EP2473511A1 - Pteridines and their use as agrochemicals - Google Patents
Pteridines and their use as agrochemicalsInfo
- Publication number
- EP2473511A1 EP2473511A1 EP09792110A EP09792110A EP2473511A1 EP 2473511 A1 EP2473511 A1 EP 2473511A1 EP 09792110 A EP09792110 A EP 09792110A EP 09792110 A EP09792110 A EP 09792110A EP 2473511 A1 EP2473511 A1 EP 2473511A1
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- European Patent Office
- Prior art keywords
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- compounds
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- lower alkyl
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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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
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/04—Amoebicides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
- A61P33/12—Schistosomicides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
-
- 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
- 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
- C07D401/14—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 three or more hetero rings
Definitions
- the present disclosure relates to 1- or 2-(4-(aryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and 1- or 2-(4-(heteroaryloxy)-phenyl)ethylamino-, oxy- or
- the present disclosure provides novel organic compounds that may demonstrate activity as pesticides, meaning that they may control fungi, insects, mites, and/or animal parasites.
- the disclosure also provides novel pesticide methods and compositions utilizing the novel compounds.
- R is H, CH 3 , phenyl, or a heterocycle comprising a 5 or 6 membered single ring or a fused ring system comprising at least one 5 or 6 membered heterocycle optionally substituted with H, halo, lower alkyl, lower alkoxy, benzyloxy, lower alkenyl, lower alkynyl, haloalkyl, haloalkoxy, NO 2 , CN, lower alkoxycarbonyl, lower alkylcarbonyl, lower alkyl-SO q , and aldoximes and lower alkyloximes, optionally substituted on oxygen by lower alkyl.
- Z is H, a C-C single bond, CH 2 , NH, O, S, CN, CH 2 O, OCH 2 , CH 2 CH 2 O, or OCH 2 CH 2 ; m is 4; p is 0 or 1 ; q is an integer from 0 to 2;
- R 1 is independently H, halo, lower alkyl, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, haloalkyl, haloalkoxy, NO 2 , CN, lower alkylcarbonyl, lower alkoxycarbonyl, mercapto, lower alkylthio, aldoximes and lower alkyloximes, optionally substituted on oxygen by lower alkyl;
- Y is a C-C single bond, C(R 5 n )O or C(R 5 n ); n is 2; alternatively R : m , Z, and R p may be taken together to form a fused 5 or 6 membered heterocycle optionally substituted with H, halo, lower alkyl, lower alkoxy, benzyloxy, lower alkenyl, lower alkynyl, haloalkyl, haloalkoxy, NO 2 , CN, lower alkylcarbonyl, lower alkoxycarbonyl and lower alkyl-SO q ;
- R 2 are independently H or lower alkyl
- R 4 is H, halogen, lower alkyl, lower alkoxy or lower haloalkyl
- R 5 are independently H or lower alkyl
- X 1 is NR 3 , O, and S, where R 3 is selected from H, lower alkyl, lower alkylcarbonyl, lower alkoxycarbonyl, hydroxy, lower alkoxy, lower alkyl-SO q , phenyl-SO q or substituted phenyl-SO q ;
- X is H, halogen or lower alkyl; and X 3 is H, halogen or lower alkyl; with the proviso that when Y is C(R 5 n ) , R 2 n and R : m may be taken together to form
- the invention also provides new compounds of formula (I-B):
- R is H, CH 3 , haloalkyl, phenyl, or a heterocycle comprising a 5 or 6 membered single ring or a fused ring system comprising at least one 5 or 6 membered heterocycle optionally substituted with H, halo, lower alkyl, lower alkoxy, benzyloxy, lower alkenyl, lower alkynyl, haloalkyl, haloalkoxy, NO 2 , CN, lower alkoxycarbonyl, lower alkylcarbonyl, lower alkyl- SO q , aldoximes and lower alkyloximes, optionally substituted on oxygen by lower alkyl;
- Z is H, a C-C single bond, CH 2 , NH, O, S, CN, CH 2 O, OCH 2 , CH 2 CH 2 O, or
- R 1 is independently H, halo, lower alkyl, lower alkenyl, lower alkynyl, hydroxy, lower alkoxy, haloalkyl, haloalkoxy, NO 2 , CN, lower alkylcarbonyl, lower alkoxycarbonyl, mercapto, lower alkylthio, aldoximes and lower alkyloximes, optionally substituted on oxygen by lower alkyl;
- Y is a C-C single bond, C(R 5 n )O or C(R 5 n );
- n is 2; alternatively R ⁇ m , Z, and R ⁇ may be taken together to form a fused 5 or 6 membered heterocycle optionally substituted with H, halo, lower alkyl, lower alkoxy, benzyloxy, lower alkenyl, lower alkynyl, haloalkyl, haloalkoxy, NO 2 , CN, lower alkylcarbonyl, lower alkoxycarbony
- R 2 are independently H or lower alkyl
- R 4 is H, halogen, lower alkyl, lower alkoxy or lower haloalkyl
- R 5 are independently H or lower alkyl
- X 1 is NR 3 , O, and S, where R 3 is selected from H, lower alkyl, lower alkylcarbonyl, lower alkoxycarbonyl, hydroxy, lower alkoxy, lower alkyl-SO q , phenyl-SO q or substituted phenyl-SO q ;
- X is H, halogen or lower alkyl; and X 3 is H, halogen or lower alkyl; with the proviso that when Y is C(Renfin) , R 2 n and R : m may be taken together to form
- the invention also provides new pesticide methods and compositions utilizing the compounds of formula (I- A) and compounds of formula (I-B).
- the invention includes fungicidal, insecticidal, acaricidal, and anti-parasitic compositions comprising an effective amount of a compound of the present invention in a mixture with an agriculturally acceptable or pharmaceutically acceptable adjuvant or carrier.
- the invention also includes methods of controlling a fungus, insect, mite, or parasite comprising applying an effective amount of a compound of the present invention to the fungus, insect or mite, soil, plant, root, foliage, seed, locus, or animal (for which purpose they may be administered orally, parenterally, percutaneously or topically) in which the infestation is to be prevented or cured.
- the compounds of the present invention are directed to compounds of formula (I- A) and (I-B)
- R may be an optionally substituted phenyl or a heterocycle comprising a 5 or 6 membered single ring or a fused ring system comprising at least one 5 or 6 membered heterocycle. More specifically, R may be selected from the list including but not limited to: optionally substituted pyridinyl
- r 1 optionally substituted pyrazinyl
- N :V optionally substituted pyrimidinyl optionally substituted pyridazinyl optionally substituted thiazolyl optionally substituted 1,2,3-thiadiazolyl optionally substituted 1,2,4-thiadiazolyl optionally substituted 1,3,4-thiadiazolyl as well as pyridinyl-N-oxide, thienyl, furyl, oxazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, furazanyl, pyrrolyl, pyrazolyl, and imidazolyl, where r is 4 in the case of pyridinyl, 3 in the case of pyrazinyl, pyrimidinyl, and pyridazinyl, 2 in the case of thiazolyl and 1 in the case of thiadiazolyl, and R 7 are independently H, halo, lower alkyl, lower alkoxy, benzyloxy, lower alkenyl, lower
- alkyl alkenyl and alkynyl
- derivative terms such as “alkoxy” and “alkylthio,” as used herein, include within their scope straight chain, branched chain and cyclic moieties.
- alkenyl and alkynyl are intended to include one or more unsaturated bonds.
- halo refers to F, Cl, Br, and I atoms.
- lower alkyl refers to Ci to Ce straight hydrocarbon chains and C 3 to Ce branched and cyclic hydrocarbon groups.
- lower alkenyl and lower alkynyl refer to C 2 to Ce straight hydrocarbon chains and C 3 (or C 4 in the case of lower alkynyl) to Ce branched hydrocarbon groups containing at least one unsaturated bond.
- lower alkoxy and “lower alkylthio” refer to 0-lower alkyl and S-lower alkyl groups.
- haloalkyl refers to lower alkyl groups substituted with one or more halo atoms.
- haloalkoxy refers to lower alkoxy groups substituted with one or more halo atoms.
- substituted phenyl refers to phenyl substituted with lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, lower alkylthio, halo, hydroxy, NO 2 , haloalkyl, haloalkoxy, haloalkylthio, CN, phenyl, substituted phenyl, O-phenyl, O-substituted phenyl, Ci-C 4 alkanoyloxy, Ci-C 4 alkoxycarbonyl, lower alkylcarbonyl, benzyloxy, or and lower alkyl-SO q and q is an integer from 0 to 2.
- fused ring system refers to two rings joined, as defined in Moss, G.P. Pure and Applied Chemistry, 1998, 70, 143: "For ring systems... two rings which have two atoms and one bond in common may be regarded as being derived from the two rings as separate entities. The process of joining rings in this way is termed fusion.”
- the compounds of this invention are made using well known chemical procedures.
- the required starting materials are commercially available or are readily synthesized using standard procedures.
- R 4 , X 2 and X 3 are as defined as for compounds of formula (I-A); and L is a group such as F, Cl, Br, 1,2,3-triazol-l-yl, 1,2,4-triazol-l-yl, OH, arylthio, alkylthio, alkylsulfonyl, arylsulfonyl, alkoxy, alkylsulfinyl, or arylsulfinyl; with a compound of the formula (III- A)
- DMSO dimethylsulfoxide
- DMF N,N-dimethylformamide
- compounds of formula (I-A) can be made by reaction of a dicarbonyl or equivalent compound with a compound of formula (I ⁇ T-B)
- R, R 1 , R 2 , X 3 , Y, Z. m, n, and/? are as defined for compounds of formula (I-A) and X 1 is O, as in step c of Scheme I.
- Representative dicarbonyl compounds include glyoxal, 2,3- butanedione and l,4-dioxane-2,3-diol.
- the reaction is preferably carried out in an alcohol solvent, alternatively containing toluene, at a temperature in the range of 0 0 C to reflux temperature.
- compounds of formula (INT-B) can be synthesized by reduction of a 6-amino- 5-nitropyrimidine compound of formula (INT-A)
- R, R 1 , R 2 , X 3 , Y, Z, m, n, and/? are as defined for compounds of formula (I- A) as in step b of Scheme I.
- Reduction can be achieved by hydrogenation in the presence of a palladium catalyst in an alcohol solvent.
- reaction is preferably carried out in the presence of a base in a non- reactive solvent, such as CH 2 CI 2 , THF, DMSO or DMF, at a temperature in the range of 0° to reflux temperature.
- a non- reactive solvent such as CH 2 CI 2 , THF, DMSO or DMF
- Compounds of formula (III-A), where R is a phenyl or heteroaryl may be synthesized by reaction of compounds of formula (III-A) where R is H, with a compound of formula M-Het where M is a group such as F, Cl, Br, I, 1,2,3-triazol-l-yl, 1,2,4-triazol-l-yl, OH, arylthio, alkylthio, alkylsulfonyl, arylsulfonyl, alkoxy, alkylsulfinyl, or arylsulfinyl; and wherein Het is a phenyl or heterocycle, as in step /of Scheme I.
- M is a group such as F, Cl, Br, I, 1,2,3-triazol-l-yl, 1,2,4-triazol-l-yl, OH, arylthio, alkylthio, alkylsulfonyl, arylsul
- Het may be optionally substituted with one or more groups selected from H, halo, lower alkyl, lower alkoxy, benzyloxy, lower alkenyl, lower alkynyl, haloalkyl, haloalkoxy, NO 2 , CN, lower alkoxycarbonyl, lower alkylcarbonyl and lower alkyl-SO q .
- the reaction is preferably carried out in the presence of a base in a non-reactive solvent, such as CH 2 CI 2 , THF, DMSO or DMF, at a temperature in the range of 0 0 C to reflux temperature.
- a non-reactive solvent such as CH 2 CI 2 , THF, DMSO or DMF
- the compounds of formula (I- A) wherein X 1 is NH or N-lower alkyl and R, R 1 , R 2 , R 4 , X 2 , X 3 , Y, Z, m, n and/? are as defined for compounds of formula (I- A), can be made in the same manner as described for Scheme I, from compounds of the formulas (II), (III- A), (INT-A), (INT-B) wherein R, R 1 , R 2 , R 4 , X 2 , X 3 , Y, Z, m, n and/? are as defined for formula (I- A), and X 1 is NH or N-lower alkyl.
- the compounds of formula (I-A) wherein X 1 is NH or N-lower alkyl and Z is as defined for compounds of formula (I-A), can be made by condensing a compound of formula (II)
- R 4 , X 2 , and X 3 are as defined as for compounds of formula (I- A); and L is a group, such as F, Cl, Br, 1,2,3-triazol-l-yl, 1,2,4-triazol-l-yl, OH, arylthio, alkylthio, alkylsulfonyl, arylsulfonyl, alkoxy, alkylsulfinyl, or arylsulfinyl; with a compound of the formula (III-A)
- R, R 1 , R 2 , Y, Z, m, n, and/? are as defined for compounds of formula (I- A) and X 1 is NH or N-lower alkyl, optionally as a salt (e.g., HCl), as in Scheme II.
- the reaction is preferably carried out in the presence of base, such as triethylamine, in a non-reactive solvent, such as CH 2 CI 2 , THF or DMF.
- the reaction may be carried out in hexamethyldisilazane in the presence of ammonium sulfate.
- R 1 , R 2 , R 4 , X 2 , X 3 , Y, Z, m and n are as defined for compounds of formula (I-A) and X 1 is NH or N-lower alkyl; with a compound of formula
- M-Het where M is a group such as F, Cl, Br, I, 1,2,3-triazol-l-yl, 1,2,4-triazol-l-yl, OH, arylthio, alkylthio, alkylsulfonyl, arylsulfonyl, alkoxy, alkylsulfinyl, or arylsulfinyl; and wherein Het is a phenyl or heterocycle, as in step c of Scheme III.
- Het may be optionally substituted with one or more groups selected from H, halo, lower alkyl, lower alkoxy, benzyloxy, lower alkenyl, lower alkynyl, haloalkyl, haloalkoxy, NO 2 , CN, lower alkoxycarbonyl, lower alkylcarbonyl and lower alkyl-SO q .
- the reaction is preferably carried out in the presence of a base in a non-reactive solvent, such as CH 2 CI 2 , THF, DMSO or DMF, at a temperature in the range of 0 0 C to reflux temperature.
- a non-reactive solvent such as CH 2 CI 2 , THF, DMSO or DMF
- R 1 , R 2 , R 3 , R 4 , Y, m and n are as defined for compounds of formula (I-A), X 1 is NH or N-lower alkyl, Z is oxygen, and R 6 is lower alkyl; with a reagent such as BBr 3 in a nonreactive organic solvent, such as CH 2 CI 2 .
- the compounds of formula (IV) alternatively may be prepared by treatment of compounds of formula (VI) wherein R 4 , X 2 and X 3 are as described for compound of formula (I-A),
- R 1 , R 2 , Y, m and n are as defined for compounds of formula (I-A), and R 3 is H; in the presence of acetic acid, optionally as a solution in an appropriate solvent such as ethanol; with heating at temperatures from 25° to reflux.
- the compounds of formula (IV) alternatively may be prepared by treatment of compounds of formula (II)
- R 4 , X 2 and X 3 are as defined for compounds of formula (I- A); and L is a leaving group, such as F, Cl, Br, I, NO 2 , 1,2,3-triazol-l-yl, 1,2,4-triazol-l-yl, OSiMe 3 , arylthio, alkylthio, alkylsulfonyl, arylsulfonyl, alkoxy, alkylsulfinyl or arylsulfinyl; with a compound of formula (VII), optionally as a salt (e.g., HCl),
- a salt e.g., HCl
- R 1 , R 2 , R 3 , Y, m and n are as defined for compounds of formula (I- A); optionally in the presence of a base, in a solvent such as acetonitrile, THF or DMF.
- R 1 , R 2 , Y, m and n are as defined for compounds of formula (I- A), R 3 is H, and R 6 is lower alkyl as defined for compounds of formula (I- A); in the presence of acetic acid, optionally as a solution in an appropriate solvent such as ethanol; with heating at temperatures from 25 0 C to reflux.
- Amines of formula (VIII-A) where R 1 , R 2 , R 3 , Y, m and n are as defined for compounds of formula (I- A) and R is lower alkyl as defined for compounds of formula (I- A); are commercially available or may be prepared by well-known methods.
- compounds of formula (VIII-A), where R 1 , R 2 , m and n are as defined for compounds of formula (I- A), R is lower alkyl, R 3 is H, and Y is Rvisor are prepared as their hydrochloride salts by treatment of appropriately substituted (4-alkoxyphenyl)-acetonitriles with hydrogen in the presence of hydrochloric acid, a catalyst such as palladium on carbon, and an appropriate solvent such as ethanol.
- compounds of formula (VIII-A), where R 1 , R 2 , m and n are as defined for compounds of formula (I- A), R 6 is lower alkyl, R 3 is H, Y is R 5 n are prepared by treatment of appropriately substituted (4-alkoxyphenyl)-acetonitriles with borane-dimethyl sulfide complex or lithium aluminum hydride in an appropriate solvent such as
- compounds of formula (VIII-A), where R 1 , R 2 , m and n are as defined for compounds of formula (I- A), R is lower alkyl, R 3 is H, and Y is R Paint are prepared as their hydrochloride salts by treatment of appropriately substituted l-alkoxy-4-((E)-2-nitrovinyl)- benzenes with hydrogen in the presence of hydrochloric acid, a catalyst such as palladium on carbon, and an appropriate solvent such as ethanol.
- compounds of formula (VIII-A), where R 1 , R 2 , m and n are as defined for compounds of formula (I-A), R 6 is alkyl or benzyl, R 3 is H, and Y is R 5 n are prepared by treatment of the appropriately substituted l-alkoxy-4-((E)-2-nitrovinyl)-benzenes with lithium aluminum hydride in an appropriate solvent such as tetrahydrofuran.
- the l-alkoxy-4-((E)-2-nitrovinyl)-benzenes are prepared by treatment of the appropriately substituted benzaldehyde with nitromethane in the presence of ammonium acetate.
- the compounds of formula (I- A) wherein X is NH alternatively are prepared by treatment of a compound of formula (VI), as defined above, with a compound of formula (III- A), optionally as a salt (e.g., HCl), where R, R 1 , R 2 , Y, Z, m, n and/? are as defined for compounds of formula (I- A) and X is NH; in the presence of acetic acid, optionally as a solution in an appropriate solvent such as ethanol; with heating at temperatures from 25° to reflux.
- acetic acid optionally as a solution in an appropriate solvent such as ethanol
- compounds of formula (I-B), wherein X 1 is NH can be prepared by treatment of a compound of formula (VI), as defined above, with a compound of formula (III- B)
- I ⁇ -B optionally as a salt (e.g., HCl), where R, R 1 , R 2 , Y, Z, m, n and/? are as defined for compounds of formula (I-B) and X is NH; in the presence of acetic acid, optionally as a solution in an appropriate solvent such as ethanol; with heating at temperatures from 25° to reflux.
- a salt e.g., HCl
- R, R 1 , R 2 , Y, Z, m, n and/? are as defined for compounds of formula (I-B) and X is NH
- acetic acid optionally as a solution in an appropriate solvent such as ethanol
- heating at temperatures from 25° to reflux Compounds of formula (III-B) can be prepared by the methods in the Preparations and Examples section.
- R, R 1 , R 2 , Y, Z, m, n, and/? are as defined for formula (I- A); and M is as defined in the reacting partner M-Het in Scheme III, step c.
- M is preferably chlorine or bromine.
- the reaction is preferably carried out in the presence of base, such as triethylamine, in a non-reactive solvent, such as CH 2 CI 2 , THF or DMF.
- the compounds of the present invention may be pesticides that have fungitoxic activity against harmful fungi including, but not limited to, fungi that are pathogens of plants, animals, and humans. They are active against fungi of a number of classes including Oomycetes, Deuteromycetes (Fungi Imperfecti), Basidiomycetes, and Ascomycetes.
- one embodiment of a method of the present invention provides for activity against phytopathogenic organisms including, but not limited to, Pyricularia oryzae, Colletotrichum species, Erysiphe species, Puccinia species, Cochliobolus species, Alternaria species, Septoria species, Rhynchosporium secalis, Cercospora and Cercosporella species, and Pyrenophora species.
- phytopathogenic organisms including, but not limited to, Pyricularia oryzae, Colletotrichum species, Erysiphe species, Puccinia species, Cochliobolus species, Alternaria species, Septoria species, Rhynchosporium secalis, Cercospora and Cercosporella species, and Pyrenophora species.
- Additional diseases controlled include powdery mildews incited by Sphaerotheca fulignea (cucurbit powdery mildew) and Uncinula necator (grape powdery mildew), soybean rust incited by Phakopsora pachyrhizi, downy mildews such as cucumber downy mildew (Pseudoperonospora cubensis), grape downy mildew (Plasmopara viticola), apple scab incited by Venturia inaequalis, late blight incited by Phytophthora infestans, and Maize smut (Ustilago maydis).
- Sphaerotheca fulignea cucurbit powdery mildew
- Uncinula necator soybean rust incited by Phakopsora pachyrhizi
- downy mildews such as cucumber downy mildew (Pseudoperonospora cubensis), grape downy mildew (P
- the compounds of the present invention may have insecticidal activity against harmful insects and mites including, but not limited to, insects that are pests or parasites of plants, animals, and humans.
- the invention disclosed in this document may be used to control pests of Phylum Nematoda, the Phylum Arthropoda, the Subphylum Chelicerata, the Class Arachnida, the Subphylum Myriapoda, the Class Symphyla, the Subphylum Hexapoda, the Class Insecta.
- the invention disclosed in this document may be use to control Coleoptera (beetles).
- a non-exhaustive list of these such pests includes, but is not limited to, Acanthoscelides spp.
- Ataenius spretulus Black Turfgrass Ataenius
- Atomaria linearis pygmy mangold beetle
- Aulacophore spp. Bothynoderes punctiventris (beet root weevil), Bruchus spp. (weevils), Bruchus pisorum (pea weevil), Cacoesia spp., Callosobruchus maculatus (southern cow pea weevil), Carpophilus hemipteras (dried fruit beetle), Cassida vittata, Cerosterna spp., Cerotoma spp.
- Conoderus stigmosus Conotrachelus nenuphar (plum curculio), Cotinus nitidis (Green June beetle), Crioceris asparagi (asparagus beetle), Cryptolestes ferrugineus (rusty grain beetle), Cryptolestes pusillus (flat grain beetle), Cryptolestes turcicus (Turkish grain beetle), Ctenicera spp. (wireworms), Curculio spp. (weevils), Cyclocephala spp. (grubs),
- Cylindrocpturus adspersus (sunflower stem weevil), Deporaus marginatus (mango leaf- cutting weevil), Dermestes lardarius (larder beetle), Dermestes maculates (hide beetle), Diabrotica spp. (chrysolemids), Epilachna varivestis (Mexican bean beetle), Faustinus cubae, Hy lobius pales (pales weevil), Hypera spp. (weevils), Hypera postica (alfalfa weevil), Hyperdoes spp.
- the invention disclosed in this document may be used to control Dermaptera (earwigs).
- the invention disclosed in this document may be used to control Dictyoptera (cockroaches).
- Dictyoptera cockroaches
- a non-exhaustive list of such pests includes, but is not limited to, Blattella germanica (German cockroach), Blatta orientalis (oriental cockroach), Parcoblatta pennsylvanica, Periplaneta americana (American cockroach), Periplaneta australoasiae (Australian cockroach), Periplaneta brunnea (brown cockroach), Periplaneta fuliginosa (smokybrown cockroach), Pycnoselus surinamensis (Surinam cockroach), and Supella longipalpa (brownbanded cockroach).
- the invention disclosed in this document may be used to control Diptera (true flies).
- a non-exhaustive list of such pests includes, but is not limited to, Aedes spp. (mosquitoes), Agromyza frontella (alfalfa blotch leafminer), Agromyza spp. (leaf miner flies), Anastrepha spp. (fruit flies), Anastrepha suspensa (Caribbean fruit fly), Anopheles spp. (mosquitoes), Batrocera spp. (fruit flies), Bactrocera cucurbitae (melon fly), Bactrocera dorsalis (oriental fruit fly), Ceratitis spp. (fruit flies), Ceratitis capitata
- Muscid flies Musca autumnalis (face fly), Musca domestica (house fly), Oestrus ovis (sheep bot fly), Oscinellafrit (frit fly), Pegomyia betae (beet leafminer), Phorbia spp., Psila rosae (carrot rust fly), Rhagoletis cerasi (cherry fruit fly), Rhagoletis pomonella (apple maggot), Sitodiplosis mosellana (orange wheat blossom midge), Stomoxys calcitrans (stable fly), Tabanus spp. (horse flies), and Tipula spp. (crane flies).
- the invention disclosed in this document may be used to control Hemiptera (true bugs).
- a non-exhaustive list of such pests includes, but is not limited to, Acrosternum hilare (green stink bug), Blissus leucopterus (chinch bug), Calocoris norvegicus (potato mirid), Cimex hemipterus (tropical bed bug), Cimex lectularius (bed bug), Dagbertus fasciatus, Dichelops furcatus, Dysdercus suturellus (cotton stainer), Edessa meditabunda, Eurygaster maura (cereal bug), Euschistus heros, Euschistus servus (brown stink bug), Helopeltis antonii, Helopeltis theivora (tea blight plantbug), Lagynotomus spp.
- the invention disclosed in this document may be used to control Homoptera (aphids, scales, whiteflies, leafhoppers).
- Homoptera aphids, scales, whiteflies, leafhoppers.
- a non-exhaustive list of such pests includes, but is not limited to, Acrytho siphon pisum (pea aphid), Adelges spp.
- adelgids Aleurodes proletella (cabbage whitefly), Aleurodicus disperses, Aleurothrixus floccosus (woolly whitefly), Aluacaspis spp., Amrasca bigutella bigutella, Aphrophora spp. (leafhoppers), Aonidiella aurantii (California red scale), Aphis spp. (aphids), Aphis gossypii (cotton aphid), Aphis pomi (apple aphid), Aulacorthum solani (foxglove aphid), Bemisia spp.
- Rhapalosiphum spp. aphids
- Rhapalosiphum maida corn leaf aphid
- Rhapalosiphum padi oat bird-cherry aphid
- Saissetia spp. scales
- Saissetia oleae black scale
- Schizaphis graminum greenbug
- Sitobion avenae English grain aphid
- Sogatella furcifera white- backed planthopper
- Therioaphis spp. aphids
- Toumeyella spp. scales
- Toxoptera spp. aphids
- the invention disclosed in this document may be used to control Hymenoptera (ants, wasps, and bees).
- Hymenoptera ants, wasps, and bees.
- a non-exhaustive list of such pests includes, but is not limited to, Acromyrrmex spp., Athalia rosae, Atta spp. (leafcutting ants),
- Camponotus spp. (carpenter ants), Diprion spp. (sawflies), Formica spp. (ants), Iridomyrmex humilis (Argentine ant), Monomorium spp., Monomorium minumum (little black ant), Monomorium pharaonis (Pharaoh ant), Neodiprion spp. (sawflies), Pogonomyrmex spp. (harvester ants), Polistes spp. (paper wasps), Solenopsis spp. (fire ants), Tapoinoma sessile (odorous house ant), Tetranomorium spp. (pavement ants), Vespula spp. (yellow jackets), and Xylocopa spp. (carpenter bees).
- the invention disclosed in this document may be used to control Isoptera (termites).
- a non-exhaustive list of such pests includes, but is not limited to, Coptotermes spp., Coptotermes curvignathus, Coptotermes frenchii, Coptotermes formosanus (Formosan subterranean termite), Cornitermes spp. (nasute termites), Cryptotermes spp. (drywood termites), Heterotermes spp. (desert subterranean termites), Heterotermes aureus, Kalotermes spp. (drywood termites), Incistitermes spp. (drywood termites), Macrotermes spp. (fungus growing termites), Marginitermes spp. (drywood termites), Microcerotermes spp. (harvester termites), Microtermes obesi, Procornitermes spp., Reticulitermes spp.
- Reticulitermes tibialis Reticulitermes virginicus
- Schedorhinotermes spp. and Zootermopsis spp. (rotten-wood termites).
- the invention disclosed in this document may be used to control Lepidoptera (moths and butterflies).
- Lepidoptera moths and butterflies.
- a non-exhaustive list of such pests includes, but is not limited to, Achoeajanata, Adoxophyes spp., Adoxophyes orana, Agrotis spp.
- Carposina niponensis peach fruit moth
- Chilo spp. Chlumetia transversa (mango shoot borer), Choristoneura rosaceana (obliquebanded leafroller), Chrysodeixis spp.,
- Cnaphalocerus medinalis grass leafroller
- Colias spp. Conpomorpha cramerella, Cossus cossus (carpenter moth), Crambus spp. (Sod webworms), Cydia funebrana (plum fruit moth), Cydia molesta (oriental fruit moth), Cydia nignicana (pea moth), Cydia pomonella (codling moth), Darna diducta, Diaphania spp. (stem borers), Diatraea spp.
- Polychrosis viteana (grape berry moth), Prays endocarpa, Prays oleae (olive moth), Pseudaletia spp. (noctuid moths), Pseudaletia unipunctata (armyworm), Pseudoplusia includens (soybean looper), Rachiplusia nu, Scirpophaga incertulas, Sesamia spp.
- the invention disclosed in this document may be used to control Mallophaga (chewing lice).
- Mallophaga chewing lice
- a non-exhaustive list of such pests includes, but is not limited to, Bovicola ovis (sheep biting louse), Menacanthus stramineus (chicken body louse), and Menopon gallinea (common hen louse).
- the invention disclosed in this document may be used to control Orthoptera (grasshoppers, locusts, and crickets).
- a non-exhaustive list of such pests includes, but is not limited to, Anabrus simplex (Mormon cricket), Gryllotalpidae (mole crickets), Locusta migratoria, Melanoplus spp. (grasshoppers), Microcentrum retinerve (angularwinged katydid), Pterophylla spp. (katydids), Schistocerca gregaria, Scudderia furcata (forktailed bush katydid), and Valanga nigricornis (short horned grasshopper).
- the invention disclosed in this document may be used to control Phthiraptera (sucking lice).
- Phthiraptera sucing lice
- a non-exhaustive list of such pests includes, but is not limited to, Haematopinus spp. (cattle and hog lice), Linognathus ovillus (sheep louse), Pediculus humanus capitis (human body louse), Pediculus humanus humanus (human body lice), and Pthirus pubis (crab louse).
- the invention disclosed in this document may be used to control Siphonaptera (fleas).
- Siphonaptera pests
- a non-exhaustive list of such pests includes, but is not limited to, Ctenocephalides canis (dog flea), Ctenocephalides felis (cat flea), and Pulex irritans (human flea).
- the invention disclosed in this document may be used to control Thysanoptera (thrips).
- Thysanoptera Thrips
- a non-exhaustive list of such pests includes, but is not limited to, Frankliniella fusca (tobacco thrips), Frankliniella occidentalis (western flower thrips), Frankliniella shultzei, Frankliniella williamsi (corn thrips), Heliothrips haemorrhaidalis (greenhouse thrips), Riphiphorothrips cruentatus, Scirtothrips spp., Scirtothrips citri (citrus thrips), Scirtothrips dorsalis (yellow tea thrips), Taeniothrips rhopalantennalis, and Thrips spp.
- the invention disclosed in this document may be used to control Thysanura (bristletails).
- Thysanura bristletails
- a non-exhaustive list of such pests includes, but is not limited to, Lepisma spp. (silverfish) and Thermobia spp. (firebrats).
- the invention disclosed in this document may be used to control Acarina (mites and ticks).
- a non-exhaustive list of such pests includes, but is not limited to, Acarapsis woodi (tracheal mite of honeybees), Acarus spp. (food mites), Acarus siro (grain mite), Aceria mangiferae (mango bud mite), Aculops spp., Aculops lycopersici (tomato russet mite), Aculops pelekasi, Aculus pelekassi, Aculus convincedendali (apple rust mite), Amblyomma americanum (lone star tick), Boophilus spp.
- Dermatophagoides pteronyssinus house dust mite
- Eotetranycus spp. Eotetranychus carpini (yellow spider mite)
- Epitimerus spp. Eriophyes spp.
- Ixodes spp. ticks
- Tetranychus urticae two-spotted spider mite
- Varroa destructor honey bee mite
- the invention disclosed in this document may be used to control Nematoda (nematodes).
- Nematoda nematodes
- a non-exhaustive list of such pests includes, but is not limited to, Aphelenchoides spp. (bud and leaf & pine wood nematodes), Belonolaimus spp. (sting nematodes), Criconemella spp. (ring nematodes), Dirofilaria immitis (dog heartworm), Ditylenchus spp. (stem and bulb nematodes), Heterodera spp. (cyst nematodes), Heterodera zeae (corn cyst nematode), Hirschmanniella spp.
- root nematodes Hoplolaimus spp. (lance nematodes), Meloidogyne spp. (root knot nematodes), Meloidogyne incognita (root knot nematode), Onchocerca volvulus (hook-tail worm), Pratylenchus spp. (lesion nematodes), Radopholus spp. (burrowing nematodes), and Rotylenchus reniformis (kidney- shaped nematode).
- the invention disclosed in this document may be used to control Symphyla (symphylans).
- Symphyla symphylans
- a non-exhaustive list of such pests includes, but is not limited to, Scutigerella immaculata.
- the invention disclosed in this document may be used to control animal and human parasites.
- a non-exhaustive list of such pests includes, but is not limited to, arthropods such as mites (e.g., mesostigmatids, itch, mange, scabies, chiggers), ticks (e.g., soft-bodied and hard-bodied), lice (e.g., sucking, biting), fleas (e.g., dog flea, cat flea, oriental rat flea, human flea), true bugs (e.g., bed bugs, Triatomid bugs), bloodsucking adult flies (e.g., horn fly, horse fly, stable fly, black fly, deer fly, louse fly, tsetse fly, mosquitoes), and parasitic fly maggots (e.g, bot fly, blow fly, screwworm, cattle grub, fleeceworm); helminths such as nematodes (e.g., threadworm, lungworm, hook
- compositions suitable for administration to vertebrates or man include preparations suitable for oral, parenteral, percutaneous, e.g. pour-on, or topical administration.
- compositions for oral administration comprise one or more of the compounds of general formula (I- A) or (I-B) in association with pharmaceutically acceptable carriers or coatings and include, for example, tablets, pills, capsules, pastes, gels, drenches, medicated feeds, medicated drinking water, medicated dietary supplements, slow-release boluses or other slow-release devices intended to be retained within the gastrointestinal tract. Any of these may incorporate active ingredient contained within microcapsules or coated with acid- labile or alkali-labile or other pharmaceutically acceptable enteric coatings. Feed premixes and concentrates containing compounds of the present invention for use in preparation of medicated diets, drinking water or other materials for consumption by animals may also be used.
- compositions for parenteral administration include solutions, emulsions or suspensions in any suitable pharmaceutically acceptable vehicle and solid or semisolid subcutaneous implants or pellets designed to release active ingredient over a protracted period and may be prepared and made sterile in any appropriate manner known to the art.
- compositions for percutaneous and topical administration include sprays, dusts, baths, dips, showers, jets, greases, shampoos, creams, wax-smears, or pour-on preparations and devices (e.g. ear tags) attached externally to animals in such a way as to provide local or systemic arthropod control.
- formulations for application to plants, seeds, or soil are applied following dilution of the concentrated formulation with water as aqueous solutions, suspensions or emulsions, or combinations thereof.
- solutions, suspensions or emulsions are produced from water-soluble, water-suspended or water-suspendable, water-emulsified or water- emulsifiable formulations or combinations thereof which are solids, including and usually known as wettable powders or water dispersible granules; or liquids including and usually known as emulsifiable concentrates, aqueous suspensions or suspension concentrates, and aqueous emulsions or emulsions in water, or mixtures thereof such as suspension-emulsions.
- any materials to which this composition can be added may be used, provided they yield the desired utility without significant interference with the desired activity of the pesticidally active ingredients as pesticidal agents.
- Wettable powders which may be compacted to form water dispersible granules, comprise an intimate mixture of one or more of the pesticidally active ingredients, an inert carrier and surfactants.
- concentration of the pesticidally active ingredient in the wettable powder is usually 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 pesticidally active ingredients can 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 pesticidally active ingredient comprise a convenient concentration, such as from about 10 weight percent to about 50 weight percent of the pesticidally active ingredient, in a suitable liquid, based on the total weight of the pesticidally active ingredient
- the pesticidally active ingredients are 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, such as, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2- ethoxyethanol.
- Emulsifiers which can be advantageously employed herein can 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 esterified with the polyol or polyoxyalkylene.
- Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts.
- Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulfonic acids, oil-soluble salts of sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.
- organic liquids which can be employed in preparing emulsifiable concentrates 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; and glycol ethers such as the H-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 amides of various fatty acids, particularly the dimethyl amide
- Surface- active emulsifying 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 emulsifying agents.
- 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 pesticidally active ingredients dispersed in an aqueous vehicle at a concentration in the range from about 5 to about 70 weight percent, based on the total weight of the aqueous suspension.
- Suspensions are prepared by finely grinding one or more of the pesticidally active ingredients, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above.
- Other components such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle. It is often most effective to grind and mix at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.
- Aqueous emulsions comprise emulsions of one or more water-insoluble pesticidally active ingredients emulsified in an aqueous vehicle at a concentration typically in the range from about 5 to about 70 weight percent, based on the total weight of the aqueous emulsion. If the pesticidally active ingredient is a solid it must be dissolved in a suitable water- immiscible solvent prior to the preparation of the aqueous emulsion.
- Emulsions are prepared by emulsifying the liquid pesticidally active ingredient or water-immiscible solution thereof into an aqueous medium typically with inclusion of surfactants that aid in the formation and stabilization of the emulsion as described above.
- compositions of the present invention can also be granular formulations, which are particularly useful for applications to the soil.
- Granular formulations usually contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the pesticidally active ingredient(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 pesticidally active ingredients 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 can be prepared by intimately mixing one or more of the pesticidally active ingredients 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 pesticidally active ingredients onto the target site such as a crop or 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 of sulfosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines and blends of surfactants with mineral or vegetable oils.
- the formulations may optionally include combinations that contain one or more other pesticidal compounds.
- additional pesticidal compounds may be fungicides,
- the compounds of the present invention, and the pesticidal compound in the combination can generally be present in a weight ratio of from 1 : 100 to 100: 1.
- the compounds disclosed in this invention can be in the form of pesticidally acceptable acid addition salts.
- an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids.
- an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines.
- preferred cations include sodium, potassium, magnesium, and aminium cations.
- the salts are prepared by contacting the free base form with a sufficient amount of the desired acid to produce a salt.
- the free base forms may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous NaOH, potassium carbonate, ammonia, and sodium bicarbonate.
- a pesticide is modified to a more water soluble form e.g. 2,4-dichlorophenoxy acetic acid dimethyl amine salt is a more water soluble form of 2,4-dichlorophenoxy acetic acid, a well known herbicide.
- the compounds disclosed in this invention can also form stable complexes with solvent molecules that remain intact after the non-complexed solvent molecules are removed from the compounds. These complexes are often referred to as "solvates”.
- stereoisomers The various stereoisomers include geometric isomers, diastereomers, and enantiomers.
- the compounds disclosed in this invention include racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the others. Individual stereoisomers and optically active mixtures may be obtained by selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures.
- the compounds of the present invention can also be combined with other agricultural fungicides to form fungicidal mixtures and synergistic mixtures thereof.
- the fungicidal compounds of the present invention are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases.
- the presently claimed compounds can 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 include but are not limited to 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, BYF 1047, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chloroneb, chlorothalonil, chl
- the compounds of the present invention can be combined with other pesticides, including insecticides, nematicides, 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 pesticidal compounds of the present invention are often applied in conjunction with one or more other insecticides, miticides, or other pesticides to control a wider variety of undesirable pests.
- the presently claimed compounds can 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, rf-limonene, nicotine, pyrethrins, cinerins, cinerin I, cinerin II, jasmolin I, jas
- insecticides such as acrylonitrile, carbon disulfide, carbon tetrachloride, chloroform, chloropicrin, para-dichlorobenzene, 1 ,2-dichloropropane, ethyl formate, ethylene dibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, iodomethane, methyl bromide, methylchloroform, methylene chloride, naphthalene, phosphine, sulfuryl fluoride and tetrachloroethane; inorganic insecticides such as borax, calcium polysulfide, copper oleate, mercurous chloride, potassium thiocyanate and sodium thiocyanate; chitin synthesis inhibitors such as bistrifluron, buprofezin, chlorfluazuron, cyromazine, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron
- methoxyfenozide and tebufenozide moulting hormones such as ⁇ -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, 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, propa
- 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 pesticidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants, diseases, and pests.
- 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,
- 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-TB A and tricamba; pyrimidinyloxy benzoic acid herbicides such as bispyribac and py ⁇ minob3ic; 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 benzofluor, perfluidone, pyrimisulfan and profluazol;
- diphenyl ether herbicides such as ethoxyfen; nitrophenyl ether herbicides such as acifluorfen, aclonifen, bifenox, chlomethoxyfen, chlornitrofen, etnipromid, fluorodifen, fluoroglycofen, fluoronitrofen, fomesafen, furyloxyfen, halosafen, lactofen, nitrofen, 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,
- 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
- thiocarbonate herbicides such as dimexano, EXD and proxan
- thiourea herbicides such as methiuron
- triazine herbicides such as dipropetryn, indaziflam, triaziflam and
- 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,
- 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,
- 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, thiazafluron 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, flurochloridone, flurtamone, fluthiacet, indanofan, methyl isothiocyanate, OCH, oxaziclomefone, pentachlorophenol, pentoxazone, phenylmercury a
- the compounds of the present invention may have broad ranges of efficacy as pesticides.
- 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 pathogen or pest to be controlled, and the stage of growth thereof, as well as the part of the plant, animal or other medium 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 pathogen and pest species.
- the compounds are effective in use with plants in a phytologically acceptable amount.
- phytologically acceptable amount refers to an amount of a compound that kills or inhibits the pest or 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 parts per million (ppm), with 1 to 500 ppm being preferred.
- concentration of compound required varies with the pest or disease to be controlled, the type of formulation employed, the method of application, the particular plant or animal species, climate conditions, and the like.
- fungicides dilution and rate of application will depend upon the type of equipment employed, the method and frequency of application desired and diseases to be controlled, but the effective amount is usually from about 0.01 kilogram (kg) to about 20 kg of active ingredient (a.i.) per hectare (ha).
- a compound of the present invention is usually applied to growing plants at a rate of about 0.1 to about 5 and preferably from about 0.125 to about 0.5 kg per hectare.
- the amount of toxicant coated on the seed is usually at a dosage rate of about 0.1 to about 250 grams (g) and preferably from about 1 to about 60 g per 100 kg of seed.
- the chemical can be incorporated in the soil or applied to the surface of the soil or a rice nursery box usually at a rate of about 0.1 to about 5 kg per hectare.
- the actual amount of insecticide or miticide to be applied to loci of pests is generally not critical and can readily be determined by those skilled in the art. In general, concentrations from about 10 g of pesticide per hectare to about 5000 g of pesticide per hectare are expected to provide good control.
- the locus to which a pesticide is applied can be any locus inhabited by a pest, for example, vegetable crops, fruit and nut trees, grape vines, ornamental plants, domesticated animals, the interior or exterior surfaces of buildings, and the soil around buildings.
- Controlling pests generally means that pest populations, activity, or both, are reduced in a locus. This can come about when: pest populations are repulsed from a locus; when pests are incapacitated, partially or completely, temporarily or permanently, in or around a locus; or pests are exterminated, in whole or in part, in or around a locus. Of course a combination of these results can occur.
- pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent, even more preferably 99 percent.
- the baits are placed in the ground where, for example, termites can come into contact with the bait.
- Baits can also be applied to a surface of a building, (horizontal, vertical, or slant, surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with the bait.
- Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying the pesticides to a different portion of the plant, or to a location where the root system of a plant can uptake pesticides.
- control of foliar-feeding insects can be controlled by drip irrigation or furrow application, or by treating the seed before planting.
- Seed treatment can be applied to all types of seeds, including those from which plants genetically transformed to express specialized traits will germinate.
- Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as "Roundup Ready” seed, or those with "stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement or any other beneficial traits.
- seed treatments with the invention disclosed in this document can further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time.
- the invention may be used with plants genetically transformed to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement or any other beneficial traits.
- specialized traits such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement or any other beneficial traits.
- An example of such a use is spraying such plants with the invention disclosed in this document.
- the invention disclosed in this document may be suitable for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of animal keeping.
- Compounds according to the invention are applied here in a known manner, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.
- the invention disclosed in this document may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese.
- Suitable formulations may be administered orally to the animals with the drinking water or feed.
- the dosages and formulations that are suitable depend on the species.
- Example 1 r2-(4-Benzyloxyphenyl)-ethyll-pteridin-4-yl-amine.
- pteridin-4- ol 282 mg, 1.9 mmol
- 2-(4-benzyloxyphenyl)-ethylamine 476 mg, 2.1 mmol
- hexamethyldisilazane 5 mL
- ammonium sulfate 100 mg, 0.76 mmol
- Example 2 4- r2-(Pteridin-4-ylamino)-ethyll -phenol.
- iV-(3-cyanopyrazin-2- yl)-N,N-dimethylformamidine prepared as in Albert and Ohta, /. Chem. Soc. C 1971, 3727- 3730, which is expressly incorporated by reference herein; 2.0 g, 11.4 mmol
- ethyl alcohol EtOH; 50 mL
- 4-(2-aminoethyl)-phenol 4.7 g, 34 mmol
- acetic acid 3.9 mL, 4.1 g, 68 mmol.
- Example 3 Alt. Pteridin-4-yl- ⁇ 2- r4-(4-trifluoromethylpyridin-2-yloxy Vphenyll -ethyl 1 - amine.
- 4-[2-(pteridin-4-ylamino)ethyl]phenol (2.5 g, 9.3 mmol) and DMSO (20 mL) in a 100 mL round bottom flask, equipped with reflux condenser, drying tube and magnetic stir bar was added 2-fluoro-4-(trifluoromethyl)pyridine (prepared as in U.S.
- Patent 4,775,762 which is expressly incorporated by reference herein; 1.7 g, 10 mmol) and cesium carbonate (Cs 2 COs; 3.7 g, 11.5 mmol).
- This mixture was heated to 57 0 C for 16 h, then cooled to ambient temperature and poured into ice H 2 O (150 mL), precipitating an off-white solid. This was collected by suction filtration and the filter cake was washed with H 2 O and then pentane. The cake was then dissolved in CH 2 Cl 2 , dried with Na 2 SO 4 , and the solution was filtered.
- Example 5 ⁇ 2- r4-(6-Methoxypyridin-2-yloxy)-phenyl] -ethyl 1 -pteridin-4-yl-amine. ⁇ 2- [4- (6-Fluoropyridin-2-yloxy)-phenyl] -ethyl ⁇ -pteridin-4-ylamine (200 mg, 0.55 mmol) was dissolved in 4 mL dry DMSO and treated with sodium methoxide (300 mg, 5.5 mmol, 10 eq) and stirred for 20 h at 25 0 C. The mixture was poured into H 2 O (15 mL) and extracted with CH 2 Cl 2 (2 x 25 ml).
- Pteridin-4-yl-(2- ⁇ 4-r6-(2,2,2-trifluoroethoxy)-pyridin-2-yloxyl-phenylj-ethyl)-amine from sodium 2,2,2-trifluoroethoxide, prepared by treatment of 2,2,2-trifluoroethanol with sodium hydride.
- Example 8 (2- ⁇ 4-r6-(2-Methoxyethoxy)-4-trifluoromethyl-pyridin-2-yloxyl-phenyll-ethyl)- pteridin-4-yl-amine.
- ⁇ 2-[4-(6-chloro-4-trifluoromethylpyridin-2-yloxy)- phenyl] -ethyl ⁇ -pteridin-4-yl-amine 320 mg, 0.7 mmol
- NaH 50 mg, 60% dispersion in oil
- Example 9 Pteridin-4-yl-(2- ⁇ 4-r4-(2,2,2-trifluoroethoxy)-pyridin-2-yloxyl-phenylj-ethyl)- amine.
- N-(2- ⁇ 4-[(4-iodopyridin-2-yl)oxy]phenyl ⁇ ethyl)pteridin-4-amine 300 mg, 0.64 mmol
- 2,2,2-trifluoroethanol 5 mL, 1.27 mmol
- Cs 2 CO 3 (412 mg, 1.27 mmol)
- 1,10-phenanthroline 22 mg, 0.127 mmol
- CuI (12 mg, 0.064 mmol
- Example 10 ⁇ 2-r4-(6-Fluoropyridin-3-yl)-phenyll-ethyll-pteridin-4-yl-amine.
- To a round bottom flask was added [2-(4-bromophenyl)-ethyl]-pteridin-4-yl-amine (200 mg, 0.61 mmol), 2-fluoro-5-pyridineboronic acid (102 mg, 0.73 mmol), NaHCO 3 (102 mg, 1.21 mmol), PdCl 2 (PPh 3 ) 2 (213 mg) and 50% aqueous ethylene glycol dimethyl ether (DME; 3.0 niL).
- DME 50% aqueous ethylene glycol dimethyl ether
- 6-Chloronicotinic acid methyl ester.
- oxalyl chloride 123.3 niL, 0.15 mol
- DMF dimethyl methoxylate
- 6-(4-Trifluoromethylphenoxy)-nicotinic acid methyl ester 6-(4-Trifluoromethylphenoxy)-nicotinic acid methyl ester.
- a solution of NaH (60% dispersion in oil; 1.2 g, 30 mmol) in 30 mL of DMSO was added a solution of 4- (trifluoromethyl)phenol (1.86 g, 30 mmol) in 20 mL of DMSO and the mixture was stirred for 30 min.
- methyl 6-chloronicotinate 5.13 g, 30 mmol
- the solution washed with H 2 O, brine, dried with Na 2 SO 4 , suction filtered, and the solvent removed in vacuo.
- Example 11 ⁇ 2- r4-(4-Isopropylphenoxy)-phenyll -ethyl j -pteridin-4-yl-amine. 4- [2- (Pteridin-4-ylamino)-ethyl] -phenol (500 mg, 1.9 mmol), 4-isopropylphenylboronic acid (400 mg, 2.4 mmol), anh.
- Example 13 ⁇ 2-r4-(ferf-Butyldimethylsilanyloxy)-phenyll-ethylj-pteridin-4-yl-carbamic acid ferf-butyl ester.
- 2- [4-(ferz-Butyldimethylsilanyloxy)-phenyl] -ethyl ⁇ -pteridin-4-yl- amine (10.15 g, 3.0 mmol) was dissolved in dry DMF (50 mL), treated with ⁇ i-tert- butyldicarbonate (730 mg, 3.3 mmol) plus approximately DMAP (N,N-dimethyl-4- aminopyridine; 25 mg) and stirred at 25 0 C for 22 h.
- Example 15 5-r2-(Pteridin-4-ylamino)-ethyll-2-(4-trifluoromethyl-pyridin-2-yloxy)-benzoic acid, methyl ester.
- ⁇ 2-[3-bromo-4-(4-trifluoromethylpyridin-2-yloxy)- phenyl] -ethyl ⁇ -pteridin-4-yl-amine 243 mg, 0.5 mmol
- Pd(OAc) 2 5.6 mg, 0.25 mmol
- DPPB 21 mg, 0.5 mmol
- K 2 CO 3 138 mg, 1 mmol
- the reactor was sealed and charged with 300 psi of CO.
- the reaction was heated to 110 0 C for 15 h, cooled to ambient temperature, filtered through Celite, and concentrated in vacuo.
- the residue was dissolved in CH 2 Cl 2 , washed with H 2 O, brine, dried over Na 2 SO 4 , suction filtered and concentrated in vacuo.
- the residue was slurried in Et 2 O and pentane.
- Example 16 Pteridin-4-yl- ⁇ 2-r4-(3,5,6-trifluoro-4-trifluoromethyl-pyridin-2-yloxy)-phenyll-ethyll- amine.
- 4- [2-(Pteridin-4-ylamino)-ethyl] -phenol (0.27 g, 1.0 mmol), 2,3,5,6-tetrafluoro-4- trifluoromethylpyridine (0.24 g, 1.0 mmol) and DMF (5 mL) were added to a 25 mL round bottom flask equipped with magnetic stirring bar and dry nitrogen line. To the reaction mixture was added Et 3 N (0.12 g, 1.2 mmol).
- Example 18 2-r4-(l,l-Difluoroethyl)-pyridin-2-yloxyl-5-r2-(pteridin-4-ylamino)-ethyll- phenol.
- (2- ⁇ 4-[4-(l,l-difluoroethyl)-pyridin-2-yloxy]-3-methoxyphenyl ⁇ - ethyl)-pteridin-4-yl-amine (1.37 g, 3.13 mmol) in CH 2 Cl 2 (15 mL) cooled to O 0 C, was added IM BBr 3 /hexane (9.4 mL, 9.4 mmol). The solution was allowed to warm to room
- Example 19 ⁇ 2-r3-(Isopropoxy)-4-(4-trifluoromethy-pyridin-2-yloxy)-phenyl1-ethyl)- pteridin-4-ylamine.
- 2-iodopropane 62 mg, 0.5 mmol
- K 2 CO 3 97 mg, 0.7 mmol
- Example 20 Acetic acid 5- r2-(pteridin-4-ylamino)-ethyH -2-(4-trifluoromethylpyridin-2- yloxy) -phenyl ester.
- 5-[2-(Pteridin-4-ylamino)- ethyl]-2-(4-trifluoromethylpyridin-2-yloxy)-phenol 330 mg, 0.7 mmol
- pyridine 0.5 mL
- DMAP 5 mg
- the solution was stirred at ambient temperature for 15 h, then diluted with CH 2 Cl 2 and washed sequentially with H 2 O and saturated aqueous NaHCO 3 solution.
- Example 21 (2- ⁇ 4- [4-( 1 , 1 -Difluoroethyl)-6-methoxypyridin-2-yloxy1 -phenyl j -ethyl)- pteridin-4-yl-amine.
- the organic layer was filtered and concentrated in vacuo to provide a black oil (20.66 g).
- the oil was extracted with isopentane (3 x 150 mL) and the pooled isopentane fractions were concentrated in vacuo to provide an orange oil (10 g); the dark insoluble residue was set aside.
- the orange oil was passed over a Si ⁇ 2 column with Et 2 O/pentane (1 :1) eluent.
- the appropriate fractions were pooled and concentrated in vacuo to provide 7.0 g of l,4-bisbenzyloxy-2-methylbenzene as a pale yellow oil, which solidified on standing.
- reaction mixture was concentrated in vacuo, then taken up in H 2 O (200 mL). After adjusting pH to 4 with 2N HCl, the aqueous layer was washed with an equi volume of Et 2 O /pentane (1:1). The organic layer was concentrated in vacuo to provide a yellow-brown oil (6.45 g). The oil was subjected to preparative HPLC to provide a slightly purified product, after pooling appropriate fractions.
- Example 22 4- ⁇ 2- r4-(4-Trifluoromethylpyridin-2-yloxy)-phenyll -ethoxy j -pteridine.
- 2-r4-(4-Trifluoromethylpyridin-2-yloxy)-phenyll-ethanol 2-(4-Hydroxyphenyl)ethanol (4.0 g, 29 mmol), K 2 CO 3 (8.0 g, 58 mmol) and 2-fluoro-4-trifluoromethylpyridine (3.6 g, 22 mmol) were combined in DMSO (30 mL) and stirred at 25°C for 20 h. The mixture was poured into H 2 O and extracted twice with Et 2 O.
- the crude diamino ether (6- ⁇ 2- [4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethoxy ⁇ -pyrimidine-4,5-diamine) was obtained by removal of the solvent in vacuo to provide 6- ⁇ 2-[4-(4-trifluoromethylpyridin-2- yloxy) -phenyl] -ethoxy ⁇ -pyrimidine-4,5-diamine, which was used in the next step without further purification.
- Example 23 ⁇ 2-r4-(4-tert-Butylpyridin-2-yloxy)-phenyll-ethylj-pteridin-4-ylamine. ⁇ 2-[4- (4-?er?-Butyl-l-oxypyridin-2-yloxy)-phenyl] -ethyl ⁇ -pteridin-4-ylamine (500 mg, 1.2 mmol) and triphenylphosphine (310 mg,1.2 mmol) were dissolved in dry THF (15 mL) and treated with rhenium bis-thiolate catalyst (5 mg; prepared according to Y. Wang and J.H. Espenson, Org.
- Example 24 r2-(4-Methoxyphenyl)-ethyll-(2,6,7-trimethylpteridin-4-yl)-amine.
- BIOLOGICAL TESTING The following Table 2 shows characterizing mass spectrometry and biological activity of representative compounds of formula (I- A) and (I-B).
- the compounds of the present invention 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. In particular, the compounds effectively control a variety of undesirable fungi that infect useful plant crops. Activity has been demonstrated for a variety of fungi, including for example the following representative fungi species: Anthracnose of Cucumber (Collatotrichum lagenarium - COLLLA); Spot Blotch of Wheat (Cochliobolus sativus-COCHSA), Downy Mildew of Cucumber
- Formulated test compounds were applied to plants using a turn table sprayer fitted with two opposing air atomization nozzles which delivered approximately 1500 L/ha of spray volume.
- Cucumber Anthracnose (causal agent Colletotricum lagenarium; Bayer code CQLLLA): Cucumber plants (variety Bush Champion) were grown from seed in a soil-less peat-based potting mixture (Metromix) until the first true leaf was 20-80% expanded. Each pot contained 1 seedling. These plants were sprayed until wet with the formulated test compound. On the following day, the leaves were inoculated with an aqueous spore suspension of Colletotricum lagenarium and the plants were kept in high humidity for one day to permit spores to germinate and infect the leaf. The plants were then transferred to a growth chamber until disease developed on untreated control plants.
- Cucumber Downy Mildew (causal agent Pseudoperonospora cubensis: Bayer code PSPECU): Cucumber plants (variety Bush Champion) were grown from seed in a soil-less peat-based potting mixture (Metromix) until the first true leaf was 20-80% expanded. Each pot contained 1 seedling. These plants were sprayed until wet with the formulated test compound. On the following day, the leaves were inoculated with an aqueous suspension of downy mildew sporangia and the plants were kept in high humidity for one day to permit sporangia to germinate and infect the leaf. The plants were then incubated in a growth chamber until disease developed on untreated control plants.
- Table 2 presents the activity of typical compounds of the present invention when evaluated in these experiments.
- the effectiveness of the test compounds at controlling disease when sprayed on leaves 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. Data are the level (in percent) at which the given disease was controlled when the given compound was applied to the foliage of the plants at 200 ppm. In a few cases (noted in the table) the compound was applied to the plants at 75 ppm or 8.3 ppm.
- the compounds of the present invention have been found to have insecticidal activity. Activity may be demonstrated for a variety of insects, including for example the following representative insect species: Beet Army worm (Spodoptera exigua -LAPHEG) or Tobacco Budworm (Heliothus virescens- HELIVI); Mosquito (Aedes aegypti - AEDSAE), Fruit Fly (Drosophila melanogaster - DROSME). It will be understood by those skilled in the art that the efficacy of the compounds against the foregoing insects establishes the general utility of the compounds as insecticides.
- the activity of the compounds as effective insecticides was determined by applying the compounds to diet or water, placing insects in the water or on the diet, and observing mortality after an appropriate incubation time.
- the compounds were formulated at 4000 ppm or 400 ppm in dimethyl sulfoxide (DMSO) giving a "formulated test compound.”
- Formulated test compounds were diluted in 96-well plates with acetone:water solutions and applied to species-specific diet or water. The plates were infested and evaluated as described below. Results were averaged over 2-6 replications.
- DRQSME Formulated test compounds were applied to microtiter plates containing fruit fly agar (10% sugar-water) to give a dose of 80 ⁇ g test compound per well. Plates were infested by placing at least three flies in each well and sealing the plate. Mortality was evaluated after incubation for two days at room temperature.
- AEDSAE Plates containing formulated test compounds at 6 ⁇ g per well were diluted with water containing mosquito larvae. Each well contained at least two larvae. Mortality was evaluated after incubation for three days at room temperature.
- LAPHEG or HELIVI Formulated test compounds were applied to 96-well plates containing Lepidoptera diet at 12 ⁇ g per well (one-tenth the rate was used for HELIVI). Plates were infested by placing at least four fresh armyworm or budworm eggs in each well and sealing the plate with cotton batting and plastic. Mortality was evaluated after incubation for seven days at 28 0 C.
- Table 2 presents the activity of typical compounds of the present invention when evaluated in these experiments.
- the effectiveness of the test compounds at controlling insects was determined by assessing the mortality in treated test plates, then converting the average mortality to percent control.
- Each compound was tested on at least two species. If any of the species DROSME, AEDSAE, LAPHEG, or HELIVI was controlled at 80% or more, the compound was considered active (shown as "+” in Table T). If no species was controlled at 80% or more, the compound was considered inactive (shown as "-" in Table 2).
- the compounds of the present invention have been found to have significant potential as anti-parasitics for animal health.
- Table 3, shown below, presents the activity of typical compounds of the present invention when evaluated in these experiments. Activity has been demonstrated by four out of five compounds screened against Caenorhabditis elegans, a free- living nematode that is an indicator species for animal parasites. It will be understood by those in the art that the efficacy of four compounds against Caenorhabditis elegans, which at 10 ⁇ g/mL was equivalent to the commercial anti-parastitic product ivermectin, establishes the potential utility of these compounds to control parasites that attack animals.
- the activity of the compounds against Caenorhabditis elegans was determined by dissolving compounds in DMSO, then applying them to petri dishes containing Nematode Growth Medium agar to a final concentration of 10 ⁇ g compound per milliliter agar.
- Escherichia coli bacteria were grown on the plates to provide a food source for the larvae of Caenorhabditis elegans.
- the bacteria were heat-killed at 65 0 C before compounds were added to the plates.
- the plates with compound and heat-killed bacteria were infested with 10 microliter drops containing eggs from wild- type Caenorhabditis elegans worms.
- Adult worms were dissolved in KOH and bleach and washed in Ringers solution to generate the egg suspension.
- Each compound was screened with approximately 400 eggs, divided between two petri dishes. Egg hatching was evaluated after 24 h at 20 0 C. Mortality was averaged over the two plates.
Abstract
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WO2013113773A1 (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 |
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EA022487B1 (en) | 2016-01-29 |
CN102574855A (en) | 2012-07-11 |
IL218377A0 (en) | 2012-04-30 |
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