This present disclosure is related to the field of 2-aldoximino-5-fluoropyrimidines and their derivatives and to the use of these compounds as fungicides.

BACKGROUND AND SUMMARY OF THE INVENTION

Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.

The present disclosure relates to 2-aldoximino-5-fluoropyrimidine compounds and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.

One embodiment of the present disclosure may include compounds of Formula I:

wherein R1is:H;C1-C6alkyl optionally substituted with R4;C1-C6alkenyl optionally substituted with R4;C3-C6alkynyl optionally substituted with R4;phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R5, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R5;—(CHR6)mOR7;—C(═O)R8;—C(═S)R8;—C(═O)OR8;—C(═S)OR8;—(CHR6)mN(R9)R10;—C(═O)N(R9)R10; or—C(═S)N(R9)R10;
m is an integer from 1 to 3;
R2is:H; orC1-C6alkyl optionally substituted with R4;
alternatively R1and R2may be taken together to form:═CR11N(R12)R13;
R3is independently C1-C6alkyl, C1-C6cycloalkyl, C1-C5haloalkyl, C2-C6alkylcarbonyl, C2-C6alkylaminocarbonyl, (hetero)arylcarbonyl, (hetero)aryloxycarbonyl, (hetero)arylaminocarbonyl, benzyl, phenyl, or 5- or 6-membered heteroaromatic ring, wherein each (hetero)aryl, phenyl, benzyl, or 5- or 6-membered heteroaromatic ring may be optionally substituted with 1 to 3 substituents independently selected from R5;
R4is independently halogen, C1-C6alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, C1-C4alkylthio, C1-C4haloalkylthio, amino, C1-C3alkylamino, C2-C6alkoxycarbonyl, C2-C6alkylcarbonyl, or C2-C6alkylaminocarbonyl;
R5is independently halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylthio, C1-C6haloalkylthio, amino, C1-C6alkylamino, C2-C6dialkylamino, C2-C6alkoxycarbonyl, or C2-C6alkylcarbonyl, nitro, or cyano;
R6is H, C1-C6alkyl, C1-C6alkoxy, phenyl or benzyl wherein each of the phenyl or benzyl may be optionally substituted with 1 to 3 substituents independently selected from R5;
R7is H, C1-C6alkyl, C2-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C1-C6alkoxyalkyl, C2-C6alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or benzyl may be optionally substituted with 1 to 3 R5, or a 5- or 6-membered saturated or unsaturated ring containing 1 to 3 heteroatoms wherein each ring may be optionally substituted with 1 to 3 substituents independently selected from R5;
R8is H, C1-C6alkyl, C2-C6alkenyl, C3-C6alkynyl, C1-C6haloalkyl, C1-C6alkoxyalkyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1 to 3 R5, or a 5- or 6-membered saturated or unsaturated ring containing 1 to 3 heteroatoms wherein each ring may be optionally substituted with 1 to 3 substituents independently selected from R5;
R9is H, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyalkyl, C2-C6alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R5, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R5;
R10is H, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxyalkyl, C2-C6alkylcarbonyl, benzyl, wherein the benzyl may be optionally substituted with 1-3 R5
alternatively R9and R10may be taken together to form:a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R5;
R11is H or C1-C4alkyl;
R12is H, C1-C4alkyl, C1-C6alkoxy, C2-C6, alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R5;
alternatively R11and R12may be taken together to form:a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R5;
R13is H, C1-C4alkyl, C1-C6alkoxy, C2-C6, alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R5;
alternatively R12and R13may be taken together to form:a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R5.

Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described below and a phytologically acceptable carrier material.

Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described below to at least one of the fungus, the plant, an area adjacent to the plant, and the seed adapted to produce the plant.

The term “alkenyl” refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclohexenyl, and the like.

The term “alkynyl” refers to a branched or unbranched carbon chain containing one or more triple bonds including propynyl, butynyl and the like.

As used throughout this specification, the term ‘R’ refers to the group consisting of C2-C8alkyl, C3-C8alkenyl, or C3-C8alkynyl, unless stated otherwise.

The term “alkoxy” refers to an —OR substituent.

The term “alkoxycarbonyl” refers to a —C(O)—OR substituent.

The term “alkylcarbonyl” refers to a —C(O)—R substituent.

The term “alkylsulfonyl” refers to an —SO2—R substituent.

The term “haloalkylsulfonyl” refers to an —SO2—R substituent where R is fully or partially substituted with Cl, F, I, or Br or any combination thereof.

The term “alkylthio” refers to an —S—R substituent.

The term “haloalkylthio” refers to an alkylthio, which is substituted with Cl, F, I, or Br or any combination thereof.

The term “alkylaminocarbonyl” refers to a —C(O)—N(H)—R substituent.

The term “dialkylaminocarbonyl” refers to a —C(O)—NR2substituent.

The term “alkylcycloalkylamino” refers to a cycloalkylamino substituent that is substituted with an alkyl group.

The term “trialkylsilyl” refers to —SiR3.

The term “cyano” refers to a —C≡N substituent.

The term “hydroxyl” refers to an —OH substituent.

The term “amino” refers to a —NH2substituent.

The term “alkylamino” refers to a —N(H)—R substituent.

The term “dialkylamino” refers to a —NR2substituent.

The term “alkoxyalkoxy” refers to —O(CH2)nO(CH2)nwhere n is an integer from 1-3.

The term “alkoxyalkyl” refers to an alkoxy substitution on an alkyl.

The term “haloalkoxyalkyl” refers to an alkoxy substitution on an alkyl which may be partially substituted with Cl, F, Br, or I, or any combination thereof.

The term “hydroxyalkyl” refers to an alkyl which is substituted with a hydroxyl group.

The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.

The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.

The term “haloalkenyl” refers to an alkenyl, which is substituted with Cl, F, I, or Br or any combination thereof.

The term “haloalkynyl” refers to an alkynyl which is substituted with Cl, F, I, or Br or any combination thereof.

The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.

The term “hydroxycarbonyl” refers to a —C(O)—OH substituent.

The term “nitro” refers to a —NO2substituent.

Throughout the disclosure, reference to the compounds of Formula I is read as also including optical isomers and salts of Formula I, and hydrates thereof. Specifically, when Formula I contains a branched chain alkyl group, it is understood that such compounds include optical isomers and racemates thereof. Exemplary salts include: hydrochloride, hydrobromide, hydroiodide, and the like. Additionally, the compounds of Formula I may include tautomeric forms.

Certain compounds disclosed in this document can exist as one or more isomers. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the present disclosure are drawn in only one geometric form for clarity, but are intended to represent all geometric and tautomeric forms of the molecule.

It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.

Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or seeds.

Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.

Additional features and advantages of the present invention will become apparent to those skilled in the art upon consideration of the following detailed description of the illustrative embodiments exemplifying the best mode of carrying out the invention as presently perceived.

DETAILED DESCRIPTION OF THE PRESENT DISCLOSURE

The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots, seeds or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrates, or emulsifiable concentrates.

Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.

The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and use as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.

Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.

Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 10 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.

Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulfonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.

Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present invention are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, and the methyl ether of triethylene glycol and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.

Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 5 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle. It is often most effective to grind and mix at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.

The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.

Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.

The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulfosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines and blends of surfactants with mineral or vegetable oils. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.

The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.

Another embodiment of the present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, seed or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.

The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants. Additional benefits may include, but are not limited to, improving the health of a plant; improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients); improving the vigor of a plant (e.g. improved plant growth and/or greener leaves); improving the quality of a plant (e.g. improved content or composition of certain ingredients); and improving the tolerance to abiotic and/or biotic stress of the plant.

It will be understood by those in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.

The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, wheat leaf blotch (Septoria tritici, also known asMycosphaerella graminicola), apple scab (Venturia inaequalis), andCercosporaleaf spots of sugar beets (Cercospora beticola), leaf spots of peanut (Cercospora arachidicolaandCercosporidium personatum) and other crops, and black sigatoka of bananas (Mycosphaerella fujiensis). The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.

The compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount. The term “disease-inhibiting and phytologically acceptable amount” refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact amount of a compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m2).

Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.

The compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.

The following examples are presented to illustrate the various aspects of the compounds of the present disclosure and should not be construed as limitations to the claims.

Preparation of N′-{5-fluoro-2-[1-phenylmethylideneamino-oxy]pyrimidin-4-yl}-N,N-dimethylformamidine (1)

Step A. To a solution of 2-chloro-5-fluoropyrimidin-4-amine (15.50 grams (g), 105 millimoles (mmol)) in ethyl alcohol (EtOH; 420 milliliters (mL)) was added sodium thiomethoxide (NaSCH3; 9.20 g, 131 mmol), and the resulting turbid mixture was warmed to reflux and stirred for 3 hours (h). The reaction mixture was cooled to room temperature, the solvent evaporated, and the residue partitioned between ethyl acetate (EtOAc; 250 mL) and water (H2O; 250 mL). The phases were separated, and the aqueous phase was extracted with additional EtOAc (100 mL). The organic phases were combined, dried over sodium sulfate (Na2SO4), filtered, and concentrated to an off-white solid. The solid was purified by flash chromatography (330 g silica gel (SiO2); 0→30% EtOAc/hexanes) to give 5-fluoro-2-methylsulfanylpyrimidin-4-ylamine (16.38 g, 98%) as a white solid: mp 114-115° C.;1H NMR (400 MHz, CDCl3) δ 7.99 (d, J=3.0 Hz, 1H), 5.29 (s, 2H), 2.50 (s, 3H); CIMS m/z 159 ([M]+).

Compounds 2 and 3 in Table I were prepared as in Example 1.

Preparation of N-{5-fluoro-2-[1-phenylmethylideneamino-oxy]pyrimidin-4-yl}formamide (4)

Step A. To a solution of 5-fluoro-2-methylsulfanylpyrimidin-4-ylamine (5.02 g, 31.6 mmol) in methyl alcohol (MeOH; 105 mL) was added dropwise a solution of OXONE™ (Registered trademark of E.I. du Pont de Nemours & Co, Inc.; 42.7 g, 69.4 mmol) in H2O (210 mL) over a 20 minute (min) period at −45° C., and the resulting mixture was slowly warmed to 10° C. over a period of 14 h. The mixture was treated with sodium bisulfite (10 g) and the majority of the MeOH was removed on the rotary evaporator. The aqueous residue was extracted with EtOAc (2×250 mL), and the organic extracts were combined, washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated to give 5-fluoro-2-methanesulfonylpyrimidin-4-ylamine (3.79 g, 63%) as a white solid: mp 157-159° C.;1H NMR (300 MHz, DMSO-d6) δ 8.35 (d, J=3.6 Hz, 1H), 8.11 (s, 2H), 3.27 (s, 3H); CIMS m/z 191 ([M]+).

Step B. To a suspension of 60% NaH (0.063 g, 1.57 mmol) in anhydrous tetrahydrofuran (THF; 5 mL) was added in portions a solution of 2-chlorobenzaldehyde oxime (0.254 g, 1.64 mmol in 1 mL of THF) at room temperature, and the resulting frothy mixture was stirred for 1 h. To the resulting tan mixture was added 5-fluoro-2-methanesulfonylpyrimidin-4-ylamine (0.25 g, 1.31 mmol), at which point the reaction mixture turned orange and most of the solids dissolved. Within minutes of the addition a new solid had precipitated, and the resulting orange mixture was stirred at room temperature for 16 h. The entire reaction mixture was adsorbed to Celite (2.5 g) and the adsorbed material was purified by flash chromatography (24 g SiO2; 0→100% EtOAc/hexanes) to give 2-chlorobenzaldehyde O-(4-amino-5-fluoropyrimidin-2-yl)oxime (0.173 g, 50%) as a white solid: mp 220-230° C. dec;1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.05 (d, J=3.1 Hz, 1H), 7.92 (dd, J=7.8, 1.5 Hz, 1H), 7.54 (m, 5H); ESIMS m/z 267 ([M+H]+), 265 ([M−H]−).

Compounds 6-12 in Table I were prepared as in Example 3.

Preparation of N′-{5-Fluoro-2-[1-(4-methoxyphenyl)-methylideneaminooxy]pyrimidin-4-yl}-N,N-dimethylformamidine (13)

Compounds 14 and 15 were prepared as in Example 4.

Step A. To a magnetically stirred solution of 2,4-dichloro-5-fluoropyrimidine (0.105 g, 0.63 mmol) in anhydrous THF (5 mL) were added 2-fluorobenzylamine (0.085 g, 0.68 mmol) and triethylamine (0.127 g, 1.26 mmol), and the mixture was warmed to reflux and stirred for 5 h. The reaction mixture was cooled to room temperature and partitioned between CH2Cl2(15 mL) and 1 N HCl (10 mL). The phases were separated and the aqueous phase was extracted with additional CH2Cl2(15 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and filtered. The solvent was removed under reduced pressure to yield (2-chloro-5-fluoropyrimidin-4-yl)-(2-fluorobenzyl)amine (0.157 g, 97%) as a yellow solid: mp 117-118° C.;1H NMR (300 MHz, CDCl3) δ 7.95 (s, 1H), 7.45 (t, 1H), 7.35 (m, 1H), 7.15 (m, 2H), 5.60 (br s, 1H), 4.80 (d, 2H); ESIMS m/z 256 ([M+H]+). Alternatively, 2-chloro-5-fluoropyrimidin-4-yl)-(2-fluorobenzyl)amine was prepared using methods known in the literature, such as Boebel, T. et al. U.S. Patent Application Publication 2010/0022538.

Compounds 17-55 were prepared as in Example 5.

TABLE ICompounds and Their StructuresCompoundStructure2367891011121415171819202122232425262728293031323334353637383940414243444546474849505152535455

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension ofSeptoria triticieither prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse for disease to develop.

The following table presents the activity of typical compounds of the present disclosure when evaluated in these experiments. The effectiveness of the test compounds in controlling disease was determined by assessing the severity of disease on treated plants, then converting the severity to percent control based on the level of disease on untreated, inoculated plants.

In each case of Table III the rating scale is as follows: