. Alternatively, novel plants with modified properties can be generated with the aid of recombinant methods (see, for example, EP-A-0221044, EP-A-0131624). For example, the following have been described in several cases: - recombinant modifications of crop plants for the purposes of modifying the starch synthetized in the plants (for example WO 92/11376, WO 92/14827, 0 WO 91/19806), - transgenic crop plants which are resistant to certain herbicides of the glufosinate type (cf., for example, EP-A-0242236, EP-A-242246) or of the glyphosate type (WO 92/00377) or of the sulfonylurea type (EP-A-0257993, WO 2009/118125 PCT/EP2009/002029 12 US-A-5013659), - transgenic crop plants, for example cotton, which is capable of producing Bacillus thuringiensis toxins (Bt toxins), which make the plants resistant to certain pests (EP-A-0142924, EP-A-0193259), 5 - transgenic crop plants with a modified fatty acid composition (WO 91/13972), - genetically modified crop plants with novel constituents or secondary metabolites, for example novel phytoalexins, which bring about an increased disease resistance (EPA 309862, EPA0464461), - genetically modified plants with reduced photorespiration which feature higher 10 yields and higher stress tolerance (EPA 0305398), - transgenic crop plants which produce pharmaceutically or diagnostically important proteins ("molecular pharming"), - transgenic crop plants which are distinguished by higher yields or better quality, 5 - transgenic crop plants which are distinguished by a combination, for example of the abovementioned novel properties ("gene stacking"). A large number of molecular-biological techniques by means of which novel transgenic plants with modified properties can be generated are known in principle; 0 see, for example, I. Potrykus and G. Spangenberg (eds.) Gene Transfer to Plants, Springer Lab Manual (1995), Springer Verlag Berlin, Heidelberg. or Christou, "Trends in Plant Science" 1 (1996) 423-431). To carry out such recombinant manipulations, it is possible to introduce nucleic acid 5 molecules into plasmids, which permit a mutagenesis or sequence modification by recombination of DNA sequences. For example, base substitutions can be carried out, part-sequences can be removed, or natural or synthetic sequences may be added with the aid of standard methods. To link the DNA fragments with one another, it is possible to add adapters or linkers to the fragments; see, for example, 0 Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual, 2. ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; or Winnacker "Gene und Klone", VCH Weinheim 2. ed., 1996 WO 2009/118125 PCT/EP2009/002029 13 The generation of plant cells with a reduced activity for a gene product can be achieved for example by the expression of at least one corresponding antisense RNA, a sense RNA for achieving a cosuppression effect or by the expression of at 5 least one correspondingly constructed ribozym, which specifically cleaves transcripts of the abovementioned gene product. To do this, it is possible firstly to use DNA molecules which comprise all of the coding sequence of a gene product, including any flanking sequences which may be present, or else DNA molecules which only comprise parts of the coding sequence, it being necessary for these parts to be long 0 enough to bring about an antisense effect in the cells. It is also possible to use DNA sequences which have a high degree of homology with the coding sequences of a gene product, but which are not entirely identical. When expressing nucleic acid molecules in plants, the protein synthetized may be 5 localized in any compartment of the plant cell. In order to achieve localization in a particular compartment, however, it is possible for example to link the coding region to DNA sequences which ensure the localization in a specific compartment. Such sequences are known to the skilled worker (see, for example, Braun et al., EMBO J. 11 (1992), 3219-3227; Wolter et al., Proc. Nati. Acad. Sci. USA 85 (1988), 846-850; 0 Sonnewald et al., Plant J. 1 (1991), 95-106). However, the nucleic acid molecules can also be expressed in the organelles of the plant cells. The transgenic plant cells can be regenerated by known techniques to give intact plants. In principle, the transgenic plants may be plants of any plant species, that is 5 to say both monocotyledonous and dicotyledonous plants. Thus, transgenic plants can be obtained which feature modified properties as the result of overexpression, suppression or inhibition of homologous (= natural) genes or gene sequences or expression of heterologous (= foreign) genes or gene 0 sequences. It is preferred to employ the compounds according to the invention in transgenic WO 2009/118125 PCT/EP2009/002029 14 crops which are resistant to growth regulators such as, for example, dicamba, or against herbicides which inhibit essential plant enzymes, for example acetolactate synthases (ALS), EPSP synthases, glutamine synthases (GS) or hydroxyphenylpyruvate dioxygenases (HPPD), or against herbicides from the group 5 of the sulfonylureas, glyphosate, glufosinate or benzoylisoxazoles and analogous active substances. When the active substances according to the invention are used in transgenic crops, effects are frequently observed - in addition to the effects on harmful plants which 0 can be observed in other crops - which are specific for the application in the transgenic crop in question, for example a modified or specifically widened spectrum of weeds which can be controlled, modified application rates which may be employed for application, preferably good combiningability with the herbicides to which the transgenic crop is resistant, and an effect on growth and yield of the 5 transgenic crop plants. The invention therefore also relates to the use of the compounds according to the invention as herbicides for controlling harmful plants in transgenic crop plants. 0 The compounds according to the invention can be employed in the customary preparations in the form of wettable powders, emulsifiable concentrates, sprayable solutions, dusts or granules. The invention therefore also relates to herbicidal and plant-growth-regulating compositions which comprise the compounds according to the invention. 5 The compounds according to the invention can be formulated in various ways, depending on the prevailing biological andlor physico-chemical parameters. Examples of possible formulations are: wettable powders (WP), water-soluble powders (SP), water-soluble concentrates, emulsifiable concentrates (EC), 0 emulsions (EW), such as oil-in-water and water-in-oil emulsions, sprayable solutions, suspension concentrates (SC), oil- or water-based dispersions, oil-miscible solutions, capsule suspensions (CS), dusts (DP), seed-dressing products, granules for application by broadcasting and on the soil, granules (GR) in the form of WO 2009/118125 PCT/EP2009/002029 15 microgranules, spray granules, coated granules and adsorption granules, water dispersible granules (WG), water-soluble granules (SG), ULV formulations, microcapsules and waxes. These individual types of formulation are known in principle and are described, for 5 example, in: Winnacker-KOchler, "Chemische Technologie" [Chemical technology], volume 7, C. Hanser Verlag Munich, 4th Ed. 1986; Wade van Valkenburg, "Pesticide Formulations", Marcel Dekker, N.Y., 1973; K. Martens, "Spray Drying" Handbook, 3rd Ed. 1979, G. Goodwin Ltd. London. 0 The formulation auxiliaries required, such as inert materials, surfactants, solvents and further additives, are also known and are described, for example, in: Watkins, "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Darland Books, Caldwell N.J., H.v. Olphen, "Introduction to Clay Colloid Chemistry"; 2nd Ed., J. Wiley & Sons, N.Y.; C. Marsden, "Solvents Guide"; 2nd Ed., Interscience, N.Y. 1963; 5 McCutcheon's "Detergents and Emulsifiers Annual", MC Pubi. Corp., Ridgewood N.J.; Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem. PubL. Co. Inc., N.Y. 1964; Schbnfeldt, "Grenzf1schenaktive Athylenoxidaddukte" [Interface active ethylene oxide adducts], Wiss. Verlagsgesell., Stuttgart 1976; Winnacker-KOchler, "Chemische Technologie" [Chemical technology], volume 7, 0 C. Hanser Verlag Munich, 4th Ed. 1986. Based on these formulations, it is also possible to prepare combinations with other pesticidally active substances such as, for example, insecticides, acaricides, herbicides, fungicides, and with safeners, fertilizers and/or growth regulators, for 5 example in the form of a ready mix or a tank mix. Wettable powders are preparations which are uniformly dispersible in water and which, besides the active substance, also comprise ionic and/or nonionic surfactants (wetters, dispersers), for example polyoxyethylated alkylphenols, polyoxyethylated 0 fatty alcohols, polyoxyethylated fatty amines, fatty alcohol polyglycol ether sulfates, alkanesulfonates, alkylbenzenesulfonates, sodium lignosulfonate, sodium 2,2'-dinaphthylmethane-6,6'-disulfonate, sodium dibutylnaphthalenesulfonate or else WO 2009/118125 PCT/EP2009/002029 16 sodium oleoylmethyltaurinate, besides a diluent or inert substance. To prepare the wettable powders, the herbicidally active substances are ground finely, for example in customary apparatuses such as hammer mills, blower mills and air-jet mills, and mixed with the formulation auxiliaries, either simultaneously or subsequently. 5 Emulsifiable concentrates are prepared by dissolving the active substance in an organic solvent, for example butanol, cyclohexanone, dimethylformamide, xylene or else higher-boiling aromatics or hydrocarbons or mixtures of the organic solvents with addition of one or more ionic and/or nonionic surfactants (emulsifiers). 0 Examples of emulsifiers which may be used are: calcium alkylarylsulfonates such as calcium dodecylbenzenesulfonate, or nonionic emulsifiers such as fatty acid polyglycol esters, alkylarylpolyglycol ethers, fatty alcohol polyglycol ethers, propylene oxide/ethylene oxide condensates, alkyl polyethers, sorbitan esters such as, for example, sorbitan fatty acid esters or polyoxyethylene sorbitan esters such as, for 5 example, polyoxyethylene sorbitan fatty acid esters. Dusts are obtained by grinding the active substance with finely divided solid materials such as, for example, talcum, natural clays such as kaolin, bentonite and pyrophyllite, or diatomaceous earth. 0 Suspension concentrates can be water- or oil-based. They can be prepared for example by wet-grinding by means of commercially available bead mills, if appropriate with addition of surfactants as already listed above for example in the case of the other formulation types. 5 Emulsions, for example oil-in-water emulsions (EW), can be prepared for example by means of stirrers, colloid mills and/or static mixers using aqueous organic solvents and, if appropriate, surfactants, as have already been mentioned for example above for the other formulation types. Granules can be prepared either by spraying the active substance onto adsorptive, granulated inert material, or by applying active substance concentrates to the WO 2009/118125 PCT/EP2009/002029 17 surface of carriers such as sand, kaolinites or granulated inert material with the aid of stickers, for example polyvinyl alcohol, sodium polyacrylate or else mineral oils. Suitable active substances can also be granulated in the manner which is customary for the production of fertilizer granules, if desired as a mixture with fertilizers. 5 Water-dispersible granules are generally prepared by customary methods such as spray drying, fluidized-bed granulation, disk granulation, mixing with high-speed stirrers, and extrusion without solid inert material. 10 To prepare disk granules, fluidized-bed granules, extruder granules and spray granules, see, for example, methods in "Spray-Drying Handbook" 3rd ed. 1979, G. Goodwin Ltd., London; J.E. Browning, "Agglomeration", Chemical and Engineering 1967, pages 147 et seq.; "Perry's Chemical Engineer's Handbook", 5th Ed., McGraw-Hill, New York 1973, p. 8-57. 5 For further details of the formulation of crop protection products see, for example, G.C. Klingman, "Weed Control as a Science", John Wiley and Sons, Inc., New York, 1961, pages 81-96 and J.D. Freyer, S.A. Evans, 'Weed Control Handbook", 5th Ed., Blackwell Scientific Publications, Oxford, 1968, pages 101-103. 0 As a rule, the agrochemical preparations comprise from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of compounds according to the invention. In wettable powders, the active substance concentration is, for example, approximately 10 to 90% by weight, the remainder to 100% by weight.being 5 composed of customary formulation constituents. In the case of emulsifiable concentrates, the active substance concentration can amount to approximately 1 to 90, preferably 5 to 80% by weight. Formulations in the form of dusts comprise from I to 30% by weight of active substance, preferably in most cases from 5 to 20% by weight of active substance, and sprayable solutions comprise approximately from 0 0.05 to 80, preferably from 2 to 50% by weight of active substance. In the case of water-dispersible granules, the active substance content depends partly on whether the active compound is in liquid or solid form, and on the granulation auxiliaries, WO 2009/118125 PCT/EP2009/002029 18 fillers and the like which are being used. In the case of the water-dispersible granules, for example, the active substance content is between 1 and 95% by weight, preferably between 10 and 80% by weight. 5 In addition, the active substance formulations mentioned comprise, if appropriate, the auxiliaries which are conventional in each case, such as stickers, wetters, dispersants, emulsifiers, penetrations, preservatives, antifreeze agents, solvents, fillers, carriers, colorants, antifoams, evaporation inhibitors, and pH and viscosity regulators. 0 Based on these formulations, it is also possible to prepare combinations with other pesticidally active substances such as, for example, insecticides, acaricides, herbicides, fungicides, and with safeners, fertilizers and/or growth regulators, for example in the form of a ready mix or a tank mix. 5 Active substances which can be employed in combination with the compounds according to the invention in mixed formulations or in the tank mix are, for example, known active substances which are based on the inhibition of, for example, acetolactate synthase, acetyl-CoA carboxylase, cellulose synthase, 0 enolpyruvylshikimate-3-phosphate synthase, glutamine synthetase, p-hydroxyphenylpyruvate dioxygenase, phytoen desaturase, photosystem I, photosystem II, protoporphyrinogen oxidase, as are described in, for example, Weed Research 26 (1986) 441-445 or "The Pesticide Manual", 14th edition, The British Crop Protection Council and the Royal Soc. of Chemistry, 2003 and the literature 5 cited therein. Known herbicides or plant growth regulators which can be combined with the compounds according to the invention are, for example, the following active substances (the compounds are either designated by the common name according to the International Organization for Standardization (ISO) or by a chemical name, if appropriate together with the code number) and always comprise all use forms such 0 as acids, salts, esters and isomers such as stereoisomers and optical isomers. In this context, one and in some cases also several use forms are mentioned by way of example: WO 2009/118125 PCT/EP2009/002029 19 acetochlor, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-sodium, aclonifen, alachlor, allidochlor, alloxydim, alloxydim-sodium, ametryne, amicarbazone, amidochlor, amidosulfuron, aminocyclopyrachlor, aminopyralid, amitrole, ammonium sulfamate, ancymidol, anilofos, asulam, atrazine, azafenidin, 5 azimsulfuron, aziprotryne, BAH-043, BAS-140H, BAS-693H, BAS-714H, BAS-762H, BAS-776H, BAS-800H, beflubutamid, benazolin, benazolin-ethyl, bencarbazone, benfluralin, benfuresate, bensulide, bensulfuron-methyl, bentazone, benzfendizone, benzobicyclon, benzofenap, benzofluor, benzoylprop, bifenox, bilanafos, bilanafos sodium, bispyribac, bispyribac-sodium, bromacil, bromobutide, bromofenoxim, 0 bromoxynil, bromuron, buminafos, busoxinone, butachlor, butafenacil, butamifos, butenachlor, butralin, butroxydim, butylate, cafenstrole, carbetamide, carfentrazone, carfentrazone-ethyl, chlomethoxyfen, chloramben, chlorazifop, chlorazifop-butyl, chlorbromuron, chlorbufam, chlorfenac, chlorfenac-sodium, chlorfenprop, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, 5 chlormequat-chloride, chlornitrofen, chlorophthalim, chlorthal-dimethyl, chlorotoluron, chlorsulfuron, cinidon, cinidon-ethyl, cinmethylin, cinosulfuron, clethodim, clodinafop clodinafop-propargyl, clofencet, clomazone, clorneprop, cloprop, clopyralid, cloransulam, cloransulam-methyl, cumyluron, cyanamide, cyanazine, cyclanilide, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyhalofop-butyl, D cyperquat, cyprazine, cyprazole, 2,4-D, 2,4-DB, daimuron/dymron, dalapon, daminozide, dazomet, n-decanol, desmedipham, desmetryn, detosyl-pyrazolate (DTP), di-allate, dicamba, dichlobenil, dichlorprop, dichlorprop-P, diclofop, diclofop methyl, diclofop-P-methyl, diclosulam, diethatyl, diethatyl-ethyl, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, diflufenzopyr-sodium, dimefuron, dikegulac 5 sodium, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimetrasulfuron, dinitramine, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, diquat-dibromide, dithiopyr, diuron, DNOC, eglinazine-ethyl, endothal, EPTC, esprocarb, ethalfluralin, ethametsulfuron-methyl, ethephon, ethidimuron, ethiozin, ethofumesate, ethoxyfen, ethoxyfen-ethyl, ethoxysulfuron, etobenzanid, F-5331, i.e. N-[2-chloro-4-fluoro-5-[4-(3-fluoro-propyl) 4,5-dihydro-5-oxo-1 H-tetrazol-1 -yl]-phenyl]ethanesulfonamide, fenoprop, fenoxaprop, fenoxaprop-P, fenoxaprop-ethyl, fenoxaprop-P-ethyl, fentrazamide, WO 2009/118125 PCT/EP2009/002029 20 fenuron, flamprop, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, florasulam, fluazifop, fluazifop-P, fluazifop-butyl, fluazifop-P-butyl, fluazolate, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flufenacet (thiafluamide), flufenpyr, flufenpyr-ethyl, flumetralin, flumetsulam, flumiclorac, 5 flumiclorac-pentyl, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, flupoxam, flupropacil, flupropanate, flupyrsulfuron, flupyrsulfuron-methyl-sodium, flurenol, flurenol-butyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-meptyl, flurprimidol, flurtamone, fluthiacet, fluthiacet-methyl, fluthiamide, fomesafen, foramsulfuron, forchlorfenuron, fosamine, furyloxyfen, 0 gibberellic acid, glufosinate, L-glufosinate, L-glufosinate-ammonium, glufosinate ammonium, glyphosate, glyphosate-isopropylammonium, H-9201, halosafen, halosulfuron, halosulfuron-methyl, haloxyfop, haloxyfop-P, haloxyfop-ethoxyethyl, haloxyfop-P-ethoxyethyl, haloxyfop-methyl, haloxyfop-P-methyl, hexazinone, HNPC 9908, HOK-201, HW-02, imazamethabenz, imazamethabenz-methyl, imazamox, 5 imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, inabenfide, indanofan, indoleacetic acid (IAA), 4-indol-3-ylbutyric acid (IBA), iodosulfuron, iodosulfuron methyl-sodium, ioxynil, isocarbamid, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, KUH-043, KUH-071, karbutilate, ketospiradox, lactofen, lenacil, linuron, maleic hydrazide, MCPA, MCPB, MCPB 0 methyl, -ethyl and -sodium, mecoprop, mecoprop-sodium, mecoprop-butotyl, mecoprop-P-butotyl, mecoprop-P-dimethylammonium, mecoprop-P-2-ethylhexyl, mecoprop-P-potassium, mefenacet, mefluidide, mepiquat-chloride, mesosulfuron, mesosulfuron-methyl, mesotrione, methabenzthiazuron, metam, metamifop, metamitron, metazachlor, methazole, methoxyphenone, methyldymron, 5 1-methylcyclopropene, methyl isothiocyanate, metobenzuron, metobenzuron, metobromuron, metolachlor, S-metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, metsulfuron-methyl, molinate, monalide, monocarbamide, monocarbamide dihydrogen sulfate, monolinuron, monosulfuron, monuron, MT 128, MT-5950, i.e. N-[3-chloro-4-(1-methylethyl)-phenyl]-2-methylpentanamide,
NGGC
0 011, naproanilide, napropamide, naptalam, NC-310, i.e. 4-(2,4-dichlorobenzoyl) 1-methyl-5-benzyloxypyrazole, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrophenolat-sodium (isomer mixture), nitrofluorfen, nonanoic acid, norflurazon, WO 2009/118125 PCT/EP2009/002029 21 orbencarb, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxasulfuron, oxaziclomefone, oxyfluorfen, paclobutrazole, paraquat, paraquat dichloride, pelargonic acid (nonanoic acid), pendimethalin, pendralin, penoxsulam, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, 5 phenmedipham-ethyl, picloram, picolinafen, pinoxaden, piperophos, pirifenop, pirifenop-butyl, pretilachlor, primisulfuron, primisulfuron-methyl, probenazole, profluazol, procyazine, prodiamine, prifluraline, profoxydim, prohexadione, prohexadione-calcium, prohydrojasmone, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, 0 propoxycarbazone-sodium, propyzamide, prosulfalin, prosulfocarb, prosulfuron, prynachlor, pyracionil, pyraflufen, pyraflufen-ethyl, pyrasulfotole, pyrazolynate (pyrazolate), pyrazosulfuron-ethyl, pyrazoxyfen, pyribambenz, pyribambenz isopropyl, pyribenzoxim, pyributicarb, pyridafol, pyridate, pyriftalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac, pyrithiobac-sodium, pyroxasulfone, 5 pyroxsulam, quinclorac, quinmerac, quinoclamine, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, rimsulfuron, saflufenacil, secbumeton, sethoxydim, siduron, simazine, simetryn, SN-106279, sulcotrione, sulf allate (CDEC), suifentrazone, sulfometuron, sulfometuron-methyl, sulfosate (glyphosate-trimesium), sulfosulfuron, SYN-523, SYP-249, SYP-298, SYP-300, 0 tebutam, tebuthiuron, tecnazene, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryne, TH-547, thenylchior, thiafluamide, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thiobencarb, tiocarbazil, topramezone, tralkoxydim, tri-allate, triasulfuron, triaziflam, 5 triazofenamide, tribenuron, tribenuron-methyl, trichloroacetic acid (TCA), triclopyr, tridiphane, trietazine, trifloxysulfuron, trifloxysulfuron-sodium, trifluralin, triflusulfuron, triflusulfuron-methyl, trimeturon, trinexapac, trinexapac-ethyl, tritosulfuron, tsitodef, uniconazole, uniconazole-P, vernolate, ZJ-0166, ZJ-0270, ZJ-0543, ZJ-0862 and the following compounds 0 WO 2009/118125 PCT/EP2009/002029 22 0 a N%.
0 0 0 O N CH 3 N CH
SCF
3 0
CF
3 C F 0 H 3
OH
3
OH
3
CF
3 / cH
-
N- SN
H
3 C 0 0 / H N EtO200H 2 O O HOC H 3 0 OH 3 / s N / 00 So02
O-H
3 For use, the formulations, which are present in commercially available form, if appropriate, are diluted in the customary manner, for example using water in the case of wettable powders, emulsifiable concentrates, dispersions and water 5 dispersible granules. Preparations in the form of dusts, soil granules, granules for broadcasting, and sprayable solutions, are usually not diluted further with further inert substances prior to use. The application rate required of the compounds of the formula (1) varies as a function 0 of the external conditions such as temperature, humidity, the nature of the herbicide used and the like. It can vary within wide limits, for example between 0.001 and 1.0 kg/ha and more of active substance, but it is preferably between 0.005 and 750 g/ha. 5 The examples which follow are intended to illustrate the invention.
WO 2009/118125 PCT/EP2009/002029 23 A. Chemical examples 1. Preparation of 5-cyclopropyl-4-(3-methylamino-2-methylsufonyl 4-trifluoromethylbenzoyl)isoxazole (No. 184 of table A) 5 Step 1: Synthesis of 3-fluoro-2-methylthio-4-trifluoromethylbenzoic acid 25.0 g (120.1 mmol) of 3-fluoro-4-trifluoromethylbenzoic acid were dissolved in 250 ml of dry tetrahydrofuran (THF), and 100.9 ml of n-butyllithium (2.5 M in hexane, 252.3 mmol) were added dropwise at -40"C. The mixture was stirred for 3 h, and a solution of 32.5 ml (360.4 mmol) of dimethyl disulfide in 50 ml of dry THF was then 0 added dropwise. The mixture was stirred for 16 h, during which process, after half an hour, the temperature climbed slowly to RT. For work-up, 2 M HCI was added carefully. The mixture was extracted with diethyl ether, and the organic phase was subsequently extracted with 2 M NaOH. The aqueous phase was acidified and extracted with diethyl ether. The organic phase was washed with water, dried, and 5 the solvent was removed in vacuo. The residue was stirred with n-heptane and the solid was separated off by a filtration. This gave 17.0 g of crude product, which was employed in the next synthesis step without further purification. Step 2: Synthesis of 3-fluoro-2-methylsulfonyl-4-trifluoromethylbenzoic acid 0 18.6 g (73.2 mmol) of 3 -fluoro-2-methylthio-4-trifluoromethylbenzoic acid were introduced into 180 ml of glacial acetic acid. 724 mg (2.2 mmol) of sodium tungstate(VI) dihydrate were added, and the mixture was then heated to 50 - 60'C. 15.0 ml (30% strength, 146.8 mmol) of an aqueous hydrogen peroxide solution were added dropwise at this temperature. The mixture was stirred for 4.5 h at this 5 temperature. To complete the reaction, 14.9 ml (30% strength, 145.9 mmol) of an aqueous H 2 0 2 solution were subsequently carefully added dropwise, and the contents stirred for another 3 h at 50 - 60'C. The reaction mixture was cooled and, for work-up, poured into water. The mixture was extracted twice using ethyl acetate, the combined organic phases were washed with an aqueous saturated sodium ) hydrogen sulfite solution, and, after the absence of peroxides has been determined analytically, the mixture was dried and the solvent was removed in vacuo. This gave 19.8 g of product in 95% purity.
WO 2009/118125 PCT/EP2009/002029 24 Step 3: Synthesis of 3-methylamino-2-methylsulfonyl-4-trifluoromethylbenzoic acid 2.40 g (8.4 mmol) of 3-fluoro-2-methylsulfonyl-4-trifluoromethylbenzoic acid were treated with 12.1 ml (168 mmol; 40 percent strength) of aqueous methylamine solution and the mixture was stirred for 4 h at RT. For work-up, the contents were 5 poured into 6 N HCI, the mixture was subsequently cooled in an ice-bath. The precipitate was filtered off with suction. This gave 2.50 g of product in 95% purity. Step 4: Synthesis of tert-butyl 3-cyclopropyl-2-(3-methylamino-2-methylsulfonyl 4-trifluoroethylbenzoyl)-3-oxopropanoate 0 2.50 g (8.4 mmol) of 3-methylamino-2-methylsulfonyl-4-trifluoromethylbenzoic acid were introduced into 50 ml of CH 2
CI
2 and treated with 1.1 ml (12.6 mmol) oxalyl dichloride and two drops of DMF. The mixture was heated at reflux until the evolution of gas had ceased. To complete the reaction, another 0.8 ml (9.2 mmol) of oxalyl dichloride and two more drops of DMF were added. After the evolution of gas had 5 ceased, the contents were heated at reflux for another 15 min. Thereafter, the mixture was concentrated on a rotary evaporator. To remove a residual oxalyl dichloride, the residue was coevaporated with toluene. The residue was taken up in 50 ml of toluene. 4.01 g (16.8 mmol) of magnesium (3-tert.-butoxy-1-cyclopropyl 3-oxoprop-1 -en-1 -olate) methoxide (synthesis described for example in EP 0918056) 0 were added, and the mixture was stirred for 16 h at RT. The contents were concentrated and the residue was taken up in ethyl acetate. The solution was washed with dilute HCI, the organic phase was dried, and the solvent was removed in vacuo. This gave 5.3 g of crude product in approximately 70% purity, which was employed in the next synthesis step without further purification. 5 Step 5: Synthesis of 1 -cyclopropyl-3-(3-methylamino-2-methylsulfonyl 4-trifluoromethylphenyl)propane- 1,3-d ione 5.0 ml of trifluoroacetic acid were heated at 55 0 -60'C. A solution of 5.3 g (8.0 mmol; 70% purity) of tert-butyl-3-cyclopropyl-2-(3-methylamino-2-methylsulfonyl 0 4-trifluoromethylbenzoyl)-3-oxopropanoate in 10 ml of CH 2
CI
2 was added dropwise and the mixture was then heated at reflux for 15 min. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel. This WO 2009/118125 PCT/EP2009/002029 25 gave 1.22 g of product in 95% purity. Step 6: Synthesis of 1-cyclopropyl-2-(dimethylaminomethylidene)-3-(3-methylamino 2-methylsulfonyl-4-trifl uoromethyl phenyl)propane- 1,3-dione 1.22 g (3.4 mmol) of 1-cyclopropyl-3-(3-methylamino-2-methylsulfonyl 5 4-trifluoromethylphenyl)propane-1,3-dione were treated with 3.0 ml (22.7 mmol) of N,N-dimethyl formamide dimethyl acetal and the mixture was stirred for 16 h at RT. Then, a little n-heptane was added, and the contents were stirred for a further 10 min at RT. The precipitate was filtered off with suction. This gave 1.29 g of product in 95% purity. 0 Step 7: Synthesis of 5-cyclopropyl-4-(3-methylamino-2-methylsulfonyl 4-trifluoromethylbenzoyl)isoxazole 1.29 g (3.1 mmol) of 1 -cyclopropyl-2-(dimethylaminomethylidene)-3-(3-methylamino 2 -methylsulfonyl-4-trifluoromethylphenyl)propane-1,3-d ione were introduced into 5 50 ml of ethanol. 0.30 g (4.3 mmol) of hydroxylammonium chloride was added, and the mixture was stirred for 30 min at RT. Thereafter, 0.33 g (4.0 mmol) of sodium acetate was added, and the contents were stirred for 16 h at RT. Thereupon, a further 0.15 g (2.2 mnmol) of hydroxylammonium chloride was added, and, again, the mixture was stirred for 16 h at RT. Thereafter, a further 0.15 g (2.2 mmol) of 0 hydroxylammonium chloride was added, and the mixture was stirred for a further 3 d at RT. The solvent was removed in vacuo, and the residue was taken up in ethyl acetate. The solution was washed with 1 N HC, the organic phase was dried, and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel. This gave 1.00 g of product in 95% purity. 5 2. Preparation of 5-cyclopropyl-4-(3-methylamino-2-methyl-4-methylsulfonyl benzoyl)isoxazole (No. 2 of Table A) Step 1: Synthesis of 1 -cyclopropyl-2-(dimethylaminomethylidene)-3-(3-methylamino 2 -methyl-4-methylsulfonylphenyl)propane- 1,3-dione ) A solution of 1.58 g (5.1 mmol) of 1-cyclopropyl-3-(3-methylamino-2-methyl 4-methylsulfonylphenyl)propane-1,3-dione and 2.0 ml (15.3 mmol) of N,N-dimethyl formamide dimethyl acetal was stirred for 3 h at RT. The mixture was treated with WO 2009/118125 PCT/EP2009/002029 26 10 ml of CH 2
CI
2 , stirred for 2 h at an oil-bath temperature of 50CC, left to stand overnight, stirred for 1 d at an oil-bath temperature of 50 0 C, and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel. This gave 0.85 g of product in 93% purity. 5 Step 2: Synthesis of 5-cyclopropyl-4-(3-methylamino-2-methyl-4-methylsulfonyl benzoyl)isoxazole 0.19 g (2.8 mmol) of hydroxylammonium chloride was added to a solution of 0.85 g (2.3 mmol) of 1-cyclopropyl-2-(dimethylaminomethylidene)-3-(3-methylamino 10 2-methyl-4-methylsulfonylphenyi)propane-1,3-dione in 100 ml of ethanol. The mixture was stirred for 3 h at RT, and the solvent was removed in vacuo. The residue was taken up in CH 2 Cl 2 , washed with 10% strength H 2
SO
4 and dried over MgSO 4 . The solvent was removed in vacuo, and the residue was purified by column chromatography on silica gel. This gave 0.50 g of product in 95% purity. 15 The examples listed in the tables hereinbelow were prepared analogously to abovementioned methods or are obtainable analogously to abovementioned methods. These compounds are very particularly preferred. 20 The abbreviations used are: All = allyl Et = ethyl Me = methyl Pr = propyl WO 2009/118125 PCT/EP2009/002029 27 Table A: Compounds of the formula (1) according to the invention 0 x A N: z Y No. X Y A ZPhysical data: 1H NMR: 5 [CDC1 3 ] 8.18 (s,1H), 7.76 (d, 1H), 6.80 (d, 1H), 1 Me SO 2 Me NH 2 H 5.32 (br, 2H), 3.11 (s, 3H), 2.62-2.71 (m, 1H), 2.18 (s, 3H), 1.34-1.40 (m, 2H), 1.22-1.29 (m, 2H) 8.21 (s,1H), 7.82 (d, 1H), 6.96 (d, IH), 2 Me SO 2 Me NHMe H 5.62 (br, 1 H), 3.09 (s, 3H), 3.01 (s, 3H), 2.56-2.64 (m, 1H), 2.32 (s, 3H), 1.33 1.40 (m, 2H), 1.21-1.27 (m, 2H) 8.21 (s,1H), 7.82 (d, 1H), 6.97 (d, 1H), 5.55 (br, 1H), 3.27 (q, 2H), 3.11 (s, 3H), 3 Me SO 2 Me NHEt H 2.57-2.65 (m, 1H), 2.29 (s, 3H), 1.33 1.39 (m, 2H), 1.31 (t, 3H), 1.22-1.28 (m, 2H) 8.21 (s,IH), 7.82 (d, 1H), 6.95 (d, 1H), 5.68 (br, 1H), 3.18 (dd, 2H), 3.11 (s, 4 Me SO 2 Me NH-n-Pr H 3H), 2.56-2.63 (m, 1H), 2.29 (s, 3H), 1.66-1.76 (m, 2H), 1.34-1.39 (m, 2H), 1.21-1.28 (m, 2H), 1.03 (t, 3H) 8.19 (s,1H), 7.84 (d, 1H), 6.98 (d, 1H), 5.93.6.05 (m, 1H), 5.68 (br, 1H), 5.32 5 Me SO 2 Me NHAII H 5.39 (m, 1H), 5.20-5.25 (m, 1H), 3.82 3.88 (m, 2H), 3.11 (s, 3H), 2.58-2.66 (m, 1H), 2.29 (s, 3H), 1.33-1.39 (m, 2H), 1.21-1.28 (m, 2H) 8.21 (s,1H), 7.84 (d, 1H), 6.97 (d, 1H), 5.81 (br, 1 H), 3.62 (dd, 2H), 3.42 (br, 6 Me SO 2 Me NH(CH 2
)
2 0-Me H 2H), 3.41 (s, 3H), 3.21 (s, 3H), 2.54-2.62 (m, 1H), 2.29 (s, 3H), 1.33-1.39 (m, 2H), 1.21-1.28 (m, 2H) 7 Me SO 2 Me NH(CH2) 2 0-Et H 8.22 (s,1H),~7.84 (d, 1H), 6.97 (d, 1H), 5.84 (br, 1H), 3.66 (dd, 2H), 3.57 (q, 2H), 3.42 (dd, 2H), 3.21 (s, 3H), 2.53 2.63 (m, 1H), 2.29 (s, 3H), 1.32-1.40 (m, 2H), 1.24 (t, 3H), 1.19-1.29 (m, 2H) 8 Me SO 2 Me NH(CH 2
)
3 0-Me H 8.21 (s,1H), 7.83 (d, 1H), 6.98 (d, 1H), 5.64 (br, 1H), 3.55 (t, 2H), 3.37 (s, 3H), 3.32 (t, 2H), 3.13 (s, 3H), 2.55-2.63 (m, 1H), 2.30 (s, 3H), 1.90-1.99 (m, 2H), 1.34-1.39 (m, 2H), 1.21-1.28 (m, 2H) WO 2009/118125 PCT/EP2009/002029 28 No. X Y AZPhysical data: H NMR: 6 [CDCis] 9 Me SO 2 Me N=CH-NMe 2 H 10 Me SO 2 Me NH 2
CO
2 Me 11 Me SO 2 Me NHMe CO 2 Me 12 Me SO 2 Me NHEt CO 2 Me 13 Me SO 2 Me NH-n-Pr CO 2 Me 14 Me SO 2 Me NHAII CO 2 Me 15 Me SO 2 Me NH(CH 2
)
2 0-Me CO 2 Me 16 Me SO 2 Me N=CH-NMe 2
CO
2 Me 17 Me SO 2 Me N=CH-NMe 2
CO
2 Et 18 Me SO 2 Me NH 2
CO
2 Et 19 Me SO 2 Me NHMe CO 2 Et 20 Me SO 2 Me NHEt CO 2 Et 21 Me SO 2 Me NH-n-Pr CO 2 Et 22 Me SO 2 Me NHAII CO 2 Et 23 Me SQ 2 Me NH(CH 2
)
2 0-Me CO 2 Et 8.18 (s,1H), 8.04 (d, 1H), 7.32 (d, 1H), 24 Me SO 2 Me NMe 2 H 3.29 (s, 3H), 2.93 (s, 6H), 2.58-2.66 (m, 1 H), 2.37 (s, 3H), 1.34-1.40 (m, 2H), 1.22-1.29 (m, 2H) 25 Me SO 2 Me N(Me)Et H 26 Me SO 2 Me N(Me)-n-Pr H 27 Me SO 2 Me N(Me)AII H 28 Me SO 2 Me N(Me)(CH 2
)
2 0-Me H 29 Me SO 2 Me NMe 2
CO
2 Me 30 Me SO 2 Me N(Me)Et CO 2 Me 31 Me SO 2 Me N(Me)-n-Pr CO 2 Me 32 Me SC 2 Me N(Me)AIl CO 2 Me 33 Me SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Me 34 Me SO 2 Me NMe 2
CO
2 Et 35 Me SO 2 Me N(Me)Et CO 2 Et 36 Me SO 2 Me N(Me)-n-Pr CO 2 Et 37 Me SO 2 Me N(Me)AII CO 2 Et 38 Me SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Et WO 2009/118125 PCT/EP2009/002029 29 No. X Y A Z Physical data: 'H NMR: 6 [CDCI] 39 Me CF 3
NH
2 H 40 Me CF 3 NHMe H 41 Me CF 3 NHEt H 42 Me CF 3 NH-n-Pr H 43 Me CF 3 NHAII H 44 Me CFa NH(CH 2
)
2 0-Me H 45 Me CF 3 N=CH-NMe 2 H 46 Me CF 3
NH
2
CO
2 Me 47 Me CF 3 NHMe CO 2 Me 48 Me CF 3 NHEt CO 2 Me 49 Me CF 3 NH-n-Pr
CO
2 Me 50 Me CF 3 NHAI CO 2 Me 51 Me CF 3
NH(CH
2
)
2 0-Me CO2Me 52 Me CF 3 N=CH-NMe 2
CO
2 Me 53 Me CF 3
NH
2
CO
2 Et 54 Me CF 3 NHMe CO 2 Et 55 Me CF 3 NHEt CO 2 Et 56 Me CF 3 NH-n-Pr CO 2 Et 57 Me CF 3 NHAII CO 2 Et 58 Me CF 3
NH(CH
2
)
2 0-Me CO 2 Et 59 Me CF 3 N=CH-NMe 2
CO
2 Et 60 Me CF 3 NMe 2 H 61 Me CF 3 N(Me)Et H 62 Me CF 3 N(Me)-n-Pr H 63 Me CF 3 N(Me)AII H 64 Me CF 3 N(Me)(CH 2
)
2 0-Me H 65 Me CF 3 NMe 2
CO
2 Me 66 Me CF 3 N(Me)Et CO 2 Me 67 Me CF 3 N(Me)-n-Pr CO 2 Me 68 Me CF 3 N(Me)AII CO 2 Me 69 Me CF 3 N(Me)(CH 2
)
2 0-Me CO 2 Me WO 2009/118125 PCT/EP2009/002029 30 Physical data:. No. X YA Z 1 NR6CC 3 H NMR: 6 [CD Cla] 70 Me CF 3 NMe 2
CO
2 Et 71 Me CF 3 N(Me)Et CO 2 Et 72 Me CF 3 N(Me)-n-Pr CO 2 Et 73 Me CF 3 N(Me)Al CO 2 Et 74 Me CF N(Me)(CH 2
)
2 0-Me CO 2 Et 75 Me C NH 2 H 76 Me CI NHMe H 77 Me Cl NHEt H 78 Me CI NH-n-Pr H 79 Me CI NHAII H 80 Me C1 NH(CH 2
)
2 0-Me H 81 Me CI N=CH-NMe 2 H 82 Me CI NH 2
CO
2 Me 83 Me CI NHMe CO 2 Me 84 Me C1 NHEt CO 2 Me 85 Me CI NH-n-Pr CO 2 Me 86 Me C1 NHAII CO 2 Me 87 Me CI NH(CH 2
)
2 0-Me CO 2 Me 88 Me CI N=CH-NMe 2
CO
2 Me 89 Me CI NH 2
CO
2 Et 90 Me CI NHMe CO 2 Et 91 Me CI NHEt CO 2 Et 92 Me C1 NH-n-Pr CO 2 Et 93 Me CI NHAII CO 2 Et 94 Me CI NH(CH2)20-Me CO 2 Et 95 Me CI N=CH-NMe 2
CO
2 Et 96 Me Cl NMe 2 H 97 Me CI N(Me)Et H 98 Me CI N(Me)-n-Pr H 99 Me CI N(Me)AII H 100 Me C N(Me)(CH 2
)
2 0-Me H WO 2009/118125 PCT/EP2009/002029 31 No.. X Y Z Physical data: No. X Y. A Z 1 NR5CC 3 H N.MR: 5 [CDC13] 101 Me CI NMe 2
CO
2 Me 102 Me CI N(Me)Et CO 2 Me 103 Me CI N(Me)-n-Pr CO 2 Me 104 Me CI N(Me)AII CO 2 Me 105 Me CI N(Me)(CH2) 2 O-Me CO 2 Me 106 Me CI NMe 2
CO
2 Et 107 Me CI N(Me)Et CO 2 Et 108 Me Cl N(Me)-n-Pr CO 2 Et 109 Me CI N(Me)AI CO 2 Et 110 Me CI N(Me)(CH 2
)
2 0-Me CO 2 Et 111 Me OMe NH 2 H 112 Me OMe NHMe H 113 Me OMe NHEt H 114 Me OMe NH-n-Pr H 115 Me OMe NHAII H 116 Me OMe NH(CH 2
)
2 0-Me H 117 Me OMe N=CH-NMe 2 H 118 Me OMe
NH
2
CO
2 Me 119 Me OMe NHMe
CO
2 Me 120 Me OMe NHEt CO 2 Me 121 Me OMe NH-n-Pr CO 2 Me 122 Me OMe NHAII CO 2 Me 123 Me OMe NH(CH 2
)
2 0-Me CO 2 Me 124 Me OMe N=CH-NMe 2
CO
2 Me 125 Me OMe NH 2
CO
2 Et 126 Me OMe NHMe CO 2 Et 127 Me OMe NHEt CO 2 Et 128 Me OMe NH-n-Pr CO 2 Et 129 Me OMe NHAII CO 2 Et 130 Me OMe NH(CH 2
)
2 0-Me CO 2 Et 131 Me OMe N=CH-NMe 2
CO
2 Et WO 2009/118125 PCT/EP2009/002029 32 No .A zPhysical data: l NMR: 6CDC 3 ] 132 Me OMe NMe 2 H 133 Me OMe N(Me)Et H 134 Me OMe N(Me)-n-Pr H 135 Me OMe N(Me)Al H 136 Me OMe N(Me)(CH 2
)
2 0-Me H 137 Me OMe NMe 2
CO
2 Me 138 Me OMe N(Me)Et CO 2 Me 139 Me OMe N(Me)-n-Pr CO 2 Me 140 Me OMe N(Me)AII CO 2 Me 141 Me OMe N(Me)(CH 2
)
2 0-Me CO 2 Me 142 Me OMe NMe 2
CO
2 Et 143 Me OMe N(Me)Et CO 2 Et 144 Me OMe N(Me)-n-Pr CO 2 Et 145 Me OMe N(Me)AII CO 2 Et 146 Me OMe N(Me)(CH 2
)
2 0-Me CO 2 Et 147 SO 2 Me SO 2 Me NH 2 H 148 SO 2 Me SO 2 Me NHMe H 149 SO 2 Me SO 2 Me NHEt H 150 SO 2 Me SO 2 Me NH-n-Pr H 151 SO 2 Me SO 2 Me NHAII H 152 SO 2 Me SO 2 Me NH(CH 2
)
2 0-Me H 153 SO 2 Me SO 2 Me N=CH-NMe 2 H 154 SO 2 Me SQ 2 Me NH 2
CO
2 Me 155 SO 2 Me SO 2 Me NHMe CO 2 Me 156 SO 2 Me SO 2 Me NHEt CO 2 Me 157 SO 2 Me SO 2 Me NH-n-Pr CO 2 Me 158 SO 2 Me SO 2 Me NHAII CO 2 Me 159 SO 2 Me SO 2 Me NH(CH 2
)
2 0-Me CO 2 Me 160 SO 2 Me SO 2 Me N=CH-NMe 2
CO
2 Me 161 SO 2 Me SO 2 Me NH 2
CO
2 Et 162 SO 2 Me SO 2 Me NHMe CO 2 Et 163 SO 2 Me SO 2 Me NHEt CO 2 Et 164 SO 2 Me SO 2 Me NH-n-Pr CO 2 Et 165 SO 2 Me SO 2 Me NHAI CO 2 Et WO 2009/118125 PCT/EP2009/002029 33 No. X Y A ZPhysical data: __________ H NMR: .6 [CDC 3 ] 166 SO 2 Me SO 2 Me NH(GH 2
)
2 0-Me CO 2 Et 167 SO 2 Me SO 2 Me N=CH-NMe 2
CO
2 Et 168 SO 2 Me SO 2 Me NMe 2 H 169 SO 2 Me SO 2 Me N(Me)Et H 170 SO 2 Me SO 2 Me N(Me)-n-Pr H 171 SO 2 Me SO 2 Me N(Me)AII H 172 SO 2 Me SO 2 Me N(Me)(CH 2
)
2 0-Me H 173 SO 2 Me SO 2 Me NMe 2
CO
2 Me 174 SO 2 Me SO 2 Me N(Me)Et CO 2 Me 175 SO 2 Me SO 2 Me N(Me)-n-Pr CO 2 Me 176 SO 2 Me SO 2 Me N(Me)AII CO 2 Me 177 SC 2 Me SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Me 178 SO 2 Me SO 2 Me NMe 2
CO
2 Et 179 SO 2 Me SO 2 Me N(Me)Et CO 2 Et 180 SO 2 Me SO 2 Me N(Me)-n-Pr CO 2 Et 181 SO 2 Me SO 2 Me N(Me)AII CO 2 Et 182 SO 2 Me SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Et 8.21 (s, IH), 7.72 (d, 1H), 6.67 (d, 1H), 183 SO 2 Me CF 3
NH
2 H 6.12 (br. s, 2H), 3.25 (s, 3H), 2.57 (m, 1 H), 1.38 - 1.32 (m, 2H), 1.25 - 1.22 (m, 2H) 8.19 (s, 1H), 7.83 (d, 1H), 6.97 (q, 1H), 184 SO 2 Me CF 3 NHMe H 6.68 (d, 1H), 3.23 (s, 3H), 3.12 (m, 3H), 2.57 (m, 1 H), 1.37 - 1.32 (m, 2H), 1.26 1.20 (m, 2H) 8.21 (s, 1 H), 7.83 (d, 1H), 6.71 (d, 1H), 185 SO 2 Me CF 3 NHEt H 6.63 (t, 1H), 3.42 (m, 2H), 3.27 (s, 3H), 2.58 (m, 1H), 1.38 - 1.32 (m, 2H), 1.25 1.20 (m, 2H) 186 SO 2 Me CF 3 NH-n-Pr H 187 SO 2 Me CF 3 NHAII H 188 SO 2 Me CF 3
NH(CH
2
)
2 0-Me H 189 SO 2 Me CF 3 N=CH-NMe 2 H 190 SO 2 Me CF 3
NH
2
CO
2 Me 191 SO 2 Me CF 3 NHMe CO 2 Me 192 SO 2 Me CF 3 NHEt CO 2 Me 193 SO 2 Me CF 3 NH-n-Pr CO 2 Me 194 SO 2 Me CF 3 NHAII CO 2 Me 195 SO 2 Me CF 3
NH(CH
2
)
2 0-Me CO 2 Me 196 SO 2 Me CF 3 N=CH-NMe 2
CO
2 Me WO 2009/118125 PCT/EP2009/002029 34 No. X Y A Z Physical data: 1H NMR: 6,[CDC 3 ]. 7.68 (d, 1 H), 6.66 (d, 1 H), 6.08 (br. s, 197 SO 2 Me CF 3
NH
2 C02Et 2H), 4.18 (q, 2H), 3.27 (s, 3H), 2.48 (m, 1 H), 1.37 - 1.32 (m, 2H), 1.28 - 1.20 (t + m, 5H) 198 SO 2 Me CF 3 NHMe CO 2 Et 199 SO 2 Me CF 3 NHEt CO 2 Et 200 SO 2 Me CF 3 NH-n-Pr CO 2 Et 201 SO 2 Me CF 3 NHAII CO 2 Et 202 SO 2 Me CF 3
NH(CH
2
)
2 0-Me CO 2 Et 203 SO 2 Me CF 3 N=CH-NMe 2
CO
2 Et 8.12 (s, 1H), 7.98 (d, IH), 7.32 (d, 1H), 204 SO 2 Me CF 3 NMe 2 H 3.32 (s, 3H), 2.92 (s, 6H), 2.67 (m, 1H), -_ 1.38 - 1.33 (m, 2H), 1.27 - 1.22 (m, 2H) 205 SO 2 Me CF 3 N(Me)Et H 206 SO 2 Me CF 3 N(Me)-n-Pr H 207 SO 2 Me CF 3 N(Me)AII H 208 SO 2 Me CF 3 N(Me)(CH 2
)
2 0-Me H 209 SO 2 Me CF 3 NMe 2
CO
2 Me 210 SO 2 Me CF 3 N(Me)Et CO 2 Me 211 SO 2 Me CF 3 N(Me)-n-Pr CO 2 Me 212 SO 2 Me CF 3 N(Me)AIl CO 2 Me 213 SO 2 Me CF 3 N(Me)(CH 2
)
2 0-Me CO 2 Me 214 SO 2 Me CF 3 NMe 2
CO
2 Et 215 SO 2 Me CF 3 N(Me)Et CO 2 Et 216 SQ 2 Me CF 3 N(Me)-n-Pr CO 2 Et 217 SO 2 Me CF 3 N(Me)AII CO 2 Et 218 SO 2 Me CF 3 N(Me)(CH 2
)
2 0-Me CO 2 Et 219 SO 2 Me CI NH 2 H 220 SO 2 Me Cl NHMe H 221 SO 2 Me Cl NHEt H 222 SO 2 Me CI NH-n-Pr H 223 SO 2 Me CI NHAII H 224 SO 2 Me C1 NH(CH 2
)
2 0-Me H 225 SO 2 Me Cl N=CH-NMe 2 H 226 SO 2 Me CI
NH
2
CO
2 Me WO 2009/118125 PCT/EP2009/002029 35 No.. X Y A Z Physical data: H NMR: 6 [CDC 3 ] 227 SO 2 Me CI NHMe CO 2 Me 228 SO 2 Me CI NHEt CO 2 Me 229 SO 2 Me CI NH-n-Pr CO 2 Me 230 SO 2 Me CI NHAII CO 2 Me 231 SO 2 Me C1 NH(CH 2
)
2 0-Me CO 2 Me 232 SO 2 Me CI N=CH-NMe 2
CO
2 Me 233 SO 2 Me Cl NH 2
CO
2 Et 234 SO 2 Me C1 NHMe CO 2 Et 235 SO 2 Me CI NHEt CO 2 Et 236 SO 2 Me CI NH-n-Pr CO 2 Et 237 SO 2 Me CI NHAII CO 2 Et 238 SO 2 Me Cl NH(CH 2
)
2 0-Me CO 2 Et 239 SO 2 Me CI N=CH-NMe 2
CO
2 Et 240 SO 2 Me C NMe 2 H 241 SO 2 Me CI N(Me)Et H 242 SO 2 Me C N(Me)-n-Pr H 243 SO 2 Me Cl N(Me)AII H 244 SO 2 Me CI N(Me)(CH 2
)
2 0-Me H 245 SO 2 Me CI NMe 2
CO
2 Me 246 SO 2 Me CI N(Me)Et CO 2 Me 247 SO 2 Me C1 N(Me)-n-Pr CO 2 Me 248 SQ 2 Me C1 N(Me)AII CO 2 Me 249 SO 2 Me CI N(Me)(CH 2
)
2 0-Me CO 2 Me 250 SO 2 Me CI NMe 2
CO
2 Et 251 SO 2 Me Cl N(Me)Et CO 2 Et 252 SO 2 Me CI N(Me)-n-Pr CO 2 Et 253 SO 2 Me CI N(Me)AII CO 2 Et 254 SO 2 Me CI N(Me)(CH 2
)
2 0-Me CO 2 Et 255 SO 2 Me OMe NH 2 H 256 SO 2 Me OMe NHMe H 257 SO 2 Me OMe NHEt H WO 2009/118125 PCT/EP2009/002029 36 No. X Y A Z Physical data: 1 H NMR: 5 jCDC 3 ] 258 SO 2 Me OMe NH-n-Pr H 259 SO 2 Me OMe NHAII H 260 SO 2 Me OMe NH(CH 2
)
2 0-Me H 261 SO 2 Me OMe N=CH-NMe 2 H 262 SO 2 Me OMe NH 2
CO
2 Me 263 SO 2 Me OMe NHMe CO 2 Me 264 SO 2 Me OMe NHEt CO 2 Me 265 SO 2 Me OMe NH-n-Pr CO 2 Me 266 SO 2 Me OMe NHAII CO 2 Me 267 SO 2 Me OMe NH(CH 2
)
2 0-Me CO 2 Me 268 SO 2 Me OMe N=CH-NMe 2
CO
2 Me 269 SO 2 Me OMe NH 2
CO
2 Et 270 SO 2 Me OMe NHMe CO 2 Et 271 SO 2 Me OMe NHEt CO 2 Et 272 SO 2 Me OMe NH-n-Pr CO 2 Et 273 SO 2 Me OMe NHAI CO 2 Et 274 SO 2 Me OMe NH(CH 2
)
2 0-Me CO 2 Et 275 SO 2 Me OMe N=CH-NMe 2
CO
2 Et 276 SO 2 Me OMe NMe 2 H 277 SQ 2 Me OMe N(Me)Et H 278 SO 2 Me OMe N(Me)-n-Pr H 279 SO 2 Me OMe N(Me)AII H 280 SO 2 Me OMe N(Me)(CH 2
)
2 0-Me H 281 SO 2 Me OMe NMe 2
CO
2 Me 282 SO 2 Me OMe N(Me)Et
CO
2 Me 283 SO 2 Me OMe N(Me)-n-Pr
CO
2 Me 284 SO 2 Me OMe N(Me)AII CO 2 Me 285 SO 2 Me OMe N(Me)(CH 2
)
2 0-Me CO 2 Me 286 SO 2 Me OMe NMe 2
CO
2 Et 287 SO 2 Me OMe N(Me)Et CO 2 Et 288 SO 2 Me OMe N(Me)-n-Pr CO 2 Et WO 2009/118125 PCT/EP2009/002029 37 No. X Y A Z ~1 Physical data: H NMR: 6 {CDCis] 289 SO 2 Me OMe N(Me)AII CO 2 Et 290 SO 2 Me OMe N(Me)(CH 2
)
2 0-Me CO 2 Et 291 CF 3
SO
2 Me NH 2 H 292 CF 3
SO
2 Me NHMe H 293 CF 3
SO
2 Me NHEt H 294 CF 3
SO
2 Me NH-n-Pr H 295 CF 3
SO
2 Me NHAI H 296 CF 3
SO
2 Me NH(CH 2
)
2 0-Me H 297 CF 3
SO
2 Me N=CH-NMe 2 H 298 CF 3
SO
2 Me NH 2
CO
2 Me 299 CF 3
SO
2 Me NHMe CO 2 Me 300 CF SO 2 Me NHEt CO 2 Me 301 CF 3
SO
2 Me NH-n-Pr CO 2 Me 302 CF 3
SO
2 Me NHAII CO 2 Me 303 CF 3
SO
2 Me NH(CH 2
)
2 0-Me CO 2 Me 304 CF 3
SO
2 Me N=CH-NMe 2
CO
2 Me 305 CF 3
SQ
2 Me NH 2
CO
2 Et 306 CF 3
SO
2 Me NHMe
CO
2 Et 307 CF 3
SO
2 Me NHEt
CO
2 Et 308 CF 3
SC
2 Me NH-n-Pr CO 2 Et 309 CF 3
SO
2 Me NHAII CO 2 Et 310 CF 3
SO
2 Me NH(CH 2
)
2 0-Me CO 2 Et 311 CF 3
SO
2 Me N=CH-NMe 2
CO
2 Et 312 CFa SO 2 Me NMe 2 H 313 CF 3
SO
2 Me N(Me)Et H 314 CF 3
SO
2 Me N(Me)-n-Pr H 315 CF 3
SO
2 Me N(Me)AII H 316 CF 3
SO
2 Me N(Me)(CH 2
)
2 0-Me H 317 CF 3
SO
2 Me NMe 2
CO
2 Me 318 CF 3
SQ
2 Me N(Me)Et CO 2 Me 319 CF 3
SO
2 Me N(Me)-n-Pr
CO
2 Me WO 2009/118125 PCTIEP2009/002029 38 No. X Y -A Physical data: 'H NMR. 6 [CDC 3 I 320 CF 3
SO
2 Me N(Me)AII
CO
2 Me 321 CF 3
SO
2 Me N(Me)(CH 2
)
2 0-Me CO 2 Me 322 CF 3
SO
2 Me NMe 2
CO
2 Et 323 CF 3
SO
2 Me N(Me)Et CO 2 Et 324 CF 3
SO
2 Me N(Me)-n-Pr CO 2 Et 325 CF 3
SO
2 Me N(Me)AII CO 2 Et 326 CF 3
SO
2 Me N(Me)(CH 2
)
2 0-Me CO 2 Et 327 CF 3 CI NH 2 H 328 CF 3 Cl NHMe H 329 CF 3 CI NHEt H 330 CF 3 CI NH-n-Pr H 331 CF 3 Cl NHAII H 332 CF 3 CI NH(CH2)20-Me H 333 CF 3 CI N=CH-NMe 2 H 334 CF 3 CI NH 2
CO
2 Me 335 CF 3 C NHMe CO 2 Me 336 CF 3 CI NHEt CO 2 Me 337 CF 3 CI NH-n-Pr CO 2 Me 338 CF 3 CI NHAII CO 2 Me 339 CF 3 CI NH(CH 2
)
2 0-Me CO 2 Me 340 CF 3 C N=CH-NMe 2
CO
2 Me 341 CF 3 CI NH 2
CO
2 Et 342 CF 3 CI NHMe CO 2 Et 343 CF 3 CI NHEt CO 2 Et 344 CF 3 CI NH-n-Pr CO 2 Et 345 CF 3 CI NHAII CO 2 Et 346 CF 3 CI NH(CH 2
)
2 0-Me CO 2 Et 347 CF 3 CI N=CH-NMe 2
CO
2 Et 348 CF 3 CI NMe 2 H 349 CF 3 CI N(Me)Et H 350 CF 3 CI N(Me)-n-Pr H WO 2009/118125 PCT/EP2009/002029 39 N. YA Physical data: 1 HNMR: 6 [CDCI 3 j 351 CF 3 CI N(Me)AII H 352 CF 3 Cl N(Me)(CH 2
)
2 0-Me H 353 CF 3 Cl NMe 2
CO
2 Me 354 CF 3 CI N(Me)Et CO 2 Me 355 CF 3 CI N(Me)-n-Pr CO 2 Me 356 CF 3 Cl N(Me)AII CO 2 Me 357 CF 3 CI N(Me)(CH 2
)
2 0-Me CO 2 Me 358 CF 3 CI NMe 2
CO
2 Et 359 CF 3 CI N(Me)Et CO 2 Et 360 CF 3 CI N(Me)-n-Pr CO 2 Et 361 CF 3 Cl N(Me)AI CO 2 Et 362 CF 3 CI N(Me)(CH 2
)
2 0-Me CO 2 Et 363 CF 3 OMe NH 2 H 364 CF 3 OMe NHMe H 365 CF 3 OMe NHEt H 366 CF 3 OMe NH-n-Pr H 367 CF 3 OMe NHAII H 368 CF 3 OMe NH(CH 2
)
2 0-Me H 369 CF 3 OMe N=CH-NMe 2 H 370 CF 3 OMe NH 2
CO
2 Me 371 CF 3 OMe NHMe CO 2 Me 372 CF 3 OMe NHEt CO 2 Me 373 CF 3 OMe NH-n-Pr CO 2 Me 374 CF 3 OMe NHAII CO 2 Me 375 CF 3 OMe NH(CH 2
)
2 0-Me CO 2 Me 376 CF 3 OMe N=CH-NMe 2
CO
2 Me 377 CF 3 OMe NH 2
CO
2 Et 378 CF 3 OMe NHMe CO 2 Et 379 CF 3 OMe NHEt CO 2 Et 380 CF 3 OMe NH-n-Pr CO 2 Et 381 CF 3 OMe NHAII CO 2 Et WO 2009/118125 PCT/EP2009/002029 40 No. X Y A z. Physical data: :H NMR:6[CDC 3 ] 382 CF 3 OMe NH(CH 2
)
2 0-Me CO 2 Et 383 CF 3 OMe N=CH-NMe 2
CO
2 Et 384 CF 3 OMe NMe 2 H 385 CF 3 OMe N(Me)Et H 386 CF 3 OMe N(Me)-n-Pr H 387 CF 3 OMe N(Me)AII H 388 CF 3 OMe N(Me)(CH 2
)
2 0-Me H 389 CF 3 OMe NMe 2
CO
2 Me 390 CF 3 OMe N(Me)Et CO 2 Me 391 CF 3 OMe N(Me)-n-Pr CO 2 Me 392 CF 3 OMe N(Me)AII CO 2 Me 393 CF 3 OMe N(Me)(CH 2
)
2 0-Me CO 2 Me 394 CF 3 OMe NMe 2
CO
2 Et 395 CF 3 OMe N(Me)Et CO 2 Et 396 CF 3 OMe N(Me)-n-Pr CO 2 Et 397 CF 3 OMe N(Me)AII CO 2 Et 398 CF 3 OMe N(Me)(CH 2
)
2 0-Me CO 2 Et 8.18 (s,1H), 7.81 (d, 1H), 6.83 (d, 1H), 399 Cl SO 2 Me NH 2 H 5.77 (br, 2H), 3.12 (s, 3H), 2.66-2.75 (m, 1H), 1.36-1.41 (m, 2H), 1.24-1.31 (m, 2H) 400 CI SO 2 Me NHMe H 401 CI SO 2 Me NHEt H 8.18 (s,1H), 7.89 (d, 1H), 6.93 (d, 1H), 402 CI SO 2 Me NH-n-Pr H 3.51 (t, 2H), 3.14 (s, 3H), 2.61-2.72 (m, 1 H), 1.64-1.78 (m, 2H), 1.34-1.42 (m, 2H), 1.22-1-33 (m, 2H), 1.03 (t, 3H) 403 Cl SO 2 Me NHAII H 404 Cl SO 2 Me NH(CH 2
)
2 0-Me H 8.16 (s,1H), 8.03 (d, 1H), 7.45 (s, 1H), 405 CI SO 2 Me N=CH-NMe 2 H 7.09 (d, 1H), 3.32 (s, 3H), 3.13 (s, 3H), 3.09 (s, 3H), 2.69-2.82 (m, 1H), 1.35 1.44 (m, 2H), 1.23-1.34 (m, 2H) 406 CI SO 2 Me NH 2
CO
2 Me 407 Cl SO 2 Me NHMe CO 2 Me WO 2009/118125 PCT/EP2009/002029 41 No. X YPhysical data: H NMR>6[CDCIa 408 CI SO 2 Me NHEt
CO
2 Me 409 CI SO 2 Me NH-n-Pr CO 2 Me 410 CI SO 2 Me NHAII CO 2 Me 411 CI SO 2 Me NH(CH 2
)
2 0-Me CO 2 Me 412 CI SO 2 Me N=CH-NMe 2
CO
2 Me 413 CI SO 2 Me NH 2
CO
2 Et 414 Ci SO 2 Me NHMe CO 2 Et 415 CI SO 2 Me NHEt CO 2 Et 416 CI SO 2 Me NH-n-Pr CO 2 Et 417 CI SO 2 Me NHAII CO 2 Et 418 Ci SO 2 Me NH(CH 2
)
2 0-Me CO 2 Et 419 C SO 2 Me N=CH-NMe 2
CO
2 Et 420 CI SO 2 Me NMe 2 H 421 Cl SO 2 Me N(Me)Et H 422 CI SO 2 Me N(Me)-n-Pr H 423 CI SO 2 Me N(Me)AII H 424 Cl SO 2 Me N(Me)(CH 2
)
2 0-Me H 425 Ci SO 2 Me NMe 2
CO
2 Me 426 Cl SO 2 Me N(Me)Et CO 2 Me 427 CI SO 2 Me N(Me)-n-Pr CO 2 Me 428 CI SO 2 Me N(Me)AII CO 2 Me 429 CI SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Me 430 C SQ 2 Me NMe 2
CO
2 Et 431 C1 SO 2 Me N(Me)Et CO 2 Et 432 Cl SO 2 Me N(Me)-n-Pr CO 2 Et 433 CI SO 2 Me N(Me)AI CO 2 Et 434 CI SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Et 435 CI CF 3
NH
2 H 436 CI CF 3 NHMe H 437 Cl CF 3 NHEt H 438 CI CF 3 NH-n-Pr H WO 2009/118125 PCT/EP2009/002029 42 No. X 'F A Z Physical data: I [ 1 'H NMR 6{CDC 3 ] 439 C1 CF 3 NHAJI H 440 CI CF 3
NH(CH
2
)
2 0-Me H 441 Cl CF 3 N=CH-NMe 2 H 442 CI CF 3
NH
2
CO
2 Me 443 CI CF 3 NHMe CO 2 Me 444 CI CF 3 NHEt CO 2 Me 445 CI CF 3 NH-n-Pr
CO
2 Me 446 Cl CF 3 NHAII CO 2 Me 447 CI CF 3
NH(CH
2
)
2 0-Me CO 2 Me 448 CI CF 3 N=CH-NMe 2
CO
2 Me 449 Ci CF 3
NH
2
CO
2 Et 450 CI CF 3 NHMe CO 2 Et 451 C , CF 3 NHEt CO 2 Et 452 CI CF 3 NH-n-Pr CO 2 Et 453 CI CF 3 NHAII CO 2 Et 454 CI CF 3
NH(CH
2
)
2 0-Me CO 2 Et 455 CI CF 3 N=CH-NMe 2
CO
2 Et 456 C1 CF 3 NMe 2 H 457 CI CF 3 N(Me)Et H 458 CI CF 3 N(Me)-n-Pr H 459 C CF 3 N(Me)AII H 460 CI CF 3 N(Me)(CH 2
)
2 0-Me H 461 CI CF 3 NMe 2
CO
2 Me 462 C1 CF 3 N(Me)Et CO 2 Me 463 CI CF 3 N(Me)-n-Pr CO 2 Me 464 CI CF 3 N(Me)AII CO 2 Me 465 CI CF 3 N(Me)(CH 2
)
2 0-Me CO 2 Me 466 CI CF 3 NMe 2
CO
2 Et 467 CI CF 3 N(Me)Et CO 2 Et 468 CI CF 3 N(Me)-n-Pr CO 2 Et 469 CI CF 3 N(Me)AII CO 2 Et WO 2009/118125 PCT/EP2009/002029 43 No. X Y A Z ,Physical data: H NMR: & [CDCis] 470 CI CF 3 N(Me)(CH 2
)
2 0-Me CQ 2 Et 471 CI CI NH 2 H 472 C1 CI NHMe H 473 CI CI NHEt H 474 Ci C1 NH-n-Pr H 475 CI CI NHAJI H 476 CI CI NH(CH 2
)
2 0-Me H 477 CI CI N=CH-NMe 2 H 478 CI C1 NH 2
CO
2 Me 479 CI CI NHMe CO 2 Me 480 CI CI NHEt CO 2 Me 481 CI CI NH-n-Pr CO 2 Me 482 C] C1 NHAJI CO 2 Me 483 CI Cl NH(CH 2
)
2 0-Me CO 2 Me 484 CI C1 N=CH-NMe 2
CO
2 Me 485 Cl CI NH 2
CO
2 Et 486 CI CI NHMe CO 2 Et 487 CI CI NHEt CO 2 Et 488 CI CI NH-n-Pr CO 2 Et 489 C1 Ci NHAII CO 2 Et 490 C C NH(CH 2
)
2 0-Me CO 2 Et 491 CI CI N=CH-NMe 2
CO
2 Et 492 C1 CI NMe 2 H 493 CI CI N(Me)Et H 494 CI CI N(Me)-n-Pr H 495 CI CI N(Me)AII H 496 C1 CI N(Me)(CH 2
)
2 0-Me H 497 CI CI NMe 2
CO
2 Me 498 CI C1 N(Me)Et CO 2 Me 499 C C N(Me)-n-Pr CO 2 Me 500 CA CI N(Me)AII
CO
2 Me WO 2009/118125 PCT/EP2009/002029 44 No. X Y A ZPhysical data: 1H NMR: 6 [CDCI 3 ] 501 CI C1 N(Me)(CH 2
)
2 0-Me CO 2 Me 502 CI CI NMe 2
CO
2 Et 503 CI C1 N(Me)Et CO 2 Et 504 C1 CI N(Me)-n-Pr CO 2 Et 505 CI CI N(Me)AIJ CO 2 Et 506 CI C1 N(Me)(CH 2
)
2 0-Me CO 2 Et 507 CI OMe NH 2 H 508 CI OMe NHMe H 509 Cl OMe NHEt H 510 CI OMe NH-n-Pr H 511 C1 OMe NHAII H 512 CI OMe NH(CH 2 )20-Me H 513 C1 OMe N=CH-NMe 2 H 514 CI OMe NH 2
CO
2 Me 515 CI OMe NHMe
CO
2 Me 516 CI OMe NHEt
CO
2 Me 517 C1 OMe NH-n-Pr CO 2 Me 518 CI OMe NHAII CO 2 Me 519 CI OMe NH(CH 2
)
2 0-Me CO 2 Me 520 CI OMe N=CH-NMe 2
CO
2 Me 521 CI OMe NH 2
CO
2 Et 522 CI OMe NHMe CO 2 Et 523 Cl OMe NHEt CO 2 Et 524 CI OMe NH-n-Pr CO 2 Et 525 CI OMe NHAI CO 2 Et 526 CI OMe NH(CH 2
)
2 0-Me CO 2 Et 527 Cl OMe N=CH-NMe 2
CO
2 Et 528 CI OMe NMe 2 H 529 Ci OMe N(Me)Et H 530 CI OMe N(Me)-n-Pr H 531 C1 OMe N(Me)AII H WO 2009/118125 PCT/EP2009/002029 45 No. X Y A Z 1Physical data: H NMR: 5 [CDCl3] 532 Cl OMe N(Me)(CH2)20-Me H 533 Cl OMe NMe 2
CO
2 Me 534 C1 OMe N(Me)Et CO 2 Me 535 C1 OMe N(Me)-n-Pr CO 2 Me 536 CI OMe N(Me)AI CO 2 Me 537 CI OMe N(Me)(CH 2
)
2 0-Me CO 2 Me 538 CI OMe NMe 2
CO
2 Et 539 CI OMe N(Me)Et CO 2 Et 540 Cl OMe N(Me)-n-Pr CO 2 Et 541 CI OMe N(Me)Ali CO 2 Et 542 CI OMe N(Me)(CH 2
)
2 0-Me CO 2 Et 8.24 (s,1H), 7.60 (d, IH), 6.80 (d, 1H), 543 OMe SO 2 Me NH 2 H 5.48 (br, 2H), 3.78 (s, 3H), 3.12 (s, 3H), 2.75-2.85 (m, 1 H), 1.35-1.40 (m, 2H), 1.22-1.35 (m, 2H) 8.25 (s,1H), 7.66 (d, 1H), 6.80 (d, 1H), 544 OMe SO 2 Me NHMe H 5.95 (br, 1H), 3.68 (s, 3H), 3.15 (d, 3H), 3.08 (s, 3H), 2.78-2.85 (m, 1 H), 1.35 1.40 (m, 2H), 1.25-1.30 (m, 2H) 545 OMe SO 2 Me NHEt H 546 OMe SO 2 Me NH-n-Pr H 547 OMe SO 2 Me NHAII H 548 OMe SO 2 Me NH(CH 2
)
2 0-Me H 7.80 (s,1IH), 7.65 (s, IH), 7.35 (d, 1H), 6.40 (s, 1H), 3.65 (s, 3H), 3.35 (s, 3H), 549 OMe SO 2 Me N=CH-NMe 2 H 3.08 (s, 3H), 3.05 (s, 3H), 1.75-1.85 (s, 1H), 1.20-1.25 (m, 2H), 0.98-1.05 (m, 2H) 550 OMe SO 2 Me NH 2
CO
2 Me 551 OMe SO 2 Me NHMe CO 2 Me 552 OMe SO 2 Me NHEt CO 2 Me 553 OMe SO 2 Me NH-n-Pr CO 2 Me 554 OMe SO 2 Me NHAII
CO
2 Me 555 OMe SO 2 Me NH(CH 2
)
2 0-Me CO 2 Me 556 OMe SO 2 Me N=CH-NMe 2
CO
2 Me 557 OMe SO 2 Me NH 2
CO
2 Et WO 2009/118125 PCT/EP2009/002029 46 No. X Y A Z 1Physical data: H NMR:6 [CDC1 3 ] 558 OMe SO 2 Me NHMe CO 2 Et 559 OMe SO 2 Me NHEt CO 2 Et 560 OMe SO 2 Me NH-n-Pr CO 2 Et 561 OMe SO 2 Me NHAII CO 2 Et 562 OMe SO 2 Me NH(CH 2
)
2 0-Me CO 2 Et 563 OMe SO 2 Me N=CH-NMe 2
CO
2 Et 8.20 (s,1H), 7,90 (d, 1H), 7.40 (d, 1H), 564 OMe SO2Me NMe2 H 3.78 (s, 3H), 3.35 (d, 3H), 3,90 (s, 6H), 2.78-2.85 (m, 1H), 1.38-1.42 (m, 2H), 1.25-1.32 (m, 2H) 565 OMe SO 2 Me N(Me)Et H 566 OMe SO 2 Me N(Me)-n-Pr H 567 OMe SO 2 Me N(Me)AII H 568 OMe SO 2 Me N(Me)(CH 2
)
2 0-Me H 569 OMe SO 2 Me NMe 2
CO
2 Me 570 OMe SO 2 Me N(Me)Et CO 2 Me 571 OMe SO 2 Me N(Me)-n-Pr CO 2 Me 572 OMe SQ 2 Me N(Me)AII CO 2 Me 573 OMe SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Me 574 OMe SO 2 Me NMe 2
CO
2 Et 575 OMe SO 2 Me N(Me)Et CO 2 Et 576 OMe SO 2 Me N(Me)-n-Pr CO 2 Et 577 OMe SO 2 Me N(Me)AII CO 2 Et 578 OMe SO 2 Me N(Me)(CH 2
)
2 0-Me CO 2 Et 579 OMe CF 3
NH
2 H 580 OMe CF 3 NHMe H 581 OMe CF 3 NHEt H 582 OMe CF 3 NH-n-Pr H 583 OMe CF 3 NHAII H 584 OMe CF 3 NH(CH2)20-Me H 585 OMe CF 3 N=CH-NMe 2 H 586 OMe CF 3
NH
2
CO
2 Me WO 2009/118125 PCT/EP2009/002029 47 Physical data: No. X V A >2 'H NMR: 6 [CDC 3 ] 587 OMe CF 3 NHMe CO 2 Me 588 OMe CF 3 NHEt CO 2 Me 589 OMe CF 3 NH-n-Pr
CO
2 Me 590 OMe CF 3 NHAII CO 2 Me 591 OMe CF 3 NH(CH2)20-Me CO 2 Me 592 OMe CF 3 N=CH-NMe 2
CO
2 Me 593 OMe CF 3
NH
2
CO
2 Et 594 OMe CF 3 NHMe CO 2 Et 595 OMe CF 3 NHEt CO 2 Et 596 OMe CF 3 NH-n-Pr CO 2 Et 597 OMe CF 3 NHAII CO 2 Et 598 OMe CF 3
NH(CH
2
)
2 0-Me CO 2 Et 599 OMe CF 3 N=CH-NMe 2
CO
2 Et 600 OMe CF 3 NMe 2 H 601 OMe CF 3 N(Me)Et H 602 OMe CFa N(Me)-n-Pr H 603 OMe CF 3 N(Me)AII H 604 OMe CF 3 N(Me)(CH 2
)
2 0-Me H 605 OMe CF 3 NMe 2
CO
2 Me 606 OMe CF 3 N(Me)Et CO 2 Me 607 OMe CF 3 N(Me)-n-Pr CO 2 Me 608 OMe CF 3 N(Me)AII
CO
2 Me 609 OMe CF 3 N(Me)(CH 2
)
2 0-Me CO 2 Me 610 OMe CF 3 NMe 2
CO
2 Et 611 OMe CF 3 N(Me)Et CO 2 Et 612 OMe CF 3 N(Me)-n-Pr CO 2 Et 613 OMe CF 3 N(Me)AII CO 2 Et 614 OMe CF 3 N(Me)(CH 2
)
2 0-Me CO 2 Et 8.24 (s,1H), 7.15 (d, 1H), 6.76 (d, 1H), 615 OMe CI NH 2 H 4.38 (br, 2H), 3.75 (s, 3H), 2.75-2.82 (m, 1H), 1.30-1.38 (m, 2H), 1.20-1.30 (m, 2H) 616 OMe Cl NHMe H 8.22 (s,1H), 7.15 (d, 1H), 6.80 (d, 1H), WO 2009/118125 PCT/EP2009/002029 48 Physical data: ____H KHNMR.6[CDC 3 ] v 3.70 (s, 3H), 3.05 (s, 3H), 2.75-2.82 (m, 1H), 1.30-1.38 (m, 2 H), 1.20-1.30 (m, 2H) 617 OMe CI NHEt H 618 OMe CI NH-n-Pr H 619 OMe CI NHAI H 620 OMe CI NH(CH 2
)
2 0-Me H 7.42 (s,1H), 7.12 (s, 1H), 7.05 (d, 1H), 621 OMe CI N=CH-NMe 2 H 3.75 (s, 3H), 2.85 (s, 6H), 2.0-2.10 (s, 1 H), 0.95-1.0 (m, 2H), 0.65-0.70 (m, 2H) 622 OMe CI NH 2
CO
2 Me 623 OMe CI NHMe CO 2 Me 624 OMe CI NHEt CO 2 Me 625 OMe Cl NH-n-Pr CO 2 Me 626 OMe CI NHAII CO 2 Me 627 OMe C1 NH(CH 2
)
2 0-Me CO 2 Me 628 OMe CI N=CH-NMe 2
CO
2 Me 629 OMe CI NH 2
CO
2 Et 630 OMe C NHMe CO 2 Et 631 OMe CI NHEt CO 2 Et 632 OMe CI NH-n-Pr CO 2 Et 633 OMe C] NHAII CO 2 Et 634 OMe CI NH(CH 2
)
2 0-Me CO 2 Et 635 OMe CI N=CH-NMe 2
CO
2 Et 8.22 (s,1H), 7.20 (d, 1H), 7.05 (d, 1H), 636 OMe CI NMe 2 H 3.68 (s, 3H), 2.92 (s, 6H), 2.75-2.80 (m, 1 H), 1.30-1.38 (m, 2H), 1.20-1.30 (m, 2H) 637 OMe C1 N(Me)Et H 638 OMe CI N(Me)-n-Pr H 639 OMe CI N(Me)AII H 640 OMe CI N(Me)(CH2)20-Me H 641 OMe CI NMe 2
CO
2 Me 642 OMe CI N(Me)Et CO 2 Me WO 2009/118125 PCT/EP2009/002029 49 No. X Y A Z Physical data: H NMR: 5 [CDCI 3 ] 643 OMe CI N(Me)-n-Pr CO 2 Me 644 OMe C1 N(Me)AII CO 2 Me 645 OMe Cl N(Me)(CH 2
)
2 0-Me CO 2 Me 646 OMe CI NMe 2
CO
2 Et 647 OMe Cl N(Me)Et CO 2 Et 648 OMe CI N(Me)-n-Pr CO 2 Et 649 OMe C1 N(Me)AII CO 2 Et 650 OMe CI N(Me)(CH2)20-Me CO 2 Et B. Formulation examples a) A dust is obtained by mixing 10 parts by weight of a compound of the 5 formula (I) and/or its salts and 90 parts by weight of talc as inert substance and comminuting the mixture in a hammer mill. b) A wettable powder which is readily dispersible in water is obtained by mixing 25 parts by weight of a compound of the formula (1) and/or its salts, 64 parts 0 by weight of kaolin-containing quartz as inert substance, 10 parts by weight of potassium lignosulfonate and 1 part by weight of sodium oleoylmethyltaurinate as wetter and dispersant, and grinding the mixture in a pinned-disk mill. 5 c) A dispersion concentrate which is readily dispersible in water is obtained by mixing 20 parts by weight of a compound of the formula (1) and/or its salts with 6 parts by weight of alkylphenol polyglycol ether (@Triton X 207), 3 parts by weight of isotridecanol polyglycol ether (8 EO) and 71 parts by weight of paraffinic mineral oil (boiling range for example approximately 255 up to over 0 277"C) and grinding the mixture in a bowl mill to a fineness of below 5 microns. d) An emulsifiable concentrate is obtained from 15 parts by weight of a WO 2009/118125 PCT/EP2009/002029 50 compound of the formula (I) and/or its salts, 75 parts by weight of cyclohexanone as solvent and 10 parts by weight of oxethylated nonylphenol as emulsifier. 5 e) Water-dispersible granules are obtained by mixing 75 parts by weight of a compound of the formula (I) and/or its salts, 10 parts by weight of calcium lignosulfonate, 5 parts by weight of sodium lauryl sulfate, 3 parts by weight of polyvinyl alcohol and 10 7 parts by weight of kaolin, grinding the mixture in a pinned-disk mill and granulating the powder in a fluidized bed by spraying on water as granulation liquid. f) Water-dispersible granules are also obtained by homogenizing and 5 precomminuting, in a colloid mill, 25 parts by weight of a compound of the formula (1) and/or its salts, 5 parts by weight of sodium 2,2'-dinaphthylmethane-6,6'-disulfonate, 2 parts by weight of sodium oleoylmethyltaurinate, 1 part by weight of polyvinyl alcohol, 0 17 parts by weight of calcium carbonate and 50 parts by weight of water subsequently grinding the mixture in a bead mill, and atomizing and drying the resulting suspension in a spray tower by means of a single-substance nozzle. 5 C. Biological examples 1. Herbicidal pre-emergence effect against harmful plants Seeds of monocotyledonous or dicotyledonous weeds or crop plants are placed in 0 sandy loam soil in wood-fiber pots and covered with soil. The compounds according to the invention, formulated in the form of wettable powders (WP) or emulsion concentrates (EC), are then applied to the surface of the soil cover in the form of an WO 2009/118125 PCT/EP2009/002029 51 aqueous suspension or emulsion at a water application rate of 600 to 800 I/ha (converted), with addition of 0.2% wetter. After the treatment, the pots are placed in the greenhouse and kept under good growth conditions for the test plants. The damage to the test plants is scored visually in comparison with untreated controls 5 after an experimental time of 3 weeks has elapsed (herbicidal activity in percent (%): 100% activity = plants have died, 0% activity = like control plants). In this context, for example the compounds Nos. 543, 564, 616 and 621 show in each case at least 90% activity against Abutilon theophrasti, Amaranthus retroflexus and Echinochloa crus galli at an application rate of 320 g/ha. Compounds Nos. 4 and 564 show in 10 each case at least 90% activity against Setaria viridis and Stellaria media at an application rate of 320 g/ha. 2. Herbicidal post-emergence activity against harmful plants Seeds of monocotyledonous or dicotyledonous weeds or crop plants are placed in 5 sandy loam soil in wood-fiber pots, covered with soil and grown in the greenhouse under good growth conditions. 2 to 3 weeks after sowing, the test plants are treated in the one-leaf stage. The compounds according to the invention, formulated in the form of wettable powders (WP) or emulsion concentrates (EC), are then sprayed on to the green plant parts in the form of an aqueous suspension or emulsion at a water 0 application rate of 600 to 800 I/ha (converted), with addition of 0.2% wetter. After the test plants have been left to stand under optimal growth conditions in the greenhouse for approximately 3 weeks, the activity of the preparations is scored visually in comparison with untreated controls (herbicidal activity in percent (%): 100% activity = plants have died, 0% activity = like control plants). In this context, for 5 example the compounds Nos. 4 and 564 show in each case at least 80% activity against Setaria viridis, Stellaria media and Viola tricolor at an application rate of 80 g/ha. Compounds Nos. 616 and 621 show in each case at least 90% activity against Abutilon theophrasti, Amaranthus retroflexus and Echinochloa crus galli at an application rate of 80 g/ha.

权利要求:
Claims (11)
[1] 1. A 4-(3-aminobenzoyl)-5-cyclopropylisoxazole of the formula (1) or a salt thereof 5 0 A N A is NR 1 R 2 or N=CR 3 NR4R 5 , 0 R 1 and R 2 independently of one another are hydrogen, (G 1 -C 6 )-alkyl, (C1C4) alkoxy-(Cl-C 6 )-alkyl, (C2-C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 3 -C 6 )-cyc[oalkyl or (C3-C6) cycloalkyl-(C 1 -r)-alkyl, where the six abovementioned radicals are substituted by m halogen atoms, 5 R 3 , R 4 and R' independently of one another are hydrogen, (0 1 -C 6 )-alkyl or (C 3 -C 6 )-cycloalkyl, where the three last-mentioned radicals are substituted by m halogen atoms, X and Y independently of one another are hydrogen, (C-C 6 )-alkyl, (Cr1C4) 0 alkoxy, (C1 C4)-alkoxy-(C-C6)-alkyl, (C 2 -C 6 )-alkenyl, (C2-C)-alkynyl, (C3-C6) cycloalkyl, (C3-Ce)-cycloalkyl-(0 1 -C 6 )-alkyl, (C-Cs)-haloalkyl, halogen, (C-C4)-alkyl S(O)n, (C3-Ce)-cycloalkyl-S(O),, nitro or cyano, Z is hydrogen or C0 2 R, 5 R 6 is (C-C 6 )-alkyl or (C3-C)-cycloalkyl, m is 0,1, 2, 3, 4 or 5, WO 2009/118125 PCT/EP2009/002029 53 n is 0, 1 or2.
[2] 2. A 4 -( 3 -arminobenzoyl)-5-cyclopropylisoxazole as claimed in claim 1, wherein 5 A is NR 1 R 2 or N=CR 3 NR 4 R 5 , R 1 and R 2 independently of one another are hydrogen, (C 1 -C 6 )-alkyl, (Cr1C4) alkoxy-(C C 6 )-alkyl, (C2-C6)-alkenyl, (C3-C 6 )-cycloalkyl or (C 3 -C 6 )-cycloalkyl-(C 1 -C 6 ) o alkyl, R 3 , R 4 , R 5 independently of one another are hydrogen or (CI-C 6 )-alkyl, X and Y independently of one another are methyl, methoxy, trifluoromethyl, 5 chlorine, bromine, fluorine or methylsulfonyl, Z is hydrogen or C0 2 R 6 , R 6 is methyl or ethyl. 0
[3] 3. A 4 -( 3 -aminobenzoyl)-5-cyclopropylisoxazole as claimed in claim 1 or 2, wherein A is NR'R 2 or N=CR 3 NR 4 R 5 , 5 R 1 and R 2 independently of one another are hydrogen, methyl, ethyl, propyl, methoxyethyl, ethoxyethyl or methoxypropyl, R 3 , R 4 , R 5 independently of one another are hydrogen or methyl, X and Y independently of one another are methyl, methoxy, trifluoromethyl, chlorine, bromine, fluorine or methylsulfonyl, WO 2009/118125 PCT/EP2009/002029 54 Z is hydrogen or C0 2 R, R 6 is methyl or ethyl. 5
[4] 4. A herbicidal composition, characterized in that they have a herbicidally active content of at least one compound of the formula (1) as claimed in any of claims 1 to 3. 0
[5] 5. The herbicidal composition as claimed in claim 4 in a mixture with formulation auxiliaries.
[6] 6. A method of controlling undesired plants, characterized in that an effective amount of at least one compound of the formula (1) as claimed in any of claims 1 to 3 5 or of a herbicidal composition as claimed in claim 4 or 5 is applied to the plants or to the location of the undesired plant growth.
[7] 7. The use of a compound of the formula (1) as claimed in any of claims 1 to 3 or of a herbicidal composition as claimed in claim 4 or 5 for controlling undesired plants. 0
[8] 8. The use as claimed in claim 7, characterized in that the compounds of the formula (1) are employed for controlling undesired plants in crops of useful plants.
[9] 9. The use as claimed in claim 8, characterized in that the useful plants are 5 transgenic useful plants.
[10] 10. A compound of the formula (II) 0 0 X A I I (11) L Y wherein A, X and Y are as defined in any of claims 1 to 3 and L is ethoxy or WO 2009/118125 PCT/EP2009/002029 55 dimethylamino.
[11] 11. A compound of the formula (Ila) 0 0 x A (Ila) H 2 N z Y 5 wherein A, X, Y and Z are as defined in any of claims 1 to 3. BCS 08-1008 Abstract 4-(3-Aminobenzoyl)-5-cyclopropylisoxazoles 5 4 -( 3 -Aminobenzoyl)-5-cyclopropylisoxazoles of the formula (I) are described as herbicides. 0 x z Y 0 In this formula (1), A, X, Y and Z are radicals such as hydrogen, organic radicals such as alkyl, and other radicals such as halogen.

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同族专利:

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公开号 | 公开日

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AR071082A1|2010-05-26|

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AT514685T|2011-07-15|

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US20110015073A1|2011-01-20|

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CA2719533A1|2009-10-01|

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EA201001347A1|2011-04-29|

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US8188009B2|2012-05-29|

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法律状态:
2012-05-03| MK1| Application lapsed section 142(2)(a) - no request for examination in relevant period|

优先权:

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申请号 | 申请日 | 专利标题

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EP08005632A|EP2105437A1|2008-03-26|2008-03-26|4--5-cyclopropylisoxazols as herbicides|

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EP08005632.8||2008-03-26||

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PCT/EP2009/002029|WO2009118125A1|2008-03-26|2009-03-19|4--5-cyclopropylisoxazoles effective as herbicides|

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