US20100022538A1 - 5-fluoro pyrimidine derivatives - Google Patents

5-fluoro pyrimidine derivatives Download PDF

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Publication number
US20100022538A1
US20100022538A1 US12/537,504 US53750409A US2010022538A1 US 20100022538 A1 US20100022538 A1 US 20100022538A1 US 53750409 A US53750409 A US 53750409A US 2010022538 A1 US2010022538 A1 US 2010022538A1
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United States
Prior art keywords
optionally substituted
alkyl
phenyl
ring
haloalkyl
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US12/537,504
Inventor
Timothy A. Boebel
Kristy Bryan
Carla J.R. Klittich
Beth Lorsbach
Timothy P. Martin
W. John OWEN
Mark A. Pobanz
Michael T. Sullenberger
Jeffery D. Webster
Chenglin Yao
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Corteva Agriscience LLC
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Dow AgroSciences LLC
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Priority to US12/537,504 priority Critical patent/US20100022538A1/en
Assigned to DOW AGROSCIENCES LLC reassignment DOW AGROSCIENCES LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BOEBEL, TIMOTHY A., BRYAN, KRISTY, KLITTICH, CARLA J.R., LORSBACH, BETH, MARTIN, TIMOTHY P., OWEN, W. JOHN, POBANZ, MARK A., SULLENBERGER, MICHAEL T., WEBSTER, JEFFERY D., YAO, CHENGLIN
Publication of US20100022538A1 publication Critical patent/US20100022538A1/en
Priority to US14/031,920 priority patent/US9204653B2/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/18—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, directly attached to a heterocyclic or cycloaliphatic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/24—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing the groups, or; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/36—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< directly attached to at least one heterocyclic ring; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44—Guanidine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/26—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-nitrogen bonds
    • A01N57/32—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-nitrogen bonds containing heterocyclic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This present disclosure is related to the field of 5-fluoro pyrimidines and their derivatives and to the use of these compounds as fungicides.
  • Fungicides are compounds, of natural or synthetic origin, which act to protect and cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
  • the present disclosure relates to 5-fluoro pyrimidine compounds and their use as fungicides.
  • the compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
  • R 1 is —N(R 3 )R 4 ;
  • R 2 is —OR 21 ;
  • R 3 is:
  • R 4 is:
  • R 21 is:
  • R 23 is:
  • R 26 is:
  • R 29 is:
  • R 34 is:
  • R 35 is:
  • Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
  • Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, an area adjacent to the plant, and the seed adapted to produce the plant.
  • alkyl refers to an unbranched, branched, or cyclic carbon chain, including methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.
  • 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.
  • alkynyl refers to refers to a branched or unbranched carbon chain containing one or more triple bonds including propynyl, butynyl and the like.
  • R refers to the group consisting of C 2-8 alkyl, C 3-8 alkenyl or C 3-8 alkynyl, unless stated otherwise.
  • alkoxy refers to an —OR substituent.
  • alkoxycarbonyl refers to a —C(O)—OR substituent.
  • alkylcarbonyl refers to a —C(O)—R substituent.
  • alkylsulfonyl refers to an —SO 2 —R substituent.
  • haloalkylsulfonyl refers to a sulfonyl substitution on an alkyl which is partially substituted with halogen atoms
  • alkylthio refers to an —S—R substituent.
  • alkylaminocarbonyl refers to a —C(O)—N(H)—R substituent.
  • dialkylaminocarbonyl refers to a —C(O)—NR 2 substituent.
  • alkylcycloalkylamino refers to a cycloalkylamino substituent that is substituted with an alkyl group.
  • cyano refers to a —C ⁇ N substituent.
  • hydroxyl refers to a —OH substituent
  • amino refers to a —NH 2 substituent
  • alkylamino refers to a —N(H)—R substituent
  • dialkylamino refers to a —NR 2 substituent
  • alkoxyalkoxy refers to —O(CH 2 ) n —O—(CH 2 ) n where n is an integer from 1-3
  • alkoxyalkyl refers to an alkoxy substitution on an alkyl.
  • haloalkoxyalkyl refers to an alkoxy substitution on an alkyl which may be partially substituted with halogen atoms
  • hydroxyalkyl refers to an alkyl which is substituted with a hydroxyl group.
  • haloalkoxy refers to a —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
  • haloalkyl refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • haloalkenyl refers to an alkenyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • haloalkynyl refers to an alkynyl which is substituted with Cl, F, I, or Br or any combination thereof.
  • halogen refers to one or more halogen atoms, defined as F, Cl, Br, and I.
  • hydroxycarbonyl refers to a —C(O)—OH substituent.
  • nitro refers to a —NO 2 substituent.
  • thienyl refers to a 5-member aromatic ring with one sulfur atom.
  • Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or seeds.
  • 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.
  • the compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds.
  • the compounds may be applied to the roots, seeds or foliage of plants for the control of various fungi, without damaging the commercial value of the plants.
  • the materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrates, or emulsifiable concentrates.
  • the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier.
  • Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment.
  • the formulations can be prepared according to procedures that are conventional in the agricultural chemical art.
  • the present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and use as a fungicide.
  • formulations are applied as aqueous suspensions or emulsions.
  • Such suspensions or emulsions may be produced from water-soluble, water suspendable, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates.
  • any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.
  • Wettable powders which may be compacted to form water dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants.
  • 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.
  • 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.
  • the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
  • Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 10 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate.
  • the compounds may be dissolved in an inert carrier, which is either a water miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers.
  • the concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions.
  • Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.
  • Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers.
  • nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene.
  • Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts.
  • Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.
  • organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present invention are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, and the methyl ether of triethylene glycol and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate.
  • aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amide
  • Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases.
  • Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds.
  • the formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
  • Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 5 to about 50 weight percent, based on the total weight of the aqueous suspension.
  • Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above.
  • Other components such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.
  • the compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil.
  • Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance.
  • Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm.
  • a suitable solvent is a solvent in which the compound is substantially or completely soluble.
  • Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.
  • Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • a suitable dusty agricultural carrier such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • the formulations may additionally contain adjuvant surfactants to enhance deposition, wetting and penetration of the compounds onto the target crop and organism.
  • adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix.
  • the amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent.
  • Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines and blends of surfactants with mineral or vegetable oils.
  • the formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.
  • the formulations may optionally include combinations that contain other pesticidal compounds.
  • additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds.
  • the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use.
  • the compounds of Formula I, and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.
  • the compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases.
  • 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, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis , azaconazole, azoxystrobin, Bacillus subtilis , benalaxyl, benomyl, benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chloroneb, chlorothalonil, chlozolinate, Coniothy
  • the compounds of the present invention may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests.
  • 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, jasmol
  • the compounds of the present invention may be combined with herbicides that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants.
  • 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, diflufenican, etobenzanid, fenasulam, flufenacet, flufenican, mefenacet, mefluidide, metamifop, monalide,
  • Another embodiment of the present disclosure is a method for the control or prevention of fungal attack.
  • This method comprises applying to the soil, plant, roots, foliage, seed or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidal effective amount of one or more of the compounds of Formula I.
  • the compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity.
  • the compounds may be useful both in a protectant and/or an eradicant fashion.
  • the compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.
  • the compounds have broad ranges of activity against fungal pathogens.
  • exemplary pathogens may include, but are not limited to, wheat leaf blotch ( Septoria tritici , also known as Mycosphaerella graminicola ), apple scab ( Venturia inaequalis ), and Cercospora leaf spots of sugar beets ( Cercospora beticola ), peanuts ( 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 dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.
  • the compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount.
  • disease inhibiting and phytologically acceptable amount refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred.
  • concentration of 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 2 ).
  • 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.
  • N,N-dimethylpropionamide (0.202 g, 2.0 mmol) in CHCl 3 (2 mL) was added phosphorous oxychloride (POCl 3 , 0.066 g, 0.43 mmol) and the mixture was agitated on an orbital shaker at room temperature for 1 h.
  • Triethylamine (0.22 g, 2.2 mmol) and 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.10 g, 0.40 mmol) were added, and the mixture was agitated at 50° C. for 3 h, cooled to room temperature, partitioned between chloroform and water, the phases separated, and the organics evaporated under reduced pressure.
  • N-(5-Fluoro-2-hydroxypyrimidin-4-yl)-acetamide* (200 mg, 1.17 mmol) was suspended in pyridine (5 mL) and stirred at ambient temperature. To the stirred suspension was added benzenesulfonyl chloride (226 mg, 1.29 mmol) and agitation was continued for 16 hours.
  • N′-(5-Fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine 100 mg, 0.54 mmol
  • cesium carbonate 196 mg, 0.60 mmol
  • chloromethyl pivalate 90 mg, 0.6 mmol
  • the reaction mixture was partitioned between ethyl acetate and water, dried over magnesium sulfate, filtered and evaporated to yield a colorless oil which was treated with diethyl ether (3-4 mL) to produce a solid.
  • N′-(5-Fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine 100 mg, 0.54 mmol
  • cesium carbonate 196 mg, 0.60 mmol
  • bromomethyl methyl ether 75 mg, 0.6 mmol
  • t-butyl N-methyl-N-hydroxycarbamate can be prepared through known literature methods:
  • N-(5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl)acetamide (50 mg, 0.42 mmol) was stirred in a Biotage Initiator® microwave vessel with 1,2-dichloroethane (3 mL) and Lawesson's reagent (170 mg, 0.42 mmol).
  • the vessel was heated in a Biotage Initiator® microwave to 100° C. for 5 minutes then cooled room temperature, filtered, and diluted with CH 2 Cl 2 .
  • the reaction mixture was then washed brine, and the layers were separated.
  • the organic extract was dried onto silica and purified by flash chromatography.
  • the crude mixture was diluted with ethanol (60 mL) and aqueous potassium hydroxide (2.0 M, 240 mL, 480 mmol), and the resulting biphasic mixture was heated at reflux for 18 h. After cooling to room temperature, the crude material was washed with Et 2 O (200 mL ⁇ 2) and then acidified with 2.0 M HCl ( ⁇ 215 mL) to obtain a turbid solution with a pH of 3. This mixture was then diluted with saturated aqueous NaCl solution (200 mL) and extracted with EtOAc (200 mL ⁇ 2).
  • the crude reaction mixture was diluted with CH 2 Cl 2 (50 mL) and washed with water (50 mL), saturated aqueous NaHCO 3 (50 mL), and water (50 mL). The organic solution was dried over MgSO 4 , filtered, and concentrated under reduced pressure.
  • 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% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Septoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse for disease to develop.
  • Leaf Spot of Sugar Beets ( Cercospora beticola ; Bayer Code CERCBE):
  • Sugar beets (variety HH-88) were grown in soil-less Metro mix in a greenhouse. The spores were harvested from moisturized infected leaf surface by washing whole leaves in water, and then filtered through two layers of cheesecloth. The young seedlings were inoculated with the spore suspension. The plants were kept in a dark dew room for 48 hrs, and then placed under a plastic hood in a greenhouse with a temperature of 26° C.
  • Leaf Spot of Peanut Mycosphaerella arachidis ; Bayer Code MYCOAR; Anamorph: Cercospora arachidicola ):
  • Peanuts seedlings (variety Star) were grown in soil-less Metro mix. The spores were harvested from moisturized infected leaf surface by washing whole leaves in water, and then filtered through two layers of cheesecloth. The young seedlings were inoculated with the spore suspension. The plants were kept in a dark dew room for 48 hrs, and then placed under a plastic hood in a greenhouse with a temperature of 26° C.
  • Apple seedlings (McIntosh or Golden Delicious) were grown in Metro mix in a greenhouse. Fungal spores were collected from infected leaf tissue. Plants were inoculated with the spore suspension. Plants were placed in a dew room for 24 hours with 100% relative humidity and then transferred to a greenhouse with a temperature of 18° C. for disease to develop.
  • Efficacy against Mycosphaerella fijiensis was tested using newly emerged leaves of field grown banana plants. 20 ml of a diluted formulation of compound 1 of the required concentration were sprayed onto each test leaf over a delineated area of 20 ⁇ 20 cm. The leaves were subsequently allowed to become infected by natural inoculum, and were visually assessed for percent disease control ⁇ 40-45 days later.
  • Leaf Blotch of Wheat Mycosphaerella graminicola ; Anamorph: Septoria tritici ; Bayer Code SEPTTR
  • Seeds of wheat variety Yuma were treated with 10% SC formulation of compound 15 (Table 1) at rates of 120, 40, 13.3, 4.44, 1.48, and 0 g ai/100 kg seeds. Seeds (10 seeds/pot) were planted in 1 inch pot containing 50% mineral soil/50% soil-less Metro mix. 8-day old seedlings were inoculated with an aqueous spore suspension of Septoria tritici , and 8 pots of plants were inoculated for each fungicide rate. After inoculation, plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted mist room) to allow establishment of infection. The plants were then transferred to a greenhouse for disease to develop.
  • the following tables present the activity of typical compounds of the present disclosure when evaluated in these experiments.
  • the effectiveness of the test compounds in controlling disease was determined by assessing the severity of disease on treated plants, then converting the severity to percent control based on the level of disease on untreated, inoculated plants.

Abstract

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

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application is a continuation-in-part application of U.S. patent application Ser. No. 12/357,710, filed Jan. 22, 2009, which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/011,799 filed Jan. 22, 2008, and U.S. Provisional Patent Application Ser. No. 61/115,297 filed Nov. 17, 2008.
    • FIELD OF THE INVENTION
  • This present disclosure is related to the field of 5-fluoro pyrimidines and their derivatives and to the use of these compounds as fungicides.
    • BACKGROUND AND SUMMARY OF THE INVENTION
  • Fungicides are compounds, of natural or synthetic origin, which act to protect and cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
  • The present disclosure relates to 5-fluoro pyrimidine compounds and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
  • One embodiment of the present disclosure may include compounds of Formula I:
  • Figure US20100022538A1-20100128-C00001
  • wherein R1 is —N(R3)R4;
    • R2 is —OR21; R3 is:
      • H;
      • C1-C6 alkyl optionally substituted with 1- to 3 R5;
      • C2-C6 alkenyl optionally substituted with 1-3 R5;
      • a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, each heteroaromatic ring being optionally substituted with 1-3 R30;
      • imidazole fused with an aromatic or heteroaromatic ring selected from the group consisting of benzene, oxazole, isoxazole, furan, thiazole, pyrimidine, pyridine, pyrrole, pyrazine, thiophene, each aromatic or heteroaromatic ring being optionally substituted with 1 to 3 R30;
      • benzo[1,3]dioxolyl;
      • 3H-isobenzofuran-1-onyl;
      • cyano;
      • C3-C6 alkynyl optionally substituted with 1-3 R5;
      • —C(═O)R6;
      • —C(═O)OCH2C(═O)R8;
      • —C(═S)R6;
      • —C(═S)NHR8;
      • —C(═O)N(R8)R10;
      • —OR7;
      • —P(O)(OR15)2;
      • —S(O)2R8;
      • —SR8;
      • —Si(R8)3;
      • —N(R9)R10;
      • —N═C(R15)R16;
      • —(CHR22)mR37;
      • —(CHR24)OR29;
      • —C(═NR16)SR16; or
      • —C(═NR27)NR13R28;
        wherein m is an integer from 1-3;
    R4 is:
      • H;
      • hydroxyl;
      • amino;
      • C1-C6 alkyl, optionally substituted with 1-3 R5;
      • —C(═O)R6; or
      • —C(═O)N(R8)R10;
        alternatively R3 and R4 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 R11;
      • ═C(R12)N(R13)R14;
      • ═C(R13)(R25);
      • ═C(R15)OR15;
      • ═S(R34)2; or
      • ═NR35;
        R5 is independently halogen, C1-C6 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, amino, C1-C3 alkylamino, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C2-C6 alkylaminocarbonyl, —OH, N-methyl piperazine or C3-C6 trialkylsilyl;
        R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl optionally substituted with 1-3 R30, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy C2-C6 alkoxycarbonyl, C1-C4 alkoxyalkoxy, C2-C6 alkylaminocarbonyl; 1-benzo[1,2,3]thiadiazol-7-yl, thiazolyl, benzyl, phenyl, phenoxy, or benzyloxy wherein the thiazolyl, benzyl, phenyl, phenoxy, or benzyloxy may be optionally substituted with 1-3 R20, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C1-C5 haloalkyl, benzyl which may be optionally substituted with 1-5 R20, —CHR18C(O)OR19, —(CHR27)R28, —Si(R8)3, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R8 is independently C1-C6 alkyl, C1-C6 haloalkyl, amino, C1-C6 alkylamino, C2-C6 dialkylamino, methylene-2-furanyl, —CHR15C(O)OR19, benzyl optionally substituted with 1-3 R30, phenyl optionally substituted with 1-3 R30, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R9 is H, C1-C6 alkyl C1-C6 haloalkyl, —C(═O)R17, benzothiazoyl, quinazolinyl, or phenyl optionally substituted with 1-3 R20, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R10 is H or C1-C6 alkyl, C1-C6 haloalkyl, or phenyl optionally substituted with 1-3 R20;
        R11 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, amino, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C6 alkoxycarbonyl, or C2-C6 alkylcarbonyl;
        R12 is H or C1-C4 alkyl;
        R13 and R14 are independently H, cyano, —OH, C1-C4 alkyl, C1-C6 alkoxy, C2-C6, alkylcarbonyl, phenyl, or benzyl wherein the phenyl or benzyl may be optionally substituted with 1-3 R20;
        alternatively R13 and R14 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 R11, or 3,4-dihydro-1H-isoquinolin-2-yl;
        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 R11;
        R15 is H or C1-C6 alkyl, C2-C6 alkenyl, 2-benzofuranyl, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R16 is H, C1-C6 alkyl, or phenyl optionally substituted with 1-3 R20;
        alternatively R15 and R16 may be taken together as —(CH2)4— or —(CH2)5
        R17 is H, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, C1-C6 alkoxy, benzyl, phenyl, phenoxy, or benzyloxy wherein each ring may be optionally substituted with 1-3 R20, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R18 is H, C1-C6 alkyl, or C1-C6 haloalkyl;
        R19 is H, C1-C6 alkyl, C1-C6 haloalkyl, or benzyl;
        R20 is independently halogen, cyano, nitro, amino, C1-C6 alkoxyalkoxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C3-C6 trialkylsilyl, 2-[(E)-methoxyimino]-N-methyl-acetamidyl, phenyl, benzyl, benzyloxy, phenoxy, or a 5- or 6-membered heteroaromatic ring wherein each phenyl, benzyl, benzyloxy, phenoxy, or 5- or 6-membered heteroaromatic ring may be optionally substituted with 1-3 substitutents independently selected from R31;
    R21 is:
      • H;
      • C1-C14 alkyl;
      • C1-C6 haloalkyl;
      • C2-C4 alkenyl;
      • C2-C4 haloalkenyl;
      • C3-C4 alkynyl;
      • C3-C4 haloalkynyl;
      • phenyl, naphthyl, or tetrahydroquinolinyl each optionally substituted with 1-3 R20;
      • —(CHR22)R23;
      • —(CHR24)mC(O)OR25;
      • —(CHR24)mC(O)R26;
      • —(CHR24)mC(O)N(R27)R28;
      • —(CHR24)mOR29;
      • —(CHR24)mSR29
      • —(CHR24)mN(R27)R28;
      • —C(═O)R32;
      • —N═C(R32)(R36);
      • —NR25C(═O)OR25
      • —Si(R8)3;
      • —SO2R33;
      • C2-C6 alkoxy carbonyl;
      • C2-C6 alkylaminocarbonyl;
      • C2-C6 alkylcarbonyl;
      • sugars selected from the group consisting of beta-D-glucose-tetraacetate, rhamnose, fructose, and pentose; or
      • a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl or isoxazolyl wherein each 5- or 6-member heteroaromatic ring may be optionally substituted with 1-5 R20;
        R22 is independently:
      • H;
      • halogen;
      • cyano;
      • nitro;
      • C1-C6 alkyl;
      • C1-C6 haloalkyl;
      • phenyl or benzyl optionally substituted with 1-3 R20;
      • C1-C6 hydroxyalkyl;
      • C2-C6 alkoxylalkyl;
      • C3-C6 haloalkynyl;
      • C2-C6 alkenyl;
      • C2-C6 haloalkenyl;
      • C3-C6 alkynyl;
      • C1-C6 alkoxy;
      • C1-C6 haloalkoxy;
      • C1-C6 alkylthio;
      • C1-C6 alkylamino;
      • C2-C8 dialkylamino;
      • C3-C6 cycloalkylamino;
      • C4-C6 (alkyl)cycloalkylamino;
      • C2-C6 alkylcarbonyl;
      • C2-C6 alkoxycarbonyl;
      • C2-C6 alkylaminocarbonyl;
      • C3-C8 dialkylaminocarbonyl;
      • C3-C6 trialkylsilyl;
      • ring-fused heteroaromatic rings selected from the group consisting of benzothiophenyl, quinolinyl, isoquinolinyl, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, and benzoimidazolyl, wherein each of the rings may be further substituted with 1-3 R20; or
      • a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl and thienyl;
    R23 is:
      • H;
      • halogen;
      • C1-C6 alkyl;
      • C1-C6 haloalkyl;
      • C2-C6 dialkylamino;
      • phenyl optionally substituted with 1-5 R20;
      • ring-fused heteroaromatic rings selected from the group consisting of benzothiophenyl, quinolinyl, isoquinolinyl, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, benzofuranyl and benzoimidazolyl, 2,3-dihydro-benzofuran-2-yl, 4-methyl-4H-thieno[3,2-b]pyrrol-5-yl, 1-methyl-1H-indol-5-yl, imidazo[1,2-a]pyridin-2-yl, imidazo[2,1-b]thiazol-6-yl, benzothiazol-2-yl, benzo[b]thiophen-7-yl, and 1-methyl-1H-indazol-3-yl, wherein each of the rings may be further substituted with 1-3 R20;
      • naphthyl;
      • benzo[1,3]dioxolyl;
      • pyrrolidinonyl;
      • oxetanyl;
      • C1-C6 alkylthio optionally substituted with 1-5 R20;
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11; or
      • a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, imidazolyl, thiophene-2-yl and thiophen-3-yl wherein each heteroaromatic ring may be optionally substituted with 1-3 R20;
        R24 is H, C1-C6 alkyl, C1-C6 alkoxy, benzyl, or phenyl wherein each of the benzyl or phenyl may be optionally substituted with 1-3 R20;
        R25 is H, C1-C6 alkyl, phenyl or benzyl optionally substituted with 1-3 R20;
    R26 is:
      • H;
      • C1-C6 alkyl;
      • C1-C6 alkoxy;
      • phenyl optionally substituted with 1-3 R20; or
      • a 5- or 6 membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl and isoxazolyl;
        R27 and R28 are independently:
      • H;
      • C1-C6 alkyl;
      • benzyl or phenyl wherein each of the benzyl or phenyl may be optionally substituted with 1-3 R20; or
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
    R29 is:
      • H;
      • C1-C6 alkyl;
      • C1-C6 haloalkyl;
      • C1-C6 alkoxyalkyl;
      • C2-C6 alkylcarbonyl;
      • benzyl, benzoyl, or phenyl wherein each of the benzyl, benzoyl or phenyl may be optionally substituted with 1-3 R20; or
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R30 is independently halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl, thiazolyl, phenyl, pyrimidinyl, or pyridyl, wherein the thiazolyl, phenyl, pyridyl, or pyrimidinyl may be optionally substituted with 1-3 R20;
        R31 is independently halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, or C3-C6 trialkylsilyl;
        R32 is independently:
      • C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl;
      • phenyl wherein the phenyl ring may be optionally substituted with 1-3 R20; or
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R33 is independently:
      • C1-C6 alkyl, C1-C6 haloalkyl, phenyl or thienyl optionally substituted with 1-3 R20; or
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
    R34 is:
      • C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkoxyalkyl, C1-C6 alkylamino; or
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
    R35 is:
      • C1-C6 alkyl, C2-C6 alkylcarbonyl; or
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
        R36 is H, cyano, C1-C6 alkyl, C1-C6 alkoxy, benzyl, or phenyl wherein each of the benzyl, or phenyl may be optionally substituted with 1-3 R20;
        alternatively R32 and R36 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 R11; and
        R37 is independently:
      • H, halogen, or phenyl optionally substituted with 1-5 R20;
      • C1-C6 alkyl, C1-C6 haloalkyl, hydroxyl, C1-C6 alkoxy, or C1-C6 haloalkoxy; or
      • a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11.
  • Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
  • Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above 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 an unbranched, branched, 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 refers to a branched or unbranched carbon chain containing one or more triple bonds including propynyl, butynyl and the like.
  • As used throughout this specification, the term ‘R’ refers to the group consisting of C2-8 alkyl, C3-8 alkenyl or C3-8 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 a sulfonyl substitution on an alkyl which is partially substituted with halogen atoms
  • The term “alkylthio” refers to an —S—R substituent.
  • 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 “trialkylsilyl” refers to —SiR3.
  • The term “cyano” refers to a —C≡N substituent.
  • The term “hydroxyl” refers to a —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 “alkoxyalkoxy” refers to —O(CH2)n—O—(CH2)n where n is an integer from 1-3
  • The term “alkoxyalkyl” refers to an alkoxy substitution on an alkyl.
  • The term “haloalkoxyalkyl” refers to an alkoxy substitution on an alkyl which may be partially substituted with halogen atoms
  • The term “hydroxyalkyl” refers to an alkyl which is substituted with a hydroxyl group.
  • The term “haloalkoxy” refers to a —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
  • The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • The term “haloalkenyl” refers to an alkenyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • The term “haloalkynyl” refers to an alkynyl which is substituted with Cl, F, I, or Br or any combination thereof.
  • The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.
  • The term “hydroxycarbonyl” refers to a —C(O)—OH substituent.
  • The term “nitro” refers to a —NO2 substituent.
  • The term “thienyl” refers to a 5-member aromatic ring with one sulfur atom.
  • Throughout the disclosure, reference to the compounds of Formula I is read as also including optical isomers and salts of Formula I, and hydrates thereof. Specifically, when Formula I contains a branched chain alkyl group, it is understood that such compounds include optical isomers and racemates thereof. Exemplary salts include: hydrochloride, hydrobromide, hydroiodide, and the like.
  • It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.
  • Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or seeds.
  • Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
    • DETAILED DESCRIPTION OF THE PRESENT DISCLOSURE
  • The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots, seeds or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrates, or emulsifiable concentrates.
  • Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.
  • The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and use as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water suspendable, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.
  • Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
  • Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 10 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.
  • Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.
  • Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present invention are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, and the methyl ether of triethylene glycol and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
  • Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 5 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.
  • The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.
  • Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines and blends of surfactants with mineral or vegetable oils. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.
  • The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I, and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.
  • The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present 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, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxide, 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, difenzoquation, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, 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, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, folpet, formaldehyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mepanipyrim, mepronil, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, mefenoxam, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl iodide, 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, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-ZO71, 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., (RS)—N-(3,5-dichlorophenyl)-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-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide, 2-methoxyethylmercury 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(tributyltin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, climbazole, copper bis(3-phenylsalicylate), copper zinc chromate, cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf, fenapanil, fenitropan, fluotrimazole, 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, N-3,5-dichlorophenyl-succinimide, N-3-nitrophenylitaconimide, natamycin, N-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, urbacid, XRD-563, and zarilamid, IK-1140, and any combinations thereof.
  • Additionally, the compounds of the present invention may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present 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, ryania and sabadilla; carbamate insecticides such as bendiocarb and carbaryl; benzofuranyl methylcarbamate insecticides such as benfuracarb, carbofuran, carbosulfan, decarbofuran and furathiocarb; dimethylcarbamate insecticides dimitan, dimetilan, 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, cyantraniliprole 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 bistrifluoron, buprofezin, chlorfluazuron, cyromazine, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluoron, teflubenzuron and triflumuron; juvenile hormone mimics such as epofenonane, fenoxycarb, hydroprene, kinoprene, methoprene, pyriproxyfen and triprene; juvenile hormones such as juvenile hormone I, juvenile hormone II and juvenile 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 flonicamid; nitroguanidine insecticides such as clothianidin, dinotefuran, 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, demeton-O-methyl, demeton-5-methyl, demeton-5-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 isoxathion and zolaprofos; pyrazolopyrimidine 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, parathion, 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, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, dimethrin, empenthrin, fenfluthrin, fenpirithrin, fenpropathrin, fenvalerate, esfenvalerate, flucythrinate, fluvalinate, tau-fluvalinate, furethrin, imiprothrin, metofluthrin, permethrin, biopermethrin, transpermethrin, phenothrin, prallethrin, profluthrin, pyresmethrin, resmethrin, bioresmethrin, cismethrin, tefluthrin, terallethrin, tetramethrin, 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 diafenthiuron; urea insecticides such as flucofuron and sulcofuron; and unclassified insecticides such as closantel, copper naphthenate, crotamiton, EXD, fenazaflor, fenoxacrim, hydramethylnon, isoprothiolane, malonoben, metaflumizone, nifluridide, plifenate, pyridaben, pyridalyl, pyrifluquinazon, rafoxanide, sulfoxaflor, triarathene and triazamate, and any combinations thereof.
  • Additionally, the compounds of the present invention may be combined with herbicides that are compatible with the compounds of the present invention in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present 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, diflufenican, etobenzanid, fenasulam, flufenacet, flufenican, mefenacet, mefluidide, metamifop, monalide, naproanilide, pentanochlor, picolinafen and propanil; arylalanine herbicides such as benzoylprop, flampropand flamprop-M; chloroacetanilide herbicides such as acetochlor, alachlor, butachlor, butenachlor, delachlor, diethatyl, dimethachlor, metazachlor, metolachlor, S-metolachlor, 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, MAMA, 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, cycloxydim, profoxydim, sethoxydim, tepraloxydim and tralkoxydim; cyclopropylisoxazole herbicides such as isoxachlortole and isoxaflutole; dicarboximide herbicides such as cinidon-ethyl, flumezin, flumiclorac, flumioxazin and flumipropyn; dinitroaniline herbicides such as benfluralin, butralin, dinitramine, ethalfluralin, fluchloralin, isopropalin, methalpropalin, nitralin, oryzalin, pendimethalin, prodiamine, profluralin and trifluralin; dinitrophenol herbicides such as dinofenate, dinoprop, dinosam, dinoseb, dinoterb, DNOC, etinofen and medinoterb; diphenyl ether herbicides such as ethoxyfen; nitrophenyl ether herbicides such as acifluorfen, aclonifen, bifenox, chlomethoxyfen, chlomitrofen, etnipromid, fluorodifen, fluoroglycofen, fluoronitrofen, fomesafen, furyloxyfen, halosafen, lactofen, nitrofen, nitrofluorfen 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, glufosinate-P, glyphosate and piperophos; phenoxy herbicides such as bromofenoxim, clomeprop, 2,4-DEB, 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, MCPA-thioethyl 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, mecopropand 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, fluoroxypyr, haloxydine, picloram, picolinafen, 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, tiocarbazil, tri-allate and vemolate; 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 atrazine, chlorazine, cyanazine, 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; triazole 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, parafluoron, phenobenzuron, siduron, tetrafluoron 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; triazinylsulfonylurea herbicides such as chlorsulfuron, cinosulfuron, ethametsulfuron, iodosulfuron, metsulfuron, prosulfuron, thifensulfuron, triasulfuron, tribenuron, triflusulfuron and tritosulfuron; thiadiazolylurea herbicides such as buthiuron, ethidimuron, tebuthiuron, thiazafluoron and thidiazuron; and unclassified herbicides such as acrolein, allyl alcohol, aminocyclopyrachlor, azafenidin, bentazone, benzobicyclon, bicyclopyrone, buthidazole, calcium cyanamide, cambendichlor, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, cinmethylin, clomazone, CPMF, cresol, cyanamide, ortho-dichlorobenzene, dimepiperate, endothal, fluoromidine, fluridone, fluorochloridone, 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 present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, seed or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidal effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.
  • The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.
  • It will be understood by those in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.
  • The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, wheat leaf blotch (Septoria tritici, also known as Mycosphaerella graminicola), apple scab (Venturia inaequalis), and Cercospora leaf spots of sugar beets (Cercospora beticola), peanuts (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 dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.
  • The compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount. The term “disease inhibiting and phytologically acceptable amount” refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m2).
  • Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.
  • The compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.
  • The following examples are presented to illustrate the various aspects of the compounds of the present disclosure and should not be construed as limitations to the claims.
    • EXAMPLES Preparation of 5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine (1)
  • Figure US20100022538A1-20100128-C00002
  • To a solution of 4-fluorobenzyl alcohol (2.56 g, 20.3 mmol) in 1,4-dioxane (20 mL) was added 60% NaH (0.813 g, 20.3 mmol) in several portions over a period of 10 min. To the magnetically stirred solution was added 4-amino-2-chloro-5-fluoropyrimidine * (2.00 g, 13.6 mmol) and the mixture was stirred at room temperature until gas evolution subsided. The reaction mixture was then heated in a CEM Discover microwave reactor at 120° C. for 90 min. The cooled reaction mixture was partitioned between ethyl acetate and water, the organic phase was concentrated, and the product was purified by column chromatography (hexane/ethyl acetate gradient) to yield 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine (1.66 g, 52% yield) as a white solid: mp 129-131° C.; 1H NMR (300 MHz, CDCl3) δ 7.91 (d, J=2.6 Hz, 1H), 7.42 (m, 2H), 7.03 (m, 2H), 5.27 (s, 2H), 5.05 (br s, 2H); MS (ESI) m/z 238 (M+H)+. *4-Amino-2-chloro-5-fluoropyrimidine can be purchased commercially or can be prepared through known literature methods.
    • 1. Hayashi, T.; Kawakami, T. JP Patent 2005126389
    • 2. Durr, G. J. J. Med. Chem. 1965, 8(2), 253.
    2-(3-Bromobenzyloxy)-5-fluoropyrimidin-4-ylamine (2)
  • Figure US20100022538A1-20100128-C00003
  • To a magnetically stirred mixture of t-BUOK (1.0 M in t-BuOH, 1.36 ml, 1.36 mmol) was added (3-bromophenyl)methanol (0.25 g, 1.36 mmol). To the resulting solution was added 4-amino-2-chloro-5-fluoropyrimidine (0.10 g, 0.68 mmol) and the mixture was capped and stirred at 90° C. for 4 h. The reaction mixture was cooled to room temperature, diluted with water, and the resulting precipitate was collected by filtration. The solid was washed with water, washed with cyclohexane, and dried in a vacuum oven. A CH2Cl2 solution of the compound was loaded onto Biotage SCX column and eluted with CH2Cl2 followed by 2.0 M NH3 in MeOH. The solvent was evaporated under reduced pressure to give the title compound (0.100 g, 49%) as an off-white solid: mp 143-145° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.90 (d, J=2.5 Hz, 1H), 7.61 (s, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.36 (d, J=7.7 Hz, 1H), 7.22 (t, J=7.7 Hz, 1H), 5.28 (s, 2H), 5.20 (br s, 2H); GCMS (EI) m/z 297, 299 (M)+.
    • Preparation of 5-Fluoro-2-[1-(4-fluorophenyl)ethoxyl]pyrimidin-4-ylamine (3)
  • Figure US20100022538A1-20100128-C00004
  • To a magnetically stirred mixture of 4-amino-2-chloro-5-fluoropyrimidine (11.10 g, 75.2 mmol) in 1-(4-fluorophenyl)ethanol (11.70 g, 82.8 mmol) was added a 1.0 M solution of t-BuOK in t-BuOH (82.8 mL, 82.8 mmol) in one portion, and the resulting tan mixture was heated to reflux and stirred for 24 h. The solvent was removed in vacuo and the resulting red-orange oil was purified by flash chromatography (SiO2, 010% MeOH/CH2Cl2) to give 5.5 g of red-orange oil. The oil was suspended in hexanes (100 mL) and stirred for 16 h. Water (100 mL) was added to the unchanged mixture, and the biphasic system was stirred vigorously for 1 h. The resulting cream colored solid was collected by vacuum filtration, washed with warm water (55° C., 2×100 mL), and dried under vacuum at 55° C. for 16 h to give 5-fluoro-2-[1-(4-fluorophenyl)ethoxy]pyrimidin-4-ylamine (3.30 g, 17.2% yield) as a white solid: mp 96-98° C.; 1H NMR (300 MHz, CDCl3) δ 7.84 (d, J=2.6 Hz, 1H), 7.42-7.38 (m, 2H), 7.03-6.97 (m, 2H), 5.99 (q, J=6.6 Hz, 1H), 5.09 (br s, 2H), 1.61 (d, J=6.6 Hz, 3H); MS (ESI) m/z 252 (M+H)+,
  • m/z 250 (M−H)−.
    • Preparation of 1-Phenyl-ethanone-O-(4-amino-5-fluoropyrimidin-2-yl)oxime (4)
  • Figure US20100022538A1-20100128-C00005
  • To a magnetically stirred mixture of 4-amino-2-chloro-5-fluoropyrimidine (0.10 g, 0.68 mmol) and acetophenone oxime (0.092 g, 0.68 mmol) in dry DMF (3 mL) in a 5 mL Biotage Iniator microwave vessel was added NaH (0.027 g of a 60 wt. % suspension, 0.68 mmol) under a N2 atmosphere. After gas evolution ceased, the resulting mixture was sealed with a Biotage Initiator microwave septa cap and heated to 100° C. in a Biotage Initiator microwave for 60 min. The contents were poured into a vial with water (5 mL) and CH2Cl2 (5 mL), and neutralized with a few drops of 2N HCl. The phases were separated and the organic extract was dried over MgSO4, filtered, and evaporated under a stream of nitrogen. The crude contents were purified on silica (EtOAc/hexanes gradient) and evaporation of the product fractions gave 0.057 g (34%) of 1-phenyl-ethanone-O-(4-amino-5-fluoro-pyrimidin-2-yl)oxime as an off-white solid: mp 163-165° C.; 1H NMR (300 MHz, CDCl3) δ 8.04 (d, J=2.6 Hz, 1H), 7.75 (m, 2H), 7.42 (m, 3H), 5.25 (bs, 2H), 2.51 (s, 3H); HPLC-MS (ESI) m/z 247 (M+H)+.
    • Preparation of 5-Fluoro-2-(thiophen-2-ylmethoxy)-pyrimidin-4-ylamine (5)
  • Figure US20100022538A1-20100128-C00006
  • To a mixture of 4-amino-2-chloro-5-fluoropyrimidine (2.00 g, 13.5 mmol) and thiophen-2-ylmethanol (1.92 g, 16.9 mmol) with a magnetic stir bar in a 20 mL Biotage Initiator microwave reaction vessel was added t-BuOK (17.0 mL of 1M in t-BuOH, 17.0 mmol). The resulting mixture was sealed with a Biotage Initiator microwave septa cap and heated in a Biotage Initiator microwave to 100° C. for 30 min. The heating cycle was repeated (2×) for a total reaction time of 90 min. The contents were poured into ice-water and the pH was adjusted to neutral with 2N HCl. The resulting solid was filtered and washed with water (2×) and then 20% ether/hexanes (100 mL). The remaining solid was dried overnight at 50° C. under vacuum to give 4.17 g (68%) of 5-fluoro-2-(thiophen-2-ylmethoxy)pyrimidin-4-ylamine as a pale yellow powder: mp 92-94° C.; 1H NMR (300 MHz, CDCl3) δ 7.92 (d, J=2.7 Hz, 1H), 7.29 (m, 1H), 7.13 (d, J=3.6 Hz, 1H), 6.97 (m, 1H), 5.46 (s, 2H), 5.17 (br s, 2H); MS (ESI) m/z 226 (M+H)+.
    • Preparation of N-[5-Fluoro-2-(thiophen-2-ylmethoxy)pyrimidin-4-yl]acetamide (6)
  • Figure US20100022538A1-20100128-C00007
  • In a 2 dram screw cap vial, a solution of 5-fluoro-2-(thiophen-2-ylmethoxy)-pyrimidin-4-ylamine (0.10 g, 0.4 mmol) in CH2Cl2 was treated with acetyl chloride (0.032 g, 0.4 mmol,) and PS-NMM (0.42 g, 0.8 mmol), a resin-bound equivalent of N-methyl morpholine (NMM). The mixture was shaken at RT for 12 h. The reaction mixture was filtered and the solvent evaporated to yield 0.084 g (75%) of the title compound as white solid: mp 134-136° C.; 1H NMR (300 MHz, CDCl3) δ 8.24 (d, J=2.6 Hz, 1H), 7.86 (bs, 1H), 7.31 (m, 1H), 7.23 (m, 1H), 7.00 (m, 1H), 5.54 (s, 2H), 2.58 (s, 3H); MS (ESI) m/z 268 (M+H)+.
    • Preparation of [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-(4-methylpiperazin-1-ylmethyl)amine (7)
  • Figure US20100022538A1-20100128-C00008
  • To a magnetically stirred mixture of paraformaldehyde (0.24 g, 8 mmol) in CH2Cl2 (20 mL) was added N-methylpiperazine (0.80 g, 8.0 mmol). The suspension was stirred overnight at ambient temperature on an orbital shaker, and then 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.47 g, 2.0 mmol) was added. The resulting mixture was stirred over the weekend at RT. The solvent was evaporated and the crude residue was washed twice with 50% ether/petroleum ether and dried under a stream of N2 to give 0.21 g (30%) of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl](4-methylpiperazin-1-ylmethyl)amine as a beige solid: mp 125-126° C.; 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J=2.3 Hz, 1H), 7.43 (m, 2H), 7.03 (t, J=8.5 Hz, 2H), 5.40 (bs, 1H), 5.27 (s, 2H), 4.41 (d, J=6.8 Hz, 2H), 2.63 (bs, 4H), 2.47 (bs, 4H), 2.30 (s, 3H); HPLC-MS (ESI) m/z 350 (M+H)+.
    • Preparation of [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]triethylsilanylamine (8)
  • Figure US20100022538A1-20100128-C00009
  • To a magnetically stirred mixture of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.25 g, 1.05 mmol) in dry THF (5 mL) at 0° C. was added NaH (0.042 g of 60 wt. % suspension in mineral oil, 1.05 mmol). When bubbling ceased, triethylsilyl chloride (0.158 g, 1.05 mmol) was added dropwise (neat) via syringe. After stirring overnight at ambient temperature, the reaction mixture was poured into ether and washed with a mixture of aqueous saturated sodium bicarbonate and brine solution. The organic layer was separated, dried over Na2SO4, filtered, and evaporated to give a white solid. This crude material was purified on silica by column chromatography (EtOAc/hexanes gradient) to give 0.121 g (33%) of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-triethylsilanylamine as a clear yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.89 (d, J=2.5 Hz, 1H), 7.39 (m, 2H), 7.03 (t, J=8.6 Hz, 2H), 5.27 (s, 2H), 4.53 (s, 1H), 0.99 (m, 9H), 0.83 (m, 6H); HPLC-MS (ESI) m/z 352 (M+H)+.
    • Preparation of [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]bis-carbamic acid 4-fluorophenyl ester (9)
  • Figure US20100022538A1-20100128-C00010
  • To a magnetically stirred ice-cold mixture of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.25 g, 1.05 mmol) in dry THF (5 mL) was added NaH (0.042 g of a 60 wt. % suspension in mineral oil, 1.05 mmol). After bubbling ceased, 4-fluorophenyl chloroformate (0.184 g, 1.05 mmol) was added dropwise as a solution in dry THF. After stirring one hour, the reaction was partitioned between EtOAc and brine solution. The organic extract was dried over Na2SO4, filtered, and evaporated. The crude material was purified on silica using a gradient of EtOAc/Hex and then MeOH/EtOAc to give 0.054 g (14%) of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]bis-carbamic acid 4-fluoro-phenyl ester as a white solid: mp 103-105° C.; 1H NMR (300 MHz, CDCl3) δ 8.58 (d, J=2.2 Hz, 1H), 7.43 (m, 2H), 7.08 (m, 10H), 5.40 (s, 2H); HPLC-MS (ESI) m/z 514 (M+H)+.
    • Preparation of [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]carbamic acid phenyl ester (10)
  • Figure US20100022538A1-20100128-C00011
  • To a stirred mixture of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.20 g, 0.84 mmol) in dry THF (3 mL) at ice-bath temperature was added NaH (0.034 g of 60 wt. % suspension in mineral oil, 0.84 mmol). When bubbling ceased, the resulting mixture was transferred (dropwise) via cannula to an ice-cold, stirred mixture of diphenyl carbonate (1.8 g, 8.4 mmol) in dry THF (5 mL). The mixture was stirred overnight, poured into EtOAc, and washed with saturated aq. NH4Cl solution followed by brine solution. The EtOAc layer was separated, dried over Na2SO4, filtered, and evaporated. The crude material was purified on silica gel using a gradient of EtOAc and hexanes to give 0.063 g (21%) of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]carbamic acid phenyl ester as a white solid: mp 129-131° C.; 1H NMR (300 MHz, CDCl3) δ 8.28 (d, J=2.3 Hz, 1H), 7.43 (m, 5H), 7.30-7.20 (m, 2H), 7.02 (t, J=8.6 Hz, 2H), 5.38 (s, 2H); HPLC-MS (ESI) m/z 358 (M+H)+.
    • Preparation of N-[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]oxalamic acid ethyl ester (11)
  • Figure US20100022538A1-20100128-C00012
  • To a mixture of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.235 g, 0.99 mmol), N-methyl morpholine on polystyrene (0.538 g, 1.24 mmol), and CH2Cl2 (5 mL) was added chloro-oxo-acetic acid ethyl ester (0.135 g, 0.99 mmol) and the resulting mixture was agitated on an orbital shaker for 16 h. The reaction contents were filtered onto an acidic SPE cartridge and eluted with CH2Cl2. The CH2Cl2 filtrate was evaporated to give 0.165 g (50%) of N-[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]oxalamic acid ethyl ester as a clear oil: 1H NMR (300 MHz, CDCl3) δ 9.21 (bs, 1H), 8.38 (d, J=2.3 Hz, 1H), 7.48 (m, 2H), 7.03 (t, J=8.5 Hz, 2H), 5.40 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 1.45 (t, J=7.1 Hz, 3H); HPLC-MS (ESI) m/z 338 (M+H)+.
    • Preparation of 3,4-Dichloroisothiazole-5-carboxylic acid [5-fluoro-2-(4-fluorobenzyl-oxy)pyrimidin-4-yl]amide (12)
  • Figure US20100022538A1-20100128-C00013
  • To a suspension of 3,4-dichloroisothiazole-5-carboxylic acid (0.15 g, 0.76 mmol) in oxalyl chloride (2 mL) was added a catalytic amount of dimethylformamide (2 drops) and the mixture was heated to 80° C. and stirred for 2 h. The excess oxalyl chloride was removed on the rotary evaporator. Meanwhile, 5-fluoro-2-(4-fluorobenzyloxy)-pyrimidin-4-ylamine (0.17 g, 0.68 mmol) was dissolved in THF (1 mL), treated with LiHMDS (1M in THF, 0.76 mL, 0.76 mmol) and stirred for 10 min. The freshly prepared 3,4-dichlorothiazole-5-carbonyl chloride*, dissolved in THF (1 mL), was added and the reaction was capped and stirred for 12 h. The reaction was diluted with water and the target compound was extracted with CH2Cl2 (3×5 mL). The combined extracts were dried over MgSO4 and then evaporated under reduced pressure. The mixture was eluted with CH2Cl2 through an anionic-exchange solid phase extraction column and then further purified by reverse-phase chromatography to give 3,4-dichloroisothiazole-5-carboxylic acid [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]amide (0.035 g, 12%) as a tan solid: mp 87-90° C.; 1H NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 8.67 (s, 1H), 7.51-7.48 (m, 2H), 7.24-7.19 (m, 2H), 5.25 (s, 2H); MS (ESI) m/z 417 (M+H)+, 415 (M−H)−. *Nagata, T.; Kogure, A.; Yonekura, N.; Hanai, R.; Kaneko, I.; Nakano, Y. JP 2007211002 A
    • Preparation of [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]phosphoramidic acid diethyl ester (13)
  • Figure US20100022538A1-20100128-C00014
  • To a magnetically stirred solution of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.10 g, 0.42 mmol) in dry THF (5 mL) under a nitrogen atmosphere was added NaH (0.017 g of a 60 wt. % suspension, 0.42 mmol) and the mixture was stirred until bubbling ceased. Diethyl chlorophosphate (0.073 g, 0.42 mmol) was added dropwise, and the mixture was stirred at ambient temperature for 1 h. The reaction mixture was evaporated to dryness and the residue dissolved in EtOAc and washed with saturated aqueous NH4Cl solution. The organic layer was separated, dried over Na2SO4, filtered, and evaporated. The crude material was purified on silica (acetone/CH2Cl2 gradient) to give 0.017 g (11%) of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]phosphoramidic acid diethyl ester as a white solid: mp 109-111° C.; 1H NMR (300 MHz, CDCl3) δ8.10 (t, J=1.8 Hz, 1H), 7.43 (m, 2H), 7.03 (t, J=8.5 Hz, 2H), 6.18 (br s, 1H), 5.35 (s, 2H), 4.25 (m, 4H), 1.38 (t, J=7.1 Hz, 6H); HPLC-MS (ESI) m/z 374 (M+H)+.
    • Preparation of [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl] (1-methoxypropyl)amine (14)
  • Figure US20100022538A1-20100128-C00015
  • To a solution of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.10 g, 0.42 mmol) in propionaldehyde (2 mL) was added a catalytic amount of camphorsulfonic acid. The mixture was agitated on an orbital shaker at room temperature for 4 h and then evaporated to dryness. Methanol (2 mL) was added, and the resulting solution was warmed to 60° C. for 1 h. After evaporation, the crude product was purified by reverse phase chromatography to yield the title compound (0.030 g, 24% yield) as a clear, colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.91 (d, J=2.5 Hz, 1H), 7.47-7.41 (m, 2H), 7.09-7.01 (m, 2H), 5.41 (dt, J=9.9 and 6.0 Hz, 1H), 5.30 (s, 2H), 5.2 (bd, J ˜10 Hz, 1H), 3.12 (s, 3H), 1.88-1.60 (m, 2H), 0.98 (t, J=7.1 Hz, 3H). HPLC-MS 308 (ES−), 310 (ES+).
    • Preparation of [5-Fluoro-2-(4-methylbenzyloxy)pyrimidin-4-ylamino]methanol (16)
  • Figure US20100022538A1-20100128-C00016
  • To a solution of 5-fluoro-2-(4-methylbenzyloxy)pyrimidin-4-ylamine (0.10 g, 0.43 mmol) in dioxane (2 mL) was added paraformaldehyde (0.060 g, 2 mmol) and the mixture was agitated on an orbital shaker at 90° C. for 16 h, cooled, and evaporated to dryness. Purification by reverse phase chromatography afforded 0.070 g (63%) of the title compound as a white solid: mp 97-98° C.; 1H NMR (CDCl3) δ 7.94 (d, J=2.5 Hz, 1H), 7.36 (d, J=7.9 Hz, 2H), 7.19 (d, J=7.9 Hz, 2H), 5.97 (bs, 1H), 5.33 (s, 2H), 5.04-4.99 (m, 2H), 3.39 (t, J=8.0 Hz, 1H), 2.37 (s, 3H); MS (ESI) m/z 264 (M+H)+.
    • Preparation of Benzyloxymethyl[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]amine (18)
  • Figure US20100022538A1-20100128-C00017
  • To a mixture of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamino]methanol (0.10 g, 3.7 mmol) in benzyl alcohol (1 mL) was added a catalytic amount of p-toluene sulfonic acid. After 30 min, the reaction was cooled to room temperature and partitioned between ethyl acetate and saturated sodium bicarbonate. The phases were separated and the organic portion was dried over anhydrous Na2SO4, filtered and evaporated to obtain the crude product. Purification by reverse phase chromatography afforded 0.094 g (70%) of the title compound as a white solid: mp 64-66° C.; 1H NMR (CDCl3) δ 7.93 (d, J=2.7 Hz, 1H), 7.47-7.40 (m, 2H), 7.37-7.29 (m, 5H), 7.08-7.00 (m, 2H), 5.81-5.70 (bm, 1H), 5.29 (s, 2H), 5.12 (d, J=6.9 Hz, 2H), 4.63 (s, 2H); MS (ESI) m/z 358 (M+H)+.
    • Preparation of 2,2-Dimethylpropionic acid [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamino]methyl ester (19)
  • Figure US20100022538A1-20100128-C00018
  • To a mixture of [5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamino]methanol (0.10 g, 0.37 mmol) in pyridine (2 mL) was added trimethylacetyl chloride (0.048 g, 0.40 mmol), and the mixture was agitated on an orbital shaker at 60° C. for 4 h. The reaction mixture was cooled, evaporated to dryness, and partitioned between EtOAc and water. The organic layer was dried over Na2SO4, filtered, and evaporated to yield the title compound (0.078 g, 60% yield) as a white solid: mp 134-135° C.; 1H NMR (300 MHz, CDCl3) δ 7.97 (d, J=2.5 Hz, 1H), 7.49-7.44 (m, 2H), 7.11-7.03 (m, 2H), 6.17 (bt, J=7 Hz, 1H), 6.17 (d, J=7.4 Hz, 2H), 5.33 (s, 2H), 1.20 (s, 9H); HPLC-MS m/z 352 (M+H)+.
    • Preparation of N-[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N,N dimethyl-formamidine (20)
  • Figure US20100022538A1-20100128-C00019
  • To a magnetically stirred solution of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (1.00 g, 4.2 mmol) in N,N-dimethylformamide (DMF, 20 mL) was added N,N-dimethylformamide dimethyl acetal (0.55 g, 4.6 mmol) and stirring was continued 16 h at RT. The solution was poured into 100 mL of ice water, whereupon a white precipitate was produced. The mixture was cooled at 0° C. for 1 h and then filtered to produce the title compound (1.10 g, 89%) as a white solid: mp 113-115° C.; 1H NMR (CDCl3) δ 8.65 (s, 1H), 8.04 (d, J=2.6 Hz, 1H), 7.46-7.40 (m, 2H), 7.07-6.98 (m, 2H), 5.30 (s, 2H), 3.17 (s, 3H), 3.16 (s, 3H); MS (ESI) m/z 292 (M+H)+. Anal. Calcd for C14H14F2N4O: C, 57.53; H, 4.83; N, 19.17. Found: C, 57.67; H, 4.84; N, 19.09.
    • Preparation of [5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-[1-pyrrolidin-1-yl-methylidene]amine (21)
  • Figure US20100022538A1-20100128-C00020
  • To a solution of N′-[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N,N-dimethylformamidine (0.10 g, 0.36 mmol) in toluene (2 mL) was added pyrrolidine (0.051 g, 0.72 mmol) and a catalytic amount of camphorsulfonic acid. The vented vial was placed on an orbital shaker, agitated at 90° C. for 16 h, cooled, and evaporated to dryness. Purification by reverse phase chromatography afforded the title compound (0.060 g, 53% yield) as a white solid: mp 102-103° C.; 1H NMR (300 MHz, CDCl3) δ 8.87 (s, 1H), 8.06 (d, J=2.7 Hz, 1H), 7.49-7.42 (m, 2H), 7.09-7.01 (m, 2H), 5.32 (s, 2H), 3.73-3.62 (m, 4H), 2.07-1.96 (m, 4H); HPLC-MS (ESI) m/z 319 (M+H)+.
    • Preparation of N-[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N′-hydroxy-formamidine (22)
  • Figure US20100022538A1-20100128-C00021
  • To a solution of N′-[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N,N-dimethyl-formamidine (0.10 g, 0.34 mmol) in EtOH (2 mL) was added hydroxylamine hydrochloride (0.047 g, 0.68 mmol) and the mixture was agitated on an orbital shaker for 1.5 h at 50° C. The reaction mixture was cooled and evaporated to dryness. Water was added to produce a slurry which was filtered to isolate the title compound (0.090 g, 94% yield) as a white solid: mp 169-171° C.; 1H NMR (300 MHz, CDCl3) δ 8.15 (d, J=2.2 Hz, 1H), 8.02 (bs, 2H), 7.49-7.43 (m, 2H), 7.11-7.02 (m, 3H), 5.35 (s, 2H); HPLC-MS (ESI) m/z 281 (M+H)+, 279 (M−H)−.
    • Preparation of N-[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N′-cyanoformamidine (23)
  • Figure US20100022538A1-20100128-C00022
  • Cyanamide (8.00 g, 190.0 mmol) was stirred at reflux in triethylorthoformate (60 mL) for 2 h. The reaction was cooled to room temperature and distilled to provide ethyl-N-cyanoimidate (12.5 g, bp=110-112° C./45 mm Hg).* To this imidate (1 mL) was added 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.05 g, 0.2 mmol) and the mixture was heated at 90° C. for 4 h, cooled, diluted with chloroform, filtered, and evaporated. The crude product was purified by reverse phase chromatography to furnish 0.053 g (17%) of the title compound as an off white solid: mp 148-149° C.; 1H NMR (300 MHz, CDCl3) δ 9.45 and 9.33 (bd, bs, J=10 Hz, 1H), 8.33 and 8.25 (2d, J≈2 Hz, 1H), 7.46-7.38 (m, 2H), 7.11-7.01 (m, 2H), 5.35 and 5.33 (2s, 2H); HPLC-MS (ESI) m/z 290 (M+H)+, 288 (M−H)−. *Bridsen, Peter K., and Wang, Xiaodong, Synthesis, 1995, 855-8.
    • Preparation of N′-[5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]-N,N-dimethyl-propionamidine (24)
  • Figure US20100022538A1-20100128-C00023
  • To a solution of N,N-dimethylpropionamide (0.202 g, 2.0 mmol) in CHCl3 (2 mL) was added phosphorous oxychloride (POCl3, 0.066 g, 0.43 mmol) and the mixture was agitated on an orbital shaker at room temperature for 1 h. Triethylamine (0.22 g, 2.2 mmol) and 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.10 g, 0.40 mmol) were added, and the mixture was agitated at 50° C. for 3 h, cooled to room temperature, partitioned between chloroform and water, the phases separated, and the organics evaporated under reduced pressure. Purification by reverse phase chromatography afforded the title compound (0.042 g, 31% yield) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 8.87 (s, 1H), 8.04 (d, J=2.5 Hz, 1H), 7.46-7.40 (m, 2H), 7.07-6.99 (m, 2H), 5.30 (s, 2H), 3.13 (s, 6H), 2.55 (q, J=7.7 Hz, 2H), 1.15 (t, J=7.7 Hz, 3H); HPLC-MS (ESI) m/z 321 (M+H)+.
    • Preparation of N′-(5-Fluoro-2-hydroxy-pyrimidin-4-yl)-N,N-dimethyl-formamidine (25)
  • Figure US20100022538A1-20100128-C00024
  • To a magnetically stirred solution of 4-amino-5-fluoro-pyrimidin-2-ol* (4.00 g, 31.0 mmol) in DMF (100 mL) was added N,N-dimethylformamide dimethyl acetal (4.00 g, 34.0 mmol). The mixture was stirred at room temperature for 72 h, diluted with diethyl ether (200 mL), and filtered. The solid product was washed with heptane to give the title compound (5.23 g, 92% yield) as a white solid: mp 240-243° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.7 (bs, 1H), 8.59 (s, 1H), 7.7 (d, J=5.6 Hz, 1H), 3.18 (s, 3H), 3.06 (s, 3H); HPLC-MS (ESI) m/z 185 (M+H)+, 183 (M−H)−. *4-amino-5-fluoro-pyrimidin-2-ol can be purchased commercially.
    • Preparation of Carbonic acid 4-(dimethylamino-methyleneamino)-5-fluoropyrimidin-2-yl ester ethyl ester (26)
  • Figure US20100022538A1-20100128-C00025
  • To a solution of N′-(5-fluoro-2-hydroxy-pyrimidin-4-yl)-N,N-dimethylformamidine (0.10, 0.54 mmol) in CH2Cl2 (2 mL) were added triethylamine (0.20 g, 2.0 mmol) and ethyl chloroformate (0.065 g, 0.60 mmol), and the mixture was agitated on an orbital shaker at room temperature overnight. The reaction was diluted with CH2Cl2 and the solution was washed with water, dried over MgSO4, filtered and evaporated. The crude product was purified by silica gel column chromatography (EtOAc/petroleum ether gradient) to yield 0.031 g (22%) of the title compound as a white solid: mp 124-126° C.; 1H NMR (300 MHz, CDCl3) δ 8.67 (s, 1H), 8.19 (d, J=2.2 Hz, 1H), 4.35 (q, J=7.14 Hz, 2H), 3.21 (s, 6H), 1.40 (t, J=7.14 Hz, 3H); HPLC-MS (ESI) m/z 258 (M+H)+.
    • Preparation of Benzoic acid 4-(dimethylamino-methyleneamino)-5-fluoropyrimidin-2-yl ester (27)
  • Figure US20100022538A1-20100128-C00026
  • To a suspension of N′-(5-fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (0.10 g, 0.54 mmol) in pyridine (2 mL) was added benzoyl chloride (0.084 g, 0.60 mmol), and the mixture was agitated on an orbital shaker for 16 h at RT. The reaction mixture was partitioned between EtOAc and saturated aq NaHCO3, and the organic phase was dried over solid MgSO4, filtered, and evaporated to give the title compound (0.147 g 94%) as a white solid: mp 136-138° C.; 1H NMR (300 MHz, CDCl3) δ 8.69 (s, 1H), 8.27 (d, J=2.4 Hz, 2H), 8.25-8.20 (m, 2H), 7.69-7.63 (m, 1H), 7.56-7.49 (m, 2H), 3.23 (s, 3H), 3.20 (s, 3H); HPLC-MS (ESI) m/z 289 (M+H)+.
    • Preparation of Benzenesulfonic acid 4-(dimethylamino-methyleneamino)-5-fluoro-pyrimidin-2-yl ester (28)
  • Figure US20100022538A1-20100128-C00027
  • To a suspension of N′-(5-fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (0.10 g, 0.54 mmol) in pyridine (2 mL) was added benzene sulfonyl chloride (0.106 g, 0.60 mmol) and the mixture was agitated on an orbital shaker for 16 h at room temperature. The reaction mixture was partitioned between EtOAc and saturated aq NaHCO3, and the organic phase was dried over solid MgSO4, filtered, and concentrated under reduced pressure. Purification by reverse phase chromatography (H2O/MeCN gradient) afforded the title compound (0.089 g, 46% yield) as a white solid: mp 124-125° C.; 1H NMR (300 MHz, CDCl3) δ 8.54 (s, 1H), 8.12-8.07 (m, 3H), 7.73-7.66 (m, 1H), 7.62-7.56 (m, 2H), 3.21 (s, 6H); HPLC-MS (ESI) m/z 325 (M+H)+.
    • Preparation of Benzenesulfonic acid 4-amino-5-fluoropyrimidin-2-yl ester (29)
  • Figure US20100022538A1-20100128-C00028
  • To a solution of 10% 1N HCl in dioxane (3 mL) was added benzenesulfonic acid 4-(dimethylamino-methyleneamino)-5-fluoropyrimidin-2-yl ester (0.090, 0.3 mmol) and the mixture was agitated on an orbital shaker at room temperature for 1.5 h. The solvent was removed by evaporation and the residue was dissolved in a 1:1 solution of dioxane and water (2.5 mL) and treated with saturated aq NaHCO3 (0.5 mL). After 16 h, the reaction mixture was partitioned between EtOAc and water and the organic phase was dried over Na2SO4, filtered, and the solvent evaporated to yield the title compound (0.059 g, 79% yield) as a white solid: mp 139-141° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.05-8.00 (m, 3H), 7.90-7.75 (m, 3H), 7.70-7.63 (m, 2H); HPLC-MS (ESI) m/z 268 (M−H)−, 270 (M+H)+.
    • Preparation of Benzenesulfonic acid 4-amino-5-fluoropyrimidin-2-yl ester (29)
  • Figure US20100022538A1-20100128-C00029
  • To a suspension of 4-amino-5-fluoro-pyrimidin-2-ol (0.177 g, 1.4 mmol) in pyridine (5 mL) was added benzene sulfonyl chloride (0.284 g, 1.6 mmol) and the mixture was stirred at room temperature for 2 h. The reaction mixture was evaporated to dryness and the crude material purified by reverse phase chromatography to yield the title compound (0.106 g, 29% yield) as a white solid: mp 145-146° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.05-8.00 (m, 3H), 7.9-7.75 (m, 3H), 7.70-7.63 (m, 2H); HPLC-MS (ESI) m/z 270 (M+H)+, 268 (M−H)−.
    • Preparation of (2-Fluorobenzyl)-[5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl]amine (30)
  • Figure US20100022538A1-20100128-C00030
  • A) A magnetically stirred solution of 2,4-dichloro-5-fluoropyrimidine* (0.105 g, 0.63 mmol) in 5 mL of dry THF was treated with 2-fluorobenzylamine (0.085 g, 0.68 mmol) and excess triethylamine, and the resulting mixture was heated at 80° C. for 5 h. The reaction mixture was partitioned between CH2Cl2 and dilute HCl, and the organic phase was washed with brine, dried over Na2SO4, and filtered. The solvent was removed under reduced pressure to yield 0.157 g (97%) of the title compound as a yellow solid: mp 117-118° C.; 1H NMR (300 MHz, CDCl3) δ 7.90 (d, J=2.6, 1H), 7.47-7.27 (m, 2H), 7.21-7.01 (m, 2H), 5.54 (s, 1H), 4.76 (d, J=5.9, 2H); MS (ESI) m/z 256 (M+H)+. *2,4-Dichloro-5-fluoropyrimidine can be purchased commercially.
  • B) A solution of (2-chloro-5-fluoropyrimidin-4-yl)-(2-fluorobenzyl)amine* (0.103 g, 0.40 mmol) in 5 mL of dry THF was treated with 4-fluorobenzylalcohol (0.062 g, 0.49 mmol) and a 1.0 M solution of KOtBu in tBuOH (0.4 mL, 0.4 mmol). The mixture was heated at 80° C. in a sealed vial for 18 h, partitioned between CH2Cl2 and water, and the organic phase was washed with brine, dried over Na2SO4, and filtered. The solvent was removed under reduced pressure and the residue purified by flash column chromatography (SiO2, 10→20% EtOAc/petroleum ether) to yield the title compound (0.157 g, 42%) as a white solid: mp 83-84° C.; 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J=2.8, 1H), 7.45-7.27 (m, 5H), 7.15-6.96 (m, 5H), 5.37 (br s, 1H), 5.29 (s, 3H), 4.74 (d, J=5.9, 3H); MS (ESI) m/z 346 (M+H)+*Singh, R.; Argade, A.; Payan, D. G.; Clough, J.; Keim, H.; Sylvain, C.; Li, H.; Bhamidipati, S., WO 2004014382 A1 20040219
    • Preparation of 5-Fluoro-2-(3-methoxybenzyloxy)-4-(1-(4-methoxyphenyl)-hydrazinyl)pyrimidine (31)
  • Figure US20100022538A1-20100128-C00031
  • A) A 1.0 M solution of t-BuOK in t-BuOH (66 mL, 66 mmol) was added to a mixture of 2,4-dichloro-5-fluoropyrimidine (5.04 g, 30.1 mmol) and 3-methoxybenzyl alcohol (7.8 mL, 62.8 mmol) in a 250 mL round bottom flask. A significant exotherm was observed and the resulting mixture was stirred at room temperature for 2 h. The reaction was diluted with EtOAc (100 mL) and washed with brine (50 mL×2). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Crystallization from hot EtOH provided a material which was collected on a fritted funnel and rinsed with ice-cold EtOH to provide the title compound (7.94 g, 71%) as a white solid: mp 81-83° C.; 1H NMR (300 MHz, CDCl3) δ 8.10 (d, J=2.3 Hz, 1H), 7.29 (m, 2H), 7.02 (m, 4H), 6.87 (dt, J=2.2, 7.8 Hz, 2H), 5.44 (s, 2H), 5.35 (s, 2H), 3.82 (s, 3H), 3.82 (s, 3H); MS (ESI) m/z 371 (M+H)+.
  • B) A solution of 2.0 N KOH in water (85 mL, 170 mmol) was added to a mixture of 5-fluoro-2,4-bis(3-methoxybenzyloxy)pyrimidine (7.9 g, 21.3 mmol) and EtOH (21 mL) in a 500 mL round bottom flask. A reflux condenser was attached, and the reaction was heated at 95° C. for 16 h. After cooling to room temperature, the reaction mixture was washed with Et2O (2×50 mL), and then acidified with 1 N HCl to pH 3. The resulting solid material was collected on a fritted funnel. Subsequent extraction with excess EtOAC, and concentration under reduced pressure provided the title compound (3.63 g, 68%) as a white solid: mp 136-139; 1H NMR (300 MHz, DMSO-d6) δ 12.97 (br s, 1H), 7.87 (d, J=3.7 Hz, 1H), 7.30 (t, J=7.9 Hz, 1H), 7.00 (m, 2H), 6.91 (dd, J=1.8, 8.0 Hz, 1H), 5.29 (s, 2H), 3.74 (s, 3H); MS (ESI) m/z 251 (M+H)+.
  • C) An oven-dried 100 mL Schlenk flask was charged with 5-fluoro-2-(3-methoxybenzyloxy)pyrimidin-4-ol (3.63 g, 14.5 mmol) and N,N-dimethylaniline (3.7 mL, 29.2 mL). Phosphorous oxychloride (POCl3, 40 mL, 429 mmol) was added, and resulting solution was heated to 95° C. under nitrogen. After 2 h, the reaction was cooled to room temperature and concentrated to constant volume under reduced pressure at 50° C. The remaining residue was diluted with Et2O (50 mL) and washed with 1 N HCl (2×50 mL). Concentration at reduced pressure provided a solid, which was washed with water and collected by vacuum filtration. The title compound (4.09 g, 105%) was isolated as a white solid: mp 96-100° C.; 1H NMR (300 MHz, DMSO-d6) δ8.81 (d, J=0.8 Hz, 1H), 7.30 (t, J=8.1 Hz, 1H), 7.02 (m, 2H), 6.91 (dd, J=2.3, 8.3 Hz, 1H), 5.34 (s, 2H), 3.75 (s, 3H); MS (ESI) m/z 269 (M+H)+.
  • D) To a mixture of 4-chloro-2-(3-methoxybenzyl)-5-fluoropyrimidine (0.153 g, 0.568 mmol) and 4-methoxyphenyl-hydrazine hydrochloride (0.324 g, 1.85 mmol) in ethanol (5 mL) was added triethylamine (0.272, 2.69 mmol) and the mixture was heated to 50° C. for 16 h. The reaction was cooled to room temperature and diluted with Et2O (50 mL). The Et2O solution was washed with water (2×50 mL), dried over MgSO4, filtered, and concentrated. The residue was triturated with Et2O to obtain 5-fluoro-2-(3-methoxy-benzyloxy)-4-(1-(4-methoxyphenyl)hydrazinyl)pyrimidine (0.113 g, 54% yield) as a white solid: mp 121-123.5° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.02 (d, J=5.4 Hz, 1H), 7.28 (t, J=8.1 Hz, 1H), 7.22 (d, J=8.5 Hz, 2H), 6.99-6.93 (m, 2H), 6.93-6.85 (m, 3H), 5.25 (s, 2H), 3.75 (s, 3H), 3.74 (s, 3H); MS (ESI) nm/z 371 (M+H)+, 354 (M-NH2)—.
    • Preparation of O-Allyl-N-(5-fluoro-2-(3-methoxybenzyloxy)pyrimidin-4-yl)hydroxyl-amine (32)
  • Figure US20100022538A1-20100128-C00032
  • To a mixture of 4-chloro-2-(3-methoxybenzyl)-5-fluoropyrimidine (0.151 g, 0.558 mmol) and O-allyl hydroxylamine hydrochloride (0.201 g, 1.83 mmol) in 5:1 MeOH:CH3CN (5 mL) was added triethylamine (0.273 g, 2.70 mmol) and the mixture was heated at 50° C. for 18 h. The reaction was cooled to room temperature and diluted with Et2O (50 mL). The organic solution was washed with water (2×50 mL), dried over MgSO4, filtered, and concentrated. Purification by flash chromatography (SiO2, 17%-->50% EtOAc/hexane) afforded O-allyl-N-(5-fluoro-2-(3-methoxybenzyloxy)-pyrimidin-4-yl)hydroxylamine (0.113 g, 66% yield) as a colorless oil: 1H NMR (300 MHz, DMSO-d6) δ 10.94 (broad singlet, 1H), 7.94 (broad singlet, 1H), 7.28 (t, J=8.0 Hz, 1H), 6.95-7.03 (m, 2H), 6.88 (dd, J=2.5, 7.9 Hz, 1H), 5.97 (tdd, J=5.8, 10.6, 17.0 Hz, 1H), 5.32 (dd, J=1.5, 17.4 Hz, 1H), 5.24 (s, 2H), 5.22 (dd, J=1.2, 10.6 Hz, 1H), 4.39 (d, J=6.0 Hz, 2H), 3.74 (s, 3H); MS (ESI) m/z 306 (M+H)+, 304 (M−H)−.
    • Preparation of 1-[2-(3-Cyanobenzyloxy)-5-fluoropyrimidin-4-yl]-3-(2-fluorobenzyl)urea (34)
  • Figure US20100022538A1-20100128-C00033
  • To a magnetically stirred mixture of 3-(4-amino-5-fluoropyrimidin-2-yloxymethyl)-benzonitrile (0.075 g, 0.31 mmol) and 2-fluorobenzylisocyanate (0.59 mL, 0.46 mmol) in dry DMF (1.5 mL) was added LiHMDS (1.0 M in THF, 0.31 ml, 0.30 mmol). The vial was capped and the mixture stirred at room temperature for 8 h. Saturated aq. NH4Cl (3 ml) was added and the mixture was stirred for 4 h. The heterogeneous mixture was filtered, and the solid was washed with hot water, washed with E2O, and then dried under vacuum to give the title compound (0.075 g, 62%) as a white solid: mp 177-178° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.90 (t, J=5.7 Hz, 1H), 8.37 (d, J=2.8 Hz, 1H), 7.85 (br s, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.42-7.38 (m, 1H), 7.35-7.29 (m, 1H), 7.20-7.14 (m, 2H), 5.33 (s, 2H), 4.49 (d, J=5.8 Hz, 2H); HPLC-MS (ESI) m/z 396.3 (M+H)+, 394.3 (M−H)−.
    • Preparation of 1-[5-Fluoro-2-(3-methoxybenzyloxy)pyrimidin-4-yl] (3′-propylcarbamoyl)-3-propyl-urea (36)
  • Figure US20100022538A1-20100128-C00034
  • To a magnetically stirred mixture of 5-fluoro-2-(3-methoxybenzyloxy)pyrimidin-4-ylamine (0.075 g, 0.30 mmol) and propylisocyanate (0.057 mL, 0.60 mmol) in dry DMF (1.5 mL) was added LiHMDS (1.0 M in THF, 0.60 ml, 0.60 mmol). The vial was capped and the reaction was stirred at room temperature for 8 h. The solvent was evaporated under reduced pressure and the crude material was purified by reverse-phase chromatography to give the title compound (0.043 g, 10%) as a tan solid: mp 75-78° C.; 1H NMR (400 MHz, DMSO-d6) δ 12.34 (s, 1H), 8.49 (s, 1H), 7.89 (s, 1H), 7.29 (t, J=7.8 Hz, 1H), 7.05-7.01 (m, 2H), 6.90 (dd, J=6.9 Hz, J=2.5 Hz, 1H), 5.30 (s, 2H), 3.75 (s, 3H), 3.74-3.68 (m, 2H), 3.15-3.10 (m, 2H), 1.58-1.44 (m, 4H), 0.89-0.85 (m, 6H); HPLC-MS (ESI) m/z 420.4 (M+H)+, 418.4 (M−H)−.
    • Preparation of 1-[2-(3-Cyanobenzyloxy)-5-fluoropyrimidin-4-yl]-3-propylthiourea (37)
  • Figure US20100022538A1-20100128-C00035
  • To a magnetically stirred mixture of 3-(4-amino-5-fluoropyrimidin-2-yloxymethyl)-benzonitrile (0.075 g, 0.31 mmol) and propylisothiocyanate (0.047 mL, 0.46 mmol) in dry DMF (1.5 mL) was added LiHMDS (1.0 M in THF, 0.31 ml, 0.31 mmol). The vial was capped and reaction was stirred for 8 h. Saturated aq NH4Cl (3 ml) was added to the vial and the mixture was stirred for 4 h. The heterogeneous mixture was filtered and the solid was washed with hot water, washed with hexanes, and dried under vacuum to give the title compound (0.055 g, 52%) as a pale-yellow solid: mp 163-165° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.77 (s, 1H), 10.38 (s, 1H), 8.47 (d, J=2.7 Hz, 1H), 7.90 (s, 1H), 7.82 (d, J=7.5 Hz, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.62 (t, J=7.7 Hz, 1H), 5.42 (s, 2H), 3.55 (dd, J=12.4, 6.8 Hz, 2H), 1.65-1.59 (m, 2H), 0.95 (t, J=7.5 Hz, 3H): HPLC-MS (ESI) m/z 346.3 (M+H)+, 344.2 (M−H)−.
    • Preparation of N-[5-Fluoro-2-(4-methylbenzyloxy)pyrimidin-4-yl]methanesulfonamide (38)
  • Figure US20100022538A1-20100128-C00036
  • To a solution of 5-fluoro-2-(4-methylbenzyloxy)pyrimidin-4-ylamine (0.100 g, 0.43 mmol) in anhydrous THF (4 mL) was added LiHMDS (1.07 mL of 1.0M, 1.07 mmol) dropwise at room temperature, and the resulting orange solution was stirred for 20 min. Methanesulfonyl chloride (0.108 g, 0.94 mmol) was added in one portion and the turbid, light orange solution was stirred for 60 min. The reaction was quenched with brine (5 mL) and the THF phase was separated. The aq. phase was extracted w/EtOAc (5 mL), and the organics were combined, dried over Na2SO4, filtered, and concentrated to an orange gummy residue. The residue was purified by flash chromatography (SiO2, 0→100% EtOac/hexanes) to give 0.034 g (26%) of the title compound as a white solid: mp 145-148° C.; 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.33 (d, J=7.9 Hz, 2H), 7.17 (d, J=7.9 Hz, 2H), 5.35 (s, 2H), 3.37 (s, 3H), 2.35 (s, 3H); HPLC-MS (ESI) m/z 312 (M+H)+, 310 (M−H)−.
    • Preparation of N-[5-Fluoro-2-(4-fluorobenzyloxy)-pyrimidin-4-yl]-S-(2-nitrophenyl)-thiohydroxylamine (39)
  • Figure US20100022538A1-20100128-C00037
  • To a solution of 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylamine (0.05 g, 0.2 mmol) and a 1.0 M solution of t-BuOK in t-BuOH (1.0 mL, 1.0 mmol) was added nitrobenzene-sulfenyl chloride (0.044 g, 0.23 mmol) in one portion, and the resulting brown solution was stirred for 60 min. The reaction was diluted with water (2 mL) and neutralized to pH 7 with 1N HCl. The aq. phase was extracted with EtOAc (5 mL), and the organics were combined, dried over Na2SO4, filtered, and concentrated. The crude material was purified by reverse phase chromatography to yield the title compound (0.020 g, 26%) as a yellow solid: mp 184° C.; 1H NMR (300 MHz, CDCl3) δ 8.36 (d, J=7.25 Hz, 1H), 8.09 (d, J=2.3 Hz, 1H), 7.59 (m, 1H), 7.36 (m 2H), 7.29 (m, 2H), 6.88 (m, 2H), 6.23 (bs, 1H), 5.19 (s, 2H); HPLC-MS (ESI) m/z 391 (M+H)+, 389 (M−H)−.
    • Preparation of Benzenesulfonic acid 4-acetylamino-5-fluoro-pyrimidin-2-yl ester (40)
  • Figure US20100022538A1-20100128-C00038
  • N-(5-Fluoro-2-hydroxypyrimidin-4-yl)-acetamide* (200 mg, 1.17 mmol) was suspended in pyridine (5 mL) and stirred at ambient temperature. To the stirred suspension was added benzenesulfonyl chloride (226 mg, 1.29 mmol) and agitation was continued for 16 hours. The solvent was evaporated under a stream of nitrogen and the residue was suspended in dichloromethane (2-3 mL), placed directly onto a silica gel column, and eluted with ethyl acetate in petroleum ether (0-50% gradient) to isolate 180 mg, 0.58 mmol (49%) of the title compound as a white solid: mp 142-143° C.; 1H NMR (DMSO-d6) δ 10.96 (s, 1H), 8.67 (d, J=2.6 Hz, 1H), 8.12-8.06 (m, 2H), 7.86-7.79 (m, 1H), 7.73-7.65 (m, 2H), 2.98 (s, 3H); HPLC-MS (ESI) m/z 312 (M+H)+, 310 (M−H)−. *N-(5-Fluoro-2-hydroxypyrimidin-4-yl)-acetamide can be prepared through known literature methods.
    • 1. Duschinsky, R., Fells, E., Hoffer, M. U.S. Pat. No. 3,309,359
    Preparation of 2,2-Dimethylpropionic acid 4-(dimethylamino-methyleneamino)-5-fluoro-pyrimidin-2-yloxymethyl ester (41)
  • Figure US20100022538A1-20100128-C00039
  • N′-(5-Fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (100 mg, 0.54 mmol), cesium carbonate (196 mg, 0.60 mmol), and chloromethyl pivalate (90 mg, 0.6 mmol) were shaken together in DMF (3 mL) at ambient temperature for 16 hours. The reaction mixture was partitioned between ethyl acetate and water, dried over magnesium sulfate, filtered and evaporated to yield a colorless oil which was treated with diethyl ether (3-4 mL) to produce a solid. The solid was removed and the ether solution was placed onto a silica gel column and eluted with ethyl acetate in petroleum ether (0-50% gradient) to isolate 14 mg, 0.05 mmol (9%) of the title compound as a white solid: mp 86-88° C.; 1H NMR (CDCl3) δ 8.73 (s, 1H), 8.06 (d, J=2.6 Hz, 1H), 6.04 (s, 2H), 3.20 (s, 3H), 3.18 (s, 3H), 1.16 (s, 9H); HPLC-MS (ESI) m/z 299 (M+H)+.
    • Preparation of N′-(5-Fluoro-2-methoxymethoxypyrimidin-4-yl)-N,N-dimethyl-formamidine (42)
  • Figure US20100022538A1-20100128-C00040
  • N′-(5-Fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (100 mg, 0.54 mmol), cesium carbonate (196 mg, 0.60 mmol), and bromomethyl methyl ether (75 mg, 0.6 mmol) were shaken together in DMF (3 mL) at ambient temperature for 4 hours. The reaction mixture was partitioned between ethyl acetate and water, dried over magnesium sulfate, filtered and evaporated to yield a colorless oil which was placed directly onto a silica gel column and eluted with ethyl acetate in petroleum ether (0-80% gradient) to isolate 23 mg, 0.1 mmol (19%) of the title compound as a colorless oil: 1H NMR (CDCl3) δ 8.66 (s, 1H), 8.05 (d, J=2.6 Hz, 1H), 5.46 (s, 2H), 3.53 (s, 3H), 3.17 (s, 3H), 3.16 (s, 3H); HPLC-MS (ESI) m/z 229 (M+H)+.
    • Preparation of [5-Fluoro-2-(3-methoxybenzyloxy)pyrimidin-4-yl]sulfamide (43)
  • Figure US20100022538A1-20100128-C00041
  • To a magnetically stirred solution of 4-chloro-5-fluoro-2-(3-methoxybenzyloxy)pyrimidine* (1.3 g, 4.84 mmol) in dry DMF (5 mL) was added a pre-mixed suspension of 60% NaH (0.45 g, 10.65 mmol) and sulfamide (0.93 g, 9.68 mmol) in dry DMF (5 mL). The resulting off-white suspension was stirred at room temperature for 72 hrs. The orange suspension was then heated to 50° C. for 48 hours and cooled to room temperature. The reaction mixture was partitioned between ethyl acetate and brine solution. The organic extract was dried over Na2SO4, filtered, and evaporated. The crude material was purified by column chromatography on normal phase silica using a gradient of EtOAc/Hex and reverse phase using a gradient of H2O/CH3CN to yield [5-fluoro-2-(3-methoxybenzyloxy)pyrimidin-4-yl]sulfamide (115 mg, 7.2% yield) as a white solid: mp 126-130° C.; 1H NMR (300 MHz, CD3OD) δ 8.01 (d, J=3.63 Hz, 1H), 7.25 (m, 1H), 7.01 (m, 2H), 6.88 (m, 1H), 5.37 (s, 2H), 3.78 (s, 3H); MS (ESI) m/z 326.9 (M−H)−. *The 4-chloro-5-fluoro-2-(3-methoxybenzyloxy)pyrimidine intermediate was prepared as described in the synthesis of 31.
    • Preparation of 5-Fluoro-4-hydrazinyl-2-(3-methoxybenzyloxy)pyrimidine (44)
  • Figure US20100022538A1-20100128-C00042
  • A 125 mL Erlenmeyer flask was charged with 4-chloro-5-fluoro-2-(3-methoxybenzyl-oxy)pyrimidine (1.50 g, 5.58 mmol) and EtOH (50 mL). Hydrazine monohydrate (900 μL, 18.5 mmol) was added, and the resulting mixture was allowed to stir at room temperature. After 22 h, the reaction was transferred to a 500 mL Erlenmeyer flask and diluted with water (200 mL), whereupon a white solid began to precipitate from solution. After stirring for 7 h, solid product was collected in a fritted funnel and rinsed with excess water. After drying on the frit, the title compound was obtained (1.23 g, 83%) as a white solid: mp 103-106° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.92 (bs, 1H), 7.86 (d, J=3.6 Hz, 1H), 7.27 (t, J=8.1 Hz, 1H), 6.94-7.01 (m, 2H), 6.87 (dd, J=2.4, 7.9 Hz, 1H), 5.24 (s, 2H), 4.46 (bs, 2H), 3.74 (s, 3H); MS (ESI) m/z 265.2 (M+H)+, 263.2 (M−H)−.
    • Preparation of (E)-5-Fluoro-2-(3-methoxybenzyloxy)-4-(2-(thiophen-2-ylmethylene)-hydrazinyl)pyrimidine(45)
  • Figure US20100022538A1-20100128-C00043
  • A 20 mL vial was charged with 5-fluoro-4-hydrazinyl-2-(3-methoxybenzyloxy)-pyrimidine (74.7 mg, 0.283 mmol), EtOH (2 mL), thiophene-2-carbaldehyde (26 μL, 0.284 mmol) and 1 M HCl in Et2O (14 μL, 0.014 mmol) and heated at 50° C. on shaker. After 90 minutes, the reaction was cooled to room temperature concentrated on high vacuum to provide the title compound (77.8 mg, 77%) as a yellow solid: mp 136-139° C.; 1H NMR (300 MHz, DMSO-d6) δ 11.46 (bs, 1H), 8.50 (bs, 1H), 8.16 (d, J=3.6 Hz, 1H), 7.64 (d, J=5.0 Hz, 1H), 7.41 (d, J=3.4 Hz, 1H), 7.28 (t, J=8.0 Hz, 1H), 7.12 (dd, J=3.8, 4.8 Hz, 1H), 7.04 (m, 2H), 6.88 (dd, J=2.4, 8.3 Hz, 1H), 5.27 (s, 2H), 3.73 (s, 3H); MS (ESI) m/z 359.2 (M+H)+, 357.2 (M−H)−.
    • Preparation of 2-(Benzyloxy)-4-[(dimethyl-λ4-sulfanylidene)amino]-5-fluoropyrimidine (47)
  • Figure US20100022538A1-20100128-C00044
  • A 10 mL oven-dried Schlenk flask was charged with 2-(benzyloxy)-5-fluoropyrimidin-4-amine (101 mg, 0.462 mmol), CH2Cl2 (2 mL), and dimethylsulfide (75.0 μL, 1.02 mmol) and was cooled to 0° C. in an ice bath. N-Chlorosuccinimide (122 mg, 0.914 mmol) was added and the resulting mixture was allowed to stir at 0° C. for 45 minutes, and then at room temperature for 30 minutes. A solution of NaOMe in MeOH (25%, 360 μL, 1.35 mmol) was added. After 20 minutes, the reaction was quenched with water (3 mL) and allowed to stir for 1 hour. The crude reaction mixture was then diluted with CH2Cl2 and washed with water (50 mL×2), dried over anhydrous Na2SO4, filtered, and concentrated by rotary evaporation and then on high vacuum to give the title compound (120 mg, 93%) as an off white solid: mp 125-129° C.; 1H NMR (300 MHz, DMSO-d6): δ 7.70 (d, J=3.9 Hz, 1H), 7.25-7.44 (m, 5H), 5.21 (s, 2H), 2.75 (s, 6H); MS (ESI) m/z 281.1 (M+H)+.
    • *Yamamoto, Y.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 4128-4129.
    Preparation of 1-[5-Fluoro-2-(4-methylbenzyloxy)-pyrimidin-4-yl]-2,3-dipropyl-isothiourea (49)
  • Figure US20100022538A1-20100128-C00045
  • To a magnetically stirred solution of 1-[5-fluoro-2-(4-methyl-benzyloxy)-pyrimidin-4-yl]-3-propyl-thiourea (0.50 g, 1.40 mmol) in CH3CN (4 mL), was added potassium carbonate (0.20 g, 1.40 mmol) at room temperature and the mixture was stirred for 20 min. N-propylbromide (0.19 g, 1.40 mmol) was added at room temperature and the resulting mixture stirred for 15 h. The reaction mixture was diluted with H2O and extracted with CH2Cl2 (3×20 mL). The combined organic layers were dried over Na2SO4, filtered, and the solvent evaporated. The crude mixture was purified on silica (EtOAc/hexanes gradient) and evaporation of the product fractions gave 0.335 g (63%) of 1-[5-fluoro-2-(4-methyl-benzyloxy)-pyrimidin-4-yl]-2,3-dipropyl-isothiourea as a pale yellow viscous liquid: 1H NMR (300 MHz, CDCl3) δ 10.56 (bs, 1H), 8.09 (d, J=2.6 Hz, 1H), 7.31 (m, 2H), 7.24 (m, 2H), 5.28 (s, 2H), 3.28 (dd, J=13.6, 6.5 Hz, 4H), 2.36 (s, 3H), 1.62 (m, 4H), 1.0 (t, J=7.4 Hz, 4H); HPLC-MS (ESI) m/z 377 (M+H)+.
    • Preparation of O-(4-Amino-5-fluoropyrimidin-2-yl)-t-butyl N-methyl-N-hydroxycarbamate (50)
  • Figure US20100022538A1-20100128-C00046
  • In a 2 dram screw cap vial, a solution of 4-amino-2-chloro-5-fluoropyrimidine (0.1 g, 0.68 mmol) and t-butyl N-methyl-N-hydroxycarbamate * (0.11 g, 0.75 mmol) was treated with a 1.0 M solution of t-BuOK in t-BuOH (1.0 mL, 1.0 mmol) in one portion, and the resulting yellow solution was heated at 100° C. and shaken for 24 h. The reaction mixture was cooled, extracted with EtOAc (3×5 mL), and the solvent evaporated. The crude mixture was purified via reverse phase chromatography to yield 0.10 g (56.9%) of the title compound as yellow solid: mp 123-125° C.; 1H NMR (300 MHz, CDCl3) δ 7.96 (d, J=2.3 Hz, 1H), 5.26 (bs, 2H), 3.32 (s, 3H), 1.43 (s, 9H); MS (ESI) m/z 259 (M+H)+.
  • t-butyl N-methyl-N-hydroxycarbamate can be prepared through known literature methods:
      • 1. Carrasco, M. R.; Brown, R. T.; Serafimova, I. M.; Silva O. J. Org. Chem., 2003, 68 (1), 195.
    Preparation of O-ethyl 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylcarbamothioate (51)
  • Figure US20100022538A1-20100128-C00047
  • 5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-amine (300 mg, 1.26 mmol) was stirred in chloroform (25 mL) and water (12 mL). Sodium bicarbonate (870 mg, 10.12 mmol) was added followed by dropwise addition of thiophosgene (218 mg, 1.9 mmol). The reaction mixture was stirred at room temperature for 16 hours, then diluted with chloroform (20 mL) and the phases were separated. The organic extract was dried over sodium sulfate, filtered, and concentrated by rotary evaporation to ⅓ volume. To this chloroform solution of crude isothiocyanate was added abs. ethanol (10 mL) and the mixture was heated in a sealed tube for 1 h. The reaction mixture was cooled to room temperature, concentrated and purified by flash chromatography on silica, to give 45 mg (11%) of O-ethyl 5-fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-ylcarbamothioate as a pale yellow solid: mp 109-119° C.; 1H NMR (CDCl3) δ 8.30 (bs, 2H), 7.44 (m, 2H), 7.06 (m, 2H), 5.36 (s, 2H), 4.66 (q, J=6 Hz, 2H), 1.45 (t, J=6 Hz, 3H); HPLC-MS (ESI): m/z 326 (ES+).
    • Preparation of N-(5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl)ethanethioamide (53)
  • Figure US20100022538A1-20100128-C00048
  • N-(5-Fluoro-2-(4-fluorobenzyloxy)pyrimidin-4-yl)acetamide (50 mg, 0.42 mmol) was stirred in a Biotage Initiator® microwave vessel with 1,2-dichloroethane (3 mL) and Lawesson's reagent (170 mg, 0.42 mmol). The vessel was heated in a Biotage Initiator® microwave to 100° C. for 5 minutes then cooled room temperature, filtered, and diluted with CH2Cl2. The reaction mixture was then washed brine, and the layers were separated. The organic extract was dried onto silica and purified by flash chromatography. The product-containing fractions were then evaporated to dryness and purified again by reverse-phase HPLC to give 4 mg of N-(5-fluoro-2-(4-fluorobenzyl-oxy)pyrimidin-4-yl)ethanethioamide (4%) as a yellow glass: 1H NMR (CDCl3) δ 9.34 (b, 1H), 8.29 (d, J=3 Hz, 1H), 7.41 (m, 2H), 7.06 (m, 2H), 5.33 (s, 2H), 3.13 (s, 3H); HPLC-MS (ESI): m/z 294 (ES−).
    • Preparation of 1-(5-Fluoro-2-hydroxypyrimidin-4-yl)-3-(2-methoxyphenyl)urea (954)
  • Figure US20100022538A1-20100128-C00049
  • To a magnetically stirred mixture of 4-amino-2-hydroxy-5-fluoropyrimidine (150 mg, 1.16 mmol) in dry DMF (3.5 mL) was added 2-methoxyphenyl isocyanate (170 μL, 1.28 mmol) and the white suspension was allowed to stir at room temperature for 60 min. The mixture was heated to 55° C. for 3 h, and then allowed to stir at room temperature overnight. The precipitate was collected by vacuum filtration and washed with Et2O (10×3 mL) to give a solid material, which was air dried for 1 h to give 1-(5-fluoro-2-hydroxypyrimidin-4-yl)-3-(2-methoxyphenyl)urea (269 mg, 83%) as a white solid: mp 247-250° C.; 1H NMR (300 MHz, DMSO-d6) δ 12.24 (bs, 1H), 11.31 (bs, 1H), 10.16 (bs, 1H), 8.14 (d, J=7.91 Hz, 1H) 8.0 (d, J=5.6, 1H), 7.03-6.99 (m, 2H), 6.95-6.88 (m, 1H), 3.87 (s, 3H) MS (ESI) m/z 276.9 (M−H)−.
    • Preparation of N-(5-Fluoro-2-(4-methylbenzyloxy)pyrimidin-4-yl)-4-methylbenzenesulfonamide (955)
  • Figure US20100022538A1-20100128-C00050
  • To a magnetically stirred solution of 5-fluoro-2-(4-methylbenzyloxy)pyrimidin-4-amine (200 mg, 0.857 mmol) in sure seal THF (4 mL) was added 1M lithium bis(trimethylsilyl)amide (LiHMDS) solution in THF (1.28 mL, 1.28 mmol) causing a slight exotherm. After stirring for 5 min, p-toluenesulfonyl chloride (196.65 mg, 1.028 mmol) was added and after 10 min the orange solution turned light yellow and turbid. The mixture was stirred at room temperature for 4 h. The solvent was removed in vacuo and the resulting viscous gold oil was diluted in EtOAc (50 mL), poured into a separatory funnel containing EtOAc (75 mL) and washed with 1N HCl aqueous solution (4×75 mL) followed by brine solution (1×100 mL). The organic extract was dried over Na2SO4, filtered, and evaporated. To the crude oil material was added distilled water (150 mL) and the resulting mixture was vigorously stirred at room temperature over 72 h forming an off-white solid. The solid was collected by vacuum filtration and air dried for 1 hour followed by drying under vacuum for 24 hours. The white solid was then suspended in Et2O (2 mL) for 1 h, then collected by vacuum filtration washed with Et2O (1×1 mL), and air dried for 1 h to yield N-(5-fluoro-2-(4-methylbenzyloxy)pyrimidin-4-yl)-4-methylbenzenesulfonamide (150 mg, 45.2% yield) as a white solid: mp 120-122° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.28 (d, J=2.9 Hz, 1H), 7.83 (d, J=8.1 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.23 Hz, 2H), 7.16 (d, J=7.92 Hz, 2H), 5.08 (s, 2H), 2.33 (s, 3H), 2.29 (s, 3H) MS (ESI) m/z 386.3 (M−H)−.
    • Preparation of N-(5-Fluoro-2-hydroxypyrimidin-4-yl)benzenesulfonamide (956)
  • Figure US20100022538A1-20100128-C00051
  • A) To a magnetically stirred solution of 5-fluoro-2-(2-methoxybenzyloxy)pyrimidin-4-amine (500 mg, 2.01 mmol) in dry THF (10 mL) was added 1M LiHMDS solution in THF (3.21 mL, 3.21 mmol) causing a slight exotherm. After stirring for 5 min, benzenesulfonyl chloride (0.346 mL, 2.71 mmol) was added and after 10 min the orange solution turned light orange and turbid. The mixture was stirred at room temperature for 5 h. The solvent was removed in vacuo and the resulting viscous gold oil was diluted in EtOAc (10 mL), poured into a separatory funnel containing EtOAc (100 mL) and washed with 1N HCl aqueous solution (4×50 mL) and brine solution (1×50 mL). The organic extract was dried over Na2SO4, filtered, and evaporated to yield N-(5-fluoro-2-(2-methoxybenzyloxy)pyrimidin-4-yl)benzenesulfonamide (714 mg, 91% yield) as a light tan solid. MS (ESI) m/z 387.99 (M−H)−.
  • B) The solid N-(5-fluoro-2-(2-methoxybenzyloxy)pyrimidin-4-yl)benzenesulfonamide (714 mg, 1.83 mmol) was dissolved in dichloromethane (10 mL) followed by the addition of trifluoroacetic acid (1.0 mL, 13.5 mmol) and allowed to stir at room temperature for 1 h. The solvent was removed in vacuo and the resulting residue was dissolved in dichloromethane:methanol in a 10:1 ratio. The product was purified by column chromatography (dichloromethane/methanol gradient) to yield N-(5-fluoro-2-hydroxypyrimidin-4-yl)benzenesulfonamide (251 mg, 51% yield) as a white solid: mp 221-223° C.; 1H NMR (300 MHz,) δ 11.57 (bs, 1H), 11.11 (bs, 1H), 8.04 (d, J=6.1 Hz, 1H), 7.94-7.84 (m, 2H), 7.71-7.51 (m, 3H).
    • Preparation of 4-(Benzylmethylamino)-5-fluoropyrimidin-2-ol (957)
  • Figure US20100022538A1-20100128-C00052
  • A) To a suspension of 2,4-dichloro-5-fluoropyrimidine (0.30 g, 1.80 mmol) in dioxane (3.6 mL) were added N-ethyl-N-isopropylpropan-2-amine (0.23 g, 1.80 mmol) and N-methyl-1-phenylmethanamine (0.24 g, 1.98 mmol), and the resulting mixture was stirred at room temperature for 16 h. The reaction was diluted with EtOAc (15 mL) and the resulting solution was washed with H2O (2×5 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to a light yellow oil which was purified by flash chromatography (40 g SiO2, EtOAc/Hexanes gradient) to give a colorless oil which solidified upon cooling. The solid was dried under high vacuum at 23° C. for 16 h to give N-benzyl-2-chloro-5-fluoro-N-methylpyrimidin-4-amine (0.34 g, 76%) as a white solid: mp 47-49° C.; 1H NMR (300 MHz, CDCl3) δ 8.18 (d, J=6.4, 1H), 7.43-7.23 (m, 5H), 4.82 (s, 2H), 3.17 (d, J=3.3, 3H); MS (EI) m/z 251 (M)+.
  • B) To a suspension of N-benzyl-2-chloro-5-fluoro-N-methylpyrimidin-4-amine (0.075 g, 0.30 mmol) in dioxane/H2O (1:1, 2 mL total volume) was added KOH (0.17 g, 3.0 mmol) and the mixture was warmed to 100° C. and stirred for 72 h. The reaction was diluted with H2O (5 mL) and the pH was adjusted to 7 with 2 N HCl. The resulting white precipitate was collected by vacuum filtration, but the majority of the product remained in the aqueous phase. The solid and filtrate were combined and the solvent was removed by azeotropic distillation with CH3CN on the rotary evaporator. The residue was dissolved/suspended in CH2Cl2 (25 mL), adsorbed onto Celite (3.0 g) and purified by flash chromatography (24 g SiO2, MeOH/CH2Cl2 gradient) to give 4-(benzylmethylamino)-5-fluoropyrimidin-2-ol (0.016 g, 23%) as a white solid: mp 175-178° C.; 1H NMR (300 MHz, CDCl3) δ 12.72 (s, 1H), 7.42-7.14 (m, 6H), 4.88 (s, 2H), 3.20 (d, J=3.2, 3H); MS (ESI) m/z 235 (M+2)+, m/z 232 (M−H)−.
    • Preparation of 2-Benzyloxy-5-fluoro-pyrimidin-4-yl)-(3-trifluoromethyl-phenyl)-diazene (958)
  • Figure US20100022538A1-20100128-C00053
  • A) A 25 mL vial was charged with 2-(benzyloxy)-4-chloro-5-fluoropyrimidine (153 mg, 0.639 mmol), (3-(trifluoromethyl)phenyl)hydrazine (338 mg, 1.92 mmol), ethanol (8 mL), and triethylamine (140 μL, 1.00 mmol). The resulting yellow solution was heated at 50° C. on an orbital shaker for 16 h. The crude material was then diluted with Et2O (100 mL) and washed with 1.0 M aqueous NaH2PO4 (50 mL) and then water (50 mL). The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography (EtOAc/hexane gradient) to afford 2-(benzyloxy)-5-fluoro-4-(2-(3-(trifluoromethyl)phenyl)hydrazinyl)pyrimidine (186 mg, 77%) as a brown oil: 1H NMR (300 MHz, DMSO-d6) δ 9.74 (bs, 1H), 8.38 (s, 1H), 8.07 (s, 1H), 7.36 (m, 1H), 7.26 (bs, 5H), 7.01 (m, 3H), 5.14 (s, 2H); MS (ESI) m/z 379 (M+H)+, 377 (M−H)−.
  • B) A 25 mL vial was charged with 2-(benzyloxy)-5-fluoro-4-(2-(3-(trifluoromethyl)phenyl)hydrazinyl)pyrimidine (140 mg, 0.371 mmol), methanol (4.6 mL), titanium(III) chloride (12% in HCl, 5.0 μL, 0.0047 mmol), hydrogen bromide
  • (33% in acetic acid, 4.0 μL, 0.022 mmol), and 35% hydrogen peroxide (64 μL, 0.744 mmol).* The resulting dark brown, homogeneous solution was agitated on an orbital shaker for 16 h at room temperature, after which a crystalline red solid was found to have formed. This solid was collected in a fritted funnel and was rinsed with a minimal amount of methanol to afford the title compound (54.5 mg, 39%) as a crystalline red solid: mp 123-125° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.07 (s, 1H), 8.22-8.37 (m, 2H), 8.12 (d, J=7.8 Hz, 1H), 7.94 (t, J=7.8 Hz, 1H), 7.46-7.53 (m, 2H), 7.30-7.44 (m, 3H), 5.43 (s, 2H); MS (ESI) m/z 377 (M+H)+. *Drug, E.; Gozin, M. J. Am. Chem. Soc. 2007, 129, 13784-13785.
    • Preparation of 1-(2-(allyloxy)-5-fluoropyrimidin-4-yl)-3-methylbenzohydrazide (959)
  • Figure US20100022538A1-20100128-C00054
  • A) A 250 mL round bottom flask was charged with 2,4-dichloro-5-fluoropyrimidine (10.0 g, 59.9 mmol) and allyl alcohol (8.60 mL, 126 mmol). t-BuOK (1.0 M in t-BuOH, 132 mL, 132 mmol) was then added, and a significant exotherm was observed. The resulting mixture was allowed to stir at room temperature for 5 h. The crude reaction mixture was then diluted with EtOAc (300 mL) and washed with saturated aqueous NaCl solution (200 mL×2). The organic layer was dried over MgSO4, filtered, and concentrated in a 500 mL round bottom flask. The crude mixture was diluted with ethanol (60 mL) and aqueous potassium hydroxide (2.0 M, 240 mL, 480 mmol), and the resulting biphasic mixture was heated at reflux for 18 h. After cooling to room temperature, the crude material was washed with Et2O (200 mL×2) and then acidified with 2.0 M HCl (˜215 mL) to obtain a turbid solution with a pH of 3. This mixture was then diluted with saturated aqueous NaCl solution (200 mL) and extracted with EtOAc (200 mL×2). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to obtain 2-(allyloxy)-5-fluoropyrimidin-4-ol (6.47 g, 64%) as an off white solid: mp 138-141° C.; 1H NMR (300 MHz, DMSO-d6) δ 13.00 (bs, 1H), 7.84 (d, J=3.7 Hz, 1H), 5.99 (m, 1H), 5.38 (m, 1H), 5.26 (m, 1H), 4.78 (m, 2H); MS (ESI) m/z 171 (M+H)+, 169 (M−H)−.
  • B) A 250 mL round bottom flask was charged with 2-(allyloxy)-5-fluoropyrimidin-4-ol 4.96 g, 29.2 mmol), N,N-dimethylaniline (5.45 mL, 43.0 mmol), phosphorous oxychloride (3.30 mL, 35.4 mmol), and acetonitrile (60 mL). The resulting solution was heated at 80° C. for 1 h. After cooling to room temperature, the crude material was diluted with Et2O (300 mL) and was washed with 1.0 M aqueous NaH2PO4 (150 mL×2) and saturated aqueous NaCl (150 mL). The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to obtain 2-(allyloxy)-4-chloro-5-fluoropyrimidine contaminated with N,N-dimethylaniline (6.71 g, 72.5% pure, 89% calcd.) as a brown oil: 1H NMR (300 MHz, DMSO-d6) δ 8.78 (bs, 1H), 6.04 (m, 1H), 5.38 (d, J=16.8 Hz, 1H), 5.26 (d, J=10.3 Hz, 1H), 4.82 (dd, J=0.8, 5.3 Hz, 2H); MS (EI) m/z 187 (M+H)+.
  • C) A 25 mL vial was charged with 2-(allyloxy)-4-chloro-5-fluoropyrimidine (72.5% pure, 175 mg, 0.673 mmol), ethanol (4 mL), triethylamine (234 μL, 1.68 mmol), and hydrazine monohydrate (34 μL, 0.706 mmol). The resulting solution was then agitated on an orbital shaker at room temperature for 90 min. 3-Methylbenzoyl chloride (93 μL, 0.706 mmol) was then added, and the reaction was further agitated for 16 h. The crude reaction mixture was concentrated under reduced pressure, and then purified by flash column chromatography (EtOAc/hexane gradient) to afford the title compound (95.8 mg, 47%) as a pale yellow solid: mp 181-185° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.44 (bs, 1H), 9.75 (bs, 1H), 8.10 (d, J=3.5 Hz, 1H), 7.65-7.75 (m, 2H), 7.37-7.43 (m, 2H), 5.95 (m, 1H), 5.25 (m, 1H), 5.15 (m, 1H), 4.63 (m, 2H), 2.37 (s, 3H); MS (ESI) m/z 303 (M+H)+, 301 (M−H)−.
    • Preparation of (E)-5-Fluoro-4-(2-(4-methoxybenzylidene)hydrazinyl)pyrimidin-2(1H)-one (960)
  • Figure US20100022538A1-20100128-C00055
  • A 25 mL vial was charged with 4-chloro-5-fluoropyrimidin-2(1H)-one (149 mg, 1.00 mmol),* ethanol (4 mL), triethylamine (148 μL, 1.06 mmol), and hydrazine monohydrate (52 μL, 1.07 mmol). The resulting yellow solution was agitated on an orbital shaker at room temperature for 3 h. 4-Methoxybenzaldehyde (123 μL, 1.01 mmol) was added, and the reaction mixture was heated at 50° C. for 16 h. After cooling to room temperature, the crude material was concentrated under reduced pressure and purified by reverse phase flash column chromatography to afford the title compound (49.3 mg, 19%) as a yellow solid: mp 202-208° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.60 (bs, 1H), 10.14 (s, 1H), 8.35 (s, 1H), 7.97 (d, J=8.8 Hz, 2H), 7.38 (t, J=5.9 Hz, 1H), 6.97 (d, J=8.9 Hz, 2H), 3.80 (s, 3H); MS (ESI) m/z 263 (M+H)+, 261 (M−H)−. Driscoll, J. S.; Marquez, V. E.; Plowman, J.; Liu, P. S.; Kelley, J. A.; Barchi, J. J. J. Med. Chem. 1991, 34, 3280-3284. Yamashita, J.; Yamawaki, I; Ueda, S.; Yasumoto, M.; Unemi, N.; Hashimoto, S. Chem. Pharm. Bull. 1982, 30, 4258-4267.
    • Preparation of N-(2-(Benzyloxy)-5-fluoropyrimidin-4-yl)formamide (961)
  • Figure US20100022538A1-20100128-C00056
  • A 10 mL Schlenk-type flask was charged with acetic anhydride (4.0 mL, 42 mmol), formic acid (2.0 mL, 53 mmol), and CH2Cl2 (20 mL), and was cooled to 0° C. under nitrogen. N,N-Dimethylpyridin-4-amine (275 mg, 2.25 mmol) was added, and the resulting solution was allowed to stir at room temperature for 10 min. Solid 2-(benzyloxy)-5-fluoropyrimidin-4-amine (495 mg, 2.26 mmol) was added, and the reaction stirred for another 21 h at room temperature. The crude reaction mixture was diluted with CH2Cl2 (50 mL) and washed with water (50 mL), saturated aqueous NaHCO3 (50 mL), and water (50 mL). The organic solution was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was then purified by flash column chromatography (EtOAc/hexane gradient) to afford the title compound (295.8 mg, 53%) as a white solid: mp 153-157° C.; 1H NMR (300 MHz, DMSO-d6) δ 11.29 (bs, 1H), 9.34 (s, 1H), 8.48 (d, J=2.6 Hz, 1H), 7.29-7.46 (m, 5H), 5.32 (s, 2H); MS (ESI) m/z 248 (M+H)+, 246 (M−H)−.
    • Preparation of (4-amino-5-fluoropyrimidin-2-yloxy)methyl cyclopentanecarboxylate (962)
  • Figure US20100022538A1-20100128-C00057
  • A) A 25 mL vial was charged with (E)-(4-((dimethylamino)methyleneamino)-5-fluoropyrimidin-2-yloxy)methyl cyclopentanecarboxylate (50.0 mg, 0.161 mmol), 1,4-dioxane (4 mL), and 1.0 M aqueous HCl (78 μL, 0.078 mmol) and was agitated on an orbital shaker for 5 h. The reaction was monitored by ultra performance liquid chromatography (HPLC) and determined to be incomplete, therefore an additional portion of 1.0 M aqueous HCl (78 μL, 0.078 mmol) was added. After 1 h, the reaction was quenched by the addition of 1.0 M aqueous NaHCO3 (260 μL, 0.260 mmol) and concentrated under reduced pressure at 45° C. The dried residue was then extracted with EtOAc (5 mL×4), and concentrated to dryness under reduced pressure to obtain (5-fluoro-4-formamidopyrimidin-2-yloxy)methyl cyclopentanecarboxylate (43.5 mg, 95%) as a white solid: mp 76-79° C.; 1H NMR (300 MHz, DMSO-d6) δ 11.38 (bs, 1H), 9.31 (d, J=5.7 Hz, 1H), 8.52 (d, J=2.6 Hz, 1H), 5.97 (s, 2H), 2.71-2.85 (m, 1H), 1.40-1.89 (m, 8H); MS (ESI) m/z 306 (M+Na)+, 282 (M−H)−.
  • B) A 25 mL vial was charged with (5-fluoro-4-formamidopyrimidin-2-yloxy)methyl cyclopentanecarboxylate (34.0 mg, 0.120 mmol), ethanol (1 mL), and hydrazine monohydrate (23.3 μL, 0.479 mmol). The resulting clear, colorless solution was then agitated on an orbital shaker at room temperature for 45 min. The crude reaction mixture was diluted with Et2O (50 mL) and was washed with saturated aqueous NaCl solution (50 mL×2). The organic was dried over MgSO4, filtered, and concentrated under reduced pressure to give the title compound (11.2 mg, 36%) as a white solid: mp 101-104° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.97 (d, J=3.4 Hz, 1H), 7.44 (bs, 1H), 5.86 (s, 2H), 2.69-2.83 (m, 1H), 1.42-1.91 (m, 8H); MS (ESI) m/z 256 (M+H)+, 254 (M−H)−.
    • Preparation of 2-Benzyloxy-5-fluoro-pyrimidin-4-yl-cyanamide (963)
  • Figure US20100022538A1-20100128-C00058
  • To a mixture of sodium hydride (0.65 g, 0.27 mol) in dry THF (10 mL), was added 2-benzyloxy-5-fluoro-pyrimidin-4-yl amine (2.0 g, 0.009 mol) dissolved in THF (15 mL) at room temperature under nitrogen. The mixture was allowed to stir at room temperature for 30 min and then cyanogen bromide (1.45 g, 0.0136 mol) in THF (10 ml) was added to the reaction mixture and allowed stir at room temperature for 16 h. The reaction was diluted with sat. sodium bicarbonate (2×5 mL) and extracted with EtOAc (3×40 mL). The organic phase was dried over Na2SO4, and concentrated to a give a crude solid which was recrystallized by adding minimum quantity of ethyl acetate and hexane until solution became turbid. The solvent was decanted and a gummy brown solid was obtained. The gummy brown solid was rinsed with Et2O (2×10 mL) and allowed to stand in Et2O while stirring for 1 h, until a free solid formed. The resulting solid was filtered and dried to give the title compound (1.7 g, 77%) as a pale brown solid: mp 150-152 dec.; 1H NMR (300 MHz, DMSO-d6) δ 7.80 (bs, 1H), 7.43 (m, 5H), 5.20 (s, 2H); MS (EI) m/z 245 (M)+.
    • Preparation of 1-[2-(Benzyloxy)-5-fluoropyrimidin-4-yl]-3-hydroxyguanidine (964)
  • Figure US20100022538A1-20100128-C00059
  • To a solution of 2-benzyloxy-5-fluoro-pyrimidin-4-yl-cyanamide (2.9 g, 0.012 mol) in n-butanol (30 mL) in a 100 mL sealed tube was added hydroxylamine hydrochloride (4.1 g, 0.059 mol) and the solution was heated at 110° C. for 2 h. The reaction was cooled and checked by TLC and was determined to be complete. The solvent was removed in vacuo and the resulting mixture was diluted with water and extracted with EtOAc (3×30 mL). The organic layers were dried over Na2SO4, filtered, and evaporated. The crude product was purified further with reverse phase chromatography to yield the title compound (500 mg, 15% yield) as an off white solid; mp 150-152 dec.; 1H NMR (300 MHz, DMSO-d6) δ 8.72 (s, 2H), 8.44 (d, J=2.6 Hz, 1H), 7.41 (m, J=13.8, 6.3 Hz, 5H), 5.34 (s, 2H); MS (EI) m/z 278 (M)+.
    • Biological Testing Protocols:
  • 1. 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% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Septoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse for disease to develop.
  • 2. Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets (Cercospora beticola; Bayer Code CERCBE):
  • Sugar beets (variety HH-88) were grown in soil-less Metro mix in a greenhouse. The spores were harvested from moisturized infected leaf surface by washing whole leaves in water, and then filtered through two layers of cheesecloth. The young seedlings were inoculated with the spore suspension. The plants were kept in a dark dew room for 48 hrs, and then placed under a plastic hood in a greenhouse with a temperature of 26° C.
  • 3. Evaluation of Fungicidal Activity: Leaf Spot of Peanut (Mycosphaerella arachidis; Bayer Code MYCOAR; Anamorph: Cercospora arachidicola):
  • Peanuts seedlings (variety Star) were grown in soil-less Metro mix. The spores were harvested from moisturized infected leaf surface by washing whole leaves in water, and then filtered through two layers of cheesecloth. The young seedlings were inoculated with the spore suspension. The plants were kept in a dark dew room for 48 hrs, and then placed under a plastic hood in a greenhouse with a temperature of 26° C.
  • 4. Evaluation of Fungicidal Activity: Apple Scab (Venturia inaequalis; Bayer Code VENTIN):
  • Apple seedlings (McIntosh or Golden Delicious) were grown in Metro mix in a greenhouse. Fungal spores were collected from infected leaf tissue. Plants were inoculated with the spore suspension. Plants were placed in a dew room for 24 hours with 100% relative humidity and then transferred to a greenhouse with a temperature of 18° C. for disease to develop.
  • 5. Evaluation of Fungicidal Activity: Black Sigatoka Disease of Banana (Mycosphaerella fijiensis; BAYER Code MYCOFI):
  • Efficacy against Mycosphaerella fijiensis was tested using newly emerged leaves of field grown banana plants. 20 ml of a diluted formulation of compound 1 of the required concentration were sprayed onto each test leaf over a delineated area of 20×20 cm. The leaves were subsequently allowed to become infected by natural inoculum, and were visually assessed for percent disease control ˜40-45 days later.
  • 6. Evaluation of Fungicidal Activity as a Seed Treatment: Leaf Blotch of Wheat (Mycosphaerella graminicola; Anamorph: Septoria tritici; Bayer Code SEPTTR)
  • Seeds of wheat variety Yuma were treated with 10% SC formulation of compound 15 (Table 1) at rates of 120, 40, 13.3, 4.44, 1.48, and 0 g ai/100 kg seeds. Seeds (10 seeds/pot) were planted in 1 inch pot containing 50% mineral soil/50% soil-less Metro mix. 8-day old seedlings were inoculated with an aqueous spore suspension of Septoria tritici, and 8 pots of plants were inoculated for each fungicide rate. After inoculation, plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted mist room) to allow establishment of infection. The plants were then transferred to a greenhouse for disease to develop. When infection levels on untreated plants reached 95 to 100%, disease severities on treated plants were assessed. At the lowest test rate of 1.48 g ai/100 kg seeds, compound 15 (Table 1) provided nearly complete control of SEPTTR (Table V), indicating that aminopyrimidine fungicides can efficiently deliver SEPTTR efficacy via seed treatment.
  • The following tables present the activity of typical compounds of the present disclosure when evaluated in these experiments. The effectiveness of the test compounds in controlling disease was determined by assessing the severity of disease on treated plants, then converting the severity to percent control based on the level of disease on untreated, inoculated plants.
  • In each case of Tables I-V 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 I
    Three day curative (3DC) and one day protectant (1DP) Activity of Compounds on SEPTTR at 25 and 100 ppm
    SEPTTR SEPTTR SETTTR SEPTTR Mass Mass
    3DC 3DC 1DP 1DP Spec. Spec.
    Cmpd Structure 25 ppm 100 ppm 25 ppm 100 ppm Phys. App. MP (ES+) (ES−) GCMS
    1
    Figure US20100022538A1-20100128-C00060
         		A A A A white solid 130-132 238 236
    2
    Figure US20100022538A1-20100128-C00061
         		A A A A off-white powder 143-145 297, 298
    3
    Figure US20100022538A1-20100128-C00062
         		A A A A oil product 250
    4
    Figure US20100022538A1-20100128-C00063
         		A A A A off-white solid 163-165 247
    5
    Figure US20100022538A1-20100128-C00064
         		A A A A White Solid 90-92 226
    6
    Figure US20100022538A1-20100128-C00065
         		A A A A white solid 134-136 268 266
    7
    Figure US20100022538A1-20100128-C00066
         		A A A A beige solid 125-126 350 348
    8
    Figure US20100022538A1-20100128-C00067
         		A A A A clear yellow oil 352 350
    9
    Figure US20100022538A1-20100128-C00068
         		A A A A white solid 103-105 514
    10
    Figure US20100022538A1-20100128-C00069
         		A A A A white solid 129-131 358 356
    11
    Figure US20100022538A1-20100128-C00070
         		A A A A clear oil 338 336
    12
    Figure US20100022538A1-20100128-C00071
         		A A A A tan solid 87-90 417 415
    13
    Figure US20100022538A1-20100128-C00072
         		D D C B white solid 109-111 374 372
    14
    Figure US20100022538A1-20100128-C00073
         		A A A A clear colorless oil 310 308
    15
    Figure US20100022538A1-20100128-C00074
         		A A A A White Solid 135-137 234 232
    16
    Figure US20100022538A1-20100128-C00075
         		A A A A white solid 97-98 264 262
    17
    Figure US20100022538A1-20100128-C00076
         		A A A A white solid 108-110 268 266
    18
    Figure US20100022538A1-20100128-C00077
         		B B B A white solid 64-66 358 356
    19
    Figure US20100022538A1-20100128-C00078
         		B A A A white solid 134-135 352
    20
    Figure US20100022538A1-20100128-C00079
         		A A A A white powder 115-116 293
    21
    Figure US20100022538A1-20100128-C00080
         		A A A A off white solid 102-103 319
    22
    Figure US20100022538A1-20100128-C00081
         		A A A A white solid 169-171 281 279
    23
    Figure US20100022538A1-20100128-C00082
         		A A A A off white solid 148-149 290 288
    24
    Figure US20100022538A1-20100128-C00083
         		A A A A clear yellow oil 321
    25
    Figure US20100022538A1-20100128-C00084
         		A A A A tan solid 240-243 183
    26
    Figure US20100022538A1-20100128-C00085
         		A A A A white solid 124-126 258
    27
    Figure US20100022538A1-20100128-C00086
         		A A A A white crystalline solid 136-138 289
    28
    Figure US20100022538A1-20100128-C00087
         		A A A A white solid 124-125 325
    29
    Figure US20100022538A1-20100128-C00088
         		B A A A white solid 139-140 270 268
    30
    Figure US20100022538A1-20100128-C00089
         		B A B A white solid 88-90 346 344
    31
    Figure US20100022538A1-20100128-C00090
         		D D D D off white solid 121-123.5 371 354
    32
    Figure US20100022538A1-20100128-C00091
         		D A C A colorless oil 306 304
    33
    Figure US20100022538A1-20100128-C00092
         		A A A A fluffy white solid 184-186 243 245
    34
    Figure US20100022538A1-20100128-C00093
         		D D D D white solid 177-178 396 394
    35
    Figure US20100022538A1-20100128-C00094
         		A A A A yellow solid 104-106 250 248
    36
    Figure US20100022538A1-20100128-C00095
         		B A C A tan solid 75-78 420 418
    37
    Figure US20100022538A1-20100128-C00096
         		A A A A white needles 150-151 339 337
    38
    Figure US20100022538A1-20100128-C00097
         		D C C C White Solid 145-148 312 310
    39
    Figure US20100022538A1-20100128-C00098
         		D D A A yellow solid 184 391 389
    40
    Figure US20100022538A1-20100128-C00099
         		E E E E white solid 142-143 312 310
    41
    Figure US20100022538A1-20100128-C00100
         		E E E E white solid 86-88 299
    42
    Figure US20100022538A1-20100128-C00101
         		E E E E colorless oil 229
    43
    Figure US20100022538A1-20100128-C00102
         		B B C B yellow glassy solid 126-130 327
    44
    Figure US20100022538A1-20100128-C00103
         		B A D A off white solid 102-105 265 263
    45
    Figure US20100022538A1-20100128-C00104
         		C C B A yellow solid 136-139 359 357
    46
    Figure US20100022538A1-20100128-C00105
         		A A A A orange-white solid 220 218
    47
    Figure US20100022538A1-20100128-C00106
         		E E E E off white solid 125-129 281
    48
    Figure US20100022538A1-20100128-C00107
         		A A A A off-white solid 149-150 335 333
    49
    Figure US20100022538A1-20100128-C00108
         		E E E E Pale yellow viscous liquid 377
    50
    Figure US20100022538A1-20100128-C00109
         		C A C A pale yellow solid 123-125 259
    51
    Figure US20100022538A1-20100128-C00110
         		E E E E Pale yellow solid 326
    52
    Figure US20100022538A1-20100128-C00111
         		B B A A white solid 160-162 280 278
    53
    Figure US20100022538A1-20100128-C00112
         		A A A A yellow glass 294
    54
    Figure US20100022538A1-20100128-C00113
         		D D B A white solid 118-121 417 415
    55
    Figure US20100022538A1-20100128-C00114
         		A A A A white solid 124 224
    56
    Figure US20100022538A1-20100128-C00115
         		E E E E Pale yellow solid 388
    57
    Figure US20100022538A1-20100128-C00116
         		A A A A white solid 122-124 282
    58
    Figure US20100022538A1-20100128-C00117
         		A A A A white solid 170 (dec) 307
    59
    Figure US20100022538A1-20100128-C00118
         		D C D D white solid 190-191 371 369
    60
    Figure US20100022538A1-20100128-C00119
         		A A A A white solid 143 306 304
    61
    Figure US20100022538A1-20100128-C00120
         		D D A A white solid 111-113 326
    62
    Figure US20100022538A1-20100128-C00121
         		E E E E Off white solid 234
    63
    Figure US20100022538A1-20100128-C00122
         		E E E E yellow oil 325
    64
    Figure US20100022538A1-20100128-C00123
         		D C D D white solid 170-172 375 373
    65
    Figure US20100022538A1-20100128-C00124
         		C B C B brown/orange solid 60-64 383 381
    66
    Figure US20100022538A1-20100128-C00125
         		A A A A yellow solid 76-79 264 262
    67
    Figure US20100022538A1-20100128-C00126
         		E E E E Pale yellow solid 459
    68
    Figure US20100022538A1-20100128-C00127
         		D B D B WHITE SOLID 128- 130 269
    69
    Figure US20100022538A1-20100128-C00128
         		B A A A beige wax 300 298
    70
    Figure US20100022538A1-20100128-C00129
         		C A C A white solid 94-97 312
    71
    Figure US20100022538A1-20100128-C00130
         		A A A A 292 290
    72
    Figure US20100022538A1-20100128-C00131
         		A A A A beige solid 155- 156 265 263
    73
    Figure US20100022538A1-20100128-C00132
         		E E E E Gummy liquid 310
    74
    Figure US20100022538A1-20100128-C00133
         		D D B A white solid 245 243
    75
    Figure US20100022538A1-20100128-C00134
         		A A C A off-white solid 164-166 435 433
    76
    Figure US20100022538A1-20100128-C00135
         		C C C C black semi- solid 277
    77
    Figure US20100022538A1-20100128-C00136
         		C A D A colorless oil 348 346
    78
    Figure US20100022538A1-20100128-C00137
         		A A A A white solid 125-127 234
    79
    Figure US20100022538A1-20100128-C00138
         		A A A A white solid 134-135 319
    80
    Figure US20100022538A1-20100128-C00139
         		D B D D white solid  63-69* 272
    81
    Figure US20100022538A1-20100128-C00140
         		D D D D off-white solid 187-189 361 359
    82
    Figure US20100022538A1-20100128-C00141
         		D C C C orange oil 325
    83
    Figure US20100022538A1-20100128-C00142
         		A A A A clear oil 278
    84
    Figure US20100022538A1-20100128-C00143
         		E E E E Gummy liquid 262
    85
    Figure US20100022538A1-20100128-C00144
         		A A C A yellow solid 151-156 403 401
    86
    Figure US20100022538A1-20100128-C00145
         		D D C B white solid 368 366
    87
    Figure US20100022538A1-20100128-C00146
         		D A B A yellow solid 154-155 379 377
    88
    Figure US20100022538A1-20100128-C00147
         		C A C A clear colorless oil 282 280
    89
    Figure US20100022538A1-20100128-C00148
         		A A A A tan solid 129-130 331
    90
    Figure US20100022538A1-20100128-C00149
         		C B A A yellow solid 180-187 441 439
    91
    Figure US20100022538A1-20100128-C00150
         		E E E E Gummy liquid 276 [M + Na]
    92
    Figure US20100022538A1-20100128-C00151
         		E E E E Off white solid 381
    93
    Figure US20100022538A1-20100128-C00152
         		A A A A white solid 122 274 272
    94
    Figure US20100022538A1-20100128-C00153
         		A A A A off white solid 63-65 291
    95
    Figure US20100022538A1-20100128-C00154
         		A A A A yellow solid 118-120 292 —
    96
    Figure US20100022538A1-20100128-C00155
         		D D D D brown oil 334
    97
    Figure US20100022538A1-20100128-C00156
         		D D D B white solid 104-107 348 345
    98
    Figure US20100022538A1-20100128-C00157
         		D D D D white solid 168-169 389 387
    99
    Figure US20100022538A1-20100128-C00158
         		D B D A white solid 74-77 244
    100
    Figure US20100022538A1-20100128-C00159
         		D D D D white solid 163-164 254 252
    101
    Figure US20100022538A1-20100128-C00160
         		D D B B white solid 127-129 338
    102
    Figure US20100022538A1-20100128-C00161
         		D C D D dark brown solid 118-122 325
    103
    Figure US20100022538A1-20100128-C00162
         		B A A A yellow solid 90-92 312
    104
    Figure US20100022538A1-20100128-C00163
         		A A A A yellow solid 179-181 277 275
    105
    Figure US20100022538A1-20100128-C00164
         		D D D D brown solid 143-148 288 285
    106
    Figure US20100022538A1-20100128-C00165
         		D C D D yellow clear oil 240 238
    107
    Figure US20100022538A1-20100128-C00166
         		A A A A white solid 280 278
    108
    Figure US20100022538A1-20100128-C00167
         		A A A A white solid 123-124 321
    109
    Figure US20100022538A1-20100128-C00168
         		E E E E white solid 188-192 276 274
    110
    Figure US20100022538A1-20100128-C00169
         		E E E E Pale yellow solid 338
    111
    Figure US20100022538A1-20100128-C00170
         		D D D D pale yellow oil 347
    112
    Figure US20100022538A1-20100128-C00171
         		A A A A white solid 128-131 340.8 (Na+)
    113
    Figure US20100022538A1-20100128-C00172
         		D C B A pale yellow gummy solid 266
    114
    Figure US20100022538A1-20100128-C00173
         		D D D D white solid 133-135 389 307
    115
    Figure US20100022538A1-20100128-C00174
         		A A A A yellow- white wax 271
    116
    Figure US20100022538A1-20100128-C00175
         		D D D D white solid 162-164 377 375
    117
    Figure US20100022538A1-20100128-C00176
         		C C C B yellow solid 173-178 391 389
    118
    Figure US20100022538A1-20100128-C00177
         		E E E E Off white solid 338
    119
    Figure US20100022538A1-20100128-C00178
         		B A C A white powder 122-123 351 349
    120
    Figure US20100022538A1-20100128-C00179
         		A A A A off-white solid 173-174 270 268
    121
    Figure US20100022538A1-20100128-C00180
         		B A B A clear pale yellow oil 372 370
    122
    Figure US20100022538A1-20100128-C00181
         		C A D B white solid 107-108 325 323
    123
    Figure US20100022538A1-20100128-C00182
         		C A D C clear yellow oil 356 354
    124
    Figure US20100022538A1-20100128-C00183
         		E E E E Pale yellow liquid 294
    125
    Figure US20100022538A1-20100128-C00184
         		D D C C yellow solid 175-180 509 507
    126
    Figure US20100022538A1-20100128-C00185
         		A A A A brown oil 405 403
    127
    Figure US20100022538A1-20100128-C00186
         		A A A A white solid 126 284 282
    128
    Figure US20100022538A1-20100128-C00187
         		E E E E Off white solid 363
    129
    Figure US20100022538A1-20100128-C00188
         		A A C A white solid 119-120 302 300
    130
    Figure US20100022538A1-20100128-C00189
         		A A A A white solid 139-141 269
    131
    Figure US20100022538A1-20100128-C00190
         		C A C B white crystals 133-134 263
    132
    Figure US20100022538A1-20100128-C00191
         		A A A A beige solid 171-173 316 (M + Na)
    133
    Figure US20100022538A1-20100128-C00192
         		B A B A white solid 120-123 248
    134
    Figure US20100022538A1-20100128-C00193
         		B A D B 350 348
    135
    Figure US20100022538A1-20100128-C00194
         		B A A A off-white solid 144-146 391 389
    136
    Figure US20100022538A1-20100128-C00195
         		A A A A off-white solid 103-105 286 284
    137
    Figure US20100022538A1-20100128-C00196
         		C A C A white solid 55-57 214 212
    138
    Figure US20100022538A1-20100128-C00197
         		A A A A off white solid 111-116 254 252
    139
    Figure US20100022538A1-20100128-C00198
         		D C C B white solid 106 356 354
    140
    Figure US20100022538A1-20100128-C00199
         		A A A A white solid 120-125 317
    141
    Figure US20100022538A1-20100128-C00200
         		B C D A beige solid 175-176 290
    142
    Figure US20100022538A1-20100128-C00201
         		D D D D off-white solid 204-205 382 380
    143
    Figure US20100022538A1-20100128-C00202
         		E E E E Off white solid 296
    144
    Figure US20100022538A1-20100128-C00203
         		A A A A white solid 101 306 304
    145
    Figure US20100022538A1-20100128-C00204
         		A A A A clear oil 260
    146
    Figure US20100022538A1-20100128-C00205
         		A A A A white solid 295
    147
    Figure US20100022538A1-20100128-C00206
         		C C D B off white solid 146.8-149.4 297 294
    148
    Figure US20100022538A1-20100128-C00207
         		D D B B yellow solid 125-129 374 372
    149
    Figure US20100022538A1-20100128-C00208
         		D B C A yellow oil 356 354
    150
    Figure US20100022538A1-20100128-C00209
         		C A D A 322 320
    151
    Figure US20100022538A1-20100128-C00210
         		C C D D yellow oil 417 415
    152
    Figure US20100022538A1-20100128-C00211
         		C A C A white solid 157-161 341 339
    153
    Figure US20100022538A1-20100128-C00212
         		A A A A white solid 144-145 275 273
    154
    Figure US20100022538A1-20100128-C00213
         		A A A A white solid 158 335
    155
    Figure US20100022538A1-20100128-C00214
         		A A B A white solid 94-96 330
    156
    Figure US20100022538A1-20100128-C00215
         		A A A A white solid 128-130 318 316
    157
    Figure US20100022538A1-20100128-C00216
         		C C C C yellow solid 170- 175 379 377
    158
    Figure US20100022538A1-20100128-C00217
         		A A A A white solid 91-93 342 340
    159
    Figure US20100022538A1-20100128-C00218
         		C D D D off white solid 327
    160
    Figure US20100022538A1-20100128-C00219
         		A A A A clear yellow oil 333
    161
    Figure US20100022538A1-20100128-C00220
         		C A A A white solid 121.5-125   267 264
    162
    Figure US20100022538A1-20100128-C00221
         		D D C A white solid 71-73 354 352
    163
    Figure US20100022538A1-20100128-C00222
         		D D D D off-white solid 161-162 330 328
    164
    Figure US20100022538A1-20100128-C00223
         		D B C B clear oil 360
    165
    Figure US20100022538A1-20100128-C00224
         		E E E E Off white solid 397
    166
    Figure US20100022538A1-20100128-C00225
         		A A A A brown semi- solid 291
    167
    Figure US20100022538A1-20100128-C00226
         		D D D C white tacky solid 265 363
    168
    Figure US20100022538A1-20100128-C00227
         		D C D C 334
    169
    Figure US20100022538A1-20100128-C00228
         		D D B A off-white solid 154-155 393 391
    170
    Figure US20100022538A1-20100128-C00229
         		D D D D off-white solid 169-171 353 351
    171
    Figure US20100022538A1-20100128-C00230
         		A A A A off-white solid 85-87 248 246
    172
    Figure US20100022538A1-20100128-C00231
         		D D D D white solid 77-78 188 186
    173
    Figure US20100022538A1-20100128-C00232
         		D B B A white solid 141-147 322
    174
    Figure US20100022538A1-20100128-C00233
         		A A A A 322 320
    175
    Figure US20100022538A1-20100128-C00234
         		D D A A yellow solid 177-179 388
    176
    Figure US20100022538A1-20100128-C00235
         		A A B A 362
    177
    Figure US20100022538A1-20100128-C00236
         		A A A A white solid 119-120 342
    178
    Figure US20100022538A1-20100128-C00237
         		A A A A white solid 153 264 262
    179
    Figure US20100022538A1-20100128-C00238
         		A A A A white solid 155-156 276 274
    180
    Figure US20100022538A1-20100128-C00239
         		D D D B white solid 163-165 417 415
    181
    Figure US20100022538A1-20100128-C00240
         		A A A A white solid 203-205 259 257
    182
    Figure US20100022538A1-20100128-C00241
         		A A A A white solid 160-161 307 305
    183
    Figure US20100022538A1-20100128-C00242
         		D D D D white solid 175-177 378 376
    184
    Figure US20100022538A1-20100128-C00243
         		B A A A white solid 147-148 289
    185
    Figure US20100022538A1-20100128-C00244
         		A A A A pale yellow glass 268
    186
    Figure US20100022538A1-20100128-C00245
         		D D B B fluffy white solid 172-173 323 321
    187
    Figure US20100022538A1-20100128-C00246
         		D B D D light green solid 90-92 291
    188
    Figure US20100022538A1-20100128-C00247
         		A A A A white solid 92-94 234 232
    189
    Figure US20100022538A1-20100128-C00248
         		B A B A white solid 163-164 279
    190
    Figure US20100022538A1-20100128-C00249
         		D D D D white solid 74-75 312 310
    191
    Figure US20100022538A1-20100128-C00250
         		A A A A viscous yellow oil 354 352
    192
    Figure US20100022538A1-20100128-C00251
         		B A A A white solid foam
    193
    Figure US20100022538A1-20100128-C00252
         		A A A A yellow solid 120 326 324
    194
    Figure US20100022538A1-20100128-C00253
         		A A A A white solid 154 274 272
    195
    Figure US20100022538A1-20100128-C00254
         		C A B A light yellow solid 51-53 387 385
    196
    Figure US20100022538A1-20100128-C00255
         		A A A A white solid 93-95 256 254
    197
    Figure US20100022538A1-20100128-C00256
         		B A B A white solid 65-66 262 260
    198
    Figure US20100022538A1-20100128-C00257
         		E E E E Pale yellow solid 441
    199
    Figure US20100022538A1-20100128-C00258
         		B A D A 368 366
    200
    Figure US20100022538A1-20100128-C00259
         		D D D C yellow solid 181-186 421 419
    201
    Figure US20100022538A1-20100128-C00260
         		D D D D white solid 161-162 401 399
    202
    Figure US20100022538A1-20100128-C00261
         		E E E E Pale yellow solid 380
    203
    Figure US20100022538A1-20100128-C00262
         		D B D D white solid 159-161 — 303
    204
    Figure US20100022538A1-20100128-C00263
         		E E E E Pale yellow solid 368
    205
    Figure US20100022538A1-20100128-C00264
         		D B D D pale yellow oil 321 318
    206
    Figure US20100022538A1-20100128-C00265
         		E E E E Off white solid 352
    207
    Figure US20100022538A1-20100128-C00266
         		D D D C tan solid 142-147 298 296
    208
    Figure US20100022538A1-20100128-C00267
         		D C D D white solid 196-198 371 369
    209
    Figure US20100022538A1-20100128-C00268
         		A A A A white solid 84-85 275
    210
    Figure US20100022538A1-20100128-C00269
         		A A A A white solid 121-123 256 254
    211
    Figure US20100022538A1-20100128-C00270
         		A A A A off-white solid 173-174 326 324
    212
    Figure US20100022538A1-20100128-C00271
         		A A A A off-white solid 122-124 346 344
    213
    Figure US20100022538A1-20100128-C00272
         		A A A A White Solid 90-92 226
    214
    Figure US20100022538A1-20100128-C00273
         		D D D D white solid 110-113 291
    215
    Figure US20100022538A1-20100128-C00274
         		E E E E Off white solid 248
    216
    Figure US20100022538A1-20100128-C00275
         		B A A A white solid 108-112 298 296
    217
    Figure US20100022538A1-20100128-C00276
         		E E E E Pale yellow liquid 376
    218
    Figure US20100022538A1-20100128-C00277
         		E E E E Pale yellow solid 473
    219
    Figure US20100022538A1-20100128-C00278
         		D B B A off-white solid 141-143 262 260
    220
    Figure US20100022538A1-20100128-C00279
         		A A A A 372 370
    221
    Figure US20100022538A1-20100128-C00280
         		E E E E white solid 113-115 215
    222
    Figure US20100022538A1-20100128-C00281
         		E E E E Pale yellow viscous liquid 423
    223
    Figure US20100022538A1-20100128-C00282
         		A A A A white solid 132-134 236 234
    224
    Figure US20100022538A1-20100128-C00283
         		D C C A white solid 184 347 345
    225
    Figure US20100022538A1-20100128-C00284
         		E E E E 306
    226
    Figure US20100022538A1-20100128-C00285
         		A A A A white glassy solid 68-77 370
    227
    Figure US20100022538A1-20100128-C00286
         		A A A A white solid 56-57 324 322
    228
    Figure US20100022538A1-20100128-C00287
         		B A C A light yellow solid 362 360
    229
    Figure US20100022538A1-20100128-C00288
         		E E E E Off white solid 322
    230
    Figure US20100022538A1-20100128-C00289
         		D D A A yellow solid 159-163 403 401
    231
    Figure US20100022538A1-20100128-C00290
         		D D D D white solid 193-194 375 373
    232
    Figure US20100022538A1-20100128-C00291
         		A A A A white solid 105-107 252 250
    233
    Figure US20100022538A1-20100128-C00292
         		A A B A white solid 114-115
    234
    Figure US20100022538A1-20100128-C00293
         		A A A A pale yellow solid 357
    235
    Figure US20100022538A1-20100128-C00294
         		B A A A viscous yellow oil 345 342
    236
    Figure US20100022538A1-20100128-C00295
         		A A A A white solid 111-113 238
    237
    Figure US20100022538A1-20100128-C00296
         		D D D D white solid 62-65 240 238
    238
    Figure US20100022538A1-20100128-C00297
         		D C D B clear colorless oil 515 513
    239
    Figure US20100022538A1-20100128-C00298
         		B A A A white solid 165-166 403 401
    240
    Figure US20100022538A1-20100128-C00299
         		D D D C white solid 86-87 268 266
    241
    Figure US20100022538A1-20100128-C00300
         		A B A A white solid 161-165 365
    242
    Figure US20100022538A1-20100128-C00301
         		E E E E Pale yellow solid 320
    243
    Figure US20100022538A1-20100128-C00302
         		E E E E Pale yellow solid 429
    244
    Figure US20100022538A1-20100128-C00303
         		D A D A pale yellow solid 138-142 332 329
    245
    Figure US20100022538A1-20100128-C00304
         		B A B A white solid 145-148 254 252
    246
    Figure US20100022538A1-20100128-C00305
         		E E D D white solid 157-158 254 252
    247
    Figure US20100022538A1-20100128-C00306
         		A A A A off white solid 94-95 295
    248
    Figure US20100022538A1-20100128-C00307
         		A A D A off white solid 102-104 304
    249
    Figure US20100022538A1-20100128-C00308
         		C B C A off white solid 92-93 358 356
    250
    Figure US20100022538A1-20100128-C00309
         		E E E E white solid 117-118 254 252
    251
    Figure US20100022538A1-20100128-C00310
         		A A A A beige solid 120-122 300
    252
    Figure US20100022538A1-20100128-C00311
         		D D C C white solid 132-135
    253
    Figure US20100022538A1-20100128-C00312
         		B A C A yellow oil 263 261
    254
    Figure US20100022538A1-20100128-C00313
         		E E E E Gummy liquid 268
    255
    Figure US20100022538A1-20100128-C00314
         		E E E E Off white solid 200
    256
    Figure US20100022538A1-20100128-C00315
         		D C D D white solid 83-84 184 182
    257
    Figure US20100022538A1-20100128-C00316
         		B A B A white soid 90-91 296 294
    258
    Figure US20100022538A1-20100128-C00317
         		C B B A off white solid 80-82 236 233
    259
    Figure US20100022538A1-20100128-C00318
         		A A B A white solid 103-105 310
    260
    Figure US20100022538A1-20100128-C00319
         		A A A A off white slid 95 (dec) 357
    261
    Figure US20100022538A1-20100128-C00320
         		B A B A pale amber oil 340
    262
    Figure US20100022538A1-20100128-C00321
         		A A B A white solid 101-105
    263
    Figure US20100022538A1-20100128-C00322
         		E E E E Off white solid 270 M + Na
    264
    Figure US20100022538A1-20100128-C00323
         		A A B A white solid 131-133 356
    265
    Figure US20100022538A1-20100128-C00324
         		E E E E Yellow solid 344
    266
    Figure US20100022538A1-20100128-C00325
         		D A A A white solid 137-138 391 389
    267
    Figure US20100022538A1-20100128-C00326
         		D D D D white solid 104-105 172 170
    268
    Figure US20100022538A1-20100128-C00327
         		C B D C white solid 126-127 247
    269
    Figure US20100022538A1-20100128-C00328
         		D D D D pale green solid 91-94 265 237
    270
    Figure US20100022538A1-20100128-C00329
         		D D D D white solid 111-112 239
    271
    Figure US20100022538A1-20100128-C00330
         		B A A A white solid 119 306 304
    272
    Figure US20100022538A1-20100128-C00331
         		A A A A clear yellow oil 349
    273
    Figure US20100022538A1-20100128-C00332
         		A A B A 340 338
    274
    Figure US20100022538A1-20100128-C00333
         		A A A A off white solid 84-86 319
    275
    Figure US20100022538A1-20100128-C00334
         		A A A A beige solid 136 227
    276
    Figure US20100022538A1-20100128-C00335
         		A A A A 322 320
    277
    Figure US20100022538A1-20100128-C00336
         		E E E E 290
    278
    Figure US20100022538A1-20100128-C00337
         		E E E E Off white solid 411
    279
    Figure US20100022538A1-20100128-C00338
         		A A B A yellow gummy solid 316
    280
    Figure US20100022538A1-20100128-C00339
         		A A A A 340 338
    281
    Figure US20100022538A1-20100128-C00340
         		E E E E Pale yellow solid 427
    282
    Figure US20100022538A1-20100128-C00341
         		C B D C dark brown solid 158-163 312 309
    283
    Figure US20100022538A1-20100128-C00342
         		D C B A yellow solid 166-176 441 439
    284
    Figure US20100022538A1-20100128-C00343
         		D D D D white solid 196-198 236 234
    285
    Figure US20100022538A1-20100128-C00344
         		C C B A pale brown solid 118-120 331 329
    286
    Figure US20100022538A1-20100128-C00345
         		B A A A off-white solid 121-123 248 246
    287
    Figure US20100022538A1-20100128-C00346
         		A A A A white solid 115-116 363 361
    288
    Figure US20100022538A1-20100128-C00347
         		D D D D white solid 188-190 401 399
    289
    Figure US20100022538A1-20100128-C00348
         		A A A A white solid 128 254
    290
    Figure US20100022538A1-20100128-C00349
         		E E E E Pale yellow solid 425
    291
    Figure US20100022538A1-20100128-C00350
         		D C D D off-white solid 198-200 357 355
    292
    Figure US20100022538A1-20100128-C00351
         		A A A A colorless oil 369
    293
    Figure US20100022538A1-20100128-C00352
         		D D D D white solid 200-202 340 337
    294
    Figure US20100022538A1-20100128-C00353
         		D A D A yellow oil 347
    295
    Figure US20100022538A1-20100128-C00354
         		A A A A 366
    296
    Figure US20100022538A1-20100128-C00355
         		D C D D white solid 235 233
    297
    Figure US20100022538A1-20100128-C00356
         		E E E E Pale yellow liquid 368
    298
    Figure US20100022538A1-20100128-C00357
         		A A A A 354 352
    299
    Figure US20100022538A1-20100128-C00358
         		E E E E off white solid 83-88 562
    300
    Figure US20100022538A1-20100128-C00359
         		A A A A white solid 106-107 250 248
    301
    Figure US20100022538A1-20100128-C00360
         		B A C C tan solid 136-139 386 384
    302
    Figure US20100022538A1-20100128-C00361
         		A A A A grey solid 105-107 286
    303
    Figure US20100022538A1-20100128-C00362
         		B A C A thick oil 290
    304
    Figure US20100022538A1-20100128-C00363
         		E E E E Yellow liquid 276 [M + Na]
    305
    Figure US20100022538A1-20100128-C00364
         		E E E E white solid 292 290
    306
    Figure US20100022538A1-20100128-C00365
         		C C D A brown solid 108-112 341 339
    307
    Figure US20100022538A1-20100128-C00366
         		A A A A white solid 161-163 261 258
    308
    Figure US20100022538A1-20100128-C00367
         		A A A A yellow solid 182-183 256
    309
    Figure US20100022538A1-20100128-C00368
         		A A A A white solid 292 290
    310
    Figure US20100022538A1-20100128-C00369
         		E E E E colorless oil 400 398
    311
    Figure US20100022538A1-20100128-C00370
         		A A A A white solid 160-161 286
    312
    Figure US20100022538A1-20100128-C00371
         		A A A A white solid 196-200 309 307
    313
    Figure US20100022538A1-20100128-C00372
         		A A A A white solid 99-102 246
    314
    Figure US20100022538A1-20100128-C00373
         		A A A A 317 315
    315
    Figure US20100022538A1-20100128-C00374
         		A A B A white solid 64-65 202 200
    316
    Figure US20100022538A1-20100128-C00375
         		A A A A yellow solid 138-140 303
    317
    Figure US20100022538A1-20100128-C00376
         		C A B A pale amber oil 345
    318
    Figure US20100022538A1-20100128-C00377
         		E E E E 314
    319
    Figure US20100022538A1-20100128-C00378
         		E E E E Pale yellow viscous liquid 393
    320
    Figure US20100022538A1-20100128-C00379
         		C C D D yellow solid 209 377
    321
    Figure US20100022538A1-20100128-C00380
         		A A A A LIGHT YELLOW SOLID 112- 114 244
    322
    Figure US20100022538A1-20100128-C00381
         		D D D D yellow solid 235- 237 267 265
    323
    Figure US20100022538A1-20100128-C00382
         		A A A A white solid 153 248 246
    324
    Figure US20100022538A1-20100128-C00383
         		D C A A yellow solid 185-189 409 407
    325
    Figure US20100022538A1-20100128-C00384
         		A A A A off white solid 138-141 250 248
    326
    Figure US20100022538A1-20100128-C00385
         		B A A A pale amber oil 333
    327
    Figure US20100022538A1-20100128-C00386
         		B A B A pale amber oil 345
    328
    Figure US20100022538A1-20100128-C00387
         		A A A A off-white solid 116-117 264 262
    329
    Figure US20100022538A1-20100128-C00388
         		D D D D white solid 187-188 387 385
    330
    Figure US20100022538A1-20100128-C00389
         		D C D A white solid 75-77 340 338
    331
    Figure US20100022538A1-20100128-C00390
         		A A A A clear colorless oil 308 306
    332
    Figure US20100022538A1-20100128-C00391
         		B C A A yellow-white solid 121-123 356 354
    333
    Figure US20100022538A1-20100128-C00392
         		E E E E Gummy liquid 388
    334
    Figure US20100022538A1-20100128-C00393
         		A A A A white solid 79-80 301
    335
    Figure US20100022538A1-20100128-C00394
         		A A A A orange oil 282
    336
    Figure US20100022538A1-20100128-C00395
         		E E E E Gummy liquid 262
    337
    Figure US20100022538A1-20100128-C00396
         		C C C A white solid 191-192 208 206
    338
    Figure US20100022538A1-20100128-C00397
         		A A A A white solid 102-103 349
    339
    Figure US20100022538A1-20100128-C00398
         		C B D C white solid 63-65 264 262
    340
    Figure US20100022538A1-20100128-C00399
         		C A D A yellow oil 294 291
    341
    Figure US20100022538A1-20100128-C00400
         		A A A A white solid 129 268 266
    342
    Figure US20100022538A1-20100128-C00401
         		A A A A off-white crystals 147-149 305 303
    343
    Figure US20100022538A1-20100128-C00402
         		A A C A white solid 55-57 284 282
    344
    Figure US20100022538A1-20100128-C00403
         		D C C C off white solid 117-121 363 361
    345
    Figure US20100022538A1-20100128-C00404
         		A A A A white solid 154-156 276
    346
    Figure US20100022538A1-20100128-C00405
         		A A A A clear oil 352 350
    347
    Figure US20100022538A1-20100128-C00406
         		A A A A white solid 134-135 317
    348
    Figure US20100022538A1-20100128-C00407
         		A A A A white solid 128-130
    349
    Figure US20100022538A1-20100128-C00408
         		E E E E Pale yellow liquid 278
    350
    Figure US20100022538A1-20100128-C00409
         		A A A A white solid 117 314 312
    351
    Figure US20100022538A1-20100128-C00410
         		A A A A white solid 151 280 278
    352
    Figure US20100022538A1-20100128-C00411
         		D D D D colorless liquid 310 307
    353
    Figure US20100022538A1-20100128-C00412
         		D D D D white solid 68-72 335 333
    354
    Figure US20100022538A1-20100128-C00413
         		C A B A clear pale yellow oil 370 368
    355
    Figure US20100022538A1-20100128-C00414
         		A A A A white solid 150-152 330
    356
    Figure US20100022538A1-20100128-C00415
         		C B C B orange oil 301
    357
    Figure US20100022538A1-20100128-C00416
         		D B C C off white solid 173-177 313 311
    358
    Figure US20100022538A1-20100128-C00417
         		C A D B brown solid 120-123 293 291
    359
    Figure US20100022538A1-20100128-C00418
         		A C A A white solid 172-174 360
    360
    Figure US20100022538A1-20100128-C00419
         		A A A A white solid 105-106 390 388
    361
    Figure US20100022538A1-20100128-C00420
         		A A B A white solid 150-153 339
    362
    Figure US20100022538A1-20100128-C00421
         		B A B A white solid 115-116 282 280
    363
    Figure US20100022538A1-20100128-C00422
         		E E E E Pale yellow viscous liquid 441
    364
    Figure US20100022538A1-20100128-C00423
         		A A A A white solid 114-115 342 340
    365
    Figure US20100022538A1-20100128-C00424
         		A A A A tacky yellow glass 252
    366
    Figure US20100022538A1-20100128-C00425
         		B A A A yellow solid 186-192 377 375
    367
    Figure US20100022538A1-20100128-C00426
         		D D D D off white solid 94-97.5 341
    368
    Figure US20100022538A1-20100128-C00427
         		A A A A tan solid 95-96 286 284
    369
    Figure US20100022538A1-20100128-C00428
         		A A A A white solid 138-139 323
    370
    Figure US20100022538A1-20100128-C00429
         		D D D D white solid 93-94 212 210
    371
    Figure US20100022538A1-20100128-C00430
         		D D D D white solid 168-169 371 369
    372
    Figure US20100022538A1-20100128-C00431
         		E E C A white solid 138-139 263 261
    373
    Figure US20100022538A1-20100128-C00432
         		C B D D brown solid 44-50 313 310
    374
    Figure US20100022538A1-20100128-C00433
         		A A B A clear pale yellow oil 282 280
    375
    Figure US20100022538A1-20100128-C00434
         		C A D D yellow oil 322 320
    376
    Figure US20100022538A1-20100128-C00435
         		D C D D lavender powder 214-216 363 361
    377
    Figure US20100022538A1-20100128-C00436
         		B A A A pale amber oil 329
    378
    Figure US20100022538A1-20100128-C00437
         		A A B A white solid 177-179 290 288
    379
    Figure US20100022538A1-20100128-C00438
         		B A A A white solid 84-85 310 308
    380
    Figure US20100022538A1-20100128-C00439
         		D A A A off white solid 73-76 343
    381
    Figure US20100022538A1-20100128-C00440
         		A A A A light yellow solid 173-175 276 274
    382
    Figure US20100022538A1-20100128-C00441
         		D A A A white solid 149-152 336
    383
    Figure US20100022538A1-20100128-C00442
         		C D D D yellow solid 118-120 — 299
    384
    Figure US20100022538A1-20100128-C00443
         		C A B A dark oil 241 239
    385
    Figure US20100022538A1-20100128-C00444
         		A A A A ivory solid 104-105 292 290
    386
    Figure US20100022538A1-20100128-C00445
         		A A A A white solid 124 264 262
    387
    Figure US20100022538A1-20100128-C00446
         		A A A A orange oil 274
    388
    Figure US20100022538A1-20100128-C00447
         		E E E E Pale yellow solid 384
    389
    Figure US20100022538A1-20100128-C00448
         		A A A A light yellow solid 88.5-89.5 308.8 (Na+)
    390
    Figure US20100022538A1-20100128-C00449
         		A A A A off white solid 96-100 236 234
    391
    Figure US20100022538A1-20100128-C00450
         		C A B A off-white solid 132-135 346 344
    392
    Figure US20100022538A1-20100128-C00451
         		A A A A off-white solid 210
    393
    Figure US20100022538A1-20100128-C00452
         		C A C A clear oil 277
    394
    Figure US20100022538A1-20100128-C00453
         		A A A A white solid 177-179 356 354
    395
    Figure US20100022538A1-20100128-C00454
         		C B D D yellow oil 249 247
    396
    Figure US20100022538A1-20100128-C00455
         		A A A A off-white solid 181-183 274 272
    397
    Figure US20100022538A1-20100128-C00456
         		D D D D colorless oil 282 279
    398
    Figure US20100022538A1-20100128-C00457
         		D C D D white solid 176-178 385 383
    399
    Figure US20100022538A1-20100128-C00458
         		A A B A white solid 174 249 247
    400
    Figure US20100022538A1-20100128-C00459
         		A A A A off-white solid 154-156 264 262
    401
    Figure US20100022538A1-20100128-C00460
         		A A A A off-white solid 271
    402
    Figure US20100022538A1-20100128-C00461
         		A A A A white solid 121-122 331
    403
    Figure US20100022538A1-20100128-C00462
         		C A A A white solid 93-94 292
    404
    Figure US20100022538A1-20100128-C00463
         		A A A A white solid 289 287
    405
    Figure US20100022538A1-20100128-C00464
         		A A A A clear pale yellow oil 305
    406
    Figure US20100022538A1-20100128-C00465
         		A A A A white solid 134-138 312
    407
    Figure US20100022538A1-20100128-C00466
         		D D D D yellow oil 318
    408
    Figure US20100022538A1-20100128-C00467
         		D A D A yellow solid 144-145 377 375
    409
    Figure US20100022538A1-20100128-C00468
         		A A A A tan solid 210
    410
    Figure US20100022538A1-20100128-C00469
         		B A B A white solid 114-115 336
    411
    Figure US20100022538A1-20100128-C00470
         		C C A A white solid 138-142 400 398
    412
    Figure US20100022538A1-20100128-C00471
         		D B D A colorless oil 344 342
    413
    Figure US20100022538A1-20100128-C00472
         		A A A A white solid 245-247 234 232
    414
    Figure US20100022538A1-20100128-C00473
         		E E E E white solid 125 (dec) 319
    415
    Figure US20100022538A1-20100128-C00474
         		A A B A 384 382
    416
    Figure US20100022538A1-20100128-C00475
         		D C D D 358
    417
    Figure US20100022538A1-20100128-C00476
         		A A A A white solid 105-115 (dec) 253
    418
    Figure US20100022538A1-20100128-C00477
         		A A A A brown oil 300
    419
    Figure US20100022538A1-20100128-C00478
         		A A A A 336 334
    420
    Figure US20100022538A1-20100128-C00479
         		A A A A white solid 93-94 255
    421
    Figure US20100022538A1-20100128-C00480
         		A A A A pale amber oil 315
    422
    Figure US20100022538A1-20100128-C00481
         		A A A A white solid 111-112 317
    423
    Figure US20100022538A1-20100128-C00482
         		D D D D white solid 236 234
    424
    Figure US20100022538A1-20100128-C00483
         		B A B A pale amber solid 93-100 347
    425
    Figure US20100022538A1-20100128-C00484
         		A A A A white solid 95-99 372
    426
    Figure US20100022538A1-20100128-C00485
         		E E E E Colourless liquid 324
    427
    Figure US20100022538A1-20100128-C00486
         		A A A A yellow white solid 125-126 302
    428
    Figure US20100022538A1-20100128-C00487
         		C A B B light yellow solid 309 307
    429
    Figure US20100022538A1-20100128-C00488
         		A A A A beige solid 168-169 261 259
    430
    Figure US20100022538A1-20100128-C00489
         		A A A A dark brown solid 128-130 235 233
    431
    Figure US20100022538A1-20100128-C00490
         		A A A A clear yellow oil 238
    432
    Figure US20100022538A1-20100128-C00491
         		E E E E Pale yellow solid 411
    433
    Figure US20100022538A1-20100128-C00492
         		D D D D yellow solid 214 212
    434
    Figure US20100022538A1-20100128-C00493
         		A A A A clear oil 338
    435
    Figure US20100022538A1-20100128-C00494
         		B A A A white solid 115-117 324 322
    436
    Figure US20100022538A1-20100128-C00495
         		A A A A white solid 115 241
    437
    Figure US20100022538A1-20100128-C00496
         		D B D B brown solid 182- 183 246 244
    438
    Figure US20100022538A1-20100128-C00497
         		D D B A white solid 162-164 387 385
    439
    Figure US20100022538A1-20100128-C00498
         		E E E E Yellow solid 298 [M + Na]
    440
    Figure US20100022538A1-20100128-C00499
         		C D D D yellow solid 172-179 401 399
    441
    Figure US20100022538A1-20100128-C00500
         		A A A A light yellow solid 61-62 278 276
    442
    Figure US20100022538A1-20100128-C00501
         		A A A A fluffy off-white solid 195-196 297 293
    443
    Figure US20100022538A1-20100128-C00502
         		C C A A yellow solid 173-177 387 385
    444
    Figure US20100022538A1-20100128-C00503
         		A A A A white solid 121-123 336
    445
    Figure US20100022538A1-20100128-C00504
         		A A B A brown oil 408 406
    446
    Figure US20100022538A1-20100128-C00505
         		E E E E white solid 152-153 347 345
    447
    Figure US20100022538A1-20100128-C00506
         		E E E E Pale yellow liquid 214
    448
    Figure US20100022538A1-20100128-C00507
         		E E E E Pale yellow solid 364
    449
    Figure US20100022538A1-20100128-C00508
         		E E E E Off white solid 489
    450
    Figure US20100022538A1-20100128-C00509
         		A B A A white solid 155 294 292
    451
    Figure US20100022538A1-20100128-C00510
         		D D D D white solid 158-160 263 261
    452
    Figure US20100022538A1-20100128-C00511
         		A A A A white solid 108-109 326 324
    453
    Figure US20100022538A1-20100128-C00512
         		B A A A light yellow glass 344 342
    454
    Figure US20100022538A1-20100128-C00513
         		C D D A off white solid 153.5-157.9 337 334
    455
    Figure US20100022538A1-20100128-C00514
         		C A B A white solid 101-103 268 266
    456
    Figure US20100022538A1-20100128-C00515
         		D A B A yellow oil 377
    457
    Figure US20100022538A1-20100128-C00516
         		B A B A LIGHT YELLOW SOLID 53-55 257
    458
    Figure US20100022538A1-20100128-C00517
         		D D D B white tacky solid 358 356
    459
    Figure US20100022538A1-20100128-C00518
         		A A B A 352 350
    460
    Figure US20100022538A1-20100128-C00519
         		A A A A white solid 304 302
    461
    Figure US20100022538A1-20100128-C00520
         		E E E E Gummy liquid 290
    462
    Figure US20100022538A1-20100128-C00521
         		B C B A white solid 143-144 278 276
    463
    Figure US20100022538A1-20100128-C00522
         		C B D B colorless oil 308 306
    464
    Figure US20100022538A1-20100128-C00523
         		D C D D off-white solid 171-174 419 417
    465
    Figure US20100022538A1-20100128-C00524
         		A A A A tan solid 155-157 271 269
    466
    Figure US20100022538A1-20100128-C00525
         		D D D D light yellow glass 386 384
    467
    Figure US20100022538A1-20100128-C00526
         		A A A A white solid 120-121 292.8 (Na+)
    468
    Figure US20100022538A1-20100128-C00527
         		A A A A white powder 143-145 254
    469
    Figure US20100022538A1-20100128-C00528
         		A A A A white solid 98-99 288
    470
    Figure US20100022538A1-20100128-C00529
         		C C D D pale pink solid 154.4-157.2 342 340
    471
    Figure US20100022538A1-20100128-C00530
         		E E E E Gummy liquid 282
    472
    Figure US20100022538A1-20100128-C00531
         		A A A A yellow solid 58-61 266 264
    473
    Figure US20100022538A1-20100128-C00532
         		C A C A fluffy white solid 123-124 253 251
    474
    Figure US20100022538A1-20100128-C00533
         		A A A A clear oil 324
    475
    Figure US20100022538A1-20100128-C00534
         		B A B A white solid 170-171 349 351
    476
    Figure US20100022538A1-20100128-C00535
         		A A A A white solid 123-125 318 316
    477
    Figure US20100022538A1-20100128-C00536
         		D B D D white solid 189-191 389 387
    478
    Figure US20100022538A1-20100128-C00537
         		A A B A 372 370
    479
    Figure US20100022538A1-20100128-C00538
         		B B A A yellow solid 143-150 488
    480
    Figure US20100022538A1-20100128-C00539
         		D D D D pale yellow solid 150-154 324 322
    481
    Figure US20100022538A1-20100128-C00540
         		A A A A white solid 169-174 (dec)
    482
    Figure US20100022538A1-20100128-C00541
         		D C D D off white solid 111-115 312 309
    483
    Figure US20100022538A1-20100128-C00542
         		A A A A clear yellow oil 307
    484
    Figure US20100022538A1-20100128-C00543
         		A A A A yellow oil 323
    485
    Figure US20100022538A1-20100128-C00544
         		D D D D white solid 206-207 357 355
    486
    Figure US20100022538A1-20100128-C00545
         		C C D D ivory solid 188-189 302 300
    487
    Figure US20100022538A1-20100128-C00546
         		D A D A white solid 153.8-157.1 268 266
    488
    Figure US20100022538A1-20100128-C00547
         		D D D D white solid 191-192 238 236
    489
    Figure US20100022538A1-20100128-C00548
         		A A D B white solid 122-123 182 180
    490
    Figure US20100022538A1-20100128-C00549
         		A A A A 306 304
    491
    Figure US20100022538A1-20100128-C00550
         		E E E E Pale yellow solid 411
    492
    Figure US20100022538A1-20100128-C00551
         		D C D C pale brown solid 139-143 335 333
    493
    Figure US20100022538A1-20100128-C00552
         		D D D C pale yellow solid 95-98 318 315
    494
    Figure US20100022538A1-20100128-C00553
         		A A A A off white solid 77-78 293
    495
    Figure US20100022538A1-20100128-C00554
         		E E E E Yellow solid 350
    496
    Figure US20100022538A1-20100128-C00555
         		E E E E Pale yellow solid 463
    497
    Figure US20100022538A1-20100128-C00556
         		D C B A white solid 123-124 352 350
    498
    Figure US20100022538A1-20100128-C00557
         		A A A A white solid 56-58 296 294
    499
    Figure US20100022538A1-20100128-C00558
         		E E E E 292
    500
    Figure US20100022538A1-20100128-C00559
         		A A A A white solid 147-150 306 304
    501
    Figure US20100022538A1-20100128-C00560
         		A A A A viscous semisolid 316 314
    502
    Figure US20100022538A1-20100128-C00561
         		D D D D white solid 130-134 336
    503
    Figure US20100022538A1-20100128-C00562
         		A A A A clear oil 341 339
    504
    Figure US20100022538A1-20100128-C00563
         		D D D B off-white solid 165-166 412 410
    505
    Figure US20100022538A1-20100128-C00564
         		E E E E Brown liquid 294
    506
    Figure US20100022538A1-20100128-C00565
         		D D C A white solid 95-97 346 344
    507
    Figure US20100022538A1-20100128-C00566
         		D A B A YELLOW GUMMY SOLID 382
    508
    Figure US20100022538A1-20100128-C00567
         		A A A A tan solid 226
    509
    Figure US20100022538A1-20100128-C00568
         		C D D D tan solid 72-77 220 218
    510
    Figure US20100022538A1-20100128-C00569
         		B A B A white solid 150 262 260
    511
    Figure US20100022538A1-20100128-C00570
         		C C B B yellow oil 271
    512
    Figure US20100022538A1-20100128-C00571
         		D D D B off white solid 63-67 318
    513
    Figure US20100022538A1-20100128-C00572
         		A A A A sticky solid 264
    514
    Figure US20100022538A1-20100128-C00573
         		A A A A yellow oil 288
    515
    Figure US20100022538A1-20100128-C00574
         		D D D A brown solid 123-129 363 361
    516
    Figure US20100022538A1-20100128-C00575
         		A A A A clear pale yellow oil 303 301
    517
    Figure US20100022538A1-20100128-C00576
         		A A A A white solid 125-127 243
    518
    Figure US20100022538A1-20100128-C00577
         		A A A A tan oil 335
    519
    Figure US20100022538A1-20100128-C00578
         		D D D D white solid 208-211 405 403
    520
    Figure US20100022538A1-20100128-C00579
         		E E E E Pale yellow solid 308
    521
    Figure US20100022538A1-20100128-C00580
         		E E E E Pale yellow solid 278
    522
    Figure US20100022538A1-20100128-C00581
         		D D D C rust solid 188-189 246 244
    523
    Figure US20100022538A1-20100128-C00582
         		A A A A white solid 127-130 356.8 (Na+)
    524
    Figure US20100022538A1-20100128-C00583
         		D B D B white solid 100-101 264 262
    525
    Figure US20100022538A1-20100128-C00584
         		A A A A yellow solid 154-160 427 425
    526
    Figure US20100022538A1-20100128-C00585
         		D D D B yellow solid 216-218 404
    527
    Figure US20100022538A1-20100128-C00586
         		D D B A yellow solid 178-182 459 457
    528
    Figure US20100022538A1-20100128-C00587
         		D B A A tan solid 121-124 327 325
    529
    Figure US20100022538A1-20100128-C00588
         		D D D D OFF WHITE SOLID 188-190
    530
    Figure US20100022538A1-20100128-C00589
         		B A A A pale amber oil 321
    531
    Figure US20100022538A1-20100128-C00590
         		A A A A 384 382
    532
    Figure US20100022538A1-20100128-C00591
         		D C C B off white solid 157-162 343 341
    533
    Figure US20100022538A1-20100128-C00592
         		D C B B white solid 120-123 331 329
    534
    Figure US20100022538A1-20100128-C00593
         		D C D C white solid 147-148 335 333
    535
    Figure US20100022538A1-20100128-C00594
         		D D D D white solid 182-183 387 385
    536
    Figure US20100022538A1-20100128-C00595
         		C C D D white solid 171-172 319 317
    537
    Figure US20100022538A1-20100128-C00596
         		A A A A off-white solid 112-113 292 290
    538
    Figure US20100022538A1-20100128-C00597
         		B A C B pale biege solid 103-107 250 247
    539
    Figure US20100022538A1-20100128-C00598
         		D D A A white solid 142-144 373 371
    540
    Figure US20100022538A1-20100128-C00599
         		A A A A white solid 185 289 287
    541
    Figure US20100022538A1-20100128-C00600
         		A A A A white solid  99-100 347
    542
    Figure US20100022538A1-20100128-C00601
         		E E E E Off white solid 266
    543
    Figure US20100022538A1-20100128-C00602
         		A A A A colorless oil 276
    544
    Figure US20100022538A1-20100128-C00603
         		D D D C white solid 134-140 322
    545
    Figure US20100022538A1-20100128-C00604
         		D B D C white solid 134-135 199
    546
    Figure US20100022538A1-20100128-C00605
         		B D B B white solid 235-238 360
    547
    Figure US20100022538A1-20100128-C00606
         		A A A A white solid 130-132 273 271
    548
    Figure US20100022538A1-20100128-C00607
         		D D D D white solid 196-198 330 328
    549
    Figure US20100022538A1-20100128-C00608
         		D D C D white solid 187-188 241 239
    550
    Figure US20100022538A1-20100128-C00609
         		A A A A white solid 105-106 292 290
    551
    Figure US20100022538A1-20100128-C00610
         		E E D C white solid 155-156 240 238
    552
    Figure US20100022538A1-20100128-C00611
         		D A D A off-white solid 148-149 369 367
    553
    Figure US20100022538A1-20100128-C00612
         		A A A A clear oil 334 332
    554
    Figure US20100022538A1-20100128-C00613
         		C A C A white solid 123-124 260 258
    555
    Figure US20100022538A1-20100128-C00614
         		D D D D white solid 203-205 (dec) 364 362
    556
    Figure US20100022538A1-20100128-C00615
         		D A C A WHITE SOLID 100-103 323
    557
    Figure US20100022538A1-20100128-C00616
         		D D C D white solid 208-210 343 341
    558
    Figure US20100022538A1-20100128-C00617
         		C C A A yellow solid 167-171 373 371
    559
    Figure US20100022538A1-20100128-C00618
         		A A B A PALE YELLOW SOLID 212
    560
    Figure US20100022538A1-20100128-C00619
         		D A D C yellow solid 261 259
    561
    Figure US20100022538A1-20100128-C00620
         		A A A A clear oil 349
    562
    Figure US20100022538A1-20100128-C00621
         		D C D D yellow oil 333 331
    563
    Figure US20100022538A1-20100128-C00622
         		E E E E Colourless liquid 290
    564
    Figure US20100022538A1-20100128-C00623
         		C A B A white solid 109 248 246
    565
    Figure US20100022538A1-20100128-C00624
         		E E E E White solid 445
    566
    Figure US20100022538A1-20100128-C00625
         		D D D D white solid 158-159 323 321
    567
    Figure US20100022538A1-20100128-C00626
         		C A C B clear yellow oil 388 386
    568
    Figure US20100022538A1-20100128-C00627
         		A A B A off-white solid 125-126 339 337
    569
    Figure US20100022538A1-20100128-C00628
         		B A A A white solid 90 320 318
    570
    Figure US20100022538A1-20100128-C00629
         		A A A A off white solid 101-102 281
    571
    Figure US20100022538A1-20100128-C00630
         		A A A A white solid 132-133 280 278
    572
    Figure US20100022538A1-20100128-C00631
         		C B C A off-white solid 178-179 405 403
    573
    Figure US20100022538A1-20100128-C00632
         		D D C B white solid 201-202 236 234
    574
    Figure US20100022538A1-20100128-C00633
         		A A A A white solid 131 289 287
    575
    Figure US20100022538A1-20100128-C00634
         		E E E E yellow oil 321
    576
    Figure US20100022538A1-20100128-C00635
         		C A C A white solid 117-122 277
    577
    Figure US20100022538A1-20100128-C00636
         		A A A A off-white solid 86-88 240
    578
    Figure US20100022538A1-20100128-C00637
         		A A A A pale yellow solid 140-142 277
    579
    Figure US20100022538A1-20100128-C00638
         		E E E E Pale yellow solid 262
    580
    Figure US20100022538A1-20100128-C00639
         		D B B A white solid 185-187 256
    581
    Figure US20100022538A1-20100128-C00640
         		A A A A white solid 120 268 266
    582
    Figure US20100022538A1-20100128-C00641
         		A A A A off-white solid 162 290 288
    583
    Figure US20100022538A1-20100128-C00642
         		A A D A white solid 108-109 249 247
    584
    Figure US20100022538A1-20100128-C00643
         		D A D A off white solid 153-154 224 222
    585
    Figure US20100022538A1-20100128-C00644
         		A A A A white solid 125 (dec) 323
    586
    Figure US20100022538A1-20100128-C00645
         		D D D D colorless oil 320
    587
    Figure US20100022538A1-20100128-C00646
         		C A D D white solid 200-201 363 361
    588
    Figure US20100022538A1-20100128-C00647
         		D D D D white solid 86.3-89.8 335
    589
    Figure US20100022538A1-20100128-C00648
         		D D D D white solid >200 294 292
    590
    Figure US20100022538A1-20100128-C00649
         		A A A A white solid 154 268 266
    591
    Figure US20100022538A1-20100128-C00650
         		E E E E Off white solid 282
    592
    Figure US20100022538A1-20100128-C00651
         		A A A A yellow oil 260
    593
    Figure US20100022538A1-20100128-C00652
         		E E D B white solid 134-135 240 238
    594
    Figure US20100022538A1-20100128-C00653
         		D C D B white solid 104.4-107 356 354
    595
    Figure US20100022538A1-20100128-C00654
         		D D C A off-white solid 160-161 391 389
    596
    Figure US20100022538A1-20100128-C00655
         		A A A A off-white solid 105-107 305 302
    597
    Figure US20100022538A1-20100128-C00656
         		A A A A clear oil 280
    598
    Figure US20100022538A1-20100128-C00657
         		A A B A white solid 156-160 356
    599
    Figure US20100022538A1-20100128-C00658
         		A A B A clear oil 359 357
    600
    Figure US20100022538A1-20100128-C00659
         		A A A A clear oil 365
    601
    Figure US20100022538A1-20100128-C00660
         		A A A A white solid 53-54 308 306
    602
    Figure US20100022538A1-20100128-C00661
         		D D D B white solid 144 247
    603
    Figure US20100022538A1-20100128-C00662
         		D D C A off white solid 173-176 374 372
    604
    Figure US20100022538A1-20100128-C00663
         		A A A A off-white solid 106-108 #### ####
    605
    Figure US20100022538A1-20100128-C00664
         		D A B A WHITE SOLID 64-67 350
    606
    Figure US20100022538A1-20100128-C00665
         		E E E E 316
    607
    Figure US20100022538A1-20100128-C00666
         		D C D D white solid 112-113 334
    608
    Figure US20100022538A1-20100128-C00667
         		B A B A dark red oil 279 262
    609
    Figure US20100022538A1-20100128-C00668
         		A A A A white solid 112 280 278
    610
    Figure US20100022538A1-20100128-C00669
         		C B A A white solid 157-159 319
    611
    Figure US20100022538A1-20100128-C00670
         		A A A A white solid 143-145
    612
    Figure US20100022538A1-20100128-C00671
         		A A A A yellow solid 165-172 398 396
    613
    Figure US20100022538A1-20100128-C00672
         		A A A A 368 366
    614
    Figure US20100022538A1-20100128-C00673
         		A A A A white solid 75-76 310 308
    615
    Figure US20100022538A1-20100128-C00674
         		A A C A YELLOW SOLID 58-60 237
    616
    Figure US20100022538A1-20100128-C00675
         		A A A A white solid 149-151 287
    617
    Figure US20100022538A1-20100128-C00676
         		A A A A clear oil 288
    618
    Figure US20100022538A1-20100128-C00677
         		E E E E Off white solid 429
    619
    Figure US20100022538A1-20100128-C00678
         		E E E E Gummy liquid 306
    620
    Figure US20100022538A1-20100128-C00679
         		E E E E Pale yellow solid 350
    621
    Figure US20100022538A1-20100128-C00680
         		E E E E Off white solid 266
    622
    Figure US20100022538A1-20100128-C00681
         		E E E E Pale yellow liquid 296
    623
    Figure US20100022538A1-20100128-C00682
         		B A A A white solid 112 280 278
    624
    Figure US20100022538A1-20100128-C00683
         		B A B A LIGHT BROWN SOLID 128-130 310
    625
    Figure US20100022538A1-20100128-C00684
         		D C D C white solid 114-115 202
    626
    Figure US20100022538A1-20100128-C00685
         		A A A A white solid 130-131 317
    627
    Figure US20100022538A1-20100128-C00686
         		E E E E Pale yellow solid 475
    628
    Figure US20100022538A1-20100128-C00687
         		B A C A beige solid 101-103 227
    629
    Figure US20100022538A1-20100128-C00688
         		D B D B light yellow solid 374 372
    630
    Figure US20100022538A1-20100128-C00689
         		A A A A white solid 167-169 276
    631
    Figure US20100022538A1-20100128-C00690
         		D D D D clear yellow oil 184 182
    632
    Figure US20100022538A1-20100128-C00691
         		A A A A white solid 128-131 320 318
    633
    Figure US20100022538A1-20100128-C00692
         		A A A A white solid 308
    634
    Figure US20100022538A1-20100128-C00693
         		A A A A white solid 130-133 359
    635
    Figure US20100022538A1-20100128-C00694
         		D A C A white solid 117-118 247
    636
    Figure US20100022538A1-20100128-C00695
         		A A A A white solid 132-135 319
    637
    Figure US20100022538A1-20100128-C00696
         		A A A A white solid 158-160 249
    638
    Figure US20100022538A1-20100128-C00697
         		D B B A white solid 77-78 370 368
    639
    Figure US20100022538A1-20100128-C00698
         		B A A A white solid 136-137 403 401
    640
    Figure US20100022538A1-20100128-C00699
         		A A A A yellow white solid 218-220 258
    641
    Figure US20100022538A1-20100128-C00700
         		E E E E Pale yellow liquid 276
    642
    Figure US20100022538A1-20100128-C00701
         		E E E E white foam 61-65 410 (M + Na)
    643
    Figure US20100022538A1-20100128-C00702
         		A A A A pasty off-white solid
    644
    Figure US20100022538A1-20100128-C00703
         		A A A A white solid 164-166 255
    645
    Figure US20100022538A1-20100128-C00704
         		D B C A white solid 117-118 264 262
    646
    Figure US20100022538A1-20100128-C00705
         		A A B A white solid 185-187 298 296
    647
    Figure US20100022538A1-20100128-C00706
         		A A A A white solid 89-90 290.8 (Na+)
    648
    Figure US20100022538A1-20100128-C00707
         		A A A A white solid 132 344 342
    649
    Figure US20100022538A1-20100128-C00708
         		D A D C LIGHT YELLOW SOLID 130-132 278
    650
    Figure US20100022538A1-20100128-C00709
         		A A A A yellow solid 108 322 320
    651
    Figure US20100022538A1-20100128-C00710
         		D B D D white solid 381 379
    652
    Figure US20100022538A1-20100128-C00711
         		D A D B yellow oil 350 348
    653
    Figure US20100022538A1-20100128-C00712
         		C A D D white solid 58-59 184
    654
    Figure US20100022538A1-20100128-C00713
         		A A A A white solid 118-121 324
    655
    Figure US20100022538A1-20100128-C00714
         		B C B A yellow solid 144-146 461 459
    656
    Figure US20100022538A1-20100128-C00715
         		A A A A clear oil 334
    657
    Figure US20100022538A1-20100128-C00716
         		E E E E Off white solid 459
    658
    Figure US20100022538A1-20100128-C00717
         		D B D B YELLOW GUMMY SOLID
    659
    Figure US20100022538A1-20100128-C00718
         		E E E E Pale yellow solid 477
    660
    Figure US20100022538A1-20100128-C00719
         		C D A A white solid 160-161
    661
    Figure US20100022538A1-20100128-C00720
         		E E E E Off white solid 280
    662
    Figure US20100022538A1-20100128-C00721
         		C C D A yellow solid 176 409 407
    663
    Figure US20100022538A1-20100128-C00722
         		A A A A yellow solid 123-124 323
    664
    Figure US20100022538A1-20100128-C00723
         		D D D C OFF WHITE SOLID 125- 127 356
    665
    Figure US20100022538A1-20100128-C00724
         		E E E E Colourless liquid 242
    666
    Figure US20100022538A1-20100128-C00725
         		E E E E Yellow solid 248
    667
    Figure US20100022538A1-20100128-C00726
         		D A D A brown solid 108-111 357 355
    668
    Figure US20100022538A1-20100128-C00727
         		A A C A 347 345
    669
    Figure US20100022538A1-20100128-C00728
         		A A A A white solid 135-136 305
    670
    Figure US20100022538A1-20100128-C00729
         		B A B A off-white solid 188-190 401 399
    671
    Figure US20100022538A1-20100128-C00730
         		A A A A white solid 153-154
    672
    Figure US20100022538A1-20100128-C00731
         		A A A A off-white solid 127-129 314
    673
    Figure US20100022538A1-20100128-C00732
         		A A A A off-white solid 94-95 266 264
    674
    Figure US20100022538A1-20100128-C00733
         		A A A A clear oil 366 364
    675
    Figure US20100022538A1-20100128-C00734
         		A A A A light tan waxy solid 292 290
    676
    Figure US20100022538A1-20100128-C00735
         		D D C A yellow oil 354 352
    677
    Figure US20100022538A1-20100128-C00736
         		A A A A white solid 113-114 250 248
    678
    Figure US20100022538A1-20100128-C00737
         		C A D A off-white crystals 128-129 321 319
    679
    Figure US20100022538A1-20100128-C00738
         		A A A A off white solid 98-99 363
    680
    Figure US20100022538A1-20100128-C00739
         		C C D D yellow solid 175-182 433 431
    681
    Figure US20100022538A1-20100128-C00740
         		A A A A white solid 86-88 285
    682
    Figure US20100022538A1-20100128-C00741
         		A A A A off-white solid 153-155 290
    683
    Figure US20100022538A1-20100128-C00742
         		E E E E Colourless liquid 236 [M + Na]
    684
    Figure US20100022538A1-20100128-C00743
         		A A A A white solid 94-95 335
    685
    Figure US20100022538A1-20100128-C00744
         		D D D A yellow solid 175-183 433 431
    686
    Figure US20100022538A1-20100128-C00745
         		E E E E white solid 160-161 262 260
    687
    Figure US20100022538A1-20100128-C00746
         		D D C A yellow solid 122 338 336
    688
    Figure US20100022538A1-20100128-C00747
         		A A A A white solid 93-95 289
    689
    Figure US20100022538A1-20100128-C00748
         		A A A A white solid 126-128 254 252
    690
    Figure US20100022538A1-20100128-C00749
         		A A B A 379 377
    691
    Figure US20100022538A1-20100128-C00750
         		B A B A yellow solid 162 262 260
    692
    Figure US20100022538A1-20100128-C00751
         		A A A A clear yellow oil 305
    693
    Figure US20100022538A1-20100128-C00752
         		A A A A white solid 127-130 292 290
    694
    Figure US20100022538A1-20100128-C00753
         		D C D C white solid 181-183 451 449
    695
    Figure US20100022538A1-20100128-C00754
         		D C D A WHITE SOLID 100- 102 256
    696
    Figure US20100022538A1-20100128-C00755
         		B A A A off-white solid 98-102 276 274
    697
    Figure US20100022538A1-20100128-C00756
         		C C D D LIGHT YELLOW SOLID 393
    698
    Figure US20100022538A1-20100128-C00757
         		A A A A white solid 117 314 312
    699
    Figure US20100022538A1-20100128-C00758
         		B A A A tannish solid 222
    700
    Figure US20100022538A1-20100128-C00759
         		C A D B tan solid 185-187 375 373
    701
    Figure US20100022538A1-20100128-C00760
         		D A D A pale yellow solid 138-142 332 329
    702
    Figure US20100022538A1-20100128-C00761
         		A A A A clear oil 382 380
    703
    Figure US20100022538A1-20100128-C00762
         		D D D C white solid 116-117 435 433
    704
    Figure US20100022538A1-20100128-C00763
         		A A A A white solid 76-77 347
    705
    Figure US20100022538A1-20100128-C00764
         		B A A A white solid 117-119 288 286
    706
    Figure US20100022538A1-20100128-C00765
         		D B D A light yellow solid 163-165 346 344
    707
    Figure US20100022538A1-20100128-C00766
         		A A A A orange solid 156 299 297
    708
    Figure US20100022538A1-20100128-C00767
         		A A A A white solid 89-90 292 290
    709
    Figure US20100022538A1-20100128-C00768
         		D B D A clear colorless oil 388 386
    710
    Figure US20100022538A1-20100128-C00769
         		B A B A clear colorless oil 262 260
    711
    Figure US20100022538A1-20100128-C00770
         		C A B A white solid 138-139 379 377
    712
    Figure US20100022538A1-20100128-C00771
         		E E E E Off white solid 415
    713
    Figure US20100022538A1-20100128-C00772
         		B A A A brown solid 95-98 238
    714
    Figure US20100022538A1-20100128-C00773
         		A A A A yellow oil 294 292
    715
    Figure US20100022538A1-20100128-C00774
         		D D C B white solid 198-201 251 249
    716
    Figure US20100022538A1-20100128-C00775
         		A A A A yellow solid 93 326 324
    717
    Figure US20100022538A1-20100128-C00776
         		A A B A 338
    718
    Figure US20100022538A1-20100128-C00777
         		C C C A pale yellow solid 135-139 356 353
    719
    Figure US20100022538A1-20100128-C00778
         		E E D B white solid 103-104 300 298
    720
    Figure US20100022538A1-20100128-C00779
         		A A A A white solid 115 299
    721
    Figure US20100022538A1-20100128-C00780
         		E E E E 370 368
    722
    Figure US20100022538A1-20100128-C00781
         		D C D D light yellow solid 58-59 184 182
    723
    Figure US20100022538A1-20100128-C00782
         		E E E E Pale yellow solid 400
    724
    Figure US20100022538A1-20100128-C00783
         		D D D C white solid 170-171 335 333
    725
    Figure US20100022538A1-20100128-C00784
         		A A A A yellow solid 146-147 346 344
    726
    Figure US20100022538A1-20100128-C00785
         		A A A A white solid 109-110 305
    727
    Figure US20100022538A1-20100128-C00786
         		A A A A clear yellow oil 307 305
    728
    Figure US20100022538A1-20100128-C00787
         		E E E E Brown liquid 228
    729
    Figure US20100022538A1-20100128-C00788
         		B B B C light yellow solid 178-180 307
    730
    Figure US20100022538A1-20100128-C00789
         		A A A A clear yellow oil 279
    731
    Figure US20100022538A1-20100128-C00790
         		D D D D white solid 84-85 200 198
    732
    Figure US20100022538A1-20100128-C00791
         		B A A A pale amber oil 362
    733
    Figure US20100022538A1-20100128-C00792
         		A A A A white solid 96-98 234 232
    734
    Figure US20100022538A1-20100128-C00793
         		A A A A White Solid 110-111 250 248
    735
    Figure US20100022538A1-20100128-C00794
         		A A A A white solid 278
    736
    Figure US20100022538A1-20100128-C00795
         		D D D D white solid 370 368
    737
    Figure US20100022538A1-20100128-C00796
         		D D D D YELLOW SOLID 361
    738
    Figure US20100022538A1-20100128-C00797
         		E E E E Pale yellow solid 334
    739
    Figure US20100022538A1-20100128-C00798
         		A A A A white solid 87-88 295 293
    740
    Figure US20100022538A1-20100128-C00799
         		E E D D yellow oil 242 240
    741
    Figure US20100022538A1-20100128-C00800
         		A A C A clear colorless oil 280 278
    742
    Figure US20100022538A1-20100128-C00801
         		E E E E Pale yellow solid 284 [M + Na]
    743
    Figure US20100022538A1-20100128-C00802
         		A A A A yellow solid 93 320
    744
    Figure US20100022538A1-20100128-C00803
         		A A A A tan oil 335
    745
    Figure US20100022538A1-20100128-C00804
         		A A A A WHITE SOLID 158-160 224
    746
    Figure US20100022538A1-20100128-C00805
         		D A D D orange solid 106-108 168 166
    747
    Figure US20100022538A1-20100128-C00806
         		B A D A tan oil — 196
    748
    Figure US20100022538A1-20100128-C00807
         		E E D D white solid 112-113 250 248
    749
    Figure US20100022538A1-20100128-C00808
         		A A A A 324 322
    750
    Figure US20100022538A1-20100128-C00809
         		C B C A 328
    751
    Figure US20100022538A1-20100128-C00810
         		C A B A pale amber oil 319
    752
    Figure US20100022538A1-20100128-C00811
         		A A A A colorless oil 308 306
    753
    Figure US20100022538A1-20100128-C00812
         		A A A A clear pale yellow oil 278 276
    754
    Figure US20100022538A1-20100128-C00813
         		D C D D colorless oil 336 333
    755
    Figure US20100022538A1-20100128-C00814
         		D D C C pale yellow oil 331
    756
    Figure US20100022538A1-20100128-C00815
         		C D D D white solid 199-200 348 346
    757
    Figure US20100022538A1-20100128-C00816
         		A A A A light yellow needles 127-129 299 297
    758
    Figure US20100022538A1-20100128-C00817
         		C B C A yellow solid 163-170 459 457
    759
    Figure US20100022538A1-20100128-C00818
         		C A B A yellow oil 330 328
    760
    Figure US20100022538A1-20100128-C00819
         		E E E E Off white solid 356
    761
    Figure US20100022538A1-20100128-C00820
         		E E E E Brown liquid 306
    762
    Figure US20100022538A1-20100128-C00821
         		A A A A white solid 61-62 352 350
    763
    Figure US20100022538A1-20100128-C00822
         		A A A A off-white solid 221
    764
    Figure US20100022538A1-20100128-C00823
         		D D D D white solid 145-146 278 276
    765
    Figure US20100022538A1-20100128-C00824
         		D D D C white solid 44-49 335 333
    766
    Figure US20100022538A1-20100128-C00825
         		D C D B dark brown solid 132-140 325 323
    767
    Figure US20100022538A1-20100128-C00826
         		A A A A white solid 110 (dec) 319
    768
    Figure US20100022538A1-20100128-C00827
         		D C D C white solid 183-184 249 247
    769
    Figure US20100022538A1-20100128-C00828
         		D A B A off-white solid 150-152 421 419
    770
    Figure US20100022538A1-20100128-C00829
         		A A A A yellow oil 306
    771
    Figure US20100022538A1-20100128-C00830
         		A A A A 386 384
    772
    Figure US20100022538A1-20100128-C00831
         		A A A A yellow solid 180-181 255
    773
    Figure US20100022538A1-20100128-C00832
         		D D C A white solid 132-134 368 366
    774
    Figure US20100022538A1-20100128-C00833
         		D D D D LIGHT YELLOW SOLID 339
    775
    Figure US20100022538A1-20100128-C00834
         		D D D D white solid 77-80 310 307
    776
    Figure US20100022538A1-20100128-C00835
         		D D D D white solid 157-158 311 309
    777
    Figure US20100022538A1-20100128-C00836
         		D C D D white solid 404 402
    778
    Figure US20100022538A1-20100128-C00837
         		A A A A white solid 146-147 387 385
    779
    Figure US20100022538A1-20100128-C00838
         		A A A A white solid 118-120 201
    780
    Figure US20100022538A1-20100128-C00839
         		A A A A white solid 107-108 268 266
    781
    Figure US20100022538A1-20100128-C00840
         		D C D B light yellow solid 160-162 398 396
    782
    Figure US20100022538A1-20100128-C00841
         		C A D C 375 373
    783
    Figure US20100022538A1-20100128-C00842
         		A A A A off-white solid 51-54 278 276
    784
    Figure US20100022538A1-20100128-C00843
         		D D D D white solid 112-115 250
    785
    Figure US20100022538A1-20100128-C00844
         		A A A A white solid 163-164 340
    786
    Figure US20100022538A1-20100128-C00845
         		E E E E Pale yellow semi solid 370
    787
    Figure US20100022538A1-20100128-C00846
         		A A A A white solid 171 286 284
    788
    Figure US20100022538A1-20100128-C00847
         		A A A A white solid 59-60 285
    789
    Figure US20100022538A1-20100128-C00848
         		A A A A white solid 134-141 353
    790
    Figure US20100022538A1-20100128-C00849
         		A A A A clear oil 304
    791
    Figure US20100022538A1-20100128-C00850
         		E E E E clear oil 365
    792
    Figure US20100022538A1-20100128-C00851
         		C B A A white solid 123-125 338 336
    793
    Figure US20100022538A1-20100128-C00852
         		D D D D off white solid 158-166 323 321
    794
    Figure US20100022538A1-20100128-C00853
         		A A A A white solid 108 266
    795
    Figure US20100022538A1-20100128-C00854
         		A A A A white solild 124-125 335
    796
    Figure US20100022538A1-20100128-C00855
         		A A A A white solid 149 286 284
    797
    Figure US20100022538A1-20100128-C00856
         		C A B A off-white solid 167-168 417 415
    798
    Figure US20100022538A1-20100128-C00857
         		A A A A clear oil 358
    799
    Figure US20100022538A1-20100128-C00858
         		D D D D white solid 200-202 363 361
    800
    Figure US20100022538A1-20100128-C00859
         		A A A A tan solid 238
    801
    Figure US20100022538A1-20100128-C00860
         		E E E E Off white solid 338
    802
    Figure US20100022538A1-20100128-C00861
         		D D D D white solid 98-99 230 228
  • TABLE II
    1 DP Activity of Compounds on SEPTTR at 50 and 200 ppm
    SEPTTR SEPTTR Mass Mass
    1DP 1DP Phys. Spec. Spec.
    Cmpd Structure 50 ppm 200 ppm App. MP (ES+) (ES−) GCMS
    803
    Figure US20100022538A1-20100128-C00862
         		D B 320
    804
    Figure US20100022538A1-20100128-C00863
         		C B 360
    805
    Figure US20100022538A1-20100128-C00864
         		B A 342
    806
    Figure US20100022538A1-20100128-C00865
         		E A 384
    807
    Figure US20100022538A1-20100128-C00866
         		E A 294
    808
    Figure US20100022538A1-20100128-C00867
         		A A 350
    809
    Figure US20100022538A1-20100128-C00868
         		B A 346
    810
    Figure US20100022538A1-20100128-C00869
         		E A 350
    811
    Figure US20100022538A1-20100128-C00870
         		A A 412
    812
    Figure US20100022538A1-20100128-C00871
         		E A 290
    813
    Figure US20100022538A1-20100128-C00872
         		A A 412
    814
    Figure US20100022538A1-20100128-C00873
         		E A 384
    815
    Figure US20100022538A1-20100128-C00874
         		A A white solid 115- 118 354 352
    816
    Figure US20100022538A1-20100128-C00875
         		A A 378
    817
    Figure US20100022538A1-20100128-C00876
         		C A 318
    818
    Figure US20100022538A1-20100128-C00877
         		D D 317
    819
    Figure US20100022538A1-20100128-C00878
         		E A off white solid 328
    820
    Figure US20100022538A1-20100128-C00879
         		C A 362
    821
    Figure US20100022538A1-20100128-C00880
         		E A 290
    822
    Figure US20100022538A1-20100128-C00881
         		C A 332
    823
    Figure US20100022538A1-20100128-C00882
         		E A 290
    824
    Figure US20100022538A1-20100128-C00883
         		A A 346
    825
    Figure US20100022538A1-20100128-C00884
         		B A 364
    826
    Figure US20100022538A1-20100128-C00885
         		E A 328
    827
    Figure US20100022538A1-20100128-C00886
         		D C 314
    828
    Figure US20100022538A1-20100128-C00887
         		D D 304
    829
    Figure US20100022538A1-20100128-C00888
         		C A 428
    830
    Figure US20100022538A1-20100128-C00889
         		D D 308
    831
    Figure US20100022538A1-20100128-C00890
         		B A 322
    832
    Figure US20100022538A1-20100128-C00891
         		D D white solid 167- 169 238 236
    833
    Figure US20100022538A1-20100128-C00892
         		C B 318
    834
    Figure US20100022538A1-20100128-C00893
         		E A 296
    835
    Figure US20100022538A1-20100128-C00894
         		E A 384
    836
    Figure US20100022538A1-20100128-C00895
         		B A 304
    837
    Figure US20100022538A1-20100128-C00896
         		D D 316
    838
    Figure US20100022538A1-20100128-C00897
         		E A 384
    839
    Figure US20100022538A1-20100128-C00898
         		E A 360
    840
    Figure US20100022538A1-20100128-C00899
         		B A 362
    841
    Figure US20100022538A1-20100128-C00900
         		B A 346
    842
    Figure US20100022538A1-20100128-C00901
         		A A 388
    843
    Figure US20100022538A1-20100128-C00902
         		C A 330
    844
    Figure US20100022538A1-20100128-C00903
         		A A 357
    845
    Figure US20100022538A1-20100128-C00904
         		A A 296
    846
    Figure US20100022538A1-20100128-C00905
         		D C white solid 108- 110 226 224
    847
    Figure US20100022538A1-20100128-C00906
         		A E white solid 155- 157 288 286
    848
    Figure US20100022538A1-20100128-C00907
         		D D white solid 212 210
    849
    Figure US20100022538A1-20100128-C00908
         		A A 316
    850
    Figure US20100022538A1-20100128-C00909
         		D B yellow- white solid 189-191 144
    851
    Figure US20100022538A1-20100128-C00910
         		A A 380
    852
    Figure US20100022538A1-20100128-C00911
         		B A 278
    853
    Figure US20100022538A1-20100128-C00912
         		D D white solid 112-114 158
    854
    Figure US20100022538A1-20100128-C00913
         		B A 368
    855
    Figure US20100022538A1-20100128-C00914
         		E A 344
    856
    Figure US20100022538A1-20100128-C00915
         		E A off-white solid 221
    857
    Figure US20100022538A1-20100128-C00916
         		B A 397
    858
    Figure US20100022538A1-20100128-C00917
         		D C 335
    859
    Figure US20100022538A1-20100128-C00918
         		A A 344
    860
    Figure US20100022538A1-20100128-C00919
         		E A 400
    861
    Figure US20100022538A1-20100128-C00920
         		D C 316
    862
    Figure US20100022538A1-20100128-C00921
         		B A 338
    863
    Figure US20100022538A1-20100128-C00922
         		A A 398
    864
    Figure US20100022538A1-20100128-C00923
         		D C white solid 115- 117 212 210
    865
    Figure US20100022538A1-20100128-C00924
         		C A 358
    866
    Figure US20100022538A1-20100128-C00925
         		D A 266
    867
    Figure US20100022538A1-20100128-C00926
         		A A 334
    868
    Figure US20100022538A1-20100128-C00927
         		B A 414
    869
    Figure US20100022538A1-20100128-C00928
         		E A 346
    870
    Figure US20100022538A1-20100128-C00929
         		E A 330
    871
    Figure US20100022538A1-20100128-C00930
         		D C 338
    872
    Figure US20100022538A1-20100128-C00931
         		C B 316
    873
    Figure US20100022538A1-20100128-C00932
         		D D 335
    874
    Figure US20100022538A1-20100128-C00933
         		D D 351
    875
    Figure US20100022538A1-20100128-C00934
         		D A 316
    876
    Figure US20100022538A1-20100128-C00935
         		D D 249
    877
    Figure US20100022538A1-20100128-C00936
         		E A 330
    878
    Figure US20100022538A1-20100128-C00937
         		A A yellow gummy solid 312 310
    879
    Figure US20100022538A1-20100128-C00938
         		A A 380
    880
    Figure US20100022538A1-20100128-C00939
         		D C 359
    881
    Figure US20100022538A1-20100128-C00940
         		A A 274
    882
    Figure US20100022538A1-20100128-C00941
         		A A 372
    883
    Figure US20100022538A1-20100128-C00942
         		A A 398
    884
    Figure US20100022538A1-20100128-C00943
         		A A orange oil 350 348
    885
    Figure US20100022538A1-20100128-C00944
         		C B 334
    886
    Figure US20100022538A1-20100128-C00945
         		A A 360
    887
    Figure US20100022538A1-20100128-C00946
         		E A 294
    888
    Figure US20100022538A1-20100128-C00947
         		D B 329
    889
    Figure US20100022538A1-20100128-C00948
         		A A 397
    890
    Figure US20100022538A1-20100128-C00949
         		E A 352
    891
    Figure US20100022538A1-20100128-C00950
         		A A yellowish solid 221
    892
    Figure US20100022538A1-20100128-C00951
         		B A 358
    893
    Figure US20100022538A1-20100128-C00952
         		A A 362
    894
    Figure US20100022538A1-20100128-C00953
         		D D 320
    895
    Figure US20100022538A1-20100128-C00954
         		A A 294
    896
    Figure US20100022538A1-20100128-C00955
         		E A 384
    897
    Figure US20100022538A1-20100128-C00956
         		D B 308
    898
    Figure US20100022538A1-20100128-C00957
         		D D 250
    899
    Figure US20100022538A1-20100128-C00958
         		C A 306
    900
    Figure US20100022538A1-20100128-C00959
         		B A 344
    901
    Figure US20100022538A1-20100128-C00960
         		B A 363
    902
    Figure US20100022538A1-20100128-C00961
         		E A 317
    903
    Figure US20100022538A1-20100128-C00962
         		D A 336
    904
    Figure US20100022538A1-20100128-C00963
         		D C 368
    905
    Figure US20100022538A1-20100128-C00964
         		C B 336
    906
    Figure US20100022538A1-20100128-C00965
         		E A 346
    907
    Figure US20100022538A1-20100128-C00966
         		B A 398
    908
    Figure US20100022538A1-20100128-C00967
         		A A 358
    909
    Figure US20100022538A1-20100128-C00968
         		E A 328
    910
    Figure US20100022538A1-20100128-C00969
         		E A 334
    911
    Figure US20100022538A1-20100128-C00970
         		D D 358
    912
    Figure US20100022538A1-20100128-C00971
         		E A 350
    913
    Figure US20100022538A1-20100128-C00972
         		A A 329
    914
    Figure US20100022538A1-20100128-C00973
         		D A 314
    915
    Figure US20100022538A1-20100128-C00974
         		D D 337
    916
    Figure US20100022538A1-20100128-C00975
         		A A 340
    917
    Figure US20100022538A1-20100128-C00976
         		D B yellow white soild 54- 56 278 276
    918
    Figure US20100022538A1-20100128-C00977
         		A A 362
    919
    Figure US20100022538A1-20100128-C00978
         		E A 304
    920
    Figure US20100022538A1-20100128-C00979
         		A A 359
    921
    Figure US20100022538A1-20100128-C00980
         		A A 364
    922
    Figure US20100022538A1-20100128-C00981
         		B C 330
    923
    Figure US20100022538A1-20100128-C00982
         		E A 352
    924
    Figure US20100022538A1-20100128-C00983
         		A A 362
    925
    Figure US20100022538A1-20100128-C00984
         		D D 324
    926
    Figure US20100022538A1-20100128-C00985
         		A A 338
    927
    Figure US20100022538A1-20100128-C00986
         		B A 278
    928
    Figure US20100022538A1-20100128-C00987
         		A A 372
    929
    Figure US20100022538A1-20100128-C00988
         		B A 374
    930
    Figure US20100022538A1-20100128-C00989
         		D A 342
    931
    Figure US20100022538A1-20100128-C00990
         		E A 346
    932
    Figure US20100022538A1-20100128-C00991
         		A A white solid 49- 51 170 168
    933
    Figure US20100022538A1-20100128-C00992
         		C B white solid 145- 149 223
    934
    Figure US20100022538A1-20100128-C00993
         		D C 340
    935
    Figure US20100022538A1-20100128-C00994
         		C A 345
    936
    Figure US20100022538A1-20100128-C00995
         		A A white solid 88- 91 234 232
    937
    Figure US20100022538A1-20100128-C00996
         		A A 330
    938
    Figure US20100022538A1-20100128-C00997
         		E A 296
    939
    Figure US20100022538A1-20100128-C00998
         		D A off- white solid 225
    940
    Figure US20100022538A1-20100128-C00999
         		D D 274
    941
    Figure US20100022538A1-20100128-C01000
         		D D 282
    942
    Figure US20100022538A1-20100128-C01001
         		A A 414
    943
    Figure US20100022538A1-20100128-C01002
         		B A 398
    944
    Figure US20100022538A1-20100128-C01003
         		D D 280
    945
    Figure US20100022538A1-20100128-C01004
         		A A 350
    946
    Figure US20100022538A1-20100128-C01005
         		B A 334
    947
    Figure US20100022538A1-20100128-C01006
         		A A white soild 144- 146 330 328
    948
    Figure US20100022538A1-20100128-C01007
         		D D 342
    949
    Figure US20100022538A1-20100128-C01008
         		B A 330
    950
    Figure US20100022538A1-20100128-C01009
         		D D 346
    951
    Figure US20100022538A1-20100128-C01010
         		B A 342
    952
    Figure US20100022538A1-20100128-C01011
         		E C 261
    953
    Figure US20100022538A1-20100128-C01012
         		C A 412
  • TABLE III
    1DP Activity of Compounds on CERCBE, VENTIN, and MYCOFI
    VENTIN VENTIN MYCOFI MYCOFI
    CERCBE 1DP CERCBE 1DP 1DP 1DP 1DP 1DP
    Cmpd # 25 ppm 75 ppm 25 ppm 75 ppm 50 ppm 200 ppm
    1 C C A A C B
    3 E E D A E E
    4 A A A A E E
    5 E E A A E E
    7 B B A A E E
    9 D D A C E E
    10 D D B A E E
    11 D D A A E E
    14 D D A A E E
    15 E E A A E E
    20 E E B A E E
    23 D B B A E E
    24 D D C A E E
    35 E E A A E E
    36 B B B A E E
    46 E E A A E E
    61 D D A B E E
    68 B B B A E E
    69 D C B A E E
    79 D C C C E E
    121 D D A C E E
    122 C C A A E E
    125 C C C A E E
    135 C C B B E E
    137 D D D A E E
    141 D D D C E E
    155 D D C D E E
    158 D D B B E E
    163 D D D C E E
    164 D D C B E E
    169 D D B C E E
    180 D C C D E E
    187 D C B C E E
    189 C D B B E E
    190 C C C C E E
    207 D D D C E E
    209 E E B A E E
    211 D D C B E E
    214 B B A A E E
    221 C B D C E E
    226 D C C A E E
    233 D D D B E E
    236 E E A A E E
    248 D D D B E E
    251 D B A A E E
    260 A B A A E E
    270 C C D C E E
    271 C C C B E E
    288 D C B C E E
    311 C C C C E E
    313 E E C B E E
    316 B A A A E E
    335 C A A A E E
    337 B A B A E E
    341 D D C D E E
    342 C A A A E E
    343 A A A B E E
    345 E E B A E E
    347 E E A C E E
    352 D D D C E E
    353 C C C A E E
    356 B D B C E E
    370 C C C C E E
    373 D D D C E E
    384 D D B D E E
    410 C C C B E E
    411 C C B B E E
    418 D D B B E E
    436 B C A A E E
    452 D D D C E E
    469 E E B A E E
    481 C A A A E E
    483 D D C A E E
    488 D D C C E E
    510 E E A A E E
    524 D D B B E E
    538 D D C B E E
    554 D B A A E E
    560 D C D A E E
    569 C A A A E E
    570 D C C A E E
    582 B B A A E E
    584 C C C C E E
    593 C B A A E E
    626 D D C A E E
    630 D D B A E E
    631 D D D C E E
    635 C C C A E E
    649 D D C C E E
    651 C C D D E E
    687 D D C B E E
    694 C C C B E E
    707 B C B B E E
    710 D D C C E E
    719 D C B B E E
    720 D B B A E E
    730 C C B B E E
    732 C A C A E E
    734 E E A A E E
    739 D D C B E E
    741 D D B A E E
    764 C D C C E E
    800 A A A A E E
    804 D D D D E E
    845 D D C C E E
    849 C C A B E E
    858 C C C D E E
    860 D C C B E E
    894 D D D C E E
    933 C C D C E E
    941 D D B C E E
    952 D D D D E E
  • TABLE IV
    Three day curative (3DC) and one day protectant (1DP) Activity of
    Compounds on SEPTTR at 25 and 100 ppm
    SEPTTR SEPTTR SETTTR SETTTR Mass Mass
    Cmpd 3DC 3DC 1DP 1DP Spec. Spec.
    # MOLSTRUCTURE 25 ppm 100 ppm 25 ppm 25 ppm Appearance MP (ES+) (ES−) GCMS
    954
    Figure US20100022538A1-20100128-C01013
         		C B C C white solid 247-250 276.96
    955
    Figure US20100022538A1-20100128-C01014
         		D D D D white solid 120-122 386.3
    956
    Figure US20100022538A1-20100128-C01015
         		D D D D off white solid 221-223 267.9
    957
    Figure US20100022538A1-20100128-C01016
         		C C D D White Solid 175-178 235 [M + 2] 232
    958
    Figure US20100022538A1-20100128-C01017
         		C C D D red crystalline solid 123-125 377
    959
    Figure US20100022538A1-20100128-C01018
         		D D D D pale yellow solid 181-185 303 301
    960
    Figure US20100022538A1-20100128-C01019
         		D D D D yellow solid 202-208 263 261
    961
    Figure US20100022538A1-20100128-C01020
         		A A A A white solid 153-157 248 246
    962
    Figure US20100022538A1-20100128-C01021
         		A A A A white solid 101-104 256 254
    963
    Figure US20100022538A1-20100128-C01022
         		C D D D Pale brown solid 150-152 dec. 245
    964
    Figure US20100022538A1-20100128-C01023
         		D C D D Off white solid 150-152 dec. 278
    965
    Figure US20100022538A1-20100128-C01024
         		C C C A tan solid 236-238 269 267
    966
    Figure US20100022538A1-20100128-C01025
         		B B C B white solid 249-251 280.88
    967
    Figure US20100022538A1-20100128-C01026
         		B B C C white solid 255-257 246.93
    968
    Figure US20100022538A1-20100128-C01027
         		B B B B white solid 255-257 260.93
    969
    Figure US20100022538A1-20100128-C01028
         		C B C C white solid 244-246 260.93
    970
    Figure US20100022538A1-20100128-C01029
         		C C C B white solid 257-259 278.91
    971
    Figure US20100022538A1-20100128-C01030
         		B A C C white solid 289-293 213
    972
    Figure US20100022538A1-20100128-C01031
         		B B B A white solid 255-260 242.2
    973
    Figure US20100022538A1-20100128-C01032
         		A B C C white solid 290-295 240.34
    974
    Figure US20100022538A1-20100128-C01033
         		B C B A white solid 218-220 260 258
    975
    Figure US20100022538A1-20100128-C01034
         		D D D D white solid 270-280 228.2
    976
    Figure US20100022538A1-20100128-C01035
         		D D D D white solid 218-222 256.9
    977
    Figure US20100022538A1-20100128-C01036
         		D A D B off white solid 234-235 252 250
    978
    Figure US20100022538A1-20100128-C01037
         		D D D D white solid 244-245 272 270
    979
    Figure US20100022538A1-20100128-C01038
         		D B D C white solid 243-234 240 238
    980
    Figure US20100022538A1-20100128-C01039
         		D D D D white solid 230-240 213
    981
    Figure US20100022538A1-20100128-C01040
         		D D D D white solid 224-230 250.89
    982
    Figure US20100022538A1-20100128-C01041
         		A A A A Off white solid 60.4-63 332
    983
    Figure US20100022538A1-20100128-C01042
         		A A A A Pale yellow solid 83.3-85.8 302
    984
    Figure US20100022538A1-20100128-C01043
         		A A A A Off white solid 63.2-65.5 350
    985
    Figure US20100022538A1-20100128-C01044
         		A A A A Off white solid 60.8-62.9 320
    986
    Figure US20100022538A1-20100128-C01045
         		A A A A Off white solid 62.3-65.9 346
    987
    Figure US20100022538A1-20100128-C01046
         		A A A A Off white solid 88.2-89.2 316
    988
    Figure US20100022538A1-20100128-C01047
         		A A A A Pale yellow liquid NA 362
    989
    Figure US20100022538A1-20100128-C01048
         		B A A A Pale yellow liquid NA 334
    990
    Figure US20100022538A1-20100128-C01049
         		D D D D colorless oil 438
    991
    Figure US20100022538A1-20100128-C01050
         		D D D D red oil 309
    992
    Figure US20100022538A1-20100128-C01051
         		D C D D red oil 323
    993
    Figure US20100022538A1-20100128-C01052
         		D B D C red solid 95-98 310
    994
    Figure US20100022538A1-20100128-C01053
         		D D D C white solid 155-157 372.2
    995
    Figure US20100022538A1-20100128-C01054
         		D D D C red solid 104-108 353 351
    996
    Figure US20100022538A1-20100128-C01055
         		C B C B brown semi- solid 354 353
    997
    Figure US20100022538A1-20100128-C01056
         		A A A A white solid 151-152 185
    998
    Figure US20100022538A1-20100128-C01057
         		A A A A yellow solid 160-161 237 235
    999
    Figure US20100022538A1-20100128-C01058
         		A A A A tan solid 168-169 275
    1000
    Figure US20100022538A1-20100128-C01059
         		A A A A tan solid 183-184 279
    1001
    Figure US20100022538A1-20100128-C01060
         		C A C A tan solid 181-182 347 345
    1002
    Figure US20100022538A1-20100128-C01061
         		C B B A tan solid 185-186 354 352
    1003
    Figure US20100022538A1-20100128-C01062
         		D B D D off-white solid 134-137 313.87
    1004
    Figure US20100022538A1-20100128-C01063
         		D C D D white solid 152-155 341.94
    1005
    Figure US20100022538A1-20100128-C01064
         		D D D D white solid 147-150 375.96
    1006
    Figure US20100022538A1-20100128-C01065
         		D D D D white solid 129-131 324.2
    1007
    Figure US20100022538A1-20100128-C01066
         		D D D D white solid 150-153 336.2
    1008
    Figure US20100022538A1-20100128-C01067
         		D D D D white solid 134-136 295.9
    1009
    Figure US20100022538A1-20100128-C01068
         		D D D D white solid 139-142 323.92
    1010
    Figure US20100022538A1-20100128-C01069
         		D D D D white solid 150-153 357.93
    1011
    Figure US20100022538A1-20100128-C01070
         		D D D D white solid 117-119 325.92
    1012
    Figure US20100022538A1-20100128-C01071
         		D D D D white solid 120-122 353.97
    1013
    Figure US20100022538A1-20100128-C01072
         		D D D D white solid 129-131 387.93
    1014
    Figure US20100022538A1-20100128-C01073
         		D A D D red solid 114-118 361
    1015
    Figure US20100022538A1-20100128-C01074
         		C A D D white solid 141-144 473.92
    1016
    Figure US20100022538A1-20100128-C01075
         		B B D D off-white solid 158-160 (dec) 436.88
    1017
    Figure US20100022538A1-20100128-C01076
         		D B D C pale yellow solid 109-115 289
    1018
    Figure US20100022538A1-20100128-C01077
         		D D D D off white solid 88-92 240 239
    1019
    Figure US20100022538A1-20100128-C01078
         		D D C C yellow solid 161-165 299
    1020
    Figure US20100022538A1-20100128-C01079
         		C D D D off white solid 173-177 263
    1021
    Figure US20100022538A1-20100128-C01080
         		C C D C white solid 132-135 241 239
    1022
    Figure US20100022538A1-20100128-C01081
         		D C D D pale yellow solid 129-134 210 209
    1023
    Figure US20100022538A1-20100128-C01082
         		D D D D yellow solid 196-202 236 235
    1024
    Figure US20100022538A1-20100128-C01083
         		D D D D yellow solid 220-226 235 251
    1025
    Figure US20100022538A1-20100128-C01084
         		C D D D yellow solid 104-108 294
    1026
    Figure US20100022538A1-20100128-C01085
         		D D D D yellow solid 110-114 279 277
    1027
    Figure US20100022538A1-20100128-C01086
         		D C C C white solid 162-166 456.1
    1028
    Figure US20100022538A1-20100128-C01087
         		D D D D brown solid 115-119 329 327
    1029
    Figure US20100022538A1-20100128-C01088
         		D D D D brown oil 379 377
    1030
    Figure US20100022538A1-20100128-C01089
         		D D D D brown solid 143-147 403 403
    1031
    Figure US20100022538A1-20100128-C01090
         		D D D D brown solid 126-130 253 251
    1032
    Figure US20100022538A1-20100128-C01091
         		D D C C white solid 165-170 371 369
    1033
    Figure US20100022538A1-20100128-C01092
         		D C D D off white solid 151-155 224 223
    1034
    Figure US20100022538A1-20100128-C01093
         		D D D D of white solid 136-139 267
    1035
    Figure US20100022538A1-20100128-C01094
         		D D D D brown solid 122-127 391 389
    1036
    Figure US20100022538A1-20100128-C01095
         		D D D D brown oil 339 337
    1037
    Figure US20100022538A1-20100128-C01096
         		D D D C brown oil 379
    1038
    Figure US20100022538A1-20100128-C01097
         		D D D D brown solid 105-109 381 379
    1039
    Figure US20100022538A1-20100128-C01098
         		D D D D red solid 119-124 343 341
    1040
    Figure US20100022538A1-20100128-C01099
         		D D D D brown oil solid 361 359
    1041
    Figure US20100022538A1-20100128-C01100
         		D D D D dark red 102-108 394 393
    1042
    Figure US20100022538A1-20100128-C01101
         		D C D D red solid 112-118 347 345
    1043
    Figure US20100022538A1-20100128-C01102
         		D D D D brown solid 110-116 400 397
    1044
    Figure US20100022538A1-20100128-C01103
         		D D D D brown oil 386 384
    1045
    Figure US20100022538A1-20100128-C01104
         		D D D D red solid 140-143 412 409
    1046
    Figure US20100022538A1-20100128-C01105
         		D D D D purple oil 398 396
    1047
    Figure US20100022538A1-20100128-C01106
         		C C D D brown solid 194-197 348 346
    1048
    Figure US20100022538A1-20100128-C01107
         		D D D D red semi- solid 269
    1049
    Figure US20100022538A1-20100128-C01108
         		C C D D red oil 305 303
    1050
    Figure US20100022538A1-20100128-C01109
         		D C D D red solid 71-76 236 234
    1051
    Figure US20100022538A1-20100128-C01110
         		C D D D yellow solid 197-201 287 285
    1052
    Figure US20100022538A1-20100128-C01111
         		D D D D off white solid 120-123 264 263
    1053
    Figure US20100022538A1-20100128-C01112
         		D D D D white semi- solid 239 238
    1054
    Figure US20100022538A1-20100128-C01113
         		D D D D yellow oil 283
    1055
    Figure US20100022538A1-20100128-C01114
         		D D D D off white solid 136-139 305
    1056
    Figure US20100022538A1-20100128-C01115
         		C C D D pale yellow oil 187
    1057
    Figure US20100022538A1-20100128-C01116
         		D D D D white solid 152-155 215 213
    1058
    Figure US20100022538A1-20100128-C01117
         		D D D D white solid 80-85 174 172
    1059
    Figure US20100022538A1-20100128-C01118
         		D C D D colored solid 115-120 185 183
    1060
    Figure US20100022538A1-20100128-C01119
         		D D D D yellow solid 83-88 304 303
    1061
    Figure US20100022538A1-20100128-C01120
         		D D C D yellow solid 118-123 327 325
    1062
    Figure US20100022538A1-20100128-C01121
         		D D D D yellow solid 104-107 237 235
    1063
    Figure US20100022538A1-20100128-C01122
         		D D D D brown solid 102-107 251 249
    1064
    Figure US20100022538A1-20100128-C01123
         		D D D D brown solid 179-182 262 261
    1065
    Figure US20100022538A1-20100128-C01124
         		D D D D pale brown 250
    1066
    Figure US20100022538A1-20100128-C01125
         		D D D D pale yellow oil 174 172
    1067
    Figure US20100022538A1-20100128-C01126
         		D D D D pale yellow oil 201 200
    1068
    Figure US20100022538A1-20100128-C01127
         		D D D D White Solid 218-222 269 [M + 2] 266
    1069
    Figure US20100022538A1-20100128-C01128
         		B B D D White Solid 200-203 249 [M + 2] 246
    1070
    Figure US20100022538A1-20100128-C01129
         		D D C D White Solid 206-209 264 262
    1071
    Figure US20100022538A1-20100128-C01130
         		C C D C White Solid 258-261 (dec) 303 [M + 2] 300
    1072
    Figure US20100022538A1-20100128-C01131
         		D D D D off white solid 64-67 214 212
    1073
    Figure US20100022538A1-20100128-C01132
         		D D C D peach colored solid 146-150 295 293
    1074
    Figure US20100022538A1-20100128-C01133
         		D C D D brown solid 151-155 289 287
    1075
    Figure US20100022538A1-20100128-C01134
         		D D D D brown oil 299 298
    1076
    Figure US20100022538A1-20100128-C01135
         		D C D D beige solid 110 279 278
    1077
    Figure US20100022538A1-20100128-C01136
         		D C D D brown solid 86-89 278 277
    1078
    Figure US20100022538A1-20100128-C01137
         		C D D D brown solid 130-133 341 339
    1079
    Figure US20100022538A1-20100128-C01138
         		D D D D yellow oil 275 272
    1080
    Figure US20100022538A1-20100128-C01139
         		C C D D pale yellow solid 79-83 248
    1081
    Figure US20100022538A1-20100128-C01140
         		D D D D off white solid 70-75 277
    1082
    Figure US20100022538A1-20100128-C01141
         		D D D D white gum   250.1 248.1
    1083
    Figure US20100022538A1-20100128-C01142
         		A A A A white solid 71-3  257
    1084
    Figure US20100022538A1-20100128-C01143
         		A A A A white solid 62-4  311
    1085
    Figure US20100022538A1-20100128-C01144
         		A A A A white solid 110-2  319
    1086
    Figure US20100022538A1-20100128-C01145
         		D D D D brown oil 280 278
    1087
    Figure US20100022538A1-20100128-C01146
         		D D D D tacky brown solid 276 274
    1088
    Figure US20100022538A1-20100128-C01147
         		D D D C yellow oil 276 274
    1089
    Figure US20100022538A1-20100128-C01148
         		C C D D red solid 114-118 351
    1090
    Figure US20100022538A1-20100128-C01149
         		C C D D red solid 84-89 395
    1091
    Figure US20100022538A1-20100128-C01150
         		C C D D brown solid 72-75 265 263
    1092
    Figure US20100022538A1-20100128-C01151
         		D C D C off white solid 201-206 201 199
    1093
    Figure US20100022538A1-20100128-C01152
         		D D D D brown oil 235 233
    1094
    Figure US20100022538A1-20100128-C01153
         		C C D D brown solid 164-169 236 234
    1095
    Figure US20100022538A1-20100128-C01154
         		D D D D off white solid 146-150 236 234
    1096
    Figure US20100022538A1-20100128-C01155
         		D A D D off white solid 180-190 174 172
    1097
    Figure US20100022538A1-20100128-C01156
         		D C D D dark red solid 110-113 301
    1098
    Figure US20100022538A1-20100128-C01157
         		D D D D grey solid 209-213 255 253
    1099
    Figure US20100022538A1-20100128-C01158
         		D D D D red oil 277
    1100
    Figure US20100022538A1-20100128-C01159
         		C C D D red solid 68-71 339 337
    1101
    Figure US20100022538A1-20100128-C01160
         		D D D D white solid 215-217 205.97
    1102
    Figure US20100022538A1-20100128-C01161
         		C C D D white solid 216-218 297.88
    1103
    Figure US20100022538A1-20100128-C01162
         		D D D D white solid 236-239 301.85
    1104
    Figure US20100022538A1-20100128-C01163
         		D D D D off white solid 203-205 231.91
    1105
    Figure US20100022538A1-20100128-C01164
         		D D D D white solid 157-159 219.96
    1106
    Figure US20100022538A1-20100128-C01165
         		D D D D off-white solid 209-211 369.89
    1107
    Figure US20100022538A1-20100128-C01166
         		D D D D light tan solid 124-128 (dec) 363.95
    1108
    Figure US20100022538A1-20100128-C01167
         		D D D D brown solid 248-251 327 323
    1109
    Figure US20100022538A1-20100128-C01168
         		D D D D red solid 35-37 287
    1110
    Figure US20100022538A1-20100128-C01169
         		D D D D red solid 92-95 267 267
    1111
    Figure US20100022538A1-20100128-C01170
         		D D D D yellow solid 242-246 267 265
    1112
    Figure US20100022538A1-20100128-C01171
         		D C D D brown solid 216-218 223 221
    1113
    Figure US20100022538A1-20100128-C01172
         		A A A A white solid 116-121 270
    1114
    Figure US20100022538A1-20100128-C01173
         		C A D D light yellow solid 173-175 239 237
    1115
    Figure US20100022538A1-20100128-C01174
         		C A C A grey solid   188.1 186.2
    1116
    Figure US20100022538A1-20100128-C01175
         		E E E E White solid   292.64
    1117
    Figure US20100022538A1-20100128-C01176
         		E E E E White solid   277.57
    1118
    Figure US20100022538A1-20100128-C01177
         		D D D D yellow solid 235-237 267 265
    1119
    Figure US20100022538A1-20100128-C01178
         		A A A A white solid 106-110 244 242
    1120
    Figure US20100022538A1-20100128-C01179
         		D D D D off white solid 158-160 277 275
    1121
    Figure US20100022538A1-20100128-C01180
         		D D D D white solid 209-212 297 295
    1122
    Figure US20100022538A1-20100128-C01181
         		D D D D white solid 194-197 379 377
    1123
    Figure US20100022538A1-20100128-C01182
         		D D D D brown solid 143-146 267 265
    1124
    Figure US20100022538A1-20100128-C01183
         		D D D D off white solid 164-171 290 288
    1125
    Figure US20100022538A1-20100128-C01184
         		A A A A white solid 138-141 252 228
    1126
    Figure US20100022538A1-20100128-C01185
         		A A A A white solid 76-79 306 282
    1127
    Figure US20100022538A1-20100128-C01186
         		A A A A white solid 83-87 267 183
    1128
    Figure US20100022538A1-20100128-C01187
         		D D D D off white solid 131-135 435 433
    1129
    Figure US20100022538A1-20100128-C01188
         		D D D D white solid 83-89 269 267
    1130
    Figure US20100022538A1-20100128-C01189
         		C D D D Pale brown solid 119-122 dec. 259
    1131
    Figure US20100022538A1-20100128-C01190
         		A A A A Pale yellow solid 190-191 213 211
    1132
    Figure US20100022538A1-20100128-C01191
         		A A B B white solid 220-230 284 282
  • TABLE V
    Percent SEPTTR control delivered by compound 15 (Table1) treated
    Yuma seeds
    Rate g/
    100 kg Pot %
    seeds Pot 1 Pot 2 3 Pot 4 Pot 5 Pot 6 Pot 7 Pot 8 Control
    120 0 0 0 0 0 0 0 0 A
    40 0 1 1 1 0 0 0 0 A
    13.3 0 1 0 1 1 1 0 0 A
    4.44 0 0 1 1 0 1 0 0 A
    1.48 3 3 1 1 0 3 0 0 A
    0 100 100 95 100 100 95 100 95 0

Claims (5)

1. A compound of formula I
Figure US20100022538A1-20100128-C01192
wherein R1 is —N(R3)R4;
R2 is —OR21;
R3 is:
H;
C1-C6 alkyl optionally substituted with 1- to 3 R5;
C2-C6 alkenyl optionally substituted with 1-3 R5;
a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, each heteroaromatic ring being optionally substituted with 1-3 R30;
imidazole fused with an aromatic or heteroaromatic ring selected from the group consisting of benzene, oxazole, isoxazole, furan, thiazole, pyrimidine, pyridine, pyrrole, pyrazine, thiophene, each aromatic or heteroaromatic ring being optionally substituted with 1 to 3 R30;
benzo[1,3]dioxolyl;
3H-isobenzofuran-1-onyl;
cyano;
C3-C6 alkynyl optionally substituted with 1-3 R5;
—C(═O)R6;
—C(═O)OCH2C(═O)R8;
—C(═S)R6;
—C(═S)NHR8;
—C(═O)N(R8)R10;
—OR7;
—P(O)(OR15)2;
—S(O)2R8;
—SR8;
—Si(R8)3;
—N(R9)R10;
—N═C(R15)R16;
—(CHR22)R37;
—(CHR24)OR29; or
—C(═NR16)SR16; or
—C(═NR27)NR13R28;
wherein m is an integer from 1-3;
R4 is:
H;
hydroxyl;
amino;
C1-C6 alkyl, optionally substituted with 1-3 R5;
—C(═O)R6; or
—C(═O)N(R8)R10;
alternatively R3 and R4 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 R11;
═C(R12)N(R13)R14;
═C(R13)(R14);
═C(R15)OR15;
═S(R34)2; or
═NR35;
R5 is independently halogen, C1-C6 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, amino, C1-C3 alkylamino, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C2-C6 alkylaminocarbonyl, —OH, N-methyl piperazine or C3-C6 trialkylsilyl;
R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl optionally substituted with 1-3 R30, C1-C5 haloalkyl, C1-C5 alkoxy, C1-C5 haloalkoxy C2-C6 alkoxycarbonyl, C1-C4 alkoxyalkoxy, C2-C6 alkylaminocarbonyl; 1-benzo[1,2,3]thiadiazol-7-yl, thiazolyl, benzyl, phenyl, phenoxy, or benzyloxy wherein the thiazolyl, benzyl, phenyl, phenoxy, or benzyloxy may be optionally substituted with 1-3 R20, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R7 is H, C1-C6 alkyl, C2-C6 alkenyl, C1-C5 haloalkyl, benzyl which may be optionally substituted with 1-5 R20, —CHR18C(O)OR19, —(CHR27)R28, —Si(R8)3, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R8 is independently C1-C6 alkyl, C1-C6 haloalkyl, amino, C1-C6 alkylamino, C2-C6 dialkylamino, methylene-2-furanyl, —CHR15C(O)OR19, benzyl optionally substituted with 1-3 R30, phenyl optionally substituted with 1-3 R30, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R9 is H, C1-C6 alkyl C1-C6 haloalkyl, —C(═O)R17, benzothiazoyl, quinazolinyl, or phenyl optionally substituted with 1-3 R20, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R10 is H or C1-C6 alkyl, C1-C6 haloalkyl, or phenyl optionally substituted with 1-3 R20;
R11 is independently halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, amino, C1-C6 alkylamino, C2-C6 dialkylamino, C2-C6 alkoxycarbonyl, or C2-C6 alkylcarbonyl;
R12 is H or C1-C4 alkyl;
R13 and R14 are independently H, cyano, —OH, C1-C4 alkyl, C1-C6 alkoxy, C2-C6, alkylcarbonyl, phenyl, or benzyl wherein the phenyl or benzyl may be optionally substituted with 1-3 R20;
alternatively R13 and R14 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 R11, or 3,4-dihydro-1H-isoquinolin-2-yl;
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 R11;
R15 is H or C1-C6 alkyl, C2-C6 alkenyl, 2-benzofuranyl, or a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R16 is H, C1-C6 alkyl, or phenyl optionally substituted with 1-3 R20;
alternatively R15 and R16 may be taken together as —(CH2)4— or —(CH2)5—;
R17 is H, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 haloalkyl, C1-C6 alkoxy, benzyl, phenyl, phenoxy, or benzyloxy wherein each ring may be optionally substituted with 1-3 R20, a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R18 is H, C1-C6 alkyl, or C1-C6 haloalkyl;
R19 is H, C1-C6 alkyl, C1-C6 haloalkyl, or benzyl;
R20 is independently halogen, cyano, nitro, amino, C1-C6 alkoxyalkoxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyl, C3-C6 trialkylsilyl, 2-[(E)-methoxyimino]-N-methyl-acetamidyl, phenyl, benzyl, benzyloxy, phenoxy, or a 5- or 6-membered heteroaromatic ring wherein each phenyl, benzyl, benzyloxy, phenoxy, or 5- or 6-membered heteroaromatic ring may be optionally substituted with 1-3 substitutents independently selected from R31;
R1 is:
H;
C1-C14 alkyl;
C1-C6 haloalkyl;
C2-C4 alkenyl;
C2-C4 haloalkenyl;
C3-C4 alkynyl;
C3-C4 haloalkynyl;
phenyl, naphthyl, or tetrahydroquinolinyl each optionally substituted with 1-3 R20;
—(CHR22)mR23;
—(CHR24)mC(O)OR25;
—(CHR24)mC(O)R26;
—(CHR24)mC(O)N(R27)R28;
—(CHR24)mOR29;
—(CHR24)SR29;
—(CHR24)mN(R27)R28;
—C(═O)R32;
—N═C(R32)(R36);
—NR25C(═O)OR25;
—Si(R8)3;
—SO2R33;
C2-C6 alkoxy carbonyl;
C2-C6 alkylaminocarbonyl;
C2-C6 alkylcarbonyl;
sugars selected from the group consisting of beta-D-glucose-tetraacetate, rhamnose, fructose, and pentose; or
a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl or isoxazolyl wherein each 5- or 6-member heteroaromatic ring may be optionally substituted with 1-5 R20;
R22 is independently:
H;
halogen;
cyano;
nitro;
C1-C6 alkyl;
C1-C6 haloalkyl;
phenyl or benzyl optionally substituted with 1-3 R20;
C1-C6 hydroxyalkyl;
C2-C6 alkoxylalkyl;
C3-C6 haloalkynyl;
C2-C6 alkenyl;
C2-C6 haloalkenyl;
C3-C6 alkynyl;
C1-C6 alkoxy;
C1-C6 haloalkoxy;
C1-C6 alkylthio;
C1-C6 alkylamino;
C2-C8 dialkylamino;
C3-C6 cycloalkylamino;
C4-C6 (alkyl)cycloalkylamino;
C2-C6 alkylcarbonyl;
C2-C6 alkoxycarbonyl;
C2-C6 alkylaminocarbonyl;
C3-C8 dialkylaminocarbonyl;
C3-C6 trialkylsilyl;
ring-fused heteroaromatic rings selected from the group consisting of benzothiophenyl, quinolinyl, isoquinolinyl, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, and benzoimidazolyl, wherein each of the rings may be further substituted with 1-3 R20; or
a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl and thienyl;
R23 is:
H;
halogen;
C1-C6 alkyl;
C1-C6 haloalkyl;
C2-C6 dialkylamino;
phenyl optionally substituted with 1-5 R20;
ring-fused heteroaromatic rings selected from the group consisting of benzothiophenyl, quinolinyl, isoquinolinyl, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, benzofuranyl and benzoimidazolyl, 2,3-dihydro-benzofuran-2-yl, 4-methyl-4H-thieno[3,2-b]pyrrol-5-yl, 1-methyl-1H-indol-5-yl, imidazo[1,2-a]pyridin-2-yl, imidazo[2,1-b]thiazol-6-yl, benzothiazol-2-yl, benzo[b]thiophen-7-yl, and 1-methyl-1H-indazol-3-yl, wherein each of the rings may be further substituted with 1-3 R20;
naphthyl;
benzo[1,3]dioxolyl;
pyrrolidinonyl;
oxetanyl;
C1-C6 alkylthio optionally substituted with 1-5 R20;
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11; or
a 5- or 6-membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, imidazolyl, thiophene-2-yl and thiophen-3-yl wherein each heteroaromatic ring may be optionally substituted with 1-3 R20;
R24 is H, C1-C6 alkyl, C1-C6 alkoxy, benzyl, or phenyl wherein each of the benzyl or phenyl may be optionally substituted with 1-3 R20;
R25 is H, C1-C6 alkyl, phenyl or benzyl optionally substituted with 1-3 R20;
R26 is:
H;
C1-C6 alkyl;
C1-C6 alkoxy;
phenyl optionally substituted with 1-3 R20; or
a 5- or 6 membered heteroaromatic ring selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl and isoxazolyl;
R27 and R28 are independently:
H;
C1-C6 alkyl;
benzyl or phenyl wherein each of the benzyl or phenyl may be optionally substituted with 1-3 R20; or
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R29 is:
H;
C1-C6 alkyl;
C1-C6 haloalkyl;
C1-C6 alkoxyalkyl;
C2-C6 alkylcarbonyl;
benzyl, benzoyl, or phenyl wherein each of the benzyl, benzoyl, or phenyl may be optionally substituted with 1-3 R20; or
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R30 is independently halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl, thiazolyl, phenyl, pyrimidinyl, or pyridyl, wherein the thiazolyl, phenyl, pyridyl, or pyrimidinyl may be optionally substituted with 1-3 R20;
R31 is independently halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, or C3-C6 trialkylsilyl;
R32 is independently:
C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C3-C6 alkynyl, C3-C6 haloalkynyl, hydroxyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C3-C6 alkynyloxy, C3-C6 haloalkynyloxy, C1-C6 alkylthio, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C2-C6 alkenylthio, C2-C6 haloalkenylthio, C2-C6 haloalkenylsulfonyl, C3-C6 alkynylthio, C3-C6 alkynylsulfonyl, C3-C6 haloalkynylsulfonyl, C1-C6 alkylamino, C2-C8 dialkylamino, C3-C8 dialkylaminocarbonyl, C3-C6 trialkylsilyl;
phenyl wherein the phenyl ring may be optionally substituted with 1-3 R20; or
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R33 is independently:
C1-C6 alkyl, C1-C6 haloalkyl, phenyl or thienyl optionally substituted with 1-3 R20; or
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R34 is:
C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkoxyalkyl, C1-C6 alkylamino; or
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R35 is:
C1-C6 alkyl, C2-C6 alkylcarbonyl; or
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11;
R36 is H, cyano, C1-C6 alkyl, C1-C6 alkoxy, benzyl, or phenyl wherein each of the benzyl, or phenyl may be optionally substituted with 1-3 R20;
alternatively R32 and R36 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 R11; and
R37 is independently:
H, halogen, or phenyl optionally substituted with 1-5 R20;
C1-C6 alkyl, C1-C6 haloalkyl, hydroxyl, C1-C6 alkoxy, or C1-C6 haloalkoxy; or
a 5- or 6-membered saturated or unsaturated ring containing 1-3 heteroatoms wherein each ring may be optionally substituted with 1-3 R11.
2. A composition for the control of a fungal pathogen including the compound of claim 1 and a phytologically acceptable carrier material.
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 Spot of peanut (Cercospora arachidicola), and Black Sigatoka (Mycosphaerella fijiensis).
4. A method for the control and prevention 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.
5. The method of claim 4 wherein the fungal attach is caused by Leaf Blotch of Wheat (Septoria tritici).
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Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090203647A1 (en) * 2008-01-22 2009-08-13 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
US20100298336A1 (en) * 2009-05-21 2010-11-25 Giorgio Attardo Pyrimidines as novel therapeutic agents
US20110034493A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-sulfonyl-5-fluoropyrimidinone derivatives
US20110034492A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-substituted-5-fluoro-2-oxopyrimidinone-1(2h)-carboxamide derivatives
US20110034490A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-acyl-5-fluoropyrimidinone derivatives
US20110053891A1 (en) * 2009-08-07 2011-03-03 Dow Agrosciences Llc 5-fluoropyrimidinone derivatives
US20110166164A1 (en) * 2010-01-07 2011-07-07 Dow Agrosciences Llc THIAZOLO[5,4-d] PYRIMIDINES AND THEIR USE AS AGROCHEMICALS
US20110263627A1 (en) * 2010-04-26 2011-10-27 Dow Agrosciences Llc N3-substituted-n1-sulfonyl-5-fluoropyrimidinone derivatives
US20130045985A1 (en) * 2011-08-17 2013-02-21 Dow Agrosciences Llc N-(5-fluoro-2-((4-methylbenzyl)oxy)pyrimidin-4-yl)benzamide derivatives
WO2013113781A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds i
WO2013113791A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113716A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113776A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113773A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113719A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds ii
WO2013113782A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113715A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113863A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013135672A1 (en) 2012-03-13 2013-09-19 Basf Se Fungicidal pyrimidine compounds
WO2013135671A1 (en) 2012-03-13 2013-09-19 Basf Se Fungicidal pyrimidine compounds
US8658660B2 (en) 2011-08-17 2014-02-25 Dow Agrosciences, Llc. 5-fluoro-4-imino-3,4-dihydropyrimidin-2-(1H)-ones derivatives
WO2014118099A1 (en) 2013-01-30 2014-08-07 Basf Se Fungicidal naphthoquinones and derivatives
US20150141446A1 (en) * 2012-11-12 2015-05-21 Dow Agrosciences, Llc Pesticidal pyrimidine compounds
WO2015089003A1 (en) * 2013-12-10 2015-06-18 E. I. Du Pont De Nemours And Company Herbicidal substituted pyrimidinyloxy benzene compounds
US9073875B2 (en) 2012-11-20 2015-07-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of indoleamine 2,3-dioxygenase
US9271497B2 (en) 2012-12-28 2016-03-01 Dow Agrosciences Llc 1-(substituted-benzoyl)-5-fluoro-4-imino-3-methyl-3,4-dihydropyrimidin-2(1H)-one derivatives
US9321734B2 (en) 2012-12-28 2016-04-26 Dow Agrosciences Llc N-(substituted)-5-fluoro-4-imino-3-methyl-2-oxo-3,4-dihydropyrimidine-1(2H)-carboxamide derivatives
US9526245B2 (en) 2013-12-31 2016-12-27 Adama Makhteshim Ltd. Synergistic fungicidal mixtures comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control in cereals
US9622474B2 (en) 2012-12-28 2017-04-18 Adama Makhteshim Ltd. N-(substituted)-5-fluoro-4-imino-3-methyl-2-oxo-3,4-dihydropyrimidine-1(2H)-carboxylate derivatives
US20170121326A1 (en) * 2015-10-28 2017-05-04 Northwestern University Substituted aromatic n-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (mnk1) and 2 (mnk2)
US9642368B2 (en) 2012-12-31 2017-05-09 Adama Makhteshim Ltd. 3-alkyl-5-fluoro-4-substituted-imino-3,4-dihydropyrimidin-2(1H)-one derivatives as fungicides
US9840476B2 (en) 2013-12-31 2017-12-12 Adama Makteshim Ltd. 5-fluoro-4-imino-3-(alkyl/substituted alkyl)-1-(arylsulfonyl)-3,4-dihydropyrimidin-2(1H)-one and processes for their preparation
US20180244654A1 (en) * 2015-10-28 2018-08-30 Northwestern University Substituted aromatic n-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (mnk1) and 2 (mnk2)
US10131652B2 (en) 2014-01-16 2018-11-20 E. I. Du Pont De Nemours And Company Pyrimidinyloxy benzene derivatives as herbicides
US10485235B2 (en) 2015-07-13 2019-11-26 Fmc Corporation Aryloxypyrimidinyl ethers as herbicides
US11006631B2 (en) 2015-03-18 2021-05-18 Fmc Corporation Substituted pyrimidinyloxy pyridine derivatives as herbicides
US11053204B2 (en) 2015-06-05 2021-07-06 Fmc Corporation Pyrimidinyloxy benzene derivatives as herbicides
US11427549B2 (en) 2017-05-02 2022-08-30 Fmc Corporation Pyrimidinyloxy benzo-fused compounds as herbicides
US11632954B2 (en) 2017-07-17 2023-04-25 Adama Makhteshim Ltd. Polymorphs of 5-fluoro-4-imino-3-methyl-1 -tosyl-3,4-dihydropyrimidin-2-one

Families Citing this family (190)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL2317851T3 (en) * 2008-08-01 2014-06-30 Dow Agrosciences Llc Use of 5-fluorocytosine as a fungicide
EA019396B1 (en) * 2009-09-01 2014-03-31 ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи Synergistic fungicidal compositions containing a 5-fluoropyrimidine derivative for fungal control in cereals
WO2011032656A1 (en) 2009-09-18 2011-03-24 Bayer Cropscience Ag 5-fluor-2-thio-substituted pyrimidine derivatives
US20110082162A1 (en) * 2009-10-07 2011-04-07 Dow Agrosciences Llc Synergistic fungicidal composition containing 5-fluorocytosine for fungal control in cereals
IN2012DN06286A (en) * 2009-12-17 2015-09-25 Dow Agrosciences Llc
CN102971309A (en) 2010-04-28 2013-03-13 拜尔农科股份公司 Fungicide hydroximoyl-heterocycles derivatives
WO2011134913A1 (en) 2010-04-28 2011-11-03 Bayer Cropscience Ag Fungicide hydroximoyl-heterocycles derivatives
WO2011134911A2 (en) 2010-04-28 2011-11-03 Bayer Cropscience Ag Fungicide hydroximoyl-tetrazole derivatives
AU2011258217B2 (en) * 2010-05-26 2016-12-15 Sunovion Pharmaceuticals Inc. Heteroaryl compounds and methods of use thereof
US9232799B2 (en) 2010-06-03 2016-01-12 Bayer Intellectual Property Gmbh N-[(het)arylethyl)] pyrazole(thio)carboxamides and their heterosubstituted analogues
US8999956B2 (en) 2010-06-03 2015-04-07 Bayer Intellectual Property Gmbh N-[(het)arylalkyl)] pyrazole(thio)carboxamides and their heterosubstituted analogues
UA110703C2 (en) 2010-06-03 2016-02-10 Байєр Кропсайнс Аг Fungicidal n-[(trisubstitutedsilyl)methyl]carboxamide
US9125408B2 (en) 2010-09-01 2015-09-08 North Carolina State University Use of aryl carbamates in agriculture and other plant-related areas
BR112013006612A2 (en) 2010-09-22 2017-10-24 Bayer Ip Gmbh use of biological or chemical control agents for insect and nematode control in resistant crops
EP2624699B1 (en) 2010-10-07 2018-11-21 Bayer CropScience Aktiengesellschaft Fungicide composition comprising a tetrazolyloxime derivative and a thiazolylpiperidine derivative
CA2815105A1 (en) 2010-10-21 2012-04-26 Bayer Intellectual Property Gmbh N-benzyl heterocyclic carboxamides
EP2630135B1 (en) 2010-10-21 2020-03-04 Bayer Intellectual Property GmbH 1-(heterocyclic carbonyl) piperidines
EP2635564B1 (en) 2010-11-02 2017-04-26 Bayer Intellectual Property GmbH N-hetarylmethyl pyrazolylcarboxamides
BR112013012082A2 (en) 2010-11-15 2016-07-19 Bayer Ip Gmbh 5-halopyrazole carboxamides
BR112013012080A2 (en) 2010-11-15 2016-07-19 Bayer Ip Gmbh n-aryl pyrazole (thio) carboxamides
CN103369962A (en) 2010-11-15 2013-10-23 拜耳知识产权有限责任公司 5-halogenopyrazole(thio)carboxamides
BR112013012966A2 (en) 2010-11-29 2016-08-23 Bayer Ip Gmbh alpha, beta imines - unsaturated
AP3519A (en) 2010-12-01 2016-01-11 Bayer Ip Gmbh Use of fluopyram for controlling nematodes in crops and for increasing yield
AR083987A1 (en) 2010-12-01 2013-04-10 Bayer Cropscience Ag USED PIRAZOLCARBOXILIC ACID AMIDAS FOR REDUCTION OF MICOTOXIN POLLUTION IN PLANTS
RU2013132730A (en) * 2010-12-16 2015-01-27 ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи Synergistic Fungicidal Interactions of 5-Fluorocytosine and Other Fungicides
AU2011341547A1 (en) * 2010-12-16 2013-07-04 Dow Agrosciences Llc Synergistic fungicidal interactions of aminopyrimidines and other fungicides
JP2014502611A (en) 2010-12-29 2014-02-03 バイエル・インテレクチユアル・プロパテイー・ゲー・エム・ベー・ハー Fungicide hydroxymoyl-tetrazole derivative
EP2532233A1 (en) 2011-06-07 2012-12-12 Bayer CropScience AG Active compound combinations
CA2843120A1 (en) 2011-07-27 2013-01-31 Bayer Intellectual Property Gmbh Seed dressing for controlling phytopathogenic fungi
AU2012357896B9 (en) 2011-12-19 2016-12-15 Bayer Cropscience Ag Use of anthranilic acid diamide derivatives for pest control in transgenic crops
EP2606726A1 (en) 2011-12-21 2013-06-26 Bayer CropScience AG N-Arylamidine-substituted trifluoroethylsulfide derivatives as acaricides and insecticides
TWI568721B (en) 2012-02-01 2017-02-01 杜邦股份有限公司 Fungicidal pyrazole mixtures
AU2013224170B2 (en) 2012-02-22 2016-11-03 Bayer Cropscience Ag Use of succinate dehydrogenase inhibitors (SDHIs) for controlling wood diseases in grape.
CN102659689B (en) * 2012-05-16 2014-12-17 浙江工业大学 4-substituted-2-butoxy-5-fluoropyrimidine compounds, and preparation method and application thereof
BR112015031291A2 (en) 2013-06-20 2017-07-25 Bayer Cropscience Ag aryl sulfide derivatives and arylalkyl sulfoxide derivatives as acaricides and insecticides
US9981928B2 (en) 2013-06-20 2018-05-29 Bayer Cropscience Aktiengesellschaft Aryl sulfide derivatives and aryl sulfoxide derivatives as acaricides and insecticides
WO2015039333A1 (en) * 2013-09-22 2015-03-26 Merck Sharp & Dohme Corp. TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
CN103766393A (en) * 2014-02-08 2014-05-07 山东省联合农药工业有限公司 Pyrimidine-containing organophosphorus fungicide and application
UA121030C2 (en) 2014-03-20 2020-03-25 Міцуі Кемікалз Аґро, Інк. Plant disease control composition and method for controlling plant disease by application of same
CN104725323A (en) * 2014-10-16 2015-06-24 江苏华益科技有限公司 Synthetic process of 2-methoxyl-4-diazanyl-5-fluoropyrimidine
US10779536B2 (en) 2014-11-07 2020-09-22 Basf Se Pesticidal mixtures
WO2016163379A1 (en) * 2015-04-09 2016-10-13 住友化学株式会社 Oxalyl amide compound and use thereof for noxious arthropod control
WO2016163383A1 (en) * 2015-04-09 2016-10-13 住友化学株式会社 Oxalyl amide compound and use thereof for noxious arthropod control
RU2724555C2 (en) * 2015-07-06 2020-06-23 Байер Кропсайенс Акциенгезельшафт Heterocyclic compounds as pesticides
US20190135798A1 (en) 2015-11-02 2019-05-09 Basf Se Substituted Oxadiazoles for Combating Phytopathogenic Fungi
BR112018008288A2 (en) 2015-11-04 2018-10-30 Basf Se use of formula compounds, formula compounds, mixture, agrochemical composition and method for combating fungi
BR112018009566A2 (en) 2015-11-13 2018-11-06 Basf Se compounds, mixture, agrochemical composition, use of compounds and method to combat phytopathogenic harmful fungi
BR112018009579A2 (en) 2015-11-13 2018-11-06 Basf Se compound of formula i, mixture, agrochemical composition, compound use and fungal control method
WO2017085100A1 (en) 2015-11-19 2017-05-26 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
WO2017085098A1 (en) 2015-11-19 2017-05-26 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
EP3202267A1 (en) 2016-02-05 2017-08-09 Basf Se Pesticidal mixtures
EP3426044A1 (en) 2016-03-10 2019-01-16 Basf Se Fungicidal mixtures iii comprising strobilurin-type fungicides
WO2017157910A1 (en) 2016-03-16 2017-09-21 Basf Se Use of tetrazolinones for combating resistant phytopathogenic fungi on cereals
BR112018068705B1 (en) 2016-03-16 2022-09-06 Basf Se METHOD TO CONTROL PHYTOPATOGENIC FUNGI
CA3015456A1 (en) 2016-03-16 2017-09-21 Basf Se Use of tetrazolinones for combating resistant phytopathogenic fungi on fruits
CA3020532A1 (en) 2016-04-11 2017-10-19 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
EP3512337A1 (en) 2016-09-13 2019-07-24 Basf Se Fungicidal mixtures i comprising quinoline fungicides
WO2018054721A1 (en) 2016-09-26 2018-03-29 Basf Se Pyridine compounds for controlling phytopathogenic harmful fungi
WO2018054723A1 (en) 2016-09-26 2018-03-29 Basf Se Pyridine compounds for controlling phytopathogenic harmful fungi
WO2018054711A1 (en) 2016-09-26 2018-03-29 Basf Se Pyridine compounds for controlling phytopathogenic harmful fungi
WO2018065182A1 (en) 2016-10-04 2018-04-12 Basf Se Reduced quinoline compounds as antifuni agents
WO2018073110A1 (en) 2016-10-20 2018-04-26 Basf Se Quinoline compounds as fungicides
BR112019011293A2 (en) 2016-12-19 2019-10-08 Basf Se compounds of formula I, intermediates, agrochemical composition, use and method for combating phytopathogenic harmful fungi
EP3339297A1 (en) 2016-12-20 2018-06-27 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
EP3338552A1 (en) 2016-12-21 2018-06-27 Basf Se Use of a tetrazolinone fungicide on transgenic plants
US20190359589A1 (en) 2017-01-23 2019-11-28 Basf Se Fungicidal pyridine compounds
WO2018149754A1 (en) 2017-02-16 2018-08-23 Basf Se Pyridine compounds
US11425910B2 (en) 2017-02-21 2022-08-30 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
KR102551432B1 (en) 2017-03-31 2023-07-05 바스프 에스이 Pyrimidinium compounds and mixtures thereof for combating animal pests
WO2018184882A1 (en) 2017-04-06 2018-10-11 Basf Se Pyridine compounds
US20200045974A1 (en) 2017-04-07 2020-02-13 Basf Se Substituted Oxadiazoles for Combating Phytopathogenic Fungi
WO2018188962A1 (en) 2017-04-11 2018-10-18 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
EP3612514B1 (en) 2017-04-20 2022-03-30 PI Industries Ltd Novel phenylamine compounds
US20210084902A1 (en) 2017-05-02 2021-03-25 Basf Se Fungicidal mixture comprising substituted 3-phenyl-5-(trifluoromethyl)-1,2,4-oxadiazoles
JP7160487B2 (en) 2017-05-04 2022-10-25 ビーエーエスエフ ソシエタス・ヨーロピア Substituted 5-(haloalkyl)-5-hydroxy-isoxazoles for combating plant pathogens
WO2018202491A1 (en) 2017-05-04 2018-11-08 Basf Se Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi
EP3618628A1 (en) 2017-05-05 2020-03-11 Basf Se Fungicidal mixtures comprising triazole compounds
WO2018210658A1 (en) 2017-05-15 2018-11-22 Basf Se Heteroaryl compounds as agrochemical fungicides
WO2018210661A1 (en) 2017-05-15 2018-11-22 Basf Se Heteroaryl compounds as agrochemical fungicides
WO2018210660A1 (en) 2017-05-15 2018-11-22 Basf Se Heteroaryl compounds as agrochemical fungicides
WO2018210659A1 (en) 2017-05-15 2018-11-22 Basf Se Heteroaryl compounds as agrochemical fungicides
CR20190580A (en) 2017-05-30 2020-02-10 Basf Se Pyridine and pyrazine compounds
WO2018219797A1 (en) 2017-06-02 2018-12-06 Basf Se Substituted oxadiazoles for combating phytopathogenic fungi
EP3642187A1 (en) 2017-06-19 2020-04-29 Basf Se 2-[[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]aryloxy](thio)acetamides for combating phytopathogenic fungi
WO2019002158A1 (en) 2017-06-30 2019-01-03 Basf Se Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi
WO2019025250A1 (en) 2017-08-04 2019-02-07 Basf Se Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi
RU2668556C1 (en) * 2017-08-07 2018-10-02 Александр Валерьевич Чичварин Fungicide based on fullerene adducts
WO2019038042A1 (en) 2017-08-21 2019-02-28 Basf Se Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi
EP3915379A1 (en) 2017-08-29 2021-12-01 Basf Se Pesticidal mixtures
WO2019042932A1 (en) 2017-08-31 2019-03-07 Basf Se Method of controlling rice pests in rice
EP3453706A1 (en) 2017-09-08 2019-03-13 Basf Se Pesticidal imidazole compounds
US11076596B2 (en) 2017-09-18 2021-08-03 Basf Se Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi
WO2019057660A1 (en) 2017-09-25 2019-03-28 Basf Se Indole and azaindole compounds with substituted 6-membered aryl and heteroaryl rings as agrochemical fungicides
WO2019068810A1 (en) 2017-10-06 2019-04-11 Bayer Aktiengesellschaft Use of compositions comprising fluopyram for enhancing antioxidative fitness of plants
WO2019072906A1 (en) 2017-10-13 2019-04-18 Basf Se Imidazolidine pyrimidinium compounds for combating animal pests
WO2019101511A1 (en) 2017-11-23 2019-05-31 Basf Se Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi
US11319553B2 (en) 2017-11-29 2022-05-03 Rahan Meristem (1998) Ltd. Compositions and methods conferring resistance to fungal diseases
WO2019115511A1 (en) 2017-12-14 2019-06-20 Basf Se Fungicidal mixture comprising substituted 3-phenyl-5-(trifluoromethyl)-1,2,4-oxadiazoles
WO2019115343A1 (en) 2017-12-15 2019-06-20 Basf Se Fungicidal mixture comprising substituted pyridines
WO2019123196A1 (en) 2017-12-20 2019-06-27 Pi Industries Ltd. Fluoralkenyl compounds, process for preparation and use thereof
WO2019121143A1 (en) 2017-12-20 2019-06-27 Basf Se Substituted cyclopropyl derivatives
BR112020012487A2 (en) 2017-12-20 2020-11-24 Bayer Aktiengesellschaft use of fungicides to control apple scab by mosaic
EP3737235A1 (en) 2018-01-09 2020-11-18 Basf Se Silylethynyl hetaryl compounds as nitrification inhibitors
WO2019137995A1 (en) 2018-01-11 2019-07-18 Basf Se Novel pyridazine compounds for controlling invertebrate pests
WO2019150311A1 (en) 2018-02-02 2019-08-08 Pi Industries Ltd. 1-3 dithiol compounds and their use for the protection of crops from phytopathogenic microorganisms
CA3088722A1 (en) 2018-02-07 2019-08-15 Basf Se New pyridine carboxamides
WO2019154665A1 (en) 2018-02-07 2019-08-15 Basf Se New pyridine carboxamides
EP3530118A1 (en) 2018-02-26 2019-08-28 Basf Se Fungicidal mixtures
EP3530116A1 (en) 2018-02-27 2019-08-28 Basf Se Fungicidal mixtures comprising xemium
BR112020016425A2 (en) 2018-02-28 2020-12-15 Basf Se USE OF ALCOXIPYRAZOL COMPOUND, COMPOSITION FOR USE IN REDUCING NITRIFICATION, AGRICULTURAL MIXTURE AND METHODS OF REDUCING NITRIFICATION AND TREATMENT OF FERTILIZER OR COMPOSITION
IL302719A (en) 2018-02-28 2023-07-01 Basf Se Use of n-functionalized alkoxy pyrazole compounds as nitrification inhibitors
CA3089381A1 (en) 2018-02-28 2019-09-06 Basf Se Use of pyrazole propargyl ethers as nitrification inhibitors
BR112020015467A2 (en) 2018-02-28 2020-12-08 Basf Se FUNGICIDAL MIXTURES, FUNGICIDAL COMPOSITION, METHODS TO CONTROL PHYTOPATOGENIC FUNGI, TO IMPROVE PLANT HEALTH AND TO PROTECT PLANT PROPAGATION MATERIAL AGAINST PHYTOPHOGENIC FUNGI AND PLANT PROPAGATION MATERIAL
WO2019166257A1 (en) 2018-03-01 2019-09-06 BASF Agro B.V. Fungicidal compositions of mefentrifluconazole
EP3533333A1 (en) 2018-03-02 2019-09-04 Basf Se Fungicidal mixtures comprising pydiflumetofen
EP3533331A1 (en) 2018-03-02 2019-09-04 Basf Se Fungicidal mixtures comprising pydiflumetofen
EP3536150A1 (en) 2018-03-06 2019-09-11 Basf Se Fungicidal mixtures comprising fluxapyroxad
WO2019175713A1 (en) 2018-03-14 2019-09-19 Basf Corporation New catechol molecules and their use as inhibitors to p450 related metabolic pathways
WO2019175712A1 (en) 2018-03-14 2019-09-19 Basf Corporation New uses for catechol molecules as inhibitors to glutathione s-transferase metabolic pathways
JP7433244B2 (en) 2018-05-15 2024-02-19 ビーエーエスエフ ソシエタス・ヨーロピア Mixtures containing benzpyrimoxane and oxazosulfil and methods of use and application thereof
WO2019219464A1 (en) 2018-05-15 2019-11-21 Basf Se Substituted trifluoromethyloxadiazoles for combating phytopathogenic fungi
WO2019224092A1 (en) 2018-05-22 2019-11-28 Basf Se Pesticidally active c15-derivatives of ginkgolides
WO2020002472A1 (en) 2018-06-28 2020-01-02 Basf Se Use of alkynylthiophenes as nitrification inhibitors
DK3826982T3 (en) 2018-07-23 2024-01-22 Basf Se USE OF A SUBSTITUTED THIAZOLIDE COMPOUND AS A NITRIFICATION INHIBITOR
US20210340073A1 (en) 2018-07-23 2021-11-04 Basf Se Use of substituted 2-thiazolines as nitrification inhibitors
AR115984A1 (en) 2018-08-17 2021-03-17 Pi Industries Ltd 1,2-DITIOLONE COMPOUNDS AND THEIR USES
EP3613736A1 (en) 2018-08-22 2020-02-26 Basf Se Substituted glutarimide derivatives
EP3628156A1 (en) 2018-09-28 2020-04-01 Basf Se Method for controlling pests of sugarcane, citrus, rapeseed, and potato plants
EP3628158A1 (en) 2018-09-28 2020-04-01 Basf Se Pesticidal mixture comprising a mesoionic compound and a biopesticide
CA3112042A1 (en) 2018-09-28 2020-04-02 Basf Se Method of controlling pests by seed treatment application of a mesoionic compound or mixture thereof
EP3628157A1 (en) 2018-09-28 2020-04-01 Basf Se Method of controlling insecticide resistant insects and virus transmission to plants
EP3643705A1 (en) 2018-10-24 2020-04-29 Basf Se Pesticidal compounds
WO2020095161A1 (en) 2018-11-05 2020-05-14 Pi Industries Ltd. Nitrone compounds and use thereof
EP3670501A1 (en) 2018-12-17 2020-06-24 Basf Se Substituted [1,2,4]triazole compounds as fungicides
EP3696177A1 (en) 2019-02-12 2020-08-19 Basf Se Heterocyclic compounds for the control of invertebrate pests
EP3730489A1 (en) 2019-04-25 2020-10-28 Basf Se Heteroaryl compounds as agrochemical fungicides
CN113923987A (en) 2019-05-29 2022-01-11 巴斯夫欧洲公司 Mesoionic imidazolium compounds and derivatives for combating animal pests
EP3769623A1 (en) 2019-07-22 2021-01-27 Basf Se Mesoionic imidazolium compounds and derivatives for combating animal pests
AU2020286573A1 (en) 2019-06-06 2021-12-23 Basf Se Fungicidal n-(pyrid-3-yl)carboxamides
WO2020244970A1 (en) 2019-06-06 2020-12-10 Basf Se New carbocyclic pyridine carboxamides
WO2020244969A1 (en) 2019-06-06 2020-12-10 Basf Se Pyridine derivatives and their use as fungicides
EP3766879A1 (en) 2019-07-19 2021-01-20 Basf Se Pesticidal pyrazole derivatives
WO2021063735A1 (en) 2019-10-02 2021-04-08 Basf Se New bicyclic pyridine derivatives
WO2021063736A1 (en) 2019-10-02 2021-04-08 Basf Se Bicyclic pyridine derivatives
BR112022012469A2 (en) 2019-12-23 2022-09-06 Basf Se METHOD AND COMPOSITION FOR THE PROTECTION OF PLANT OR VEGETABLE PROPAGATION MATERIAL, USE OF AT LEAST ONE ACTIVE COMPOUND AND AT LEAST ONE ENZYME, SEEDS AND KIT OF PARTS
WO2021170463A1 (en) 2020-02-28 2021-09-02 BASF Agro B.V. Methods and uses of a mixture comprising alpha-cypermethrin and dinotefuran for controlling invertebrate pests in turf
BR112022017563A2 (en) 2020-03-04 2022-10-18 Basf Se USE OF COMPOUNDS, AGROCHEMICAL COMPOSITION AND METHOD TO FIGHT HARMFUL PHYTOPATOGENIC FUNGI
WO2021209360A1 (en) 2020-04-14 2021-10-21 Basf Se Fungicidal mixtures comprising substituted 3-phenyl-5-(trifluoromethyl)-1,2,4-oxadiazoles
BR112022021631A2 (en) 2020-04-28 2022-12-06 Basf Se COMPOUNDS, COMPOSITION, METHODS TO COMBAT OR CONTROL INVERTEBRATE PEST, TO PROTECT GROWING PLANTS AND TO TREAT OR PROTECT AN ANIMAL, SEED AND USE OF A COMPOUND
EP3903581A1 (en) 2020-04-28 2021-11-03 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors i
EP3903584A1 (en) 2020-04-28 2021-11-03 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors iv
EP3903582A1 (en) 2020-04-28 2021-11-03 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors ii
EP3903583A1 (en) 2020-04-28 2021-11-03 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors iii
EP3909950A1 (en) 2020-05-13 2021-11-17 Basf Se Heterocyclic compounds for the control of invertebrate pests
EP3945089A1 (en) 2020-07-31 2022-02-02 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors v
WO2021249800A1 (en) 2020-06-10 2021-12-16 Basf Se Substituted [1,2,4]triazole compounds as fungicides
EP3939961A1 (en) 2020-07-16 2022-01-19 Basf Se Strobilurin type compounds and their use for combating phytopathogenic fungi
WO2022017836A1 (en) 2020-07-20 2022-01-27 BASF Agro B.V. Fungicidal compositions comprising (r)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1- (1,2,4-triazol-1-yl)propan-2-ol
EP3970494A1 (en) 2020-09-21 2022-03-23 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors viii
TW202229241A (en) 2020-09-26 2022-08-01 印度商皮埃企業有限公司 Nematocidal compounds and use thereof
CN116209355A (en) 2020-10-27 2023-06-02 巴斯夫农业公司 Composition containing haloxyfop-methyl
WO2022090069A1 (en) 2020-11-02 2022-05-05 Basf Se Compositions comprising mefenpyr-diethyl
WO2022090071A1 (en) 2020-11-02 2022-05-05 Basf Se Use of mefenpyr-diethyl for controlling phytopathogenic fungi
WO2022106304A1 (en) 2020-11-23 2022-05-27 BASF Agro B.V. Compositions comprising mefentrifluconazole
EP4018830A1 (en) 2020-12-23 2022-06-29 Basf Se Pesticidal mixtures
AR124796A1 (en) 2021-02-02 2023-05-03 Basf Se SYNERGIC ACTION OF DCD AND ALCOXYPYRAZOLES AS INHIBITORS OF NITRIFICATION
EP4043444A1 (en) 2021-02-11 2022-08-17 Basf Se Substituted isoxazoline derivatives
EP4337012A1 (en) 2021-05-11 2024-03-20 Basf Se Fungicidal mixtures comprising substituted 3-phenyl-5-(trifluoromethyl)-1,2,4-oxadiazoles
WO2022243109A1 (en) 2021-05-18 2022-11-24 Basf Se New substituted quinolines as fungicides
CA3218889A1 (en) 2021-05-18 2022-11-24 Wassilios Grammenos New substituted pyridines as fungicides
EP4341258A1 (en) 2021-05-18 2024-03-27 Basf Se New substituted pyridines as fungicides
BR112023024012A2 (en) 2021-05-21 2024-02-06 Basf Se USE OF ETHYNYLPYRIDINE COMPOUND, COMPOSITION FOR USE IN NITRIFICATION REDUCTION, AGROCHEMICAL MIXTURE AND METHODS OF NITRIFICATION REDUCTION AND FERTILIZER TREATMENT OR COMPOSITION
CA3219128A1 (en) 2021-05-21 2022-11-24 Barbara Nave Use of an n-functionalized alkoxy pyrazole compound as nitrification inhibitor
EP4094579A1 (en) 2021-05-28 2022-11-30 Basf Se Pesticidal mixtures comprising metyltetraprole
CN117500377A (en) 2021-06-21 2024-02-02 巴斯夫欧洲公司 Metal organic frameworks with pyrazole-based building units
EP4119547A1 (en) 2021-07-12 2023-01-18 Basf Se Triazole compounds for the control of invertebrate pests
WO2023011958A1 (en) 2021-08-02 2023-02-09 Basf Se (3-pirydyl)-quinazoline
WO2023011957A1 (en) 2021-08-02 2023-02-09 Basf Se (3-quinolyl)-quinazoline
EP4140986A1 (en) 2021-08-23 2023-03-01 Basf Se Pyrazine compounds for the control of invertebrate pests
EP4140995A1 (en) 2021-08-27 2023-03-01 Basf Se Pyrazine compounds for the control of invertebrate pests
EP4151631A1 (en) 2021-09-20 2023-03-22 Basf Se Heterocyclic compounds for the control of invertebrate pests
WO2023072671A1 (en) 2021-10-28 2023-05-04 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors ix
WO2023072670A1 (en) 2021-10-28 2023-05-04 Basf Se Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors x
EP4194453A1 (en) 2021-12-08 2023-06-14 Basf Se Pyrazine compounds for the control of invertebrate pests
EP4198033A1 (en) 2021-12-14 2023-06-21 Basf Se Heterocyclic compounds for the control of invertebrate pests
EP4198023A1 (en) 2021-12-16 2023-06-21 Basf Se Pesticidally active thiosemicarbazone compounds
EP4238971A1 (en) 2022-03-02 2023-09-06 Basf Se Substituted isoxazoline derivatives
WO2023203066A1 (en) 2022-04-21 2023-10-26 Basf Se Synergistic action as nitrification inhibitors of dcd oligomers with alkoxypyrazole and its oligomers
WO2024028243A1 (en) 2022-08-02 2024-02-08 Basf Se Pyrazolo pesticidal compounds
EP4342885A1 (en) 2022-09-20 2024-03-27 Basf Se N-(3-(aminomethyl)-phenyl)-5-(4-phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-amine derivatives and similar compounds as pesticides

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3309359A (en) * 1965-10-22 1967-03-14 Hoffmann La Roche N-mono-acyl-5-fluorocytosine derivatives and process
US3368938A (en) * 1966-01-13 1968-02-13 Hoffmann La Roche Controlling fungi with 5-fluorocytosine
US3868373A (en) * 1970-01-27 1975-02-25 Hoffmann La Roche 4-Amino-5-fluoro-2-tri(lower alkyl) silyloxypyrimidines
US4845081A (en) * 1984-10-18 1989-07-04 University Of Florida Aminomethyl derivatives of biologically active substances, and enhanced delivery thereof across topical membranes
US4996208A (en) * 1988-06-28 1991-02-26 Bayer Aktiengesellschaft Pesticidal thiazolopyrimidine derivatives
US5962489A (en) * 1992-07-16 1999-10-05 Basf Aktiengesellschaft Heteroaromatic compounds and crop protection agents containing them
US6066638A (en) * 1995-07-05 2000-05-23 E. I. Du Pont De Nemours And Company Fungicidal pyrimidinones
US20030039667A1 (en) * 2001-08-27 2003-02-27 Vic Jira Anti-fungal composition
US6617330B2 (en) * 1998-11-06 2003-09-09 Syngenta Participations Ag Pyrimidin-4-enamine as fungicide
US20080004253A1 (en) * 2006-06-30 2008-01-03 Bryan James Branstetter Thiazolopyrimidine modulators of TRPV1
US20080269238A1 (en) * 2004-04-01 2008-10-30 Takeda Pharmaceutical Company Limited Thiazolopyrimidine Derivative
WO2009094442A2 (en) * 2008-01-22 2009-07-30 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
US20110034493A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-sulfonyl-5-fluoropyrimidinone derivatives

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US368373A (en) * 1887-08-16 Valve for water-gages
US3354160A (en) 1965-07-22 1967-11-21 Hoffmann La Roche Tri-lower alkyl-silyl-5-fluoropyrimidines
CH579057A5 (en) * 1973-09-07 1976-08-31 Hoffmann La Roche
FR2530636A1 (en) 1982-07-23 1984-01-27 Rhone Poulenc Agrochimie NOVEL DERIVATIVES OF 2,3,6,7-TETRAHYDRO 5H-THIAZOLO (3,2-A) PYRIMIDINE, THEIR PREPARATION AND THEIR USE AS HERBICIDES
GR80171B (en) * 1983-08-29 1985-01-02 Ciba Geigy Ag N-(2-nitrophenyl)-4-aminopyrimidine derivatives process for the preparation thereof and use
EP0332579B1 (en) * 1988-03-09 1994-08-10 Ciba-Geigy Ag Method for protecting plants from diseases
JP3109012B2 (en) 1992-06-18 2000-11-13 クミアイ化学工業株式会社 Thiazolo [5,4-d] pyrimidine derivatives and fungicides for agricultural and horticultural use
TW254946B (en) * 1992-12-18 1995-08-21 Hoffmann La Roche
US5480991A (en) 1993-11-05 1996-01-02 Dowelanco 2-Alkoxy-4-hydroazinopyrimidine compounds and their use in the preparation of 5-alkoxy-1,2,4-triazolo[4,3-c]pyrimidine-3(2H)-thione compounds
JPH11514642A (en) * 1995-11-02 1999-12-14 チョング クン ダング シーオーアールピー． Novel nucleoside derivative and method for producing the same
KR100482919B1 (en) 1996-03-11 2005-10-12 신젠타 파티서페이션즈 아게 Pyrimidine-4-one derivatives as insecticides
HRP970239B1 (en) 1997-05-09 2004-04-30 Inst Ru Er Bouekovic Process for the preparation of sulfonyl-pyrimidine derivatives with antitumor activity
ZA984796B (en) 1997-06-10 1998-12-29 Chong Kun Dang Corp Novel optically active nucleoside derivative its manufacturing method and anti-HBV composition containing the derivative thereof
DE19806438A1 (en) 1998-02-17 1999-08-19 Basf Ag New pyrimidinyloxy-propionic acid derivatives useful as endothelin receptor antagonists in treatment of e.g. cardiac insufficiency, restenosis, hypertension, kidney failure, asthma and prostate cancer
CN1325504C (en) * 2002-01-10 2007-07-11 宾夕法尼亚州研究基金会 Methods for the preparation of alkyl diaryl borinates and complexed diarylboronic acids
CN1329407C (en) 2002-04-12 2007-08-01 阿奇林医药品公司 Method for synthesizing beta-L-fluoro-2',3'-dideoxy-didehydrocytidine (beta-L-FD4C)
US7517886B2 (en) 2002-07-29 2009-04-14 Rigel Pharmaceuticals, Inc. Methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds
US20050038041A1 (en) * 2003-08-15 2005-02-17 Yuki Nakagawa Fungicidal pyrimidine derivatives
JP2005126389A (en) 2003-10-27 2005-05-19 Sumitomo Chemical Co Ltd Method for producing 2,4-dichloro-5-fluoropyrimidine
JP2009507894A (en) * 2005-09-13 2009-02-26 バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト Pesticide pyrimidinyloxy substituted phenylamidine derivatives
WO2007077505A2 (en) 2005-12-30 2007-07-12 Ranbaxy Laboratories Limited Crystalline l-menthyl (2r, 5s)-5-(4-amino-5-fluoro-2-oxo-2h-pyrimidin-1-yl)[1, 3]oxathiolan-2-carboxylate and process for preparation thereof
JP5039375B2 (en) 2006-01-10 2012-10-03 クミアイ化学工業株式会社 Isothiazole compounds and plant disease control agents for agriculture and horticulture
KR101176699B1 (en) 2006-10-19 2012-08-23 에프. 호프만-라 로슈 아게 Aminomethyl-4-imidazoles
US20100130734A1 (en) * 2007-04-20 2010-05-27 Dr. Reddy's Laboratories Ltd. Process for preparing capecitabine
PL2317851T3 (en) 2008-08-01 2014-06-30 Dow Agrosciences Llc Use of 5-fluorocytosine as a fungicide
PT2389375E (en) 2009-01-23 2015-09-17 Euro Celtique Sa Hydroxamic acid derivatives
EA019396B1 (en) * 2009-09-01 2014-03-31 ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи Synergistic fungicidal compositions containing a 5-fluoropyrimidine derivative for fungal control in cereals
IN2012DN06286A (en) * 2009-12-17 2015-09-25 Dow Agrosciences Llc

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3309359A (en) * 1965-10-22 1967-03-14 Hoffmann La Roche N-mono-acyl-5-fluorocytosine derivatives and process
US3368938A (en) * 1966-01-13 1968-02-13 Hoffmann La Roche Controlling fungi with 5-fluorocytosine
US3868373A (en) * 1970-01-27 1975-02-25 Hoffmann La Roche 4-Amino-5-fluoro-2-tri(lower alkyl) silyloxypyrimidines
US4845081A (en) * 1984-10-18 1989-07-04 University Of Florida Aminomethyl derivatives of biologically active substances, and enhanced delivery thereof across topical membranes
US4996208A (en) * 1988-06-28 1991-02-26 Bayer Aktiengesellschaft Pesticidal thiazolopyrimidine derivatives
US5962489A (en) * 1992-07-16 1999-10-05 Basf Aktiengesellschaft Heteroaromatic compounds and crop protection agents containing them
US6066638A (en) * 1995-07-05 2000-05-23 E. I. Du Pont De Nemours And Company Fungicidal pyrimidinones
US6617330B2 (en) * 1998-11-06 2003-09-09 Syngenta Participations Ag Pyrimidin-4-enamine as fungicide
US20030039667A1 (en) * 2001-08-27 2003-02-27 Vic Jira Anti-fungal composition
US7914799B2 (en) * 2001-08-27 2011-03-29 Immunitor USA, Inc. Anti-fungal composition
US20080269238A1 (en) * 2004-04-01 2008-10-30 Takeda Pharmaceutical Company Limited Thiazolopyrimidine Derivative
US20080004253A1 (en) * 2006-06-30 2008-01-03 Bryan James Branstetter Thiazolopyrimidine modulators of TRPV1
WO2009094442A2 (en) * 2008-01-22 2009-07-30 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
US20090203647A1 (en) * 2008-01-22 2009-08-13 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
US20110034493A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-sulfonyl-5-fluoropyrimidinone derivatives

Cited By (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090203647A1 (en) * 2008-01-22 2009-08-13 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
US9174970B2 (en) 2008-01-22 2015-11-03 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
US9204653B2 (en) 2008-01-22 2015-12-08 Dow Agrosciences Llc 5-fluoro pyrimidine derivatives
EP2432776A1 (en) * 2009-05-21 2012-03-28 Chlorion Pharma, Inc. Methyl sulfanyl pyrmidmes useful as antiinflammatories, analgesics, and antiepileptics
US20100298336A1 (en) * 2009-05-21 2010-11-25 Giorgio Attardo Pyrimidines as novel therapeutic agents
US9040538B2 (en) 2009-05-21 2015-05-26 Universite Laval Pyrimidines as novel therapeutic agents
US9315521B2 (en) 2009-05-21 2016-04-19 UNIVERSITé LAVAL Pyrimidines as novel therapeutic agents
EP2432776A4 (en) * 2009-05-21 2012-10-24 Chlorion Pharma Inc Methyl sulfanyl pyrmidmes useful as antiinflammatories, analgesics, and antiepileptics
US20110053891A1 (en) * 2009-08-07 2011-03-03 Dow Agrosciences Llc 5-fluoropyrimidinone derivatives
WO2011017545A1 (en) 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-substituted-5-fluoro-2-oxopyrimidinone-1(2h)-carboxamide derivatives
US8552020B2 (en) 2009-08-07 2013-10-08 Dow Agrosciences, Llc. N1-substituted-5-fluoro-2-oxopyrimidinone-1(2H)-carboxamide derivatives
US8916579B2 (en) 2009-08-07 2014-12-23 Dow Agrosciences, Llc. 5-fluoropyrimidinone derivatives
US9000002B2 (en) 2009-08-07 2015-04-07 Dow Agrosciences Llc N1-substituted-5-fluoro-2-oxopyrimidinone-1(2H)-carboxamide derivatives
US8470839B2 (en) 2009-08-07 2013-06-25 Dow Agrosciences, Llc. N1-acyl-5-fluoropyrimidinone derivatives
US9862686B2 (en) 2009-08-07 2018-01-09 Adama Makhteshim Ltd. N1-sulfonyl-5-fluoropyrimidinone derivatives
US9006259B2 (en) 2009-08-07 2015-04-14 Dow Agrosciences Llc N1-sulfonyl-5-fluoropyrimidinone derivatives
US20110034490A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-acyl-5-fluoropyrimidinone derivatives
US20110034493A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-sulfonyl-5-fluoropyrimidinone derivatives
US20110034492A1 (en) * 2009-08-07 2011-02-10 Dow Agrosciences Llc N1-substituted-5-fluoro-2-oxopyrimidinone-1(2h)-carboxamide derivatives
US8921382B2 (en) 2010-01-07 2014-12-30 Dow Agrosciences, Llc. Thiazolo[5,4-d] pyrimidines and their use as agrochemicals
US20110166164A1 (en) * 2010-01-07 2011-07-07 Dow Agrosciences Llc THIAZOLO[5,4-d] PYRIMIDINES AND THEIR USE AS AGROCHEMICALS
US20110263627A1 (en) * 2010-04-26 2011-10-27 Dow Agrosciences Llc N3-substituted-n1-sulfonyl-5-fluoropyrimidinone derivatives
US8263603B2 (en) * 2010-04-26 2012-09-11 Dow Agrosciences, Llc N3-substituted-N1-sulfonyl-5-fluoropyrimidinone derivatives
US8658660B2 (en) 2011-08-17 2014-02-25 Dow Agrosciences, Llc. 5-fluoro-4-imino-3,4-dihydropyrimidin-2-(1H)-ones derivatives
US20130045985A1 (en) * 2011-08-17 2013-02-21 Dow Agrosciences Llc N-(5-fluoro-2-((4-methylbenzyl)oxy)pyrimidin-4-yl)benzamide derivatives
WO2013025796A3 (en) * 2011-08-17 2014-05-15 Dow Agrosciences Llc N-(5-fluoro-2((4-methylbenzyl)oxy)pyrimidin-4-yl) benzamide derivatives
WO2013113719A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds ii
WO2013113776A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113781A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds i
WO2013113791A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113863A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113715A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113782A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113716A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013113773A1 (en) 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds
WO2013135672A1 (en) 2012-03-13 2013-09-19 Basf Se Fungicidal pyrimidine compounds
WO2013135671A1 (en) 2012-03-13 2013-09-19 Basf Se Fungicidal pyrimidine compounds
US20150141446A1 (en) * 2012-11-12 2015-05-21 Dow Agrosciences, Llc Pesticidal pyrimidine compounds
US9227957B2 (en) * 2012-11-12 2016-01-05 Dow Agrosciences Llc Pesticidal pyrimidine compounds
US9499497B2 (en) 2012-11-20 2016-11-22 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of indoleamine 2,3-dioxygenase
US9073875B2 (en) 2012-11-20 2015-07-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of indoleamine 2,3-dioxygenase
US9271497B2 (en) 2012-12-28 2016-03-01 Dow Agrosciences Llc 1-(substituted-benzoyl)-5-fluoro-4-imino-3-methyl-3,4-dihydropyrimidin-2(1H)-one derivatives
US9321734B2 (en) 2012-12-28 2016-04-26 Dow Agrosciences Llc N-(substituted)-5-fluoro-4-imino-3-methyl-2-oxo-3,4-dihydropyrimidine-1(2H)-carboxamide derivatives
US9908855B2 (en) 2012-12-28 2018-03-06 Adama Makhteshim Ltd. N-(substituted)-5-fluoro-4-imino-3-methyl-2-oxo-3,4-dihydropyrimidine-1(2H)-carboxylate derivatives
US9840475B2 (en) 2012-12-28 2017-12-12 Adama Makhteshim Ltd. N-(substituted)-5-fluoro-4-imino-3-methyl-2-oxo-3,4-dihydropyrimidine-1(2H)-carboxamide derivatives
US9622474B2 (en) 2012-12-28 2017-04-18 Adama Makhteshim Ltd. N-(substituted)-5-fluoro-4-imino-3-methyl-2-oxo-3,4-dihydropyrimidine-1(2H)-carboxylate derivatives
US10059703B2 (en) 2012-12-31 2018-08-28 Adama Makhteshim Ltd. 3-alkyl-5-fluoro-4-substituted-imino-3,4-dihydropyrimidin-2(1H)-one derivatives as fungicides
US9642368B2 (en) 2012-12-31 2017-05-09 Adama Makhteshim Ltd. 3-alkyl-5-fluoro-4-substituted-imino-3,4-dihydropyrimidin-2(1H)-one derivatives as fungicides
WO2014118099A1 (en) 2013-01-30 2014-08-07 Basf Se Fungicidal naphthoquinones and derivatives
US9695155B2 (en) 2013-12-10 2017-07-04 E I Du Pont De Nemours And Company Herbicidal substituted pyrimidinyloxy benzene compounds
CN106232594A (en) * 2013-12-10 2016-12-14 纳幕尔杜邦公司 Substituted 2-pyrimidinyl oxy benzene compound herbicide
RU2703460C1 (en) * 2013-12-10 2019-10-17 ЭфЭмСи Корпорейшн Herbicidal substituted pyrimidinyloxybenzole compounds
WO2015089003A1 (en) * 2013-12-10 2015-06-18 E. I. Du Pont De Nemours And Company Herbicidal substituted pyrimidinyloxy benzene compounds
US9526245B2 (en) 2013-12-31 2016-12-27 Adama Makhteshim Ltd. Synergistic fungicidal mixtures comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control in cereals
US10426167B2 (en) 2013-12-31 2019-10-01 Adama Makhteshim Ltd. Synergistic fungicidal mixtures and compositions comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control
US10919864B2 (en) 2013-12-31 2021-02-16 Adama Makhteshim Ltd. 5-fluoro-4-imino-3(alkyl/substituted alkyl)-1-(arylsulfonyl)-3,4-dihydropyrimidin-2(1H)-one and processes for their preparation
US9532570B2 (en) 2013-12-31 2017-01-03 Adama Makhteshim Ltd. Synergistic fungicidal mixtures comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control in cereals
US10045534B2 (en) 2013-12-31 2018-08-14 Adama Makhteshim Ltd. Synergistic fungicidal mixtures and compositions comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control
US10045533B2 (en) 2013-12-31 2018-08-14 Adama Makhteshim Ltd. Synergistic fungicidal mixtures and compositions comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control
US10051862B2 (en) 2013-12-31 2018-08-21 Adama Makhteshim Ltd. Synergistic fungicidal mixtures and compositions comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control
US9840476B2 (en) 2013-12-31 2017-12-12 Adama Makteshim Ltd. 5-fluoro-4-imino-3-(alkyl/substituted alkyl)-1-(arylsulfonyl)-3,4-dihydropyrimidin-2(1H)-one and processes for their preparation
US9538753B2 (en) 2013-12-31 2017-01-10 Adama Makhteshim Ltd. Synergistic fungicidal mixtures comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control in cereals
US9850215B2 (en) 2013-12-31 2017-12-26 Adama Makhteshim Ltd. 5-fluoro-4-imino-3-(alkyl/substituted alkyl)-1-(arylsulfonyl)-3,4-dihydropyrimidin-2(1 H)-one and processes for their preparation
US10426166B2 (en) 2013-12-31 2019-10-01 Adama Makhteshim Ltd. Synergistic fungicidal mixtures and compositions comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control
US10426165B2 (en) 2013-12-31 2019-10-01 Adama Makhteshim Ltd. Synergistic fungicidal mixtures and compositions comprising 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one for fungal control
US10131652B2 (en) 2014-01-16 2018-11-20 E. I. Du Pont De Nemours And Company Pyrimidinyloxy benzene derivatives as herbicides
US11447476B2 (en) 2014-01-16 2022-09-20 Fmc Corporation Pyrimidinyloxy benzene derivatives as herbicides
US10654840B2 (en) 2014-01-16 2020-05-19 Fmc Corporation Pyrimidinyloxy benzene derivatives as herbicides
US11006631B2 (en) 2015-03-18 2021-05-18 Fmc Corporation Substituted pyrimidinyloxy pyridine derivatives as herbicides
US11053204B2 (en) 2015-06-05 2021-07-06 Fmc Corporation Pyrimidinyloxy benzene derivatives as herbicides
US10485235B2 (en) 2015-07-13 2019-11-26 Fmc Corporation Aryloxypyrimidinyl ethers as herbicides
US10851082B2 (en) * 2015-10-28 2020-12-01 Northwestern University Substituted aromatic n-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (MNK1) and 2 (MNK2)
US20170121326A1 (en) * 2015-10-28 2017-05-04 Northwestern University Substituted aromatic n-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (mnk1) and 2 (mnk2)
US10093668B2 (en) * 2015-10-28 2018-10-09 Northwestern University Substituted aromatic N-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (Mnk1) and 2 (Mnk2)
US20180244654A1 (en) * 2015-10-28 2018-08-30 Northwestern University Substituted aromatic n-heterocyclic compounds as inhibitors of mitogen-activated protein kinase interacting kinase 1 (mnk1) and 2 (mnk2)
US11427549B2 (en) 2017-05-02 2022-08-30 Fmc Corporation Pyrimidinyloxy benzo-fused compounds as herbicides
US11632954B2 (en) 2017-07-17 2023-04-25 Adama Makhteshim Ltd. Polymorphs of 5-fluoro-4-imino-3-methyl-1 -tosyl-3,4-dihydropyrimidin-2-one

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