OA16417A - 5-Fluoropyrimidinone derivatives - Google Patents

Abstract

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

Description

5-FLUOROPYRIMIDINONE DERIVATIVES

Cross Reference to Related Applications

This application claims the benefit of U.S. Provisional Patent Application Serial No. 61/232,177 filed August 7, 2009.

Background and Summarv of the Invention

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

The présent disclosure relates to 5-fluoropyrimidinone compounds and their use as fungicides. The compounds of the présent disclosure may offer protection against ascomycètes, basidiomycetes, deuteromycetes and oomycetes.

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

Formula I wherein R¹ is:

H;

C-i-Ce alkyl optionally substituted with 1-3 R⁴;

C_rC₆aikenyl optionally substituted with 1-3 R⁴;

C₃-C₀alkynyl optionally substituted with 1-3 R⁴;

phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1- 3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring system, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

-(CHR⁶)_mOR⁷;

-(CHR^e)_m N(R⁹)R¹⁰;

-C(=O)R⁸;

-C(=S)R⁸;

-S(O)₂R⁸;

*

J

-C(=O)OR⁸;

-C(=S)OR⁰;

-(CHR⁶)_mN(R⁹)R¹⁰;

-C(=O)N(R^S)R¹⁰; or

-C(=S)N(R^e)R¹⁰;

wherein m is an înteger 1-4;

R² is:

H; or

CrC₆ alkyl optionally substituted with R⁴;

alternatively R¹ and R² may be taken together to form:

=CR¹¹N(R¹²)R¹³;

R³ is:

C_rC_ealkyl optionally substituted with 1-3 R⁴, CrC8 haloalkyl, C^-Ce hydroxyalkyl, C2C6 alkoxyalkyl, C2-Ce haloalkoxyalkyl, C2-C6 alkenyl optionally substituted with R¹⁴, C2-C_e haloalkenyl, C₃-C₆ alkynyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring system, or with a 5-6 fused ring system, or with a 6-6 fused ring system each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

-(CHR^e)_mOR⁷;

-(CHR⁶)_m SR⁸; or

-(CHR^B)_m N(R⁹)R¹⁰;

R⁴ is independently halogen, CrC₆ alkyl, CrC₄ haloalkyl, C_rC₄ alkoxy, C_rC₄ haloalkoxy, C-|-C₄ alkylthio, C_rC₄ haloalkylthio, amino, halothio, CrC₃ alkylamino, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylcarbonyl, C₂-C_e alkylaminocarbonyl, hydroxyl, C₃-C₈ trialkylsilyl, phenyl optionally substituted with 1-3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵;

R⁵ is independently halogen, C_rC_e alkyl, Ci-C_s haloalkyl, Ci-C₈ alkoxy, CK-Ce haloalkoxy, Ci-Ce alkylthio, CrCe haloalkylthio, halothio, amino, CrC₆ alkylamino, C₂-C_e dialkylamîno,

« >

C_z-C₆ alkoxycarbonyl, C₂-C_s alkylcarbonyl, C_rCe alkylsulfonyl, nitro, hydroxyl, or cyano;

R⁶ is H, C_rC₆ alkyl, C_rC_e alkoxy, Ci-C_ealkoxycarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1 -3 R⁵;

R⁷ is H, Cj-Ce alkyl, C₂-C₀ alkenyl, C₃-C_e alkynyl, Ο,-Ο_θ haloalkyl, Ο,-Ο₀ alkoxyalkyl, C₂-C_e trialkylsilyl, C₂-C_e trialkylsilylalkyl C₂-C₆ alkylcarbonyl, C^-Ce alkoxycarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a

5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

R⁸ is H, CrC_e alkyl, C₂-C_B alkenyl, C₃-C₆ alkynyl, Ci-C₆ haloalkyl, CrC_e alkoxyalkyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 13 R⁵;

R^eis H, CrCe alkyl, Ο,-Οθ haloalkyl, C_rC_e alkoxyalkyl, C_z-C_e alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a

5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

R¹⁰ is H, Ci-C₆ alkyl, Ο,-Ce haloalkyl, Ci-C_e alkoxyalkyl, C₂-C₆ alkylcarbonyl, or benzyl, wherein the benzyl may be optionally substituted with 1-3 R⁵;

alternative^ R⁹ and R¹⁰ may 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;

R¹¹ is H or C1-C4 alkyl;

R¹²is H, cyano, hydroxyl, 0,-04 alkyl, ΟγΟ₆ alkoxy, Ο₂-Ο_6ι alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵; or with a

5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵; alternatively R¹¹ and R¹² may 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;

R¹³ is H, CtC₄ alkyl, CrCe alkoxy, C₂-C₆. alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵; or with a 5- or 6membered saturated or unsaturated ring System, or with a 5-6 fused ring system, or with a

6-6 fused ring system each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

and alternatively R¹² and R¹³ may 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.

R¹⁴ is phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵.

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

Yet another embodiment of the présent disclosure may include a method for the control or prévention 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 alkyl refers to a branched, unbranched, or cyclic carbon chain, including methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

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 spécification, the term ‘R’ refers to the group consisting of C₂-_B alkyl, C₃._B alkenyl or C₃._B alkynyl, 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 “halothio” refers to a sulfur substituted with three or five F substituents.

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

The term dialkylaminocarbonyl refers to a -C(O)-NR₂ substituent.

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

The term “trialkyIsilyl 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 -NH₂ substituent.

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

The term “dialkylamino” refers to a -NR₂ substituent.

The term “trialkylsilylalkyl” refers to a -SiR₃ substituent on an alkyl.

The term “alkoxyalkoxy refers to -O(CH₂)_r1O(CH₂)_niCH₃ where n is an integerfrom 1-3 and m is 0-2.

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

The term haloalkoxyalkyl” refers to an alkoxy substitution on an alkyl which is fully or 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 ‘'halo¹' 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 -NO₂ substituent.

Throughout the disclosure, reference to the compounds of Formula I is read as also încluding 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 présent disclosure are drawn in only one géométrie form for clarity, but are intended to represent ali géométrie and tautomeric forms of the molécule. 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 présent 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 présent 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 présent invention will become apparent to those skilled in the art upon considération 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 Disclosure

The compounds of the présent 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 concentrâtes, or emulsifiable concentrâtes. Preferably, the compounds of the présent 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 présent disclosure contemplâtes ail 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 émulsions. Such suspensions or émulsions 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 concentrâtes, aqueous suspensions, or suspension concentrâtes. 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 interférence 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 préparation 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 concentrâtes 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 concentrâtes may be diluted with water and oil to form spray mixtures in the form of oil-in-water émulsions. 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 dérivatives, 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 concentrâtes include the polyalkylene glycol ethers and condensation products of alkyl and aryl phénols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phénols 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.

Représentative organic liquids which may be employed in preparing the emulsifiable concentrâtes of the compounds of the présent invention are the aromatîc liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, minerai oils, substituted aromatîc organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol dérivatives such as the nbutyl 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 préparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surfaceactive 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, bail mill, or piston-type homogenizer.

Aqueous émulsions comprise émulsions of one or more water-insoluble pesticidally active ingrédients emulsified in an aqueous vehicle at a concentration typically in the range from about 5 to about 50 weight percent, based on the total weight of the aqueous émulsion. If the pesticidally active ingrédient is a solid it must be dissolved in a suitable water-immiscible solvent prior to the préparation of the aqueous émulsion. Emulsions are prepared by emulsifying the liquid pesticidally active ingrédient or water-immiscible solution thereof into an aqueous medium typically with inclusion of surfactants that aid in the formation and stabilization of the émulsion as described above. This is often accomplished with the aid of vigorous mixing provided by high shear mixers or homogenizers.

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), dîspersed 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 agriculture! 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 déposition, wetting and pénétration of the compounds onto the target crop and organisai. 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 phénols, ethoxylated synthetic or naturel alcohols, salts of the esters or sulfosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines and blends of surfactants with minerai or vegetable oils. The formulations may also include oil-in-water émulsions such as those disclosed in U.S. Patent Application Serial No. 11/495,228, the disclosure of which is expressly încorporated by reference herein.

The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fongicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactéricides or combinations thereof that are compatible with the compounds of the présent invention in the medium selected for application, and not antagonistic to the activity of the présent compounds. Accordîngly, in such embodiments, the other pesticidal compound is employed as a supplémentai 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 présent in a weight ratio of from 1:100 to 100:1.

The compounds of the présent disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the présent disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the presently claimed compounds may be formulated with the other fungicide(s), tank mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis, Bacillus subtîlis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) sait, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxîde, copper octanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin, dîniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxîde, ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopîcolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldéhyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acétates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), iodocarb, ipconazole, ïpfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxim-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb, mepanipyrim, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, mefenoxam, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl îodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl, oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenyl laurate, penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium hydroxyquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propïneb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quîntozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazoie, sodium

2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z071, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp., (Æ?S)-A/-(3,5-dichtorophenyl)-2(methoxymethyl)-succinimide, 1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide, 2methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl, bis(methylmercury) sulfate, bis(tributyitin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, climbazole, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf, fenapanil, fenitropan, 5fluorocytosine and profungicides thereof, fiuotrimazole, furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos, isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride, myclozolin, A/“3,5-dichlorophenyl-succinimide, N-3nitrophenylitaconimide, natamycin, A/-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, picolinamide UK-2A and dérivatives thereof, prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, rabenzazole, salicylanilide, SSF109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, urbacid, zarilamide, and any combinations thereof.

Addïtionally, the compounds ofthe présent invention may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactéricides or combinations thereof that are compatible with the compounds ofthe présent invention in the medium selected for application, and not antagonistic to the activity of the présent compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the présent disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests. When used in conjunction with other pesticides, the presently claimed compounds may be formulated with the other pesticide(s), tank mixed with the other pesticide(s) or applied sequentially with the other pesticide(s). Typical insecticides include, but are not limited to: antibiotic insecticides such as allosamidin and thuringiensin; macrocyclic lactone insecticides such as spinosad and spinetoram; avermectin insecticides such as abamectin, doramectin, emamectin, eprinomectin, ivermectin and selamectin; milbemycin insecticides such as lepimectin, milbemectin, milbemycin oxime and moxidectin; arsenical insecticides such as calcium arsenate, copper acetoarsenite, copper arsenate, lead arsenate, potassium arsenite and sodium arsenite; botanical insecticides such as anabasine, azadirachtin, d-limonene, nicotine, pyrethrins, cinerins, cinerin I, cinerin II, jasmolin I, jasmolin II, pyrethrin I, pyrethrin II, quassia, rotenone, ryanîa and sabadilla; carbamate insecticides such as bendiocarb and carbaryl; benzofuranyi methylcarbamate insecticides such as benfuracarb, carbofuran, carbosulfan, decarbofuran and furathiocarb; dimethylcarbamate insecticides dimitan, dîmetilan, hyquincarb and pirimicarb; oxime carbamate insecticides such as alanycarb, aldicarb, aldoxycarb, butocarboxim, butoxycarboxim, methomyl, nitrilacarb, oxamyl, tazimcarb, thiocarboxime, thiodicarb and thiofanox; phenyl methylcarbamate insecticides such as allyxycarb, aminocarb, bufencarb, butacarb, carbanolate, cloethocarb, dicresyl, dioxacarb, EMPC, ethiofencarb, fenethacarb, fenobucarb, isoprocarb, methiocarb, metolcarb, mexacarbate, promacyl, promecarb, propoxur, trimethacarb, XMC and xylylcarb; dessicant insecticides such as boric acid, diatomaceous earth and silica gel; diamide insecticides such as chlorantraniliprole, cyantranïlïprole and flubendiamide; dinitrophenol »

insecticides such as dinex, dinoprop, dinosam and DNOC; fluorine insecticides such as barium hexafluorosilicate, cryolite, sodium fluoride, sodium hexafluorosilicate and sulfluramid; formamidine insecticides such as amitraz, chlordimeform, formetanate and formparanate; fumigant insecticides such as acrylonitrile, carbon disulfide, carbon tetrachloride, chloroform, chloropicrin, para-dichlorobenzene, 1,2-dichloropropane, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, iodomethane, methyl bromide, methylchloroform, methylene chloride, naphthalene, phosphine, sulfuryl fluoride and tetrachloroethane; inorganic insecticides such as borax, calcium polysulfide, copper oleate, mercurous chloride, potassium thiocyanate and sodium thiocyanate; chitin synthesis inhibitors such as bistrifluron, buprofezin, chlorfluazuron, cyromazine, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron and triflumuron; juvénile hormone mimics such as epofenonane, fenoxycarb, hydroprene, kinoprene, methoprene, pyriproxyfen and triprene; juvénile hormones such as juvénile hormone I, juvénile hormone II and juvénile hormone III; moulting hormone agonists such as chromafenozide, halofenozide, methoxyfenozide and tebufenozide; moulting hormones such as α-ecdysone and ecdysterone; moulting inhibitors such as diofenolan; precocenes such as precocene I, precocene II and precocene III; unclassified insect growth regulators such as dicyclanil; nereistoxin analogue insecticides such as bensultap, cartap, thiocyclam and thiosultap; nicotinoid insecticides such as fiontcamid; nitroguanidine insecticides such as clothianidin, dînotefuran, imidacloprid and thiamethoxam; nitromethylene insecticides such as nitenpyram and nithiazine; pyridylmethyl-amine insecticides such as acetamiprid, imidacloprid, nitenpyram and thiacloprid; organochlorine insecticides such as bromo-DDT, camphechlor, DDT, pp'-DDT, ethyl-DDD, HCH, gamma-HCH, lindane, methoxychlor, pentachlorophenol and TDE; cyclodiene insecticides such as aldrin, bromocyclen, chlorbicyclen, chlordane, chlordecone, dieldrin, dilor, endosulfan, alpha-endosulfan, endrin, HEOD, heptachlor, HHDN, isobenzan, isodrin, kelevan and mirex; organophosphate insecticides such as bromfenvinfos, chlorfenvinphos, crotoxyphos, dichlorvos, dicrotophos, dimethylvinphos, fospirate, heptenophos, methocrotophos, mevinphos, monocrotophos, naled, naftalofos, phosphamidon, propaphos, TEPP and tetrachlorvinphos; organothiophosphate insecticides such as dioxabenzofos, fosmethilan and phenthoate; aliphatic organothiophosphate insecticides such as acethion, amiton, cadusafos, chlorethoxyfos, chlormephos, demephion, demephion-O, demephion-S, demeton, demeton-O, demeton-S, demeton-methyl, demetonO-methyl, demeton-S-methyl, demeton-S-methylsulphon, disulfoton, ethion, ethoprophos, IPSP, isothioate, malathion, methacrifos, oxydemeton-methyl, oxydeprofos, oxydisulfoton, phorate, sulfotep, terbufos and thiometon; aliphatic amide organothiophosphate insecticides such as amidithion, cyanthoate, dimethoate, ethoate-methyl, formothion, mecarbam, omethoate, prothoate, sophamide and vamidothion; oxime organothiophosphate insecticides such as chlorphoxim, phoxim and phoxim-methyl; heterocyclic organothiophosphate insecticides such as azamethiphos, coumaphos, coumithoate, dioxathion, endothion, menazon, morphothion, phosalone, pyraclofos, pyridaphenthion and quinothion; benzothiopyran organothiophosphate insecticides such as dithicrofos and thicrofos; benzotriazine organothiophosphate insecticides such as azinphos-ethyl and azinphos-methyl; isoindole organothiophosphate insecticides such as dialifos and phosmet; isoxazole organothiophosphate insecticides such as isoxathîon and zolaprofos; pyrazoiopynmidine organothiophosphate insecticides such as chlorprazophos and pyrazophos; pyridine organothiophosphate insecticides such as chlorpyrifos and chlorpyrifos-methyl; pyrimidine organothiophosphate insecticides such as butathiofos, diazinon, etrimfos, lirimfos, pirimiphos-ethyl, pirimiphos-methyl, primidophos, pyrimitate and tebupirimfos; quinoxaline organothiophosphate insecticides such as quinalphos and quinalphos-methyl; thiadiazole organothiophosphate insecticides such as athidathion, lythidathion, methidathion and prothidathion; triazole organothiophosphate insecticides such as isazofos and triazophos; phenyl organothiophosphate insecticides such as azothoate, bromophos, bromophos-ethyl, carbophenothion, chlorthiophos, cyanophos, cythioate, dicapthon, dichlofenthion, etaphos, famphur, fenchlorphos, fenitrothion fensulfothion, fenthion, fenthion-ethyl, heterophos, jodfenphos, mesulfenfos, parathîon, parathion-methyl, phenkapton, phosnichlor, profenofos, prothiofos, sulprofos, temephos, trichlormetaphos-3 and trifenofos; phosphonate insecticides such as butonate and trichlorfon; phosphonothioate insecticides such as mecarphon; phenyl ethylphosphonothioate insecticides such as fonofos and trichloronat; phenyl phenylphosphonothioate insecticides such as cyanofenphos, EPN and leptophos; phosphoramidate insecticides such as crufomate, fenamiphos, fosthietan, mephosfolan, phosfolan and pirimetaphos; phosphoramidothioate insecticides such as acephate, isocarbophos, isofenphos, isofenphos-methyl, methamidophos and propetamphos; phosphorodiamide insecticides such as dimefox, mazidox, mipafox and schradan; oxadiazine insecticides such as indoxacarb; oxadiazoline insecticides such as metoxadiazone; phthalimide insecticides such as dialifos, phosmet and tetramethrin; pyrazole insecticides such as tebufenpyrad, tolefenpyrad; phenylpyrazole insecticides such as acetoprole, ethiprole, fipronil, pyrafluprole, pyriprole and vaniliprole; pyrethroid ester insecticides such as acrinathrin, allethrin, bioallethrin, barthrin, bifenthrin, bioethanomethrin, cyclethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambdacyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zetacypermethrin, cyphenothrin, deltamethrin, dimefluthrin, dimethrin, empenthrin, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate, esfenvalerate, flucythrinate, fluvalinate, taufluvalinate, furethrin, imiprothrin, meperfluthrin, metofluthrin, permethrin, biopermethrin, transpermethrin, phenothrin, prallethrin, profluthrin, pyresmethrin, resmethrin, bioresmethrin, cismethrin, tefluthrin, terallethrin, tetramethrin, tetramethylfluthrin, tralomethrin and transfluthrin; pyrethroid ether insecticides such as etofenprox, flufenprox, halfenprox, protrifenbute and silafluofen; pyrimidinamine insecticides such as flufenerim and pyrimidifen; pyrrole insecticides such as chlorfenapyr; tetramic acid insecticides such as spirotetramat; tetronic acid insecticides such as spiromesifen; thiourea insecticides such as dîafenthiuron; urea insecticides such as flucofuron and sulcofuron; and unclassified insecticides such as closantel, copper naphthenate, crotamiton, EXD, fenazaflor, fenoxacrim, hydramethylnon, isoprothiolane, malonoben, metafiumizone, nifluridide, plifenate, pyridaben, pyrîdalyl, pyrifluquinazon, rafoxanide, sulfoxaflor, triarathene and triazamate, and any combinations thereof.

Additionally, the compounds of the présent invention may be combined with herbicides that are compatible with the compounds of the présent invention in the medium selected for application, and not antagonistic to the activity of the présent compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the présent disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants. When used in conjunction with herbicides, the presently claimed compounds may be formulated with the herbicide(s), tank mixed with the herbicide(s) or applied sequentially with the herbicide(s). Typical herbicides include, but are not limited to: amide herbicides such as allidochlor, beflubutamid, benzadox, benzipram, bromobutide, cafenstrole, CDEA, cyprazole, dimethenamid, dimethenamid-P, diphenamid, epronaz, etnipromid, fentrazamide, flupoxam, fomesafen, halosafen, isocarbamid, isoxaben, napropamide, naptalam, pethoxamid, propyzamide, quinonamid and tebutam; anilide herbicides such as chloranocryl, cisanilide, clomeprop, cypromid, dïflufenican, etobenzanid, fenasulam, flufenacet, flufenican, mefenacet, mefluidide, metamifop, monalide, naproanilide, pentanochlor, picolinafen and propanil; arylalanine herbicides such as benzoylprop, flamprop and flamprop-M; chloroacetanilide herbicides such as acetochlor, alachlor, butachlor, butenachlor, delachlor, diethatyl, dimethachlor, metazachlor, metolachlor, Smetolachlor, pretilachlor, propachlor, propisochlor, prynachlor, terbuchlor, thenylchlor and xylachlor; sulfonanilide herbicides such as benzofluor, perfluidone, pyrimisulfan and profluazol; sulfonamide herbicides such as asulam, carbasulam, fenasulam and oryzalin; thioamide herbicides such as chlorthiamid; antibiotic herbicides such as bilanafos; benzoic acid herbicides such as chloramben, dicamba, 2,3,6-TBA and tricamba; pyrimidinyloxybenzoic acid herbicides such as bispyribac and pyriminobac; pyrimidinylthiobenzoic acid herbicides such as pyrithiobac; phthalic acid herbicides such as chlorthal; picolinic acid herbicides such as aminopyralid, clopyralid and picloram; quinolinecarboxylic acid herbicides such as quinclorac and quinmerac; arsenical herbicides »

) such as cacodylic acid, CMA, DSMA, hexaflurate. MAA, ΜΑΜΑ, MSMA, potassium arsenite and sodium arsenite; benzoylcyclohexanedione herbicides such as mesotrione, sulcotrione, tefuryltrione and tembotrione; benzofuranyl alkylsulfonate herbicides such as benfuresate and ethofumesate; benzothiazole herbicides such as benzazolin; carbamate herbicides such as asulam, carboxazole chlorprocarb, dichlormate, fenasulam, karbutilate and terbucarb; carbanilate herbicides such as barban, BCPC, carbasulam, carbetamide, CEPC, chlorbufam, chlorpropham, CPPC, desmedipham, phenisopham, phenmedipham, phenmedipham-ethyl, propham and swep; cyclohexene oxime herbicides such as alloxydim, butroxydim, clethodim, cloproxydim, cycloxydîm, profoxydim, sethoxydim, tepraloxydim and tralkoxydim; cyclopropylisoxazole herbicides such as isoxachlortole and isoxaflutole; dicarboximide herbicides such as cinidon-ethyi, flumezin, flumiclorac, flumioxazin and flumipropyn; dinitroaniline herbicides such as benfluralin, butralin, dinitramine, ethalfluralin, fluchloralin, isopropalin, methalpropalin, nitralin, oryzalin, pendimethalin, prodiamine, profluralin and trifluralin; dinitropheno! herbicides such as dinofenate, dinoprop, dinosam, dinoseb, dinoterb, DNOC, etinofen and medînoterb; diphenyl ether herbicides such as ethoxyfen; nitrophenyl ether herbicides such as acifluorfen, aclonifen, bifenox, chlomethoxyfen, chlornitrofen, etnipromid, fluorodifen, fluoroglycofen, fluoronitrofen, fomesafen, furyloxyfen, halosafen, lactofen, nitrofen, nitrofiuorfen and oxyfluorfen; dithiocarbamate herbicides such as dazomet and metam; halogenated aliphatic herbicides such as alorac, chloropon, dalapon, flupropanate, hexachloroacetone, iodomethane, methyl bromide, monochloroacetic acid, SMA and TCA; imidazolinone herbicides such as imazamethabenz, imazamox, imazapic, imazapyr, imazaquin and imazethapyr; inorganic herbicides such as ammonium sulfamate, borax, calcium chlorate, copper sulfate, ferrous sulfate, potassium azide, potassium cyanate, sodium azide, sodium chlorate and sulfuric acid; nitrile herbicides such as bromobonil, bromoxynil, chloroxynil, dichlobenil, iodobonil, ioxynil and pyraclonil; organophosphorus herbicides such as amiprofos-methyl, anilofos, bensulide, bilanafos, butamifos, 2,4-DEP, DMPA, EBEP, fosamine, glufosinate, glufosinateP, glyphosate and piperophos; phenoxy herbicides such as bromofenoxim, clomeprop, 2,4DEB, 2,4-DEP, difenopenten, disul, erbon, etnipromid, fenteracol and trifopsime; oxadiazoline herbicides such as methazole, oxadiargyl, oxadiazon; oxazole herbicides such as fenoxasulfone; phenoxyacetic herbicides such as 4-CPA, 2,4-D, 3,4-DA, MCPA, MCPAthioethyl and 2,4,5-T; phenoxybutyric herbicides such as 4-CPB, 2,4-DB, 3,4-DB, MCPB and 2,4,5-TB; phenoxypropionic herbicides such as cloprop, 4-CPP, dichlorprop, dichlorprop-P, 3,4-DP, fenoprop, mecoprop and mecoprop-P; aryloxyphenoxypropionic herbicides such as chlorazifop, clodinafop, clofop, cyhalofop, diclofop, fenoxaprop, fenoxaprop-P, fenthiaprop, fluazifop, fluazifop-P, haloxyfop, haloxyfop-P, isoxapyrifop, metamifop, propaquizafop, quizalofop, quizalofop-P and trifop; phenylenediamine herbicides such as dinitramine and prodiamine; pyrazole herbicides such as pyroxasulfone; benzoylpyrazole herbicides such as benzofenap, pyrasulfotole, pyrazolynate, pyrazoxyfen, and topramezone; phenylpyrazole herbicides such as fluazolate, nipyraclofen, pioxaden and pyraflufen; pyridazine herbicides such as credazine, pyridafol and pyridate; pyridazinone herbicides such as brompyrazon, chloridazon, dimidazon, flufenpyr, metflurazon, norflurazon, oxapyrazon and pydanon; pyridine herbicides such as aminopyralid, cliodinate, clopyralid, dithiopyr, fluroxypyr, haloxydine, pîcloram, picolïnafen, pyriclor, thiazopyr and triclopyr; pyrimidinediamine herbicides such as iprymidam and tioclorim; quaternary ammonium herbicides such as cyperquat, diethamquat, difenzoquat, diquat, morfamquat and paraquat; thiocarbamate herbicides such as butylate, cycloate, di-allate, EPTC, esprocarb, ethiolate, isopolinate, methiobencarb, molinate, orbencarb, pebulate, prosulfocarb, pyributicarb, sulfallate, thiobencarb, tiocarbazîl, tri-allate and vernolate; thiocarbonate herbicides such as dimexano, EXD and proxan; thiourea herbicides such as methiuron; triazine herbicides such as dipropetryn, indaziflam, triaziflam and trihydroxytriazine; chlorotriazine herbicides such as atrazîne, chlorazine, cyanazîne, cyprazine, eglinazine, ipazine, mesoprazine, procyazine, proglinazine, propazine, sebuthylazine, simazine, terbuthylazine and trietazine; methoxytriazine herbicides such as atraton, methometon, prometon, secbumeton, simeton and terbumeton; methylthiotriazine herbicides such as ametryn, aziprotryne, cyanatryn, desmetryn, dimethametryn, methoprotryne, prometryn, simetryn and terbutryn; triazinone herbicides such as ametridione, amibuzin, hexazinone, isomethiozin, metamitron and metribuzin; triazoie herbicides such as amitrole, cafenstrole, epronaz and flupoxam; triazolone herbicides such as amicarbazone, bencarbazone, carfentrazone, flucarbazone, ipfencarbazone, propoxycarbazone, sulfentrazone and thiencarbazone-methyl; triazolopyrimidine herbicides such as cloransulam, diclosulam, florasulam, flumetsulam, metosulam, penoxsulam and pyroxsulam; uracil herbicides such as benzfendizone, bromacil, butafenacil, flupropacil, isocil, lenacil, saflufenacil and terbacil; urea herbicides such as benzthiazuron, cumyluron, cycluron, dichloralurea, diflufenzopyr, isonoruron, isouron, methabenzthiazuron, monisouron and noruron; phenylurea herbicides such as anisuron, buturon, chlorbromuron, chloreturon, chlorotoluron, chloroxuron, daimuron, difenoxuron, dimefuron, diuron, fenuron, fluometuron, fluothiuron, isoproturon, linuron, methiuron, methyldymron, metobenzuron, metobromuron, metoxuron, monolinuron, monuron, neburon, parafluron, phenobenzuron, siduron, tetrafluron and thidiazuron; pyrimidinylsulfonylurea herbicides such as amidosulfuron, azimsulfuron, bensulfuron, chlorimuron, cyclosulfamuron, ethoxysulfuron, flazasulfuron, flucetosulfuron, flupyrsulfuron, foramsulfuron, halosulfuron, imazosulfuron, mesosulfuron, metazosulfuron, nicosulfuron, orthosulfamuron, oxasulfuron, primisulfuron, propyrisulfuron, pyrazosulfuron, rimsulfuron, sulfometuron, sulfosulfuron and trifloxysulfuron;

Λ » triazinylsulfonylurea herbicides such as chlorsulfuron, cinosulfuron, ethametsulfuron, iodosulfuron, metsulfuron, prosulfuron, thifensulfuron, triasulfuron, tribenuron, triflusulfuron and tritosulfuron; thiadiazolylurea herbicides such as buthiuron, ethidimuron, tebuthiuron, thiazafluron and thidiazuron; and unclassified herbicides such as acrolein, allyl alcohol, aminocyclopyrachlor, azafenidin, bentazone, benzoblcyclon, bicyclopyrone, buthidazole, calcium cyanamide, cambendichlor, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, cinmethylin, clomazone, CPMF, cresol, cyanamide, ortho-dichlorobenzene, dimepiperate, endothal, fluoromidine, fluridone, flurochloridone, flurtamone, fluthiacet, indanofan, methyl isothiocyanate, OCH, oxaziclomefone, pentachlorophenol, pentoxazone, phenylmercury acetate, prosulfalin, pyribenzoxim, pyriftalid, quinoclamine, rhodethanil, sulglycapin, thidiazimin, tridiphane, trimeturon, tripropindan and tritac.

Another embodiment of the présent disclosure is a method for the control or prévention 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 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 hâve been found to hâve 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 ingrédients); 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 ingrédients); and improving the tolérance 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 hâve broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, wheat leaf blotch (Septoria tritici, also known as Mycosphaerella graminicola), apple scab (Venturia inaequalis), and Cercospora leaf spots of sugar beets (Cercospora beticola), leaf spots of peanut (Cercospora arachidicola and Cercosporidium personatum) and other crops, and black sigatoka of bananas (Mycosphaerella fujiensis). The exact amount of the active material to be applied is dépendent not only on the spécifie 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, ail the » Λ 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 phytologîcally acceptable amount The term disease-inhibiting and phytologîcally 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/m^z).

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 présent disclosure and should not be construed as limitations to the daims.

Example 1: Préparation of 5-fluoro-1-morpholin-4-ylmethyl-4-[(morpholin-4-ylmethyl)amino]1H-pyrimidin-2-one (1)

This material was prepared as described in Int. J. Pharm. 1987, 35, 243-252. To a mixture of paraformaldéhyde (240 milligrams (mg), 8 millimoles (mmol) of monomer) in dichloromethane (CH₂CI₂; 20 mL) in a 25 milliliter (mL) screw-cap vial was added morpholine (697 mg, 8 mmol). The reaction mixture was agitated on an orbital shaker overnight at room température. 4-Amino-5-fluoropyrimidin-2-ol* (250 mg, 2 mmol) was added, and the resulting heterogeneous mixture was agitated at room température for 48 hours (h). The reaction mixture was evaporated to dryness and the residue was treated with ether (Et₂O) to give a white solid, which was filtered and dried to give the title compound (381 mg, 65%): mp 156-158 °C; ¹H NMR (300 MHz, CDCI₃) □□ 7.46 (d, J = 2.5 Hz, 1H), 5.69 (br t, 1 H), 4.53 (s, 2H), 4.46 (d, J = 2.6 Hz, 2H), 3.72 (m, 8H), 2.64 (m, 8H); IR (ATR) 3483 (br), 3293 (br), 1680 (s), 1639 (s), 1574 (s), 1521 (s) cm'¹.

l X *4-Amino-5-fluoropyrimidîn-2-ol can be purchased commercially.

Example 2: Préparation of 5-fluoro-1-(4-methylpiperazin-1-ylmethyl)-4-[(4-methylpiperazin1 -ylmethyl)-amino]-1 /7-pyrimidin-2-one (2)

This material was prepared as described in Int. J. Pharm. 1987, 35, 243-252. To a mixture of paraformaldéhyde (240 mg, 8 mmol of monomer) in CH₂CI₂ (20 mL) in a 25 mL screw-cap vial was added A/-methylpiperazine (813 mg, 8 mmol). The reaction mixture was agitated on an orbital shaker overnight at room température. 4-Amino-5-fluoropyrimidin-2-ol (250 mg, 2 mmol) was added and the resulting heterogeneous mixture was agitated at room température for 48 h. The reaction mixture was evaporated to dryness and the residue was treated with Et₂O to give a beige solid, which was filtered and dried to give the title compound (247 mg, 31%): mp 165-166 °C; ¹H NMR (300 MHz, CDCI₃) □ 7.45 (d, J= 2.5 Hz, 1 H), 5.62 (br t, 1 H), 4.55 (s, 2H), 4.5 (d, J = 2.6 Hz, 2H), 2.69 (m, 8H), 2.44 (br, 8H), 2.38 (s, 6H); IR (ATR) 3465 (br), 1679 (s). 1646 (s), 1574 (s), 1522 (s) cm’¹.

Compound 3 in Table I was synthesized as in Example 2.

Example 3: Préparation of /V-[5-fluoro-1-(4-fluorobenzyl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]/V,/V-dimethylformamidine (4)

To an 8 mL screw-cap vial was added Λ/,/V-dimethylformamide (DMF; 1.5 mL), A/’-(5-fluoro2-hydroxypyrimidin-4-yl)-/V,A/-dimethylformarnidine (100 mg, 0.54 mmol), anhydrous potassium carbonate (K₂CO₃; 138 mg, 1.0 mmol), and 4-fluorobenzyl bromide (113 mg, 0.60 mmol). The mixture was shaken and heated to 70 °C for 2 h and then at room température for an additional 16 h. The crude reaction mixture was filtered and placed directly onto a reverse phase chromatography column. After elution, the title compound was isolated as a white solid (30 mg, 20%): mp 134-136 °C; ¹H NMR (300 MHz, CDCI₃) Π 8.68 (s, 1H), 8.07 (d, J = 2.5 Hz, 1H), 7.49-7.43 (m, 2H), 7.10-7.01 (m, 2H), 5.33 (s, 2H), 3.20 (s, 3H), 3.18 (s, 3H); ESIMS m/z 293 ([M+Hf).

Compounds 5-7 in Table I were synthesized as in Example 3.

Example 4: Préparation of /V-(5-fluoro-1-methyl-2-oxo-1,2-dihydro-pyrimidin-4-yl)-4-methylbenzamide (8)

To /V-(5-fluoro-2-hydroxypyrimidin-4-yl)-4-methylbenzamide (200 mg, 0.81 mmol) in DMF (5 mL) was added K₂CO₃ (224 mg, 1.6 mmol), and iodomethane (230 mg, 1.6 mmol). The mixture was stirred and heated to 60 °C for 30 min and then stirred for 16 h at room température. The mixture was partitioned between ethyl acetate (EtOAc) and water (H₂O). The organic phase was dried over magnésium sulfate (MgSO₄), filtered and evaporated. The crude material was purified by reverse phase chromatography to yield the title compound as a white solid (17 mg, 8%): mp 229-230 °C; ¹H NMR (300 MHz, CDCI₃) Π 13.2 (br s, 1H), 8.23-8.15 (br m, 2H), 7.42-7.37 (br m, 1H), 7.30-7.25 (br m, 2H), 3.45 (s, 3H), 2.44 (s, 3H); ESIMS m/z 262 ([M+H]⁺), m/z 260 ([M-H] ).

Example 5: Préparation of W-(5-fluoro-1-methyl-2-oxo-1,2-dihydropyrimidin-4-yl)-/\/-methylC-phenylmethanesulfonamide (9)

4-Amino-5-fluoropyrimidin-2-ol (2 grams (g), 15.5 mmol) was stirred in acetonitrile (CH₃CN; 80 mL) at 50 °C. To the warm mixture was added A/,O-bis(trimethylsilyl)acetamide (BSA; 9.4 g, 46.3 mmol), and stirring and heating were continued for 1.5 h. Phenylmethanesulfonyl chloride (3.2 g, 16.8 mmol) was added. After 2 h, the reaction mixture was cooled to room température and partitioned between CH₃CN and brine. The organic phase was dried over MgSO₄, filtered, evaporated and placed directly onto a silica gel column which was eluted (gradient, 0 to 100% EtOAc in petroleum ether). Combining fractions containing the major UV absorbing portion of the product mixture yielded a white solid which was used without further purification. To a portion of this material (100 mg) was added DMF (3 mL), K₂CO₃ (100 mg), and iodomethane (100 mg), and the mixture was stirred at 60 °C for 1 h. The reaction mixture was cooled to room température and an excess of sodium hydride (NaH; 60% dispersion in minerai oil) was added. The whole mixture was stirred for 30 min and then heated to 45 °C for 2.5 h. The crude mixture was filtered and purified by reverse phase chromatography followed by normal phase chromatography (gradient, 30 to 100% EtOAc in petroleum ether) to yield the title compound as a white solid (28 mg, 27%): mp 159-160 °C; ¹H NMR (300 MHz, CDCI₃) □ 7.6 (m, 1H), 7.42-7.41 (m, 2H), 7.38-7.36 (m, 3H), 4.8 (s, 2H),

3.5 (s, 3H), 2.82 (s, 3H); ESIMS m/z 312 ([M+H]⁺), m/z 310 ([M-H]').

i

Example 6: Préparation of (5-fluoro-1-methyl-2-oxo-1,2-dihydropyrimidin-4-yl)carbamic acid isobutyl ester (10) and (5-fluoro-1-methyl-2-oxo-1,2-dihydropyrimidin-4-yl)methylcarbamic acid isobutyl ester (11) o

3. NaH 10 11

4- Amino-5-fluoropyrimidin-2-ol (0.5 g, 3.9 mmol) and isobutyl chloroformate (0.58 g, 4.2 mmol) were shaken in pyridine (5 mL) at 60 °C for 1.5 h. The crude mixture was partitioned between EtOAc and 1 N hydrochloric acid (HCl). The organic phase was dried over MgSO₄, filtered and evaporated. The residue was precipitated from ethyl alcohol (EtOH) to furnish a white solid which was used without further purification. A portion of this material (100 mg), K₂CO₃ (125 mg), and iodomethane (125 mg) were added to DMF (3 mL), and the mixture was stirred at 60 °C for 1 h. The mixture was cooled to room température and an excess of NaH (60% dispersion in minerai oil) was added. The entire mixture was stirred for 30 min and then heated to 45 °C for 2 h. The crude mixture was filtered and purified by reverse phase chromatography to yield the title compounds.

(5-Fluoro-1-methyl-2-oxo-1,2-dihydropyrimidin-4-yl)carbamic acid isobutyl ester was isolated as a white solid (16 mg): mp 126-128 °C; ¹H NMR (300 MHz, CDCI₃) □ 12.2 (br s, 1H), 7.32 (br s, 1H), 3.98 (d, J = 6.6 Hz, 2H), 3.4 (s, 3H). 2.02 (sept, J = 6.6 Hz, 1H), 1.01 (d. J =

6,6 Hz, 6H); ESIMS m/z 244 ([M+H]*), m/z 242 ([M-H]‘).

(5-Fluoro-1-methyl-2-oxo-1,2-dihydropyrimidin-4-yl)methylcarbamic acid isobutyl ester was isolated as a clear colorless oil (22 mg): ¹H NMR (300 MHz, CDCI3) Π 7.52 (d, J = 5.5 Hz, 1H), 4.02 (d, J = 6.8 Hz, 2H), 3.55 (s, 3H), 3.40 (s, 3H), 1.99 (sept, J = 6.8 Hz, 1H), 0.95 (d, J = 6.8 Hz, 6H); ¹³C NMR (150 MHz, CDCI3) □ 158.24, 158.17, 154.7,154.1, 140.5, 138.8, 134.0, 133.7, 73.6, 38.6, 34.9, 27.9, 19.2; ESIMS m/z 258 ([M+H]*).

Example 7: Préparation of 2,2-dimethylpropionic acid 4-(dîrnethylamino-methyleneamino)-

5- fluoro-2-oxo-2H-pyrimidin-1-ylmethyl ester (12)

To DMF (3 mL) were added N’-(5-fluoro-2-hydroxypyrirnidin-4-yl)-A/,/V-dimethylformamidine (100 mg, 0.54 mmol), césium carbonate (196 mg, 0.6 mmol), and chloromethyl pivalate (90 mg, 0.6 mmol), and the mixture was shaken at room température for 16 h. The mixture was partitioned between EtOAc and H₂O. The organic phase was dried over MgSO₄, filtered, and evaporated. To the résultant crude oil Et₂O (3.5 mL) was added and a precipitate formed which was collected by filtration. The title compound was isolated as a white solid (37 mg, 23%): mp 193-194 °C; M NMR (300 MHz, DMSO-d₆) □ 8.67 (s, 1H), 8.07 (d, J = 6.3 Hz, 1 H), 5.60 (s, 2H), 3.22 (s, 3H), 3.09 (s, 3H), 1.11 (s, 9H); ESIMS m/z 299 ((M+H]⁺).

Compound 13 in Table I was synthesized as in Example 7.

Example 8: Préparation of 4-amino-1-(benzyloxymethyl)-5-fluoropyrimidin-2(1H)-°^ne (14) and 1-(benzyloxymethyl)-4-(benzyloxymethylamino)-5-fluoropyrimidin-2(1/-f)-one (15)

A 25 mL Schlenk-type flask was charged with 4-amino-5-fluoropyrimidin-2-ol (500 mg, 3.87 mmol), CH₃CN (10 mL), and BSA (1.42 mL, 5.81 mmol). The resulting white suspension was then heated at 65 °C. After 90 min, the clear, colorless solution was cooled to room température and benzyl chloromethyl ether (1.07 mL, 7.72 mmol) was added, giving a cloudy white suspension. After stirring for 2 h at room température, the reaction mixture was concentrated in vacuoto give a white residue which was purified by reverse phase column chromatography yielding 4-amino-1-(benzyloxymethyl)-5-fluoropyrimidin-2(1H)-one (14; 433 mg. 45%) as a white solid: mp 213-217 ’C; ¹H NMR (400 MHz, CDCI₃) δ 7.98 (d, J = 6.5 Hz, 1H), 7.81 (brs, 1H), 7.56 (br s, 1H), 7.24-7.36 (m, 5H), 5.11 (s, 2H), 4.54 (s, 2H); IR 3302 (s), 3082 (s), 2939 (w), 2869 (w), 1688 (s), 1619 (s), 1522 (s), 1468 (m), 1333 (m), 1131 (w), 1054 (m) cm'¹; ESIMS m/z 250 ([M+H]⁺).

1-(Benzyloxymethyl)-4-(benzyloxymethylamino)-5-fluoropyrimidin-2(1H)-one (15; 16.5 mg, 1,2%) was obtained as a colorless oil byproduct in the synthesis of 14:¹H NMR (400 MHz, CDCI₃) δ 8.85 (t, J=5.8Hz, 1H), 8.08 (d, J = 6.6Hz, 1H), 7.22-7.39 (m, 10H), 5.15 (s, 2H), 4.87 (d, J = 5.8 Hz, 2H), 4.56 (s, 2H), 4.54 (s, 2H); IR 3248 (w), 3062 (w), 3031 (w), 1683 (s), 1644 (m), 1569 (m), 1520 (s), 1454 (w), 1357 (w), 1328 (m), 1189 (w), 1069 (m) cm'¹;

ESIMS m/z 370 ([M+H]⁺).

Compounds 16-23 in Table I were synthesized as in Example 8.

Example 9: Préparation of N-(5-fluoro-1-methylsulfanylmethyl-2-oxo-1,2-dihydropyrimidin4-yl)-/V,/V-dimethylformamidine (24)

A 250 mL round bottom flask was charged with A/’-(5-fluoro-2-hydroxypyrimidin-4-yl)-A/,Ndimethylformamidine (1.00 g, 5.43 mmol) and DMF (55 mL) to give a white suspension. Solid potassium terf-butoxide (1.07 g, 9.53 mmol) was added, and the resulting pale yellow suspension was allowed to stir under nitrogen at room température for 20 min. Chloromethyl methyl sulfide (682 mîcroliters (nL), 8.14 mmol) was then added, and the mixture was heated at 60 °C for 21 h. The crude reaction mixture was concentrated in vacuo at 55 °C to give an off-white residue which was purified by reverse phase column chromatography yielding /V-(5-fluoro-1-methylsulfanylmethyl-2-oxo-1,2-dihydropyrimidin-4-yl)-/V,/Vdimethylformamidine (36 mg, 25%) as a pale yellow solid: mp 132-136 °C; ¹H NMR (400

MHz, CDCI₃) δ 8.68 (s, 1H), 8.20 (d, J= 3.2 Hz, 1H), 5.40 (s, 2H), 3.19 (s, 3H), 3.07 (s, 3H), 2.20 (s, 3H); IR 2960 (w), 2926 (w), 1640 (s), 1582 (s), 1447 (s), 1382 (m), 1319 (m), 1269 (m), 1108 (m), 1051 (m) cm'¹; ESIMS m/z 267 ([M+Na]⁺).

Example 10: Préparation of 4-amino-5-fluoro-1-(4-methylbenzyl)-pyrimidin-2(1H)-one (25)

1. DMF-DMA, DMF

3. ZnCI₂, EtOH, reflux

Step 1: To a magnetically stirred solution of 4-amino-5-fluoropyrimidin-2-ol (4,00 g, 31.0 mmol) in DMF (100 mL) was added /V,N-dirnethylformamide dimethyl acetal (DMF-DMA; 4.00 g, 34.0 mmol). The mixture was stirred at room température for 72 h, diluted with Et₂O (200 mL), and filtered. The solid product was washed with heptane to give (EJ-A/’-fS-fîuoro2-oxo-1,2-dihydropyrimidin-4-yl)-A/,/\/-dimethylformimidamide (5.23 g, 92%) as a white solid: mp 240-243 °C; ¹H NMR (300 MHz, DMSO-d_B) Π 10.7 (brs, 1H), 8.59 (s, 1H), 7.7 (d, J =

5.6 Hz, 1H), 3.18 (s, 3H), 3.06 (s, 3H); ESIMS m/z 185 ([M+Hf), m/z 183 ([M-H]').

Step 2: Powdered K₂CO₃ (325 mesh; 2.03 g, 14.7 mmol) was added to a mixture of the product from Step 1 (1.35 g, 7.35 mmol) and Π-bromo-p-xylene (1.36 g, 7.35 mmol) in DMF (20 mL), under N₂, at room température. The résultant white slurry was warmed to 80 °C. After stirring at 80 °C for 2 h, the reaction mixture was cooled, diluted with EtOAc (150 mL) and the solution washed with H₂O (4 x 50 mL) and saturated (satd) NaCI (1 x 50 mL). The organic phase was dried (Na₂SO<i), filtered and concentrated in vacuo to give 1.01 g of a light yellow solid. The crude material was dissolved in a mixture of EtOAc/CH₂CI₂ and treated with Celite (3 g). The solvent was removed in vacuo and the residue purified by normal phase chromatography (gradient, 0 to 100% EtOAc/hexanes) to remove the isomeric O-alkylated product. The column was then eluted with 90% CH₂CI₂/10% CH₃OH to obtain the desired N-alkylated product, /\f-[5-fluoro-1-(4-methylbenzyl)-2-oxo-1,2-dihydropyrimidin4-yl]-/V,A/-dirnethylforamidine (0.668 g, 32%) as a white solid: mp 178-179 °C; ¹H NMR (300 MHz, CDCI₃) □ 8.82 (s, 1H), 7.22-7.15 (m, 4H), 4.97 (s, 2H), 3.18 (s, 3H), 3.17 (s, 3H), 2.34 (s, 3H); ESIMS m/z 289 ([M+H]⁺).

Step 3: Zinc chloride (1.24 g, 9.12 mmol) was added to a mixture of the formamidine product from Step 2 (0.656 g, 2.28 mmol) in absolute EtOH (10 mL). The résultant mixture was heated to reflux under N₂. The mixture gradually turned into a light yellow, homogeneous solution. After refluxing for 90 min a precipitate had formed, and after 2 h,the reaction mixture was allowed to cool to room température and was concentrated in vacuo. The residue was treated with CH₂CI₂ (75 mL, slightly turbid in appearance) and washed with H₂O (25 mL). As soon as H₂O was added a white precipitate formed in both layers in the separatory funnel. The solid was removed by vacuum filtration. The solid was washed with H_ZO followed by Et₂O. After air-drying overnight the white solid (0.58 g) was treated with 1:1 CH₂CI₂/MeOH (—70 mL) and heated to reflux (turbid mixture). The mixture was filtered and the filtrate was concentrated in vacuo. The residual solid was slurried with hexanes/Et₂O (~3:1) and isolated by vacuum filtration, air-dried and then vacuum oven dried (70-80 °C) to give /V-(5-fluoro-2-hydroxypyrimidin-4-yl)-A/,/V-dimethylformamidine (0.417 g, 78%) as a white powder: mp 291-293 °C dec; ¹H NMR (300 MHz, DMSO-de) □ 8.03 (d, J = 6.9 Hz, 1H), 7.62 (br s, 1H), 7.40 (brs, 1H), 7.17 (d, J = 7.8 Hz, 2H), 7.12 (d, J= 8.1 Hz, 2H), 4.73 (s, 2H), 2.25 (s, 3H); ¹³C NMR (150 MHz, DMSO-d6) □ 158.2, 154.8, 137.3, 136.3 (d, J = 240 Hz), 135.3, 131.1 (d, 0 = 30.6 Hz), 129.7, 128.3, 51.8, 21.3; ESIMS m/z 234 ([M+H]*), m/z 232 ([M-H]'); IR 3298 (m, br), 3100 (m, br), 1685 (s), 1619 (s), 1518 (s), 1447 (m), 1383 (m), 1343 (w), 1120 (w), 776 (w) cm'¹.

Example 11: Préparation of 4-amino-5-fluoro-1-(4-iodobutyl)-1H-pyrimidin-2-one (26)

To a suspension of 4-amino-5-fluoropyrimidin-2-ol (0.50 g, 3.87 mmol) in acetonitrile (CH₃CN; 20 mL) was added BSA (1.58 g, 7.75 mmol), and the mixture was heated to 70 °C for 1 h resulting in a clear solution. After cooling to room température, 1,4-diiodobutane (1.2 g, 3.87 mmol) was added, and the mixture was stirred for 16 h at room température and then at 70 °C for 3 h. The solvent was evaporated and the residue was purified by normal phase chromatography (24 g SiO₂; gradient, 0 to 15% MeOH/CH₂CI₂) to give an orange oil. The oil was dissolved in EtOAc and the solution was slowly cooled. The resulting solid was collected by filtration, washed with additional EtOAc, and dried to give 4-amino-5-fluoro-1-(4Îodobutyl)-1H-pyrimidin-2-one (0.52 g, 43%) as a tan solid: mp 181-184 °C; ’H NMR (400 MHz, DMSO-de) δ 8.56 (s, 2H), 8.25 (d, J = 6.7 Hz, 1 H), 3.70 (t, J = 6.7 Hz, 2H), 3.29 (t, J =

6.7 Hz, 2H), 1.73 (m, 4H); ESIMS m/z 312 ([M+H]*).

Example 12: Préparation of 4-amino-5-fiuoro-1 ~(4-[ 1,2,4]triazol-1 -yl-butyI)-1 H-pyrimidin-2one (27)

1.CH₃CN, KOtBu, 18C6

To a mixture of 1,2,4-triazole (0.044 g, 0.64 mmol), potassium 'butoxide (KO'Bu; 0.072 g,

0.64 mmol), and 18-crown-6 (18C6; 0.008 g, 0.03 mmol) in CH₃CN (3.5 mL) was added 4 amino-5-fluoro-1-(4-iodobutyl)-1/-/“pyrimidin-2-one (0.10 g, 0.32 mmol), and the mixture was warmed to 70 ’C and stirred for 16 h. The resulting homogeneous solution was concentrated in vacuo to give the crude product as a white solid. Purification by reverse phase chromatography (13 g C18; gradient, 0 to 20% CH₃CN/water) afforded 4-amino-5fluoro-l^-tl^^ltriazol-l-yl-butyO-IH-pyrimidin-Z-one (0.023 g, 28%) as a white solid: mp 197-200 ’C; ’H NMR (400 MHz, DMSO-d₆) δ 8.50 (s, 1H), 7.94 (m, 2H), 7.56 (s, 1H), 7.35 (s, 1H), 4.19 (t, J =6.9 Hz, 2H), 3.61 (t, J - 7.0 Hz, 2H), 1.73 (m, 2H), 1.51 (m, 2H); ESIMS m/z 253 ([M+H]⁺), m/z 251 ([M-H]').

Example 13: Préparation of 4-amino-5-fluoro-1-methylpyrimidin-2(1/-/)-one (28)

K,CO₃. ie-crown-6

MeSOjMe. DMF

A 25 mL screw-top vial was charged with 4-amino-5-fluoropyrimidin-2-ol (151.0 mg, 1.17 mmol), K₂CO₃ (289.2 mg, 2.09 mmol), 18C6 (278.6 mg, 0.901 mmol) and anhydrous DMF (10 mL). Methyl methanesulfonate (0.0814 mL, 0.961 mmol) was added, and the resulting mixture was agitated on a rotary shaker at 85 ’C for 21 h. After cooling to room température, the crude material was concentrated in vacuo and purified by reverse phase column chromatography to afford 4-amino-5-fluoro-1-methylpyrimidin-2(1H)“One (61.9 mg, 37%) as a beige solid: mp 195 ’C (dec.); Ή NMR (400 MHz, DMSO-c/_e) δ 7.94 (d, J = 6.8 Hz, 1H),

7.52 (s, 1H), 7.32 (s, 1H), 3.18 (s, 3H); ESIMS m/z 144 ([M+H]⁺.

Compounds 29-33 were prepared as in Example 13.

Example 14: Préparation of (E)-W-(1-ethyl-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)-N_JA/dimethylformimidamide (34)

A 25 mL screw-top vial was charged with (E)-N'-(5-fluoro-2-hydroxypyrimidin-4-yl)-A/,/Vdimethylformimïdamide (99.5 mg, 0.540 mmol), DMF (2 mL), and NaH (60% dispersion in minerai oil; 24.5 mg, 0.613 mmol) and was agitated on a rotary shaker at 50 ’C for 40 min. After cooling to room température, carbon disulfide (0.036 mL, 0.599 mmol) was added, and the reaction mixture was agitated on a rotary shaker at room température for 90 min. At this point, iodoethane (0.052 mL, 0.650 mmol) was added, and the reaction mixture was further agitated at room température for 3.5 h, whereupon the crude mixture was concentrated in vacuo. The crude material was purified by normal phase chromatography (gradient, 0 to 30% MeOH/CH₂Cl2) to afford (E)-/V-(1-ethyl-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)-/V,/\/dimethylformimidamide (105 mg, 67%) as a white solid: mp 157-160 °C; ¹H NMR (400 MHz, DMSO-de) δ 8.62 (s, 1H), 8.09 (d, J = 6.2 Hz, 1H), 3.70 (q, J= 7.1 Hz, 2H), 3.20 (s, 3H), 3.07 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H); ESIMS m/z 213 ([M+H]*.

Compounds 35 and 36 were prepared as in Example 14.

Example 15: Préparation of 1-(ethoxymethyl)-5-fluoro-4-(2-fluorobenzylamino)-pyrimidin2(1H)-one (37)

A 25 mL screw-top vial was charged with 5-fluoro-4-(2-fluorobenzylamino)pyrimidin-2-ol (49.7 mg, 0.210 mmol), CH₃CN (1 mL), and BSA (0.054 mL, 0.0221 mmol), and the mixturew was agitated on an rotary shaker at 65 ’C for 30 min. After cooling to room température, (chloromethoxy)ethane (0.022 mL, 0.237 mmol) was added, and the resulting mixture was agitated on a rotary shaker at room température for 16 h. The crude reaction mixture was concentrated in vacuo and was purified by normal phase chromatography (gradient, 0 to 25% MeOH/CH₂CI₂) to afford 1-(ethoxymethyl)-5-fluoro-4-(2fluorobenzylamino)-pyrimidin-2(1H)-one (55.0 mg, 89%) as a yellow oil: ¹H NMR (400 MHz, DMSO-d₆) δ 8.60 (t, J= 5.8 Hz, 1H), 8.05-7.95 (m, 1H), 7.40-7.26 (m, 2H), 7.26-7.10 (m, 2H), 5.01 (s, 2H), 4.59 (d, J = 5.9 Hz, 2H), 3.49 (q, J = 7.0 Hz, 2H), 1.09 (dd, J = 9.0, 5.0 Hz, 3H); ESIMS m/z 296 ([M+H]*), m/z 294 ([M-H] ).

Example 16: Préparation of 5-fluoro-4-((2-fluorobenzyl)(methyl)amino)-1-(4methylbenzyl)pyrimidin-2(1 H)-one (38)

A 25 mL screw-top vial was charged with NaH (60% dispersion in minerai oil; 20.5 mg,

0.513 mmol) and DMF (2.5 mL). 5-Fluoro-/\/-(2-fluorobenzyl)-2-(4methylbenzyloxy)pyrimidin-4-amine (149 mg, 0.436 mmol) was added, and the mixture was allowed to stir at room température. After 10 min, iodomethane (0.033 mL, 0.530 mmol) was added, and the resulting mixture was allowed to stir at room température for an additional 28 h. After this time, the crude reaction mixture was concentrated in vacuo and purified by normal phase chromatography (gradient, 0 to 40% EtOAc/Hexanes) to afford 5-fluoro-4-((2fluorobenzyl)(methyl)amino)-1-(4-methylbenzyl)pyrimidin-2(1H)-one (119.7 mg, 77%) as a colorless oil: ¹H NMR (400 MHz, DMSO-cfe) δ 8.16 (d, J = 9.5 Hz, 1H), 7.45-7.06 (m, 8H), 4.83 (s, 2H), 4.79 (s, 2H), 3.13 (d, J = 3.3 Hz, 3H), 2.27 (s, 3H); ¹³C NMR (101 MHz, DMSOd_e) δ 160.1 (d, J =244.4 Hz), 154.9 (d, J = 7.1 Hz), 152.9, 136.8, 136.2 (d, J = 243.2 Hz), 134.2, 132.8 (d, J =37.3 Hz), 129.2 (d, J = 8.2 Hz), 129.0, 128.7, 127.8, 124.6 (d, J = 3.4 Hz), 124.0 (d, J = 14.5 Hz), 115.3 (d, J = 21.0 Hz), 51.0, 47.7, 37.2 (d, J = 8.3 Hz), 20.6; ESIMS m/z 356 ([M+H]⁺).

Example 17: Préparation of 4-amino-5-fluoro-1-(thiophen-3-yl)pyrimidin-2(1/-/)-one (39)

PjS,, NaHCO₃ diglyma

H

NaOMe, MeOH

(HO)_aB

C

Cu(OAc),, pyridine.

3A MS, air, CHjCI,

To a solution of phosphorus pentasulfide (102.6 g, 0.46 mol) in diglyme (1 L) was added 5-fluoropyrimidine-2,4(1H,3/-0-dîone (30 g, 0.23 mol). Solid sodium hydrogen carbonate (NaHCO₃; 77.3 g, 1.04 mol) was added at a rate determined by the évolution of carbon dioxide. The reaction mixture was stirred overnight at 110 °C. The yellow mixture was cooled and poured into 1 L of cold water. The precipitated solid product was isolated by filtration and purified by normal phase chromatography (gradient, 10 to 50% EtOAc/Petroleum ether) to give 5-fluoro-4-thioxo-3,4-dihydropyrimidin2(1H)-one (13.4 g, 40%) as a yellow solid: mp 254-255 °C; ¹H NMR (301 MHz, DMSO-d_e) δ 7.81 (d, J = 4.0 Hz, 1 H); ESIMS m/z 145 ([M-H]’).

B) This material was prepared by the procedure described in Tetrahedron 1985, 41, 52895293. To a solution of 5-fluoro-4-thioxo-3,4-dihydropyrimidin-2(1H)-one (12.4 g, 84.9 mmol) and sodium methoxide (4.54 g, 84.9 mmol) in MeOH (100 mL) was added dropwise allyl bromide (10.27 g, 84.9 mmol) at room température. The reaction mixture was stirred overnight at room température. After removal of solvent, the residue was purified by normal phase chromatography (gradient, 10 to 33% EtOAc/hexane), to give 4-(allylthio)-5fluoropyrimidin-2(1/-/)-one (6 g, 38%) as a white solid: mp 150-152 °C; ¹H NMR (301 MHz, DMSO-d_B)6 11.60 (s, 1H),8.00 (d, J = 4.5Hz, 1H), 5.90 (ddt, J= 16.8, 10.0, 6.8 Hz, 1H), 5.34 (dd, J = 16.9, 1.4 Hz, 1H), 5.15 (dd, J= 10.0, 0.7 Hz, 1 H), 3.83 (d, J= 6.8 Hz, 2H); ESIMS m/z 187 ([M+H]⁺).

C) This material was prepared by the procedure described in J. Org. Chem. 2006, 71, 91839190. To a stirred suspension of dry Cu(OAc)₂ (1.02 g,5.64 mmol), 4-(allylthio)-5-fluoro- pyrimidin-2(1H)-one (700 mg, 3.76 mmol), thiophen-3-ylboronic acid (962 mg, 7.52 mmol), and activated 3 A molecular sieves (2 g) in dry CH₂CI₂ (30 mL) was added pyridine (595 mg,

7.52 mmol) at room température. The mixture was stirred for 24 h at ambrent température in the presence of air. The reaction mixture was diluted with CH₂CI₂ (30 mL), filtered through a pad of Celite, and washed with water (50 mL) in the presence of ethylenediaminetetraacetic acid (EDTA; 700 mg, 2.4 mmol). The colorless organic phase was dried over MgSO₄ and was concentrated in vacuo . The residue was purified by normal phase chromatography (isocratic, 2:1 petroleum ether: EtOAc) to afford 4-(allylthio)-5-fluoro-1-(thiophen-3yl)pyrimidin-2(1H)-one (290 mg, 29%) as a yellow solid: mp 125-127 °C; ¹H NMR (301 MHz, DMSO-cfe) δ 8.52-6.35 (m, 1H), 7.81 (s, 1H), 7.69-7.55 (m, 1H), 7,32 (d, J =3.5 Hz, 1H), 6.05-5.81 (m, 1H), 5.36 (d, J =16.9 Hz, 1H), 5.18 (d, J = 9.8 Hz, 1H), 3.89 (d, J=6.4 Hz, 2H); ESIMS m/z 269 ([M+H]⁺).

D) This material was prepared by the procedure described in J. Org. Chem. 2006, 71, 91839190. 4-(Allylthio)-5-fluoro-1-(thtophen-3-yl)pyrimidin-2(1W)-one (330 mg, 1.23 mmol) was dissolved in a methanol solution of ammonia (7 N, 5 mL). The reaction mixture was stirred overnight at 100 °C in a pressure vessel. After removal of solvent, the residue was purified by préparative thin layer chromatography to give 4-amino-5-fluoro-1-(thiophen-3yl)pyrimidin-2(1 H)-one (177 mg, 68%) as a yellow solid: mp 228-229 °C; ¹H NMR (300 MHz, DMSO-c/_e) δ 8.11 (d, J = 6.9 Hz, 1H), 7.89 (s, 1H), 7,65 (d, J = 1.9 Hz, 2H), 7.56 (dd, 5.1, 3.3 Hz, 1H), 7.29 (dd, J= 5.1. 1.0 Hz, 1 H); ESIMS m/z 212 ([M+Hf). Compounds 40-55 were prepared as described in Example 17.

Example 18: Préparation of (E)-/V’-(5-fluoro-2-oxo-1-(thiophen-3-yl)-1,2-dihydropyrimidin-4yl)-N, /V-dimethylformimidamide (56)

4-Amino-5-fluoro-1-(thiophen-3-yl)pyrimidin-2(1/-/)-one (140 mg, 0.66 mmol) was dissolved in DMF-DMA (5 mL). The reaction mixture was stirred at reflux overnight. The residual DMFDMA was removed in vacuo, and the residue was purified by préparative thin layer chromatography to give (E)-/V-(5-fluoro-2-oxo-1-(thiophen-3-yl)-1,2-dihydropyrimidin-4-yl)N,/V-dimethylformimidamide (75 mg, 43%) as a yellow solid: mp 211-213 °C; ¹H NMR (300 MHz, DMSO-d₆) δ 8.73 (s, 1 H), 8.22 (d, J = 6.4 Hz, 1 H), 7.75 (dd, J = 3.2, 1.4 Hz, 1 H), 7.60 (dd, J= 5.2, 3.2 Hz, 1H), 7.34 (dd, J = 5.2, 1.4 Hz, 1H), 3.26 (s, 3H), 3.13 (s, 2H); ESIMS m/z 267 ([M+H]⁺).

Compounds 57-64 were prepared as described in Example 18.

Example 19: Préparation of 5-fluoro-4-(2-fluorobenzylamino)-1-(thiophen-3-yl)pyrimidin2(1H)-one (65)

To a solution of 4-(allylthio)-5-fluoro-1-(thiophen-3-yl)pyrimidin-2(1H)-one (140 mg, 0.66 mmol) in MeOH (1 mL) was added (2-fluorophenyl)methanamine (50 mg, 0.186 mmol).The reaction mixture was heated at 100 °C for 30 min in a microwave. After cooling, the mixture was purified by préparative thin layer chromatography to give 5-fluoro-4-(2fluorobenzylamino)-1-(thiophen-3-yl)pyrimidin-2(1/-/)-one (41 mg, 20%) as a white solid: mp

75-78 °C; ¹H NMR (300 MHz, DMSO-d_e) δ 8.70 (s, 1H), 8.16 (d, J = 7.0 Hz, 1H), 7.66 (dd, J = 3.2, 1.4 Hz, 1H), 7.57 (dd, J= 5.2, 3.2 Hz, 1H), 7.43-7.13 (m, 5H), 4.63 (d, J = 5.5 Hz, 2H); ESIMS m/z 320 ([M+H]⁺).

Compounds 66-73 were prepared as described in Example 19.

Example 20: Préparation of 4-amino-1-(cyclopropylmethyl)-5-fluoropyrimidin-2(1H)-one (74)

KiCOj. DMF

To a solution of (bromomethyl)cyclopropane (1.0 g, 7.4 mmol) in DMF (20 mL) was added molecular sieves (~2 g), and the resulting mixture was stirred at room température. After 1 h, 4-amino-5-fluoropyrimidin-2-ol (1.9 g, 14.8 mmol) and K₂CO₃ (5.1 g, 37 mmol) were added, and the reaction mixture was heated at 90 °C for 12 h. After cooling to room température, the crude reaction mixture was filtered through a Büchner funnel, and the solid residue was washed with EtOAc. The collected filtrate was concentrated in vacuo to give a residue which was purified by normal phase chromatography (isocratic, 5% MeOH/EtOAc). Following recrystallization from methyl tert-butylether, 4-amino-1-(cyclopropylmethyl)-5fluoropyrimldin-2(1/7)-one (1.12 g, 83%) was isolated as a white solid: mp 224-226 °C; ¹H NMR (400 MHz, methanol-ct,) δ 7.86 (d, J = 6.2 Hz, 1 H), 3.61 (d, J = 7.2 Hz, 2H), 1.24 (ddd, J= 12.8, 7.6, 4.8 Hz, 1H), 0.65-0.50 (m, 2H), 0.39 (q, J = 4.8 Hz, 2H); ESIMS m/z 184 ([M+HD.

Compounds 75-79 were prepared as described in Example 20.

Example 21: Préparation of ethyl 1-(cyclopropylmethyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin4-ylcarbamate (80)

4-Amino-1-(cyclopropylmethyl)-5-fluoropyrimidin-2(1/7)-one (200 mg, 1.09 mmol) was dissolved in CH₂CI₂ (0.90 mL) and pyridine (172.4 mg, 2.18 mmol) at room température and then was cooled to -20 °C. Ethyl chloroformate (166 mg, 1.53 mmol) was then added to the reaction mixture dropwise, keeping the reaction température between -20 and -5 °C. After the addition was complété, the reaction was allowed to warm slowly to room température and stirred for 2 h. The reaction mixture was filtered, and the solids were rinsed with EtOAc (15 mL x 3). The filtrate was concentrated in vacuo, and purified by préparative thin layer chromatography, to afford ethyl 1-(cyclopropylmethyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4ylcarbamate (70 mg, 30%) as a pale yellow solid: mp 90-92 °C; ¹H NMR (400 MHz, methanol-dj δ 8.20 (s, 1 H), 4.26 (q. J = 7.1 Hz, 2H), 3.70 (d, J = 7.2 Hz, 2H), 1.24-1.36 (m, 4H), 0.65-0.57 (m, 2H), 0.46-0.39 (m, 2H); ESIMS m/z 256 ([M+H]⁺).

Compounds 81-84 were prepared as described in Example 21.

Example 22: Préparation of 1-(2-chlorophenyl)-3-(1-(cyclopropylmethyl)-5-fluoro-2-oxo-1,2dihydropyrimidin-4-yl)urea (85)

To a stirred solution of 4-amino-1-(cyclopropylmethyl)-5-fluoropyrimidin-2(1/-/)-one (150 mg, 0.819 mmol) in dry CH₃CN (7.5 mL) at room température and under nitrogen was added 2chlorophenylisocyanate (138.3 mg, 0.90 mmol). After stirring for 1 h, the crude reaction mixture was filtered, and the solids were rinsed with CH₃CN (10 mL). The collected filtrate was then concentrated in vacuo and dried under high vacuum to afford 1-(2-chlorophenyl)-3(1-(cyclopropylmethyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)urea (160 mg, 58%) as an off-white solid: mp 197-199 °C; ¹H NMR (400 MHz, methanol-d₄) δ 8.26 (d, J = 6.0 Hz, 1H), 8.21 (dd, J — 8.3, 1.5 Hz, 1H), 7.47 (dd, J = 8.0,1.4 Hz, 1H), 7.35-7.28 (m, 1H), 7.13 (td, J = 7.8, 1.5 Hz, 1H), 3.74 (d, J= 7.3 Hz, 2H), 1.32 (m, 1H), 0.69-0.58 (m, 2H), 0.50-0.38 (m, 2H); ESIMS m/z 337 ([M+Hf).

Compounds 86-93 were prepared as described in Example 22.

Example 23: Préparation of A/-(5-fluoro-2-oxo-1-((tetrahydrofuran-2-yl)methyl)-1,2dihydropyrimidin-4-yl)thiophene-2-carboxamide (94)

This material was prepared by the procedure described in J. Org. Chem. 2005, 70, 74597467. To a solution of 4-amino-5-fluoro-1-((tetrahydrofuran-2-yl)methyl)pyrimidin-2(1/-0-one (200 mg, 0.94 mmol) in dry THF (1 mL) at room température were added 1 -ethyl-3-(3dimethylaminopropyl) carbodiimide (EDC; 180 mg, 0.94 mmol) and 1Hbenzo[c(][1,2,3]triazol-1-ol (HOBt; 139 mg, 1.03 mmol). After stirring for 10 min, thiophene-2carboxylic acid (145 mg, 1.13 mmol) was added, and the resulting solution was allowed to stir at room température for 12 h. The reaction mixture was concentrated in vacuo, quenched with satd aq NaHCO₃ solution (10 mL), and extracted with EtOAc (25 mL x 3). The combined extracts were washed with satd aq sodium chloride (NaCI) solution, dried over Na₂SO₄, filtered, and concentrated by rotary évaporation. Purification by normal phase chromatography (gradient, 0 to 2% MeOH/CH₂CI₂) afforded 4-amino-5-fluoro-1((tetrahydrofuran-2-yl)methyl)pyrimidin-2(1/-/)-one (60 mg, 20%) as a white solid: mp 168170 °C; ¹H NMR (400 MHz, CDCI₃) δ 12.96 (s, 1H), 7.96 (d, J = 3.7 Hz, 1H), 7.63 (d, J =5.7 Hz, 1H), 7.60 (d, J = 4.9 Hz, 1H), 7.16-7.11 (m, 1H), 4.20-4.08 (m, 2H), 3.89 (dd, J= 15.1, 6.9 Hz, 1H), 3.80 (dd, J = 14.5, 7.5 Hz, 1 H), 3.57 (dd, J = 14.4, 7.7 Hz, 1H), 2.10 (dt, J = 12.8, 6.7 Hz, 1H), 1.99-1.87 (m, 2H), 0.88 (m, 1H); ESIMS m/z 324 ([M+H]⁺).

Compounds 95-101 were prepared as described in Example 23.

Example 24: Préparation of 5-fluoro-1-((tetrahydrofuran-2-yl)methyl)-4-(thiophen-2ylmethylamino)pyrimidin-2(1/7)-one (102)

BSA. DIPEA BU,, THF

This material was prepared by the procedure described in J. Org. Chem. 2005, 70, 74597467. To a solution of 4-amino-5-fluoro-1-((tetrahydrofuran-2-yl)methyl)pyrimidin-2(1H)-one (160 mg, 0.495 mmol) in THF (4 mL) at room température was added BSA (0.61 mL, 2.47 mmol) dropwise. After the addition was complété, borane-A/,A/-diisopropylethylamine complex (DIPEA-BH₃; 0.90 mL, 4.95 mL) was added dropwise, and the resulting solution was stirred at room température for 15 min. The reaction mixture was quenched by the addition of MeOH (20 mL), and the mixture was concentrated in vacuo. The resulting mixture was dissolved in a 1:1 (v:v) mixture of 17% ammonia in methanol:28% ammonia in water (135 mL) and heated at 50 °C for 13 h. After cooling to room température, the mixture was extracted with chloroform (CHCI₃; 100 mL x 2). The combined extracts were washed with aq NaCI solution, dried over Na₂SO₄₁ filtered, and concentrated in vacuo. Purification by préparative thin layer chromatography afforded 5-fluoro-1-((tetrahydrofuran-2-yl)methyl)-4(thiophen-2-ylmethylamino)pyrimidin-2(1/-/)-one (40 mg, 26%) as a gummy white solid: ¹H NMR (400 MHz, acetone-d_s) δ 7.69 (d, J = 6.7 Hz, 1H), 7.52 (s, 1H), 7.32 (dd, J =5.1, 1.2 Hz, 1H), 7.08 (dd, J=3.4, 0.9 Hz, 1H), 6.95 (dd, J = 5.1, 3.5 Hz, 1H), 4.85 (d, J = 6.0 Hz, 2H), 4.12 (ddd, J = 14.6, 7.1,3.2 Hz, 1H), 4.00 (dd, J= 13.6, 2.8 Hz, 1H), 3.83 (dt, J = 8.1, 6.7 Hz, 1H), 3.72-3.64 (m, 1H), 3.56 (dd, J= 13.6, 7.7 Hz, 1H), 2.02-1.93 (m, 1H), 1.86 (ddd, J= 11.0, 8.1, 1.6 Hz, 2H), 1.67-1.54 (m, 1H); IR (thin film) 3222, 3125, 3068, 2950, 2875, 1673, 1623, 1586, 1556, 1508, 1368, 1329, 1186, 1139, 1065, 906 cm’¹; ESIMS m/z 310 ([M+Hf).

Compounds 103 and 104 were prepared as described in Example 24.

Example 25: Préparation of 5-fluoro-4-(2-fluorobenzylamino)-1-isobutyl-pyrimidin-2(1/7)-one (105)

c

To a solution of 5-fluoropyrimidine-2,4(1/7,3/7)-dione (5.0 g, 38 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; 6.4 g, 42 mmol) in dry CH₃CN (150 mL) at room température and under nitrogen was added 1-bromo-2methylpropane (5.3 g, 38 mmol) dropwise. The reaction was then heated to reflux for 18 h. After cooling to room température, the solvent was removed in vacuo. The crude residue was purified by normal phase chromatography (gradient, Oto 20% EtOAc/Petroleum ether), providing 5-fluoro-1isobutylpyrirnidine-2,4(1/7,3/7)-dione (2.5 g, 35%) as a white solid: mp 173174 °C; ¹H NMR (400 MHz, CDCI₃) δ 8.61 (s, 1H), 7.21 (d, J = 5.5 Hz, 1H),

3.53 (d, J=7.5Hz, 2H), 2.13-2.01 (m, 1H), 0.98 (d, J = 6.7 Hz, 6H); ESIMS m/z 185 ([M-H]').

B) Phosphoryl trichloride (3.3 g, 21 mmol) was added to a solution of 1,2,4-triazole (6.7 g, 97 mmol) in CH₃CN (53 mL) under nitrogen at room température. The mixture was cooled to 0 °C, whereupon triethylamine (Et₃N; 9.5 g, 92 mmol) was added dropwise followed by the addition of a solution of 5-fluoro-1-isobutylpyrimidine-2,4(1/7,3/7)-dione (2.0 g, 11 mmol) in CH₃CN (30 mL). After stirring for 1 h at room température, Et₃N (3.6 g, 36 mmol) and then water (5 mL, 280 mmol) were added, and the reaction mixture was stirred for an additional 10 min. The crude reaction mixture was then concentrated in vacuo. Recrystallization from EtOAc/petroleum ether provided 5-fluoro-1-isobutyl-4-(1 /7-1,2,4-triazol-1-yl)pyrimidin-2(1/7)one (1.9 g, 74%) as an off white crystalline solid: mp 150-153 °C; ’H NMR (400 MHz, CDCI₃) δ 9.26 (s, 1 H), 8.23 (s, 1 H), 7.84 (d, J = 5.7 Hz, 1 H), 3.79 (d, J = 7.4 Hz, 2H), 2.28 (dt, J= 13.7, 6.9 Hz, 1H), 1.02 (d, J = 6.7 Hz, 6H); ESIMS m/z 238 ([M+H]⁺).

C) A solution of 5-fluoro-1-isobutyl-4-(1/7-1,2,4-triazol-1-yl)pyrimidin-2(1H)-one (500 mg, 2.1 mmol) and 2-fluorobenzylamine (313 mg, 2.5 mmol) in dry 1,4-dioxane (10 mL) was heated to reflux for 1 h under nitrogen. After cooling to room température, the reaction mixture was concentrated in vacuo. Recrystallization from EtOAc/methyl tert-butylether afforded 5-fluoro4-(2-fluorobenzylamino)-1-isobutylpyrimidin-2(1/-/)-one (545 mg, 89%) as an off white solid: mp 118-119 °C; ¹H NMR (400 MHz, CDCI₃) δ 7.45 (td, J= 7.6, 1.7 Hz, 1H), 7.35-7.28 (m, 2H), 7.13 (ddd, J = 21.9, 13.9, 7.3 Hz, 3H), 5.58 (s, 1H), 4.81 (d, J = 5.4 Hz, 2H), 3.56 (d, J = 7.5 Hz, 2H), 2.16 (dt, J= 13.6, 6.8 Hz, 1H), 0.95 (d, J = 6.7 Hz, 6H); ESIMS m/z 295 ([M+Hf).

Compounds 106-110 were prepared as described for Example 25.

TABLE I: Compounds and Related Characterization Data

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
3	f'Y^n^'n'CH3 η^ν-νΛνΛ 6h> ch3 H	white solid	157 187 dec		(CDCI3) 7.47 (d, J = 6.1 Hz, 1H), 5.91 (s, 1H), 4.45 (s, 2H), 4.38 (d, J = 5.2 Hz, 2H), 2.36 (s, 12H)
5	Cl a /=nx^njZ^O h3c-k ch3	yellow oil		ESIMS m/z 343 ([M+H] +)	(CDCI3) 8.81 (s, 1H), 7.40 (d, J = 2.3 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 5.6 Hz, 1H), 7.22 (dd, J = 8.2, 2.3 Hz, 1H), 5.06 (s, 2H), 3.18 (s, 6H)

t

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
6	9 HjC N CHj	white solid	186 188	ESIMS m/z 275 ([M+H] +)	(CDCI3) 8.85 (s, 1H). 7.41-7.31 (m, 5H), 7.24 (d, J = 5.5 Hz, 1H), 5.04 (s, 2H), 3.22 (s, 1H), 3.21 (s, 3H)
7	ÇHj Ô jxi HjC-rç CH;	white solid	178 179	ESIMS m/z 289 ([M+H] +)	(CDCI3) 8.85 (s, 1H), 7.26-7.17 (m. 5H), 4.99 (s, 2H), 3.21 (s, 6H), 2.37 (s, 3H)
1 3	0 Z^rFrFo XH, HjC-h{ CHj	white solid	109 111	ESIMS m/z 285 ([M+H] +)	(600 MHz, DMSO-de) 8.65 (s, 1H), 8.04 (d, J = 6.2 Hz, 1H), 5.58 (s, 2H), 3.20 (s, 3H), 3.07 (s, 3H), 2.27 (t, J = 7.3 Hz, 2H), 1.53-1.46 (m ,2H), 0.83 (t, J = 7.3 Hz, 3H)

J

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
1 6	h3c'°^o h2nAAo	white solid	160 163	ESIMS m/z 218 ([M+H] +)	(DMSO-de) 7.97 (d, J - 6.6 Hz, 1H), 7.83 (s, 1H), 7.58 (s, 1H), 5.03 (s, 2H), 3.65-3.53 (m, 2H), 3.46-3.38 (m, 2H), 3.22 (s, 3H)
1 7	h3c ch3 h3c's,-^o γν h2n SAo	offwhite solid	187 192	ESIMS m/z 260 ([M+H] +)	(DMSO-de) δ 7.96 (d, J = 6.6 Hz, 1H), 7.80 (s, 1H), 7.57 (s, 1H), 4.99 (s, 2H), 3.51 (dd, J = 20.2, 12.2 Hz, 2H), 0.85 (t, J = 7.9 Hz, 2H), -0.03 (s, 9H).

C m P d	Structure	Appear ance	mp (’C )	MS	1H NMRa (□, solvent)
1 8	CH3 Fyÿ'N^o^>	off- white solid	166 170	ESIMS m/z 272 ([M+H] +)	(DMSO-d6) 7.98 (d, J = 6.5 Hz, 1H), 7.85 (s, 1H), 7.62 (s, 1H), 5.01 (s, 2H), 3.44 (t, J = 6.4 Hz, 2H), 1.47 (m, 2H), 1.24 (m, 10H), 0.86 (t, J = 5.9 Hz, 3H)
1 9	°O, Fyi'N-J h2n^iAo	white	240 245	ESIMS m/z 270 ([M+H] +)	(DMSO-d6) 8.09 (d, J = 6.6 Hz, 1H), 7.97 (s, 1H), 7.72 (s, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.07 (d, J = 8.9 Hz, 2H), 5.58 (s, 2H)

t

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR° (□, solvent)
2 0	Ογ<ΜΗ3 F''Y^N^O'^CH3 Η2Ν'^Ν'ζ^Ο	white solid	150 154	ESIMS m/z 260 ([M+H] +)	(DMSO-de) 7.97 (s, 1H), 7.81 (d, J = 6.3 Hz, 1H), 7.72 (s, 1H), 5.84 (s, 1H), 4.15 (dd, J = 13.7, 6.8 Hz, 2H), 3.59 (dd, J = 13.3, 6.4 Hz, 2H), 1.28-1.04 (m, 6H)
2 1	0 Fy^N^cA^CH3 HjN'^N'^O	white solid	210 214	ESIMS m/z 230 ([M+H] +)	(DMSO-d6) 7.99 (m, J = 6.7 Hz, 2H), 7.72 (s, 1H), 5.55 (s, 2H), 2.30 (t, J = 7.2 Hz, 2H), 1.68-1.39 (m, 2H), 0.86 (t, J = 7.4 Hz, 3H)
2 2	0 F-y^N^oA<CH3 L L H.C CH, Η,Ν^Ν^Ο	white solid	259 264	ESIMS m/z 244 ([M+H] +)	(DMSO-de) 7.99 (d, J = 6.7 Hz, 1H), 7.97 (s, 1H), 7.71 (s, 1H), 5.54 (s, 2H), 1.12 (s, 9H)

t y

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
2 3	CH3 0 F <A O'''· C H3 H-AnA	white solid	162 166	ESIMS m/z 246 ([M+H] +)	(DMSO-de) 8.08 (d, J = 7.0 Hz, 1H), 7.95 (s, 1H), 7.69 (s, 1H), 6.72 (q, J = 5.2 Hz, 1H), 4.12 (q,J = 7.0 Hz, 2H), 1.55 (d, J = 6.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H)
2 9	Fy^N^cH 3	white solid	279 dec	ESIMS m/z 158 ([M+H] +)	(DMSO-de) 7.98 (d, J = 6.8 Hz, 1H), 7.57 (s, 1H), 7.39 (s, 1H), 3.63 (q, J = 7.1 Hz, 2H), 1.14 (t, J = 7.1 Hz, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	’H NMRa (□, solvent)
3 0	h2n'Zn'Zo	white solid	168 189	ESIMS m/z 264 ([M+H] +)	(DMSO-d6) 7.93 (d, J = 3.3 Hz, 1H), 7.31 (s, 2H), 7.19 (d, J = 8.6 Hz, 2H), 6.90-6.82 (m, 2H), 4.28 (t, J = 6.9 Hz, 2H), 3.72 (s, 3H), 2.89 (t, J~ 6.9 Hz, 2H)
3 1	HjN^N^O	white solid	252 254	ESIMS m/z 268 ([M+H] +)	(DMSO-d6) 7.97 (d, J = 3.5 Hz, 1H), 7.46 (s, 2H), 7.39-7.34 (m, 2H), 7.34-7.28 (m, 2H), 4.34 (t, J = 6.7 Hz, 2H), 2.97 (t, J = 6.7 Hz, 2H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
3 2	’rxx- h2n n^o	pale yellow solid	255 dec	ESIMS m/z 214 ([M+H] *)	(DMSO-de) 7.92 (d, J = 3.2 Hz. 1H), 7.27 (s, 2H), 4.10 (dd, J = 10.5, 6.7 Hz, 1H), 4.02 (dd, J = 10.5, 8.0 Hz, 1H), 3.78-3.69 (m, 2H), 3.63 (dd, J = 15.0, 7.8 Hz, 1H), 3.47 (dd, J = 8.6, 5.6 Hz, 1H), 2.59 (dt, 7 = 14.1, 7.2 Hz, 1H), 1.97 (dtd, J = 13.8, 8.2, 5.6 Hz, 1H), 1.65-1.53 (m, 1H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
3 3	F HjN^N^O	beige solid	250 254	ESIMS m/z 256 ([M+H] +)	(DMSO-d6) 8.04 (d, J = 6.6 Hz, 1H), 7.74 (s, 1H), 7.50 (s, 1H), 7.35-7.20 (m, 2H), 7.06 (td, J = 8.5, 1.8 Hz, 1H), 4.82 (s, 2H)
3 5	FyN^YF H3C'N^N'¥-nA;.o ch3	white solid	196 200	ESIMS m/z 311 ([M+H] +)	(DMSO-cfe) 8.64 (s, 1H), 8.24 (d, J = 6.2 Hz, 1H), 7.48-7.35 (m, 2H), 7.23-7.13 (m, 1H), 4.85 (s, 2H), 3.21 (s, 3H), 3.08 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
3 6	Fy-N'~y°^CH3 h3%mAA 0 ch3	white solid	196 199	ESIMS m/z 271 ([M+H] +)	(DMSO-c/e) 8.67 (s, 1H), 8.05 (d, J = 6.2 Hz, 1H), 4.48 (s, 2H), 4.14 (q, J = 7.1 Hz, 2H), 3.22 (s, 3H), 3,10 (s, 3H), 1.20 (t, J = 7.1 Hz, H)
4 0	f'^nA^Ao'ch^ η2ν'^ν'^ο	white solid	244 .8- 245 .6	ESIMS m/z 266 ([M+H] Ί	(DMSO-de) 7.98 (d, J = 6.7 Hz, 1H), 7.80 (s,1H), 7.57 (s, 1H), 7.00 (m, 2H), 6.89 (dd, J =8.6, 2.3 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 3H)

C m P d	Structure	Appear ance	mp (’C }	MS	1H NMRa (□, solvent)
4 1	fV^-n^ch2 h2n'^n'^>o	white solid	213 .5- 214 .4	ESIMS m/z 156 ([M+H] +)	(DMSO-d6) 8.28 (d, J = 7.1 Hz, 1H), 8.01 (s, 1H), 7.77 (s, 1H), 7.18 (dd, J = 15.4, 10.3 Hz, 1H), 5.27 (d, J = 16.2 Hz, 1H), 4.78 (d, J = 8.0 Hz, 1H)
4 2	HjN^N^O	offwhite solid	233 235	ESIMS m/z 206 ([M+H] +)	(DMSO-d6) 8.05 (dd, J = 6.8, 1.7 Hz, 1H), 7.86 (s, 1H), 7.62 (s, 1H), 7.51-7.31 (m, 5H)
4 3	f rr Η^'Ί^'Χ)	off- white solid	225 227	ESIMS m/z 220 ([M+H] +)	(DMSO-d6) 8.00 (d, J = 6.7 Hz, 1H), 7.83 (s, 1H), 7.59 (s, 1H), 7.25 (s, 4H), 2.34 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRB (□, solvent)
4 4	fT°'CH· F'vYnzA HjN^N^O	brown solid	230 232	ESIMS m/z 236 ([M+H] +)	(DMSO-c/a) 7.99 (d, J = 6.7 Hz, 1H), 7.81 (s, 1H), 7.57 (s,1H), 7.29 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 3.78 (s, J = 8.6 Hz, 3H)
4 5	jOfcl HzN'Yf^O	off- white solid	255 257	ESIMS m/z 240 ([M+H] *)	(DMSO-dg) 8.07 (d, J = 6.3 Hz, 1H), 7.93 (s, 1H), 7.68 (s, 1H), 7.51 (dd, J = 8.6, 1.0 Hz, 2H), 7.43 (dd, J = 8.7, 1.1 Hz, 2H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR“ (□, solvent)
4 6		pale brown solid	175 178	ESIMS m/z 231 ([M+H] +)	(DMSO-d6) 8.16 (d, J = 6.9 Hz, 1H), 7.98-7.94 (m, 1H), 7.86-7.82 (m, 1H), 7.82-7.76 (m, 1H), 7.67 (d, J = 8.0 Hz, 1H)
4 7	rr0> Η^'Ί^Ο	offwhite solid	275 279	ESIMS m/z 250 ([M+H] +)	(DMSO-c/e) 7.96 (d, J = 6.7 Hz, 1H), 7.82 (s,1H), 7.57 (s, 1H), 6.99 (d, J = 2.1 Hz, 1H), 6.96 (d, J = 8.2 Hz, 1H), 6.82 (dd, J = 8.3, 2.1 Hz, 1H), 6.08 (s, 2H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR8 (□, solvent)
4 8	h2n%''^o	yellow solid	256 258	ESIMS m/z 232 ([M+H] +)	(DMSO-cfs) δ 8.42 (d, J = 7.2 Hz, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.66 (d, J = 15.0 Hz, 1H), 7,44 (d, J = 7.9 Hz, 2H), 7.36 (t, J = 7.6 Hz, 2H), 7.26 (dd, J — 10.5,4.0 Hz, 1H), 6.81 (d, J = 15.0 Hz, 1H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR8 (□, solvent)
4 9		pale brown solid	212 214	ESIMS m/z 246 ([M+H] +)	(DMSO-d6) 8.24 (d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 7.69 (s, 1H), 7.31 (m, 2H), 7.22 (dd, J = 14.9, 7.1 Hz. 3H), 7.03 (dd, J = 14.5, 1.6 Hz, 1H), 5.95 (dt, J = 14.5, 7.3 Hz, 1H), 3.45 (d, J = 7.1 Hz, 2H)
5 0	%O f rr-	off- white solid	244 .4- 245 .7	ESIMS m/z 284 ([M+H] +)	(DMSO-de) 8.14 (d, J = 6.8 Hz, 1H), 8.04-7.92 (m, 3H), 7.75 (s, J = 7.8 Hz, 1H), 7.69 (d, J 8.4 Hz, 2H), 3.26 (s, 3H).

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
5 1	F η·νΚνΟ 0	white solid	190 .6- 192 .7	ESIMS m/z 210 ([M+H] +)	(DMSO-de) 7.75 (d, J = 6.6 Hz, 1H), 7.62 (s, 1H), 7.41 (s, 1H), 5.66 (t, J = 3.7 Hz, 1H), 2.15 (d,J = 36.9 Hz, 4H), 1.60 (dt, J = 10.5, 5.0 Hz, 4H)
5 2	HjN'^N'^O	yellow solid	211 .2- 213 .0	ESIMS m/z 232 ([M+H] +)	(DMSO-de) 7.97 (d, J = 6.5 Hz, 1H), 7.83 (s, 1H), 7.60 (s, 1H), 7.45-7.24 (m, 5H), 5.86 (d, J = 0.9 Hz, 1H), 5.37 (d, J = 0.9 Hz, 1H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR8 (□, solvent)
5 3	HjN'^N'^O	white solid	152 .8- 153 .4	ESIMS m/z 198 ([M+H] +)	(DMSO-d6) 8.17 (d, J = 7.1 Hz. 1H), 7.85 (s, 1H), 7.62 (s, 1H), 6.88 (d, J = 14.5 Hz, 1H), 5.74 (dt, J = 14.3,7.1 Hz, 1H), 2.06 (q, J = 7.1 Hz, 2H), 1.48-1.31 (m, 2H), 0.89 (t, J = 7.3 Hz, 3H)
5 4	ΓΎ%η> HjN'^N'^O	yellow solid	263 .3- 265 .1	ESIMS m/z 262 ([M+H] +)	(CD3OD) 8.20 (d, J = 6.7 Hz, 1H), 7.55 (dd, J - 14.8, 1.9 Hz, 1H), 7.40 (d, J = 8.7 Hz, 2H), 6.94-6.87 (m, 2H), 6.68 (d, J = 14.7 Hz, 1H), 3.80 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
5 5		white solid	272 .8- 274 .2	ESIMS m/z 256 ([M+H] +)	(DMSO-de) 8.17 (d, J = 6.7 Hz, 1H), 8.00-7.85 (m, 5H), 7.65 (s, 1H), 7.61-7.49 (m, 3H)
5 7	YY°'CH’ μ AAq' CH’ CH,	yellow solid	196 .1- 198 .0	ESIMS m/z 321 ([M+H] +)	(DMSO-d6) 8.72 (s, 1H), 8.09 (d, J = 6.2 Hz, 1H), 7.07-7.02 (m, 1H), 7.00 (s, 1H), 6.94 (dd, J = 8.5, 2.3 Hz, 1H), 3.80 (s, 3H), 3.77 (s, 3H), 3.25 (s, 3H), 3.13 (s, 3H)

5l

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR8 (□, solvent)
5 8	F'Y^N'x>fCH2 h3c.^nAnA0 ch3	yellow solid	179 .6- 181 .3	ESIMS m/z 211 ([M+H] +)	(DMSO-cfe) 8.69 (d, J = 17.4 Hz, 1H), 8.37 (d, J = 6.6 Hz, 1H), 7.21 (ddd, J = 22.7, 11.3, 6.8 Hz, 1H), 5.41 (d, J = 16.2 Hz, 1 H), 4.89 (d, J = 9.2 Hz, 1H), 3.25 (s, 3H), 3.11 (d, J = 11.5 Hz, 3H)
5 9	°s'-° f ΧΎ 'CHi ^ÂAo ch3	white solid	284 .6- 186 .9	ESIMS m/z 339 ([M+H] Ί	(DMSO-c/6) 8.75 (s, 1H), 8.23 (d, J = 6.3 Hz, 1H), 8.01 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 8.6 Hz, 2H), 3.27 (s, 3H), 3.26 (s, 3H), 3.14 (s. 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
6 0	F h>c- H3C 0	white solid	173 .ΣΙ 74 .4	ESIMS m/z 265 ([M+H] +)	(DMSO-de) 8.63 (s, 1H), 7.87 (d, J = 6.0 Hz, 1H), 5.72 (s, 1H), 3.21 (s, 3H), 3.08 (s, 3H), 2.18 (d, J = 37.4 Hz, 4H), 1.62 (dd, J = 29.1, 4.7 Hz, 4H)
6 1	F^^N^CHj h’c'n-^n-^n-^o Ôh3	yellow solid	147 Ό- 147 .9	ESIMS m/z 287 ([M+H] +)	(DMSO-de) 8.69 (s, 1H), 8.08 (d, J6.0 Hz, 1H), 7.40-7.27 (m, 5H), 5.92 (d, J = 1.2 Hz, 1H), 5.44 (d, J = 1.1 Hz, 1H), 3.23 (s, 3H), 3.12 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
6 2	h’c'n^nAAo ch3	white solid	144 .7- 146 .3	ESIMS m/z 253 ([M+H] Ί	(CD3OD) 8.72 (s,1H), 8.06 (d, J = 6.0 Hz, 1H), 6.96 (dd, J = 14.3, 1.6 Hz, 1H), 5.89 (dt, J = 14.4, 7.2 Hz, 1H), 3.27 (s, 3H), 3.21 (s, 3H), 2.18 (ddd, J = 14.7, 7.3, 1.4 Hz, 2H), 1.59-1.44 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR® (□, solvent)
6 3	ÔH,	Yellow solid	264 .3- 265 .3	ESIMS m/z 317 ([M+H] +)	DMSO-de) 8.72 (s, 1H), 8.44 (d, J = 6.8 Hz, 1H), 7.56 (dd, J = 14.9, 1.8 Hz, 1H), 7.40 (d, J = 8.7 Hz, 2H), 6.93 (d, J = 8.7 Hz, 2H), 6.86 (d, J~ 14.9 Hz, 1H), 3.76 (s, 3H), 3.25 (s, 3H), 3.12 (s, 3H)
6 4	ch3	yellow solid	222 .4- 224 .4	ESIMS m/z 311 ([M+H] +)	(DMSO-de) 8,74 (s, 1 H), 8.27 (d, J = 6.2 Hz, 1H), 8.04-7.90 (m, 4H), 7.65-7.49 (m, 3H), 3.25 (s, 3H). 3.13 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
6 6	.rV- J-vO°CH· F °	white solid	206 .3- 207 .9	ESIMS m/z 374 {[M+H] +)	(DMSO-de) 8.60 (t, J = 6.0 Hz, 1H), 8.03 (d, J = 6.8 Hz, 1H), 7.43-7.29 (m, 2H), 7.26-7.16 (m, J = 12.8, 5.9 Hz, 2H), 7.03-6.97 (m, 2H), 6.90 (dd, J = 8.5, 2.0 Hz, 1H), 4.63 (d, J = 5.7 Hz, 2H), 3.79 (s, 3H), 3.75 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
6 7	fY^n^ch2 O? Λο	white solid	168 .6- 169 .1	ESIMS m/z 264 ([M+H] +)	(DMSO-de) 8.81 (s, 1H), 8.32 (d, J = 7.3 Hz, 1H), 7.34 (dd, J = 14.4, 6.6 Hz, 2H), 7.27-7.09 (m, 2H), 5.30 (dd, J = 16.1, 1.5 Hz, 1H), 4.80 (dd, J = 9.2, 1.5 Hz, 1H), 4.62 (d, J = 5.8 Hz, 2H)
6 8	a? fA	white solid	231 .6- 233 .1	ESIMS m/z 392 ([M+H] +)	(CDjOD) 8.11 -8.00 (m, 2H), 7.94 (d, J = 6.3 Hz, 1H), 7.76-7.66 (m, 2H), 7.47 (t, J = 6.9 Hz, 1 H), 7.37-7.25 (m, 1 H), 7.20-7.04 (m, 2H), 4.78 (s, 2H), 3.16 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
6 9	F F	white solid	151 .5- 152 .6	ESIMS m/z 318 ([M+H] +)	(DMSO-de) 8.45 (t, J = 5.7 Hz, 1H), 7.80 (d, J = 6.7 Hz, 1H), 7.37-7.10 (m, 4H), 5.68 (s, 1H), 4.57 (d, J = 5.8 Hz, 2H), 2.15 (d, J - 33.7 Hz, 4H), 1.75- 1.47 (m,4H)
7 0	F S^ljAc^	white solid	138 .9- 140 .2	ESIMS m/z 340 ([M+H] +)	(DMSO-de) 8.63 (t, J = 5.9 Hz, 1H), 8.02 (d, J = 6.6 Hz, 1H), 7.46-7.25 (m, 7H), 7.25-7.12 (m, 2H), 5.89 (d, J = 0.9 Hz, 1H), 5.39 (d, J = 0.9 Hz, 1H), 4.62 (d, J5.8 Hz, 2H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
7 1	CÇ 0	white oil		ESIMS m/z 306 ([M+H] +)	(DMSO-c/e) 8.68 (t, J = 5.7 Hz, 1H), 8.22 (d, J = 7.2 Hz, 1H), 7.39-7.23 (m, J = 7.5 Hz, 2H), 7.23-7.05 (m, J = 15.2, 8.1 Hz, 2H), 6.88 (d, J = 14.4 Hz, 1H), 5.76 (dt, J = 14.4, 7.2 Hz, 1H), 4.60 (d, J = 5.8 Hz, 2H), 2.06 (dd, J = 14.3, 7.1 Hz, 2H), 1.48-1.29 (m, 2H). 0.89 (t, J = 7.3 Hz, 3H)

J

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
7 2	νΝ^σ0'^ C? Λ°	yellow solid	196 .8- 198 .5	ESIMS m/z 370 ([M+H] +)	(CD3OD) 8.18 (d, J = 6.8 Hz, 1H), 7.56 (dd, J - 14.8, 2.0 Hz, 1H), 7.50-7.36 (m, 3H). 7.35-7.24 (m, 1H), 7.14 (dd, J = 7.6, 6.4 Hz, 1H), 7.10-7.03 (m, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6,68 (d, J = 14.7 Hz, 1H), 4.76 (s, 2H), 3.80 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
7 3	a? A	white solid	207 .5- 209 .0	ESIMS m/z 364 ([M+H] *)	(DMSO-de) 8,76-8.60 (m, 1H), 8.21 (d, J = 6.8 Hz, 1H), 8.01-7.87 (m, 4H), 7.64-7.47 (m, 3H), 7.10-7.45 (m, 4H), 4.65 (d, J = 6.2 Hz, 2H)
7 5	h2nAA	brown solid	229 .2- 231 .3	ESIMS m/z 221 ([M+H] +)	(CD3OD) 8.58 (d, J = 2.0 Hz, 1H), 8.49 (dd, J = 4.9, 1.5 Hz, 1H), 7.98 (d, J = 6.2 Hz, 1H), 7.90-7.82 (m, 1H), 7.44 (dd, J = 7.9, 4.9 Hz, 1H), 4.98 (s, 2H)

6l

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
7 6		offwhite solid	179 2- 181 .1	ESIMS m/z 214 ([M+H] +)	(DMSO-c/6) 7.83 (d, J = 6.8 Hz, 1H), 7.58 (s, 1H), 7.37 (s, 1H), 4.08-3.98 (m, 1H), 3.84-3.71 (m, 2H), 3.63 (dd, J = 14.3, 7.3 Hz, 1H), 3.50 (dd, J = 13.5, 7.8 Hz, 1H), 1.98-1.72 (m, 3H). 1.61-1.43 (m, 1H)
7 7	F\4^N-''Y/CH3 η2ιΆιΑο CH3	white solid	140 142 .8	ESIMS m/z 186 ([M+H] +)	(DMSO-d5) 8.57 (d, J = 6.8 Hz, 1H), 8.15 (s, 1H), 7.98 (s, 1H), 4.06 (d, J = 7.4 Hz, 2H), 2.72-2.54 (m, 1H), 1.47 (d, J = 6.6 Hz, 6H)

C m P d	Structure	Appear ance	mp (°C )	MS	’H NMR8 (□, solvent)
7 8	0-vX CHs h2nx^nx^o	off- white solid	207 .3- 208 .2	ESIMS m/z 202 ([M+H] +)	(CDCIa) 7.56 (d, J = 5.3 Hz, 1H), 3.99-3.91 (m, 2H), 3.68-3.62 (m, 2H), 3.48 (q, J = 7.0 Hz, 2H), 1.17 (t, J = 7.0 Hz, 3H)
7 9	f^n^s'CH3 h2n'^%,n'^o	offwhite solid	128 .5- 130 .6	ESIMS m/z 190 ([M+H] *). 188 ([Μ-HD	(CD3OD) 7.52 (d, J = 5.8 Hz. 1H), 4.59 (s, 2H), 2.21 (s, 3H)
8 1	O F'Y^n'~'\7 (Q^cAnAAo	offwhite solid	228 230	ESIMS m/z 318 ([M+H] Ί,	(CD3OD) 8.22 (s, 1H), 7.54-7.25 (m, 5H), 5.26 (s, 2H). 3.71 (d, J = 6.4 Hz, 2H), 1.30 (s, 1H), 0.68-0.53 (m, 2H), 0.50-0.33 (m, 2H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR8 (□, solvent)
8 2	OjXx> o^o ό	offwhite solid	159 161	ESIMS m/z 424 ([M+H] +)	(CD3OD) 8.72 (d, J = 4.9 Hz, 1H), 7.52-7.41 (m, 4H), 7.36-7.31 (m, 2H), 7.28-7.23 (m, 4H), 3.87 (d, J = 7.3 Hz, 2H), 1.41-1.33 (m, 1H), 0.71-0.63 (m, 2H), 0.53-0.45 (m, 2H)

I

c m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
8 3		gum		ESIMS m/z 293 ([M+H] +)	(CD3OD) 8.62 (d, J = 1.6 Hz, 1H), 8.51 (dd, J = 4.9, 1.3 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.45 (dd, J = 8.0,4.9 Hz, 1H), 5.06 (s, 2H), 4.25 (q, 7 = 7.1 Hz, 2H), 1.32 (t, 7 = 7.1 Hz, 3H)
8 4	o Fy-N^S'CH3 H,C—O'^'N'^N'^O 3 H	offwhite solid	137 .1- 138 .8	ESIMS m/z 260 ([M-HD	(Acetonecfe) 8.18 (s, 1H), 8.00 (d, 7 = 7.2 Hz, 1H), 4.64 (d, 7 = 6.3 Hz, 2H), 4.37 (q, 7 = 7.1 Hz, 2H), 2.23 (d, 7 = 4.4 Hz, 3H), 1.35 (t, 7=7.1 Hz, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
8 6	N^°	yellow solid	181 .8- 183 .5	ESIMS m/z 343 ([M+H] +)	(CD3OD) 8.28 (d, J = 5.9 Hz, 1H), 8.22 (dd, J = 8.3, 1.4 Hz, 1H), 7.47 (dd, J = 8.0, 1.4 Hz, 1H), 7.35-7.27 (m, 1H), 7.17-7.09 (m. 1H), 4.98 (s, 2H), 2.23 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	’H NMRa (□, solvent)
8 7	o FV^nXX\7	offwhite solid	113 .0- 114 .9	ESIMS m/z 297 ([M+H] +)	(DMSO) 9.87 (s, 1 H), 9.38 (s, 1H), 8.34 (d, J = 5.9 Hz, 1H), 3.56 (d, J = 7.2 Hz, 2H), 3.21 (d, J = 5.8 Hz, 2H), 1.58-1.41 (m, 2H), 1.40-1.09 (m, 5H), 0.88 (t, J = 6.8 Hz, 3H), 0.56-0.41 (m, 2H), 0.41 -0.29 (m, 2H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR (□, solvent)
8 8		off- white solid	205 ΌΣΟ? .5	ESIMS m/z 317 ([M+H] +)	(CD3OD) 8.25 (d, J = 6.0 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.3 Hz, 2H), 3,75 (d, J = 7.3 Hz, 2H), 2.32 (s, 3H), 1.37-1.26 (m, 1H), 0.67-0.59 (m, 2H), 0.45 (q, J = 4.7 Hz, 2H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
8 9		offwhite solid	146 .Ο- Ι 47 .6	ESIMS m/z 334 ([M+H] +),	(DMSO-d6) 9.96 (s, 1H), 9.33 (t, J = 5.4 Hz, 1H), 8.59 (d, J = 1.7 Hz, 1H), 8.51 (s, 1H), 8.50 (s, 1H), 7.76 (d, J~ 8.0 Hz, 1H), 7.38 (dd, J = 7.6, 4.9 Hz, 1H), 4.93 (s, 1H), 3.20 (dd, J = 12.7,6.7 Hz, 2H), 1.55-1.38 (m, 2H), 1.29 (dd, J = 8.7, 5.4 Hz, 4H), 0.87 (t, J = 6.7 Hz, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRB (□, solvent)
9 0	H,cnBx;xOT	offwhite solid	178 .2- 180	ESIMS m/z 354 ([M+H] +)	(CD3OD) 8.66 (d, J = 1.7 Hz, 1H), 8.52 (dd, J = 4.9, 1.6 Hz, 1H), 8.37 (d, J = 5.9 Hz, 1H), 7.96-7.90 (m, 1H), 7.51 (d, J = 8.5 Hz, 2H), 7.47 (dd, J = 8.2, 5.2 Hz, 1H), 7.15 (d, J = 8.3 Hz, 2H), 5.11 (s, 2H), 2.32 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMR® (□, solvent)
9 1		offwhite solid	210 .5- 212 .3	ESIMS m/z 374 ([M+H] +)	(DMSO-de) 12.29 (s, 1H), 10.59 (s, 1H), 8.64 (m, 2H), 8.52 (d, J = 4.8 Hz, 1H), 8.31 (dd, J = 8.3, 1.2 Hz, 1H), 7.83-7.77 (m, 1H), 7.52 (dd, J = 8.0, 1.2 Hz, 1H), 7.43-7.31 (m, 2H), 7.12 (td, J = 7.9, 1.5 Hz, 1H), 4.98 (s, 2H)

7l

C m P d	Structure	Appear ance	mp (°C )	MS	’H NMRa (□, solvent)
9 2	o F'Y^N'^'S'CH) ^nA0	offwhite solid	100 .2- 101 .8	ESIMS m/z 301 ([M-HD	(CD3OD) 8.43 (d, J = 7.4 Hz, 1H), 4.62 (S, 2H), 3.37 (t, J = 7.0 Hz, 2H), 2.22 (s, J = 5.7 Hz, 3H), 1.61 (dd, J = 14.1, 7.1 Hz, 2H), 1.44-1.32 (m, 4H), 0.94 (t, J = 7.0 Hz, 3H)
9 3	π^Ύ^Τι o f'y!!^n'xxs'CH1	offwhite solid	188 .8- 190 .2	ESIMS m/z 323 ([M+H] *)	(CD3OD) 8.27 (d, J = 5.9 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.16 (d, J- 8.2 Hz, 2H), 5.00 (s, 2H), 2.32 (s, 3H), 2.24 (s, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
9 5	AÂ A U H.C N N^O 3 H	pale yellow gum		ESIMS m/z 256 ([M+H] +)	(CDCI3) 7,76 (d. J = 5.5 Hz, 1H), 4.30 (dd, J = 13.8, 2.1 Hz, 1H), 4.18 (dd, J = 14.8, 7.6 Hz, 1H), 3.87 (dd, J = 15.2, 6.9 Hz, 1H), 3.78 (dd, J = 14.4, 7.6 Hz, 1H), 3.57 (dd, J = 13.8, 7.9 Hz, 1H), 2.65 (s, 3H), 2.20-2.06 (m, 1H), 2.01-1.85 (m, 2H), 1.58 (ddd, J = 16.1, 12.5, 8.0 Hz, 1H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
9 6	F 0 FVXN'^Y°x	white solid	119 .8- 121 .9	ESIMS m/z 336 ([M+H] +),	(DMSO-d6) 11.22 (s, 1H), 8.38 (s, 1H), 7.70 (s, 1H), 7.63 (dd, J = 13.0, 6.4 Hz, 1H), 7.33 (t, J = 7.6 Hz, 2H), 4.11 (s, 1H), 3.96 (s, 1H), 3.80 (dd, J = 14.8, 6.9 Hz, 1H), 3.74-3.59 (m, 2H), 2.02-1.91 (m, 1H), 1.91-1.75 (m, 2H), 1.63-1.51 (m, 1H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
9 7	0 «/AA ch>	white solid	134 .5- 136 .5	ESIMS m/z 228 ([M+H] +)	(CDCh) 7.72 (s, 1H), 7.43 (d, J = 4.6 Hz, 1H), 3.63 (d, J = 7.4 Hz, 3H), 2.67 (s, 3H), 2.29-2.12 (m, 1H), 0.98 (d, J = 6.7 Hz, 6H)
9 8	F 0 ΡγχΝΧΧγ'°Η3 jV/ACH·	white solid	161 .3- 163	ESIMS m/z 308 ([M+H] +)	(DMSO-de) 11.20 (s, 1H), 8.49 (s, 1H), 7.80- 7.54 (m, 2H), 7.33 (t, J = 7.5 Hz, 2H), 3.62 (d, J = 6.5 Hz, 2H), 2.08 (s, 1H), 0.87 (d, J = 6.7 Hz, 6H)

C m P d	Structure	Appear ance	mp (°C )	MS	’H NMRa (□, solvent)
9 9	ο ργ^Ν/'Ύ°Η3 CHî	pale yellow solid	125 .6- 127 .5	ESIMS m/2 296 ([M+H] +)	(CDCh) 12.85 (s. 1H), 7.97 (dd, J = 3.8, 1.2 Hz, 1H), 7.61 (dd, J = 4.9, 1.2 Hz, 1H), 7.33 (d, J = 5.4 Hz, 1H), 7.14 (dd, J = 4.9, 3.8 Hz, 1H), 3.57 (d, J = 7.5 Hz, 2H), 2.19-2.04 (m, 1H), 0.99 (d, J = 6.7 Hz, 6H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
1 0 0	Or ΔΛ°	offwhite solid	109 110 .4	ESIMS m/z 312 ([M+H] +).	(CDCIg) 8.00-7.93 (m, 1H), 7.60 (dd, J = 4.8, 0.8 Hz, 1H), 7.56 (d, J = 5.6 Hz, 1H), 7.13 (dd, J = 4.7,4.0 Hz, 1H), 3.98-3.90 (m, 2H), 3.70-3.63 (m, 2H), 3.51 (q, J = 7.0 Hz, 2H), 1.19 (t, J = 7.0 Hz, 3H)

j»

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
1 0 1	I F 0	off- white solid	116 .8- 117 .8	ESIMS m/z 324 ([M+H] +)	(CDCI3) 8.20 (td, J = 7.8, 1.6 Hz, 1H), 8.02 (t, J = 7.6 Hz, 1H), 7.69 (d, J =5.5 Hz, 1H), 7.55 (dd, J = 13.1, 5.9 Hz, 1H), 7.32-7.24 (m, 1H), 7.18 (dd, J = 11.7, 8.3 Hz, 1H), 4.05-3.97 (m, 2H), 3.74-3.66 (m, 2H), 3.50 (q, J = 7.0 Hz, 2H), 1.19 (t, J = 7.0 Hz, 3H)

t r

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
1 0 3	H3CXX'hj'^N'^O	brown gum		ESIMS m/z 242 ([M+H] +)	(Acetoned6) 7.61 (d, J = 6.9 Hz, 1H), 7.056.84 (m, 1H), 4.154.06 (m, 1H), 3.97 (dd, J = 13.7.3.2 Hz, 1H), 3.83 (dd, J = 14.9, 6.7 Hz, 1H), 3.68 (dd, J = 14.8, 6.9 Hz, 1H). 3.51 (ddd, J = 20.0, 13.7.7.3 Hz, 3H), 2.03-1.93 (m, 1H), 1.92-1.78 (m, 2H), 1.60 (dd, J = 12.1, 8.1 Hz, 1H), 1.20 (t, J = 7.2 Hz, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
1 0 4	F'îi Λο	gum		ESIMS m/z 322 ([M+H] +)	(Acetoned8) 7.70 (d, J = 6.7 Hz, 1H), 7.537.42 (m, J = 6.9 Hz, 2H), 7.37-7.27 (m, 1H), 7.21-7.06 (m, 2H), 4.75 (d, J = 5.7 Hz, 2H), 4.11 (qd, J = 7.1, 3.2 Hz, 1H), 3.99 (dd, J = 13.6, 3.2 Hz, 1H), 3.88-3.79 (m, 1H), 3.69 (dd, J = 14.9, 6.9 Hz, 1H), 3.55 (dd, J = 13.6, 7.8 Hz, 1H), 2.03-1.93 (m, 1H), 1.92-1.80 (m, 2H), 1.67-1.53 (m, 1H)

ï

C m P d	Structure	Appear ance	mp (°C )	MS	’H NMRa (□, solvent)
1 0 6	F'^î^N'^Y'CH;> CH3	Offwhite solid	88. 8- 91. 7	ESIMS m/z 282 ([M+H] +)	(CDCI3) 7.30-7.25 (m, 2H), 7.19 (d, J = 5.8 Hz. 1H), 7.08 (d, J = 3.1 Hz, 1H), 6.99 (dd, J = 5.1, 3.5 Hz, 1H), 4.91 (d, J = 4.9 Hz, 2H), 3.57 (d, J = 7.5 Hz, 2H), 2.17 (dt, J = 13.6, 6.8 Hz. 1H), 0.96 (d, J = 6.7 Hz, 6H)
1 0 7	Ρ>^Ν'ΛγΰΗ3 h^nMo ch’ 3 H	brown gum		ESIMS m/z 214 ([M+H] +)	(CDCI3) 7.14 (d, J = 5.9 Hz, 1H), 3.65-3.50 (m, 4H), 2.16 (dt, J = 13.7, 6.9 Hz, 1H), 1.27 (t, J = 7.3 Hz, 3H), 0.94 (d, J = 6.7 Hz, 6H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
1 0 8	A A l+C N N O 3 H	brown solid	63- 65	ESIMS m/z 230 ([M+H] +)	(Acetoned6) 7.61 (d, J = 6.8 Hz, 1H), 6.99 (s, 1H), 3.85 (t, J =5.2 Hz, 2H), 3.62 (t, J =5.2 Hz, 2H), 3.54- 3.42 (m, 4H), 1.20 (t, J = 7.2 Hz, 3H), 1.12 (t, J = 7.0 Hz, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	1H NMRa (□, solvent)
1 0 9	F Fy^N-^Xz'°'-'CH3 ify-n-Vo	brown gum		ESIMS m/z 310 ([M+H] +)	(Acetoned6) 7.69 (d, J = 6.7 Hz, 1H), 7.48 (t, J = 7.0 Hz, 1H), 7.37- 7.27 (m, 1H), 7.207.05 (m, 2H), 4.75 (d, J = 5.5 Hz, 2H), 3.88 (dd, J = 11.8,6.6 Hz, 2H), 3.61 (dd, J = 12.7, 7.7 Hz, 2H), 3.54-3.41 (m, 2H), 1.18-1.05 (m, 3H)

C m P d	Structure	Appear ance	mp (°C )	MS	’H NMRa (□, solvent)
1 1 0	F'Y^N-''\x'°----CH3	gum		ESIMS m/z 298 ([M+H] +)	(Acetoned6) 7.68 (d, J = 6.7 Hz, 1H), 7.57 (s, 1H), 7.32 (dd, J=5.1, 1.2 Hz, 1H), 7.12-7.04 (m, 1H), 6.95 (dd, J = 5.1,3.5 Hz, 1H), 4.85 (d, J = 5.9 Hz, 2H), 3.88 (t, J = 5.2 Hz, 2H), 3.63 (t, J = 5.2 Hz, 2H), 3.47 (q, J = 7.0 Hz, 2H), 1.12 (t, J = 7.0 Hz, 3H)

Example 26 Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Mycosphaerella graminicola; anamorph: Septoria tritici; Bayer code SEPTTR)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% minerai soil/50% soil-less Métro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Septoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidlty (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.

I»

The following table présents the activity of typical compounds of the présent disclosure when evaluated in these experiments. The effectiveness of the test compounds in controliing 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, 5 inoculated plants.

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

% Disease Control	Rating
76-100	A
51-75	B
26-50	C
0-25	D
Not Tested	E

TABLE II: One-Day Protectant (1DP) and Three-Day Curative (3DC) Activity of Compounds on SEPTTR at 100 ppm

Cmpd	SEPTTR 100 PPM 1DP	SEPTTR 100 PPM 3DC
1	A	A
2	A	A
3	A	A
4	C	D
5	D	D
6	D	D
7	D	D
8	C	D
9	C	D
10	C	B
11	C	D
12	A	A
13	A	A
14	D	D
15	D	D
16	D	D

Cmpd	SEPTTR 100 PPM 1DP	SEPTTR 100 PPM 3DC
17	B	A
18	C	B
19	C	D
20	D	D
21	A	A
22	A	A
23	A	A
24	A	A
25	D	D
26	D	C
27	D	D
28	B	A
29	B	A
30	D	A
31	D	A
32	A	A
33	D	B
34	A	A
35	B	B
36	B	C
37	D	D
38	D	D
39	D	A
40	D	D
41	A	A
42	E	E
43	C	D
44	E	E
45	E	E
46	D	D
47	C	D
48	E	E

Cmpd	SEPTTR 100 PPM 1DP	SEPTTR 100 PPM 3DC
49	E	E
50	E	E
51	E	E
52	E	E
53	E	E
54	E	E
55	E	E
56	C	B
57	D	D
58	A	A
59	E	E
60	E	E
61	E	E
62	E	E
63	E	E
64	E	E
65	D	D
66	D	D
67	D	B
68	E	E
69	E	E
70	E	E
71	E	E
72	E	E
73	E	E
74	A	B
75	C	A
76	D	B
77	C	D
78	E	E
79	E	E
80	D	B

Claims (4)

1. WHAT IS CLAIMED IS:

   1, A compound of Formula I:

   Formula I wherein R¹ is:

   H;

   CrC_e alkyl optionally substituted with 1-3 R⁴;

   CrCg alkenyl optionally substituted with 1-3 R⁴;

   C₃-C₆alkynyl optionally substituted with 1-3 R⁴;

   phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1- 3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

   -(CHR%OR⁷;

   -(CHR⁶)_m N(R®)R¹⁰;

   -C(=O)R⁸;

   -C(=S)R⁸;

   -S(O)₂R⁸;

   -C(=O)OR⁸;

   -C(=S)OR^s;

   -(CHR^e)_mN(R⁹)R¹⁰;

   -C(=O)N(R⁹)R¹⁰; or

   -C(=S)N(R⁹)R¹⁰;

   wherein m is an integer 1-4;

   R² is:

   H; or

   CrCe alkyl optionally substituted with R⁴;

   ι ¹ · alternative^ R¹ and R² may be taken together to form:

   =CR¹¹N(R¹²)R¹³;

   R³ is:

   Ci-C₆ alkyl optionally substituted with 1-3 R⁴, C3-C6 haloalkyl, CrC6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C8 haloalkoxyalkyl, C2-Ce alkenyl optionally substituted with R¹⁴, C2-C₈ haloalkenyl, C₃-C₈ alkynyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 13 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

   -(CHR⁸)_mOR⁷;

   -(CHR⁰)_m SR⁸; or

   -(CHR^e)_m N(R⁹)R¹°;

   R⁴ is independently halogen, C_rC₈ alkyl, C_rC₄ haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, CrC4 alkylthio, C1-C4 haloalkylthio, amino, halothio, ΟτΟ₃ alkylamino, C₂-C₈ alkoxycarbonyl, C₂-C₈ alkylcarbonyl, C₂-C₆ alkylaminocarbonyl, hydroxyl, C₃-C₈ trialkylsilyl, phenyl optionally substituted with 1-3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵;

   R⁵ is independently halogen, C_rC₈ alkyl, Ci-C₈ haloalkyl, C^Ca alkoxy, Ci-C₈ haloalkoxy, Ci-C₆ alkylthio, CrC_e haloalkylthio, halothio, amino, CrCe alkylamino, C₂-C₈ dialkylamino, C₂-C_e alkoxycarbonyl, C₂-C₈ alkylcarbonyl, Ci-C₈ alkylsulfonyl, nitro, hydroxyl, or cyano;

   R⁶ is H, CrCe alkyl, C_rC₈ alkoxy, CrC₆alkoxycarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵;

   R⁷ is H, C^Ce alkyl, C₂-C₆ alkenyl, C₃-C₈ alkynyl, C^Ce haloalkyl, Ο_ΓΟ₆ alkoxyalkyl, C₂-C₈ trialkylsilyl, C₂-C_e trialkylsilylalkyl C₂-C₈ alkylcarbonyl, Ο,-Οβ alkoxycarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a 5or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a

   6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

   R^e is H, Ci“Cg alkyl, C₂-C_e alkenyl, C₃-C₀ alkynyl, CrC_B haloalkyl, CrCe alkoxyalkyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a 5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be

   5 optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

   R⁰is H, Ci-C₆ alkyl, CrC_e haloalkyl, Ci-C_e alkoxyalkyl, C₂-C₀ alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵, or with a 5or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 10 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

   R¹⁰ is H, CrC₆ alkyl, Ci-C₆ haloalkyl, C_rC₀ alkoxyalkyl, C₂-C₆ alkylcarbonyl, or benzyl, wherein the benzyl may be optionally substituted with 1-3 R⁵;

   aiternatively R⁹ and R¹⁰ may 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;

   20 R¹¹ is H or C,-C₄ alkyl;

   R¹² is H, cyano, hydroxyl, C1-C4 alkyl, C_rC₀ alkoxy, C₂-C₆, alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵; or with a 5or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 25 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R^s;

   aiternatively R¹¹ and R¹² may 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;

   R¹³ is H, C_rC₄ alkyl, C_rC₀ alkoxy, C₂-C₆, alkylcarbonyl, phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R⁵; or with a 5- or 6-membered saturated or unsaturated ring System, or with a 5-6 fused ring System, or with a 6-6 fused ring System each containing 1-3 heteroatoms wherein each ring may be optionally substituted with 35 1-3 R⁵, biphenyl or naphthyl optionally substituted with 1-3 R⁵;

   * » · ►

   and alternatively R¹² and R¹³ may 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.

   R¹⁴ is phenyl or benzyl wherein each of the phenyl or the benzyl may be optionally substituted with 1-3 R^s.
2. 2. A composition for the control of a fungal pathogen including the compound of Claim 1 and a phytologically acceptable carrier material.
3. 3. The composition of claim 2 wherein the fungal pathogen is Apple Scab (Venturia inaequalis), Leaf Blotch of Wheat (Septoria tritici), Leaf Spot of Sugarbeets (Cercospora beticola), Leaf Spots of Peanut (Cercospora arachidicola and Cercosporidium personatum ), and Black Sigatoka of Banana (Mycosphaerella fijiensis).
4. 4. A method for the control and prévention of fungal attack on a plant, the method including the steps of:

   applying a fungicidally effective amount of at least one of the compounds of Claim 1 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, foliage of the plant, and a seed adapted to produce the plant.