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WO2009094407A2 - Fungicidal amides - Google Patents

Fungicidal amides Download PDF

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Publication number
WO2009094407A2
WO2009094407A2 PCT/US2009/031618 US2009031618W WO2009094407A2 WO 2009094407 A2 WO2009094407 A2 WO 2009094407A2 US 2009031618 W US2009031618 W US 2009031618W WO 2009094407 A2 WO2009094407 A2 WO 2009094407A2
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WO
WIPO (PCT)
Prior art keywords
alkyl
independently
compound
ring
formula
Prior art date
Application number
PCT/US2009/031618
Other languages
French (fr)
Other versions
WO2009094407A3 (en
Inventor
Mary Ann Hanagan
Robert James Pasteris
Original Assignee
E. I. Du Pont De Nemours And Company
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by E. I. Du Pont De Nemours And Company filed Critical E. I. Du Pont De Nemours And Company
Priority to MX2010007974A priority Critical patent/MX2010007974A/en
Priority to EP09703779A priority patent/EP2238133A2/en
Priority to BRPI0905758-7A priority patent/BRPI0905758A2/en
Priority to US12/811,126 priority patent/US20100286147A1/en
Priority to CN200980102836.XA priority patent/CN101925598B/en
Priority to AU2009206522A priority patent/AU2009206522B2/en
Priority to JP2010544400A priority patent/JP5535941B2/en
Publication of WO2009094407A2 publication Critical patent/WO2009094407A2/en
Publication of WO2009094407A3 publication Critical patent/WO2009094407A3/en

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Classifications

    • 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
    • C07D417/14—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 three or more hetero rings
    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond

Definitions

  • This invention relates to certain carboxamides, their //-oxides, salts and compositions, and methods of their use as fungicides.
  • World Patent Publication WO 2005/003128 discloses certain thiazolylpiperidines of Formula i and their use as microsomal triglyceride transfer protein inhibitors.
  • World Patent Publication WO 2004/058751 discloses certain piperidinyl-thiazole carboxamides for altering vascular tone.
  • This invention relates to compounds of Formula 1 (including all geometric and stereoisomers), iV-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
  • R 1 is an optionally substituted phenyl or 5- or 6-membered heteroaromatic ring or optionally substituted naphthalenyl;
  • A is CHR 15 or NR 16 ;
  • R 15 is H, halogen, cyano, hydroxy, -CHO, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 2 -C 4 alkoxyalkyl, C 2 -C 4 alkylthioalkyl, C 2 -C 4 alkylsulf ⁇ nylalkyl, C 2 -C 4 alkylsulfonylalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 -C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 ⁇ C 5 dialkylaminocarbonyl, C 1 -
  • R 16 is H, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 haloalkyl, C 2 -C 4 haloalkenyl, C 2 -C 4 haloalkynyl, C 2 -C 4 alkoxyalkyl, C 2 -C 4 alkylthioalkyl, C 2 - C 4 alkylsulfmylalkyl, C 2 -C 4 alkylsulfonylalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl, C 2 -C 5 alkoxycarbonyl, C 3 ⁇ C 5 alkoxycarbonylalkyl, C 2 -C 5 alkylaminocarbonyl, C 3 ⁇ C 5 dialkylaminocarbonyl, C 1 -C 4 alkylsulfonyl or C 1 - C
  • W is O or S
  • X is a radical selected from
  • G is an optionally substituted 5-membered heterocyclic ring
  • R 25 is H, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 8 cycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 - Cg haloalkylcarbonyl, C 2 -Cg alkoxycarbonyl or C 2 -Cg haloalkoxycarbonyl;
  • R 26 is Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 8 cycloalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 haloalkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 haloalkoxycarbonyl or -Z 4 Q; each R 17 and R 18 is independently Ci-C 5 alkyl, C 2 -C 5 alkenyl, C 2 -C 5 alkynyl, C 3 - C 5 cycloalkyl, C 3 -C 6 halocycloalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C7 alkylcycloalkyl, C 5 -C 7 alkylcycloalkylalkyl, Ci-C 5 haloalkyl, Ci-C 5 alkoxy or Ci-C 5 haloalkoxy; each Q is independently phenyl,
  • this invention pertains to a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof.
  • This invention also relates to a compound selected from compounds of Formula IA and //-oxides and salts thereof
  • M is C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, hydroxy, C 1 -C 4 alkoxy, C 1 -C 2 haloalkoxy, C 1 -C 4 alkylamino, C 2 -C 8 dialkylamino, 1-piperidinyl, 1-pyrrolidinyl or 4-morpholinyl; and
  • this invention pertains to a compound of Formula IA (including all geometric and stereoisomers), an JV-oxide or salt thereof (except that the compounds of Formula IA of this invention are limited to those stereoisomer embodiments defined for J 1 in the Summary of Invention as depicted in Exhibit A below).
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising a compound of Formula 1 (including all geometric and stereoisomers, //-oxides, and salts thereof) (i.e. in a fungicidally effective amount) and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention also relates to a fungicidal composition
  • a fungicidal composition comprising a mixture of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof) and at least one other fungicide (e.g., at least one other fungicide having a different site of action).
  • This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof) (e.g., as a composition described herein).
  • a compound of Formula 1 including all geometric and stereoisomers, iV-oxides, and salts thereof
  • This invention additionally relates to fungicidal compositions and methods of controlling plant diseases as described above.
  • compositions comprising, “comprising,” “includes,” “including,” “has,” “having” or any other variation thereof, are intended to cover a non-exclusive inclusion.
  • a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.
  • “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and Both A and B are true (or present).
  • plant includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds).
  • Portions of plants include geotropic members typically growing beneath of the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds.
  • seedling used either alone or in a combination of words means a young plant developing from the embryo of a seed.
  • alkyl used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers.
  • Alkenyl includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers.
  • Alkenyl also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl.
  • Alkynyl includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers.
  • Alkynyl can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl.
  • Alkylene denotes a straight-chain or branched alkanediyl.
  • alkylene examples include CH 2 , CH 2 CH 2 , CH(CH 3 ), CH 2 CH 2 CH 2 , CH 2 CH(CH 3 ) and the different butylene isomers.
  • Cycloalkyl includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • Cycloalkenyl includes groups such as cyclopentenyl and cyclohexenyl as well as groups with more than one double bond such as 1,3- and 1,4-cyclohexadienyl.
  • alkylcycloalkyl denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl.
  • cycloalkylalkyl denotes cycloalkyl substitution on an alkyl moiety.
  • examples of “cycloalkylalkyl” include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups
  • cycloalkylcycloalkyl denotes an cycloalkyl group substituted with other cycloalkyl group.
  • Examples of “cycloalkylcycloalkyl” include 2-cyclopropylcyclopropyl and 3- cyclopropylcyclopentyl.
  • Halocycloalkylalkyl denotes halogen substitution on the cycloalkyl moiety, the alkyl moiety or both of the cycloalkyl and alkyl moieties.
  • halocycloalkylalkyl include (2-chlorocyclopropyl)methyl, 2-cyclopentyl-l-chloroethyl, and 2-(3-chlorocyclopentyl)- 1 -chloroethyl.
  • Alkoxy includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers.
  • Alkoxyalkoxy denotes at least one straight-chain or branched alkoxy substitution on a straight-chain or branched alkoxy. Examples of “alkoxyalkoxy” include CH 3 OCH 2 O-, CH 3 OCH 2 (CH 3 O)CHCH 2 O- and (CH 3 ) 2 CHOCH 2 CH 2 O-.
  • haloalkoxyalkoxy denotes an alkoxyalkoxy group substituted with a haloalkoxy moiety.
  • haloalkoxyalkoxy examples include CF 3 OCH 2 O-, CICH 2 CH 2 OCH 2 CH 2 O- and Cl 3 CCH 2 OCH 2 O- as well as branched alkyl derivatives.
  • alkoxyhaloalkoxy denotes a haloalkoxy group further substituted with an alkoxy moiety.
  • alkoxyhaloalkoxy examples include CH 3 OCHClO-, CH 3 CH 2 OCH 2 CHCIO- and CH 3 CH 2 OCCl 2 O- as well as branched alkyl derivatives.
  • haloalkoxyhaloalkoxy denotes a haloalkoxy group further substituted with a haloalkoxy moiety.
  • haloalkoxyhaloalkoxy examples include CF 3 OCHClO-, CICH 2 CH 2 OCHCICH 2 O- and C1 3 CCH 2 OCHC1O- as well as branched alkyl derivatives.
  • Alkoxyalkyl denotes alkoxy substitution on alkyl.
  • alkoxyalkyl examples include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • cycloalkoxyalkyl denotes cycloalkoxy substitution on an alkyl moiety.
  • cycloalkoxyalkyl examples include cyclopropoxymethyl, cyclopentoxyethyl, and other cycloalkoxy moieties bonded to straight-chain or branched alkyl groups.
  • Alkoxyalkoxyalkyl denotes at least one straight-chain or branched alkoxy moiety bonded to a straight-chain or branched alkoxy moiety bonded to an alkyl moiety.
  • alkoxyalkoxyalkyl include CH 3 OCH 2 OCH 2 -, CH 3 CH 2 O(CH 3 )CHOCH 2 - and (CH 3 O) 2 CHOCH 2 -.
  • alkenyloxy includes straight-chain or branched alkenyloxy moieties.
  • alkynyloxy includes straight-chain or branched alkynyloxy moieties. Examples of “alkynyloxy” include HC ⁇ CCH 2 0, CH 3 C ⁇ CCH 2 O and CH 3 C ⁇ CCH 2 CH 2 O.
  • Alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers.
  • Alkylthio alkyl denotes alkylthio substitution on alkyl. Examples of “alkylthioalkyl” include CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 .
  • Alkylsulfinyl includes both enantiomers of an alkylsulf ⁇ nyl group.
  • alkylsulfinyl examples include CH 3 S(O), CH 3 CH 2 S(O), CH 3 CH 2 CH 2 S(O), (CH 3 ) 2 CHS(O) and the different butylsulfinyl, pentylsulf ⁇ nyl and hexylsulf ⁇ nyl isomers.
  • Alkylsulfmylalkyl denotes alkylsulfinyl substitution on alkyl.
  • alkylsulfonyl examples include CH 3 S(O) 2 , CH 3 CH 2 S(O) 2 , CH 3 CH 2 CH 2 S(O) 2 , (CH 3 ) 2 CHS(O) 2 and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers.
  • Alkylsulfonylalkyl denotes alkylsulfinyl substitution on alkyl.
  • alkylcarbonyl examples include CH 3 C(O), CH 3 CH 2 CH 2 C(O) and (CH 3 ) 2 CHC(O).
  • dialkylaminocarbonyl examples include
  • Cycloalkylalkoxycarbonyl denotes cycloalkyl substituted on the alkoxy moiety of an alkoxycarbonyl group.
  • Alkoxy(alkyl)aminocarbonyl denotes straight-chain or branched alkyl and alkoxy moieties bonded to the nitrogen atom of an aminocarbonyl group. Examples of "Alkoxy(alkyl)aminocarbonyl” include
  • haloalkylsulfonylaminocarbonyl denotes halogen substitution on either the alkyl moiety or the nitrogen atom of an aminocarbonyl group or both the alkyl moiety and the nitrogen atom.
  • alkylcarbonylalkoxy denotes alkylcarbonyl bonded to an alkoxy moiety.
  • halodialkylamino denotes a dialkylamino group substituted on at least one alkyl moiety with one or more halogenatoms which may be the same or different.
  • halodialkylamino include CF 3 (CH 3 )N-, (CF 3 ) 2 N- and CH 2 Cl(CH 3 )N-.
  • Cycloalkylamino means the amino nitrogen atom is attached to a cycloalkyl radical and a hydrogen atom and includes groups such as cyclopropylamino, cyclobutylamino, cyclopentylamino and cyclohexylamino.
  • Cycloalkyl(alkyl)amino means a cycloalkylamino group wherein the amino hydrogen atom is replaced by an alkyl radical.
  • cycloalkyl(alkyl)amino examples include groups such as cyclopropyl(methyl)amino, cyclobutyl(butyl)amino, cyclopentyl(propyl)amino, cyclohexyl(methyl)amino and the like.
  • “Haloalkylaminoalkyl” denotes an alkylaminoalkyl group substituted on the amino nitrogen or either alkyl moiety or a combination thereof with one or more halogen atoms which may be the same or different.
  • Haloalkylaminoalkyl includes a halogen group attached to any alkyl groups as well as nitrogen. Examples of “haloalkylaminoalkyl” include CH 3 NHCHCl- , (CH 3 ) 2 CC1NHCH 2 - and CH 3 NClCH(CH 3 )-.
  • dialkylimido denotes two independent straight-chain or branched alkylcarbonyl moieties bonded to the nitrogen atom of an amino group.
  • Trialkylsilyl includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and te/t-butyldimethylsilyl.
  • the terms "halotrialkylsilyl” denotes one or more halogen atoms substituted on at least one alkyl moiety of the trialkylsilyl group. Examples of “halotrialkylsilyl” include CF 3 (CH 3 ) 2 Si-, (CF 3 ) 3 Si-, and CH 2 Cl(CH 3 ) 2 Si-.
  • Hydroxyalkyl denotes an alkyl group substituted with one hydroxy group.
  • Examples of “hydroxyalkyl” include HOCH 2 CH 2 , CH 3 CH 2 (OH)CH and HOCH 2 CH 2 CH 2 CH 2 .
  • halogen either alone or in compound words such as “haloalkyl” includes fluorine, chlorine, bromine or iodine. Furthermore, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” include F 3 C, ClCH 2 , CF 3 CH 2 and CF 3 CCl 2 .
  • haloalkenyl “haloalkynyl”, “halocycloalkyl”, “haloalkoxy", “haloalkylthio”, and the like, are defined analogously to the term “haloalkyl".
  • haloalkynyl examples include HC ⁇ CCHCl, CF 3 C ⁇ C, CC1 3 C ⁇ C and FCH 2 C ⁇ CCH 2 .
  • haloalkoxy examples include CF 3 O, CCl 3 CH 2 O, HCF 2 CH 2 CH 2 O and CF 3 CH 2 O.
  • haloalkylthio examples include CCl 3 S, CF 3 S, CCl 3 CH 2 S and ClCH 2 CH 2 CH 2 S.
  • haloalkylsulfmyl examples include CF 3 S(O), CCl 3 S(O), CF 3 CH 2 S(O) and CF 3 CF 2 S(O).
  • haloalkylsulfonyl examples include CF 3 S(O) 2 , CCl 3 S(O) 2 , CF 3 CH 2 S(O) 2 and CF 3 CF 2 S(O) 2 .
  • a "ring” or “ring system” as a component of Formula 1 is carbocyclic or heterocyclic.
  • the term “ring system” denotes two or more connected rings.
  • the term “spirocyclic ring system” denotes a ring system consisting of two rings connected at a single atom (so the rings have a single atom in commonality).
  • the term “bicyclic ring system” denotes a ring system consisting of two rings sharing two or more common atoms. In a "fused bicyclic ring system” the common atoms are adjacent, and therefore the rings share two adjacent atoms and bond connecting them.
  • bridged bicyclic ring system In a “bridged bicyclic ring system” the common atoms are not adjacent (i.e. there is no bond between the bridgehead atoms).
  • a “bridged bicyclic ring system” is conceptually formed by bonding a segment of one or more atoms to nonadjacent ring members of a ring.
  • a ring, a bicyclic ring system or spirocyclic ring system can be part of an extended ring system containing more than two rings wherein substituents on the ring, bicyclic ring system or spirocyclic ring system are taken together to form the additional rings, which may be in bicyclic and/or spirocyclic relationships with other rings in the extended ring system.
  • the particular J or J 1 moiety J-29-59 depicted in Exhibit A consists of a dihydro isoxazoline ring having one R 5 substituent as Z 2 Q, which is a phenyl ring substituted with a phenyl group (as Z 3 G A ) and also one R 7a group taken together with another R 5 substituent on the dihydro isoxazoline ring as -CH 2 CH 2 CH 2 - to form the additional six-membered ring component in the ring system.
  • carbocyclic ring denotes a ring wherein the atoms forming the ring backbone are selected only from carbon.
  • carrier system denotes two or more fused rings wherein the atoms forming the backbone of the rings are selected only from carbon.
  • heterocyclic ring denotes a ring wherein at least one of the atoms forming the ring backbone is other than carbon.
  • heterocyclic ring system denotes two or more fused rings wherein at least one of the atoms forming the backbone of the rings is other than carbon.
  • Aromatic indicates that each of the ring atoms is essentially in the same plane and has a/?-orbital perpendicular to the ring plane, and in which (4n + 2) ⁇ electrons, where n is a positive integer, are associated with the ring to comply with H ⁇ ckel's rule.
  • heteroheteroaromatic ring refers to a heterocyclic ring that is aromatic.
  • saturated heterocyclic ring denotes a heterocyclic ring containing only single bonds between ring members.
  • partially saturated heterocyclic ring denotes a heterocyclic ring containing at least one double bond but which is not aromatic.
  • the dotted line in Formula 1 and in other rings depicted in the present description represents that the bond indicated can be a single bond or double bond.
  • heterocyclic rings and ring systems are attached to the remainder of Formula 1 through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen, and all substituents on the heterocyclic rings and ring systems are attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
  • heteroatoms are optional, 0 to 4 heteroatoms may be present.
  • the total number of unoxidized sulfur atoms i.e.
  • the ring or ring system is carbocyclic.
  • the R 5 substituents may be attached to carbon atom ring members and to nitrogen atom ring members having an available point of attachment.
  • the substituents R 17 and R 18 are otherwise separately defined, and these ring members cannot be further substituted with R 5 .
  • R 5 substituents are optional, 0 to 5 substituents may be present, limited by the number of available points of attachment.
  • the ring is carbocyclic.
  • the 5- to 7-membered ring is optionally substituted.
  • the substituents on the atoms linking R 5 and R 7a are described in the definition of the components linking R 5 and R 7a .
  • the substituent R 20 is defined to be H, Q-C 4 alkyl or Q-C 4 haloalkyl.
  • an optional substituent is a non-hydrogen substituent that does not extinguish fungicidal activity.
  • SiR 17 R 18 ring members the substituents R 17 and R 18 are otherwise separately defined, and these ring members cannot be further substituted.
  • C ⁇ -C 4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl
  • C 2 alkoxyalkyl designates CH 3 OCH 2
  • C 3 alkoxyalkyl designates, for example, CH 3 CH(OCH 3 ), CH 3 OCH 2 CH 2 or CH 3 CH 2 OCH 2
  • C 4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH 3 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 .
  • variable group When a variable group is shown to be optionally attached to a position, for example, (R 2 ) n wherein n may be 0, or as a further example (R 4 )k wherein k may be 0 in U- 17 of Exhibit 1, then hydrogen may be at the position even if not recited in the definition of the variable group (e.g., R 2 and R 4 ).
  • R 2 and R 4 When a position on a group is said to be "not substituted” or "unsubstituted”, then hydrogen atoms are attached to take up any free valency.
  • R 1 , R 2 , R 5 , R 7a , G, J and Q refers to groups that are unsubstituted or have at least 1 non-hydrogen substituent. Unless otherwise indicated, these groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. Commonly, the number of optional substituents (when present) ranges from 1 to 3.
  • the phrase "optionally substituted with up to 2 substituents selected from R 3 on carbon ring members and selected from R 1 * on nitrogen ring members” means that 0, 1 or 2 substituents can be present (if the number of potential connection points allows), and thus the number of R 3 and R 1 * substituents can be zero.
  • the phrase “optionally substituted with 1 to 5 substituents” means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows.
  • the term “unsubstituted” in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1.
  • metala-substituted phenyl means a phenyl ring substituted with a non-hydrogen substituent at a meta position relative to attachment of the phenyl ring to the remainder of Formula 1.
  • R 1 is an optionally substituted phenyl, or 5- or 6-membered heteroaromatic ring or optionally substituted naphthalenyl
  • G is an optionally substituted 5- membered heterocyclic ring
  • substituted in connection with the definitions of R 1 , G, R 5 and R 7a refers to groups that have at least one non-hydrogen substituent that does not extinguish fungicidal activity. Since these groups are optionally substituted, they need not have any non-hydrogen substituents. As these groups are "optionally substituted” without the number of substituents indicated, these groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom.
  • Compounds of this invention can exist as one or more stereoisomers.
  • the various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers.
  • the compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form.
  • Formula 1 when J is J-29 (see Exhibit 3) bonded at the 3-position to the remainder of Formula 1 and J-29 has one Q substituent other than H at the 5-position (Z 2 being a direct bond, s being 1, and x being 0), then Formula 1 possesses a chiral center at the carbon atom to which Q is bonded.
  • the two enantiomers are depicted as Formula 1' and Formula 1" with the chiral center identified with an asterisk (*).
  • This invention comprises racemic mixtures, for example, equal amounts of the enantiomers of Formulae 1' and 1".
  • this invention includes compounds that are enriched compared to the racemic mixture in an enantiomer of Formula 1. Also included are the essentially pure enantiomers of compounds of Formula 1, for example, Formula 1' and Formula 1".
  • enantiomeric excess which is defined as (2x-l)-100 %, where x is the mole fraction of the dominant enantiomer in the mixture (e.g., an ee of 20 % corresponds to a 60:40 ratio of enantiomers).
  • compositions of this invention have at least a 50 % enantiomeric excess; more preferably at least a 75 % enantiomeric excess; still more preferably at least a 90 % enantiomeric excess; and the most preferably at least a 94 % enantiomeric excess of the more active isomer.
  • enantiomerically pure embodiments of the more active isomer are enantiomerically pure embodiments of the more active isomer.
  • Compounds of Formula 1 can comprise additional chiral centers.
  • substituents and other molecular constituents such as R 4 , R 5 , R 7a , G, J, Q and X 1 through X 9 may themselves contain chiral centers.
  • This invention comprises racemic mixtures as well as enriched and essentially pure stereoconfigurations at these additional chiral centers.
  • Compounds of this invention can exist as one or more conformational isomers due to restricted rotation about the amide bond (e.g., C(W)-N) in Formula 1.
  • This invention comprises mixtures of conformational isomers.
  • this invention includes compounds that are enriched in one conformer relative to others.
  • Some of the unsaturated rings and ring systems depicted in Exhibits 1, 2, 3, 4 and 5 can have an arrangement of single and double bonds between ring members different from that depicted. Such differing arrangements of bonds for a particular arrangement of ring atoms correspond to different tautomers.
  • the particular tautomer depicted is to be considered representative of all the tautomers possible for the arrangement of ring atoms shown.
  • the tables listing particular compounds incorporating the ring and ring systems depicted in the Exhibits may involve a tautomer different from the tautomer depicted in the Exhibits.
  • the compounds of the invention include iV-oxide derivatives.
  • nitrogen-containing heterocycles can form JV-oxides since the nitrogen requires an available lone pair of electrons for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form JV-oxides.
  • tertiary amines can form //-oxides .
  • Synthetic methods for the preparation of //-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane.
  • MCPBA peroxy acids
  • alkyl hydroperoxides such as tert-butyl hydroperoxide
  • sodium perborate sodium perborate
  • dioxiranes such as dimethyldioxirane
  • the present compounds of Formula 1 can be in the form of agriculturally suitable salts.
  • One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms.
  • salts of the compounds of Formula 1 are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable).
  • the salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids.
  • salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium.
  • Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts.
  • Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types).
  • polymorph refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice.
  • polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability.
  • a polymorph of a compound represented by Formula 1 or IA can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1 or IA. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 or IA can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
  • Embodiments of the present invention as described in the Summary of the Invention include those described below.
  • Formulae 1 and IA include iV-oxides and salts thereof, and reference to "a compound of Formula 1" or "a compound of Formula IA" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments.
  • Embodiments of the present invention include: Embodiment 1. A compound of Formula 1 wherein A is CHR 15 .
  • Embodiment Ia Embodiment Ia.
  • Embodiment Ib A compound of Embodiment Ia wherein R 15 is H, cyano, hydroxy, methyl or methoxycarbonyl.
  • Embodiment Ic A compound of Embodiment Ib wherein R 15 is H. Embodiment 2. A compound of Formula 1 wherein A is NR 16 .
  • Embodiment 2a A compound of Formula 1 or any one of Embodiments 1 through 2 wherein R 16 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl or C 2 -C 4 alkoxycarbonyl.
  • Embodiment 2b A compound of Embodiment 2a wherein R 16 is H, methyl, methylcarbonyl or methoxycarbonyl.
  • Embodiment 2c A compound of Embodiment 2b wherein R 16 is H. Embodiment 3. A compound of Formula 1 or any one of Embodiments 1 through 2c wherein W is O. Embodiment 4. A compound of Formula 1 or any one of Embodiments 1 through 2c wherein W is S. Embodiment 5. A compound of Formula 1 wherein each R 2 is independently C 1 -C 4 alkyl, C 1 -C 4 alkenyl, C 1 -C 4 haloalkyl, C 1 -
  • Embodiment 5a A compound of Embodiment 5 wherein each R 2 is independently C 1 - C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, halogen, cyano or hydroxy.
  • Embodiment 5b A compound of Embodiment 5 a wherein each R 2 is independently methyl, methoxy, cyano or hydroxy.
  • Embodiment 5c A compound of Embodiment 5b wherein each R 2 is methyl.
  • Embodiment 6 A compound of Formula 1 or any one of Embodiments 1 through 5c wherein n is 0 or 1.
  • Embodiment 7 A compound of Embodiment 6 wherein n is 0.
  • Embodiment 7a A compound of Embodiment 6 wherein n is 1.
  • Embodiment 8 A compound of Formula 1 or any one of Embodiments 1 through 7a wherein X is X 1 , X 2 or X 3 .
  • Embodiment 9 A compound of Embodiment 8 wherein X is X 1 or X 2 .
  • Embodiment 10 A compound of Embodiment 9 wherein X is X 1 .
  • Embodiment 11 A compound of Formula 1 or any one of Embodiments 1 through 10 wherein the ring comprising X is saturated (i.e. contains only single bonds).
  • Embodiment 12 A compound of Formula 1 or any one of Embodiments 1 through 11 wherein R 1 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with substituents that do not link together to make R 1 a fused ring system.
  • Embodiment 12a A compound of Embodiment 12 wherein R 1 is a phenyl or 5- or 6- membered heteroaromatic ring optionally substituted with 1-3 substituents independently selected from R 4a on carbon ring members and R 4 * 5 on nitrogen ring members; each R 4a is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C 10 alkylcycloalkyl, C 5 -C 10 alkylcycloalkylalkyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, C 3 -C 6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, Q-C 4 alkoxy, C 1
  • Embodiment 12b A compound of Embodiment 12a wherein R 1 is a phenyl or 5- or 6- membered heteroaromatic ring optionally substituted with 1-2 substituents independently selected from R 4a on carbon ring members and R 4b on nitrogen ring members.
  • Embodiment 13 A compound of Embodiment 12a wherein R 1 is a phenyl or 5- or 6- membered heteroaromatic ring optionally substituted with 1-2 substituents independently selected from R 4a on carbon ring members and R 4b on nitrogen ring members.
  • each R 4a is independently C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, cyclopropyl, C 1 -C 3 haloalkyl, C 2 -C 3 haloalkenyl, C 2 -C 3 haloalkynyl, halocyclopropyl, halogen, cyano, nitro, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, C 1 -
  • Embodiment 14 A compound of Embodiment 13 wherein each R 4a is independently
  • Embodiment 15 A compound of Embodiment 14 wherein each R 4a is independently halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 2 alkoxy or C 1 -C 2 haloalkoxy.
  • Embodiment 15 a A compound of Embodiment 15 wherin each R 4a is independently halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 2 alkoxy or C 1 -C 2 haloalkoxy.
  • Embodiment 15 a A compound of Embodiment 15 wherin each R 4a is independently
  • Embodiment 16 A compound of Embodiment 15a wherein each R 4a is independently halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl or C 1 -C 2 alkoxy.
  • Embodiment 17 A compound of Embodiment 16 wherein each R 4a is independently
  • Embodiment 18 A compound of Embodiment 17 wherein each R 4a is independently
  • Embodiment 19 A compound of any one of Embodiments 12a through 18 wherein each R 4 ⁇ is independently C 1 -C 3 alkyl, C 3 alkenyl (e.g., allyl), C 3 alkynyl (e.g., propargyl), cyclopropyl, C 1 -C 3 haloalkyl, C 3 haloalkenyl, C 3 haloalkynyl, halocyclopropyl or C 2 -C 3 alkoxyalkyl.
  • Embodiment 20 A compound of Embodiment 19 wherein each R 4 ⁇ is independently
  • Embodiment 21 A compound of Embodiment 20 wherein each R 4 ⁇ is independently
  • Embodiment 22 A compound of Embodiment 21 wherein each R 4 ⁇ is independently
  • Embodiment 23 A compound of Embodiment 22 wherein each R 4 ⁇ is independently
  • Embodiment 24 A compound of any one of Embodiments 12a through 23 wherein R 1 is one of U-I through U-50 depicted in Exhibit 1;
  • R 4 when attached to a carbon ring member, said R 4 is selected from R 4a , and when
  • R 4 is attached to a nitrogen ring member (e.g., in U-4, U-I l through U- 15, U-24 through U-26, U-31 or U-35), said R 4 is selected from R 4b ; and k is 0, 1 or 2.
  • Embodiment 24a A compound of Embodiment 24 wherein k is 1 or 2.
  • Embodiment 25 A compound of Embodiment 24 wherein k is 1 or 2 and at least one
  • Embodiment 26 A compound of Embodiment 24 wherein k is 1 or 2 and at least one
  • R 4 is Br.
  • Embodiment 27 A compound of Embodiment 24 wherein k is 1 or 2 and at least one
  • R 4 is methyl.
  • Embodiment 28 A compound of Embodiment 24 wherein k is 1 or 2 and at least one
  • R 4 is ethyl.
  • Embodiment 29 A compound of Embodiment 24 wherein k is 1 or 2 and at least one
  • R 4 is trifluoromethyl.
  • Embodiment 30 A compound of Embodiment 24 wherein k is 1 or 2 and at least one
  • R 4 is methoxy.
  • Embodiment 31 A compound of any one of Embodiments 24 through 30 wherein R 1 is selected from U-I through U-5, U-8, U-I l, U-13, U-15, U-20 through U-28, U-
  • Embodiment 32 A compound of Embodiment 31 wherein R 1 is selected from U-I through U-3, U-5, U-8, U-I l, U-13, U-20, U-22, U-23, U-25 through U-28, U-36 through U-39 and U-50.
  • Embodiment 33 A compound of Embodiment 32 wherein R 1 is selected from U-I through U-3, U-I l, U-13, U-20, U-22, U-23, U-36 through U-39 and U-50.
  • Embodiment 34 A compound of Embodiment 33 wherein R 1 is U-I, U-20 or U-50.
  • Embodiment 35 A compound of Embodiment 33 wherein R 1 is U-I, U-20 or U-50.
  • Embodiment 35a A compound of Embodiment 34 wherein R 1 is U-20.
  • Embodiment 36 A compound of Embodiment 34 wherein R 1 is U-50.
  • Embodiment 37 A compound of Embodiment 35 wherein k is 1 and R 4 is connected to the 3- or 5-position of U-I.
  • Embodiment 37a A compound of Embodiment 35 wherein k is 2 and one R 4 is connected to the 3 -position and the other R 4 is connected to the 5 -position of
  • Embodiment 38 A compound of Embodiment 35a wherein k is 1 and R 4 is connected to the 3- or 5 -position of U-20.
  • Embodiment 38a A compound of Embodiment 35a wherein k is 2 and one R 4 is connected to the 3 -position and the other R 4 is connected to the 5 -position of
  • Embodiment 39 A compound of Embodiment 36 wherein k is 1 and R 4 is connected to the 2- or 5 -position of U-50.
  • Embodiment 40 A compound of Embodiment 36 wherein k is 2 and one R 4 is connected to the 2-position and the other R 4 is connected to the 5 -position of
  • Embodiment 41 A compound of Formula 1 or any one of Embodiments 1 through 40 wherein G is a 5-membered heterocyclic ring optionally substituted with up to 2 substituents selected from R 3 on carbon ring members and selected from R 1 * on nitrogen ring members; each R 3 is independently C ⁇ -C 3 alkyl, C ⁇ -C 3 haloalkyl or halogen; and each R 11 is independently C ⁇ -C 3 alkyl.
  • Embodiment 41a A compound of Embodiment 41 wherein each R 3 is independently
  • Embodiment 41b A compound of Embodiment 41a wherein each R 3 is independently methyl or halogen.
  • Embodiment 41c A compound of Embodiment 41b wherein each R 3 is methyl.
  • Embodiment 42 A compound of any one of Embodiments 41 through 41c wherein G is one of G-I through G-59 depicted in Exhibit 2;
  • Embodiment 43 A compound of Embodiment 42 wherein G is selected from G-I through G-3, G-7, G-8, G-IO, G-I l, G-14, G-15, G-23, G-24, G-26 through
  • Embodiment 44 A compound of Embodiment 43 wherein G is selected from G-I, G-2,
  • Embodiment 45 A compound of Embodiment 44 wherein G is selected from G-I, G-2,
  • Embodiment 46 A compound of Embodiment 45 wherein G is selected from G-I, G-2,
  • Embodiment 47 A compound of Embodiment 46 wherein G is G-I.
  • G is G-I.
  • Embodiment 48 A compound of Embodiment 46 wherein G is G-2.
  • G is G-2.
  • Embodiment 49 A compound of Embodiment 46 wherein G is G-15.
  • G is G-15.
  • Embodiment 50 A compound of Embodiment 46 wherein G is G-26.
  • G is G-26.
  • Embodiment 51 A compound of Embodiment 46 wherein G is G-36.
  • G is G-36.
  • Embodiment 52 A compound of any one of Embodiments 42 through 51 wherein each R 3a is independently H, Q-C 3 alkyl or halogen.
  • Embodiment 53 A compound of Embodiment 52 wherein each R 3a is independently H or methyl.
  • Embodiment 54 A compound of any one of Embodiments 42 through 51 wherein each R 3a is H and each R l la is independently H or methyl.
  • Embodiment 55 A compound of Formula 1 or any one of Embodiments 41 through 51 wherein G is unsubstituted.
  • Embodiment 56 A compound of Formula 1 or any one of Embodiments 1 through 55 wherein each R 5 is independently H, cyano, C ⁇ -CO alkyl, C ⁇ -CO haloalkyl, C 3 - Cg cycloalkyl, C 3 -C 8 halocycloalkyl, C 2 -C 6 alkoxyalkyl, C ⁇ -C 6 alkoxy, C ⁇ -C 6 haloalkoxy, C 3 -C 8 cycloalkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 haloalkenyloxy, C 2 - C ⁇ alkynyloxy, C 2 -C 6 alkoxyalkoxy, C 2 -C 6 alkylcarbonyloxy, C 2 -C 6 haloalkylcarbonyloxy, C ⁇ -CO alkylthio, C ⁇ -CO haloalkylthio, C 3 -C 10 trialkylsilyl, -NR 25 R 26
  • Embodiment 57 A compound of Embodiment 56 wherein each R 5 is independently H, cyano, C ⁇ -C 6 alkyl, C ⁇ -C 6 haloalkyl, C ⁇ -C 6 alkoxy, C ⁇ -C 6 haloalkoxy, -NR 25 R 26 or halogen.
  • Embodiment 57a A compound of Embodiments 56 or 57 wherein R 5 is other than halogen.
  • Embodiment 58 A compound of Embodiment 57 wherein each R 5 is independently H, cyano, Q-C 4 alkyl, Q-C 4 haloalkyl, Q-C 4 alkylcarbonyl or halogen.
  • Embodiment 59 A compound of Embodiment 58 wherein each R 5 is independently H and C 1 -C 3 alkyl.
  • Embodiment 60 A compound of Formula 1 or any one of Embodiments 1 through 59 wherein J is one of J-I through J-82 depicted in Exhibit 3;
  • Embodiment 61 A compound of Embodiment 60 wherein x is 0 or 1.
  • Embodiment 61a A compound of Embodiment 61 wherein x is 0.
  • Embodiment 62 A compound of Embodiment 61a wherein s is 1 or 2.
  • Embodiment 63 A compound of Embodiment 62 wherein s is 1.
  • Embodiment 64 A compound of any one of Embodiments 60 through 63 wherein J is selected from J-I, J-2, J-3, J-4, J-5, J-7, J-8, J-9, J-IO, J-I l, J-12, J-14, J-15, J-16,
  • Embodiment 65 A compound of Embodiment 64 wherein J is selected from J-4, J-5,
  • Embodiment 66 A compound of Embodiment 65 wherein J is selected from J-4, J-5,
  • Embodiment 67 A compound of Embodiment 66 wherein J is J-11.
  • Embodiment 68. A compound of Embodiment 66 wherein J is J-29.
  • Embodiment 69. A compound of Embodiment 59 wherein J is J-69.
  • Embodiment 70. A compound of Embodiment 67 wherein the 3 -position of J-11 is connected to Z 1 and the 5 -position of J-11 is connected to Z 2 Q.
  • Embodiment 71 A compound of Embodiment 68 wherein the 3-position of J-29 is connected to Z 1 and the 5 -position of J-29 is connected to Z 2 Q.
  • Embodiment 72 A compound of Formula 1 or any one of Embodiments 1 -through 71 wherein the ring or ring system of J directly connected to Z 1 is substituted with one -Z 2 Q.
  • Embodiment 72a A compound of Embodiment 68 wherein J is one of J-29- 1 through
  • Embodiment 72b A compound of Embodiment 72a wherein J is one of J-29-1 through
  • Embodiment 73 a A compound of Embodiment 73 wherein Z 1 is a direct bond.
  • Embodiment 74a A compound of Embodiment 74 wherein Z 2 is a direct bond or NR 21 .
  • Embodiment 74b A compound of Embodiment 74a wherein Z 2 is a direct bond.
  • Embodiment 75 A compound of Formula 1 or any one of Embodiments 1 through 74b wherein Q is one of Q-I through Q- 106 depicted in Exhibit 4; Exhibit 4
  • R 12 attached to a nitrogen ring member is optionally replaced by R 7 (e.g., Q-3, Q-10 through
  • Embodiment 76 A compound of Embodiment 75 wherein Q is selected from Q-I,
  • Embodiment 77 A compound of Embodiment 76 wherein Q is Q-I, Q-45, Q-62, Q-63,
  • Embodiment 78 A compound of Embodiment 77 wherein Q is Q-45, Q-62, Q-63, Q-64,
  • Embodiment 79 A compound of Embodiment 78 wherein Q is Q-45, Q-62, Q-63, Q-65,
  • Embodiment 80 A compound of Embodiment 79 wherein Q is Q-45, Q-62, Q-63, Q-65,
  • Embodiment 80a Acompound of any one of Embodiments 77 through 80 wherein Q is other than Q-62 or Q-104.
  • Embodiment 80b A compound of Embodiment 80 wherein Q is Q-45.
  • Embodiment 80c A compound of Embodiment 80 wherein Q is Q-62.
  • Embodiment 80d A compound of Embodiment 80 wherein Q is Q- 104.
  • each Q is independently phenyl, benzyl, naphthalenyl, a 5- or 6- membered heteroaromatic ring or an 8- to 11-membered heteroaromatic bicyclic ring system, each ring or ring system substituted with 1 substituent selected from
  • Embodiment 82 A compound of Embodiment 81 wherein Q is phenyl substituted with one R 7 .
  • Embodiment 83 A compound of Embodiment 81 wherein Q is benzyl substituted with one R 7 .
  • Embodiment 84 A compound of Embodiment 81 wherein Q is an 8- to 11-membered heteroaromatic bicyclic ring system substituted with one R 7 .
  • CHR 20 , CHR 20 -CHR 20 , CR 24 CR 27 , C ⁇ C or OCHR 20 .
  • Embodiment 88 A compound of Embodiment 87 wherein each Z 3 is independently a direct bond, O, NR 22 , CHR 20 or CHR 20 -CHR 20 .
  • Embodiment 88a A compound of Embodiment 88 wherein each Z 3 is CH 2 .
  • Embodiment 89 A compound of Embodiment 88 wherein each Z 3 is independently a direct bond, O or NR 22 .
  • Embodiment 90 A compound of Embodiment 89 wherein each Z 3 is a direct bond.
  • Embodiment 91. A compound of Embodiment 89 wherein each Z 3 is O.
  • Embodiment 92. A compound of Formula 1 or any one of Embodiments 1 through 91 wherein R 7 is -Z 3 G A .
  • Embodiment 93 A compound of Embodiment 92 wherein G A is phenyl.
  • Embodiment 94 A compound of Embodiment 92 wherein G A is a 5- or 6-membered heteroaromatic ring.
  • Embodiment 95 A compound of Formula 1 or any one of Embodiments 1 through 91 wherein R 7 is -Z 3 G N .
  • Embodiment 96 A compound of Formula 1 any one of Embodiments 1 through 91 wherein R 7 is -Z 3 G P .
  • Embodiment 97 A compound of Formula 1 or any one of Embodiments 1 through 96 wherein each G A is independently one of G A -1 through G A -49, each G N is independently one of G N -1 through G N -32, and each G p is independently one of G p -1 through G p -35 respectively, as depicted in Exhibit 5.
  • Embodiment 97a A compound of Embodiment 97 wherein r is 0, 1, 2 or 3.
  • Embodiment 97b A compound of Embodiment 97 or 97a wherein G A is selected from G A -1 through G A -18, G A -23 through G A -38 and G A -49, G N is selected from G N -1, G N -2, G N -5, G N -6, G N -9 through G N -16 and G N -29, and G p is selected from G p -1 through G p -6, G p -34 and G p -38.
  • Embodiment 98 A compound of Embodiment 97b wherein G A is selected from G A -1 through G A -18, G A -23 through G A -38 and G A -49, and G N is selected from G N -1, G N -2, G N -5, G N -6, G N -9 through G N -16 and G N -29.
  • Embodiment 99 A compound of Embodiment 98 wherein G A is selected from G A -18 and G A -49.
  • Embodiment 100 A compound of Embodiment 99 wherein G A is G A -18.
  • Embodiment 101 A compound of Embodiment 99 wherein G A is G A -49.
  • Embodiment 103 A compound of Embodiment 102 wherein each R v is independently H, halogen, cyano, hydroxy, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -Cg alkylcarbonyl, C 2 -Cg alkoxycarbonyl, C 3 ⁇ Cg cycloalkyl, C 4 - C 1Q alkylcycloalkyl, C 4 -Q 0 cycloalkylalkyl, C 6 -C ⁇ cycloalkylcycloalkyl, C 2 - Cg alkoxyalkyl, C 3 -Q 0 dialkylaminoalkyl, C 2 -C 7 cyanoalkyl, C 1 -C 6 hydroxyalkyl, C 2 -Cg haloalkoxyalkyl, C 3 -Q 0 alkoxyalky
  • Embodiment 104 A compound of Embodiment 103 wherein each R v is independently H, halogen, cyano, hydroxy, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy or C 1 -C 2 haloalkoxy.
  • Embodiment 104a A compound of Embodiment 104 wherein each R v is independently H, halogen, hydroxy, or methyl.
  • Embodiment 105 A compound of Formula 1 or any one of Embodiments 1 through 104 wherein each R 7a is independently C 1 -C 6 alkyl, C 3 ⁇ C 6 cycloalkyl, C 1 -C 6 haloalkyl, halogen, cyano, Q-C 4 alkoxy, Q-C 4 haloalkoxy or C 2 -C 6 alkoxycarbonyl.
  • Embodiment 106 A compound of Embodiment 105 wherein each R 7a is independently methyl, CF 3 , halogen or methoxy.
  • Embodiment 107 A compound of Formula 1 or any one of Embodiments 1 through 106 wherein R 21 is H, C ⁇ -C 3 alkyl, C ⁇ -C 3 alkylcarbonyl or C 2 -C 3 alkoxycarbonyl.
  • Embodiment 112 A compound of Formula 1 or any one of Embodiments 1 through 111 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z 1 in Formula 1, A is CHR 15 , Z 1 is a direct bond, and J is a substituted isoxazole ring, then J is connected to the remainder of the Formula 1 at the 3- or 5-position of the isoxazole ring.
  • Embodiment 113 A compound of Formula 1 or any one of Embodiments 1 through 112 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z 1 in Formula 1, A is CHR 15 , Z 1 is a direct bond, and J is a substituted isoxazole ring, then J is connected to the remainder of the Formula 1 at the 3-position of the isoxazole ring.
  • Embodiment 114 A compound of Formula 1 or any one of Embodiments 1 through 113 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z 1 in Formula 1, Z 1 is a direct bond, and J is a substituted isoxazole ring, then J is connected to the remainder of the Formula 1 at the 3-position of the isoxazole ring.
  • Embodiment 117 A compound of Formula 1 or any one of Embodiments 1 through 116 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z 1 in Formula 1, then J is other than substituted imidazolyl.
  • Embodiment Al A compound of Formula 1 wherein
  • R 1 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with 1-3 substituents independently selected from R 4a on carbon ring members and R 4 * 5 on nitrogen ring members;
  • G is a 5-membered heterocyclic ring optionally substituted with up to 2 substituents selected from R 3 on carbon ring members and selected from R 1 * on nitrogen ring members;
  • J is one of J-I through J-82 (as depicted in Exhibit 3) wherein the bond shown projecting to the left is bonded to Z 1 ;
  • each R 2 is independently C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, halogen, cyano or hydroxy;
  • each R 3 is independently C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or halogen;
  • each R 4a is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 - C 6 cycloalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C 10 alkylcyclo
  • R 15 is H, halogen, cyano, hydroxy, -CHO, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 2 -C 5 alkoxycarbonyl;
  • R 16 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkylcarbonyl, C 2 -C 4 haloalkylcarbonyl or C 2 -C 4 alkoxycarbonyl; x is an integer from 0 to 5; and s is an integer from 1 to 2.
  • Embodiment A2. A compound of Embodiment Al wherein
  • G is one of G-I through G-59 (as depicted in Exhibit 2) wherein the bond projecting to the left is bonded to X, and bond projecting to the right is bonded to Z 1 ;
  • J is selected from J-I, J-2, J-3, J-4, J-5, J-7, J-8, J-9, J-IO, J-I l, J-12, J-14, J-15, J-16, J-20, J-24, J-25, J-26, J-29, J-30, J-37, J-38, J-45 and J-69;
  • Q is one of Q-I through Q- 106 (as depicted in Exhibit 4);
  • R 1 is one of U-I through U-50 (as depicted in Exhibit 1) wherein when R 4 is attached to a carbon ring member, said R 4 is selected from R 4a , and when R 4 is attached to a nitrogen ring member (e.g., in U-4, U-I l through U-15, U-24 through U-26, U-31 or U-35), said R 4 is selected from R 4b ; each R 2 is independently methyl, methoxy, cyano or hydroxy; each R 3a is independently selected from H and R 3 ; each R 5 is independently H, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -Cg cycloalkyl, C 3 -Cg halocycloalkyl, C 2 -C 6 alkoxyalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -Cg cycloalkoxy, C 2 -
  • R 1 la is selected from H and R 11 ;
  • R 15 is H, cyano, hydroxy, methyl or methoxycarbonyl
  • Embodiment A3. A compound of Embodiment A2 wherein
  • G is selected from G-I, G-2, G-7, G-8, G-14, G-15, G-23, G-24, G-26, G-27,
  • J is selected from J-4, J-5, J-8, J-I l, J-15, J-16, J-20, J-29, J-30, J-37, J-38 and
  • each Q is independently Q-I, Q-20, Q-32 through Q-34, Q-45 through Q-47,
  • Z 1 is a direct bond
  • Z 2 is a direct bond or NR 21
  • R 1 is selected from U-I through U-3, U-I l, U-13, U-20, U-22, U-23, U-36 through U-39 and U-50
  • each R 3 is independently methyl or halogen
  • each R 4a is independently C j -C 2 alkyl, C j -C 2 haloalkyl, halogen, Q-C 2 alkoxy or C j -C 2 haloalkoxy
  • each R 4b is independently C j -C 2 alkyl or C j -C 2 haloalkyl
  • each R 7a is independently C j -C 6 alkyl, C 3 -C 6 cycloalkyl, C j -C 6 haloalkyl, halogen, cyano, C J -C 4 alkoxy, C J -C 4 haloalkoxy or
  • Embodiment A4 A compound of Embodiment A3 wherein A is CH 2 ; G is selected from G-I, G-2, G-15, G-26, G-27, G-36, G-37 and G-38; and G is unsubstituted; J is J-29; Q is selected from Q-I, Q-45, Q-63, Q-64, Q-65, Q-68, Q-69, Q-70, Q-71,
  • X is X 1 or X 2 ; and the ring comprising X is saturated; RMs U-I 5 U ⁇ O Or U-SO; each R 4a is independently C j -C 2 alkyl, trifluoromethyl, Cl, Br, I or methoxy; each R 4 b is independently C j -C 2 alkyl or trifluoromethyl; and each R 5 is independently H, cyano, Cj-C 6 alkyl, Cj-C 6 haloalkyl, Cj-C 6 alkoxy, C 1 -C 6 haloalkoxy or -NR 25 R 26 .
  • G is selected from G-I, G-2, G-15, G-26 and G-36; J is any one of J-29-1 to J-29-60 (depicted in Exhibit A); Q is selected from Q-45, Q-63, Q-64, Q-65, Q-68, Q-69, Q-70, Q-71, Q-72 and Q-85; and X is X 1 .
  • Embodiments of the present invention also include: Embodiment Bl.
  • Embodiment B2 A compound of Formula IA wherein M is C 1 -C 2 alkyl, C 1 -C 2 haloalkyl, hydroxy, Q-C 4 alkoxy, Q-C 2 haloalkoxy, Q-C 3 alkylamino, C 2 - C ⁇ dialkylamino, 1-piperidinyl, 1 -pyrrolidinyl or 4-morpholinyl.
  • Embodiment B2 A compound of Formula IA wherein M is C 1 -C 2 al
  • Embodiment B3 A compound of Embodiment B2 wherein M is methyl, halomethyl, hydroxy, C 2 ⁇ Cg dialkylamino, 1-piperidinyl, 1 -pyrrolidinyl or 4-morpholinyl.
  • Embodiment B4. A compound of Embodiment B3 wherein M is C 2 ⁇ Cg dialkylamino,
  • Embodiment B5 A compound of Formula IA or any one of Embodiments Bl through
  • J 1 is any one of J-29-1 through J-29-57 (as depicted in Exhibit A).
  • J-29 can be present in two or more enantiomeric forms.
  • the enantiomeric forms of J-29 embodiments for compounds of Formula IA of this invention are those depicted in Exhibit A above. All J-29 enantiomers are included in the Formula IA compounds in this invention for embodiments where no specific J-29 enantiomeric form is depicted.
  • Specific embodiments include compounds of Formula 1 selected from the group consisting of: l-[4-[4-[4,5-dihydro-5-[3-(l/f-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl]-2-thiazolyl]-l- piperidinyl] -2- [5 -methyl-3 -(trifluoromethyl)- lH-pyrazol- 1 -yl] ethanone, l-[4-[4-(5-[l,r-biphenyl]-4-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-l-piperidinyl]-2- [5 -methyl-3 -(trifluoromethyl)- lH-pyrazol- 1 -yljethanone,
  • This invention provides a fungicidal composition
  • a fungicidal composition comprising a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof, and at least one other fungicide.
  • a compound selected from compounds of Formula 1 including all geometric and stereoisomers
  • iV-oxides and salts thereof and at least one other fungicide.
  • embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
  • This invention provides a fungicidal composition
  • a fungicidal composition comprising a fungicidally effective amount of a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • a compound selected from compounds of Formula 1 including all geometric and stereoisomers
  • iV-oxides and salts thereof at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
  • This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof.
  • a fungicidally effective amount of a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments described above.
  • the compounds are applied as compositions of this invention.
  • the compounds of Formulae 1 and IA can be prepared by one or more of the following methods and variations as described in Schemes 1-29.
  • the definitions of A, G, J, W, X, Q, Z 1 , Z 2 , Z 3 , R 1 , R 2 , R 15 , R 16 and n in the compounds of Formulae 1-48 and Formulae IBa and IBb below are as defined above in the Summary of the Invention unless otherwise noted.
  • Formulae Ia-Ii are various subsets of Formula 1; Formuls 37a is an alternative depection of Formula 37.
  • compounds of Formula Ia (Formula 1 wherein A is C ⁇ R 15 ) wherein W is O can be prepared by coupling of an acid chloride of Formula 2 with an amine of Formula 3 in the presence of an acid scavenger.
  • Typical acid scavengers include amine bases such as triethylamine, N, ⁇ /-diisopropylethylamine and pyridine.
  • Other scavengers include hydroxides such as sodium and potassium hydroxide and carbonates such as sodium carbonate and potassium carbonate.
  • polymer-supported acid scavengers such as polymer-bound N,N-diisopropylethylamine and polymer- bound 4-(dimethylamino)pyridine.
  • Acid salts of the Formula 3 amines can also be used in this reaction, provided that at least 2 equivalents of the acid scavenger is present.
  • Typical acids used to form salts with amines include hydrochloric acid, oxalic acid and trifluoroacetic acid.
  • amides of Formula Ia wherein W is O can be converted to thioamides of Formula Ia wherein W is S using a variety of standard thiating reagents such as phosphorus pentasulf ⁇ de or 2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulf ⁇ de (Lawesson's reagent).
  • standard thiating reagents such as phosphorus pentasulf ⁇ de or 2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulf ⁇ de (Lawesson's reagent).
  • Polymer-supported reagents are again useful here, such as polymer- bound cyclohexylcarbodiimide. These reactions are typically run at 0-40 0 C in a solvent such as dichloromethane or acetonitrile in the presence of a base such as triethylamine or ⁇ /, ⁇ /-diisopropylethylamine.
  • a base such as triethylamine or ⁇ /, ⁇ /-diisopropylethylamine.
  • the acids of Formula 4 are known or can be prepared by methods known to one skilled in the art. For example, R 1 CH 2 COOH where R 1 is a heteroaromatic ring linked through nitrogen can be prepared by reacting the corresponding R 1 H compound with a haloacetic acid or ester in the presence of base; see, for example, U.S. Patent 4,084,955.
  • Certain compounds of Formula Ib (Formula 1 wherein A is CHR 15 and W is O) wherein R 1 is a 5-membered nitrogen-containing heteroaromatic ring linked through the nitrogen atom can be prepared by reaction of the parent heterocycle of Formula 5 and a haloacetamide of Formula 6 as shown in Scheme 3. The reaction is carried out in the presence of a base such as sodium hydride or potassium carbonate in a solvent such as tetrahydrofuran, ⁇ /, ⁇ /-dimethylformamide or acetonitrile at 0 to 80 0 C.
  • a base such as sodium hydride or potassium carbonate
  • a solvent such as tetrahydrofuran, ⁇ /, ⁇ /-dimethylformamide or acetonitrile at 0 to 80 0 C.
  • the haloacetamide of Formula 6 can be prepared by the reaction of an amine of Formula 3 with an ⁇ -halo carboxylic acid halide or an ⁇ -halo carboxylic acid or its anhydride, analogous to the amide- forming reactions described in Schemes 1 and 2, respectively.
  • R 1 is a 5-membered nitrogen-containing heteroaromatic ring unsubstituted on N; and Y 1 is Cl, Br or I.
  • Compounds of Formulae Ic (Formula 1 wherein A is NH), wherein R 1 is phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic ring, and W is O or S, can be prepared by reaction of an amine of Formula 3 with an isocyanate or isothiocyanate, respectively, of Formula 7 as depicted in Scheme 4. This reaction is typically carried out at an ambient temperature in an aprotic solvent such as dichloromethane or acetonitrile.
  • aprotic solvent such as dichloromethane or acetonitrile.
  • R 16 is H
  • Compounds of Formulae Ic can also be prepared by the reaction of an amine of Formula 8 with a carbamoyl or thiocarbamoyl chloride or imidazole of Formula 9 as shown in Scheme 5.
  • Y is chlorine
  • the reaction is typically carried out in the presence of an acid scavenger.
  • Typical acid scavengers include amine bases such as triethylamine, ⁇ /, ⁇ /-diisopropylethylamine and pyridine.
  • Other scavengers include hydroxides such as sodium and potassium hydroxide and carbonates such as sodium carbonate and potassium carbonate.
  • the carbamoyl or thiocarbamoyl chlorides of Formula 9 can be prepared from amines of Formula 3 by treatment with phosgene or thiophosgene, respectively, or their equivalents, while carbamoyl or thiocarbamoyl imidazoles of Formula 9 (wherein Y is imidazol-1-yl) can be prepared from amines of Formula 3 by treatment with l,l'-carbonyldiimidazole or 1 , l'-thiocarbonyldiimidazole, respectively, according to general methods known to one skilled in the art.
  • W is O or S; and Y is Cl or imidazol-1-yl.
  • Certain compounds of Formula Id can be prepared from compounds of Formula Ie where the ring containing X is unsaturated by catalytic hydrogenation as shown in Scheme 6.
  • Typical conditions involve exposing a compound of Formula Ie to hydrogen gas at a pressure of 70 to 700 kPa, preferably 270 to 350 kPa, in the presence of a metal catalyst such as palladium supported on an inert carrier such as activated carbon, in a weight ratio of 5 to 20 % of metal to carrier, suspended in a solvent such as ethanol at an ambient temperature.
  • a metal catalyst such as palladium supported on an inert carrier such as activated carbon
  • This type of reduction is very well known; see, for example, Catalytic Hydrogenation, L. Cerveny, Ed., Elsevier Science, Amsterdam, 1986.
  • One skilled in the art will recognize that other certain functionalities that may be present in compounds of Formula Ie can also be reduced under catalytic hydrogenation conditions, thus requiring a suitable choice of catalyst and conditions.
  • Certain compounds of Formula 1 wherein X is X 1 , X 5 , X 7 or X 9 , and G is linked to the ring containing X via a nitrogen atom, can be prepared by displacement of an appropriate leaving group Y 2 on the ring containing the X of Formula 10 with a nitrogen-containing heterocycle of Formula 11 in the presence of a base as depicted in Scheme 7.
  • Suitable bases include sodium hydride or potassium carbonate, and the reaction is carried out in a solvent such as N,N-dimethylformamide or acetonitrile at 0 to 80 0 C.
  • Suitable leaving groups in the compounds of Formula 10 include bromide, iodide, mesylate (OS(O) 2 CH 3 ), triflate (OS(O) 2 CF 3 ) and the like, and compounds of Formula 10 can be prepared from the corresponding compounds wherein Y 2 is OH, using general methods known in the art.
  • W is O or S;
  • X is X 1 , X 5 , X 7 or X 9 ; and
  • Y 2 is a leaving group such as Br, I, OS(O) 2 Me or OS(O) 2 CF 3 .
  • Compounds of Formula 1 wherein X is X 2 or X 8 can be prepared by reaction of a compound of Formula 12 with a heterocyclic halide or triflate (OS(O) 2 CF 3 ) of Formula 13 as shown in Scheme 8. The reaction is carried out in the presence of a base such as potassium carbonate in a solvent such as dimethylsulfoxide, N, ⁇ /-dimethylformamide or acetonitrile at 0 to 80 0 C.
  • a base such as potassium carbonate
  • a solvent such as dimethylsulfoxide, N, ⁇ /-dimethylformamide or acetonitrile at 0 to 80 0 C.
  • Compounds of Formula 13 wherein Y 2 is triflate can be prepared from corresponding compounds wherein Y 2 is OH by methods known to one skilled in the art.
  • W is O or S; X is X 2 or X 8 ; and Y 2 is a leaving group such as Br, I OS(O) 2 Me or OS(O) 2 CF 3 .
  • the amine compounds of Formula 3 can be prepared from the protected amine compounds of Formula 14 where Y 3 is an amine -protecting group as shown in Scheme 9.
  • Y 3 is an amine -protecting group as shown in Scheme 9.
  • a wide array of amine -protecting groups are available (see, for example, T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991), and the use and choice of the appropriate protecting groups will be apparent to one skilled in chemical synthesis.
  • the protecting group can be removed and the amine isolated as its acid salt or the free amine by general methods known in the art.
  • the compounds of Formula 14 can also be prepared by reaction of a suitably functionalized compound of Formula 15 with a suitably functionalized compound of Formula 16 as shown in Scheme 10.
  • the functional groups Y 4 and Y 5 are selected from, but not limited to, moieties such as aldehydes, ketones, esters, acids, amides, thioamides, nitriles, amines, alcohols, thiols, hydrazines, oximes, amidines, amideoximes, olefins, acetylenes, halides, alkyl halides, methanesulfonates, trifluoromethanesulfonates, boronic acids, boronates, and the like, which under the appropriate reaction conditions, will allow the construction of the various heterocyclic rings G.
  • reaction of a compound of Formula 15 where Y 4 is a thioamide group with a compound of Formula 16 where Y 5 is a bromoacetyl or chloroacetyl group will give a compound of Formula 14 where G is a thiazole ring.
  • the synthetic literature describes many general methods for forming 5- membered heteroaromatic rings and 5-membered partially saturated heterocyclic rings (e.g., G-I through G-59); see, for example, Comprehensive Heterocyclic Chemistry, Vol. 4-6, A. R. Katritzky and C. W. Rees editors, Pergamon Press, New York, 1984; Comprehensive Heterocyclic Chemistry II, Vol. 2-4, A. R. Katritzky, C. W.
  • Y 4 and Y 5 are functional groups suitable for construction of the desired heterocycle G.
  • a method analogous to Scheme 10 can be used to form the G ring from precursor groups Y 4 and Y 5 after attaching the left portion of molecule using methods analogous to Schemes 1 through 5.
  • This alternate synthetic route is demonstrated in Example 2 wherein Step A is analogous to Scheme 4, Step B is analogous to a method for preparing a starting compound for Scheme 10, Step C corresponds to Scheme 28, Step D is analogous to Scheme 20 and Step E is analogous to Scheme 10.
  • Certain compounds of Formula 14 where Z 1 is O, S, or NR 21 can be prepared by displacement of an appropriate leaving group Y 2 on G of Formula 17 with a compound of Formula 18 in the presence of a base as depicted in Scheme 11.
  • Suitable bases include sodium hydride or potassium carbonate, and the reaction is carried out in a solvent such as ⁇ /, ⁇ /-dimethylformamide or acetonitrile at 0 to 80 0 C.
  • Suitable leaving groups in the compounds of Formula 17 include bromide, iodide, mesylate (OS(O) 2 CH 3 ), triflate (OS(O ⁇ CF 3 ) and the like.
  • Compounds of Formula 17 can be prepared from corresponding compounds wherein Y 2 is OH by general methods known in the art.
  • the compounds of Formula 18 are known or can be prepared by general methods known in the art.
  • Y 2 is a leaving group such as Br, I, OS(O ⁇ Me or OS(O ⁇ CF 3 ; and Z 1 is O, S or
  • Certain compounds of Formula 14 where Z 1 is O, S, or NR 21 can also be prepared by displacement of an appropriate leaving group Y 2 on J of Formula 20 with a compound of Formula 19 in the presence of a base as depicted in Scheme 12.
  • Suitable bases include sodium hydride or potassium carbonate, and the reaction is carried out in a solvent such as ⁇ /, ⁇ /-dimethylformamide or acetonitrile at 0 to 80 0 C.
  • Suitable leaving groups in the compounds of Formula 20 include bromide, iodide, mesylate (OS(O ⁇ CH 3 ), triflate (OS(O) 2 CF 3 ) and the like.
  • Compounds of Formula 20 can be prepared from corresponding compounds wherein Y 2 is OH using general methods known in the art.
  • Y 2 is a leaving group such as Br, I, OS(O ⁇ Me or OS(O ⁇ CF 3 ; and Z 1 is O, S or
  • Compounds of Formula 14 can also be prepared by reaction of a suitably functionalized compound of Formula 21 with a suitably functionalized compound of Formula 22 as shown in Scheme 13.
  • the functional groups Y 6 and Y 7 are selected from, but not limited to, moieties such as aldehydes, ketones, esters, acids, amides, thioamides, nitriles, amines, alcohols, thiols, hydrazines, oximes, amidines, amide oximes, olefins, acetylenes, halides, alkyl halides, methanesulfonates, trifluoromethanesulfonates, boronic acids, boronates, and the like, which, under the appropriate reaction conditions will allow the construction of the various heterocyclic rings J.
  • reaction of a compound of Formula 21 where Y 6 is a chloro oxime moiety with a compound of Formula 22 where Y 7 is a vinyl or acetylene group in the presence of base will give a compound of Formula 14 where J is an isoxazoline or isoxazole, respectively.
  • the synthetic literature includes many general methods for the formation of carbocyclic and heterocyclic rings and ring systems (for example, J-I through J-82); see, for example, Comprehensive Heterocyclic Chemistry, Vol. 4-6, A. R. Katritzky and C. W. Rees editors, Pergamon Press, New York, 1984; Comprehensive Heterocyclic Chemistry II, Vol. 2-4, A. R. Katritzky, C. W.
  • An alternate preparation for the compounds of Formula 14 where Z 1 is a bond includes the well known Suzuki reaction involving Pd-catalyzed cross-coupling of an iodide or bromide of Formula 23 or 26 with a boronic acid of Formula 24 or 25, respectively, as shown in Scheme 14.
  • Many catalysts are useful for this type of transformation; a typical catalyst is tetrakis(triphenylphosphine)palladium.
  • Solvents such as tetrahydrofuran, acetonitrile, diethyl ether and dioxane are suitable.
  • the Suzuki reaction and related coupling procedures offer many alternatives for creation of the G-J bond. For leading references; see, for example, C. A. Zificsak and D. J.
  • Thioamides of Formula IBb are particularly useful intermediates for preparing compounds of Formula 1 wherein X is X 1 using the thioamide- ⁇ -haloaryl ring-forming reaction described for the method of Scheme 10.
  • a thioamide of Formula IBb can be prepared by the addition of hydrogen sulfide to the corresponding nitrile of Formula IBa as shown in Scheme 15.
  • the method of Scheme 15 can be carried out by contacting a compound of Formula IBa with hydrogen sulfide in the presence of an amine such as pyridine, diethylamine or diethanolamine.
  • hydrogen sulfide can be used in the form of its bisulfide salt with an alkali metal or ammonia. This type of reaction is well documented in the literature (e.g., A. Jackson et al., EP 696,581 (1996)). This method is demonstrated in Example 1, Step C and Example 2, Step B..
  • Certain compounds of Formula IBa wherein R 1 is a 5-membered nitrogen-containing heteroaromatic ring linked through a nitrogen atom can be prepared by reaction of the parent heterocycle of Formula 5 and a haloacetamide of Formula 27 as shown in Scheme 16. The reaction is carried out in the presence of a base such as sodium hydride or potassium carbonate in a solvent such as tetrahydrofuran, N, ⁇ /-dimethylformamide or acetonitrile at 0 to 80 0 C. This method is demonstrated in Example 1, Step B.
  • R 1 is a 5-membered nitrogen-containing heteroaromatic ring unsubstituted on N (i.e. a 5-membered heteroaromatic ring comprising a ring member of the formula -(NH)-);
  • A is CH 2 ; and
  • Y 1 is Cl, Br or I.
  • haloacetamides of Formula 27 can be prepared by the two methods shown in Scheme 17.
  • Y 1 is Cl, Br, or I; and R 31 is a tertiary alkyl group such as -C(Me) 3 .
  • 4-cyanopiperidine of Formula 29 is haloacetylated by contact with the appropriate haloacetyl chloride typically in the presence of a base according to standard methods.
  • Preferred conditions involve use of an aqueous solution of an inorganic base such as an alkali metal or alkaline-earth carbonate, bicarbonate or phosphate, and a non-water- miscible organic solvent such as toluene, ethyl acetate or 1,2-dichloroethane.
  • a particularly preferred solvent for this transformation is an JV,iV-dialkylamide such as ⁇ /, ⁇ /-dimethylformamide.
  • the reaction is typically carried out by adding 0.9 to 2 equivalents, preferably 1.1 equivalents, of phosphorus oxychloride or thionyl chloride to a mixture of a compound of Formula 28 and 0.5 to 10 parts by weight of solvent, at a temperature at which the reaction rapidly proceeds during the addition.
  • the addition time for this reaction is typically around 20 to 90 minutes at typical temperatures of around 35 to 55 0 C.
  • the compounds of Formula 28 can be prepared from the compound of Formula 30 by analogy with the haloacetylation reaction described for Scheme 17.
  • the compounds of Formula 30 are known or can be prepared from 4-cyanopyridine or isonicotinic acid using methods well-known in the art; see, for example, G. Marzolph et al., DE 3,537,762 (1986) for preparation of N-t-butyl pyridinecarboxamides from cyanopyridines and t-butanol and S. F. Nelsen et al, J. Org. Chem., 1990, 55, 3825 for hydrogenation of JV-methylisonicotinamide with a platinum catalyst.
  • Halomethyl isoxazole ketones of Formula 35 are particularly useful intermediates for preparing certain chiral compounds of Formula 1 wherein J is, for example, selected from J-29-1 through J-29-57 as depicted in Exhibit A.
  • Halomethyl isoxazole ketones of Formula 35 can be prepared by the multi-step reaction sequences shown in Scheme 19.
  • R 32 is C 2 ⁇ Cg dialkylamino, 1-piperidinyl, 1-pyrrolidinyl or 4-morpholinyl and Q is as defined above in the Summary of the Invention.
  • the preparation of the racemic carboxylic acids of Formula 32 can be accomplished according to the well-known methods of basic or acidic hydrolysis of the corresponding compounds of Formula 31, preferably using a slight excess of sodium hydroxide in a water- miscible co-solvent such as methanol or tetrahydrofuran at about 25 to 45 0 C.
  • the product can be isolated by adjusting pH to about 1 to 3 and then filtration or extraction, optionally after removal of the organic solvent by evaporation.
  • the racemic carboxylic acids of Formula 32 can be resolved by classical fractional crystallization of diastereomeric salts of suitable chiral amine bases such as cinchonine, dihydrocinchonine or a mixture thereof.
  • a cinchonine-dihydrocinchonine mixture in about a 85:15 ratio is particularly useful, as it provides, for example, the (7?)-conf ⁇ gured carboxylic acids of Formula 33, wherein R 5 is a substituted phenyl group, as the less soluble salt. Furthermore, these chiral amine bases are readily available on a commercial scale.
  • the (i?)-configured halomethyl ketone intermediates of Formula 35 afford the more fungicidally active final products of Formula 1 after coupling with thioamides of Formula IBb according to the method of Scheme 10.
  • the halomethyl ketones of Formula 35 can be prepared by first reacting the corresponding amides of Formula 31, either as pure enantiomers (i.e.
  • R 32 can be other groups besides C 2 ⁇ Cg dialkylamino, 1-piperidinyl, 1- pyrrolidinyl or 4-morpholinyl.
  • R 32 can also be C 1 -C 4 alkoxy, C ⁇ -C 2 haloalkoxy or C 1 -C 4 alkylamino.
  • methyl (CH 3 ) group in Formula 34 and halomethyl (Y 1 CF ⁇ ) group in Formula 35 are homologously representative of M in Formula IA being C ⁇ -C 3 alkyl and C ⁇ -C 3 haloalkyl, respectively.
  • the isoxazole carboxamides of Formula 31 can be prepared by cycloaddition of the corresponding hydroxamoyl chlorides of Formula 36 with olefin derivatives of Formula 37, as shown in Scheme 20.
  • the base which can either be a tertiary amine base such as triethylamine or an inorganic base such as an alkali metal or alkaline- earth carbonate, bicarbonate or phosphate, is mixed with the olefin derivative of Formula 37, and the hydroxamoyl chloride of Formula 36 is added gradually at a temperature at which the cycloaddition proceeds at a relatively rapid rate, typically between 5 and 25 0 C.
  • the base can be added gradually to the other two components (the compounds of Formulae 36 and 37).
  • This alternative procedure is preferable when the hydroxamoyl chloride of Formula 36 is substantially insoluble in the reaction medium.
  • the solvent in the reaction medium can be water or an inert organic solvent such as toluene, hexane or even the olefin derivative used in excess.
  • the product can be separated from the salt co-product by filtration or washing with water, followed by evaporation of the solvent.
  • the crude product can be purified by crystallization, or the crude product can be used directly in the methods of Scheme 19.
  • the method of Scheme 20 is demonstrated in Example 1, Step F. Also, a method analogous to Scheme 20 is demonstrated in Example 2, Step D.
  • Compounds of Formula 31 are useful precursors to the corresponding methyl ketones of Formula 34 and halomethyl ketones of Formula 35, and are also useful for preparing the resolved enantiomers of the compounds of Formulae 34 and 35 by hydrolysis, resolution, methyl ketone synthesis and halogenation, as shown in Scheme 19.
  • Y 8 is F, Cl, Br, I; Z 3 is O, S or NH; G G is G A , G N or G p .
  • This reaction (known as the Ullmann ether synthesis when Z 3 is O) is well known to one skilled in the art.
  • the reaction is typically carried out in the presence of an inorganic base such as potassium carbonate or cesium carbonate and with a metal catalyst, for example, copper iodide. Temperatures between room temperature and 150 0 C and solvents such as dimethyl sulfoxide and ⁇ /, ⁇ /-dimethylformamide are suitable for the reaction.
  • Diaryl ethers of Formula If wherein Z 3 is O can also be prepared using palladium-catalyzed Buchwald- Hartwig reaction, nucleophilic aromatic substitution or arylboronic acid diaryl ether coupling. For a recent review of these methods, including the Ullmann diaryl ether synthesis; see, for example, R. Frian and D. Kikeji, Synthesis 2006, 14, 2271-2285.
  • a similar copper-catalyzed method can be used to prepare compounds of Formula Ig (i.e. Formula If wherein Z 3 is a direct bond and G G is G Gn bonded through a nitrogen ring member) wherein G Gn is G A , G N or G p bonded through a nitrogen atom ring member of G Gn to Q from a heterocycle HG Gn in which H is connected to a nitrogen ring member, for example, triazole, or a salt thereof (e.g., sodium triazole) as shown in Scheme 22.
  • Y 8 is F, Cl, Br, I;
  • G Gn is a G A , G N or G p bonded through a ring nitrogen atom to Q.
  • a ligand such as (li?,2i?)- ⁇ /, ⁇ /-dimethyl-l,2-cyclohexenediamine can be used to increase the solubility and reactivity of the copper catalyst.
  • the reaction is typically carried out in a solvent such as dimethylsulfoxide or in a mixed solvent such as dimethylsulfoxide- water at temperatures between room temperature and 200 0 C.
  • a solvent such as dimethylsulfoxide or in a mixed solvent such as dimethylsulfoxide- water at temperatures between room temperature and 200 0 C.
  • Y 9 is Cl, Br, I, or OS(O) 2 CF 3 ;
  • G Gc is G A , G N or G p bonded through an sp 2 ring carbon atom to Q.
  • methods for preparing compounds of Formula If wherein Z 3 is -C ⁇ C- include the well-known Sonogashira reaction using Pd-catalyzed cross-coupling of a halide of Formula 40 wherein Y 9 is a halogen such as iodine or bromide with an alkyne of Formula 42 in the presence of a metal catalyst and a base.
  • Y 9 is Cl, Br, I, or OS(O) 2 CF 3 ; Z 3 is -C ⁇ C-; G G is G A , G N or G p .
  • Many catalysts are useful for this type of transformation; a typical catalyst is dichlorobis(tri-o-tolylphosphine)palladium (II).
  • Suitable solvents include tetrahydrofuran, acetonitrile and ethyl acetate.
  • Suitable metal catalysts include, for example, copper iodide.
  • Typical bases include, for example, triethylamine or Hunig's base. For leading references; see, for example, I. B. Campbell, Organocopper Reagents 1994, 217-235.
  • G G is G A , G N or G p .
  • the reduction is typically carried out under an atmosphere of hydrogen at pressures from atmospheric to 700 kPa, preferably about 400 kPa, in a solvent such as ethyl acetate or ethanol using methods well known to one skilled in the art.
  • a solvent such as ethyl acetate or ethanol
  • Many catalysts are useful for this type of transformation; a typical catalyst is tris(dibenzylideneacetone)dipalladium. Suitable solvents include ⁇ /,iV-dimethylformamide and acetonitrile.
  • Compounds of Formula Ii i.e. Formula 1 wherein Z 3 is a direct bond and G G is a tetrazole ring bonded to Q through the tetrazole ring carbon atom
  • a nitrile of Formula 46 is reacted with an azide such as sodium azide or trimethylsilyl azide in a solvent such at ⁇ /,iV-dimethylformamide or toluene at temperatures from room temperature to 140 0 C to form a compound of Formula Ii.
  • an azide such as sodium azide or trimethylsilyl azide
  • a solvent such at ⁇ /,iV-dimethylformamide or toluene at temperatures from room temperature to 140 0 C
  • Aldehydes of Formula 47 can be used to prepare olefins of Formula 37a using the well-known Wittig (this method is demonstrated in Example 1 , Step E) or Tebbe olefmation reactions as shown in Scheme 28.
  • G G is G A , G N or G p .
  • the method of Scheme 29 using reagents and reaction conditions similar to those described for Scheme 21 provides, for example, the corresponding diaryl ether when Z 3 is oxygen, (e.g., 2-phenoxybenzaldehyde is obtained starting with 2-iodobenzaldehyde and phenol).
  • Several starting aldehydes of Formula 48 are commercially available, for example, the ortho, meta and para isomers of fluorobenzaldehyde, chlorobenzaldehyde, bromobenzaldehyde and iodobenzaldehyde.
  • aldehydes of Formula 47 are also commercially available including 2-phenylbenzaldehyde, 2-phenoxybenzaldehyde 2-(furan-2-yl)benzaldehyde, 2-(thien-2- yl)benzaldehyde, 2-(imidazol-l-yl)benzaldehyde and 2-(thiazol-2-yl)benzaldehyde.
  • Step A Preparation of l-(2-chloroacetyl)-4-piperidinecarbonitrile
  • Step B Preparation of l-[2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]acetyl]-4- piperidinecarbonitrile
  • the filter cake was washed with water and dried at 50 0 C in a vacuum-oven to give 15 g of the title compound as a solid containing 3 % of its regioisomer, i.e. l-[2-[3-methyl-5-(trifluoromethyl)-lH-pyrazol- 1 -yl]acetyl]-4-piperidinecarbonitrile.
  • Step C Preparation of l-[2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]acetyl]-4- piperidinecarbothioamide
  • Hydrogen sulfide gas was passed into a solution of l-[2-[5-methyl- 3-(trifluoromethyl)-lH-pyrazol-l-yl]acetyl]-4-piperidinecarbonitrile (i.e. the product of Example 1, Step B) (9.0 g, 30 mmol) and diethanolamine (3.15 g, 30 mmol) in ⁇ /, ⁇ /-dimethylformamide (15 mL) at 50 0 C in a flask equipped with dry-ice condenser. The hydrogen sulfide feed was stopped when the reaction mixture became saturated with hydrogen sulfide, as indicated by condensation on the cold-finger. The reaction mixture was stirred for an additional 30 minutes at 50 0 C.
  • Step E Preparation of l-ethenyl-3-iodobenzene
  • 3-iodobenzaldehyde 2.0 g, 8.6 mmol
  • methyltriphenylphosphonium bromide 4.62 g, 12.9 mmol
  • tetrahydrofuran 50 mL
  • a solution of potassium te/t-butoxide (1.45 g, 12.9 mmol) in tetrahydrofuran (20 mL) was added dropwise at 0 0 C over 1 h.
  • Step F Preparation of 2-chloro-l-[4,5-dihydro-5-(3-iodophenyl)-3- isoxazolyl] ethanone To a solution of l-ethenyl-3-iodobenzene (i.e. the product of Example 1, Step E)
  • Step G Preparation of l-[4-[4-[4,5-dihydro-5-(3-iodophenyl)-3-isoxazolyl]-2- thiazolyl]- 1 -piperidinyl]-2-[5-methyl-3-(trifluoromethyl)- lH-pyrazol-1 - yl] ethanone
  • Step H Preparation of l-[4-[4-[4,5-dihydro-5-[3-(lH-l,2,4-triazol-l-yl)phenyl]-3- isoxazolyl] -2 -thiazolyl] - 1 -piperidinyl]-2- [5 -methyl-3 -(trifluoromethyl)- IH- pyrazol- 1 -yl]ethanone
  • 1,2,4-triazole 63.0 mg, 0.69 mmol
  • Example 1 the product of Example 1, Step G), (217 mg, 0.34 mmol), (+)-sodium L-ascorbate (3.4 mg, 0.017 mmol), copper iodide (6.6 mg, 0.034 mmol) and (li?,2i?)- ⁇ /,N-dimethyl-l,2-cyclohexenediamine (7.3 mg, 0.051 mmol) in 2 mL of an 80:20 solution of dimethylsulfoxide and water.
  • the reaction mixture was heated at 60 0 C for 20 h and then at 100 0 C for 24 h. After cooling, the reaction mixture was diluted with water and extracted 2 times with ethyl acetate.
  • Step A Preparation of 4-cyano- ⁇ /-(2,5-dimethylphenyl)-l-piperidinecarboxamide
  • Step B Preparation of 4-(aminothioxomethyl)- ⁇ /-(2,5-dimethylphenyl)-l-piperidine- carboxamide
  • Step D Preparation of l-(5-[l,l'-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2- chloroethanone
  • 2-ethenyl- l,l'-biphenyl i.e. the product of Example 2, Step C
  • 3-chloro- ⁇ /-hydroxy-2-oxo-propanimidoyl chloride i.e. the product of Example 1, Step D
  • sodium bicarbonate (1.05 g, 12.5 mmol
  • the reaction mixture was concentrated under reduced pressure.
  • the resultant residue was taken up in ethyl acetate, 2 mL of water added and eluted with ethyl acetate through a ChemElute® diatomaceous earth-based liquid-liquid exchange cartridge and concentrated to give 630 mg of the title compound as a colorless oil.
  • Step E Preparation of 4-[4-(5-[l, l'-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2- thiazolyl]- ⁇ /-(2,5-dimethylphenyl)- 1 -piperidinecarboxamide
  • the invention includes but is not limited to the following exemplary species.
  • A is NH; W is O.
  • A is CH 2 ; W is S Rl Rl
  • 5-chloro-2-methylphenyl RI is 5-methyl-3-(trifluoromethyl)pyrazol-l-yl; W is O.
  • ZMs a direct bond; Z 2 is a direct bond; Z 3 is CH 2 ; x is 0; G A is G A -49; r is O J2 J-orientation** J2 J-orientation** J2 J-orientation** J2 J-orientation**
  • J-24 2/4 J-44 1/3 ** J-orientation refers to the attachment points for Z ⁇ and Z 2 on the ring of fi (which is identified by reference to the J groups of Exhibit 3).
  • the first number refers to the position on the ring of J 2 (with reference to the J groups of Exhibit 3) where zS is attached, and the second number refers to the position on the ring of J 2 where Z 2 is attached.
  • R 3a isH;n isO.
  • GisG-l;R 3a is H; nis 0.
  • R 1 is 2,5-dichlorophenyl
  • X is X 2
  • G is G-I
  • R 3a is H.
  • R 1 is 2,5-dichlorophenyl; X is X 1 ; G is G-2; R 3a is H.
  • R 1 is 2,5-dichloophenyl
  • X is X 2
  • G is G-2
  • R 3a is H.
  • R 1 is 2-chloro-5-(trifluoromethyl)phenyl
  • X is X 1
  • G is G-I
  • R 3a is H.
  • R 1 is 2-chloro-5-(trifluoromethyl)phenyl
  • X is X 2
  • G is G-2
  • R 3a is H.
  • R 1 is 2,5-dimethylphenyl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 2,5-dimet lphenyl
  • X is X 2
  • G is G-I
  • R 3a is H.
  • R 1 is 2,5-dimethylphenyl; X is X 1 ; G is G-2; R 3a is H.
  • R 1 is 2-methyl-
  • R 1 is 2-methyl-
  • R 1 is 2-methyl-
  • R 1 is 3,5-dimethylpyrazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 3,5-dimethylpyrazol-l-yl
  • X is X 2
  • G is G-2
  • R 3a is H.
  • R 1 is 3,5-dichloropyrazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 3,5-dichloopyrazol-l-yl
  • X is X 2
  • G is G-I
  • R 3a is H.
  • R 1 is 3,5-dichloropyrazol-l-yl
  • X is X 1
  • G is G-2
  • R 3a is H.
  • R 1 is 3,5-dichloropyrazol-l-yl
  • X is X 2
  • G is G-2
  • R 3a is H.
  • R 1 is 3,5-dibro opyrazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 3,5-dibromopyrazol-l-yl
  • X is X 2
  • G is G-I
  • R 3a is H.
  • R 1 is 5-methyl-3-(trifluoromethyl)pyrazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 5-methyl-
  • R 1 is 5-methyl-
  • R 1 is 5-ethyl-3-(trifluoromethyl)pyrazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 5-ethyl-3-(trifluoromethyl)pyrazol-l-yl; X is X 2 ; G is G-I; R 3a is H J
  • R 1 is 5-ethyl -3-(trifluoromethyl)pyrazol-l-yl
  • X is X 1
  • G is G-2
  • R 3a is H.
  • R 1 is 3-methyl-
  • R 1 is 3-methyl-
  • R 1 is 3-chloro-5-(trifluoromethyl)pyrazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 5-methoxy-3-(trifluoromethyl)pyrazol-l-yl; X is X 2 ; G is G-I; R 3a is H.
  • R 1 is 5-difluoromethoxy-3-(trifluoromethyl)pyrazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 5-difluoromethoxy-3-(trifluoromethyl)pyrazol-l-yl; X is X 2 ; G is G-2; R 3a is H.
  • R 1 is 3,5-dichlorotriazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 3,5-dichlootriazol-l-yl
  • X is X 2
  • G is G-I
  • R 3a is H.
  • R 1 is 3,5-dichlorotriazol-l-yl; X is X 1 ; G is G-2; R 3a is H.
  • R 1 is 3,5-dichlorotriazol-l-yl
  • X is X 2
  • G is G-2
  • R 3a is H.
  • R 1 is 3,5-dibro otriazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • R 1 is 3,5-dibromotriazol-l-yl
  • X is X 2
  • G is G-I
  • R 3a is H.
  • R 1 is 3,5-dibromotriazol-l-yl; X is X 1 ; G is G-2; R 3a is H.
  • R 1 is 3,5-dibro otriazol-l-yl
  • X is X 2
  • G is G-2
  • R 3a is H.
  • R 1 is 3,5-dimethyltriazol-l-yl
  • X is X 1
  • G is G-I
  • R 3a is H.
  • R 1 is 3,5-dimethyltriazol-l-yl
  • X is X 2
  • G is G-2
  • R 3a is H.
  • R 1 is 5-methyl-3-(trifluoromethyl)triazol-l-yl; X is X 1 ; G is G-I; R 3a is H
  • R 1 is 5-methyl -3-(trifluoromethyl)triazol-l-yl; X is X 1 ; G is G-2; R 3a is H.
  • R 1 is 5-methyl-3-(trifluoromethyl)triazol-l-yl; X is X 2 ; G is G-2; R 3a is H
  • R 1 is 3 -methyl -5-(trifluoromethyl)triazol-l-yl; X is X 2 ; G is G-I; R 3a is H.
  • R 1 is 3-methyl-5-(trifluoromethyl)triazol-l-yl; X is X 1 ; G is G-2; R 3a is H.
  • R 1 is 3-methyl- -(trifluoromethyl)triazol-l-yl; X is X 2 ; G is G-2; R 3a is H.
  • R 1 is 3,5-bis-(trifluoromethyl)triazol-l-yl; X is X 1 ; G is G-I; R 3a is H.
  • Table 5 above identifies particular compounds comprising a J group selected from J-29-1 through J-29-60 (i.e. particular examples of J-29). As many J-29-1 to J-29-60 include a chiral center, these J groups are illustrated in a particular enantiomeric configuration, which in some instances may provide the greatest fungicidal activity.
  • One skilled in the art immediately recognizes the antipode (i.e. opposite enantiomer) for each of the compounds listed, and furthermore understands that the enantiomers can be present as pure enantiomers or in mixtures enriched in one enantiomer or in racemic mixtures.

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Abstract

Disclosed are compounds of Formulae 1 and 1A (including all geometric and stereoisomers), N-oxides, and salts thereof,(Formula (I, IA), wherein R1, R2, A, G, M, W, Z1, X, J, J1 and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

Description

TITLE FUNGICIDAL AMIDES
FIELD OF THE INVENTION
This invention relates to certain carboxamides, their //-oxides, salts and compositions, and methods of their use as fungicides.
BACKGROUND OF THE INVENTION
The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different sites of action.
World Patent Publication WO 2005/003128 discloses certain thiazolylpiperidines of Formula i and their use as microsomal triglyceride transfer protein inhibitors.
Figure imgf000002_0001
World Patent Publication WO 2004/058751 discloses certain piperidinyl-thiazole carboxamides for altering vascular tone.
PCT Patent Publication WO 2007/014290 discloses certain azocyclic amides of Formula ii
Figure imgf000002_0002
ii and their use as fungicides.
SUMMARY OF THE INVENTION
This invention relates to compounds of Formula 1 (including all geometric and stereoisomers), iV-oxides, and salts thereof, agricultural compositions containing them and their use as fungicides:
Figure imgf000003_0001
wherein
R1 is an optionally substituted phenyl or 5- or 6-membered heteroaromatic ring or optionally substituted naphthalenyl;
A is CHR15 or NR16;
R15 is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylsulfϊnylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3-C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3~C5 dialkylaminocarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1C4 haloalkylthio, C1-C4 alkylsulfϊnyl, C1-C4 haloalkylsulfmyl, C1-C4 alkylsulfonyl or C1-C4 haloalkylsulfonyl;
R16 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2- C4 alkylsulfmylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3~C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3~C5 dialkylaminocarbonyl, C1-C4 alkylsulfonyl or C1- C4 haloalkylsulfonyl;
W is O or S;
X is a radical selected from
Figure imgf000003_0002
χl x2 x3 χ<
Figure imgf000003_0003
X5 X6 X7
Figure imgf000004_0001
X8 X9 wherein the bond of X1, X2, X3, X4, X5, X6, X7, X8 or X9 which is identified with "t" is connected to the carbon atom identified with "q" of Formula 1, the bond which is identified with "u" is connected to the carbon atom identified with "r" of Formula 1, and the bond which is identified with "v" is connected to G; each R2 is independently Q-C4 alkyl, Q-C4 alkenyl, Q-C4 haloalkyl, C1-C 4 alkoxy, halogen, cyano or hydroxy; or two R2 are taken together as Q-C4 alkylene or C2-C4 alkenylene to form a bridged bicyclic or fused bicyclic ring system; or two R2 attached to adjacent ring carbon atoms joined by a double bond are taken together as -CH=CH-CH=CH- optionally substituted with 1 to 3 substituents selected from Q-C4 alkyl, Q-C4 haloalkyl, Q-C4 alkoxy, Q-C4 haloalkoxy, halogen, hydroxy, amino, cyano and nitro;
G is an optionally substituted 5-membered heterocyclic ring;
J is a 5-, 6- or 7-membered ring, a 8- to 11-membered bicyclic ring system or a 7- to 11-membered spirocyclic ring system, each ring or ring system containing ring members selected from carbon, up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18, each ring or ring system substituted with 1 to 2 substituents independently selected from -Z2Q and optionally substituted with 1 to 5 substituents independently selected from R5; each R5 is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH, -C(=0)NH2, -NR25R26, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C^ cycloalkylcycloalkyl, C4-C10 halocycloalkylalkyl, C5-C10 alkylcycloalkylalkyl, C3-C8 cycloalkenyl, C3-C8 halocycloalkenyl, C2-C6 alkoxyalkyl, C 4-C1O cycloalkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkylsulfinylalkyl, C2-C6 alkylsulfonylalkyl, C2-C6 alkylaminoalkyl, C3-C8 dialkylaminoalkyl, C2-C6 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C4~C8 cycloalkylcarbonyl, C2- C6 alkoxycarbonyl, C4~C8 cycloalkoxycarbonyl, C5-C10 cycloalkylalkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4~C8 cycloalkylaminocarbonyl, C2-C6 haloalkoxyalkyl, Ci-Cg hydroxyalkyl, Ci-Cg alkoxy, Ci-Cg haloalkoxy, C3-C8 cycloalkoxy, C3- Cg halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, CzpCg cycloalkylcarbonyloxy, C3-C6 alkylcarbonylalkoxy, Ci-Cg alkylthio, Ci-Cg haloalkylthio, C3-C8 cycloalkylthio, Ci-Cg alkylsulfϊnyl, Ci-Cg haloalkylsulfϊnyl, Ci-Cg alkylsulfonyl, Ci-Cg haloalkylsulfonyl, C3-C8 cycloalkylsulfonyl, C3-C10 trialkylsilyl, Ci-Cg alkylsulfonylamino or Ci-Cg haloalkylsulfonylamino;
R25 is H, Ci-C6 alkyl, Ci-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2- Cg haloalkylcarbonyl, C2-Cg alkoxycarbonyl or C2-Cg haloalkoxycarbonyl;
R26 is Ci-C6 alkyl, Ci-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 haloalkoxycarbonyl or -Z4Q; each R17 and R18 is independently Ci-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C3- C5 cycloalkyl, C3-C6 halocycloalkyl, C4-C10 cycloalkylalkyl, C4-C7 alkylcycloalkyl, C5-C7 alkylcycloalkylalkyl, Ci-C5 haloalkyl, Ci-C5 alkoxy or Ci-C5 haloalkoxy; each Q is independently phenyl, benzyl, naphthalenyl, a 5- or 6-membered heteroaromatic ring or an 8- to 11-membered heteroaromatic bicyclic ring system, each substituted with 1 to 2 substituents independently selected from R7 on carbon or nitrogen atom ring members, and each optionally substituted with 1 to 5 substituents independently selected from R7a on carbon atom ring members and R12 on nitrogen atom ring members; or a 3- to 7-membered nonaromatic carbocyclic ring, a 5-, 6- or 7-membered nonaromatic heterocyclic ring or an 8- to 11-membered nonaromatic bicyclic ring system, each optionally including ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18, and each ring or ring system substituted with 1 to 2 substituents independently selected from R7 on carbon or nitrogen atom ring members, and each optionally substituted with 1 to 5 substituents independently selected from R7a on carbon atom ring members and R12 on nitrogen atom ring members; each R7 is independently -Z3GA, -Z3GN or -Z3GP; each GA is independently a phenyl or 5- or 6-membered heteroaromatic ring, each ring substituted with up to 5 substituents independently selected from Rv on carbon atom ring members and R22 on nitrogen atom ring members; each GN is independently a 3- to 7-membered nonaromatic ring including ring members selected from (CRV)2, O, S, NR22, -C(RV)=C(RV)-, -C(RV)=N-, -N=N-, C(=O), C(=S), C(=NR23), S(=O)a(=NR23)b and SiR17R18; each Gp is independently an 8- to 10-membered aromatic or 7- to 11-membered nonaromatic bicyclic ring system, said ring system including ring members selected from (CRV)2, O, S, NR22, -C(RV)=C(RV)-, -C(RV)=N-, -N=N-, C(=O), C(=S), C(=NR23), S(=O)a(=NR23)b and SiR17R18; each Rv is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH, -C(=O)NH2, -SO2NH2, -C(=S)NH2, -C(=O)NHCN, -C(=0)NH0H, -SH, -SO2NHCN, -SO2NHOH, -OCN, -SCN, -SF5, -NHCHO, -NHNH2, -N3, -NHOH, -NHCN, -NHC(=0)NH2, -N=C=O, -N=C=S, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Q-C6 haloalkyl, C2-Cg alkylcarbonyl, C2-Cg haloalkylcarbonyl, C2-Cg alkoxycarbonyl, C4-C10 cycloalkoxycarbonyl, C5- C^2 cycloalkylalkoxycarbonyl, C2-Cg alkylaminocarbonyl, C3-CiQ dialkylaminocarbonyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-Cg cycloalkyl, C3-Cg halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C^ cycloalkylcycloalkyl, C4-C10 halocycloalkylalkyl, C5- C^2 alkylcycloalkylalkyl, C3-Cg cycloalkenyl, C3-Cg halocycloalkenyl, C2-Cg alkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-CiQ alkoxyalkoxyalkyl, C2-Cg alkylthioalkyl, C2-Cg alkylsulfϊnylalkyl, C2-Cg alkylsulfonylalkyl, C2-Cg alkylaminoalkyl, C3-CiQ dialkylaminoalkyl, C2-Cg haloalkylaminoalkyl, C4- Cio cycloalkylaminoalkyl, C4-C10 cycloalkylcarbonyl, C4-C10 cycloalkylaminocarbonyl, C2-C7 cyanoalkyl, Cj-C6 hydroxyalkyl, C4-C10 cycloalkenylalkyl, C2-Cg haloalkoxyalkyl, C2-Cg alkoxyhaloalkyl, C2-Cg haloalkoxyhaloalkyl, C4-Cio halocycloalkoxyalkyl, C4-C10 cycloalkenyloxyalkyl, C4-Cio halocycloalkenyloxyalkyl, C3-CiQ dialkoxyalkyl, C4~Ci2 trialkoxyalkyl, C3-Cg alkoxyalkenyl, C3-Cg alkoxyalkynyl, C3-CiQ halodialkylaminoalkyl, C5-Ci2 cycloalkyl(alkyl)aminoalkyl, C2-Cg alkyl(thiocarbonyl), C3-CiQ alkoxyalkylcarbonyl, C3-CiQ alkoxycarbonylalkyl, C2-Cg haloalkoxycarbonyl, C3-CiQ alkoxyalkoxycarbonyl, C2-Cg (alkylthio)carbonyl, C2-Cg alkoxy(thiocarbonyl), C2-Cg alkylthio(thiocarbonyl), C2-Cg alkylamino(thiocarbonyl), C3-CiQ dialkylamino(thiocarbonyl), C3-CiQ alkoxy(alkyl)aminocarbonyl, C2-Cg alkylsulfonylaminocarbonyl, C2-Cg haloalkylsulfonylaminocarbonyl, C2-Cg alkylamidino, C3-CiQ dialkylamidino, Ci-C6 alkoxy, Ci-C6 haloalkoxy, C2-Cg alkylcarbonyloxy, Ci-C6 alkylthio, Ci-C6 haloalkylthio, Ci-C6 alkylsulfmyl, Ci-C6 haloalkylsulfmyl, Ci-C6 alkylsulfonyl, Ci-C6 haloalkylsulfonyl, Ci-C6 alkylaminosulfonyl, C2-Cg dialkylaminosulfonyl, C3-CiQ trialkylsilyl, C3-Cg cycloalkoxy, C3-Cg halocycloalkoxy, C4-C10 cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C3-C6 haloalkynyloxy, C2-Cg alkoxyalkoxy, C2-Cg haloalkylcarbonyloxy, C4-C10 cycloalkylcarbonyloxy, C3-C10 alkylcarbonylalkoxy, C3-C8 cycloalkylthio, C3-C8 cycloalkylsulfonyl, C3-C8 cycloalkenyloxy, C3-C8 halocycloalkenyloxy, C2~Cg haloalkoxyalkoxy, C2~Cg alkoxyhaloalkoxy, C2~Cg haloalkoxyhaloalkoxy, C3-C10 alkoxycarbonylalkoxy, C2~Cg alkyl(thiocarbonyl)oxy, C2~Cg alkylcarbonylthio, C2~Cg alkyl(thiocarbonyl)thio, C3~Cg cycloalkylsulfϊnyl, C3-C10 halotrialkylsilyl, Q-Cg alkylamino, C2~Cg dialkylamino, C2~Cg alkylcarbonylamino, Q-Cg alkylsulfonylamino, Q-Cg haloalkylamino, Q-Cg halodialkylamino, Q-Cg cycloalkylamino, Q-Cg haloalkylcarbonylamino, Q- Cg haloalkylsulfonylamino, Q-Qo cycloalkylalkylamino, Q-Qo cycloalkyl(alkyl)amino, Q-QQ alkoxycarbonylalkylamino, Q-Cg alkoxyamino, Q-Cg haloalkoxyamino, C4-Q2 dialkylimido, Q-Cg alkoxycarbonylamino, Q-Cg haloalkoxycarbonylamino, Q-Cg alkylaminocarbonylamino, Q-QQ dialkylamino carbonylamino, C3-C10 alkylaminocarbonylalkylamino, C4-C12 dialkylaminocarbonylalkylamino, C2- Cg alkylamino(thiocarbonyl)amino, C3-C10 dialkylamino(thiocarbonyl)amino, C3-C10 alkylamino(thiocarbonyl)alkylamino or C4-C12 dialkylamino(thiocarbonyl)alkylamino; each R7a is independently C^-Cg alkyl, C2~Cg alkenyl, C2~Cg alkynyl, C3~Cg cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, C^-Cg haloalkyl, C2~Cg haloalkenyl, C2~Cg haloalkynyl, C3~Cg halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, Q-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfϊnyl, C1-C4 alkylsulfonyl, Q-C4 haloalkylthio, C1-C4 haloalkylsulfϊnyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2~Cg dialkylamino, C3~Cg cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2~Cg alkoxycarbonyl, C2~Cg alkylcarbonyloxy, C2~Cg alkylcarbonylthio, C2~Cg alkylaminocarbonyl, C3~Cg dialkylamino carbonyl or C3~Cg trialkylsilyl; or
R5 and R7a are taken together with the atoms linking R5 and R7a to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbon, up to 3 heteroatoms selected from up to 1 O, up to 1 S and up to 1 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18;
R12 is H, C1-C3 alkyl, C1-C3 alkylcarbonyl, Q-C 3 alkoxy or Q-C3 alkoxycarbonyl; each Z1 and Z2 is independently a direct bond, O, C(=O), S(O)1n, CHR20 or NR21; each Z3 is independently a direct bond, O, NR22, C(=O), C(=S), S(O)1n, CHR20, CHR20-CHR20, CR24=CR27, C≡C, OCHR20 or CHR20O; each Z4 is independently O, C(=0), S(O)1n or CHR20; each R20 is independently H, Q-C4 alkyl or C1-C4 haloalkyl; each R21 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl or C2-C6 haloalkoxycarbonyl; each R22 is independently H, C1-C4 alkyl or C1-C4 haloalkyl; each R23 is independently H, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylamino, C2-C8 dialkylamino, C1-C6 haloalkylamino or phenyl; each R24 and R27 is independently H, C1-C4 alkyl or C1-C4 haloalkyl; each m is independently 0, 1 or 2; n is 0, 1 or 2; and a and b are independently 0, 1 or 2 in each instance of S(=O)a(=NR23)b, provided that the sum of a and b is 1 or 2.
More particularly, this invention pertains to a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof. This invention also relates to a compound selected from compounds of Formula IA and //-oxides and salts thereof
Figure imgf000008_0001
IA wherein
M is C1-C3 alkyl, C1-C3 haloalkyl, hydroxy, C1-C4 alkoxy, C1-C2 haloalkoxy, C1-C4 alkylamino, C2-C8 dialkylamino, 1-piperidinyl, 1-pyrrolidinyl or 4-morpholinyl; and
J1 is any one of J-29-1 through J-29-60 depicted in Exhibit A as described below wherein the bond shown projecting to the left is bonded to -C(=O)M of Formula IA.
More particularly, this invention pertains to a compound of Formula IA (including all geometric and stereoisomers), an JV-oxide or salt thereof (except that the compounds of Formula IA of this invention are limited to those stereoisomer embodiments defined for J1 in the Summary of Invention as depicted in Exhibit A below).
This invention also relates to a fungicidal composition comprising a compound of Formula 1 (including all geometric and stereoisomers, //-oxides, and salts thereof) (i.e. in a fungicidally effective amount) and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
This invention also relates to a fungicidal composition comprising a mixture of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof) and at least one other fungicide (e.g., at least one other fungicide having a different site of action).
This invention further relates to a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound of Formula 1 (including all geometric and stereoisomers, iV-oxides, and salts thereof) (e.g., as a composition described herein).
This invention additionally relates to fungicidal compositions and methods of controlling plant diseases as described above.
DETAILS OF THE INVENTION
As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having" or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus. Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and Both A and B are true (or present).
Also, use of "a" or "an" are employed to describe elements and components of the invention. This is done merely for convenience and to give a general sense of the invention. This description should be read to include one or at least one and the singular also includes the plural unless it is obvious that it is meant otherwise.
As referred to in the present disclosure and claims, "plant" includes members of Kingdom Plantae, particularly seed plants (Spermatopsida), at all life stages, including young plants (e.g., germinating seeds developing into seedlings) and mature, reproductive stages (e.g., plants producing flowers and seeds). Portions of plants include geotropic members typically growing beneath of the surface of the growing medium (e.g., soil), such as roots, tubers, bulbs and corms, and also members growing above the growing medium, such as foliage (including stems and leaves), flowers, fruits and seeds. The term "seedling", used either alone or in a combination of words means a young plant developing from the embryo of a seed.
In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, /-propyl, or the different butyl, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as ethenyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl. "Alkylene" denotes a straight-chain or branched alkanediyl. Examples of "alkylene" include CH2, CH2CH2, CH(CH3), CH2CH2CH2, CH2CH(CH3) and the different butylene isomers. "Alkenylene" denotes a straight-chain or branched alkenediyl containing one olefϊnic bond. Examples of "alkenylene" include CH=CH, CH2CH=CH, CH=C(CH3), CH2CH=CH and CH2CH=CHCH2.
"Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. "Cycloalkenyl" includes groups such as cyclopentenyl and cyclohexenyl as well as groups with more than one double bond such as 1,3- and 1,4-cyclohexadienyl. The term "alkylcycloalkyl" denotes alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, z-propylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. The term "cycloalkylalkyl" denotes cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups, "cycloalkylcycloalkyl" denotes an cycloalkyl group substituted with other cycloalkyl group. Examples of "cycloalkylcycloalkyl" include 2-cyclopropylcyclopropyl and 3- cyclopropylcyclopentyl. "Halocycloalkylalkyl" denotes halogen substitution on the cycloalkyl moiety, the alkyl moiety or both of the cycloalkyl and alkyl moieties. Examples of "halocycloalkylalkyl" include (2-chlorocyclopropyl)methyl, 2-cyclopentyl-l-chloroethyl, and 2-(3-chlorocyclopentyl)- 1 -chloroethyl.
"Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkoxyalkoxy" denotes at least one straight-chain or branched alkoxy substitution on a straight-chain or branched alkoxy. Examples of "alkoxyalkoxy" include CH3OCH2O-, CH3OCH2(CH3O)CHCH2O- and (CH3)2CHOCH2CH2O-. The term "haloalkoxyalkoxy" denotes an alkoxyalkoxy group substituted with a haloalkoxy moiety. Examples of "haloalkoxyalkoxy" include CF3OCH2O-, CICH2CH2OCH2CH2O- and Cl3CCH2OCH2O- as well as branched alkyl derivatives. The term "alkoxyhaloalkoxy" denotes a haloalkoxy group further substituted with an alkoxy moiety. Examples of "alkoxyhaloalkoxy" include CH3OCHClO-, CH3CH2OCH2CHCIO- and CH3CH2OCCl2O- as well as branched alkyl derivatives. The term "haloalkoxyhaloalkoxy" denotes a haloalkoxy group further substituted with a haloalkoxy moiety. Examples of "haloalkoxyhaloalkoxy" include CF3OCHClO-, CICH2CH2OCHCICH2O- and C13CCH2OCHC1O- as well as branched alkyl derivatives. "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. The term "cycloalkoxyalkyl" denotes cycloalkoxy substitution on an alkyl moiety. Examples of "cycloalkoxyalkyl" include cyclopropoxymethyl, cyclopentoxyethyl, and other cycloalkoxy moieties bonded to straight-chain or branched alkyl groups. "Alkoxyalkoxyalkyl" denotes at least one straight-chain or branched alkoxy moiety bonded to a straight-chain or branched alkoxy moiety bonded to an alkyl moiety. Examples of "alkoxyalkoxyalkyl" include CH3OCH2OCH2-, CH3CH2O(CH3)CHOCH2- and (CH3O)2CHOCH2-. "Alkenyloxy" includes straight-chain or branched alkenyloxy moieties. Examples of "alkenyloxy" include H2C=CHCH2O, (CH3)2C=CHCH2O, (CH3)CH=CHCH2O, (CH3)CH=C(CH3)CH2O and CH2=CHCH2CH2O. "Alkynyloxy" includes straight-chain or branched alkynyloxy moieties. Examples of "alkynyloxy" include HC≡CCH20, CH3C≡CCH2O and CH3C≡CCH2CH2O.
"Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylthio alkyl" denotes alkylthio substitution on alkyl. Examples of "alkylthioalkyl" include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2 and CH3CH2SCH2CH2. "Alkylsulfinyl" includes both enantiomers of an alkylsulfϊnyl group. Examples of "alkylsulfinyl" include CH3S(O), CH3CH2S(O), CH3CH2CH2S(O), (CH3)2CHS(O) and the different butylsulfinyl, pentylsulfϊnyl and hexylsulfϊnyl isomers. "Alkylsulfmylalkyl" denotes alkylsulfinyl substitution on alkyl. Examples of "alkylsulfmylalkyl" include CH3S(=O)CH2, CH3S(=O)CH2CH2, CH3CH2S(=O)CH2 and CH3CH2S(=O)CH2CH2. Examples of "alkylsulfonyl" include CH3S(O)2, CH3CH2S(O)2, CH3CH2CH2S(O)2, (CH3)2CHS(O)2 and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "Alkylsulfonylalkyl" denotes alkylsulfinyl substitution on alkyl. Examples of "alkylsulfonylalkyl" include CH3S(=O)2CH2, CH3S(=O)2CH2CH2, CH3CH2S(=O)2CH2 and CH3CH2S(=O)2CH2CH2.
Examples of "alkylcarbonyl" include CH3C(O), CH3CH2CH2C(O) and (CH3)2CHC(O). Examples of "alkoxycarbonyl" include CH30C(=0), CH3CH2OC(=O), CH3CH2CH2OC(=O), (CH3)2CHOC(=O) and the different butoxy- or pentoxycarbonyl isomers. Examples of "alkylaminocarbonyl" include CH3NHC(=0)-, CH3CH2NHC(=O)-, CH3CH2CH2NHC(=O)-, (CH3)2CHNHC(=O)- and the different butylamino- or pentylaminocarbonyl isomers. Examples of "dialkylaminocarbonyl" include
(CH3)2NC(=O)-, (CH3CH2)2NC(=O)-, CH3CH2(CH3)NC(=O)-, (CH3)2CHN(CH3)C(=O)- and CH3CH2CH2(CH3)NC(=O)-. "Cycloalkylalkoxycarbonyl" denotes cycloalkyl substituted on the alkoxy moiety of an alkoxycarbonyl group. Examples of "cycloalkylalkoxycarbonyl" include cyclopropyl-CH2OC(=O)-, cyclopropyl- CH(CH3)0C(=0)- and cyclopentyl-CH2OC(=O)-. "Alkoxy(alkyl)aminocarbonyl" denotes straight-chain or branched alkyl and alkoxy moieties bonded to the nitrogen atom of an aminocarbonyl group. Examples of "Alkoxy(alkyl)aminocarbonyl" include
CH3O(CH3)NC(=O)-, CH3CH2O(CH3)NC(=O)- and (CH3)2CHO(CH3)NC(=O)-. The terms "haloalkylsulfonylaminocarbonyl" denotes halogen substitution on either the alkyl moiety or the nitrogen atom of an aminocarbonyl group or both the alkyl moiety and the nitrogen atom. Examples of "haloalkylsulfonylaminocarbonyl" include CF3 SO2NH(C=O)- and CF3SO2NC1(C=O)-. The term "alkylcarbonyloxy" denotes straight-chain or branched alkyl bonded to a C(=O)O moiety. Examples of "alkylcarbonyloxy" include CH3CH2C(=O)O and (CH3)2CHC(=O)O. "Alkoxycarbonylalkyl" denotes alkoxycarbonyl substitution on straight-chain or branched alkyl. Examples of "alkoxycarbonylalkyl" include CH3OC(=O)CH2CH(CH3), CH3CH2OC(=O)CH2CH2, (CH3)2CHOC(=O)CH2. The term "alkylcarbonylalkoxy" denotes alkylcarbonyl bonded to an alkoxy moiety. Examples of "alkylcarbonylalkoxy" include CH3C(=O)CH2CH2O and CH3CH2C(=O)CH2O. Examples of "alkoxycarbonyloxy" include CH3CH2CH2OC(=O)O and (CH3)2CHOC(=O)O.
"Alkyl(thiocarbonyl)" denotes straight-chain or branched alkyl moieties bonded to a C(=S) moiety. Examples of "alkyl(thiocarbonyl)" include CH3C(=S)-, CH3CH2CH2C(=S)- and (CH3)2CHC(=S)-. "Alkoxy(thiocarbonyl)" denotes straight-chain or branched alkoxy moieties bonded to a C(=S) moiety. Examples of "alkoxy(thiocarbonyl)" include CH3OC(=S)-, CH3CH2CH2OC(=S)- and (CH3)2CHOC(=S)-. "Alkylthio(thiocarbonyl)" denotes a straight-chain or branched alkylthio moiety bonded to a C(=S) moiety. Examples of "alkylthio(thiocarbonyl)" include CH3SC(=S)-, CH3CH2CH2SC(=S)- and (CH3)2CHSC(=S)-. "Alkylamino(thiocarbonyl)" denotes a straight-chain or branched alkylamino moiety bonded to a C(=S) moiety. Examples of "alkylamino(thiocarbonyl)" include CH3NHC(=S)-, CH3CH2CH2NHC(=S)- and (CH3)2CHNHC(=S)-. "Dialkylamino(thiocarbonyl)" denotes a straight-chain or branched dialkylamino moiety bonded to a C(=S) moiety. Examples of "dialkylamino(thiocarbonyl)" include (CH3)2NC(=S)-, CH3CH2CH2(CH3)NC(=S)- and (CH3)2C(CH3)NC(=S)-.
"Alkylamidino" denotes a straight-chain or branched alkylamino moiety bonded to a carbon atom of a C(=N) moiety, or an unsubstituted amino moiety bonded to the carbon atom of a C(=N) moiety and a straight-chain or branched alkyl moiety bonded to the nitrogen atom of the C(=N) moiety. Examples of "alkylamidino" include CH3NHC(=NH)-, CH3CH2NHC(=NH)- and H2NC(=NCH3)-. "Dialkylamidino" denotes a straight-chain or branched dialkylamino moiety bonded to the carbon atom of a C(=N) moiety, or a straight-chain or branched alkylamino moiety bonded to the carbon atom of a C(=N) moiety and a straight-chain or branched alkyl moiety bonded to the nitrogen atom of the C(=N) moiety. Examples of "dialkylamidino" include (CH3)2NC(=NH)-,
CH3CH2(CH3)NC(=NH)- and CH3NHC(=NCH3)-.
"Alkylamino", "dialkylamino" and the like, are defined analogously to the above examples. The term "halodialkylamino" denotes a dialkylamino group substituted on at least one alkyl moiety with one or more halogenatoms which may be the same or different. Examples of "halodialkylamino" include CF3(CH3)N-, (CF3)2N- and CH2Cl(CH3)N-. "Cycloalkylamino" means the amino nitrogen atom is attached to a cycloalkyl radical and a hydrogen atom and includes groups such as cyclopropylamino, cyclobutylamino, cyclopentylamino and cyclohexylamino. "Cycloalkyl(alkyl)amino" means a cycloalkylamino group wherein the amino hydrogen atom is replaced by an alkyl radical. Examples of "cycloalkyl(alkyl)amino" include groups such as cyclopropyl(methyl)amino, cyclobutyl(butyl)amino, cyclopentyl(propyl)amino, cyclohexyl(methyl)amino and the like. "Haloalkylaminoalkyl" denotes an alkylaminoalkyl group substituted on the amino nitrogen or either alkyl moiety or a combination thereof with one or more halogen atoms which may be the same or different. "Haloalkylaminoalkyl" includes a halogen group attached to any alkyl groups as well as nitrogen. Examples of "haloalkylaminoalkyl" include CH3NHCHCl- , (CH3)2CC1NHCH2- and CH3NClCH(CH3)-.
The term "dialkylimido" denotes two independent straight-chain or branched alkylcarbonyl moieties bonded to the nitrogen atom of an amino group. Examples of "dialkylimido" include (CH3C(=O))2N- and CH3CH2C(=O)(CH3C(=O))N-. The term "alkoxycarbonylamino" denotes a straight-chain or branched alkoxy moiety bonded to the C(=O) moiety of a carbonylamino group. Examples of "alkoxycarbonylamino" include CH3OC(=O)NH- and CH3CH2OC(=O)NH-. The term "alkylaminocarbonylamino" denotes a straight-chain or branched alkylamino moiety bonded to the C(=O) moiety of a carbonylamino group. Examples of "alkylaminocarbonylamino" include CH3NHC(=O)NH- and CH3CH2NHC(=O)NH-. The term "dialkylaminocarbonylamino" denotes a straight-chain or branched dialkylamino moiety bonded to the C(=O) moiety of a carbonylamino group. Examples of "dialkylaminocarbonylamino" include
(CH3)2NC(=O)NH- and CH3CH2(CH3)NC(=O)NH-. The term
"alkylaminocarbonylalkylamino" denotes a straight-chain or branched alkylamino moiety bonded to the C(=O) moiety of a carbonylamino group and a straight-chain or branched alkyl moiety bonded to the amino nitrogen of a carbonylamino group. Examples of "alkylaminocarbonylalkylamino" include CH3NHQ=O)N(CH3)- and
CH3CH2NHC(=O)N(CH3)-. The term "dialkylaminocarbonylalkylamino" denotes a straight-chain or branched dialkylamino moiety bonded to the C(=O) moiety of a carbonylamino group and a straight-chain or branched alkyl moiety bonded to the amino nitrogen of a carbonylamino group. Examples of "dialkylaminocarbonylalkylamino" include (CH3)2NC(=O)N(CH3)- and CH3CH2(CH3)NC(=O)N(CH3)-. The terms
"alkylamino(thiocarbonyl)amino" denotes straight-chain or branched alkylamino moieties bonded to a C(=S) moiety of carbonylamino group. Examples of
"alkylamino(thiocarbonyl)amino" include CH3NHC(=S)NH- and CH3CH2NHC(=S)NH-.
"Trialkylsilyl" includes 3 branched and/or straight-chain alkyl radicals attached to and linked through a silicon atom, such as trimethylsilyl, triethylsilyl and te/t-butyldimethylsilyl. The terms "halotrialkylsilyl" denotes one or more halogen atoms substituted on at least one alkyl moiety of the trialkylsilyl group. Examples of "halotrialkylsilyl" include CF3(CH3)2Si-, (CF3)3Si-, and CH2Cl(CH3)2Si-.
"Hydroxyalkyl" denotes an alkyl group substituted with one hydroxy group. Examples of "hydroxyalkyl" include HOCH2CH2, CH3CH2(OH)CH and HOCH2CH2CH2CH2.
The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Furthermore, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F3C, ClCH2, CF3CH2 and CF3CCl2. The terms "haloalkenyl", "haloalkynyl", "halocycloalkyl", "haloalkoxy", "haloalkylthio", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include (Cl)2C=CHCH2 and CF3CH2CH=CHCH2. Examples of "haloalkynyl" include HC≡CCHCl, CF3C≡C, CC13C≡C and FCH2C≡CCH2. Examples of "haloalkoxy" include CF3O, CCl3CH2O, HCF2CH2CH2O and CF3CH2O. Examples of "haloalkylthio" include CCl3S, CF3S, CCl3CH2S and ClCH2CH2CH2S. Examples of "haloalkylsulfmyl" include CF3S(O), CCl3S(O), CF3CH2S(O) and CF3CF2S(O). Examples of "haloalkylsulfonyl" include CF3S(O)2, CCl3S(O)2, CF3CH2S(O)2 and CF3CF2S(O)2.
Unless otherwise indicated, a "ring" or "ring system" as a component of Formula 1 (e.g., substituent J and Q) is carbocyclic or heterocyclic. The term "ring system" denotes two or more connected rings. The term "spirocyclic ring system" denotes a ring system consisting of two rings connected at a single atom (so the rings have a single atom in commonality). The term "bicyclic ring system" denotes a ring system consisting of two rings sharing two or more common atoms. In a "fused bicyclic ring system" the common atoms are adjacent, and therefore the rings share two adjacent atoms and bond connecting them. In a "bridged bicyclic ring system" the common atoms are not adjacent (i.e. there is no bond between the bridgehead atoms). A "bridged bicyclic ring system" is conceptually formed by bonding a segment of one or more atoms to nonadjacent ring members of a ring.
A ring, a bicyclic ring system or spirocyclic ring system can be part of an extended ring system containing more than two rings wherein substituents on the ring, bicyclic ring system or spirocyclic ring system are taken together to form the additional rings, which may be in bicyclic and/or spirocyclic relationships with other rings in the extended ring system. For example, the particular J or J1 moiety J-29-59 depicted in Exhibit A consists of a dihydro isoxazoline ring having one R5 substituent as Z2Q, which is a phenyl ring substituted with a phenyl group (as Z3GA) and also one R7a group taken together with another R5 substituent on the dihydro isoxazoline ring as -CH2CH2CH2- to form the additional six-membered ring component in the ring system.
The term "ring member" refers to an atom (e.g., C, O, N or S) or other moiety (e.g., C(=0), C(=S) or S(=O)a(=NR23)b) forming the backbone of a ring or ring system. The term "carbocyclic ring" denotes a ring wherein the atoms forming the ring backbone are selected only from carbon. The term "carbocyclic ring system" denotes two or more fused rings wherein the atoms forming the backbone of the rings are selected only from carbon. The term "heterocyclic ring" denotes a ring wherein at least one of the atoms forming the ring backbone is other than carbon. The term "heterocyclic ring system" denotes two or more fused rings wherein at least one of the atoms forming the backbone of the rings is other than carbon. "Aromatic" indicates that each of the ring atoms is essentially in the same plane and has a/?-orbital perpendicular to the ring plane, and in which (4n + 2) π electrons, where n is a positive integer, are associated with the ring to comply with Hϋckel's rule. The term "heteroaromatic ring" refers to a heterocyclic ring that is aromatic. The term "saturated heterocyclic ring" denotes a heterocyclic ring containing only single bonds between ring members. The term "partially saturated heterocyclic ring" denotes a heterocyclic ring containing at least one double bond but which is not aromatic.
The dotted line in Formula 1 and in other rings depicted in the present description (e.g., J-44, J-45, J-48 and J-49 in Exhibit 3) represents that the bond indicated can be a single bond or double bond. Unless otherwise indicated, heterocyclic rings and ring systems are attached to the remainder of Formula 1 through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen, and all substituents on the heterocyclic rings and ring systems are attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.
As already described, J is a 5-, 6- or 7-membered ring, a 8- to 11-membered bicyclic ring system or a 7- to 11-membered spirocyclic ring system, each ring or ring system containing ring members selected from carbon, up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18, each ring or ring system substituted with 1 to2 substituents independently selected from -Z2Q and optionally substituted with 1 to 5 substituents independently selected from R5. As the heteroatoms are optional, 0 to 4 heteroatoms may be present. In this description the heteroatoms selected from up to 2 S are atoms and not the moieties S(=O)a(=NR23)b. The heteroatoms selected from up to 4 N may be oxidized as TV- oxides, because the present invention also relates to TV-oxide derivatives of the compounds of Formula 1. Therefore the optional 1 to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18 are in addition to the optional 1 to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N. Of note is when the total number of unoxidized sulfur atoms (i.e. S) and oxidized sulfur moieties (i.e. S(=O)a(=NR23)b) does not exceed 2, so that at most two ring members selected from S and S(=O)a(=NR23)b are present in the ring or ring system. When none of the optional heteroatoms and none of the optional ring members selected from S(=O)a(=NR23)b and SiR17R18 are present, the ring or ring system is carbocyclic. The R5 substituents may be attached to carbon atom ring members and to nitrogen atom ring members having an available point of attachment. The carbon-based ring members C(=O) and C(=S) do not have available points of attachment. Furthermore in SiR17R18 ring members, the substituents R17 and R18 are otherwise separately defined, and these ring members cannot be further substituted with R5. As the R5 substituents are optional, 0 to 5 substituents may be present, limited by the number of available points of attachment.
Similarly, R5 and R7a may be taken together with the atoms linking R5 and R7a to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbon, up to 3 heteroatoms selected from up to 1 O, up to 1 S and up to 1 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18. As the heteroatoms are optional, 0 to 3 heteroatoms may be present. In this description the heteroatom selected from up to 1 S is an atom and not the moiety S(=O)a(=NR23)b. The heteroatom selected from up to 1 N may be oxidized as an JV-oxide, because the present invention also relates to iV-oxide derivatives of the compounds of Formula 1. Therefore the optional 1 to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18 are in addition to the optional 1 to 3 heteroatoms selected from up to 1 O, up to 1 S and up to 1 N. Of note is when the total number of unoxidized sulfur atoms (i.e. S) and oxidized sulfur moieties (i.e. S(=O)a(=NR23)b) does not exceed 1, so that at most one ring member selected from S and S(=O)a(=NR23)b is present in the ring. When none of the optional heteroatoms and none of the optional ring members selected from S(=O)a(=NR23)b and SiR17R18 are present, the ring is carbocyclic. The 5- to 7-membered ring is optionally substituted. The substituents on the atoms linking R5 and R7a are described in the definition of the components linking R5 and R7a. For example, when linking component Z2 is CHR20, the substituent R20 is defined to be H, Q-C4 alkyl or Q-C4 haloalkyl. Regarding optional substituents attached to the portion of the ring consisting of R5 and R7a taken together, an optional substituent is a non-hydrogen substituent that does not extinguish fungicidal activity. Optional substituents may be attached to carbon atom ring members and to nitrogen atom ring members having an available point of attachment. The carbon-based ring members C(=O) and C(=S) do not have available points of attachment. Furthermore in SiR17R18 ring members, the substituents R17 and R18 are otherwise separately defined, and these ring members cannot be further substituted. Likewise in S(=O)a(=NR23)b ring members, the substituent R23 is otherwise separately defined, and these ring members cannot be further substituted.
The total number of carbon atoms in a substituent group is indicated by the "Ci-Cj" prefix where i and j are numbers from 1 to 10. For example, C^-C4 alkylsulfonyl designates methylsulfonyl through butylsulfonyl; C2 alkoxyalkyl designates CH3OCH2; C3 alkoxyalkyl designates, for example, CH3CH(OCH3), CH3OCH2CH2 or CH3CH2OCH2; and C4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH3CH2CH2OCH2 and CH3CH2OCH2CH2.
When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can vary, then when the number of said substituents is greater than 1, said substituents are independently selected from the group of defined substituents. Furthermore when a range is indicated (e.g., i-j substituents), then the number of substituents may be selected from the integers between i and j inclusive. When a group (e.g., J) contains a substituent (e.g., R5) which can be hydrogen, then when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted. When a variable group is shown to be optionally attached to a position, for example, (R2)n wherein n may be 0, or as a further example (R4)k wherein k may be 0 in U- 17 of Exhibit 1, then hydrogen may be at the position even if not recited in the definition of the variable group (e.g., R2 and R4). When a position on a group is said to be "not substituted" or "unsubstituted", then hydrogen atoms are attached to take up any free valency. The term "optionally substituted" in connection with groups listed for R1, R2, R5, R7a, G, J and Q refers to groups that are unsubstituted or have at least 1 non-hydrogen substituent. Unless otherwise indicated, these groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. Commonly, the number of optional substituents (when present) ranges from 1 to 3. When a range specified for the number of substituents (e.g., x being an integer from 0 to 5 in Exhibit 3) exceeds the number of positions available for substituents on a ring (e.g., there is only 1 position available if s is 1 (s cannot equal 0) or no positions available if s is 2 for (R5)x on J-I in Exhibit 3), the actual higher end of the range is recognized to be the number of available positions. The term "optionally substituted" means that the number of substituents can be zero. For example, the phrase "optionally substituted with up to 2 substituents selected from R3 on carbon ring members and selected from R1 * on nitrogen ring members" means that 0, 1 or 2 substituents can be present (if the number of potential connection points allows), and thus the number of R3 and R1 * substituents can be zero. Similarly, the phrase "optionally substituted with 1 to 5 substituents" means that 0, 1, 2, 3, 4 or 5 substituents can be present if the number of available connection points allows. The term "unsubstituted" in connection with a group such as a ring or ring system means the group does not have any substituents other than its one or more attachments to the remainder of Formula 1. The term "meta-substituted phenyl" means a phenyl ring substituted with a non-hydrogen substituent at a meta position relative to attachment of the phenyl ring to the remainder of Formula 1.
As noted above, R1 is an optionally substituted phenyl, or 5- or 6-membered heteroaromatic ring or optionally substituted naphthalenyl; G is an optionally substituted 5- membered heterocyclic ring; R5 and R7a may be taken together with the atoms linking R5 and R7a to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbon, up to 3 heteroatoms selected from up to 1 O, up to 1 S and up to 1 N, and up to 1 to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18. The term "substituted" in connection with the definitions of R1, G, R5 and R7a refers to groups that have at least one non-hydrogen substituent that does not extinguish fungicidal activity. Since these groups are optionally substituted, they need not have any non-hydrogen substituents. As these groups are "optionally substituted" without the number of substituents indicated, these groups may be substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom.
When Z3 is CR24=CR27, OCHR20 or CHR20O, the left end of the radicals are connected to Q and the right end of the radicals are connected to GA, GN or Gp.
Naming of substituents in the present disclosure uses recognized terminology providing conciseness in precisely conveying to those skilled in the art the chemical structure. For sake of conciseness, locant descriptors may be omitted; "pyrazol-1-yl" means "lH-pyrazol-1-yl" according to the Chemical Abstracts system of nomenclature. The term "pyridyl" is synonymous with "pyridinyl". The order of listing substituents may be different from the Chemical Abstracts system if the difference does not affect the meaning.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form. For example, when J is J-29 (see Exhibit 3) bonded at the 3-position to the remainder of Formula 1 and J-29 has one Q substituent other than H at the 5-position (Z2 being a direct bond, s being 1, and x being 0), then Formula 1 possesses a chiral center at the carbon atom to which Q is bonded. The two enantiomers are depicted as Formula 1' and Formula 1" with the chiral center identified with an asterisk (*).
Figure imgf000018_0001
1' 1" This invention comprises racemic mixtures, for example, equal amounts of the enantiomers of Formulae 1' and 1". In addition, this invention includes compounds that are enriched compared to the racemic mixture in an enantiomer of Formula 1. Also included are the essentially pure enantiomers of compounds of Formula 1, for example, Formula 1' and Formula 1".
When enantiomerically enriched, one enantiomer is present in greater amounts than the other, and the extent of enrichment can be defined by an expression of enantiomeric excess ("ee"), which is defined as (2x-l)-100 %, where x is the mole fraction of the dominant enantiomer in the mixture (e.g., an ee of 20 % corresponds to a 60:40 ratio of enantiomers).
Preferably the compositions of this invention have at least a 50 % enantiomeric excess; more preferably at least a 75 % enantiomeric excess; still more preferably at least a 90 % enantiomeric excess; and the most preferably at least a 94 % enantiomeric excess of the more active isomer. Of particular note are enantiomerically pure embodiments of the more active isomer.
Compounds of Formula 1 can comprise additional chiral centers. For example, substituents and other molecular constituents such as R4, R5, R7a, G, J, Q and X1 through X9 may themselves contain chiral centers. This invention comprises racemic mixtures as well as enriched and essentially pure stereoconfigurations at these additional chiral centers.
Compounds of this invention can exist as one or more conformational isomers due to restricted rotation about the amide bond (e.g., C(W)-N) in Formula 1. This invention comprises mixtures of conformational isomers. In addition, this invention includes compounds that are enriched in one conformer relative to others.
Some of the unsaturated rings and ring systems depicted in Exhibits 1, 2, 3, 4 and 5 can have an arrangement of single and double bonds between ring members different from that depicted. Such differing arrangements of bonds for a particular arrangement of ring atoms correspond to different tautomers. For these unsaturated rings and ring systems, the particular tautomer depicted is to be considered representative of all the tautomers possible for the arrangement of ring atoms shown. The tables listing particular compounds incorporating the ring and ring systems depicted in the Exhibits may involve a tautomer different from the tautomer depicted in the Exhibits.
The compounds of the invention include iV-oxide derivatives. One skilled in the art will appreciate that not all nitrogen-containing heterocycles can form JV-oxides since the nitrogen requires an available lone pair of electrons for oxidation to the oxide; one skilled in the art will recognize those nitrogen-containing heterocycles which can form JV-oxides. One skilled in the art will also recognize that tertiary amines can form //-oxides . Synthetic methods for the preparation of //-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for the preparation of iV-oxides have been extensively described and reviewed in the literature; see, for example, T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285- 291, A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.
The present compounds of Formula 1 can be in the form of agriculturally suitable salts. One skilled in the art recognizes that because in the environment and under physiological conditions salts of chemical compounds are in equilibrium with their corresponding nonsalt forms, salts share the biological utility of the nonsalt forms. Thus a wide variety of salts of the compounds of Formula 1 are useful for control of plant diseases caused by fungal plant pathogens (i.e. are agriculturally suitable). The salts of the compounds of Formula 1 include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. When a compound of Formula 1 contains an acidic moiety such as a carboxylic acid or phenol, salts also include those formed with organic or inorganic bases such as pyridine, triethylamine or ammonia, or amides, hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium.
Compounds selected from Formula 1 and IA (including geometric and stereoisomers), TV-oxides, and salts thereof, typically exist in more than one form, and Formula 1 or IA thus includes all crystalline and non-crystalline forms of the compounds that Formula 1 or IA represents. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term "polymorph" refers to a particular crystalline form of a chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molecules in the crystal lattice. Although polymorphs can have the same chemical composition, they can also differ in composition due the presence or absence of co-crystallized water or other molecules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such chemical, physical and biological properties as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availability. One skilled in the art will appreciate that a polymorph of a compound represented by Formula 1 or IA can exhibit beneficial effects (e.g., suitability for preparation of useful formulations, improved biological performance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Formula 1 or IA. Preparation and isolation of a particular polymorph of a compound represented by Formula 1 or IA can be achieved by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.
Embodiments of the present invention as described in the Summary of the Invention include those described below. In the following Embodiments, Formulae 1 and IA include iV-oxides and salts thereof, and reference to "a compound of Formula 1" or "a compound of Formula IA" includes the definitions of substituents specified in the Summary of the Invention unless further defined in the Embodiments. Embodiments of the present invention include: Embodiment 1. A compound of Formula 1 wherein A is CHR15. Embodiment Ia. A compound of Formula 1 or Embodiment 1 wherein R15 is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C1-C4 haloalkyl or C2-C5 alkoxycarbonyl. Embodiment Ib. A compound of Embodiment Ia wherein R15 is H, cyano, hydroxy, methyl or methoxycarbonyl.
Embodiment Ic. A compound of Embodiment Ib wherein R15 is H. Embodiment 2. A compound of Formula 1 wherein A is NR16. Embodiment 2a. A compound of Formula 1 or any one of Embodiments 1 through 2 wherein R16 is H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl or C2-C4 alkoxycarbonyl. Embodiment 2b. A compound of Embodiment 2a wherein R16 is H, methyl, methylcarbonyl or methoxycarbonyl.
Embodiment 2c. A compound of Embodiment 2b wherein R16 is H. Embodiment 3. A compound of Formula 1 or any one of Embodiments 1 through 2c wherein W is O. Embodiment 4. A compound of Formula 1 or any one of Embodiments 1 through 2c wherein W is S. Embodiment 5. A compound of Formula 1 wherein each R2 is independently C1-C4 alkyl, C1-C4 alkenyl, C1-C4 haloalkyl, C1-
C4 alkoxy, halogen, cyano or hydroxy; or two R2 are taken together as Q-C3 alkylene or C2-C3 alkenylene to form a bridged bicyclic ring system; or two R2 attached to adjacent ring carbon atoms joined by a double bond are taken together as -CH=CH-CH=CH- optionally substituted with 1 to 3 substituents selected from Q-C4 alkyl, Q-C4 haloalkyl, Q-C4 alkoxy, C1-C4 haloalkoxy, halogen, hydroxy, amino, cyano and nitro.
Embodiment 5a. A compound of Embodiment 5 wherein each R2 is independently C1- C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, halogen, cyano or hydroxy.
Embodiment 5b. A compound of Embodiment 5 a wherein each R2 is independently methyl, methoxy, cyano or hydroxy.
Embodiment 5c. A compound of Embodiment 5b wherein each R2 is methyl.
Embodiment 6. A compound of Formula 1 or any one of Embodiments 1 through 5c wherein n is 0 or 1.
Embodiment 7. A compound of Embodiment 6 wherein n is 0.
Embodiment 7a. A compound of Embodiment 6 wherein n is 1.
Embodiment 8. A compound of Formula 1 or any one of Embodiments 1 through 7a wherein X is X1, X2 or X3.
Embodiment 9. A compound of Embodiment 8 wherein X is X1 or X2.
Embodiment 10. A compound of Embodiment 9 wherein X is X1.
Embodiment 11. A compound of Formula 1 or any one of Embodiments 1 through 10 wherein the ring comprising X is saturated (i.e. contains only single bonds).
Embodiment 12. A compound of Formula 1 or any one of Embodiments 1 through 11 wherein R1 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with substituents that do not link together to make R1 a fused ring system.
Embodiment 12a. A compound of Embodiment 12 wherein R1 is a phenyl or 5- or 6- membered heteroaromatic ring optionally substituted with 1-3 substituents independently selected from R4a on carbon ring members and R4*5 on nitrogen ring members; each R4a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, Q-C4 alkoxy, C1-C4 haloalkoxy, Q-C4 alkylthio, Q-C4 alkylsulfmyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, Q-C4 haloalkylsulfϊnyl, Q-C4 haloalkylsulfonyl, C1-C 4 alkylamino, C2-Cg dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-Cg dialkylamino carbonyl or C3-C6 trialkylsilyl; and each R4b is independently C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 halocycloalkyl or C2-C4 alkoxyalkyl. Embodiment 12b. A compound of Embodiment 12a wherein R1 is a phenyl or 5- or 6- membered heteroaromatic ring optionally substituted with 1-2 substituents independently selected from R4a on carbon ring members and R4b on nitrogen ring members. Embodiment 13. A compound of any one of Embodiments 12a through 12b wherein each R4a is independently C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, C1-C3 haloalkyl, C2-C3 haloalkenyl, C2-C3 haloalkynyl, halocyclopropyl, halogen, cyano, nitro, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-
C2 alkylthio, C1-C2 haloalkylthio, C2-C3 alkoxyalkyl, C2-C3 alkylcarbonyl,
C2-C3 alkoxycarbonyl, C2-C3 alkylaminocarbonyl or C3-C4 dialkylaminocarbonyl. Embodiment 14. A compound of Embodiment 13 wherein each R4a is independently
C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, C1-C3 haloalkyl, C2-
C3 haloalkenyl, C2-C3 haloalkynyl, halocyclopropyl, halogen, cyano, nitro, C1-
C2 alkoxy or C1-C2 haloalkoxy. Embodiment 15. A compound of Embodiment 14 wherein each R4a is independently halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C2 alkoxy or C1-C2 haloalkoxy. Embodiment 15 a. A compound of Embodiment 15 wherin each R4a is independently
C1-C2 alkyl, C1-C2 haloalkyl, halogen, C1-C2 alkoxy or C1-C2 haloalkoxy; Embodiment 16. A compound of Embodiment 15a wherein each R4a is independently halogen, C1-C2 alkyl, C1-C2 haloalkyl or C1-C2 alkoxy. Embodiment 17. A compound of Embodiment 16 wherein each R4a is independently
C1-C2 alkyl, trifluoromethyl, Cl, Br, I or methoxy. Embodiment 18. A compound of Embodiment 17 wherein each R4a is independently
C1-C2 alkyl, trifluoromethyl, Cl or Br. Embodiment 19. A compound of any one of Embodiments 12a through 18 wherein each R4^ is independently C1-C3 alkyl, C3 alkenyl (e.g., allyl), C3 alkynyl (e.g., propargyl), cyclopropyl, C1-C3 haloalkyl, C3 haloalkenyl, C3 haloalkynyl, halocyclopropyl or C2-C3 alkoxyalkyl. Embodiment 20. A compound of Embodiment 19 wherein each R4^ is independently
C1-C3 alkyl, C3 alkenyl, C3 alkynyl, cyclopropyl, C1-C3 haloalkyl, C3 haloalkenyl or halocyclopropyl. Embodiment 21. A compound of Embodiment 20 wherein each R4^ is independently
C1-C2 alkyl or C1-C2 haloalkyl. Embodiment 22. A compound of Embodiment 21 wherein each R4^ is independently
Cj-C2 alkyl or trifluoromethyl. Embodiment 23. A compound of Embodiment 22 wherein each R4^ is independently
C1-C2 alkyl. Embodiment 24. A compound of any one of Embodiments 12a through 23 wherein R1 is one of U-I through U-50 depicted in Exhibit 1;
Exhibit 1 Ok(R4)k JΓ${RX JΓ<X jτ</)k
U-I U-2 U-3 U-4
Figure imgf000024_0001
U-5 U-6 U-7 U-8
/lr(R4)l /lr(R4)k /lr(R4)t /Tl(R4)t
U-9 U-IO U-I l U-12
Figure imgf000024_0002
U-13 U-14 U-15 U-16
Figure imgf000024_0003
U-17 U-18 U-19 U-20
Figure imgf000025_0001
U-21 U-22 U-23 U-24
Figure imgf000025_0002
U-25 U-26 U-27 U-28
Figure imgf000025_0003
U-29 U-30 U-31 U-32
Figure imgf000025_0004
U-33 U-34 U-35 U-36
Figure imgf000025_0005
U-45 U-46 U-47 U-48
Figure imgf000026_0001
wherein when R4 is attached to a carbon ring member, said R4 is selected from R4a, and when
R4 is attached to a nitrogen ring member (e.g., in U-4, U-I l through U- 15, U-24 through U-26, U-31 or U-35), said R4 is selected from R4b; and k is 0, 1 or 2.
Embodiment 24a. A compound of Embodiment 24 wherein k is 1 or 2. Embodiment 25. A compound of Embodiment 24 wherein k is 1 or 2 and at least one
R4 is Cl. Embodiment 26. A compound of Embodiment 24 wherein k is 1 or 2 and at least one
R4 is Br. Embodiment 27. A compound of Embodiment 24 wherein k is 1 or 2 and at least one
R4 is methyl. Embodiment 28. A compound of Embodiment 24 wherein k is 1 or 2 and at least one
R4 is ethyl. Embodiment 29. A compound of Embodiment 24 wherein k is 1 or 2 and at least one
R4 is trifluoromethyl. Embodiment 30. A compound of Embodiment 24 wherein k is 1 or 2 and at least one
R4 is methoxy. Embodiment 31. A compound of any one of Embodiments 24 through 30 wherein R1 is selected from U-I through U-5, U-8, U-I l, U-13, U-15, U-20 through U-28, U-
31, U-36 through U-39 and U-50. Embodiment 32. A compound of Embodiment 31 wherein R1 is selected from U-I through U-3, U-5, U-8, U-I l, U-13, U-20, U-22, U-23, U-25 through U-28, U-36 through U-39 and U-50. Embodiment 33. A compound of Embodiment 32 wherein R1 is selected from U-I through U-3, U-I l, U-13, U-20, U-22, U-23, U-36 through U-39 and U-50. Embodiment 34. A compound of Embodiment 33 wherein R1 is U-I, U-20 or U-50. Embodiment 35. A compound of Embodiment 34 wherein R1 is U-I. Embodiment 35a. A compound of Embodiment 34 wherein R1 is U-20. Embodiment 36. A compound of Embodiment 34 wherein R1 is U-50. Embodiment 37. A compound of Embodiment 35 wherein k is 1 and R4 is connected to the 3- or 5-position of U-I. Embodiment 37a. A compound of Embodiment 35 wherein k is 2 and one R4 is connected to the 3 -position and the other R4 is connected to the 5 -position of
U-I. Embodiment 38. A compound of Embodiment 35a wherein k is 1 and R4 is connected to the 3- or 5 -position of U-20. Embodiment 38a. A compound of Embodiment 35a wherein k is 2 and one R4 is connected to the 3 -position and the other R4 is connected to the 5 -position of
U-20. Embodiment 39. A compound of Embodiment 36 wherein k is 1 and R4 is connected to the 2- or 5 -position of U-50. Embodiment 40. A compound of Embodiment 36 wherein k is 2 and one R4 is connected to the 2-position and the other R4 is connected to the 5 -position of
U-50. Embodiment 41. A compound of Formula 1 or any one of Embodiments 1 through 40 wherein G is a 5-membered heterocyclic ring optionally substituted with up to 2 substituents selected from R3 on carbon ring members and selected from R1 * on nitrogen ring members; each R3 is independently C^-C 3 alkyl, C^-C 3 haloalkyl or halogen; and each R11 is independently C^-C 3 alkyl. Embodiment 41a. A compound of Embodiment 41 wherein each R3 is independently
C1-C3 alkyl or halogen. Embodiment 41b. A compound of Embodiment 41a wherein each R3 is independently methyl or halogen.
Embodiment 41c. A compound of Embodiment 41b wherein each R3 is methyl. Embodiment 42. A compound of any one of Embodiments 41 through 41c wherein G is one of G-I through G-59 depicted in Exhibit 2;
Exhibit 2
Figure imgf000027_0001
G-I G-2 G-3
Figure imgf000027_0002
Figure imgf000028_0001
G-5 G-6 G-7 G-8
Figure imgf000028_0002
G-9 G-IO G-Il G-12
Figure imgf000028_0003
Figure imgf000029_0001
G-29 G-30 G-31 G-32
Figure imgf000029_0002
G-37 G-38 G-39 G-40
Figure imgf000029_0003
G-44
Figure imgf000030_0001
G-45 G-46 G-47 G-48
Figure imgf000030_0002
G-57 G-58 G-59
wherein the bond projecting to the left is bonded to X, and the bond projecting to the right is bonded to Z1; each R3a is independently selected from H or R3; and Rl la is selected from H and R1 * . Embodiment 43. A compound of Embodiment 42 wherein G is selected from G-I through G-3, G-7, G-8, G-IO, G-I l, G-14, G-15, G-23, G-24, G-26 through
G-28, G-30, G-36 through G-38 and G-49 through G-55. Embodiment 44. A compound of Embodiment 43 wherein G is selected from G-I, G-2,
G-7, G-8, G-14, G-15, G-23, G-24, G-26, G-27, G-36, G-37, G-38, G-49, G-50 and G-55. Embodiment 45. A compound of Embodiment 44 wherein G is selected from G-I, G-2,
G-15, G-26, G-27, G-36, G-37 and G-38. Embodiment 46. A compound of Embodiment 45 wherein G is selected from G-I, G-2,
G-15, G-26 and G-36. Embodiment 47. A compound of Embodiment 46 wherein G is G-I. Of note are embodiments of these compounds within Embodiments 1 through 40, Embodiments 52 through 83, and Embodiments Al through A5.
Embodiment 48. A compound of Embodiment 46 wherein G is G-2. Of note are embodiments of these compounds within Embodiments 1 through 40, Embodiments 52 through 83, and Embodiments Al through A5.
Embodiment 49. A compound of Embodiment 46 wherein G is G-15. Of note are embodiments of these compounds within Embodiments 1 through 40, Embodiments 52 through 83, and Embodiments Al through A5.
Embodiment 50. A compound of Embodiment 46 wherein G is G-26. Of note are embodiments of these compounds within Embodiments 1 through 40, Embodiments 52 through 83, and Embodiments Al through A5.
Embodiment 51. A compound of Embodiment 46 wherein G is G-36. Of note are embodiments of these compounds within Embodiments 1 through 40, Embodiments 52 through 83, and Embodiments Al through A5.
Embodiment 52. A compound of any one of Embodiments 42 through 51 wherein each R3a is independently H, Q-C 3 alkyl or halogen.
Embodiment 53. A compound of Embodiment 52 wherein each R3a is independently H or methyl.
Embodiment 54. A compound of any one of Embodiments 42 through 51 wherein each R3a is H and each Rl la is independently H or methyl.
Embodiment 55. A compound of Formula 1 or any one of Embodiments 41 through 51 wherein G is unsubstituted.
Embodiment 56. A compound of Formula 1 or any one of Embodiments 1 through 55 wherein each R5 is independently H, cyano, C^-CO alkyl, C^-CO haloalkyl, C3- Cg cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkoxyalkyl, C^-C6 alkoxy, C^-C6 haloalkoxy, C3-C8 cycloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2- Cβ alkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C^-CO alkylthio, C^-CO haloalkylthio, C3-C10 trialkylsilyl, -NR25R26 or halogen.
Embodiment 57. A compound of Embodiment 56 wherein each R5 is independently H, cyano, C^-C6 alkyl, C^-C6 haloalkyl, C^-C6 alkoxy, C^-C6 haloalkoxy, -NR25R26 or halogen.
Embodiment 57a. A compound of Embodiments 56 or 57 wherein R5 is other than halogen.
Embodiment 58. A compound of Embodiment 57 wherein each R5 is independently H, cyano, Q-C 4 alkyl, Q-C4 haloalkyl, Q-C4 alkylcarbonyl or halogen. Embodiment 59. A compound of Embodiment 58 wherein each R5 is independently H and C1-C3 alkyl. Embodiment 60. A compound of Formula 1 or any one of Embodiments 1 through 59 wherein J is one of J-I through J-82 depicted in Exhibit 3;
Exhibit 3
Figure imgf000032_0001
J-I J-2 J-3 J-4
Figure imgf000032_0002
J-5 J-6 J-7 J-8
Figure imgf000032_0003
J-9 J-IO J-I l J-12
Figure imgf000032_0004
J-13 J-14 J-15 J-16
Figure imgf000032_0005
J-17 J-18 J-19 J-20
Figure imgf000033_0001
J-21 J-22 J-23 J-24
Figure imgf000033_0002
J-25 J-26 J-27 J-28
Figure imgf000033_0003
J-29 J-30 J-31 J-32
Figure imgf000033_0004
J-33 J-34 J-35 J-36
Figure imgf000033_0005
J-37 J-38 J-39 J-40
Figure imgf000033_0006
J-41 J-42 J-43 J-44
Figure imgf000034_0001
J-45 J-46 J-47 J-48
Figure imgf000034_0002
J-49 J-50 J-51 J-52
Figure imgf000034_0003
J-53 J-54 J-55 J-56
Figure imgf000034_0004
J-61 J-62 J-63 J-64
Figure imgf000034_0005
Figure imgf000035_0001
J-69 J-70 J-71 J-72
Figure imgf000035_0002
J-73 J-74 J-75 J-76
Figure imgf000035_0003
J-77 J-78 J-79 J-80
Figure imgf000035_0004
J-81 J-82
wherein the bond shown projecting to the left is bonded to Z1; x is an integer from 0 to
5; and s is an integer from 1 to 2.
Embodiment 61. A compound of Embodiment 60 wherein x is 0 or 1. Embodiment 61a. A compound of Embodiment 61 wherein x is 0. Embodiment 62. A compound of Embodiment 61a wherein s is 1 or 2. Embodiment 63. A compound of Embodiment 62 wherein s is 1. Embodiment 64. A compound of any one of Embodiments 60 through 63 wherein J is selected from J-I, J-2, J-3, J-4, J-5, J-7, J-8, J-9, J-IO, J-I l, J-12, J-14, J-15, J-16,
J-20, J-24, J-25, J-26, J-29, J-30, J-37, J-38, J-45 and J-69. Embodiment 65. A compound of Embodiment 64 wherein J is selected from J-4, J-5,
J-8, J-I l, J-15, J-16, J-20, J-29, J-30, J-37, J-38, and J-69. Embodiment 66. A compound of Embodiment 65 wherein J is selected from J-4, J-5,
J-I l, J-20, J-29, J-37, J-38, and J-69. Embodiment 67. A compound of Embodiment 66 wherein J is J-11. Embodiment 68. A compound of Embodiment 66 wherein J is J-29. Embodiment 69. A compound of Embodiment 59 wherein J is J-69. Embodiment 70. A compound of Embodiment 67 wherein the 3 -position of J-11 is connected to Z1 and the 5 -position of J-11 is connected to Z2Q. Embodiment 71. A compound of Embodiment 68 wherein the 3-position of J-29 is connected to Z1 and the 5 -position of J-29 is connected to Z2Q. Embodiment 72. A compound of Formula 1 or any one of Embodiments 1 -through 71 wherein the ring or ring system of J directly connected to Z1 is substituted with one -Z2Q. Embodiment 72a. A compound of Embodiment 68 wherein J is one of J-29- 1 through
J-29-60 depicted in Exhibit A;
Exhibit A
Figure imgf000036_0001
J-29-1 J-29-2
Figure imgf000036_0002
J-29-3 J-29-4
Figure imgf000037_0001
J-29-9 J-29-10
Figure imgf000037_0002
J-29-13 J-29-14
Figure imgf000038_0001
J-29-15 J-29-16
Figure imgf000038_0002
J-29-21 J-29-22
Figure imgf000039_0001
J-29-25 J-29-26
Figure imgf000039_0002
Figure imgf000040_0001
J-29-31 J-29-32
Figure imgf000040_0002
J-29-33 J-29-34
Figure imgf000040_0003
J-29-35 J-29-36
Figure imgf000040_0004
J-29-37 J-29-38
Figure imgf000041_0001
J-29-39 J-29-40
Figure imgf000041_0002
J-29-41 J-29-42
Figure imgf000041_0003
J-29-43 J-29-44
Figure imgf000041_0004
J-29-45 J-29-46
Figure imgf000042_0001
J-29-49 J-29-50
Figure imgf000042_0002
J-29-53 J-29-54
Figure imgf000043_0001
J-29-59 J-29-60 wherein Ph is phenyl, and the bond shown projecting to the left is bonded to Z1 in
Formula 1. Embodiment 72b. A compound of Embodiment 72a wherein J is one of J-29-1 through
J-29-57. Embodiment 73. A compound of Formula 1 or any one of Embodiments 1 through 72b wherein Z1 is a direct bond, O, C(=O), S(O)m, CHR20 or NR21. Embodiment 73 a. A compound of Embodiment 73 wherein Z1 is a direct bond. Embodiment 74. A compound of Formula 1 or any one of Embodiments 1 through 73a wherein Z2 is a direct bond, O, C(=O), S(O)m, CHR20 or NR21.
Embodiment 74a. A compound of Embodiment 74 wherein Z2 is a direct bond or NR21. Embodiment 74b. A compound of Embodiment 74a wherein Z2 is a direct bond. Embodiment 75. A compound of Formula 1 or any one of Embodiments 1 through 74b wherein Q is one of Q-I through Q- 106 depicted in Exhibit 4; Exhibit 4
Figure imgf000044_0001
Q-I Q-2 Q-3 Q-4
Figure imgf000044_0002
Q-5 Q-6 Q-V Q-8
Figure imgf000044_0003
Q-9 Q-IO Q-I l Q-12
Figure imgf000044_0004
Q-13 Q-14 Q-15 Q-16
Figure imgf000044_0005
Q-21 Q-22 Q-23 Q-24
Figure imgf000045_0001
Q-25 Q-26 Q-27 Q-28
Figure imgf000045_0002
Q-37 Q-38 Q-39 Q-40
Figure imgf000045_0003
Q-41 Q-42 Q-43 Q-44
Figure imgf000045_0004
Q-45 Q-46 Q-47 Q-48
Figure imgf000046_0001
Q-49 Q-50 Q-51 Q-52
Figure imgf000046_0002
Q-53 Q-54 Q-55
Figure imgf000046_0003
Q-59 Q-60 Q-61
Figure imgf000046_0004
Q-62 Q-63 Q-64
Figure imgf000046_0005
Q-65 Q-66 Q-67
Figure imgf000047_0001
Q-68 Q-69 Q-70
Figure imgf000047_0002
Q-71 Q-72 Q-73
Figure imgf000047_0003
Q-74 Q-75 Q-76
Figure imgf000047_0004
Q-77 Q-78 Q-79
Figure imgf000047_0005
Q-80 Q-81 Q-82
Figure imgf000048_0001
Q-83 Q-84 Q-85
Figure imgf000048_0002
Q-86 Q-87 Q-88
Figure imgf000048_0003
Q-89 Q-90 Q-91
Figure imgf000048_0004
Q-92 Q-93 Q-94
Figure imgf000048_0005
Q-95 Q-96 Q-97
Figure imgf000049_0001
Q-98 Q-99 Q-IOO
Figure imgf000049_0002
Q-IOl Q- 102 Q-103
Figure imgf000049_0003
Q- 104 Q- 105 Q-106
wherein the bond shown projecting to the left is bonded to Z2; R12 attached to a nitrogen ring member is optionally replaced by R7 (e.g., Q-3, Q-10 through
Q-14, Q-21 through Q-23, Q-28, Q-31, Q-62, Q-75, Q-78, Q-79, Q-86, Q-88,
Q-92 or Q-95); p is 1 or 2; and q is 0, 1, 2, 3, 4 or 5. Embodiment 76. A compound of Embodiment 75 wherein Q is selected from Q-I,
Q-20, Q-32 through Q-34, Q-45 through Q-47, Q-60 through Q-73, Q-76 through Q-79, Q-84 through Q-94 and Q-98 through Q-106. Embodiment 77. A compound of Embodiment 76 wherein Q is Q-I, Q-45, Q-62, Q-63,
Q-64, Q-65, Q-68, Q-69, Q-70, Q-71, Q-72, Q-73, Q-76, Q-78, Q-79, Q-84,
Q-85, Q-98, Q-99, Q-100, Q-101 through Q-106. Embodiment 78. A compound of Embodiment 77 wherein Q is Q-45, Q-62, Q-63, Q-64,
Q-65, Q-68, Q-69, Q-70, Q-71, Q-72, Q-85 or Q-104. Embodiment 79. A compound of Embodiment 78 wherein Q is Q-45, Q-62, Q-63, Q-65,
Q-70, Q-71, Q-72, Q-85 or Q-104. Embodiment 80. A compound of Embodiment 79 wherein Q is Q-45, Q-62, Q-63, Q-65,
Q-70 or Q-104. Embodiment 80a. Acompound of any one of Embodiments 77 through 80 wherein Q is other than Q-62 or Q-104. Embodiment 80b. A compound of Embodiment 80 wherein Q is Q-45. Embodiment 80c. A compound of Embodiment 80 wherein Q is Q-62. Embodiment 80d. A compound of Embodiment 80 wherein Q is Q- 104. Embodiment 81. A compound of Formula 1 or any one of Embodiments 1 through 74b wherein each Q is independently phenyl, benzyl, naphthalenyl, a 5- or 6- membered heteroaromatic ring or an 8- to 11-membered heteroaromatic bicyclic ring system, each ring or ring system substituted with 1 substituent selected from
R7 on carbon or nitrogen atom ring members. Embodiment 82. A compound of Embodiment 81 wherein Q is phenyl substituted with one R7. Embodiment 83. A compound of Embodiment 81 wherein Q is benzyl substituted with one R7. Embodiment 84. A compound of Embodiment 81 wherein Q is an 8- to 11-membered heteroaromatic bicyclic ring system substituted with one R7. Embodiment 85. A compound of Formula 1 or any one of Embodiments 1 through 84 wherein each Z3 is independently a direct bond, O, NR22, C(=O), C(=S), S(O)1n,
CHR20, CHR20-CHR20, CR24=CR27, C≡C or OCHR20 .
Embodiment 85a. A compound of Embodiment 85 wherein each Z3 is a C(=O). Embodiment 86. A compound of Embodiment 85 wherein each Z3 is independently a direct bond, O, NR22, S(O)1n, CHR20, CHR20-CHR20, CR24=CR27, C≡C or
OCHR20. Embodiment 87. A compound of Embodiment 86 wherein each Z3 is independently a direct bond, O, NR22, S(O)1n, CHR20, CHR20-CHR20, CR24=CR27 or C≡C. Embodiment 88. A compound of Embodiment 87 wherein each Z3 is independently a direct bond, O, NR22, CHR20 or CHR20-CHR20.
Embodiment 88a. A compound of Embodiment 88 wherein each Z3 is CH2. Embodiment 89. A compound of Embodiment 88 wherein each Z3 is independently a direct bond, O or NR22.
Embodiment 90. A compound of Embodiment 89 wherein each Z3 is a direct bond. Embodiment 91. A compound of Embodiment 89 wherein each Z3 is O. Embodiment 92. A compound of Formula 1 or any one of Embodiments 1 through 91 wherein R7 is -Z3GA.
Embodiment 93. A compound of Embodiment 92 wherein GA is phenyl. Embodiment 94. A compound of Embodiment 92 wherein GA is a 5- or 6-membered heteroaromatic ring. Embodiment 95. A compound of Formula 1 or any one of Embodiments 1 through 91 wherein R7 is -Z3GN. Embodiment 96. A compound of Formula 1 any one of Embodiments 1 through 91 wherein R7 is -Z3GP.
Embodiment 97. A compound of Formula 1 or any one of Embodiments 1 through 96 wherein each GA is independently one of GA-1 through GA-49, each GN is independently one of GN-1 through GN-32, and each Gp is independently one of Gp-1 through Gp-35 respectively, as depicted in Exhibit 5.
Exhibit 5
Figure imgf000051_0001
GA-1 GA-2 GA-3 GA-4
Figure imgf000051_0002
GA-5 GA-6 GA-7 GA-8
Figure imgf000051_0003
GA-9 GA-10 GA-11 GA-12
Figure imgf000051_0004
GA-13 GA-14 GA-15 GA-16
Figure imgf000051_0005
GA-17 GA-18 GA-19 GA-20
Figure imgf000052_0001
GA-21 GA-22 GA-23 GA-24
Figure imgf000052_0002
GA-25 GA-26 GA-27 GA-28
Figure imgf000052_0003
GA-29 GA-30 GA-31 GA-32
Figure imgf000052_0004
GA-33 GA-34 GA-35 GA-36
Figure imgf000052_0005
Figure imgf000053_0001
GA-45 GA-46 GA-47 GA-48
Figure imgf000053_0002
GA-49
Figure imgf000053_0003
GN-1 GN-2 GN-3 GN-4
Figure imgf000053_0004
GN-5 GN-6 GN-7 GN-8
Figure imgf000053_0005
GN-9 GN-10 GN-11 GN-12
Figure imgf000053_0006
GN-13 GN-14 GN-15 GN-16
Figure imgf000053_0007
GN-17 GN-18 GN-19 GN-20
Figure imgf000054_0001
GN-21 GN-22 GN-23 GN-24
Figure imgf000054_0002
GN-25 GN-26 GN-27 GN-28
Figure imgf000054_0003
GN-29 GN-30 GN-31 GN-32
Figure imgf000054_0004
Gp-1 Gp-2 GP-3
Figure imgf000054_0005
Gp-4 Gp-5 Gp-6
Figure imgf000054_0006
Gp-7 Gp-8 Gp-9
Figure imgf000055_0001
Gp-10 Gp-l l Gp-12
Figure imgf000055_0002
GP- 13 Gp-14 Gp-15
Figure imgf000055_0003
Gp-16 Gp-17 Gp-18
Figure imgf000055_0004
Gp-19 Gp-20 Gp-21
Figure imgf000055_0005
Gp-22 Gp-23 Gp-24
Figure imgf000056_0001
Gp-25 Gp-26 Gp-27
Figure imgf000056_0002
Gp-28 Gp-29 Gp-30
Figure imgf000056_0003
Gp-31 Gp-32 Gp-33
Figure imgf000056_0004
Gp-34 Gp-35
wherein the bond shown projecting to the left is bonded to Z3; and r is O, 1, 2, 3, 4 or 5.
Embodiment 97a. A compound of Embodiment 97 wherein r is 0, 1, 2 or 3.
Embodiment 97b. A compound of Embodiment 97 or 97a wherein GA is selected from GA-1 through GA-18, GA-23 through GA-38 and GA-49, GN is selected from GN-1, GN-2, GN-5, GN-6, GN-9 through GN-16 and GN-29, and Gp is selected from Gp-1 through Gp-6, Gp-34 and Gp-38.
Embodiment 98. A compound of Embodiment 97b wherein GA is selected from GA-1 through GA-18, GA-23 through GA-38 and GA-49, and GN is selected from GN-1, GN-2, GN-5, GN-6, GN-9 through GN-16 and GN-29.
Embodiment 99. A compound of Embodiment 98 wherein GA is selected from GA-18 and GA-49.
Embodiment 100. A compound of Embodiment 99 wherein GA is GA-18.
Embodiment 101. A compound of Embodiment 99 wherein GA is GA-49. Embodiment 102. A compound of Formula 1 or any one of Embodiments 1 through 101 wherein each Rv is independently H, halogen, cyano, hydroxy, -C(=O)OH, -C(K))NH2, -SO2NH2, -SH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-Cg alkylcarbonyl, C2-Cg alkoxycarbonyl, C^C1Q cycloalkoxycarbonyl, C5~C12 cycloalkylalkoxycarbonyl, C2-Cg alkylaminocarbonyl, C3-Q0 dialkylaminocarbonyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3~Cg cycloalkyl, C3~Cg halocycloalkyl, C 4-C1O alkylcycloalkyl, C4-Q0 cycloalkylalkyl, C6-C^ cycloalkylcycloalkyl, C 4-C1Q halocycloalkylalkyl, C5~C12 alkylcycloalkylalkyl, C2-Cg alkoxyalkyl, C 4-C1Q cycloalkoxyalkyl, C3-Q0 alkoxyalkoxyalkyl, C2-Cg alkylthioalkyl, C2-Cg alkylsulfinylalkyl, C2-Cg alkylsulfonylalkyl, C2-Cg alkylaminoalkyl, C3-Q0 dialkylaminoalkyl, C2-Cg haloalkylaminoalkyl, C4-Q0 cycloalkylaminoalkyl, C4-Q0 cycloalkylcarbonyl, C4-Q0 cycloalkylaminocarbonyl, C2-C7 cyanoalkyl, C1-C6 hydroxyalkyl, C4-Q0 cycloalkenylalkyl, C2-Cg haloalkoxyalkyl, C2-Cg alkoxyhaloalkyl, C3-Q0 alkoxyalkylcarbonyl, C3-Q0 alkoxycarbonylalkyl, C3-Q0 alkoxy(alkyl)aminocarbonyl, C2-Cg alkylamidino, C3-Q0 dialkylamidino, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-Cg alkylcarbonyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylaminosulfonyl, C2-Cg dialkylaminosulfonyl, Cs-C1Q trialkylsilyl, C2-Cg alkoxyalkoxy, C1-C6 alkylamino, C2-Cg dialkylamino, C2-Cg alkylcarbonylamino, C1-C6 alkylsulfonylamino or C1-C6 haloalkylamino.
Embodiment 103. A compound of Embodiment 102 wherein each Rv is independently H, halogen, cyano, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-Cg alkylcarbonyl, C2-Cg alkoxycarbonyl, C3~Cg cycloalkyl, C4- C1Q alkylcycloalkyl, C4-Q0 cycloalkylalkyl, C6-C^ cycloalkylcycloalkyl, C2- Cg alkoxyalkyl, C3-Q0 dialkylaminoalkyl, C2-C7 cyanoalkyl, C1-C6 hydroxyalkyl, C2-Cg haloalkoxyalkyl, C3-Q0 alkoxyalkylcarbonyl, C3-Q0 alkoxycarbonylalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-Cg alkylcarbonyloxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylamino or C2-Cg dialkylamino.
Embodiment 104. A compound of Embodiment 103 wherein each Rv is independently H, halogen, cyano, hydroxy, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy or C1-C2 haloalkoxy.
Embodiment 104a. A compound of Embodiment 104 wherein each Rv is independently H, halogen, hydroxy, or methyl.
Embodiment 105. A compound of Formula 1 or any one of Embodiments 1 through 104 wherein each R7a is independently C1-C6 alkyl, C3~C6 cycloalkyl, C1-C6 haloalkyl, halogen, cyano, Q-C4 alkoxy, Q-C4 haloalkoxy or C2-C6 alkoxycarbonyl.
Embodiment 106. A compound of Embodiment 105 wherein each R7a is independently methyl, CF3, halogen or methoxy.
Embodiment 107. A compound of Formula 1 or any one of Embodiments 1 through 106 wherein R21 is H, C^-C 3 alkyl, C^-C 3 alkylcarbonyl or C2-C3 alkoxycarbonyl.
Embodiment 108. A compound of Formula 1 or any one of Embodiments 1 through 107 wherein each Z4 is independently C(=O) or S(O)2-
Embodiment 109. A compound of Embodiment 108 wherein each Z4 is C(=O).
Embodiment 110. A compound of Formula 1 or any one of Embodiments 1 through 109 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z1 in Formula 1, A is CHR15, and J is a substituted isoxazole ring connected at its 4-position to Z1, then Z1 is O, C(=O), S(O)1n, CHR20 Or NR21.
Embodiment 111. A compound of Formula 1 or any one of Embodiments 1 through 110 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z1 in Formula 1, and J is a substituted isoxazole ring connected at its 4-position to Z1, then Z1 is O, C(=O), S(O)m, CHR20 Or NR21.
Embodiment 112. A compound of Formula 1 or any one of Embodiments 1 through 111 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z1 in Formula 1, A is CHR15, Z1 is a direct bond, and J is a substituted isoxazole ring, then J is connected to the remainder of the Formula 1 at the 3- or 5-position of the isoxazole ring.
Embodiment 113. A compound of Formula 1 or any one of Embodiments 1 through 112 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z1 in Formula 1, A is CHR15, Z1 is a direct bond, and J is a substituted isoxazole ring, then J is connected to the remainder of the Formula 1 at the 3-position of the isoxazole ring.
Embodiment 114. A compound of Formula 1 or any one of Embodiments 1 through 113 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z1 in Formula 1, Z1 is a direct bond, and J is a substituted isoxazole ring, then J is connected to the remainder of the Formula 1 at the 3-position of the isoxazole ring.
Embodiment 115. A compound of Formula 1 or any one of Embodiments 1 through 114 wherein when X is X1 and the ring containing X is saturated, A is NH, G is an optionally substituted thiazole ring connected at its 2-position to X and at its A- position to Z1 in Formula 1, and J is a substituted imidazole ring connected at its 2-position to the remainder of Formula 1, then Z1 is O, C(=O), S(O)1n, CHR20 or NR21.
Embodiment 116. A compound of Formula 1 or any one of Embodiments 1 through 115 wherein when X is X1 and the ring containing X is saturated, A is NR16, G is an optionally substituted thiazole ring connected at its 2-position to X and at its A- position to Z1 in Formula 1, and J is a substituted imidazole ring connected at its 2-position to the remainder of Formula 1, then Z1 is O, C(=O), S(O)1n, CHR20 or NR21.
Embodiment 117. A compound of Formula 1 or any one of Embodiments 1 through 116 wherein when G is an optionally substituted thiazole ring connected at its 2- position to X and at its 4-position to Z1 in Formula 1, then J is other than substituted imidazolyl.
Combinations of Embodiments 1-117 are illustrated by: Embodiment Al . A compound of Formula 1 wherein
R1 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with 1-3 substituents independently selected from R4a on carbon ring members and R4*5 on nitrogen ring members;
G is a 5-membered heterocyclic ring optionally substituted with up to 2 substituents selected from R3 on carbon ring members and selected from R1 * on nitrogen ring members; J is one of J-I through J-82 (as depicted in Exhibit 3) wherein the bond shown projecting to the left is bonded to Z1; each R2 is independently C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, halogen, cyano or hydroxy; each R3 is independently C1-C3 alkyl, C1-C3 haloalkyl or halogen; each R4a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3- C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5- C10 alkylcycloalkylalkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfϊnyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfϊnyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-Cg dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-Cg dialkylaminocarbonyl or C3-C6 trialkylsilyl; each R4b is independently C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3- C6 cycloalkyl, C1-C6 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 halocycloalkyl or C2-C4 alkoxyalkyl; each R11 is independently C1-C3 alkyl;
R15 is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C1-C4 haloalkyl or C2-C5 alkoxycarbonyl;
R16 is H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl or C2-C4 alkoxycarbonyl; x is an integer from 0 to 5; and s is an integer from 1 to 2. Embodiment A2. A compound of Embodiment Al wherein
G is one of G-I through G-59 (as depicted in Exhibit 2) wherein the bond projecting to the left is bonded to X, and bond projecting to the right is bonded to Z1;
J is selected from J-I, J-2, J-3, J-4, J-5, J-7, J-8, J-9, J-IO, J-I l, J-12, J-14, J-15, J-16, J-20, J-24, J-25, J-26, J-29, J-30, J-37, J-38, J-45 and J-69;
Q is one of Q-I through Q- 106 (as depicted in Exhibit 4);
R1 is one of U-I through U-50 (as depicted in Exhibit 1) wherein when R4 is attached to a carbon ring member, said R4 is selected from R4a, and when R4 is attached to a nitrogen ring member (e.g., in U-4, U-I l through U-15, U-24 through U-26, U-31 or U-35), said R4 is selected from R4b; each R2 is independently methyl, methoxy, cyano or hydroxy; each R3a is independently selected from H and R3; each R5 is independently H, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C3-Cg cycloalkyl, C3-Cg halocycloalkyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-Cg cycloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C1-C6 alkylthio, C1- C6 haloalkylthio, C3-C10 trialkylsilyl or -NR25R26;
R1 la is selected from H and R11 ;
R15 is H, cyano, hydroxy, methyl or methoxycarbonyl;
R16 is H, methyl, methylcarbonyl or methoxycarbonyl; each Z4 is C(=O); k is 0, 1 or 2; p is 1 or 2; q is 0, 1, 2, 3, 4 or 5; and s is 1. Embodiment A3. A compound of Embodiment A2 wherein
G is selected from G-I, G-2, G-7, G-8, G-14, G-15, G-23, G-24, G-26, G-27,
G-36, G-37, G-38, G-49, G-50 and G-55; J is selected from J-4, J-5, J-8, J-I l, J-15, J-16, J-20, J-29, J-30, J-37, J-38 and
J-69; each Q is independently Q-I, Q-20, Q-32 through Q-34, Q-45 through Q-47,
Q-60 through Q-73, Q-76 through Q-79, Q-84 through Q-94 and Q-98 through Q- 106; A is CH2 or NH; W is O;
X iS X^ X2 Or X3; Z1 is a direct bond; Z2 is a direct bond or NR21; R1 is selected from U-I through U-3, U-I l, U-13, U-20, U-22, U-23, U-36 through U-39 and U-50; each R3 is independently methyl or halogen; each R4a is independently Cj-C2 alkyl, Cj-C2 haloalkyl, halogen, Q-C2 alkoxy or Cj-C2 haloalkoxy; each R4b is independently Cj-C2 alkyl or Cj-C2 haloalkyl; each R7a is independently Cj-C6 alkyl, C3-C6 cycloalkyl, Cj-C6 haloalkyl, halogen, cyano, CJ-C4 alkoxy, CJ-C4 haloalkoxy or C2-C6 alkoxycarbonyl; k is 1 or 2; and n is 0.
Embodiment A4. A compound of Embodiment A3 wherein A is CH2; G is selected from G-I, G-2, G-15, G-26, G-27, G-36, G-37 and G-38; and G is unsubstituted; J is J-29; Q is selected from Q-I, Q-45, Q-63, Q-64, Q-65, Q-68, Q-69, Q-70, Q-71,
Q-72, Q-73, Q-76, Q-78, Q-79, Q-84, Q-85, Q-98, Q-99, Q-IOO and
Q-IOl through Q- 106;
X is X1 or X2; and the ring comprising X is saturated; RMs U-I5 U^O Or U-SO; each R4a is independently Cj-C2 alkyl, trifluoromethyl, Cl, Br, I or methoxy; each R4b is independently Cj-C2 alkyl or trifluoromethyl; and each R5 is independently H, cyano, Cj-C6 alkyl, Cj-C6 haloalkyl, Cj-C6 alkoxy, C1-C6 haloalkoxy or -NR25R26. Embodiment A5. A compound of Embodiment A4 wherein G is selected from G-I, G-2, G-15, G-26 and G-36; J is any one of J-29-1 to J-29-60 (depicted in Exhibit A); Q is selected from Q-45, Q-63, Q-64, Q-65, Q-68, Q-69, Q-70, Q-71, Q-72 and Q-85; and X is X1.
Embodiments of the present invention also include: Embodiment Bl. A compound of Formula IA wherein M is C1-C2 alkyl, C1-C2 haloalkyl, hydroxy, Q-C4 alkoxy, Q-C2 haloalkoxy, Q-C 3 alkylamino, C2- Cβ dialkylamino, 1-piperidinyl, 1 -pyrrolidinyl or 4-morpholinyl. Embodiment B2. A compound of Formula IA wherein M is C^-C 3 alkyl, C^-C 3 haloalkyl, hydroxy, C2~Cg dialkylamino, 1-piperidinyl, 1 -pyrrolidinyl or 4-morpholinyl.
Embodiment B3. A compound of Embodiment B2 wherein M is methyl, halomethyl, hydroxy, C2~Cg dialkylamino, 1-piperidinyl, 1 -pyrrolidinyl or 4-morpholinyl. Embodiment B4. A compound of Embodiment B3 wherein M is C2~Cg dialkylamino,
1-piperidinyl, 1 -pyrrolidinyl or 4-morpholinyl. Embodiment B5. A compound of Formula IA or any one of Embodiments Bl through
B4 wherein J1 is any one of J-29-1 through J-29-57 (as depicted in Exhibit A). With regards to the compounds of Formula IA of this invention, it is noted that various embodiments of J-29 can be present in two or more enantiomeric forms. The enantiomeric forms of J-29 embodiments for compounds of Formula IA of this invention are those depicted in Exhibit A above. All J-29 enantiomers are included in the Formula IA compounds in this invention for embodiments where no specific J-29 enantiomeric form is depicted.
Specific embodiments include compounds of Formula 1 selected from the group consisting of: l-[4-[4-[4,5-dihydro-5-[3-(l/f-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl]-2-thiazolyl]-l- piperidinyl] -2- [5 -methyl-3 -(trifluoromethyl)- lH-pyrazol- 1 -yl] ethanone, l-[4-[4-(5-[l,r-biphenyl]-4-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-l-piperidinyl]-2- [5 -methyl-3 -(trifluoromethyl)- lH-pyrazol- 1 -yljethanone,
4-[4-(5-[l,r-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-N-(2,5- dimethylphenyl)- 1 -piperidinecarboxamide,
4-[4-(4,5-dihydro-5-[2-(lH-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl)-2-thiazolyl]-N- (2,5-dimethylphenyl)- 1 -piperidinecarboxamide, l-[4-[4-[4,5-dihydro-5-[2-(l/f-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl]-2-thiazolyl]-l- piperidinyl] -2- [5 -methyl-3 -(trifluoromethyl)- lH-pyrazol- 1 -yl] ethanone, l-[4-[4-[5-[2-fluoro-6-(lH-l,2,4-triazol-l-yl)phenyl]-4,5-dihydro-3-isoxazolyl]-2- thiazolyl]- 1 -piperidinyl]-2-[5-methyl-3-(trifluoromethyl)- lH-pyrazol-1 -yljethanone, and l-[4-[4-(5-[l,r-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-l-piperidinyl]-2- [5-methyl-3-(trifluoromethyl)- lH-pyrazol- 1 -yljethanone.
This invention provides a fungicidal composition comprising a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof, and at least one other fungicide. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
This invention provides a fungicidal composition comprising a fungicidally effective amount of a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of note as embodiments of such compositions are compositions comprising a compound corresponding to any of the compound embodiments described above.
This invention provides a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed, a fungicidally effective amount of a compound selected from compounds of Formula 1 (including all geometric and stereoisomers) and iV-oxides and salts thereof. Of note as embodiments of such methods are methods comprising applying a fungicidally effective amount of a compound corresponding to any of the compound embodiments described above. Of particular note are embodiments where the compounds are applied as compositions of this invention.
Also of note are the above embodiments, including Embodiments 1 through 117, Al through A5, and Bl through B5 wherein Formulae 1 and IA do not include iV-oxides thereof, do not include salts thereof, or do not include iV-oxides and salts thereof.
The compounds of Formulae 1 and IA can be prepared by one or more of the following methods and variations as described in Schemes 1-29. The definitions of A, G, J, W, X, Q, Z1, Z2, Z3, R1, R2, R15, R16 and n in the compounds of Formulae 1-48 and Formulae IBa and IBb below are as defined above in the Summary of the Invention unless otherwise noted. Formulae Ia-Ii are various subsets of Formula 1; Formuls 37a is an alternative depection of Formula 37.
As shown in Scheme 1, compounds of Formula Ia (Formula 1 wherein A is CΗR15) wherein W is O can be prepared by coupling of an acid chloride of Formula 2 with an amine of Formula 3 in the presence of an acid scavenger. Typical acid scavengers include amine bases such as triethylamine, N,Λ/-diisopropylethylamine and pyridine. Other scavengers include hydroxides such as sodium and potassium hydroxide and carbonates such as sodium carbonate and potassium carbonate. In certain instances it is useful to use polymer- supported acid scavengers such as polymer-bound N,N-diisopropylethylamine and polymer- bound 4-(dimethylamino)pyridine. Acid salts of the Formula 3 amines can also be used in this reaction, provided that at least 2 equivalents of the acid scavenger is present. Typical acids used to form salts with amines include hydrochloric acid, oxalic acid and trifluoroacetic acid. In a subsequent step, amides of Formula Ia wherein W is O can be converted to thioamides of Formula Ia wherein W is S using a variety of standard thiating reagents such as phosphorus pentasulfϊde or 2,4-bis(4-methoxyphenyl)-l,3-dithia-2,4- diphosphetane-2,4-disulfϊde (Lawesson's reagent).
Scheme 1
R1
Figure imgf000064_0001
Ia wherein W is O
An alternate procedure for the preparation of compounds of Formula Ia wherein W is O is depicted in Scheme 2 and involves coupling of an acid of Formula 4 with an amine of Formula 3 (or its acid salt) in the presence of a dehydrative coupling reagent such as dicyclohexylcarbodiimide (DCC), 1 -(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) or 0-benzotriazol-l-yl-Λf,Λ/,ΛfyV-tetramethyluronium hexafluoro- phosphate (HBTU). Polymer-supported reagents are again useful here, such as polymer- bound cyclohexylcarbodiimide. These reactions are typically run at 0-40 0C in a solvent such as dichloromethane or acetonitrile in the presence of a base such as triethylamine or Λ/,Λ/-diisopropylethylamine. The acids of Formula 4 are known or can be prepared by methods known to one skilled in the art. For example, R1CH2COOH where R1 is a heteroaromatic ring linked through nitrogen can be prepared by reacting the corresponding R1H compound with a haloacetic acid or ester in the presence of base; see, for example, U.S. Patent 4,084,955. R1CH2COOH wherein R1 is a phenyl or a heteroaromatic ring linked through carbon can be prepared from the corresponding R1 CH2 -halogen compounds by displacement of the halogen with cyanide followed by hydrolysis; see, for example, K. Adachi, Yuki Gosei Kagaku Kyokaishi 1969, 27, 875-876; from R1Q=O)CH3 by the Willgerodt-Kindler reaction; see, for example, H. R. Darabi et al., Tetrahedron Letters 1999, 40, 7549-7552 and M. M. Alam and S. R. Adapa, Synthetic Communications 2003, 33, 59- 63 and references cited therein; or from R1Br or R1I by palladium-catalyzed coupling with tert-butyl acetate or diethyl malonate followed by ester hydrolysis; see, for example, W. A. Moradi and S. L. Buchwald, J. Am. Chem. Soc. 2001, 123, 7996-8002 and J. F. Hartwig et al., J. Am. Chem. Soc. 2002, 124, 12557-12565.
Scheme 2
Figure imgf000065_0001
4 3 Ia wherein W is O
As the synthetic literature includes many amide-forming methods, the synthetic procedures of Schemes 1 and 2 are simply representative examples of an wide variety of methods useful for the preparation of Formula 1 compounds. One skilled in the art also realizes that acid chlorides of Formula 2 can be prepared from acids of Formula 4 by numerous well-known methods.
Certain compounds of Formula Ib (Formula 1 wherein A is CHR15 and W is O) wherein R1 is a 5-membered nitrogen-containing heteroaromatic ring linked through the nitrogen atom can be prepared by reaction of the parent heterocycle of Formula 5 and a haloacetamide of Formula 6 as shown in Scheme 3. The reaction is carried out in the presence of a base such as sodium hydride or potassium carbonate in a solvent such as tetrahydrofuran, Λ/,Λ/-dimethylformamide or acetonitrile at 0 to 80 0C. The haloacetamide of Formula 6 can be prepared by the reaction of an amine of Formula 3 with an α-halo carboxylic acid halide or an α-halo carboxylic acid or its anhydride, analogous to the amide- forming reactions described in Schemes 1 and 2, respectively.
Scheme 3
Figure imgf000065_0002
wherein R1 is a 5-membered nitrogen-containing heteroaromatic ring unsubstituted on N; and Y1 is Cl, Br or I.
Compounds of Formulae Ic (Formula 1 wherein A is NH), wherein R1 is phenyl, naphthalenyl or a 5- or 6-membered heteroaromatic ring, and W is O or S, can be prepared by reaction of an amine of Formula 3 with an isocyanate or isothiocyanate, respectively, of Formula 7 as depicted in Scheme 4. This reaction is typically carried out at an ambient temperature in an aprotic solvent such as dichloromethane or acetonitrile.
Scheme 4
Figure imgf000066_0001
3 7 Ic wherein W is O or S, and
R16 is H
Compounds of Formulae Ic can also be prepared by the reaction of an amine of Formula 8 with a carbamoyl or thiocarbamoyl chloride or imidazole of Formula 9 as shown in Scheme 5. When Y is chlorine, the reaction is typically carried out in the presence of an acid scavenger. Typical acid scavengers include amine bases such as triethylamine, Λ/,Λ/-diisopropylethylamine and pyridine. Other scavengers include hydroxides such as sodium and potassium hydroxide and carbonates such as sodium carbonate and potassium carbonate. The carbamoyl or thiocarbamoyl chlorides of Formula 9 (wherein Y is Cl) can be prepared from amines of Formula 3 by treatment with phosgene or thiophosgene, respectively, or their equivalents, while carbamoyl or thiocarbamoyl imidazoles of Formula 9 (wherein Y is imidazol-1-yl) can be prepared from amines of Formula 3 by treatment with l,l'-carbonyldiimidazole or 1 , l'-thiocarbonyldiimidazole, respectively, according to general methods known to one skilled in the art.
Scheme 5
Figure imgf000066_0002
wherein W is O or S; and Y is Cl or imidazol-1-yl.
Certain compounds of Formula Id (i.e. Formula 1 in which the ring containing X is saturated) can be prepared from compounds of Formula Ie where the ring containing X is unsaturated by catalytic hydrogenation as shown in Scheme 6. Typical conditions involve exposing a compound of Formula Ie to hydrogen gas at a pressure of 70 to 700 kPa, preferably 270 to 350 kPa, in the presence of a metal catalyst such as palladium supported on an inert carrier such as activated carbon, in a weight ratio of 5 to 20 % of metal to carrier, suspended in a solvent such as ethanol at an ambient temperature. This type of reduction is very well known; see, for example, Catalytic Hydrogenation, L. Cerveny, Ed., Elsevier Science, Amsterdam, 1986. One skilled in the art will recognize that other certain functionalities that may be present in compounds of Formula Ie can also be reduced under catalytic hydrogenation conditions, thus requiring a suitable choice of catalyst and conditions.
Scheme 6
Figure imgf000067_0001
Catalyst
Figure imgf000067_0002
Figure imgf000067_0003
Ie Id wherein X is X1, X2, X5, X8 or X9.
Certain compounds of Formula 1 wherein X is X1, X5, X7 or X9, and G is linked to the ring containing X via a nitrogen atom, can be prepared by displacement of an appropriate leaving group Y2 on the ring containing the X of Formula 10 with a nitrogen-containing heterocycle of Formula 11 in the presence of a base as depicted in Scheme 7. Suitable bases include sodium hydride or potassium carbonate, and the reaction is carried out in a solvent such as N,N-dimethylformamide or acetonitrile at 0 to 80 0C. Suitable leaving groups in the compounds of Formula 10 include bromide, iodide, mesylate (OS(O)2CH3), triflate (OS(O)2CF3) and the like, and compounds of Formula 10 can be prepared from the corresponding compounds wherein Y2 is OH, using general methods known in the art.
Scheme 7
Figure imgf000067_0004
wherein W is O or S; X is X1, X5, X7 or X9; and Y2 is a leaving group such as Br, I, OS(O)2Me or OS(O)2CF3.
Compounds of Formula 1 wherein X is X2 or X8 can be prepared by reaction of a compound of Formula 12 with a heterocyclic halide or triflate (OS(O)2CF3) of Formula 13 as shown in Scheme 8. The reaction is carried out in the presence of a base such as potassium carbonate in a solvent such as dimethylsulfoxide, N,Λ/-dimethylformamide or acetonitrile at 0 to 80 0C. Compounds of Formula 13 wherein Y2 is triflate can be prepared from corresponding compounds wherein Y2 is OH by methods known to one skilled in the art.
Scheme 8
Figure imgf000068_0001
wherein W is O or S; X is X2 or X8; and Y2 is a leaving group such as Br, I OS(O)2Me or OS(O)2CF3.
The amine compounds of Formula 3 can be prepared from the protected amine compounds of Formula 14 where Y3 is an amine -protecting group as shown in Scheme 9. A wide array of amine -protecting groups are available (see, for example, T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991), and the use and choice of the appropriate protecting groups will be apparent to one skilled in chemical synthesis. The protecting group can be removed and the amine isolated as its acid salt or the free amine by general methods known in the art. One skilled in the art will also recognize that the protected amines of Formula 14 can be prepared by methods analogous to those described in Schemes 6, 7, and 8 above where the group R1 AC(=W) is replaced by Y3 to give useful intermediates of Formula 14 for the preparation of compounds of Formula 1.
Scheme 9
Deprotection
Figure imgf000068_0004
Figure imgf000068_0003
Figure imgf000068_0002
14 wherein Y3 is an amine protecting group 3
The compounds of Formula 14 can also be prepared by reaction of a suitably functionalized compound of Formula 15 with a suitably functionalized compound of Formula 16 as shown in Scheme 10. The functional groups Y4 and Y5 are selected from, but not limited to, moieties such as aldehydes, ketones, esters, acids, amides, thioamides, nitriles, amines, alcohols, thiols, hydrazines, oximes, amidines, amideoximes, olefins, acetylenes, halides, alkyl halides, methanesulfonates, trifluoromethanesulfonates, boronic acids, boronates, and the like, which under the appropriate reaction conditions, will allow the construction of the various heterocyclic rings G. As an example, reaction of a compound of Formula 15 where Y4 is a thioamide group with a compound of Formula 16 where Y5 is a bromoacetyl or chloroacetyl group will give a compound of Formula 14 where G is a thiazole ring. The synthetic literature describes many general methods for forming 5- membered heteroaromatic rings and 5-membered partially saturated heterocyclic rings (e.g., G-I through G-59); see, for example, Comprehensive Heterocyclic Chemistry, Vol. 4-6, A. R. Katritzky and C. W. Rees editors, Pergamon Press, New York, 1984; Comprehensive Heterocyclic Chemistry II, Vol. 2-4, A. R. Katritzky, C. W. Rees, and E. F. Scriven editors, Pergamon Press, New York, 1996; and the series, The Chemistry of Heterocyclic Compounds, E. C. Taylor, editor, Wiley, New York. The use of intermediates of Formula 15 where X is X1 and Y4 is Br, I, methanesulfonate or trifluoromethanesulfonate to prepare organozinc reagents for use in cross-coupling reactions with aromatic rings has been described; see, for example, S. Bellotte, Synlett 1998, 379-380, and M. Nakamura et al, Synlett 2005, 1794-1798. One skilled in the art knows how to select the appropriate functional groups to construct the desired heterocyclic rings such as G. Compounds of Formula 15 and 16 are known or can be prepared by general methods known in the art. For example, compounds of Formula 15 wherein Y4 is a thioamide group can be prepared from corresponding compounds wherein Y4 is cyano by treatment with sodium hydrosulfϊde, analogous to the method demonstrated in Example 2, Step B.
Scheme 10
Figure imgf000069_0001
wherein Y4 and Y5 are functional groups suitable for construction of the desired heterocycle G.
One skilled in the art recognizes that the methods particularly described herein are illustrative of a wide variety of methods known in the synthetic organic chemistry art that are useful for preparing compounds of Formula 1. The order of assembling the molecular components of Formula 1 can be varied, and analogous starting compounds and reagents can be selected to prepare the various compounds within the scope of Formula 1. For example, the method of Scheme 10 involves forming the G ring from precursor groups Y4 and Y5 before removing protecting group Y3 as shown in Scheme 9 and attaching the left portion of the molecule (R1AQ=W)-) as shown in Schemes 1 through 5. Alternatively, a method analogous to Scheme 10 can be used to form the G ring from precursor groups Y4 and Y5 after attaching the left portion of molecule using methods analogous to Schemes 1 through 5. This alternate synthetic route is demonstrated in Example 2 wherein Step A is analogous to Scheme 4, Step B is analogous to a method for preparing a starting compound for Scheme 10, Step C corresponds to Scheme 28, Step D is analogous to Scheme 20 and Step E is analogous to Scheme 10.
Certain compounds of Formula 14 where Z1 is O, S, or NR21 can be prepared by displacement of an appropriate leaving group Y2 on G of Formula 17 with a compound of Formula 18 in the presence of a base as depicted in Scheme 11. Suitable bases include sodium hydride or potassium carbonate, and the reaction is carried out in a solvent such as Λ/,Λ/-dimethylformamide or acetonitrile at 0 to 80 0C. Suitable leaving groups in the compounds of Formula 17 include bromide, iodide, mesylate (OS(O)2CH3), triflate (OS(O^CF3) and the like. Compounds of Formula 17 can be prepared from corresponding compounds wherein Y2 is OH by general methods known in the art. The compounds of Formula 18 are known or can be prepared by general methods known in the art.
Scheme 11
Figure imgf000070_0001
17 18 14 wherein Y2 is a leaving group such as Br, I, OS(O^Me or OS(O^CF3; and Z1 is O, S or
NR21.
Certain compounds of Formula 14 where Z1 is O, S, or NR21 can also be prepared by displacement of an appropriate leaving group Y2 on J of Formula 20 with a compound of Formula 19 in the presence of a base as depicted in Scheme 12. Suitable bases include sodium hydride or potassium carbonate, and the reaction is carried out in a solvent such as Λ/,Λ/-dimethylformamide or acetonitrile at 0 to 80 0C. Suitable leaving groups in the compounds of Formula 20 include bromide, iodide, mesylate (OS(O^CH3), triflate (OS(O)2CF3) and the like. Compounds of Formula 20 can be prepared from corresponding compounds wherein Y2 is OH using general methods known in the art.
Scheme 12
Figure imgf000070_0002
wherein Y2 is a leaving group such as Br, I, OS(O^Me or OS(O^CF3; and Z1 is O, S or
NR21. Compounds of Formula 14 can also be prepared by reaction of a suitably functionalized compound of Formula 21 with a suitably functionalized compound of Formula 22 as shown in Scheme 13. The functional groups Y6 and Y7 are selected from, but not limited to, moieties such as aldehydes, ketones, esters, acids, amides, thioamides, nitriles, amines, alcohols, thiols, hydrazines, oximes, amidines, amide oximes, olefins, acetylenes, halides, alkyl halides, methanesulfonates, trifluoromethanesulfonates, boronic acids, boronates, and the like, which, under the appropriate reaction conditions will allow the construction of the various heterocyclic rings J. As an example, reaction of a compound of Formula 21 where Y6 is a chloro oxime moiety with a compound of Formula 22 where Y7 is a vinyl or acetylene group in the presence of base will give a compound of Formula 14 where J is an isoxazoline or isoxazole, respectively. The synthetic literature includes many general methods for the formation of carbocyclic and heterocyclic rings and ring systems (for example, J-I through J-82); see, for example, Comprehensive Heterocyclic Chemistry, Vol. 4-6, A. R. Katritzky and C. W. Rees editors, Pergamon Press, New York, 1984; Comprehensive Heterocyclic Chemistry II, Vol. 2-4, A. R. Katritzky, C. W. Rees, and E. F. Scriven editors, Pergamon Press, New York, 1996; the series, The Chemistry of Heterocyclic Compounds, E. C. Taylor, editor, Wiley, New York, and Rodd's Chemistry of Carbon Compounds, Vol. 2-4, Elsevier, New York. General procedures for cycloaddition of nitrile oxides with olefins are well documented in the chemical literature. For relevant references; see, for example, Lee, Synthesis 1982, 6, 508-509 and Kanemasa et al., Tetrahedron 2000, 56, 1057-1064 as well as references cited within. One skilled in the art knows how to select the appropriate functional groups to construct the desired heterocyclic ring J. Compounds of Formula 22 are known or can be prepared by general methods known in the art.
Scheme 13
one or more steps
Figure imgf000071_0001
Figure imgf000071_0002
21 22 14 wherein Y6 and Y7 are functional groups suitable for construction of the desired heterocycle J.
An alternate preparation for the compounds of Formula 14 where Z1 is a bond includes the well known Suzuki reaction involving Pd-catalyzed cross-coupling of an iodide or bromide of Formula 23 or 26 with a boronic acid of Formula 24 or 25, respectively, as shown in Scheme 14. Many catalysts are useful for this type of transformation; a typical catalyst is tetrakis(triphenylphosphine)palladium. Solvents such as tetrahydrofuran, acetonitrile, diethyl ether and dioxane are suitable. The Suzuki reaction and related coupling procedures offer many alternatives for creation of the G-J bond. For leading references; see, for example, C. A. Zificsak and D. J. Hlasta, Tetrahedron 2004, 60, 8991-9016. For a thorough review of palladium chemistry applicable to the synthesis of G-J bonds; see, for example, J. J. Li and G. W. Gribble, editors, Palladium in Heterocyclic Chemistry: A Guideor the Synthetic Chemist, Elsevier: Oxford, UK, 2000. Many variations of catalyst type, base and reaction conditions are known in the art for this general method.
Scheme 14
Figure imgf000072_0001
One skilled in the art will recognize that many compounds of Formula 1 can be prepared directly by methods analogous to those described in Schemes 10 through 14 above where the group Y3 is replaced by R1AQ=W). Thus, compounds corresponding to Formulae 15, 17, 19, 21, 23 and 25 in which Y3 is replaced by R1AQ=W) are useful intermediates for the preparation of compounds of Formula 1.
Thioamides of Formula IBb are particularly useful intermediates for preparing compounds of Formula 1 wherein X is X1 using the thioamide-α-haloaryl ring-forming reaction described for the method of Scheme 10. A thioamide of Formula IBb can be prepared by the addition of hydrogen sulfide to the corresponding nitrile of Formula IBa as shown in Scheme 15. Scheme 15
Figure imgf000073_0001
IBa IBb wherein R1 and A are as defined for Formula 1.
The method of Scheme 15 can be carried out by contacting a compound of Formula IBa with hydrogen sulfide in the presence of an amine such as pyridine, diethylamine or diethanolamine. Alternatively, hydrogen sulfide can be used in the form of its bisulfide salt with an alkali metal or ammonia. This type of reaction is well documented in the literature (e.g., A. Jackson et al., EP 696,581 (1996)). This method is demonstrated in Example 1, Step C and Example 2, Step B..
Certain compounds of Formula IBa wherein R1 is a 5-membered nitrogen-containing heteroaromatic ring linked through a nitrogen atom can be prepared by reaction of the parent heterocycle of Formula 5 and a haloacetamide of Formula 27 as shown in Scheme 16. The reaction is carried out in the presence of a base such as sodium hydride or potassium carbonate in a solvent such as tetrahydrofuran, N,Λ/-dimethylformamide or acetonitrile at 0 to 80 0C. This method is demonstrated in Example 1, Step B.
Scheme 16
Figure imgf000073_0002
27 IBa wherein in R1H (Formula 5), R1 is a 5-membered nitrogen-containing heteroaromatic ring unsubstituted on N (i.e. a 5-membered heteroaromatic ring comprising a ring member of the formula -(NH)-); A is CH2; and Y1 is Cl, Br or I.
The haloacetamides of Formula 27 can be prepared by the two methods shown in Scheme 17. Scheme 17
Figure imgf000074_0001
28 27 29 wherein Y1 is Cl, Br, or I; and R31 is a tertiary alkyl group such as -C(Me)3.
In one method, 4-cyanopiperidine of Formula 29 is haloacetylated by contact with the appropriate haloacetyl chloride typically in the presence of a base according to standard methods. Preferred conditions involve use of an aqueous solution of an inorganic base such as an alkali metal or alkaline-earth carbonate, bicarbonate or phosphate, and a non-water- miscible organic solvent such as toluene, ethyl acetate or 1,2-dichloroethane. In the second method depicted in Scheme 17, a l-(haloacetyl)-JV-substituted isonipecotamide derivative of Formula 28, wherein R31 is tertiary alkyl such as C(M e)3, is dehydrated using a standard amide dehydrating agent such as thionyl chloride or phosphorus oxychloride in a suitable solvent. A particularly preferred solvent for this transformation is an JV,iV-dialkylamide such as Λ/,Λ/-dimethylformamide. The reaction is typically carried out by adding 0.9 to 2 equivalents, preferably 1.1 equivalents, of phosphorus oxychloride or thionyl chloride to a mixture of a compound of Formula 28 and 0.5 to 10 parts by weight of solvent, at a temperature at which the reaction rapidly proceeds during the addition. The addition time for this reaction is typically around 20 to 90 minutes at typical temperatures of around 35 to 55 0C.
As shown in Scheme 18, the compounds of Formula 28 can be prepared from the compound of Formula 30 by analogy with the haloacetylation reaction described for Scheme 17.
Scheme 18
Figure imgf000074_0002
30 28
The compounds of Formula 30 are known or can be prepared from 4-cyanopyridine or isonicotinic acid using methods well-known in the art; see, for example, G. Marzolph et al., DE 3,537,762 (1986) for preparation of N-t-butyl pyridinecarboxamides from cyanopyridines and t-butanol and S. F. Nelsen et al, J. Org. Chem., 1990, 55, 3825 for hydrogenation of JV-methylisonicotinamide with a platinum catalyst.
Halomethyl isoxazole ketones of Formula 35 are particularly useful intermediates for preparing certain chiral compounds of Formula 1 wherein J is, for example, selected from J-29-1 through J-29-57 as depicted in Exhibit A. Halomethyl isoxazole ketones of Formula 35 can be prepared by the multi-step reaction sequences shown in Scheme 19.
Scheme 19
Figure imgf000075_0001
31a 34 35 wherein R32 is C2~Cg dialkylamino, 1-piperidinyl, 1-pyrrolidinyl or 4-morpholinyl and Q is as defined above in the Summary of the Invention.
The preparation of the racemic carboxylic acids of Formula 32 can be accomplished according to the well-known methods of basic or acidic hydrolysis of the corresponding compounds of Formula 31, preferably using a slight excess of sodium hydroxide in a water- miscible co-solvent such as methanol or tetrahydrofuran at about 25 to 45 0C. The product can be isolated by adjusting pH to about 1 to 3 and then filtration or extraction, optionally after removal of the organic solvent by evaporation. The racemic carboxylic acids of Formula 32 can be resolved by classical fractional crystallization of diastereomeric salts of suitable chiral amine bases such as cinchonine, dihydrocinchonine or a mixture thereof. A cinchonine-dihydrocinchonine mixture in about a 85:15 ratio is particularly useful, as it provides, for example, the (7?)-confϊgured carboxylic acids of Formula 33, wherein R5 is a substituted phenyl group, as the less soluble salt. Furthermore, these chiral amine bases are readily available on a commercial scale. The (i?)-configured halomethyl ketone intermediates of Formula 35 afford the more fungicidally active final products of Formula 1 after coupling with thioamides of Formula IBb according to the method of Scheme 10. The halomethyl ketones of Formula 35 can be prepared by first reacting the corresponding amides of Formula 31, either as pure enantiomers (i.e. Formula 31a) or in enantiomerically enriched or racemic mixtures, with one molar equivalent of a methylmagnesium halide (Grignard reagent) in a suitable solvent or solvent mixture such as tetrahydrofuran and toluene at about 0 to 20 0C, and the crude ketone products of Formula 34 can be isolated by quenching with aqueous acid, extraction, and concentration. Then the crude ketones of Formula 34 are halogenated with a reagent such as sulfuryl chloride to afford the chloromethyl ketones of Formula 35 wherein Y1 is Cl or molecular bromine to afford the corresponding bromomethyl ketones of Formula 35 wherein Y1 is Br. The halomethyl ketones of Formula 35 can be purified by crystallization from a solvent such as hexanes or methanol, or can be used without further purification in the condensation reaction with thioamides.
The transformation reactions depicted in Scheme 19 illustrate compounds of Formula IA corresponding to Formulae 31 through 35, which are useful as intermediates for the preparation of certain compounds of Formula 1 wherein J is any one of J-29-1 through J-29-57 depicted in Exhibit A. R32 in Formulae 31 and 31a as well as corresponding groups in Formulae 32 through 35 correspond to M in Formula IA. One skilled in the art recognizes that analogs of compounds of Formula 31 through 35 are useful for preparing other compounds of Formula 1 such as wherein J is any one of J-29-58 through J-29-60 depicted in Exhibit A. Furthermore one skilled in the art recognizes that for transformations shown in Scheme 19, R32 can be other groups besides C2~Cg dialkylamino, 1-piperidinyl, 1- pyrrolidinyl or 4-morpholinyl. For example, for the hydrolysis of a compound of Formula 31 to a compound of Formula 32 (corresponding to M in Formula IA being hydroxy), R32 can also be C1-C4 alkoxy, C^-C 2 haloalkoxy or C1-C4 alkylamino. Furthermore, the methyl (CH3) group in Formula 34 and halomethyl (Y1CF^) group in Formula 35 are homologously representative of M in Formula IA being C^-C 3 alkyl and C^-C 3 haloalkyl, respectively.
The isoxazole carboxamides of Formula 31 can be prepared by cycloaddition of the corresponding hydroxamoyl chlorides of Formula 36 with olefin derivatives of Formula 37, as shown in Scheme 20.
Scheme 20
Figure imgf000076_0001
36 37 31
In this method, all three reacting components (the compounds of Formulae 36 and 37, and the base) are contacted so as to minimize hydrolysis or dimerization of the hydroxamoyl chloride of Formula 36. In one typical procedure, the base, which can either be a tertiary amine base such as triethylamine or an inorganic base such as an alkali metal or alkaline- earth carbonate, bicarbonate or phosphate, is mixed with the olefin derivative of Formula 37, and the hydroxamoyl chloride of Formula 36 is added gradually at a temperature at which the cycloaddition proceeds at a relatively rapid rate, typically between 5 and 25 0C. Alternatively, the base can be added gradually to the other two components (the compounds of Formulae 36 and 37). This alternative procedure is preferable when the hydroxamoyl chloride of Formula 36 is substantially insoluble in the reaction medium. The solvent in the reaction medium can be water or an inert organic solvent such as toluene, hexane or even the olefin derivative used in excess. The product can be separated from the salt co-product by filtration or washing with water, followed by evaporation of the solvent. The crude product can be purified by crystallization, or the crude product can be used directly in the methods of Scheme 19. The method of Scheme 20 is demonstrated in Example 1, Step F. Also, a method analogous to Scheme 20 is demonstrated in Example 2, Step D. Compounds of Formula 31 are useful precursors to the corresponding methyl ketones of Formula 34 and halomethyl ketones of Formula 35, and are also useful for preparing the resolved enantiomers of the compounds of Formulae 34 and 35 by hydrolysis, resolution, methyl ketone synthesis and halogenation, as shown in Scheme 19.
Compounds of Formula If can be prepared by several methods. In one method, a compound of Formula 38 wherein Y8 is a leaving group such as halogen, for example iodine, is reacted with a compound of Formula 39 wherein Z3 is O, S or NH as shown in Scheme 21.
Scheme 21
Figure imgf000077_0001
38 39 lf
Y8 is F, Cl, Br, I; Z3 is O, S or NH; GG is GA, GN or Gp.
This reaction (known as the Ullmann ether synthesis when Z3 is O) is well known to one skilled in the art. The reaction is typically carried out in the presence of an inorganic base such as potassium carbonate or cesium carbonate and with a metal catalyst, for example, copper iodide. Temperatures between room temperature and 150 0C and solvents such as dimethyl sulfoxide and Λ/,Λ/-dimethylformamide are suitable for the reaction. Diaryl ethers of Formula If wherein Z3 is O can also be prepared using palladium-catalyzed Buchwald- Hartwig reaction, nucleophilic aromatic substitution or arylboronic acid diaryl ether coupling. For a recent review of these methods, including the Ullmann diaryl ether synthesis; see, for example, R. Frian and D. Kikeji, Synthesis 2006, 14, 2271-2285.
Conditions similar to those described for diaryl ethers can also be used to prepare compounds of Formula If where Z is S or NH. For a recent review of the preparation of sulfur and nitrogen analogs; see, for example, S. V. Ley and A. W Thomas, Angew. Chem., Int. Ed. Engl. 2003, 42, 5400.
A similar copper-catalyzed method can be used to prepare compounds of Formula Ig (i.e. Formula If wherein Z3 is a direct bond and GG is GGn bonded through a nitrogen ring member) wherein GGn is GA, GN or Gp bonded through a nitrogen atom ring member of GGn to Q from a heterocycle HGGn in which H is connected to a nitrogen ring member, for example, triazole, or a salt thereof (e.g., sodium triazole) as shown in Scheme 22.
Scheme 22
Figure imgf000078_0001
38 lg
Y8 is F, Cl, Br, I; GGn is a GA, GN or Gp bonded through a ring nitrogen atom to Q.
A ligand such as (li?,2i?)-Λ/,Λ/-dimethyl-l,2-cyclohexenediamine can be used to increase the solubility and reactivity of the copper catalyst. The reaction is typically carried out in a solvent such as dimethylsulfoxide or in a mixed solvent such as dimethylsulfoxide- water at temperatures between room temperature and 200 0C. For leading reference; see, for example, Andersen et al., Synlett 2005, 14, 2209-2213. This method is demonstrated in Example 1, Step H.
Compounds of Formula Ih (i.e. Formula If wherein Z3 is a direct bond, and GG is GGc bonded through a sp2 carbon atom ring member) wherein GGc is GA, GN or Gp bonded through an sp2 carbon atom ring member of GGc to Q can be prepared by a variety of general methods including the well known Suzuki reaction involving Pd-catalyzed cross-coupling as shown in Scheme 23. Scheme 23
Figure imgf000079_0001
40 41
4υ Ih
Y9 is Cl, Br, I, or OS(O)2CF3; GGc is GA, GN or Gp bonded through an sp2 ring carbon atom to Q.
The conditions for coupling an iodide or bromide of Formula 40 with a boronic acid of Formula 41 wherein the boron is attached to an sp2 ring carbon atom in GGc are similar to those described for the method of Scheme 14 above. Many catalysts are useful for this type of transformation; a typical catalyst is tetrakis(triphenylphosphine)palladium. Solvents such as tetrahydrofuran, acetonitrile, diethyl ether and dioxane are suitable. The Suzuki reaction and related coupling procedures offer many alternatives for creation of a direct bond between the Q and GGc rings. For leading references; see, for example, C. A. Zifϊcsak and D. J. Hlasta, Tetrahedron 2004, 60, 8991-9016. For a thorough review of palladium chemistry applicable to the synthesis of QGGc bonds; see, for example, J. J. Li and G. W. Gribble, editors, Palladium in Heterocyclic Chemistry: A Guide for the Synthetic Chemist, Elsevier: Oxford, UK, 2000. Many variations of catalyst type, base and reaction conditions are known in the art for this general method.
As shown in Scheme 24, methods for preparing compounds of Formula If wherein Z3 is -C≡C- include the well-known Sonogashira reaction using Pd-catalyzed cross-coupling of a halide of Formula 40 wherein Y9 is a halogen such as iodine or bromide with an alkyne of Formula 42 in the presence of a metal catalyst and a base.
Scheme 24
Figure imgf000079_0002
40 If
Y9 is Cl, Br, I, or OS(O)2CF3; Z3 is -C≡C-; GG is GA, GN or Gp. Many catalysts are useful for this type of transformation; a typical catalyst is dichlorobis(tri-o-tolylphosphine)palladium (II). Suitable solvents include tetrahydrofuran, acetonitrile and ethyl acetate. Suitable metal catalysts include, for example, copper iodide. Typical bases include, for example, triethylamine or Hunig's base. For leading references; see, for example, I. B. Campbell, Organocopper Reagents 1994, 217-235.
As shown in Scheme 25, compounds of Formula If wherein Z3 is -C≡C- can serve as starting materials to prepare compounds of Formula If wherein Z3 is -CH2CH2- by reduction with hydrogen in the presence of a catalyst, for example, palladium on carbon.
Scheme 25
Figure imgf000080_0001
l f wherein Z3 is "CiOC- If wherein Z3 is -CH2CH2-
GG is GA, GN or Gp.
The reduction is typically carried out under an atmosphere of hydrogen at pressures from atmospheric to 700 kPa, preferably about 400 kPa, in a solvent such as ethyl acetate or ethanol using methods well known to one skilled in the art. As shown in Scheme 26, preparation of the compounds of Formula If wherein Z3 is
-C=C- includes the well-known Heck reaction using Pd-catalyzed cross-coupling of a halide of Formula 44 wherein Y10 is a halogen such as iodine or bromide with an alkene of
Formula 45 in the presence of a metal catalyst and a base, such as triethylamine or sodium bicarbonate. Scheme 26
Figure imgf000080_0002
44 lf
Y10 is Cl, Br, I, N2 +, OS(O)2Ph or OS(O)2CF3; Z3 is -C=C-; GG is a GA, GN or Gp. Many catalysts are useful for this type of transformation; a typical catalyst is tris(dibenzylideneacetone)dipalladium. Suitable solvents include Λ/,iV-dimethylformamide and acetonitrile. For a review of the Heck reaction; see, for example, W. Cabri and I. Candiani, Ace. Chem Res. 1995, 28, 2-7. Compounds of Formula Ii (i.e. Formula 1 wherein Z3 is a direct bond and GG is a tetrazole ring bonded to Q through the tetrazole ring carbon atom) can be prepared from nitriles of Formula 46 as shown in Scheme 27.
Scheme 27
Figure imgf000081_0001
46
Ii
A nitrile of Formula 46 is reacted with an azide such as sodium azide or trimethylsilyl azide in a solvent such at Λ/,iV-dimethylformamide or toluene at temperatures from room temperature to 140 0C to form a compound of Formula Ii. For leading references; see, for example, B. Schmidt, D. Meid and D. Kieser, Tetrahedron 2006, 63, 492-496. Aldehydes of Formula 47 can be used to prepare olefins of Formula 37a using the well-known Wittig (this method is demonstrated in Example 1 , Step E) or Tebbe olefmation reactions as shown in Scheme 28.
Scheme 28
(Ph)3 ©PCH3 Br Θ OHC/(KZ3GG baS£ Q.
^Z-3G1
47 37a GG is GA, GN or Gp.
In the Wittig reaction, a methyltriphenylphosphonium halide such as methyltriphenylphosphonium bromide is reacted with a base such at t-BuOK. Tetrahydrofuran is a suitable solvent for this reaction. For additional leading references for the Wittig reaction; see, for example, A. Maercker Org. React. 1965, 14, 270-490; and for the Tebbe reaction; see, for example, H. Pommer, Angew. Chem. Int. Ed. Engl. 1977, 16, 423-429 and S. H. Pine, Org. React. 1993, 43 1-91. This method is demonstrated in Example 2, Step C. The olefins of Formula 37a are starting materials for the method shown in Scheme 20.
Reactions similar to those described in Scheme 21 can also be carried out on intermediates before coupling, for example, aldehydes of Formula 48 in Scheme 29 are useful starting materials to prepare the aldehydes of Formula 47.
Scheme 29
OHC/Q^Y1 1 + HZ3G0 ► OHC/Q^Z3GG
48 39 47
Y11 is F, Cl, Br, I; Z3 is O, S or NH; GG is GA, GN or Gp. The method of Scheme 29 using reagents and reaction conditions similar to those described for Scheme 21 provides, for example, the corresponding diaryl ether when Z3 is oxygen, (e.g., 2-phenoxybenzaldehyde is obtained starting with 2-iodobenzaldehyde and phenol). Several starting aldehydes of Formula 48 are commercially available, for example, the ortho, meta and para isomers of fluorobenzaldehyde, chlorobenzaldehyde, bromobenzaldehyde and iodobenzaldehyde.
Similarly, methods analogous to those described in Schemes 22-27 can also be used to prepare aldehydes of Formula 47; see, for example, W. Mansawat, et. al. Tetrahedron Letters 2007, 48(24), 4235-4238 for 2-(phenylthio)benzaldehyde; A. Cwik, Z. Hell, F. Figueras, Advanced Synthesis & Catalysis 2006, 348(4/5), 523-530 for 2-(2-phenylethenyl)benzaldehyde; T. Sakamoto, Y. Kondo, N. Miura, K. Hayashi, H. Yamanaka, Heterocycles 1986, 24(8), 2311-14 for 2-(phenylethynyl)benzaldehyde; and J. Rosevear, J. F. K. Wilshire, John F. K. Australian Journal of Chemistry 1991, 44(8), 1097-114 for 2-(l/f-l,2,4-triazol-l-yl)benzaldehyde.
Several aldehydes of Formula 47 are also commercially available including 2-phenylbenzaldehyde, 2-phenoxybenzaldehyde 2-(furan-2-yl)benzaldehyde, 2-(thien-2- yl)benzaldehyde, 2-(imidazol-l-yl)benzaldehyde and 2-(thiazol-2-yl)benzaldehyde.
It is recognized that some reagents and reaction conditions described above for preparing compounds of Formulae 1 and IA may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formulae 1 and IA. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formulae 1 and IA. One skilled in the art will also recognize that compounds of Formulae 1 and IA and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.
Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Examples illustrate a procedure for each step in an overall synthetic transformation, and the starting material for each step may not have necessarily been prepared by a particular preparative run whose procedure is described in other Examples or Steps. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. 1H NMR spectra are reported in ppm downfϊeld from tetramethylsilane; "s" means singlet, "d" means doublet, "t" means triplet, "m" means multiplet, "q" means quartet, "dd" means doublet of doublet, "br s" means broad singlet, "br d" means broad doublet, "br t" means broad triplet, "br m" means broad multiplet.
EXAMPLE 1 Preparation of l-[4-[4-[4,5-dihydro-5-[3-(l/f-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl]-2- thiazolyl]-l -piperidinyl]-2-[5-methyl-3-(trifluoromethyl)- lH-pyrazol- 1 -yljethanone (Compound 1)
Step A: Preparation of l-(2-chloroacetyl)-4-piperidinecarbonitrile
A mixture of 4-piperidinecarbonitrile (200 g, 1.80 mol) and 40 % aqueous potassium carbonate solution (342 g, 0.99 mol) in dichloromethane (1 L) was cooled to -10 0C, and a solution of chloroacetyl chloride (210 g, 1.86 mol) in dichloromethane (300 mL) was added over about 75 minutes while maintaining the reaction mixture at -10 to 0 0C. After the addition was complete, the reaction mixture was separated, the upper aqueous phase was extracted with dichloromethane (2 x 300 mL), and the combined organic phases were concentrated under reduced pressure to give 312 g of the title compound as a liquid which slowly crystallized on standing. This compound was of sufficient purity to use in subsequent reactions.
1H NMR (CDCl3) δ 1.8-2.1 (m, 4H), 2.95 (m, IH), 3.5-3.8 (m, 4H), 4.08 (q, 2H). Step Al : Alternative preparation of 1 -(2-chloroacetyl)-4-piperidinecarbonitrile
A solution of Λ/-(l,l-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to -5 0C, and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5 0C. Then 20 % aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction mixture between 0 and 5 0C. The reaction mixture was stirred for an additional 30 minutes at 0 0C, and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50 0C to give 185.5 g of l-(2-chloroacetyl)-N-(l,l-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5 0C. 1H NMR (CDCl3) δ 1.35 (s, 9H), 1.6-2.0 (m, 4H), 2.25 (m, IH), 2.8 (t, IH), 3.2 (t, IH), 3.9 (d, IH), 4.07 (s, 2H), 4.5 (d, IH), 5.3 (br s, IH).
To a solution of l-(2-chloroacetyl)-Λ/-(l,l-dimethylethyl)-4-piperidinecarboxamide (26.1 g, 0.10 mol) in Λf,Λ/-dimethylformamide (35 mL) was added phosphorus oxy chloride (18.8 g, 0.123 mol) dropwise over 30 minutes while allowing the temperature of the reaction mixture to rise to 37 0C. The reaction mixture was heated at 55 0C for 1 h and then was slowly added to water (about 150 g) cooled with ice to maintain a temperature of about 10 0C. The pH of the reaction mixture was adjusted to 5.5 with 50 % NaOH aqueous solution. The mixture was extracted with dichloromethane (4 x 100 mL), and the combined extract was concentrated under reduced pressure to give 18.1 g of the title compound as a solid. This compound was of sufficient purity to use in subsequent reactions.
Step B: Preparation of l-[2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]acetyl]-4- piperidinecarbonitrile
A solution of 3-methyl-5-trifluoromethylpyrazole (9.3 g, 62 mmol) and 45 % aqueous potassium hydroxide solution (7.79 g, 62 mmol) in Λ/,Λ/-dimethylformamide (25 mL) was cooled to 5 0C, and l-(2-chloroacetyl)-4-piperidinecarbonitrile (i.e. the product of Example 1, Step A or Al) (11.2 g, 60 mmol) was added. The reaction mixture was stirred for 8 h at 5- 10 0C, then diluted with water (100 mL), and filtered. The filter cake was washed with water and dried at 50 0C in a vacuum-oven to give 15 g of the title compound as a solid containing 3 % of its regioisomer, i.e. l-[2-[3-methyl-5-(trifluoromethyl)-lH-pyrazol- 1 -yl]acetyl]-4-piperidinecarbonitrile.
1H NMR (CDCl3) δ 1.88 (m, 4H), 2.32 (s, 3H), 2.95 (m, IH), 3.7 (m, 4H), 5.0 (q, 2H), 6.34 (s, IH). Step C: Preparation of l-[2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]acetyl]-4- piperidinecarbothioamide
Hydrogen sulfide gas was passed into a solution of l-[2-[5-methyl- 3-(trifluoromethyl)-lH-pyrazol-l-yl]acetyl]-4-piperidinecarbonitrile (i.e. the product of Example 1, Step B) (9.0 g, 30 mmol) and diethanolamine (3.15 g, 30 mmol) in Λ/,Λ/-dimethylformamide (15 mL) at 50 0C in a flask equipped with dry-ice condenser. The hydrogen sulfide feed was stopped when the reaction mixture became saturated with hydrogen sulfide, as indicated by condensation on the cold-finger. The reaction mixture was stirred for an additional 30 minutes at 50 0C. Then excess hydrogen sulfide gas was sparged into the scrubber by a subsurface nitrogen flow, and water (70 mL) was gradually added. The reaction mixture was cooled to 5 0C, filtered, and washed with water (2 x 30 mL). The filter cake was dried at 50 0C in a vacuum-oven to give 8.0 g of the title compound as a solid, melting at 185-186 0C.
1H NMR (CDCl3) δ 1.7 (m, 2H), 2.0 (m, 2H), 2.29 (s, 3H), 2.65 (t, IH), 3.0 (m, IH), 3.2 (t, IH), 4.0 (d, IH), 4.6 (d, IH), 4.96 (d, IH), 5.4 (d, IH), 6.35 (s, IH), 7.4 (br s, IH), 7.5 (br s, IH).
Step D: Preparation of 3-chloro-iV-hydroxy-2-oxo-propanimidoyl chloride
To a solution of 1,3-dichloroacetone (100 g, 0.79 mol) in 2 M solution of hydrogen chloride in diethyl ether (400 mL) at 15 0C was added t-butyl nitrite (55 g, 0.534 mol) over 10 minutes. The reaction progress was monitored by 1H NMR to obtain ~85 % conversion with no more than 3 % of the bis-nitrosation side product. The reaction mixture was concentrated under reduced pressure to leave a semi-solid, which was then thoroughly rinsed with chlorobutane. The resulting solid was collected under filtration to give a 77 g of the title compound as a white solid. The filtrate was further concentrated under reduced pressure to give a semi-solid residue, which was rinsed with additional chlorobutane. The resulting solid was collected under filtration to give additional 15 g of the title compound as a white solid.
1H NMR (DMSO-J6) δ 4.96 (s, 2H), 13.76 (s, IH). Step E: Preparation of l-ethenyl-3-iodobenzene A mixture of 3-iodobenzaldehyde (2.0 g, 8.6 mmol) and methyltriphenylphosphonium bromide (4.62 g, 12.9 mmol) in tetrahydrofuran (50 mL) was cooled to 0 0C, and a solution of potassium te/t-butoxide (1.45 g, 12.9 mmol) in tetrahydrofuran (20 mL) was added dropwise at 0 0C over 1 h. The reaction mixture was allowed to warm to room temperature and stirred for 12 h. The reaction mixture was filtered through Celite® diatomaceous filter aid with hexane, treated with DARCO® activated charcoal, and filtered a second time. The resulting oil was purified by column chromatography on silica gel using 100 % hexane to 10 % ethyl acetate in hexanes as eluant to give 1.82 g of the title compound as a yellow oil. 1H NMR (CDCl3) δ 5.28 (d, IH), 5.74 (d, IH), 6.60 (dd, IH), 7.05 (t, IH), 7.35 (d, IH),
7.56-7.59 (m, IH), 7.74-7.77 (m, IH).
Step F: Preparation of 2-chloro-l-[4,5-dihydro-5-(3-iodophenyl)-3- isoxazolyl] ethanone To a solution of l-ethenyl-3-iodobenzene (i.e. the product of Example 1, Step E)
(1.82 g, 7.9 mmol) and 3-chloro-Λ/-hydroxy-2-oxo-propanimidoyl chloride (i.e. the product of Example 1, Step D) (1.23 g, 7.9 mmol) in acetonitrile (32 mL) was added sodium bicarbonate (1.99 g, 23.7 mmol), and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated, taken up in water and extracted with dichloromethane, filtered through a ChemElute® diatomaceous earth-based liquid- liquid exchange cartridge, and concentrated to give 2.38 g of the title compound as a yellow oil. 1H NMR (CDCl3) δ 3.17 (dd, IH), 3.62 (dd, IH), 4.72 (s, 2H), 5.74 (dd, IH), 7.13 (t, IH), 7.24-7.28 (m, IH), 7.63-7.72 (m, 2H). Step G: Preparation of l-[4-[4-[4,5-dihydro-5-(3-iodophenyl)-3-isoxazolyl]-2- thiazolyl]- 1 -piperidinyl]-2-[5-methyl-3-(trifluoromethyl)- lH-pyrazol-1 - yl] ethanone
To a mixture of 2-chloro-l-[4,5-dihydro-5-(3-iodophenyl)-3-isoxazolyl]ethanone (i.e. the product of Example 1, Step F) (2.38 g, 7.8 mmol) and tetrabutylammonium bromide (238 mg, 0.74 mmol) in acetone (50 mL) was added l-[2-[5-methyl-3-(trifluoromethyl)-lH- pyrazol-1-yl] acetyl] -4-piperidinecarbothioamide (i.e. the product of Example 1, Step C) (2.56 g, 7.7 mmol). The reaction mixture was refluxed for 12 h. After cooling the reaction mixture was concentrated and then taken up in water. The pΗ was adjusted to 8 with saturated sodium bicarbonate, 1.5 mL Clorox® sodium hypochlorite bleach was added, and the mixture was extracted 2 times with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate, treated with DARCO®, filtered through Celite® diatomaceous filter aid, and concentrated. The resulting oil was purified by column chromatography on silica gel using 20 % ethyl acetate in hexanes to 50 % acetone in hexanes as eluant to give 2.76 g of the title compound as a light yellow solid foam. 1H NMR (CDCl3) δ 1.70-1.85 (m, 2H), 2.20 (br t, 2H), 2.32 (s, 3H), 2.90 (t, IH), 3.25-3.45 (m, 4H), 3.85 (dd, IH), 4.05 (d, IH), 4.58 (d, IH), 4.95-5.05 (m, 2H), 5.70 (dd, IH), 7.11 (t, IH), 7.35 (d, IH), 7.60-7.70 (m, 2H) 7.75 (s, IH).
Step H: Preparation of l-[4-[4-[4,5-dihydro-5-[3-(lH-l,2,4-triazol-l-yl)phenyl]-3- isoxazolyl] -2 -thiazolyl] - 1 -piperidinyl]-2- [5 -methyl-3 -(trifluoromethyl)- IH- pyrazol- 1 -yl]ethanone Sodium 1,2,4-triazole (63.0 mg, 0.69 mmol) was added to a mixture of l-[4-[4-[4,5- dihydro-5-(3-iodophenyl)-3-isoxazolyl]-2-thiazolyl]-l-piperidinyl]-2-[5-methyl-3- (trifluoromethyl)-lH-pyrazol-l-yl]ethanone (i.e. the product of Example 1, Step G), (217 mg, 0.34 mmol), (+)-sodium L-ascorbate (3.4 mg, 0.017 mmol), copper iodide (6.6 mg, 0.034 mmol) and (li?,2i?)-Λ/,N-dimethyl-l,2-cyclohexenediamine (7.3 mg, 0.051 mmol) in 2 mL of an 80:20 solution of dimethylsulfoxide and water. The reaction mixture was heated at 60 0C for 20 h and then at 100 0C for 24 h. After cooling, the reaction mixture was diluted with water and extracted 2 times with ethyl acetate. The combined organic extracts were washed 5 times with water, then brine, and dried over magnesium sulfate, filtered and concentrated. The resulting oil was purified by column chromatography on silica gel using 75 % ethyl acetate in hexanes as eluant to give 49 mg of the title compound, a compound of the present invention, as a pale yellow solid foam, melting at 83-85 0C. 1H NMR (CDCl3) δ 1.68-1.89 (m, 2H), 2.19 (br t, 2H), 2.32 (s, 3H), 2.83-2.94 (m, IH), 3.25-3.36 (m, 2H), 3.46 (dd, IH), 3.94 (dd, IH), 4.05 (d IH), 4.57 (d, IH), 4.91-5.05 (m, 2H), 5.84 (dd, IH), 6.33 (s, IH), 7.42-7.46 (m, IH), 7.53 (t, IH), 7.62-7.67 (m, 2H), 7.73-7.76 (m, IH), 8.10 (s, IH), 8.59 (s, IH).
EXAMPLE 2 Preparation of 4-[4-(5-[ 1 , 1 '-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-N-(2,5- dimethylphenyl)-l-piperidinecarboxamide (Compound 17)
Step A: Preparation of 4-cyano-Λ/-(2,5-dimethylphenyl)-l-piperidinecarboxamide
A solution of 4-cyanopiperidine (11.O g, 100 mmol) in diethyl ether (35O mL) was cooled to 0 0C with an ice-water bath. A solution of 2-isocyanato-l,4-dimethylbenzene (14.7 g, 100 mmol) in diethyl ether (5O mL) was added into the reaction mixture over 30 minutes to give a thick precipitate. The reaction mixture was warmed to room temperature, and the resulting solids were filtered, washed with diethyl ether and air-dried to give 25.3 g of the title compound as a white powder, melting at 187-190 0C. 1H NMR (CDCl3): δ 1.95 (m, 4H), 2.19 (s, 3H), 2.30 (s, 3H), 2.90 (m, IH), 3.45 (m, 2H), 3.70 (m, 2H), 6.10 (br s, IH), 6.85 (m, IH), 7.04 (m, IH), 7.37 (m, IH).
Step B: Preparation of 4-(aminothioxomethyl)-Λ/-(2,5-dimethylphenyl)-l-piperidine- carboxamide
A mixture of 4-cyano-Λ/-(2,5-dimethylphenyl)-l-piperidinecarboxamide (i.e. the product of Example 2, Step A) (12.75 g, 49.6 mmol), sodium hydrosulfide hydrate (11.1 g, 150 mmol) and diethylamine hydrochloride (10.9 g, 100 mmol) in Λ/,Λ/-dimethylformamide (50 mL) was stirred at room temperature for 3 days. The resulting thick, green suspension was added dropwise into ice water (600 mL). The resulting solid was filtered, washed with water and air-dried to give 12.5 g of the title compound as a tan solid decomposing at 155-156 0C. 1H NMR (DMSO-J6): δ 1.67 (m, 4H), 2.10 (s, 3H), 2.23 (s, 3H), 2.75 (m, 3H), 4.15 (m, 2H), 6.85 (m, IH), 7.0 (m, IH), 7.05 (m, IH), 7.95 (br s, IH), 9.15 (br s, IH), 9.22 (br s, IH). Step C : Preparation of 2-ethenyl- 1 , 1 '-biphenyl
A mixture of [l,l'-biphenyl]-2-carboxaldehyde (2.0O g, 11.0 mmol) and methyltriphenylphosphonium bromide (5.88 g, 16.5 mmol) in tetrahydrofuran (40 mL) was cooled to 0 0C, and a solution of potassium te/t-butoxide (1.85 g, 16.5 mmol) in tetrahydrofuran (20 mL) was added dropwise at 0 0C over 1 h. The reaction mixture was allowed to warm to room temperature and stirred for 12 h, then filtered through Celite® diatomaceous filter aid with hexane and concentrated under reduced pressure. The resulting oil was treated with hexanes, filtered again, concentrated under reduced pressure and purified by column chromatography on silica gel using 100% hexane to 10% ethyl acetate in hexanes as eluant to give 1.69 g of the title compound as a colorless oil.
1H NMR (CDCl3) 5 5.18 (dd, IH), 5.70 (dd, IH), 6.71 (dd, IH), 7.27-7.44 (m, 8H),
7.62-7.66 (m, IH).
Step D: Preparation of l-(5-[l,l'-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2- chloroethanone To a solution of 2-ethenyl- l,l'-biphenyl (i.e. the product of Example 2, Step C) (750 mg, 4.17 mmol) and 3-chloro-Λ/-hydroxy-2-oxo-propanimidoyl chloride (i.e. the product of Example 1, Step D) (646 mg, 4.17 mmol) in acetonitrile (13 mL) was added sodium bicarbonate (1.05 g, 12.5 mmol), and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure. The resultant residue was taken up in ethyl acetate, 2 mL of water added and eluted with ethyl acetate through a ChemElute® diatomaceous earth-based liquid-liquid exchange cartridge and concentrated to give 630 mg of the title compound as a colorless oil.
1H NMR (CDCl3) δ 3.14 (dd, IH), 3.37 (dd, IH), 4.63-4.73 (m, 2H), 5.79 (dd, IH), 7.26- 7.46 (m, 9H). Step E: Preparation of 4-[4-(5-[l, l'-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2- thiazolyl]-Λ/-(2,5-dimethylphenyl)- 1 -piperidinecarboxamide
To a mixture of l-(5-[l,l'-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2-chloroethanone (i.e. the product of Example 2, Step D) (200 mg, 0.67 mmol) and 4-(aminothioxomethyl)-JV- (2,5-dimethylphenyl)-l-piperidine-carboxamide (i.e. the product of Example 2, Step B) (195 mg, 0.67 mmol) in acetonitrile (5 mL) was added sodium bromide (103 mg, 1.00 mmol). The reaction mixture was refluxed overnight and then concentrated under reduced pressure. The crude residue was added to water and sodium bicarbonate (56 mg, 0.67 mmol) and then extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The resulting oil was purified by column chromatography on silica gel using 20% ethyl acetate in hexanes to 100% ethyl acetate as eluant to give 139 mg of the title compound, a compound of the present invention, as a solid white foam melting at 77-79 0C. 1H NMR (CDCl3) δ 1.77-1.89 (m, 2H), 2.12-2.21 (m, 5H), 2.29 (s, 3H), 3.00-3.09 (m, 2H), 3.20-3.29 (m, IH), 3.36 (dd, IH), 3.60 (dd IH), 4.11-4.18 (m, 2H), 5.74 (dd, IH), 6.24 (br s, IH), 6.82 (d IH), 7.03 (d, IH), 7.24-7.47 (m, 9H), 7.57 (s. IH), 7.60 (dd, IH).
By the procedures described herein, together with methods known in the art, the following compounds of Tables 1 to 15 can be prepared. The following abbreviations are used in the Tables which follow: t means tertiary, s means secondary, n means normal, i means iso, c means cyclo, Ac means acetyl, Me means methyl, Et means ethyl, Pr means propyl (i.e. n-propyl), z-Pr means isopropyl, c-Pr means cyclopropyl, Bu means butyl, Pen means pentyl, Hex means hexyl, Am means amyl, CN means cyano, SO2 means sulfonyl (S(=O)2). A dash (-) indicates no substituents.
The invention includes but is not limited to the following exemplary species.
Figure imgf000089_0001
Figure imgf000090_0001
1 -yl
Figure imgf000091_0001
Rl Rl
2 -methyl- 5 - (trimethylsilyl)phenyl 1 -methyl-4-imidazolyl
3,5-dimethyl-2-thienyl 5-(trifluoromethyl)-3-(l,2,4-oxadiazolyl)
3,5-dichloro-2-thienyl 5-(trifluoromethyl)-3 -( 1 ,2,4-thiadiazolyl)
3 , 5 -dimethyl-2 - furyl 2-bromo- 1 -(1 ,3 ,4-triazolyl)
1 -methyl-2-pyrrolyl 5-(trifluoromethyl)-3 -( 1 ,2,4-triazolyl)
4-methyl-2-(trifluoromethyl)-5-thiazolyl 2-bromo- 1 -imidazolyl
4- (trifluoromethyl) -2 -thiazolyl 3 ,6-dimethyl-2-pyridyl
4-( trifluoromethyl)-2-oxazolyl 2,5-dimethyl-3 -pyridyl
4-methyl-2-(trifluoromethyl)-5-oxazolyl 2,5-dimethyl-4-pyridyl
4-bromo-5-isothiazolyl 3 ,6-dichloro-2 -pyridyl
4-bromo-5-isoxazolyl 2,5-dichloro-3-pyridyl
1 -methyl- 5 -pyrazolyl 2,5-dichloro-4-pyridyl
1 -methyl-5-imidazolyl 4-bromo-3 -pyridazinyl l-methyl-4-(trifluoromethyl)-2-imidazolyl 4- (trifluoromethyl) -2 -pyrimidinyl
4-methyl-3 -( 1 ,3 ,4-triazolyl) 3 ,6-dimethyl-2-pyrazinyl
2-methyl-3 -( 1 ,2,4-triazolyl) 2,5-dimethyl-4-pyrimidinyl
5-(trifluoromethyl)-2-(l,3,4-thiadiazolyl) 4-methoxy-5-pyrimidinyl
5-(trifluoromethyl)-2-( 1 ,3 ,4-oxadiazolyl) 3 ,6-dimethyl-4-pyridazinyl
3-(trifluoromethyl)-5-(l,2,4-thiadiazolyl) 5-(trifluoromethyl)-3 -( 1 ,2,4-triazinyl)
3-(trifluoromethyl)-5-(l,2,4-oxadiazolyl) 5-methoxy-6-(l,2,4-triazinyl)
3 -(trifluoromethyl)- 1 -( 1 ,2,4-triazolyl) 4-(trifluoromethyl)-2-( 1 ,3 ,5-triazinyl)
2,5-dimethyl- 1 -pyrrolyl 3,6-dimethyl-5-(l,2,4-triazinyl)
1 -methyl- 3 - (trifluoromethyl)pyrazol- 5 -yl l-methyl-4-(trifluoromethyl)imidazol-2-yl
3-bromo-5-(trifluoromethyl)pyrazol-l-yl 3,5-bis-(trifluoromethyl)pyrazol-l-yl
3-iodo-5-(trifluoromethyl)pyrazol- 1 -yl 3-(2,2,2-trifluoroethyl)-5-(trifluoromethyl)pyrazol-l-yl
3-ethyl-5-(trifluoromethyl)-pyrazol-l-yl 3-(pentafluoroethyl)-5-(trifluoromethyl)pyrazol-l-yl
3 -propyl-5-(trifluoromethyl)pyrazol- 1 -yl 3 - cy ano- 5 - (trifluoromethyl)pyrazol- 1 -yl-isopropyl-5-(trifluoromethyl)pyrazol-l-yl 3-nitro-5-(trifluoromethyl)pyrazol-l-yl
3-methyl-5-(trifluoromethyl)-pyrazol-l-yl 3 - chloro- 5 - (trifluoromethyl) -pyrazol- 1 -yl -methoxy- 5 - (trifluoromethyl) -pyrazol- 1 -yl 3,5-bis-(trichloromethyl)pyrazol-l-yl
5 -difluoromethoxy-3 -methylpyrazol- 1 -yl 3 -difluoromethoxy-5-methylpyrazol- 1 -yl
5-difluoromethoxy-3 -chloropyrazol- 1 -yl 3-difluoromethoxy-5-chloropyrazol-l-yl
3 ,5 -dibromopyrazol- 1 -yl 3 -difluoromethoxy-5-bromopyrazol- 1 -yl
5-difluoromethoxy-3 -iodopyrazol- 1 -yl 3 -difluoromethoxy-5-iodopyrazol- 1 -yl
5-difluoromethoxy-3-ethylpyrazol- 1 -yl 3-difluoromethoxy-5-ethylpyrazol-l-yl
5-difluoromethoxy-3-propylpyrazol-l-yl 3-difluoromethoxy-5-(trifluoromethyl)pyrazol-l-yl-difluoromethoxy-3-isopropylpyrazol-l-yl 3-difluoromethoxy-5-(2,2,2-trifluoroethyl)pyrazol-l-yl Rl Rl
5-difluoromethoxy-3 -(trifluoromethyl)pyrazol- 1 -yl 3-difluoromethoxy-5-(pentafluoroethyl)pyrazol-l-yl
5-difluoromethoxy-3-(2,2,2-trifluoroethyl)pyrazol-l-yl S-difluoromethoxy-S-cyanopyrazol-l-yl
5-difluoromethoxy-3-(pentafluoroethyl)pyrazol-l-yl 3-difluoromethoxy-5-nitropyrazol-l-yl
S-difluoromethoxy-3-cyanopyrazol-l-yl 3,5-bis-(difluoromethoxy)pyrazol-l-yl
5-difluoromethoxy-3-nitropyrazol-l-yl 5-carbomethoxy-3-(trifluoromethyl)pyrazol-l-yl
3 - c arbomethoxy- 5 - (trifluoromethyl)pyrazol- 1 -yl 3 ,5 -dimethoxypyrazol- 1 -yl
5 -methoxy-3 -methylpyrazol- 1 -yl 5 -ethoxy-3 -methylpyrazol- 1 -yl
5-methoxy-3 -bromopyrazol- 1 -yl 5 -ethoxy- 3 -bromopyrazol- 1 -yl
5-methoxy-3 -iodopyrazol- 1 -yl 5-ethoxy-3 -iodopyrazol- 1 -yl
5 -methoxy- 3 - ethylpyrazol- 1 -yl 5 -ethoxy- 3 -ethylpyrazol- 1 -yl
5 -methoxy-3 -propylpyrazol- 1 -yl 5 -ethoxy- 3 -propylpyrazol- 1 -yl
5 -methoxy-3 -isopropylpyrazol- 1 -yl 5-ethoxy-3-isopropylpyrazol-l-yl
5-methoxy-3 -(trifluoromethyl)pyrazol- 1 -yl 5 - ethoxy- 3 - (trifluoromethyl)pyrazol- 1 -yl
5-methoxy-3-(2,2,2-trifluoroethyl)pyrazol- 1 -yl 5-ethoxy-3-(2,2,2-trifluoroethyl)pyrazol-l-yl
5-methoxy-3-(pentafluoroethyl)pyrazol-l-yl 5-ethoxy-3-(pentafluoroethyl)pyrazol-l-yl
S-methoxy-S-cyanopyrazol- 1 -yl 5-ethoxy-3 -cyanopyrazol- 1 -yl
5-methoxy-3 -nitropyrazol- 1 -yl 5 -ethoxy- 3 -nitropyrazol- 1 -yl
TABLE 2
Figure imgf000093_0001
A is NH; W is O.
Rl Rl
2 -methoxyphenyl 3 ,5 -dimethylpyrazol- 1 -yl
2,5-dichlorophenyl 3 ,5 -dichloropyrazol- 1 -yl
5-bromo-2-chlorophenyl 3 ,5 -dibromopyrazol- 1 -yl
2 - chloro- 5 -methylphenyl 5 -methyl- 3 - (trifluoromethyl)pyrazol- 1 -yl
2-chloro-5-(trifluoromethyl)phenyl 5 - chloro- 3 - (trifluoromethyl)pyrazol- 1 -yl
2,5-dibromophenyl 5-bromo-3-(trifluoromethyl)pyrazol-l-yl
2 -bromo- 5 -methylphenyl 5-ethyl-3-(trifluoromethyl)pyrazol-l-yl
2 -bromo- 5 - (trifluoromethyl)phenyl 3,5-bis-(trifluoromethyl)pyrazol-l-yl
5-chloro-2-methylphenyl 3 -methyl- 5 - (trifluoromethyl)pyrazol- 1 -yl Ri Rl
5-bromo-2-methylphenyl 3-chloro-5-(trifluoromethyl)pyrazol-l-yl
2,5-dimethylphenyl 3-bromo-5-(trifluoromethyl)pyrazol-l-yl
5 - ethyl-2 -methylphenyl 5-methoxy-3-(trifluoromethyl)pyrazol-l-yl
2 -methyl- 5 - (trifluoromethyl)phenyl 5-difluoromethoxy-3-(trifluoromethyl)pyrazol-l-yl
5-bromo-2-methoxyphenyl 3 ,5 -dichlorotriazol- 1 -yl
2 -methoxy- 5 -methylphenyl 3 ,5 -dibromotriazol- 1 -yl
2-methoxy-5-(trifluoromethyl)phenyl
A is CH2; W is S Rl Rl
3 -ethyl-5-methylpyrazol- 1 -yl 5-bromo-3-(trifluoromethyl)pyrazol-l-yl 5-methyl-3 -(trifluoromethyl)pyrazol- 1 -yl 3 ,5-diethylpyrazol- 1 -yl
3 ,5 -dichloropyrazol- 1 -yl 5-ethyl-3-(trifluoromethyl)pyrazol-l-yl
5-chloro-3-(trifluoromethyl)pyrazol-l-yl 3 ,5 -dichlorotriazol- 1 -yl
3,5-bis-(trifluoromethyl)pyrazol-l-yl 3 ,5 -dibromotriazol- 1 -yl
3 ,5-dimethylpyrazol- 1 -yl 3-methyl-5-(trifluoromethyl)pyrazol-l-yl
3 ,5 -dibromopyrazol- 1 -yl
A is NH; W is S Rl R
2 -methoxyphenyl 5-bromo-2-methylphenyl
2,5-dichlorophenyl 2 , 5 -dimethylphenyl
5-bromo-2-chlorophenyl 5-ethyl-2-methylphenyl
2 - chloro- 5 -methylphenyl 2-methyl-5-(trifluoromethyl)phenyl
2-chloro-5-(trifluoromethyl)phenyl 5-bromo-2-methoxyphenyl
2,5-dibromophenyl 2-methoxy-5-methylphenyl
2 -bromo- 5 -methylphenyl 2 -methoxy- 5 - (trifluoromethyl)phenyl
2 -bromo- 5 - (trifluoromethyl)phenyl 5-methyl-3-(trifluoromethyl)pyrazol-l-yl
5-chloro-2-methylphenyl RI is 5-methyl-3-(trifluoromethyl)pyrazol-l-yl; W is O.
Figure imgf000094_0001
TABLE 3*
Figure imgf000095_0001
* y- in the above Markush structure represents the portion of the J groups defined in Exhibit 3 of the Embodiments for J-I through J-82 excluding the substituent (Z2Q)8. Furthermore fi is identified in the following table by reference to J-I through J-82 whereby J2 is understood to be the portion of J-I through J-82 not including the substituent (Z2Q)8 shown in Exhibit 3. G^ is defined in Exhibit 5.
Figure imgf000095_0002
J2 J-orientation** J2 J-orientation** J-oπentation**
J-5 2/4 J-28 5/3 J-51 2/6
J-5 2/5 J-29 3/5 J-52 2/6
J-5 4/2 J-29 5/3 J-53 2/3
J-5 5/2 J-30 3/5 J-54 2/3
J-5 3/5 J-30 5/3 J-55 2/3
J-5 5/3 J-30 1/3 J-56 2/3
J-6 2/4 J-30 3/1 J-57 2/4
J-6 2/5 J-30 1/4 J-58 3/4
J-6 4/2 J-30 4/1 J-59 2/4
J-6 5/2 J-31 1/3 J-60 2/4
J-6 3/5 J-31 1/4 J-61 2/4
J-6 5/3 J-31 2/4 J-62 2/4
J-6 1/3 J-31 2/5 J-63 3/4
J-6 3/1 J-31 3/5 J-64 2/3
J-7 5/3 J-31 3/1 J-65 3/4
J-7 3/5 J-31 4/1 J-66 6/7
J-8 5/3 J-31 4/2 J-67 2/3
J-8 3/5 J-31 5/2 J-68 2/3
J-9 5/3 J-32 2/4 J-69 1/3
J-9 3/5 J-32 2/5 J-69 1/4
J-9 1/4 J-32 3/5 J-70 1/3
J-9 4/1 J-32 5/3 J-71 2/4
J-IO 3/5 J-32 5/2 J-71 4/2
J-IO 5/3 J-32 4/2 J-72 2/4
J-Il 3/5 J-33 2/4 J-72 4/2
J-Il 5/3 J-33 2/5 J-73 2/4
J-12 3/5 J-33 3/5 J-73 4/2
J-12 5/3 J-33 5/3 J-73 1/3
J-12 1/3 J-33 5/2 J-73 1/4
J-12 3/1 J-33 4/2 J-73 4/1
J-13 1/4 J-34 1/3 J-74 2/4
J-13 4/1 J-34 1/4 J-74 2/5
J-14 3/5 J-34 3/5 J-74 4/2
J-14 5/3 J-34 3/1 J-74 5/2
J-15 2/5 J-34 4/1 J-74 3/5
J-16 2/5 J-35 1/4 J-74 5/3
J-17 2/4 J-35 4/1 J-75 3/5 J2 J-orientation**
J-75 5/3 J-75 2/4 J-75 2/5 J-75 3/5 J-75 5/3 J-76 3/6 J-76 6/3 J-77 3/5 J-77 5/3 J-78 1/3 J-79 1/3 J-79 3/1 J-80 1/3 J-80 3/1 J-81 3/5 J-81 5/3 J-82 3/5 J-82 3/6 J-82 5/3 J-82 6/3
Figure imgf000097_0001
Figure imgf000097_0002
J2 J-orientation** J2 J-orientation** Jz J-oπentation**
J-3 4/1 J-27 2/4 J-47 5/2
J-4 2/4 J-27 2/5 J-48 3/5
J-4 2/5 J-27 3/5 J-49 2/4
J-4 4/2 J-27 4/2 J-49 2/5
J-4 5/2 J-27 5/2 J-49 4/2
J-4 3/5 J-27 5/3 J-49 5/2
J-4 5/3 J-28 3/5 J-50 2/6
J-5 2/4 J-28 5/3 J-51 2/6
J-5 2/5 J-29 3/5 J-52 2/6
J-5 4/2 J-29 5/3 J-53 2/3
J-5 5/2 J-30 3/5 J-54 2/3
J-5 3/5 J-30 5/3 J-55 2/3
J-5 5/3 J-30 1/3 J-56 2/3
J-6 2/4 J-30 3/1 J-57 2/4
J-6 2/5 J-30 1/4 J-58 3/4
J-6 4/2 J-30 4/1 J-59 2/4
J-6 5/2 J-31 1/3 J-60 2/4
J-6 3/5 J-31 1/4 J-61 2/4
J-6 5/3 J-31 2/4 J-62 2/4
J-6 1/3 J-31 2/5 J-63 3/4
J-6 3/1 J-31 3/5 J-64 2/3
J-7 5/3 J-31 3/1 J-65 3/4
J-7 3/5 J-31 4/1 J-66 6/7
J-8 5/3 J-31 4/2 J-67 2/3
J-8 3/5 J-31 5/2 J-68 2/3
J-9 5/3 J-32 2/4 J-69 1/3
J-9 3/5 J-32 2/5 J-69 1/4
J-9 1/4 J-32 3/5 J-70 1/3
J-9 4/1 J-32 5/3 J-71 2/4
J-IO 3/5 J-32 5/2 J-71 4/2
J-IO 5/3 J-32 4/2 J-72 2/4
J-Il 3/5 J-33 2/4 J-72 4/2
J-Il 5/3 J-33 2/5 J-73 2/4
J-12 3/5 J-33 3/5 J-73 4/2
J-12 5/3 J-33 5/3 J-73 1/3
J-12 1/3 J-33 5/2 J-73 1/4
J-12 3/1 J-33 4/2 J-73 4/1 J2 J-orientation**
J-74 2/4
J-74 2/5
J-74 4/2
J-74 5/2
J-74 3/5
J-74 5/3
J-75 3/5
J-75 5/3
J-75 2/4
J-75 2/5
J-75 3/5
J-75 5/3
J-76 3/6
J-76 6/3
J-77 3/5
J-77 5/3
J-78 1/3
J-79 1/3
J-79 3/1
J-80 1/3
J-80 3/1
J-81 3/5
J-81 5/3
J-82 3/5
J-82 3/6
J-82 5/3
J-82 6/3
Figure imgf000099_0001
ZMs a direct bond; Z 2 is a direct bond; Z3 is CH2; x is 0; GA is GA-49; r is O J2 J-orientation** J2 J-orientation** J2 J-orientation**
J-I 2/4 J-24 2/5 J-44 2/4 J-I 2/5 J-24 4/2 J-44 2/5 J-I 4/2 J-24 5/2 J-44 2/6 J-I 5/2 J-25 2/4 J-45 2/4 J-2 2/4 J-25 2/5 J-45 2/5 J-2 2/5 J-25 4/2 J-45 2/6
Figure imgf000100_0001
J2 J-orientation** J2 J-orientation** Jz J-oπentation**
J-IO 5/3 J-32 4/2 J-72 2/4
J-Il 3/5 J-33 2/4 J-72 4/2
J-Il 5/3 J-33 2/5 J-73 2/4
J-12 3/5 J-33 3/5 J-73 4/2
J-12 5/3 J-33 5/3 J-73 1/3
J-12 1/3 J-33 5/2 J-73 1/4
J-12 3/1 J-33 4/2 J-73 4/1
J-13 1/4 J-34 1/3 J-74 2/4
J-13 4/1 J-34 1/4 J-74 2/5
J-14 3/5 J-34 3/5 J-74 4/2
J-14 5/3 J-34 3/1 J-74 5/2
J-15 2/5 J-34 4/1 J-74 3/5
J-16 2/5 J-35 1/4 J-74 5/3
J-17 2/4 J-35 4/1 J-75 3/5
J-17 4/2 J-36 1/3 J-75 5/3
J-18 2/5 J-36 3/1 J-75 2/4
J-18 5/2 J-36 3/5 J-75 2/5
J-19 2/4 J-36 5/3 J-75 3/5
J-19 4/2 J-37 2/5 J-75 5/3
J-20 2/4 J-37 5/2 J-76 3/6
J-20 2/5 J-37 2/4 J-76 6/3
J-20 2/6 J-37 4/2 J-77 3/5
J-20 3/5 J-38 2/5 J-77 5/3
J-20 4/2 J-38 5/2 J-78 1/3
J-20 5/2 J-38 2/4 J-79 1/3
J-21 3/5 J-38 4/2 J-79 3/1
J-21 3/6 J-39 3/5 J-80 1/3
J-21 5/3 J-39 5/3 J-80 3/1
J-22 2/4 J-40 3/5 J-81 3/5
J-22 2/5 J-40 5/3 J-81 5/3
J-22 4/6 J-41 1/3 J-82 3/5
J-22 4/2 J-41 1/4 J-82 3/6
J-22 5/2 J-42 1/3 J-82 5/3
J-23 2/5 J-42 1/4 J-82 6/3
J-23 2/6 J-43 1/4
J-24 2/4 J-44 1/3 ** J-orientation refers to the attachment points for Z^ and Z2 on the ring of fi (which is identified by reference to the J groups of Exhibit 3). The first number refers to the position on the ring of J2 (with reference to the J groups of Exhibit 3) where zS is attached, and the second number refers to the position on the ring of J2 where Z2 is attached.
Figure imgf000102_0001
X is X1; R3a is H; R1 l a is Me; n is 0.
Figure imgf000102_0002
Figure imgf000102_0003
Figure imgf000102_0005
X is X2; R3a is H; R1 l a is Me; n is 0.
G
G-I G-2 G-3 G-4 G-5 G-6 G-7
Figure imgf000102_0004
Figure imgf000102_0006
Figure imgf000103_0003
Figure imgf000103_0004
Figure imgf000103_0006
X is X3; R3a is H; R1 la is Me; n is 0.
Figure imgf000103_0001
Figure imgf000103_0005
Figure imgf000103_0002
Figure imgf000103_0007
nis 0.
X G R3a X G R3a X G R3a χi G-2 Me X2 G-2 Me X3 G-2 Me χi G-2 Cl X2 G-2 Cl X3 G-2 Cl χi G-2 F X2 G-2 F X3 G-2 F χi G-2 CF3 X2 G-2 CF3 X3 G-2 CF3 χi G-14 «-Pr X2 G-14 w-Pr X3 G-14 w-Pr χi G-26 5-Me
R3aisH;n isO.
X G RlIa χi G-3 Me χi G-3 «-Pr
X2 G-3 Me
X2 G-3 «-Pr
X3 G-3 Me
X3 G-3 «-Pr
GisG-l;R3ais H; nis 0.
X X
X4 X7
X5 X8
X6 X9
Figure imgf000104_0001
* The definitions of X, G, R3a and R^ a in the compounds of this table are as defined in the Summary of the Invention and Exhibit 2 in the above Embodiments.
TABLE 5*
Figure imgf000104_0002
*The definitions of G and J-29-1 through J-29-57 in the compounds of this table are as defined in Exhibits 2 and A in the above Embodiments.
Figure imgf000104_0005
Figure imgf000104_0003
R1 is 2,5-dichlorophenyl; X is X2; G is G-I; R3a is H.
Figure imgf000104_0006
Figure imgf000104_0004
Figure imgf000105_0004
Figure imgf000105_0001
R1 is 2,5-dichlorophenyl; X is X1; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000105_0005
Figure imgf000105_0008
R1 is 2,5-dichloophenyl; X is X2; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000105_0002
Figure imgf000105_0006
Figure imgf000105_0009
R1 is 2-chloro-5-(trifluoromethyl)phenyl; X is X1; G is G-I; R3a is H.
Figure imgf000105_0007
Figure imgf000105_0003
Figure imgf000106_0004
Figure imgf000106_0001
Figure imgf000106_0005
Figure imgf000106_0006
Figure imgf000106_0002
R1 is 2-chloro-5-(trifluoromethyl)phenyl; X is X2; G is G-2; R3a is H.
Figure imgf000106_0007
Figure imgf000106_0003
Figure imgf000107_0004
Figure imgf000107_0001
R1 is 2,5-dimethylphenyl; X is X1; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000107_0005
Figure imgf000107_0008
R1 is 2,5-dimet lphenyl; X is X2; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000107_0002
Figure imgf000107_0006
Figure imgf000107_0009
R1 is 2,5-dimethylphenyl; X is X1; G is G-2; R3a is H.
Figure imgf000107_0007
Figure imgf000107_0003
Figure imgf000108_0005
Figure imgf000108_0001
Figure imgf000108_0006
Figure imgf000108_0002
R1 is 2-methyl-
Figure imgf000108_0007
Figure imgf000108_0003
Figure imgf000108_0004
Figure imgf000109_0003
R1 is 2-methyl-
Figure imgf000109_0004
R1 is 2-methyl-
Figure imgf000109_0005
Figure imgf000109_0001
R1 is 3,5-dimethylpyrazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000109_0006
Figure imgf000109_0002
Figure imgf000110_0004
Figure imgf000110_0001
Figure imgf000110_0005
Figure imgf000110_0006
Figure imgf000110_0002
R1 is 3,5-dimethylpyrazol-l-yl; X is X2; G is G-2; R3a is H.
Figure imgf000110_0007
Figure imgf000110_0003
Figure imgf000111_0004
Figure imgf000111_0001
R1 is 3,5-dichloropyrazol-l-yl; X is X1; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000111_0005
Figure imgf000111_0008
R1 is 3,5-dichloopyrazol-l-yl; X is X2; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000111_0002
Figure imgf000111_0006
Figure imgf000111_0009
R1 is 3,5-dichloropyrazol-l-yl; X is X1; G is G-2; R3a is H.
Figure imgf000111_0007
Figure imgf000111_0003
Figure imgf000112_0004
Figure imgf000112_0001
R1 is 3,5-dichloropyrazol-l-yl; X is X2; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000112_0005
Figure imgf000112_0008
R1 is 3,5-dibro opyrazol-l-yl; X is X1; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000112_0002
Figure imgf000112_0006
Figure imgf000112_0009
R1 is 3,5-dibromopyrazol-l-yl; X is X2; G is G-I; R3a is H.
Figure imgf000112_0007
Figure imgf000112_0003
Figure imgf000113_0004
Figure imgf000113_0001
Figure imgf000113_0005
Figure imgf000113_0006
Figure imgf000113_0002
R1 is 5-methyl-3-(trifluoromethyl)pyrazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000113_0007
Figure imgf000113_0003
Figure imgf000114_0003
R1 is 5-methyl-
R1 is 5-methyl-
Figure imgf000114_0005
Figure imgf000114_0001
Figure imgf000114_0002
Figure imgf000115_0003
Figure imgf000115_0001
Figure imgf000115_0004
Figure imgf000115_0005
Figure imgf000115_0002
Figure imgf000116_0003
Figure imgf000116_0001
Figure imgf000116_0004
Figure imgf000116_0005
Figure imgf000116_0002
Figure imgf000117_0004
Figure imgf000117_0001
Figure imgf000117_0005
Figure imgf000117_0006
Figure imgf000117_0002
R1 is 5-ethyl-3-(trifluoromethyl)pyrazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000117_0007
Figure imgf000117_0003
Figure imgf000118_0003
Figure imgf000118_0001
R1 is 5-ethyl-3-(trifluoromethyl)pyrazol-l-yl; X is X2; G is G-I; R3a is H J
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000118_0004
Figure imgf000118_0006
R1 is 5-ethyl -3-(trifluoromethyl)pyrazol-l-yl; X is X1; G is G-2; R3a is H. J
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000118_0005
Figure imgf000118_0007
Figure imgf000118_0002
Figure imgf000119_0003
Figure imgf000119_0001
Figure imgf000119_0004
Figure imgf000119_0005
Figure imgf000119_0002
Figure imgf000120_0005
Figure imgf000120_0001
Figure imgf000120_0006
Figure imgf000120_0002
R1 is 3-methyl-
Figure imgf000120_0007
Figure imgf000120_0003
Figure imgf000120_0004
Figure imgf000121_0003
Figure imgf000121_0004
R1 is 3-methyl-
Figure imgf000121_0005
Figure imgf000121_0001
R1 is 3-chloro-5-(trifluoromethyl)pyrazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000121_0006
Figure imgf000121_0002
Figure imgf000122_0003
Figure imgf000122_0001
Figure imgf000122_0004
Figure imgf000122_0005
Figure imgf000122_0002
Figure imgf000123_0003
Figure imgf000123_0001
Figure imgf000123_0004
Figure imgf000123_0005
Figure imgf000123_0002
Figure imgf000124_0004
Figure imgf000124_0001
Figure imgf000124_0005
Figure imgf000124_0006
Figure imgf000124_0002
R1 is 5-methoxy-3-(trifluoromethyl)pyrazol-l-yl; X is X2; G is G-I; R3a is H.
Figure imgf000124_0007
Figure imgf000124_0003
Figure imgf000125_0004
Figure imgf000125_0001
Figure imgf000125_0005
Figure imgf000125_0006
Figure imgf000125_0002
R1 is 5-difluoromethoxy-3-(trifluoromethyl)pyrazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000125_0007
Figure imgf000125_0003
Figure imgf000126_0004
Figure imgf000126_0001
Figure imgf000126_0006
Figure imgf000126_0002
R1 is 5-difluoromethoxy-3-(trifluoromethyl)pyrazol-l-yl; X is X2; G is G-2; R3a is H.
Figure imgf000126_0007
Figure imgf000126_0003
Figure imgf000127_0004
Figure imgf000127_0001
R1 is 3,5-dichlorotriazol-l-yl; X is X1; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000127_0005
Figure imgf000127_0008
R1 is 3,5-dichlootriazol-l-yl; X is X2; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000127_0002
Figure imgf000127_0006
Figure imgf000127_0009
R1 is 3,5-dichlorotriazol-l-yl; X is X1; G is G-2; R3a is H.
Figure imgf000127_0007
Figure imgf000127_0003
Figure imgf000128_0004
Figure imgf000128_0001
R1 is 3,5-dichlorotriazol-l-yl; X is X2; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000128_0005
Figure imgf000128_0008
R1 is 3,5-dibro otriazol-l-yl; X is X1; G is G-I; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000128_0002
Figure imgf000128_0006
Figure imgf000128_0009
R1 is 3,5-dibromotriazol-l-yl; X is X2; G is G-I; R3a is H.
Figure imgf000128_0007
Figure imgf000128_0003
Figure imgf000129_0004
Figure imgf000129_0001
R1 is 3,5-dibromotriazol-l-yl; X is X1; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000129_0005
Figure imgf000129_0008
R1 is 3,5-dibro otriazol-l-yl; X is X2; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000129_0002
Figure imgf000129_0006
Figure imgf000129_0009
R1 is 3,5-dimethyltriazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000129_0007
Figure imgf000129_0003
Figure imgf000130_0004
Figure imgf000130_0001
Figure imgf000130_0005
Figure imgf000130_0006
Figure imgf000130_0002
R1 is 3,5-dimethyltriazol-l-yl; X is X2; G is G-2; R3a is H.
Figure imgf000130_0007
Figure imgf000130_0003
Figure imgf000131_0003
Figure imgf000131_0001
R1 is 5-methyl-3-(trifluoromethyl)triazol-l-yl; X is X1; G is G-I; R3a is H
Figure imgf000131_0004
Figure imgf000131_0007
-(trifluoromethyl)triazol-l-yl; X is X2; G is G-I; R3a is H.
Figure imgf000131_0002
Figure imgf000131_0005
Figure imgf000131_0008
R1 is 5-methyl -3-(trifluoromethyl)triazol-l-yl; X is X1; G is G-2; R3a is H.
J
J-29-51
Figure imgf000131_0006
J-29-52
Figure imgf000132_0003
Figure imgf000132_0001
R1 is 5-methyl-3-(trifluoromethyl)triazol-l-yl; X is X2; G is G-2; R3a is H
Figure imgf000132_0004
Figure imgf000132_0007
-(trifluoromethyl)triazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000132_0002
Figure imgf000132_0005
Figure imgf000132_0008
R1 is 3 -methyl -5-(trifluoromethyl)triazol-l-yl; X is X2; G is G-I; R3a is H.
J
J-29-51
Figure imgf000132_0006
J-29-52
Figure imgf000133_0004
Figure imgf000133_0001
R1 is 3-methyl-5-(trifluoromethyl)triazol-l-yl; X is X1; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000133_0005
R1 is 3-methyl- -(trifluoromethyl)triazol-l-yl; X is X2; G is G-2; R3a is H.
J-29-1 J-29-2 J-29-3 J-29-4 J-29-5 J-29-6 J-29-7 J-29-8 J-29-9 J-29-10
Figure imgf000133_0002
Figure imgf000133_0006
Figure imgf000133_0009
R1 is 3,5-bis-(trifluoromethyl)triazol-l-yl; X is X1; G is G-I; R3a is H.
Figure imgf000133_0007
Figure imgf000133_0003
Figure imgf000134_0003
Figure imgf000134_0001
Figure imgf000134_0004
Figure imgf000134_0005
Figure imgf000134_0002
Figure imgf000135_0004
Figure imgf000135_0001
Table 5 above identifies particular compounds comprising a J group selected from J-29-1 through J-29-60 (i.e. particular examples of J-29). As many J-29-1 to J-29-60 include a chiral center, these J groups are illustrated in a particular enantiomeric configuration, which in some instances may provide the greatest fungicidal activity. One skilled in the art immediately recognizes the antipode (i.e. opposite enantiomer) for each of the compounds listed, and furthermore understands that the enantiomers can be present as pure enantiomers or in mixtures enriched in one enantiomer or in racemic mixtures.
TABLE 6*
Figure imgf000135_0002
*The definitions of G and J-29-1 through J-29-60 in the compounds of this table are as defined in Exhibits 2 and A in the above Embodiments.
Figure imgf000135_0005
Figure imgf000135_0003
Figure imgf000136_0004
Figure imgf000136_0001
TABLE 7*
Figure imgf000136_0002
* The definitions of Q groups (Q-I through Q- 106) in this table are as defined in Exhibit 4 in the above
Embodiments; p is 1, q is 0, and R' is phenyl depicted in the above molecular structure.
** Q-orientation refers to the attachment points for the remainder of the molecule and the R' (phenyl) substituent on the ring of Q. The first number refers to the position on the Q ring attaching Q to the remainder of the molecule. The second number refers to the position on the Q ring where the R ' (phenyl) substituent is attached.
Figure imgf000136_0003
Q Q-orientation** Q Q-orientation** Q Q-orientation**
Q-8 5/4 Q-47 1/2 Q-77 1/7
Q-9 5/3 Q-47 1/3 Q-78 1/5
Q-9 5/4 Q-47 1/4 Q-78 1/6
Q-IO 5/3 Q-48 1/1 Q-79 3/6
Q-IO 5/4 Q-48 1/2 Q-79 3/7
Q-I l 5/2 Q-49 1/1 Q-80 3/6
Q-I l 5/4 Q-49 1/2 Q-80 3/7
Q-12 2/4 Q-50 1/1 Q-81 3/4
Q-12 2/5 Q-50 1/2 Q-81 3/5
Q-13 2/5 Q-50 1/3 Q-82 2/5
Q-14 5/3 Q-51 1/1 Q-82 2/6
Q-15 2/5 Q-51 1/2 Q-82 2/7
Q-16 2/5 Q-51 1/3 Q-83 3/5
Q-17 3/5 Q-52 1/1 Q-84 1/5
Q-18 5/3 Q-52 1/2 Q-85 3/5
Q-19 3/2 Q-52 1/3 Q-86 3/5
Q-19 3/4 Q-53 1/1 Q-87 3/4
Q-19 3/5 Q-53 1/2 Q-87 3/5
Q-20 3/2 Q-53 1/3 Q-88 1/4
Q-20 3/4 Q-54 1/1 Q-88 1/5
Q-20 3/5 Q-54 1/2 Q-89 3/4
Q-21 3/2 Q-54 1/3 Q-89 3/5
Q-21 3/4 Q-54 1/4 Q-90 1/3
Q-21 3/5 Q-55 1/1 Q-90 1/4
Q-22 3/4 Q-55 1/2 Q-90 1/5
Q-22 3/5 Q-55 1/3 Q-91 3/4
Q-23 4/3 Q-55 1/4 Q-91 3/5
Q-23 4/5 Q-56 2/3 Q-91 3/6
Q-24 4/2 Q-56 2/5 Q-92 1/4
Q-24 4/5 Q-56 2/6 Q-92 1/5
Q-25 4/2 Q-57 3/2 Q-92 1/6
Q-25 4/5 Q-57 3/5 Q-93 3/4
Q-26 4/3 Q-57 3/6 Q-93 3/5
Q-26 4/5 Q-58 2/3 Q-93 3/6
Q-27 4/3 Q-58 2/5 Q-94 1/3
Q-27 4/5 Q-58 2/6 Q-94 1/4
Q-28 4/2 Q-59 3/2 Q-94 1/5 Q Q-orientation** Q Q-orientation** Q Q-oπentation**
Q-28 4/5 Q-59 3/5 Q-94 1/6
Q-29 3/5 Q-59 3/6 Q-95 2/5
Q-30 3/4 Q-60 1/3 Q-95 2/6
Q-31 3/5 Q-61 1/3 Q-96 2/4
Q-32 2/3 Q-62 3/5 Q-96 2/6
Q-32 2/4 Q-63 2/4 Q-97 2/5
Q-32 2/5 Q-63 2/5 Q-97 2/6
Q-32 2/6 Q-64 2/3 Q-98 2/4
Q-33 3/2 Q-64 2/4 Q-98 2/7
Q-33 3/4 Q-64 2/5 Q-99 2/5
Q-33 3/5 Q-65 1/3 Q-99 2/6
Q-33 3/6 Q-65 1/4 Q-IOO 3/5
Q-34 4/2 Q-65 1/5 Q-IOO 3/6
Q-34 4/3 Q-66 2/3 Q-IOl 3/4
Q-35 3/4 Q-66 2/4 Q-IOl 3/7
Q-35 3/5 Q-66 2/6 Q- 102 1/5
Q-35 3/6 Q-67 2/4 Q-103 1/2
Q-36 2/4 Q-67 2/5 Q-103 1/3
Q-36 2/5 Q-67 2/6 Q- 104 1/3
Q-37 2/3 Q-68 3/6 Q- 104 1/4
Q-37 2/5 Q-68 3/8 Q- 104 1/5
Q-37 2/6 Q-69 1/3 Q-105 1/2
Q-38 4/2 Q-69 1/4 Q-105 1/4
Q-38 4/5 Q-69 1/6 Q-105 1/5
Q-38 4/6 Q-70 3/4 Q-106 1/3
Q-39 5/2 Q-70 3/6 Q-106 1/5
Q-39 5/4 Q-71 3/4
TABLE 8*
Figure imgf000139_0001
wherein G^ is Gr", G^ or GF as indicated below.
*The definitions of Gr^, GF^ and GP in the compounds of this table are as defined in Exhibit 5 in the above Embodiments.
Figure imgf000139_0002
Figure imgf000139_0003
Figure imgf000139_0004
Z3 is O; r is 0; R22 is Me.
Figure imgf000140_0003
Figure imgf000140_0001
Figure imgf000140_0004
Figure imgf000140_0002
Figure imgf000140_0006
Z3 is CH2; r is 0 R22 is Me. GG GA-1 GA-2 GA-3 GA-4 GA-5 GA-6 GA-7 GA-8 GA-9 GA-10 GA-11 GA-12 GA-13 GA-14 GA-15
Figure imgf000140_0005
Figure imgf000140_0007
Figure imgf000141_0002
Figure imgf000141_0003
Figure imgf000141_0006
Figure imgf000141_0001
Figure imgf000141_0004
Figure imgf000141_0007
Z3 is -CH2CH2-; r is 0; R22 is Me. GG
GA-1 GA-2 GA-3 GA-4 GA-5 GA-6 GA-7
Figure imgf000141_0005
Figure imgf000141_0008
Figure imgf000142_0004
Figure imgf000142_0005
Figure imgf000142_0001
Figure imgf000142_0006
Figure imgf000142_0002
* The definitions of GA in the compounds of this table are as defined in Exhibit 5 in the above Embodiments.
Figure imgf000142_0007
Figure imgf000142_0008
Figure imgf000142_0003
** The left end of these substituents are connected to the phenyl group and right end of these substituent are connected to Gr \
TABLE 10*
Figure imgf000143_0001
*The definitions of GA in the compounds of this table are as defined in Exhibit 5 in the above Embodiments. GA is GA-18; r is 0.
Z5
CH2O **
Figure imgf000143_0002
Z5
CH2O **
Figure imgf000143_0003
Z3
CH2O **
Figure imgf000143_0004
** The left end of these substituents are connected to the phenyl group and right end of these substituent are connected to GA.
TABLE 11*
Figure imgf000144_0001
*The definitions of GA in the compounds of this table are as defined in Exhibit 5 in the above Embodiments. GAisGA-18;ris0.
Z3
CH2O **
Figure imgf000144_0002
GAisGA-36;ris0.
Z3
CH2O **
Figure imgf000144_0003
Z3
CH2O **
Figure imgf000144_0004
** The left end of these substituents are connected to the phenyl group and right end of these substituent are connected to Gr\
TABLE 12
Figure imgf000145_0001
Figure imgf000146_0003
Figure imgf000146_0001
TABLE 13
Figure imgf000146_0002
7? is a direct bond.
Figure imgf000147_0002
Figure imgf000147_0001
Z3 is CH2.
(Rv)r (RV)r (RV)r (RV)r 2-Cl 4-CH3 3-CH2OCH2OCH3 2-NHSO2CH3 2-F 2,6-di-CH3 3-CH2SCH3 2-C(=S)OCH3
2,6-di-F 2,3-di-CH3 3-CH2SO2CH3 2-CS2CH3 2-CN 2,4,6-tri-CH3 3-CH2N(CH3)2 2-OCH3
Figure imgf000148_0002
TABLE 14
Figure imgf000148_0001
T? is a direct bond.
Figure imgf000148_0003
Figure imgf000149_0002
Figure imgf000149_0003
Figure imgf000149_0001
TABLE 15*
Figure imgf000150_0001
* J-29-1 through J-29-60 specified for jl in the compounds of this table are as defined in Exhibit A in the above Embodiments.
Figure imgf000150_0002
Jl
J-29-55 J-29-56 J-29-57 J-29-58 J-29-59
Figure imgf000151_0002
J-29-60
Figure imgf000151_0003
Figure imgf000151_0006
Figure imgf000151_0001
Figure imgf000151_0004
Figure imgf000151_0007
M is OMe.
Jl
J-29-1 J-29-2 J-29-3 J-29-4
Figure imgf000151_0005
Figure imgf000151_0008
Jl
J-29-55 J-29-56 J-29-57 J-29-58 J-29-59
Figure imgf000152_0002
J-29-60
Figure imgf000152_0003
Figure imgf000152_0006
Figure imgf000152_0001
Figure imgf000152_0004
Figure imgf000152_0007
M is O-z-Pr.
Jl
J-29-1 J-29-2 J-29-3 J-29-4
Figure imgf000152_0005
Figure imgf000152_0008
Jl
J-29-55 J-29-56 J-29-57 J-29-58 J-29-59
Figure imgf000153_0002
J-29-60
Figure imgf000153_0003
Figure imgf000153_0006
Figure imgf000153_0001
Figure imgf000153_0004
Figure imgf000153_0007
M is NMe2-
Jl
J-29-1 J-29-2 J-29-3 J-29-4
Figure imgf000153_0005
Figure imgf000153_0008
Jl
J-29-55 J-29-56 J-29-57 J-29-58 J-29-59
Figure imgf000154_0002
J-29-60
Figure imgf000154_0003
Figure imgf000154_0006
Figure imgf000154_0001
Figure imgf000154_0004
Figure imgf000154_0007
Mis 1-piperdinyl, Jl
J-29-1
J-29-2
J-29-3
J-29-4
Figure imgf000154_0005
Figure imgf000154_0008
Jl
J-29-55 J-29-56 J-29-57 J-29-58 J-29-59
Figure imgf000155_0002
J-29-60
M is 1-pyrrolidinyl.
Figure imgf000155_0003
Figure imgf000155_0004
Figure imgf000155_0001
Table 15 above identifies particular compounds comprising a jl group selected from J-29-1 through J-29-60. As many J-29-1 through J-29-60 include a chiral center, these jl groups are illustrated in a particular enantiomeric configuration, which in some instances may provide the greatest fungicidal activity for compounds of Formula 1. One skilled in the art immediately recognizes the antipode (i.e. opposite enantiomer) for each of the compounds listed, and furthermore understands that the enantiomers can be present as pure enantiomers or in mixtures enriched in one enantiomer or in racemic mixtures. Formulation/Utility
A compound of Formula 1 (or an JV-oxide or salt thereof) according to this invention will generally be used as a fungicidal active ingredient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serve as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.
Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated emulsion, microemulsion and suspo-emulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion. The general types of solid compositions are dusts, powders, granules, pellets, pills, pastilles, tablets, filled films (including seed coatings) and the like, which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed from film- forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation. Sprayable formulations are typically extended in a suitable medium before spraying.
Such liquid and solid formulations are formulated to be readily diluted in the spray medium, usually water. Spray volumes can range from about from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerial or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto vegetable seeds as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake. The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight. Weight Percent
Active Inaredient Diluent Surfactant
Water-Dispersible and Water-soluble 0.001-90 0-99.999 0-15 Granules, Tablets and Powders.
Oil Dispersions, Suspensions, 1-50 40-99 0-50 Emulsions, Solutions (including Emulsifiable Concentrates)
Dusts 1-25 70-99 0-5
Granules and Pellets 0.001-95 5-99.999 0-15
High Strength Compositions 90-99 0-10 0-2
Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.
Liquid diluents include, for example, water, JV,iV-dimethylalkanamides (e.g., Λ/,Λ/-dimethylformamide), limonene, dimethyl sulfoxide, JV-alkylpyrrolidones (e.g., JV-methylpyrrolidinone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffms), alkylbenzenes, alkylnaphthalenes, glycerine, glycerol triacetate, sorbitol, triacetin, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactate esters, dibasic esters and γ-butyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol. Liquid diluents also include glycerol esters of saturated and unsaturated fatty acids (typically C6-C22), such as plant seed and fruit oils (e.g., oils of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, rapeseed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydrolysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950.
The solid and liquid compositions of the present invention often include one or more surfactants. Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as ethoxylated soybean, castor and rapeseed oils; alkylphenol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol ethoxylates (prepared from the phenols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based derivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs); polyethylene glycol fatty acid esters; silicone -based surfactants; and sugar- derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.
Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives such as lignosulfonates; maleic or succinic acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phenol ethoxylates; protein-based surfactants; sarcosine derivatives; styryl phenol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides such as 7V,iV-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated petroleum; sulfosuccinamates; and sulfosuccinates and their derivatives such as dialkyl sulfosuccinate salts.
Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides; amines such as JV-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary salts, ethoxylated quaternary salts and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.
Also useful for the present compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published references including McCutcheon 's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.
Compositions of this invention may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids. Such formulation auxiliaries and additives may control: pH (buffers), foaming during processing (antifoams such polyorganosiloxanes (e.g., Rhodorsil® 416)), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobials), product freezing (antifreezes), color (dyes/pigment dispersions (e.g., Pro- lzed® Colorant Red)), wash-off (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon 's Volume 2: Functional Materials, annual International and North American editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active- containing solvent upon dilution with water. Active ingredient slurries, with particle diameters of up to 2,000 μm can be wet milled using media mills to obtain particles with average diameters below 3 μm. Aqueous slurries can be made into finished suspension concentrates (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diameters in the 2 to 10 μm range. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
For further information regarding the art of formulation, see T. S. Woods, "The Formulator's Toolbox - Product Forms for Modern Agriculture" in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.
In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Table A.
Example A High Strength Concentrate
Compound 1 98.5 % silica aerogel 0.5 % synthetic amorphous fine silica 1.0 %.
Example B Wettable Powder
Compound 2 65.0 % dodecylphenol polyethylene glycol ether 2.0 % sodium ligninsulfonate 4.0 % sodium silicoaluminate 6.0 % montmorillonite (calcined) 23.0 %.
Example C Granule Compound 1 10.0 % attapulgite granules (low volatile matter, 0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0 %. Example D
Aqueous Suspension Compound 2 25.0 % hydrated attapulgite 3.0 % crude calcium ligninsulfonate 10.0 % sodium dihydrogen phosphate 0.5 % water 61.5 %.
Example E
Extruded Pellet Compound 1 25.0 % anhydrous sodium sulfate 10.0 % crude calcium ligninsulfonate 5.0 % sodium alkylnaphthalenesulfonate 1.0 % calcium/magnesium bentonite 59.0 %.
Example F
Microemulsion
Compound 2 1.0 % triacetine 30.0 %
Cg-Cio alkylpolyglycoside 30.0 % glyceryl monooleate 19.0 % water 20.0 %.
Example G
Emulsifiable Concentrate
Compound 1 10.0 %
C8-C10 fatty acid methyl ester 70.0 % polyoxy ethylene sorbitol hexoleate 20.0 %.
Compounds of this invention (i.e. compounds of Formula 1, JV-oxides, and salts thereof) are useful as plant disease control agents. The present invention therefore further comprises a method for controlling plant diseases caused by fungal plant pathogens comprising applying to the plant or portion thereof to be protected, or to the plant seed to be protected, an effective amount of a compound of the invention or a fungicidal composition containing said compound. The compounds and/or compositions of this invention provide control of diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and Deuteromycete classes. They are effective in controlling a broad spectrum of plant diseases, particularly foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops. These pathogens include: Oomycetes, including Phytophthora diseases such as Phytophthora infestans, Phytophthora megasperma, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora capsici, Pythium diseases such as Pythium aphanidermatum, and diseases in the Peronosporaceae family such as Plasmopara viticola, Peronospora spp. (including Peronospora tabacina and Peronospora parasitica), Pseudoperonospora spp. (including Pseudoperonospora cubensis) and Bremia lactucae; Ascomycetes, including Alternaria diseases such as Alternaria solani and Alternaria brassicae, Guignardia diseases such as Guignardia bidwell, Venturia diseases such as Venturia inaequalis, Septoria diseases such as Septoria nodorum and Septoria tritici, powdery mildew diseases such as Erysiphe spp. (including Erysiphe graminis and Erysiphe polygonϊ), Uncinula necatur, Sphaerotheca fuligena and Podosphaera leucotricha, Pseudocercosporella herpotrichoides, Botrytis diseases such as Botrytis cinerea, Monilinia fructicola, Sclerotinia diseases such as Sclerotinia sclerotiorum, Magnaporthe grisea, Phomopsis viticola, Helminthosporium diseases such as Helminthosporium tritici repentis, Pyrenophora teres, anthracnose diseases such as Glomerella or Colletotrichum spp. (such as Colletotrichum graminicola and Colletotrichum orbiculare), and Gaeumannomyces graminis; Basidiomycetes, including rust diseases caused by Puccinia spp. (such as Puccinia recondita, Puccinia striiformis, Puccinia hordei, Puccinia graminis and Puccinia arachidis), Hemileia vastatrix and Phakopsora pachyrhizi; other pathogens including Rhizoctonia spp. (such as Rhizoctonia solani); Fusarium diseases such as Fusarium roseum, Fusarium graminearum and Fusarium oxysporum; Verticillium dahliae; Sclerotium rolfsii; Rynchosporium secalis; Cercosporidium personatum, Cercospora arachidicola and Cercospora beticola; and other genera and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have activity against bacteria such as Erwinia amylovora, Xanthomonas campestris, Pseudomonas syringae, and other related species. Of note is control provided of disease caused by the Ascomycete and Oomycete classes. Of particular note is control provided of disease caused by the Oomycete class.
Plant disease control is ordinarily accomplished by applying an effective amount of a compound of this invention either pre- or post-infection, to the portion of the plant to be protected such as the roots, stems, foliage, fruit, seeds, tubers or bulbs, or to the media (soil or sand) in which the plants to be protected are growing. The compounds can also be applied to seeds to protect the seeds and seedlings developing from the seeds. The compounds can also be applied through irrigation water to treat plants.
Rates of application for these compounds can be influenced by many factors of the environment and should be determined under actual use conditions. Foliage can normally be protected when treated at a rate of from less than about 1 g/ha to about 5,000 g/ha of active ingredient. Seed and seedlings can normally be protected when seed is treated at a rate of from about 0.1 to about 1O g per kilogram of seed. Compounds of this invention can also be mixed with one or more other biologically active compounds or agents including fungicides, insecticides, nematocides, bactericides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Thus the present invention also pertains to a composition comprising a fungicidally effective amount of a compound of Formula 1 and a biologically effective amount of at least one additional biologically active compound or agent and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. For mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with a compound of Formula 1, to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1, and the formulations combined together before application (e.g., in a spray tank) or, alternatively, applied in succession.
Of note is a composition which in addition to the compound of Formula 1 include at least one fungicidal compound selected from the group consisting of the classes (1) methyl benzimidazole carbamate (MBC) fungicides; (2) dicarboximide fungicides; (3) demethylation inhibitor (DMI) fungicides; (4) phenylamide fungicides; (5) amine/morpholine fungicides; (6) phospholipid biosynthesis inhibitor fungicides; (7) carboxamide fungicides; (8) hydroxy(2-amino-)pyrimidine fungicides; (9) anilinopyrimidine fungicides; (10) JV-phenyl carbamate fungicides; (11) quinone outside inhibitor (QoI) fungicides; (12) phenylpyrrole fungicides; (13) quinoline fungicides; (14) lipid peroxidation inhibitor fungicides; (15) melanin biosynthesis inhibitors-reductase (MBI-R) fungicides; (16) melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides; (17) hydroxyanilide fungicides; (18) squalene-epoxidase inhibitor fungicides; (19) polyoxin fungicides; (20) phenylurea fungicides; (21) quinone inside inhibitor (QiI) fungicides; (22) benzamide fungicides; (23) enopyranuronic acid antibiotic fungicides; (24) hexopyranosyl antibiotic fungicides; (25) glucopyranosyl antibiotic: protein synthesis fungicides; (26) glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides; (27) cyanoacetamideoxime fungicides; (28) carbamate fungicides; (29) oxidative phosphorylation uncoupling fungicides; (30) organo tin fungicides; (31) carboxylic acid fungicides; (32) heteroaromatic fungicides; (33) phosphonate fungicides; (34) phthalamic acid fungicides; (35) benzotriazine fungicides; (36) benzene-sulfonamide fungicides; (37) pyridazinone fungicides; (38) thiophene-carboxamide fungicides; (39) pyrimidinamide fungicides; (40) carboxylic acid amide (CAA) fungicides; (41) tetracycline antibiotic fungicides; (42) thiocarbamate fungicides; (43) benzamide fungicides; (44) host plant defense induction fungicides; (45) multi-site contact activity fungicides; (46) fungicides other than classes (1) through (45); and salts of compounds of classes (1) through (46).
Further descriptions of these classes of fungicidal compounds are provided below. (1) "Methyl benzimidazole carbamate (MBC) fungicides" (Fungicide Resistance
Action Committee (FRAC) code 1) inhibit mitosis by binding to β-tubulin during microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Methyl benzimidazole carbamate fungicides include benzimidazole and thiophanate fungicides. The benzimidazoles include benomyl, carbendazim, fuberidazole and thiabendazole. The thiophanates include thiophanate and thiophanate-methy 1.
(2) "Dicarboximide fungicides" (Fungicide Resistance Action Committee (FRAC) code 2) are proposed to inhibit a lipid peroxidation in fungi through interference with NADH cytochrome c reductase. Examples include chlozolinate, iprodione, procymidone and vinclozolin.
(3) "Demethylation inhibitor (DMI) fungicides" (Fungicide Resistance Action Committee (FRAC) code 3) inhibit C14-demethylase, which plays a role in sterol production. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. DMI fungicides are divided between several chemical classes: azoles (including triazoles and imidazoles), pyrimidines, piperazines and pyridines. The triazoles include azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole (including diniconazole-M), epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole and uniconazole. The imidazoles include clotrimazole, imazalil, oxpoconazole, prochloraz, pefurazoate and triflumizole. The pyrimidines include fenarimol and nuarimol. The piperazines include triforine. The pyridines include pyrifenox. Biochemical investigations have shown that all of the above mentioned fungicides are DMI fungicides as described by K. H. Kuck et al. in Modern Selective Fungicides - Properties, Applications and Mechanisms of Action, H. Lyr (Ed.), Gustav Fischer Verlag: New York, 1995, 205-258.
(4) "Phenylamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 4) are specific inhibitors of RNA polymerase in Oomycete fungi. Sensitive fungi exposed to these fungicides show a reduced capacity to incorporate uridine into rRNA. Growth and development in sensitive fungi is prevented by exposure to this class of fungicide. Phenylamide fungicides include acylalanine, oxazolidinone and butyrolactone fungicides. The acylalanines include benalaxyl, benalaxyl-M, furalaxyl, metalaxyl and metalaxyl- M/mefenoxam. The oxazolidinones include oxadixyl. The butyrolactones include ofurace.
(5) "Amine/morpholine fungicides" (Fungicide Resistance Action Committee (FRAC) code 5) inhibit two target sites within the sterol biosynthetic pathway, Δ8 → Δ7 isomerase and Δ14 reductase. Sterols, such as ergosterol, are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore, exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Amine/morpholine fungicides (also known as non-DMI sterol biosynthesis inhibitors) include morpholine, piperidine and spiroketal-amine fungicides. The morpholines include aldimorph, dodemorph, fenpropimorph, tridemorph and trimorphamide. The piperidines include fenpropidin and piperalin. The spiroketal-amines include spiroxamine.
(6) "Phospholipid biosynthesis inhibitor fungicides" (Fungicide Resistance Action Committee (FRAC) code 6) inhibit growth of fungi by affecting phospholipid biosynthesis. Phospholipid biosynthesis fungicides include phophorothiolate and dithiolane fungicides. The phosphorothiolates include edifenphos, iprobenfos and pyrazophos. The dithiolanes include isoprothiolane.
(7) "Carboxamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 7) inhibit Complex II (succinate dehydrogenase) fungal respiration by disrupting a key enzyme in the Krebs Cycle (TCA cycle) named succinate dehydrogenase. Inhibiting respiration prevents the fungus from making ATP, and thus inhibits growth and reproduction. Carboxamide fungicides include benzamides, furan carboxamides, oxathiin carboxamides, thiazole carboxamides, pyrazole carboxamides and pyridine carboxamides. The benzamides include benodanil, flutolanil and mepronil. The furan carboxamides include fenfuram. The oxathiin carboxamides include carboxin and oxycarboxin. The thiazole carboxamides include thifluzamide. The pyrazole carboxamides include furametpyr, penthiopyrad, bixafen, N-[2-(15',2i?)-[l,r-bicyclopropyl]-2-ylphenyl]-3-(difluoromethyl)- 1 -methyl- lH-pyrazole-4-carboxamide and N-[2-(l ,3-dimethylbutyl)phenyl]-5-fluoro- 1,3- dimethyl-lH-pyrazole-4-carboxamide. The pyridine carboxamides include boscalid.
(8) "Hydroxy(2-amino-)pyrimidine fungicides" (Fungicide Resistance Action Committee (FRAC) code 8) inhibit nucleic acid synthesis by interfering with adenosine deaminase. Examples include bupirimate, dimethirimol and ethirimol.
(9) "Anilinopyrimidine fungicides" (Fungicide Resistance Action Committee (FRAC) code 9) are proposed to inhibit biosynthesis of the amino acid methionine and to disrupt the secretion of hydrolytic enzymes that lyse plant cells during infection. Examples include cyprodinil, mepanipyrim and pyrimethanil.
(10) 'W-Phenyl carbamate fungicides" (Fungicide Resistance Action Committee (FRAC) code 10) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include diethofencarb.
(11) "Quinone outside inhibitor (QoI) fungicides" (Fungicide Resistance Action Committee (FRAC) code 11) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol oxidase. Oxidation of ubiquinol is blocked at the "quinone outside" (Q0) site of the cytochrome bcγ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone outside inhibitor fungicides (also known as strobilurin fungicides) include methoxyacrylate, methoxycarbamate, oximinoacetate, oximinoacetamide, oxazolidinedione, dihydrodioxazine, imidazolinone and benzylcarbamate fungicides. The methoxyacrylates include azoxystrobin, enestroburin (SYP-Z071) and picoxystrobin. The methoxycarbamates include pyraclostrobin. The oximinoacetates include kresoxim-methyl and trifloxystrobin. The oximinoacetamides include dimoxystrobin, metominostrobin, orysastrobin, α-[methoxyimino]-Λ/-methyl-2-[[[ 1 -[3-(trifluoromethyl)phenyl]ethoxy]imino]- methyljbenzeneacetamide and 2-[[[3-(2,6-dichlorophenyl)-l-methyl-2-propen-l-ylidene]- amino]oxy]methyl]-α-(methoxyimino)-Λ/-methylbenzeneacetamide. The oxazolidinediones include famoxadone. The dihydrodioxazines include fluoxastrobin. The imidazolinones include fenamidone. The benzylcarbamates include pyribencarb.
(12) "Phenylpyrrole fungicides" (Fungicide Resistance Action Committee (FRAC) code 12) inhibit a MAP protein kinase associated with osmotic signal transduction in fungi.
Fenpiclonil and fludioxonil are examples of this fungicide class.
(13) "Quinoline fungicides" (Fungicide Resistance Action Committee (FRAC) code 13) are proposed to inhibit signal transduction by affecting G-proteins in early cell signaling. They have been shown to interfere with germination and/or appressorium formation in fungi that cause powder mildew diseases. Quinoxyfen is an example of this class of fungicide.
(14) "Lipid peroxidation inhibitor fungicides" (Fungicide Resistance Action Committee (FRAC) code 14) are proposed to inhibit lipid peroxidation which affects membrane synthesis in fungi. Members of this class, such as etridiazole, may also affect other biological processes such as respiration and melanin biosynthesis. Lipid peroxidation fungicides include aromatic carbon and 1,2,4-thiadiazole fungicides. The aromatic carbon fungicides include biphenyl, chloroneb, dicloran, quintozene, tecnazene and tolclofos- methyl. The 1,2,4-thiadiazole fungicides include etridiazole.
(15) "Melanin biosynthesis inhibitors-reductase (MBI-R) fungicides" (Fungicide Resistance Action Committee (FRAC) code 16.1) inhibit the naphthal reduction step in melanin biosynthesis. Melanin is required for host plant infection by some fungi. Melanin biosynthesis inhibitors-reductase fungicides include isobenzofuranone, pyrroloquinolinone and triazolobenzothiazole fungicides. The isobenzofuranones include fthalide. The pyrroloquinolinones include pyroquilon. The triazolobenzothiazoles include tricyclazole. (16) "Melanin biosynthesis inhibitors-dehydratase (MBI-D) fungicides" (Fungicide Resistance Action Committee (FRAC) code 16.2) inhibit scytalone dehydratase in melanin biosynthesis. Melanin in required for host plant infection by some fungi. Melanin biosynthesis inhibitors-dehydratase fungicides include cyclopropanecarboxamide, carboxamide and propionamide fungicides. The cyclopropanecarboxamides include carpropamid. The carboxamides include diclocymet. The propionamides include fenoxanil.
(17) "Hydroxyanilide fungicides (Fungicide Resistance Action Committee (FRAC) code 17) inhibit C4-demethylase which plays a role in sterol production. Examples include fenhexamid. (18) "Squalene-epoxidase inhibitor fungicides" (Fungicide Resistance Action
Committee (FRAC) code 18) inhibit squalene-epoxidase in ergosterol biosynthesis pathway. Sterols such as ergosterol are needed for membrane structure and function, making them essential for the development of functional cell walls. Therefore exposure to these fungicides results in abnormal growth and eventually death of sensitive fungi. Squalene- epoxidase inhibitor fungicides include thiocarbamate and allylamine fungicides. The thiocarbamates include pyributicarb. The allylamines include naftifϊne and terbinafme.
(19) "Polyoxin fungicides" (Fungicide Resistance Action Committee (FRAC) code 19) inhibit chitin synthase. Examples include polyoxin.
(20) "Phenylurea fungicides" (Fungicide Resistance Action Committee (FRAC) code 20) are proposed to affect cell division. Examples include pencycuron.
(21) "Quinone inside inhibitor (QiI) fungicides" (Fungicide Resistance Action Committee (FRAC) code 21) inhibit Complex III mitochondrial respiration in fungi by affecting ubiquinol reductase. Reduction of ubiquinol is blocked at the "quinone inside" (Qi) site of the cytochrome bcγ complex, which is located in the inner mitochondrial membrane of fungi. Inhibiting mitochondrial respiration prevents normal fungal growth and development. Quinone inside inhibitor fungicides include cyanoimidazole and sulfamoyltriazole fungicides. The cyanoimidazoles include cyazofamid. The sulfamoyltriazoles include amisulbrom.
(22) "Benzamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 22) inhibit mitosis by binding to β-tubulin and disrupting microtubule assembly. Inhibition of microtubule assembly can disrupt cell division, transport within the cell and cell structure. Examples include zoxamide.
(23) "Enopyranuronic acid antibiotic fungicides" (Fungicide Resistance Action Committee (FRAC) code 23) inhibit growth of fungi by affecting protein biosynthesis. Examples include blasticidin-S.
(24) "Hexopyranosyl antibiotic fungicides" (Fungicide Resistance Action Committee (FRAC) code 24) inhibit growth of fungi by affecting protein biosynthesis. Examples include kasugamycin. (25) "Glucopyranosyl antibiotic: protein synthesis fungicides" (Fungicide Resistance Action Committee (FRAC) code 25) inhibit growth of fungi by affecting protein biosynthesis. Examples include streptomycin.
(26) "Glucopyranosyl antibiotic: trehalase and inositol biosynthesis fungicides" (Fungicide Resistance Action Committee (FRAC) code 26) inhibit trehalase in inositol biosynthesis pathway. Examples include validamycin.
(27) "Cyanoacetamideoxime fungicides (Fungicide Resistance Action Committee (FRAC) code 27) include cymoxanil.
(28) "Carbamate fungicides" (Fungicide Resistance Action Committee (FRAC) code 28) are considered multi-site inhibitors of fungal growth. They are proposed to interfere with the synthesis of fatty acids in cell membranes, which then disrupts cell membrane permeability. Propamacarb, propamacarb-hydrochloride, iodocarb, and prothiocarb are examples of this fungicide class.
(29) "Oxidative phosphorylation uncoupling fungicides" (Fungicide Resistance Action Committee (FRAC) code 29) inhibit fungal respiration by uncoupling oxidative phosphorylation. Inhibiting respiration prevents normal fungal growth and development. This class includes 2,6-dinitroanilines such as fluazinam, pyrimidonehydrazones such as ferimzone and dinitrophenyl crotonates such as dinocap, meptyldinocap and binapacryl.
(30) "Organo tin fungicides" (Fungicide Resistance Action Committee (FRAC) code 30) inhibit adenosine triphosphate (ATP) synthase in oxidative phosphorylation pathway.
Examples include fentin acetate, fentin chloride and fentin hydroxide.
(31) "Carboxylic acid fungicides" (Fungicide Resistance Action Committee (FRAC) code 31) inhibit growth of fungi by affecting deoxyribonucleic acid (DNA) topoisomerase type II (gyrase). Examples include oxolinic acid. (32) "Heteroaromatic fungicides" (Fungicide Resistance Action Committee (FRAC) code 32) are proposed to affect DNA/ribonucleic acid (RNA) synthesis. Heteroaromatic fungicides include isoxazole and isothiazolone fungicides. The isoxazoles include hymexazole and the isothiazolones include octhilinone.
(33) "Phosphonate fungicides" (Fungicide Resistance Action Committee (FRAC) code 33) include phosphorous acid and its various salts, including fosetyl-aluminum.
(34) "Phthalamic acid fungicides" (Fungicide Resistance Action Committee (FRAC) code 34) include teclofthalam.
(35) "Benzotriazine fungicides" (Fungicide Resistance Action Committee (FRAC) code 35) include triazoxide. (36) "Benzene-sulfonamide fungicides" (Fungicide Resistance Action Committee
(FRAC) code 36) include flusulfamide.
(37) "Pyridazinone fungicides" (Fungicide Resistance Action Committee (FRAC) code 37) include diclomezine. (38) "Thiophene-carboxamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 38) are proposed to affect ATP production. Examples include silthiofam.
(39) "Pyrimidinamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 39) inhibit growth of fungi by affecting phospholipid biosynthesis and include diflumetorim.
(40) "Carboxylic acid amide (CAA) fungicides" (Fungicide Resistance Action Committee (FRAC) code 40) are proposed to inhibit phospholipid biosynthesis and cell wall deposition. Inhibition of these processes prevents growth and leads to death of the target fungus. Carboxylic acid amide fungicides include cinnamic acid amide, valinamide carbamate and mandelic acid amide fungicides. The cinnamic acid amides include dimethomorph and flumorph. The valinamide carbamates include benthiavalicarb, benthiavalicarb-isopropyl, iprovalicarb and valiphenal. The mandelic acid amides include mandipropamid, JV-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]ethyl]- 3-methyl-2-[(methylsulfonyl)amino]butanamide and Λ/-[2-[4-[[3-(4-chlorophenyl)-2-propyn- 1 -yl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(ethylsulfonyl)amino]butanamide.
(41) "Tetracycline antibiotic fungicides" (Fungicide Resistance Action Committee (FRAC) code 41) inhibit growth of fungi by affecting complex 1 nicotinamide adenine dinucleotide (NADH) oxidoreductase. Examples include oxytetracycline.
(42) "Thiocarbamate fungicides (b42)" (Fungicide Resistance Action Committee (FRAC) code 42) include methasulfocarb.
(43) "Benzamide fungicides" (Fungicide Resistance Action Committee (FRAC) code 43) inhibit growth of fungi by derealization of spectrin-like proteins. Examples include acylpicolide fungicides such as fluopicolide and fluopyram.
(44) "Host plant defense induction fungicides" (Fungicide Resistance Action Committee (FRAC) code P) induce host plant defense mechanisms. Host plant defense induction fungicides include benzo-thiadiazole, benzisothiazole and thiadiazole-carboxamide fungicides. The benzo-thiadiazoles include acibenzolar-S-methyl. The benzisothiazoles include probenazole. The thiadiazole-carboxamides include tiadinil and isotianil.
(45) "Multi-site contact fungicides" inhibit fungal growth through multiple sites of action and have contact/preventive activity. This class of fungicides includes: (45.1)
"copper fungicides" (Fungicide Resistance Action Committee (FRAC) code Ml)", (45.2) "sulfur fungicides" (Fungicide Resistance Action Committee (FRAC) code M2), (45.3) "dithiocarbamate fungicides" (Fungicide Resistance Action Committee (FRAC) code M3), (45.4) "phthalimide fungicides" (Fungicide Resistance Action Committee (FRAC) code M4), (45.5) "chloronitrile fungicides" (Fungicide Resistance Action Committee (FRAC) code M5),
(45.6) "sulfamide fungicides" (Fungicide Resistance Action Committee (FRAC) code M6),
(45.7) "guanidine fungicides" (Fungicide Resistance Action Committee (FRAC) code M7),
(45.8) "triazine fungicides" (Fungicide Resistance Action Committee (FRAC) code M8) and (45.9) "quinone fungicides" (Fungicide Resistance Action Committee (FRAC) code M9). "Copper fungicides" are inorganic compounds containing copper, typically in the copper(II) oxidation state; examples include copper oxychloride, copper sulfate and copper hydroxide, including compositions such as Bordeaux mixture (tribasic copper sulfate). "Sulfur fungicides" are inorganic chemicals containing rings or chains of sulfur atoms; examples include elemental sulfur. "Dithiocarbamate fungicides" contain a dithiocarbamate molecular moiety; examples include mancozeb, metiram, propineb, ferbam, maneb, thiram, zineb and ziram. "Phthalimide fungicides" contain a phthalimide molecular moiety; examples include folpet, captan and captafol. "Chloronitrile fungicides" contain an aromatic ring substituted with chloro and cyano; examples include chlorothalonil. "Sulfamide fungicides" include dichlofluanid and tolyfluanid. "Guanidine fungicides" include dodine, guazatine, iminoctadine albesilate and iminoctadine triacetate. "Triazine fungicides" include anilazine. "Quinone fungicides" include dithianon.
(46) "Fungicides other than fungicides of classes (1) through (45)" include certain fungicides whose mode of action may be unknown. These include: (46.1) "thiazole carboxamide fungicides" (Fungicide Resistance Action Committee (FRAC) code U5), (46.2) "phenyl-acetamide fungicides" (Fungicide Resistance Action Committee (FRAC) code U6), (46.3) "quinazolinone fungicides" (Fungicide Resistance Action Committee (FRAC) code U7) and (46.4) "benzophenone fungicides" (Fungicide Resistance Action Committee (FRAC) code U8). The thiazole carboxamides include ethaboxam. The phenyl-acetamides include cyflufenamid and N-[[(cyclopropylmethoxy)amino][6-(difluoromethoxy)-2,3- difluorophenyl]-methylene]benzeneacetamide. The quinazolinones include proquinazid and 2-butoxy-6-iodo-3-propyl-4H-l-benzopyran-4-one. The benzophenones include metrafenone. The (b46) class also includes bethoxazin, neo-asozin (ferric methanearsonate), pyrrolnitrin, quinomethionate, N-[2-[4-[[3-(4-chlorophenyl)-2-propyn-l-yl]oxy]-3-methoxy- phenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]butanamide, iV-[2-[4-[[3-(4-chloro- phenyl)-2-propyn- 1 -yl]oxy] -3 -methoxyphenyl] ethyl]-3 -methyl-2-[(ethylsulfonyl)amino] - butanamide, 2-[[2-fluoro-5-(trifluoromethyl)phenyl]thio]-2-[3-(2-methoxyphenyl)-2-thiazo- lidinylidene]acetonitrile, 3-[5-(4-chlorophenyl)-2,3-dimethyl-3-isoxazolidinyl]pyridine, 4-fluorophenyl Λ/-[l-[[[l-(4-cyanophenyl)ethyl]sulfonyl]methyl]propyl]carbamate, 5-chloro- 6-(2,4,6-trifluorophenyl)-7-(4-methylpiperidin- 1 -yl)[ 1 ,2,4]triazolo[ 1 ,5-α]pyrimidine, N-(4- chloro-2-nitrophenyl)-Λ/-ethyl-4-methylbenzenesulfonamide, N- [ [(cyclopropylmethoxy)- amino][6-(difluoromethoxy)-2,3-difluorophenyl]methylene]benzeneacetamide, 7V-[4-[4- chloro-3-(trifluoromethyl)phenoxy]-2,5-dimethylphenyl]-N-ethyl-N-methylmethanimid- amide and l-[(2-propenylthio)carbonyl]-2-(l-methylethyl)-4-(2-methylphenyl)-5-amino-lH- pyrazol-3-one.
Therefore of note is a mixture (i.e. composition) comprising a compound of Formula 1 and at least one fungicidal compound selected from the group consisting of the aforedescribed classes (1) through (46). Also of note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. Of particular note is a mixture (i.e. composition) comprising a compound of Formula 1 and at least one fungicidal compound selected from the group of specific compounds listed above in connection with classes (1) through (46). Also of particular note is a composition comprising said mixture (in fungicidally effective amount) and further comprising at least one additional surfactant selected from the group consisting of surfactants, solid diluents and liquid diluents. Examples of other biologically active compounds or agents with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, acetamiprid, acetoprole, aldicarb, amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, bistrifluron, buprofezin, carbofuran, cartap, chinomethionat, chlorfenapyr, chlorfluazuron, chlorantraniliprole, 3-bromo-l-(3-chloro-2-pyridinyl)-iV-[4- cyano-2-methyl-6-[[(l-methylethyl)amino]carbonyl]phenyl]-lH-pyrazole-5-carboxamide, 3- bromo- 1 -(3 -chloro-2-pyridinyl)-JV- [4-cyano-2-methyl-6- [(methylamino)carbonyl]phenyl] - lH-pyrazole-5-carboxamide, 3-chloro-l-(3-chloro-2-pyridinyl)-Λ/-[4-cyano-2-methyl-6- [(methylamino)carbonyl]phenyl]-lH-pyrazole-5-carboxamide, 3-chloro-l-(3-chloro-2- pyridinyl)-JV-[4-cyano-2-methyl-6- [ [( 1 -methylethyl)amino] carbonyljphenyl] - lH-pyrazole-5 - carboxamide, chlorpyrifos, chlorpyrifos-methyl, chlorobenzilate, chromafenozide, clothianidin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyhexatin, cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicofol, dieldrin, dienochlor, diflubenzuron, dimefluthrin, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etoxazole, fenamiphos, fenazaquin, fenbutatin oxide, fenothiocarb, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, tau-fluvalinate, flufenerim, flufenoxuron, fonophos, halofenozide, hexaflumuron, hexythiazox, hydramethylnon, imicyafos, imidacloprid, indoxacarb, isofenphos, lufenuron, malathion, metaflumizone, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, monocrotophos, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, spiridiclofen, spiromesifen, spirotetramat, sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumuron; and biological agents including entomopathogenic bacteria, such as Bacillus thuringiensis subsp. aizawai, Bacillus thuringiensis subsp. kurstaki, and the encapsulated delta-endotoxins of Bacillus thuringiensis (e.g., Cellcap, MPV, MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic virus including baculovirus, nucleopolyhedro virus (NPV) such as HzNPV, AfNPV; and granulosis virus (GV) such as CpGV. Compounds of this invention and compositions thereof can be applied to plants genetically transformed to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis delta-endotoxins). The effect of the exogenously applied fungicidal compounds of this invention may be synergistic with the expressed toxin proteins.
General references for agricultural protectants (i.e. insecticides, fungicides, nematocides, acaricides, herbicides and biological agents) include The Pesticide Manual, 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2001.
For embodiments where one or more of these various mixing partners are used, the weight ratio of these various mixing partners (in total) to the compound of Formula 1 (or an N-oxide or salt thereof) is typically between about 1 :3000 and about 3000:1. Of note are weight ratios between about 1 :300 and about 300:1 (for example, ratios between about 1 :30 and about 30:1). One skilled in the art can easily determine through simple experimentation the biologically effective amounts of active ingredients necessary for the desired spectrum of biological activity. It will be evident that including these additional components may expand the spectrum of diseases controlled beyond the spectrum controlled by the compound of Formula 1 alone.
In certain instances, combinations of a compound of this invention with other biologically active (particularly fungicidal) compounds or agents (i.e. active ingredients) can result in a greater-than-additive (i.e. synergistic) effect. Reducing the quantity of active ingredients released in the environment while ensuring effective pest control is always desirable. When synergism of fungicidal active ingredients occurs at application rates giving agronomically satisfactory levels of fungal control, such combinations can be advantageous for reducing crop production cost and decreasing environmental load. Of note is a combination of a compound of Formula 1 (or an N-oxide or salt thereof) with at least one other fungicidal active ingredient. Of particular note is such a combination where the other fungicidal active ingredient has different site of action from the compound of Formula 1. In certain instances, a combination with at least one other fungicidal active ingredient having a similar spectrum of control but a different site of action will be particularly advantageous for resistance management. Thus, a composition of the present invention can further comprise a biologically effective amount of at least one additional fungicidal active ingredient having a similar spectrum of control but a different site of action. Of note are these methods where plant diseases caused by Oomycete fungal plant pathogens are controlled.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pathogens. The pathogen control protection afforded by the compounds is not limited, however, to these species. See Index Tables A and B for compound descriptions. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared. Index Tables A and B lists the molecular weight of the highest isotopic abundance parent ion (M+ 1) formed by addition of H+ (molecular weight of 1) to the molecule, observed by mass spectrometry using atmospheric pressure chemical ionization (AP+). The group GG in Index Tables A and B can be either GA, GN or Gp as defined in the Summary of the Invention. The wavy line indicates the point of attachment of each QZ3 GG group to the J ring (isoxazoline). Z2 is a direct bond and thus is decicted as a line between Q and the isoxazoline ring.
INDEX TABLE A
Figure imgf000173_0001
Cmpd. QZ3GG m.p. (0C) AP+ (M+l)
1 (Ex. 1)
Figure imgf000173_0002
Cmpd. QZ3GG m.p. (0C) AP+ (M+l)
Figure imgf000174_0001
Cmpd. QZ3GG m.p. (0C) AP+ (M+l)
Figure imgf000175_0001
Cmpd. QZ3GG m.p. (0C) AP+ (M+l)
Figure imgf000176_0001
* See synthesis example for ^H NMR data.
** See Index Table B for 1H NMR data.
# This compound is a 3 to 1 mixture of the 3 -phenyl and 5 -phenyl regioisomers.
INDEX TABLE B
Figure imgf000176_0002
Cmpd. QZ3GG m.p. (0C) AP+ (M+l)
Figure imgf000177_0001
See synthesis example for ^H NMR data.
INDEX TABLE C
Cmpd. IH NMR Data (CDCI3 solution unless indicated otherwise)81 δ 1.70-1.90 (m, 2H), 2.20 (t, 2H), 2.32 (s, 3H), 2,89 (t, IH), 3.25-3.40 (m, 2H), 3.45 (dd, IH), 3.88 (dd, IH), 4.04 (d, IH), 4.57 (br d, IH), 4.92-5.05 (m, 2H), 5.80 (dd, IH), 6.33 (s, IH), 7.35 (t, IH), 7.40-7.50 (m, 4H), 7.55-7.68 (m, 5H). a ^H NMR data are in ppm downlield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (m)-multiplet, (dd)-doublet of doublets, (br d)-broad doublet.
BIOLOGICAL EXAMPLES OF THE INVENTION
General protocol for preparing test suspensions for Test A-C: The test compounds were first dissolved in acetone in an amount equal to 3 % of the final volume and then suspended at the desired concentration (in ppm) in acetone and purified water (50/50 mix by volume) containing 250 ppm of the surfactant Trem® 014 (polyhydric alcohol esters). The resulting test suspensions were then used in Tests A-C. Spraying a 40 ppm test suspension to the point of run-off on the test plants was equivalent to a rate of 100 g/ha.
TEST A
Grape seedlings were inoculated with a spore suspension of Plasmopara viticola (the causal agent of grape downy mildew) and incubated in a saturated atmosphere at 20 0C for 24 h. After a short drying period, the test suspension was sprayed to the point of run-off on the grape seedlings, which were then moved to a growth chamber at 20 0C for 5 days, after which time the grape seedling were placed back into a saturated atmosphere at 20 0C for 24 h. Upon removal, visual disease ratings were made.
TEST B
The test suspension was sprayed to the point of run-off on tomato seedlings. The following day the seedlings were inoculated with a spore suspension of Phytophthora infestans (the causal agent of tomato late blight) and incubated in a saturated atmosphere at 20 0C for 24 h, and then moved to a growth chamber at 20 0C for 5 days, after which time visual disease ratings were made.
TEST C
Tomato seedlings were inoculated with a spore suspension of Phytophthora infestans
(the causal agent of tomato late blight) and incubated in a saturated atmosphere at 20 0C for 17 h. After a short drying period, the test suspension was sprayed to the point of run-off on the tomato seedlings, which were then moved to a growth chamber at 20 0C for 4 days, after which time visual disease ratings were made.
In addition to Tests A-C, the compounds were also sprayed on tomato plants, which were inoculated with Alternaria solani 24 h after treatment, and wheat plants, which were inoculated with Erysiphe graminis f. sp. tritici 24 h after treatment. Test compounds did not show noticeable activity against these additional pathogens under the test conditions at the application rates tested.
Results for Tests A-C are given in Table A. In the table, a rating of 100 indicates 100 % disease control and a rating of 0 indicates no disease control (relative to the controls).
TABLE A
Percent Disease Control
Compound Test A Test B Test C 1 91 100 99
2 76 90 32 3 97 100 93 4 58 99 83 Percent Disease Control
Compound TestA Test B Test C 5 98 100 99 6 87 100 99
7 73 99 86
0 100 53
0 100 17
10 10 100 93 11 99 100 99 12 31 100 99 13 56 100 93 14 82 100 99 15 92 100 97 16 99 100 99 17 98 100 99 18 67 93 58 19 99 100 99

Claims

CLAIMSWhat is claimed is:
1. A compound selected from the compounds of Formula 1 and iV-oxides and salts thereof,
Figure imgf000180_0001
wherein
R1 is an optionally substituted phenyl or 5- or 6-membered heteroaromatic ring or optionally substituted naphthalenyl; A is CHR15 or NR16;
R15 is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2-C4 alkylsulfmylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3-C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3-C5 dialkylaminocarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1- C4 haloalkylthio, C1-C4 alkylsulfϊnyl, C1-C4 haloalkylsulfmyl, C1-C4 alkylsulfonyl or C1-C4 haloalkylsulfonyl;
R16 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, C2-
C4 alkylsulfinylalkyl, C2-C4 alkylsulfonylalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl, C2-C5 alkoxycarbonyl, C3-C5 alkoxycarbonylalkyl, C2-C5 alkylaminocarbonyl, C3-C5 dialkylaminocarbonyl, C1-C4 alkylsulfonyl or C1- C4 haloalkylsulfonyl; W is O or S;
X is a radical selected from
Figure imgf000180_0002
X1 X^ XJ X4
Figure imgf000181_0001
X5 X6 X7
Figure imgf000181_0002
1 X9 wherein the bond of X1, X2, X3, X4, X5, X6, X7, X8 or χ9 which is identified with "t" is connected to the carbon atom identified with "q" of Formula 1, the bond which is identified with "u" is connected to the carbon atom identified with "r" of
Formula 1, and the bond which is identified with "v" is connected to G; each R2 is independently C1-C4 alkyl, C1-C4 alkenyl, C1-C4 haloalkyl, C1-C4 alkoxy, halogen, cyano or hydroxy; or two R2 are taken together as C1-C4 alkylene or C2-C4 alkenylene to form a bridged bicyclic or fused bicyclic ring system; or two R2 attached to adjacent ring carbon atoms joined by a double bond are taken together as -CH=CH-CH=CH- optionally substituted with 1 to 3 substituents selected from C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, halogen, hydroxy, amino, cyano and nitro; G is an optionally substituted 5-membered heterocyclic ring;
J is a 5-, 6- or 7-membered ring, a 8- to 11-membered bicyclic ring system or a 7- to 11-membered spirocyclic ring system, each ring or ring system containing ring members selected from carbon, up to 4 heteroatoms selected from up to 2 O, up to 2 S and up to 4 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18, each ring or ring system substituted with 1 to 2 substituents independently selected from -Z2Q and optionally substituted with 1 to 5 substituents independently selected from R5; each R5 is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH,
-C(K))NH2, -NR25R26, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-C10 alkylcycloalkyl, C4-C10 cycloalkylalkyl, C6-C14 cycloalkylcycloalkyl, C4-C10 halocycloalkylalkyl, C5-Q0 alkylcycloalkylalkyl, C3-C8 cycloalkenyl, C3-C8 halocycloalkenyl, C2-C6 alkoxyalkyl, C4-C10 cycloalkoxyalkyl, C3-C8 alkoxyalkoxyalkyl, C2-C6 alkylthioalkyl, C2-C6 alkylsulfinylalkyl, C2-C6 alkylsulfonylalkyl, C2-C6 alkylaminoalkyl, C3-C8 dialkylaminoalkyl, C2-C6 haloalkylaminoalkyl, C4-C10 cycloalkylaminoalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C4-C8 cycloalkylcarbonyl, C2- C6 alkoxycarbonyl, C4-C8 cycloalkoxycarbonyl, C5-C1Q cycloalkylalkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl, C4~C8 cycloalkylaminocarbonyl, C2-C6 haloalkoxyalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkoxy, C3- Cg halocycloalkoxy, C 4-C1Q cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 haloalkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C4~C8 cycloalkylcarbonyloxy, C3-C6 alkylcarbonylalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, C3-C8 cycloalkylthio, C1-C6 alkylsulfmyl, C1-C6 haloalkylsulfϊnyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C3-C8 cycloalkylsulfonyl, C3-C1Q trialkylsilyl, C1-C6 alkylsulfonylamino or C1-C6 haloalkylsulfonylamino;
R25 is H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2- C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl or C2-C6 haloalkoxycarbonyl; R26 is C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 haloalkoxycarbonyl or -Z4Q; each R17 and R18 is independently C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C3- C5 cycloalkyl, C3-C6 halocycloalkyl, C 4-C1Q cycloalkylalkyl, C4-C7 alkylcycloalkyl, C5-C7 alkylcycloalkylalkyl, C1-C5 haloalkyl, C1-C5 alkoxy or C1-C5 haloalkoxy; each Q is independently phenyl, benzyl, naphthalenyl, a 5- or 6-membered heteroaromatic ring or an 8- to 11-membered heteroaromatic bicyclic ring system, each substituted with 1 to 2 substituents independently selected from R7 on carbon or nitrogen atom ring members, and each optionally substituted with 1 to 5 substituents independently selected from R7a on carbon atom ring members and R12 on nitrogen atom ring members; or a 3- to 7-membered nonaromatic carbocyclic ring, a 5-, 6- or 7-membered nonaromatic heterocyclic ring or an 8- to 11-membered nonaromatic bicyclic ring system, each optionally including ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17R18, and each ring or ring system substituted with 1 to 2 substituents independently selected from R7 on carbon or nitrogen atom ring members, and each optionally substituted with 1 to 5 substituents independently selected from R7a on carbon atom ring members and R12 on nitrogen atom ring members; each R7 is independently -Z3GA, -Z3GN or -Z3GP; each GA is independently a phenyl or 5- or 6-membered heteroaromatic ring, each ring substituted with up to 5 substituents independently selected from Rv on carbon atom ring members and R22 on nitrogen atom ring members; each GN is independently a 3- to 7-membered nonaromatic ring including ring members selected from (CRV)2, O, S, NR22, -C(RV)=C(RV)-, -C(RV)=N-, -N=N-, C(=O), C(=S), C(=NR23), S(=O)a(=NR23)b and SiR17R18; each Gp is independently an 8- to 10-membered aromatic or 7- to 11-membered nonaromatic bicyclic ring system, said ring system including ring members selected from (CRV)2, O, S, NR22, -C(RV)=C(RV)-, -C(RV)=N-, -N=N-, C(=O), C(=S), C(=NR23), S(=O)a(=NR23)b and SiR17R18; each Rv is independently H, halogen, cyano, hydroxy, amino, nitro, -CHO, -C(=O)OH, -C(=O)NH2, -SO2NH2, -C(=S)NH2, -C(=O)NHCN, -C(=0)NH0H, -SH, -SO2NHCN, -SO2NHOH, -OCN, -SCN, -SF5, -NHCHO, -NHNH2,
-N3, -NHOH, -NHCN, -NHC(=0)NH2, -N=C=O, -N=C=S, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C8 alkylcarbonyl, C2-C8 haloalkylcarbonyl, C2-C8 alkoxycarbonyl, C 4-C1Q cycloalkoxycarbonyl, C5- C12 cycloalkylalkoxycarbonyl, C2-C8 alkylaminocarbonyl, C3-C1Q dialkylaminocarbonyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C4-Q0 alkylcycloalkyl, C4-Q0 cycloalkylalkyl, C6-C^ cycloalkylcycloalkyl, C4-Q0 halocycloalkylalkyl, C5- C12 alkylcycloalkylalkyl, C3-C8 cycloalkenyl, C3-C8 halocycloalkenyl, C2-C8 alkoxyalkyl, C4-Q0 cycloalkoxyalkyl, C3-C1Q alkoxyalkoxyalkyl, C2-C8 alkylthioalkyl, C2-C8 alkylsulfmylalkyl, C2-C8 alkylsulfonylalkyl, C2-C8 alkylaminoalkyl, C3-C1Q dialkylaminoalkyl, C2-C8 haloalkylaminoalkyl, C4- C1Q cycloalkylaminoalkyl, C^C1Q cycloalkylcarbonyl, C^C1Q cycloalkylaminocarbonyl, C2-C7 cyanoalkyl, C1-C6 hydroxyalkyl, C4-Q0 cycloalkenylalkyl, C2-C8 haloalkoxyalkyl, C2-C8 alkoxyhaloalkyl, C2-C8 haloalkoxyhaloalkyl, C4-Q0 halocycloalkoxyalkyl, C4-Q0 cycloalkenyloxyalkyl, C4-Q0 halocycloalkenyloxyalkyl, C3-C1Q dialkoxyalkyl, C-^-C12 trialkoxyalkyl, C3-C8 alkoxyalkenyl, C3-C8 alkoxyalkynyl, C3-C1Q halodialkylaminoalkyl, C5-C12 cycloalkyl(alkyl)aminoalkyl, C2-C8 alkyl(thiocarbonyl), C3-C1Q alkoxyalkylcarbonyl, C3-C1Q alkoxycarbonylalkyl, C2-C8 haloalkoxycarbonyl, C3-C1Q alkoxyalkoxycarbonyl, C2-C8
(alkylthio)carbonyl, C2-C8 alkoxy(thiocarbonyl), C2-C8 alkylthio(thiocarbonyl), C2-C8 alkylamino(thiocarbonyl), C3-C1Q dialkylamino(thiocarbonyl), C3-C1Q alkoxy(alkyl)aminocarbonyl, C2-C8 alkylsulfonylaminocarbonyl, C2-C8 haloalkylsulfonylaminocarbonyl, C2-C8 alkylamidino, C3-C1Q dialkylamidino, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C8 alkylcarbonyloxy, C1-C6 alkylthio,
C1-C6 haloalkylthio, C1-C6 alkylsulfmyl, C1-C6 haloalkylsulfmyl, C1-C6 alkylsulfonyl, C1-C6 haloalkylsulfonyl, C1-C6 alkylaminosulfonyl, C2-C8 dialkylaminosulfonyl, C3-C1Q trialkylsilyl, C3-C8 cycloalkoxy, C3-C8 halocycloalkoxy, C4-C1Q cycloalkylalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C3-C6 haloalkynyloxy, C2-Cg alkoxyalkoxy, C2-Cg haloalkylcarbonyloxy, C4-C1Q cycloalkylcarbonyloxy, C3-C1Q alkylcarbonylalkoxy, C3-Cg cycloalkylthio, C3-Cg cycloalkylsulfonyl, C3-Cg cycloalkenyloxy, C3-Cg halocycloalkenyloxy, C2-Cg haloalkoxyalkoxy,
C2-Cg alkoxyhaloalkoxy, C2-Cg haloalkoxyhaloalkoxy, C3-C1Q alkoxycarbonylalkoxy, C2-Cg alkyl(thiocarbonyl)oxy, C2-Cg alkylcarbonylthio, C2-Cg alkyl(thiocarbonyl)thio, C3-Cg cycloalkylsulfϊnyl, C3-C1Q halotrialkylsilyl, C1-C6 alkylamino, C2-Cg dialkylamino, C2-Cg alkylcarbonylamino, C1-C6 alkylsulfonylamino, C1-C6 haloalkylamino, C2-Cg halodialkylamino, C3-Cg cycloalkylamino, C2-Cg haloalkylcarbonylamino, C1- C6 haloalkylsulfonylamino, C4-C1Q cycloalkylalkylamino, C4-C1Q cycloalkyl(alkyl)amino, C3-C1Q alkoxycarbonylalkylamino, C^-C6 alkoxyamino, C^-C6 haloalkoxyamino, C4-C12 dialkylimido, C2~Cg alkoxycarbonylamino, C2~Cg haloalkoxycarbonylamino, C2~Cg alkylaminocarbonylamino, C3-C10 dialkylaminocarbonylamino, C3-C10 alkylaminocarbonylalkylamino, C4-C12 dialkylaminocarbonylalkylamino, C2- Cg alkylamino(thiocarbonyl)amino, C3-C10 dialkylamino(thiocarbonyl)amino, C3-C10 alkylamino(thiocarbonyl)alkylamino or C4-C12 dialkylamino(thiocarbonyl)alkylamino; each R7a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-CJQ cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, C^-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C1-C4 alkoxy, C1-C4 haloalkoxy, C ^C4 alkylthio, C ^C4 alkylsulfϊnyl, C ^C4 alkylsulfonyl,
C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-Cg dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-Cg dialkylaminocarbonyl or C3-C6 trialkylsilyl; or
R5 and R7a are taken together with the atoms linking R5 and R7a to form an optionally substituted 5- to 7-membered ring containing ring members selected from carbon, up to 3 heteroatoms selected from up to 1 O, up to 1 S and up to 1 N, and up to 3 ring members selected from C(=O), C(=S), S(=O)a(=NR23)b and SiR17RlS;
R12 is H, C1-C3 alkyl, C1-C3 alkylcarbonyl, C1-C3 alkoxy or C1-C3 alkoxycarbonyl; each Z1 and Z2 is independently a direct bond, O, C(=O), S(O)m, CHR20 or NR21; each Z3 is independently a direct bond, O, NR22, C(=O), C(=S), S(O)m, CHR20,
CHR20-CHR20, CR24=CR27, C≡C, OCHR20 or CHR20O; each Z4 is independently O, C(=0), S(0)m or CHR20; each R20 is independently H, C1-C4 alkyl or C1-C4 haloalkyl; each R21 is independently H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl or C2-C6 haloalkoxycarbonyl; each R22 is independently H, C1-C4 alkyl or C1-C4 haloalkyl; each R23 is independently H, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C3-C8 halocycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylamino,
C2-C8 dialkylamino, C1-C6 haloalkylamino or phenyl; each R24 and R27 is independently H, C1-C4 alkyl or C1-C4 haloalkyl; each m is independently 0, 1 or 2; n is 0, 1 or 2; and a and b are independently 0, 1 or 2 in each instance of S(=O)a(=NR23)b, provided that the sum of a and b is 1 or 2.
2. A compound of Claim 1 wherein
R1 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with
1-3 substituents independently selected from R4a on carbon ring members and R4^ on nitrogen ring members;
G is a 5-membered heterocyclic ring optionally substituted with up to 2 substituents selected from R3 on carbon ring members and selected from R11 on nitrogen ring members;
J is one of J-I through J-82 (as depicted in Exhibit 3) wherein the bond shown projecting to the left is bonded to Z1;
Exhibit 3
Figure imgf000185_0001
J-I J-2 J-3 J-4
Figure imgf000185_0002
J-5 J-6 J-7 J-8
Figure imgf000186_0001
J-9 J-IO J-I l J-12
Figure imgf000186_0002
J-13 J-14 J-15 J-16
Figure imgf000186_0003
J-17 J-18 J-19 J-20
Figure imgf000186_0004
J-21 J-22 J-23 J-24
Figure imgf000186_0005
J-25 J-26 J-27 J-28
Figure imgf000186_0006
J-29 J-30 J-31 J-32
Figure imgf000187_0001
J-33 J-34 J-35 J-36
Figure imgf000187_0002
J-37 J-38 J-39 J-40
Figure imgf000187_0003
J-41 J-42 J-43 J-44
Figure imgf000187_0004
J-45 J-46 J-47 J-48
J-49 J-50 J-51 J-52
Figure imgf000187_0006
J-53 J-54 J-55 J-56
Figure imgf000188_0001
J-61 J-62 J-63 J-64
5 π (R?f"V (ZZQ) (R5)XN(Z2Q)S
Figure imgf000188_0003
Figure imgf000188_0002
J-65 J-66 J-67 J-68
Figure imgf000188_0004
J-69 J-70 J-71 J-72
Figure imgf000188_0005
J-73 J-74 J-75 J-76
Figure imgf000188_0006
J-77 J-78 J-79 J-80
Figure imgf000189_0001
J-81 J-82
each R2 is independently C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, halogen, cyano or hydroxy; each R3 is independently C1-C3 alkyl, C1-C3 haloalkyl or halogen; each R4a is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C4-C10 alkylcycloalkyl, C5-C10 alkylcycloalkylalkyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C3-C6 halocycloalkyl, halogen, hydroxy, amino, cyano, nitro, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfmyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylthio, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylamino, C2-Cg dialkylamino, C3-C6 cycloalkylamino, C2-C4 alkoxyalkyl,
C1-C4 hydroxyalkyl, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylcarbonyloxy, C2-C6 alkylcarbonylthio, C2-C6 alkylaminocarbonyl, C3-Cg dialkylaminocarbonyl or C3-C6 trialkylsilyl; each R4b is independently C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C ^C6 haloalkyl, C3-C6 haloalkenyl, C3-C6 haloalkynyl, C3-C6 halocycloalkyl or C2-C4 alkoxyalkyl; each R11 is independently C1-C3 alkyl;
R15 is H, halogen, cyano, hydroxy, -CHO, C1-C4 alkyl, C1-C4 haloalkyl or C2-C5 alkoxycarbonyl; R16 is H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkylcarbonyl, C2-C4 haloalkylcarbonyl or C2-C4 alkoxycarbonyl; x is an integer from 0 to 5; and s is an integer from 1 to 2.
3. A compound of Claim 2 wherein G is one of G-I through G-59 (as depicted in Exhibit 2) wherein the bond projecting to the left is bonded to X, and bond projecting to the right is bonded to Z1; Exhibit 2
Figure imgf000190_0001
G-5 G-6 G-7 G-8
Figure imgf000190_0002
G-9 G-IO G-I l G-12
Figure imgf000190_0003
G-20
Figure imgf000191_0001
G-29 G-30 G-31 G-32
Figure imgf000191_0002
G-37 G-38 G-39 G-40
Figure imgf000192_0001
G-45 G-46 G-47 G-48
Figure imgf000192_0002
J is selected from J-I, J-2, J-3, J-4, J-5, J-7, J-8, J-9, J-IO, J-I l, J-12, J-14, J-15, J-16,
J-20, J-24, J-25, J-26, J-29, J-30, J-37, J-38, J-45 and J-69; Q is one of Q-I through Q- 106 (as depicted in Exhibit 4); Exhibit 4
Q-5 Q-6 Q-8
Figure imgf000193_0002
Q-9 Q-IO Q-I l Q-12
Figure imgf000193_0003
Q-13 Q-14 Q-15 Q-16
Figure imgf000193_0004
Q-17 Q-18 Q-19 Q-20
Figure imgf000193_0005
Q-21 Q-22 Q-23 Q-24
Figure imgf000194_0001
Q-25 Q-26 Q-27 Q-28
Figure imgf000194_0002
Q-41 Q-42 Q-43 Q-44
Figure imgf000194_0003
Figure imgf000194_0004
Q-46 Q-47 Q-48
Figure imgf000195_0001
Q-49 Q-50 Q-51 Q-52
Figure imgf000195_0002
Q-53 Q-54 Q-55
Figure imgf000195_0003
Q-59 Q-60 Q-61
Figure imgf000195_0004
Q-62 Q-63 Q-64
Q-65 Q-66 Q-67
Figure imgf000196_0001
Q-68 Q-69 Q-70
Figure imgf000196_0002
Q-74 Q-75 Q-76
Figure imgf000196_0003
Q-77 Q-78 Q-79
Figure imgf000196_0004
Q-80 Q-81 Q-82
Figure imgf000197_0001
Q-83 Q-84 Q-85 -86 Q-87 Q-88
Figure imgf000197_0003
Q-89 Q-90 Q-91
Figure imgf000197_0004
Q-92 Q-93 Q-94
Figure imgf000197_0005
Q-95 Q-96 Q-97
Figure imgf000198_0001
Q-98 Q-99 Q-IOO
Figure imgf000198_0002
Q-IOl Q- 102 Q-103
Figure imgf000198_0003
Q- 104 Q-105 Q-106
R1 is one of U-I through U-50 (as depicted in Exhibit 1);
Exhibit 1
Figure imgf000198_0004
U-I U-2 U-3 U-4
Figure imgf000198_0005
U-5 U-6 U-7 U-8
Figure imgf000198_0006
U-9 U-IO U-I l U-12
Figure imgf000199_0001
U-13 U-14 U-15 U-16
Figure imgf000199_0002
U-17 U-18 U-19 U-20
Figure imgf000199_0003
U-21 U-22 U-23 U-24
Figure imgf000199_0004
U-25 U-26 U-27 U-28
Figure imgf000199_0005
U-29 U-30 U-31 U-32
Figure imgf000199_0006
U-33 U-34 U-35 U-36
Figure imgf000199_0007
Figure imgf000199_0008
U-38 U-39
Figure imgf000199_0009
Figure imgf000200_0001
U-45 U-46 U-47 U-48
Figure imgf000200_0002
wherein when R4 is attached to a carbon ring member, said R4 is selected from R4a, and when R4 is attached to a nitrogen ring member (e.g., in U-4, U-I l through U-15, U-24 through U-26, U-31 or U-35), said R4 is selected from R4b; each R2 is independently methyl, methoxy, cyano or hydroxy; each R3a is independently selected from H and R3; each R5 is independently H, cyano, C^-C6 alkyl, C^-C6 haloalkyl, C3~Cg cycloalkyl, C3-C8 halocycloalkyl, C2-C6 alkoxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3~Cg cycloalkoxy, C2-C6 alkenyloxy, C2-C6 haloalkenyloxy, C2-C6 alkynyloxy, C2-C6 alkoxyalkoxy, C2-C6 alkylcarbonyloxy, C2-C6 haloalkylcarbonyloxy, C^-C6 alkylthio, C^-C6 haloalkylthio, C3-C10 trialkylsilyl or -NR25R26; R1 la is selected from H and R11 ; R15 is H, cyano, hydroxy, methyl or methoxycarbonyl; R16 is H, methyl, methylcarbonyl or methoxycarbonyl; each Z4 is C(=O); k is 0, 1 or 2; p is 1 or 2; q is 0, 1, 2, 3, 4 or 5; and s is l.
4. A compound of Claim 3 wherein G is selected from G-I, G-2, G-7, G-8, G-14, G-15, G-23, G-24, G-26, G-27, G-36, G-37, G-38, G-49, G-50 and G-55;
J is selected from J-4, J-5, J-8, J-I l, J-15, J-16, J-20, J-29, J-30, J-37, J-38 and J-69; each Q is independently Q-I, Q-20, Q-32 through Q-34, Q-45 through Q-47, Q-60 through Q-73, Q-76 through Q-79, Q-84 through Q-94 and Q-98 through Q- 106;
A is CH2 or NH;
W is O;
X iS X^ X2 Or X3;
Z1 is a direct bond; Z2 is a direct bond or NR21 ;
R1 is selected from U-I through U-3, U-I l, U-13, U-20, U-22, U-23, U-36 through U-39 and U-50; each R3 is independently methyl or halogen; each R4a is independently C1-C2 alkyl, C1-C2 haloalkyl, halogen, C1-C2 alkoxy or C1-C2 haloalkoxy; each R4^ is independently C1-C2 alkyl or C1-C2 haloalkyl; each R7a is independently C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, halogen, cyano, C1-C4 alkoxy, C1-C4 haloalkoxy or C2-C6 alkoxycarbonyl; k is 1 or 2; and n is 0.
5. A compound of Claim 4 wherein A is CH2;
G is selected from G-I, G-2, G-15, G-26, G-27, G-36, G-37 and G-38; and G is unsubstituted; J is J-29;
Q is selected from Q-I, Q-45, Q-63, Q-64, Q-65, Q-68, Q-69, Q-70, Q-71, Q-72, Q-73,
Q-76, Q-78, Q-79, Q-84, Q-85, Q-98, Q-99, Q-IOO and Q-IOl through Q-106; X is X1 or X2; and the ring comprising X is saturated; RMs U-I5 U^O Or U-SO; each R4a is independently C1-C2 alkyl, trifluoromethyl, Cl, Br, I or methoxy; each R4b is independently C1-C2 alkyl or trifluoromethyl; and each R5 is independently H, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy,
C1-C6 haloalkoxy or -NR25R26.
6. A compound of Claim 5 wherein G is selected from G-I, G-2, G-15, G-26 and G-36;
J is any one of J-29- 1 to J-29-60 (depicted with Exhibit A); Exhibit A
Figure imgf000202_0001
J-29-1 J-29-2
Figure imgf000202_0002
J-29-3 J-29-4
Figure imgf000202_0003
J-29-9 J-29-10
Figure imgf000203_0001
J-29-13 J-29-14
Figure imgf000203_0002
J-29-15 J-29-16
Figure imgf000203_0003
J-29-17 J-29-18
Figure imgf000204_0001
J-29-23
Figure imgf000204_0002
J-29-25 J-29-26
Figure imgf000205_0001
J-29-29
Figure imgf000205_0002
J-29-31 J-29-32
Figure imgf000205_0003
J-29-33 J-29-34
Figure imgf000206_0001
J-29-35 J-29-36
Figure imgf000206_0002
J-29-37 J-29-38
Figure imgf000206_0003
J-29-39 J-29-40
Figure imgf000206_0004
J-29-41 J-29-42
Figure imgf000207_0001
J-29-45 J-29-46
Figure imgf000207_0002
J-29-47 J-29-48
Figure imgf000207_0003
J-29-49 J-29-50
Figure imgf000208_0001
J-29-51 J-29-52
Figure imgf000208_0002
J-29-59 J-29-60 wherein the bond shown projecting to the left is bonded to Z1 and Ph is phenyl. Q is selected from Q-45, Q-63, Q-64, Q-65, Q-68, Q-69, Q-70, Q-71, Q-72 and Q-85; and
X is X1.
7. A compound of Claim 1 selected from the group consisting of: l-[4-[4-[4,5-dihydro-5-[3-(lH-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl]-2-thiazolyl]-l- piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]ethanone, and l-[4-[4-(5-[l,l '-biphenyl]-4-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-l-piperidinyl]- 2-[5-methyl-3-(trifluoromethyl)- lH-pyrazol- 1 -yljethanone. 4-[4-(5-[l,r-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-N-(2,5- dimethylphenyl)- 1 -piperidinecarboxamide,
4-[4-(4,5-dihydro-5-[2-(lH-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl)-2-thiazolyl]-N- (2,5-dimethylphenyl)- 1 -piperidinecarboxamide, l-[4-[4-[4,5-dihydro-5-[2-(lH-l,2,4-triazol-l-yl)phenyl]-3-isoxazolyl]-2-thiazolyl]-l- piperidinyl] -2-[5 -methyl-3 -(trifluoromethyl)- lH-pyrazol- 1 -yl] ethanone, l-[4-[4-[5-[2-fluoro-6-(lH-l,2,4-triazol-l-yl)phenyl]-4,5-dihydro-3-isoxazolyl]-2- thiazolyl]-l -piperidinyl]-2-[5-methyl-3-(trifluoromethyl)- lH-pyrazol- 1 -yljethanone, and l-[4-[4-(5-[l,r-biphenyl]-2-yl-4,5-dihydro-3-isoxazolyl)-2-thiazolyl]-l-piperidinyl]-2- [5-methyl-3-(trifluoromethyl)-lH-pyrazol-l-yl]ethanone.
8. A compound selected from the compounds of Formula IA and iV-oxides and salts thereof
Figure imgf000209_0001
IA wherein M is C1-C3 alkyl, C1-C3 haloalkyl, hydroxy, C1-C4 alkoxy, C1-C2 haloalkoxy, C1-C4 alkylamino, C2-Cg dialkylamino, 1 -piperidinyl, 1-pyrrolidinyl or 4-morpholinyl; and
J1 is any one of J-29-1 through J-29-60 as depicted in Claim 6 wherin the bond shown projecting to the left is bonded to -C(=O)M of Formula IA.
9. A method for controlling plant diseases caused by Oomycete fungal plant pathogens comprising applying to the plant or portion thereof, or to the plant seed or seedling, a fungicidally effective amount of a compound of Claim 1.
10. A fungicidal composition comprising (1) a compound of Claim 1; and (2) at least one other fungicide.
11. A fungicidal composition comprising (1) a compound of Claim 1; and (2) at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.
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Cited By (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009055514A2 (en) * 2007-10-23 2009-04-30 E. I. Du Pont De Nemours And Company Fungicidal mixtures
US20100267706A1 (en) * 2009-04-20 2010-10-21 Institute For Oneworld Health Compounds, Compositions and Methods Comprising Pyridazine Derivatives
WO2011051244A1 (en) 2009-10-30 2011-05-05 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives
WO2011076699A1 (en) 2009-12-21 2011-06-30 Bayer Cropscience Ag Bis(difluormethyl)pyrazoles used as fungicides
WO2011085170A1 (en) * 2010-01-07 2011-07-14 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
WO2011134969A1 (en) 2010-04-28 2011-11-03 Bayer Cropscience Ag Ketoheteroarylpiperidine and ketoheteroarylpiperazine derivates as fungicides
WO2011144586A1 (en) 2010-05-18 2011-11-24 Bayer Cropscience Ag Bis(difluoromethyl) pyrazoles as fungicides
WO2011146182A1 (en) * 2010-05-20 2011-11-24 E. I. Du Pont De Nemours And Company Fungicidal oximes and hydrazones
WO2011147765A1 (en) 2010-05-27 2011-12-01 Bayer Cropscience Ag Pyridinylcarboxylic acid derivatives as fungicides
WO2012020060A1 (en) 2010-08-11 2012-02-16 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
EP2423210A1 (en) 2010-08-25 2012-02-29 Bayer CropScience AG Heteroarylpiperidine and heteroarylpiperazine derivatives as fungicides
WO2012025557A1 (en) 2010-08-25 2012-03-01 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
WO2012055837A1 (en) 2010-10-27 2012-05-03 Bayer Cropscience Ag Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
EP2532233A1 (en) 2011-06-07 2012-12-12 Bayer CropScience AG Active compound combinations
US8349870B2 (en) 2008-01-25 2013-01-08 E I Du Pont De Nemours And Company Fungicidal hetercyclic compounds
WO2013037768A1 (en) 2011-09-15 2013-03-21 Bayer Intellectual Property Gmbh Piperidine pyrazoles as fungicides
WO2013098229A2 (en) 2011-12-27 2013-07-04 Bayer Intellectual Property Gmbh Heteroarylpiperidine and piperazine derivatives as fungicides
WO2013127704A1 (en) 2012-02-27 2013-09-06 Bayer Intellectual Property Gmbh Active compound combinations containing a thiazoylisoxazoline and a fungicide
US8618137B2 (en) 2008-12-02 2013-12-31 E I Du Pont De Nemours And Company Fungicidal heterocyclic compounds
JP2014501246A (en) * 2010-12-17 2014-01-20 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー Bactericidal and fungicidal azo cyclic amide
US8642634B2 (en) 2006-07-27 2014-02-04 E I Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2014033164A1 (en) 2012-08-30 2014-03-06 Bayer Cropscience Ag Procedure for the decarboxylation of 3,5-bis(haloalkyl)-pyrazole-4-carboxylic acid derivatives
US8697878B2 (en) 2008-12-11 2014-04-15 Bayer Cropscience Ag Thiazolyl oxime ethers and hydrazones as crop protection agents
US8822693B2 (en) 2011-02-01 2014-09-02 Bayer Cropscience Ag Heteroarylpiperidine and-piperazine derivatives as fungicides
EP2801575A1 (en) 2013-05-07 2014-11-12 Bayer CropScience AG Heteroaryldihydropyridine derivatives as fungicides
WO2014206896A1 (en) * 2013-06-24 2014-12-31 Bayer Cropscience Ag Piperidinecarboxylic acid derivatives as fungicides
US8927551B2 (en) 2009-05-18 2015-01-06 Infinity Pharmaceuticals, Inc. Isoxazolines as inhibitors of fatty acid amide hydrolase
US9090604B2 (en) 2006-07-27 2015-07-28 E I Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2015144571A1 (en) 2014-03-24 2015-10-01 Bayer Cropscience Ag Phenylpiperidinecarboxamide derivatives as fungicides
US9149465B2 (en) 2009-05-18 2015-10-06 Infinity Pharmaceuticals, Inc. Isoxazolines as inhibitors of fatty acid amide hydrolase
US9266876B2 (en) 2012-02-02 2016-02-23 Actelion Pharmaceuticals Ltd. 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
AU2014202324B2 (en) * 2007-10-23 2016-05-19 Corteva Agriscience Llc Fungicidal compounds and mixtures
WO2016202761A1 (en) 2015-06-17 2016-12-22 Bayer Cropscience Aktiengesellschaft Active compound combinations
AU2015261660B2 (en) * 2010-08-25 2017-01-05 Bayer Cropscience Aktiengesellschaft Heteroarylpiperidine and -piperazine derivatives as fungicides
KR20170036104A (en) 2014-08-13 2017-03-31 가부시키가이샤 에스디에스 바이오텍크 Condensed 11-member ring compound and agriculture and horticultural fungicide comprising same
WO2017138069A1 (en) 2016-02-08 2017-08-17 株式会社エス・ディー・エス バイオテック Germicidal composition
US9790182B2 (en) 2014-06-11 2017-10-17 Bayer Cropscience Aktiengesellschaft Preparation of piperidine-4-carbothioamide
US9924721B2 (en) 2013-08-28 2018-03-27 Bayer Cropscience Aktiengesellschaft Malonic ester derivatives of heteroarylpiperidines and -piperazines as fungicides
US9951063B2 (en) 2014-03-24 2018-04-24 Idorsia Pharmaceuticals Ltd 8-(piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinoline derivatives
US10047080B2 (en) 2015-01-15 2018-08-14 Idorsia Pharmaceuticals Ltd. (R)-2-methyl-piperazine derivatives as CXCR3 receptor modulators
US10053457B2 (en) 2015-01-15 2018-08-21 Idorsia Pharmaceuticals Ltd. Hydroxyalkyl-piperazine derivatives as CXCR3 receptor modulators
US10093626B2 (en) 2015-03-05 2018-10-09 Bayer Cropscience Aktiengesellschaft Process for preparing piperidine-4-carbothioamide hydrochloride
WO2018193387A1 (en) 2017-04-19 2018-10-25 Pi Industries Ltd. Heterocyclic compounds with microbiocidal properties
US10160707B2 (en) 2014-06-11 2018-12-25 Bayer Cropscience Aktiengesellschaft Process for preparing 3-chloro-2-vinylphenol
US10189799B2 (en) 2015-03-05 2019-01-29 Bayer Cropscience Aktiengesellschaft Process for preparing substituted phenylisoxazoline derivatives
WO2019048988A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungidal heterocyclic compounds
WO2019048989A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungicidal heterocyclic compounds
US10259807B2 (en) 2013-07-22 2019-04-16 Idorsia Pharmaceuticals Ltd. 1-(piperazin-1-yl)-2-([1,2,4]triazol-1-yl)-ethanone derivatives
WO2021028421A1 (en) 2019-08-13 2021-02-18 Bayer Aktiengesellschaft Substituted (2-heteroaryloxyphenyl)isoxazolines and salts thereof and their use as herbicidal active substances
US11274076B2 (en) 2016-02-08 2022-03-15 Gowan Company, L.L.C. Process for preparing 1, 2-benzenedimethanol compound
WO2022130188A1 (en) 2020-12-15 2022-06-23 Pi Industries Ltd. Agrochemical composition comprising piperidine thiazole compounds
WO2022243810A1 (en) 2021-05-15 2022-11-24 Pi Industries Ltd. Novel agrochemical composition comprising piperidine thiazole compounds

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2014054635A1 (en) * 2012-10-02 2016-08-25 大日本住友製薬株式会社 Imidazole derivatives
TWI665192B (en) * 2014-05-28 2019-07-11 德商拜耳作物科學股份有限公司 Process for preparing dihydroisoxazole derivatives
CN106414437B (en) * 2014-05-28 2019-06-21 拜耳作物科学股份公司 The method for preparing thiazole
CN109456317A (en) * 2017-09-06 2019-03-12 华中师范大学 Compound containing cyclopropyl and its preparation method and application and fungicide
GB201916676D0 (en) * 2019-11-15 2020-01-01 Syngenta Crop Protection Ag Improvements in or relating to organic compounds
CN113185509A (en) * 2020-04-17 2021-07-30 华中师范大学 Compound containing indole ring structure, preparation method and application thereof, and bactericide
CN115594670A (en) * 2021-06-28 2023-01-13 浙江省化工研究院有限公司（Cn） Trifluoromethyl containing oxadiazole derivatives, preparation method and application thereof
CN116199683A (en) * 2021-11-30 2023-06-02 江苏中旗科技股份有限公司 Compound containing oxadiazole structure, preparation method and application thereof, and bactericide

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19642863A1 (en) * 1996-10-17 1998-04-23 Bayer Ag Amides
GB0230162D0 (en) * 2002-12-24 2003-02-05 Metris Therapeutics Ltd Compounds useful in inhibiting angiogenesis
WO2005087765A1 (en) * 2004-03-04 2005-09-22 Arena Pharmaceuticals, Inc. Ligands of follicle stimulating hormone receptor and methods of use thereof
JP4973191B2 (en) * 2004-11-10 2012-07-11 小野薬品工業株式会社 Nitrogen-containing heterocyclic compound and pharmaceutical use thereof
TW200738701A (en) * 2005-07-26 2007-10-16 Du Pont Fungicidal carboxamides
WO2008013622A2 (en) * 2006-07-27 2008-01-31 E. I. Du Pont De Nemours And Company Fungicidal azocyclic amides
TWI428091B (en) * 2007-10-23 2014-03-01 Du Pont Fungicide mixture

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None

Cited By (130)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9604962B2 (en) 2006-07-27 2017-03-28 E I Du Pont De Nemours And Company Fungicidal azocyclic amides
US9090604B2 (en) 2006-07-27 2015-07-28 E I Du Pont De Nemours And Company Fungicidal azocyclic amides
US8642634B2 (en) 2006-07-27 2014-02-04 E I Du Pont De Nemours And Company Fungicidal azocyclic amides
US9920030B2 (en) 2006-07-27 2018-03-20 E I Du Pont De Nemours And Company Fungicidal azocyclic amides
WO2009055514A3 (en) * 2007-10-23 2010-03-25 E. I. Du Pont De Nemours And Company Fungicidal compounds and mixtures
AU2014202324B2 (en) * 2007-10-23 2016-05-19 Corteva Agriscience Llc Fungicidal compounds and mixtures
WO2009055514A2 (en) * 2007-10-23 2009-04-30 E. I. Du Pont De Nemours And Company Fungicidal mixtures
US8449898B2 (en) 2007-10-23 2013-05-28 E I Du Pont De Nemours And Company Fungicidal mixtures
US8349870B2 (en) 2008-01-25 2013-01-08 E I Du Pont De Nemours And Company Fungicidal hetercyclic compounds
US8618137B2 (en) 2008-12-02 2013-12-31 E I Du Pont De Nemours And Company Fungicidal heterocyclic compounds
US8697878B2 (en) 2008-12-11 2014-04-15 Bayer Cropscience Ag Thiazolyl oxime ethers and hydrazones as crop protection agents
US9215875B2 (en) 2008-12-11 2015-12-22 Bayer Intellectual Property Gmbh Thiazolyl oxime ethers and hydrazones as crop protection agents
US20100267706A1 (en) * 2009-04-20 2010-10-21 Institute For Oneworld Health Compounds, Compositions and Methods Comprising Pyridazine Derivatives
US9149465B2 (en) 2009-05-18 2015-10-06 Infinity Pharmaceuticals, Inc. Isoxazolines as inhibitors of fatty acid amide hydrolase
US8927551B2 (en) 2009-05-18 2015-01-06 Infinity Pharmaceuticals, Inc. Isoxazolines as inhibitors of fatty acid amide hydrolase
US8501781B2 (en) 2009-10-30 2013-08-06 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives
WO2011051244A1 (en) 2009-10-30 2011-05-05 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives
US9167821B2 (en) 2009-12-21 2015-10-27 Bayer Intellectual Property Gmbh Bis(difluoromethyl)pyrazoles as fungicides
WO2011076699A1 (en) 2009-12-21 2011-06-30 Bayer Cropscience Ag Bis(difluormethyl)pyrazoles used as fungicides
US9751871B2 (en) 2009-12-21 2017-09-05 Bayer Intellectual Property Gmbh Bis(difluoromethyl)pyrazoles as fungicides
KR101808074B1 (en) 2009-12-21 2017-12-12 바이엘 크롭사이언스 악티엔게젤샤프트 Bis(difluoromethyl)-pyrazoles used as fungicides
JP2013515028A (en) * 2009-12-21 2013-05-02 バイエル・クロップサイエンス・アーゲー Bis (difluoromethyl) pyrazole as a fungicide
CN102781937A (en) * 2009-12-21 2012-11-14 拜尔农作物科学股份公司 Bis(difluormethyl)pyrazoles used as fungicides
US9247748B2 (en) 2009-12-21 2016-02-02 Bayer Intellectual Property Gmbh Bis(difluoromethyl)pyrazoles as fungicides
US8524743B2 (en) 2009-12-21 2013-09-03 Bayer Cropscience Ag Bis(difluoromethyl)pyrazoles as fungicides
JP2013516483A (en) * 2010-01-07 2013-05-13 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー Bactericidal and fungicidal heterocyclic compounds
CN102791133A (en) * 2010-01-07 2012-11-21 纳幕尔杜邦公司 Fungicidal heterocyclic compounds
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US9220266B2 (en) 2010-04-28 2015-12-29 Bayer Intellectual Property Gmbh Ketoheteroarylpiperidine and -piperazine derivatives as fungicides
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US8748420B2 (en) 2010-05-27 2014-06-10 Bayer Cropscience Ag Pyridinylcarboxylic acid derivatives as fungicides
WO2011147765A1 (en) 2010-05-27 2011-12-01 Bayer Cropscience Ag Pyridinylcarboxylic acid derivatives as fungicides
WO2012020060A1 (en) 2010-08-11 2012-02-16 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
JP2013539464A (en) * 2010-08-25 2013-10-24 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 Heteroarylpiperidine and -piperazine derivatives as fungicides
EA023204B9 (en) * 2010-08-25 2016-08-31 Байер Интеллектуэль Проперти Гмбх Heteroarylpiperidine and -piperazine derivatives as fungicides
US9434723B2 (en) 2010-08-25 2016-09-06 Bayer Intellectual Property Gmbh Heteroarylpiperidine and -piperazine derivatives as fungicides
US9006266B2 (en) 2010-08-25 2015-04-14 Bayer Intellectual Property Gmbh Heteroarylpiperidine and -piperazine derivatives as fungicides
EP3109248A1 (en) 2010-08-25 2016-12-28 Bayer Intellectual Property GmbH Heteroarylpiperidine and -piperazine derivatives as fungicides
US8759527B2 (en) 2010-08-25 2014-06-24 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
AU2011295045B2 (en) * 2010-08-25 2015-09-10 Bayer Cropscience Aktiengesellschaft Heteroarylpiperidine and -piperazine derivatives as fungicides
AU2015261660B2 (en) * 2010-08-25 2017-01-05 Bayer Cropscience Aktiengesellschaft Heteroarylpiperidine and -piperazine derivatives as fungicides
EA023204B1 (en) * 2010-08-25 2016-05-31 Байер Интеллектуэль Проперти Гмбх Heteroarylpiperidine and -piperazine derivatives as fungicides
US9770027B2 (en) 2010-08-25 2017-09-26 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
US9150565B2 (en) 2010-08-25 2015-10-06 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
EP3241829A1 (en) 2010-08-25 2017-11-08 Bayer Intellectual Property GmbH Heteroarylpiperidine and -piperazine derivatives as fungicides
US9930890B2 (en) 2010-08-25 2018-04-03 Bayer Intellectual Property Gmbh Heteroarylpiperidine and -piperazine derivatives as fungicides
AP3444A (en) * 2010-08-25 2015-10-31 Bayer Ip Gmbh Heteroarylpiperidine and piperazine derivatives asfungicides
US10499641B2 (en) 2010-08-25 2019-12-10 Bayer Cropscience Aktiengesellschaft Heteroarylpiperidine and -piperazine derivatives as fungicides
WO2012025557A1 (en) 2010-08-25 2012-03-01 Bayer Cropscience Ag Heteroarylpiperidine and -piperazine derivatives as fungicides
EP2423210A1 (en) 2010-08-25 2012-02-29 Bayer CropScience AG Heteroarylpiperidine and heteroarylpiperazine derivatives as fungicides
KR101797074B1 (en) 2010-10-27 2017-11-13 바이엘 인텔렉쳐 프로퍼티 게엠베하 Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
US9975889B2 (en) 2010-10-27 2018-05-22 Bayer Intellectual Property Gmbh Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
JP2016128458A (en) * 2010-10-27 2016-07-14 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ Heteroarylpiperidine and heteroarylpiperazine derivatives as fungicides
WO2012055837A1 (en) 2010-10-27 2012-05-03 Bayer Cropscience Ag Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
CN103492379A (en) * 2010-10-27 2014-01-01 拜耳知识产权有限责任公司 Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
CN103492379B (en) * 2010-10-27 2018-06-15 拜耳知识产权有限责任公司 As the heteroaryl piperidine of fungicide and heteroaryl based piperazine derivative
US9512117B2 (en) 2010-10-27 2016-12-06 Bayer Intellectual Property Gmbh Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
US9914728B2 (en) 2010-10-27 2018-03-13 Bayer Intellectual Property Gmbh Heteroaryl piperidine and heteroaryl piperazine derivatives as fungicides
JP2013542212A (en) * 2010-10-27 2013-11-21 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 Heteroarylpiperidine and heteroarylpiperazine derivatives as fungicides
JP2014501246A (en) * 2010-12-17 2014-01-20 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー Bactericidal and fungicidal azo cyclic amide
US8822693B2 (en) 2011-02-01 2014-09-02 Bayer Cropscience Ag Heteroarylpiperidine and-piperazine derivatives as fungicides
US9204649B2 (en) 2011-02-01 2015-12-08 Bayer Intellectual Property Gmbh Heteroarylpiperidine and- piperazine derivates as fungicides
EP2532233A1 (en) 2011-06-07 2012-12-12 Bayer CropScience AG Active compound combinations
US9144238B2 (en) 2011-06-07 2015-09-29 Bayer Intellectual Property Gmbh Active compound combinations
WO2012168188A1 (en) 2011-06-07 2012-12-13 Bayer Intellectual Property Gmbh Active compound combinations
US10004232B2 (en) 2011-09-15 2018-06-26 Bayer Intellectual Property Gmbh Piperidine pyrazoles as fungicides
WO2013037768A1 (en) 2011-09-15 2013-03-21 Bayer Intellectual Property Gmbh Piperidine pyrazoles as fungicides
EP2921484A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH Oxazole derivatives
US9375009B2 (en) 2011-12-27 2016-06-28 Bayer Intellectual Property Gmbh Heteroarylpiperidine and piperazine derivatives as fungicides
EP2921481A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH 4-piperidine carboxylic acid derivatives
US10426169B2 (en) 2011-12-27 2019-10-01 Bayer Intellectual Property Gmbh Heteroarylpiperidine and -piperazine derivatives as fungicides
EP2921493A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH Heteroarylpiperidine and heteroarylpiperazine derivatives
EP2921494A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH Heteroarylpiperidine and heteroarylpiperazine derivatives
WO2013098229A2 (en) 2011-12-27 2013-07-04 Bayer Intellectual Property Gmbh Heteroarylpiperidine and piperazine derivatives as fungicides
EP2921492A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH Heteroarylpiperidine and heteroarylpiperazine derivatives
EP2921495A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH Heteroarylpiperidine and heteroarylpiperazine derivatives as fungicides
EP2921491A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH Intermediates for the production of heteroarylpiperidine and heteroarylpiperazine derivatives as fungicides
EP2921485A1 (en) 2011-12-27 2015-09-23 Bayer Intellectual Property GmbH Isoxazole derivatives
US9266876B2 (en) 2012-02-02 2016-02-23 Actelion Pharmaceuticals Ltd. 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
US11147274B2 (en) 2012-02-27 2021-10-19 Bayer Intellectual Property Gmbh Active compound combinations containing a thiazoylisoxazoline and a fungicide
US9629367B2 (en) 2012-02-27 2017-04-25 Bayer Intellectual Property Gmbh Active compound combinations containing a thiazoylisoxazoline and a fungicide
WO2013127704A1 (en) 2012-02-27 2013-09-06 Bayer Intellectual Property Gmbh Active compound combinations containing a thiazoylisoxazoline and a fungicide
US10375961B2 (en) 2012-02-27 2019-08-13 Bayer Intellectual Property Gmbh Active compound combinations containing a thiazoylisoxazoline and a fungicide
US12102087B2 (en) 2012-02-27 2024-10-01 Bayer Cropscience Aktiengesellschaft Active compound combinations containing a thiazoylisoxazoline and a fungicide
WO2014033164A1 (en) 2012-08-30 2014-03-06 Bayer Cropscience Ag Procedure for the decarboxylation of 3,5-bis(haloalkyl)-pyrazole-4-carboxylic acid derivatives
US9145370B2 (en) 2012-08-30 2015-09-29 Bayer Cropscience Ag Procedure for the decarboxylation of 3,5-bis(haloalkyl)-pyrazole-4-carboxylic acid derivatives
EP2801575A1 (en) 2013-05-07 2014-11-12 Bayer CropScience AG Heteroaryldihydropyridine derivatives as fungicides
TWI632142B (en) * 2013-06-24 2018-08-11 德商拜耳作物科學股份有限公司 Piperidinecarboxylic acid derivatives as fungicides
CN105473585B (en) * 2013-06-24 2018-04-13 拜耳作物科学股份公司 Piperidine carboxylic acid derivative as fungicide
CN105473585A (en) * 2013-06-24 2016-04-06 拜耳作物科学股份公司 Piperidinecarboxylic acid derivatives as fungicides
WO2014206896A1 (en) * 2013-06-24 2014-12-31 Bayer Cropscience Ag Piperidinecarboxylic acid derivatives as fungicides
US9717243B2 (en) 2013-06-24 2017-08-01 Bayer Cropscience Aktiengesellschaft Piperidinecarboxylic acid derivatives as fungicides
US10259807B2 (en) 2013-07-22 2019-04-16 Idorsia Pharmaceuticals Ltd. 1-(piperazin-1-yl)-2-([1,2,4]triazol-1-yl)-ethanone derivatives
US9924721B2 (en) 2013-08-28 2018-03-27 Bayer Cropscience Aktiengesellschaft Malonic ester derivatives of heteroarylpiperidines and -piperazines as fungicides
WO2015144571A1 (en) 2014-03-24 2015-10-01 Bayer Cropscience Ag Phenylpiperidinecarboxamide derivatives as fungicides
US9951063B2 (en) 2014-03-24 2018-04-24 Idorsia Pharmaceuticals Ltd 8-(piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinoline derivatives
US9790182B2 (en) 2014-06-11 2017-10-17 Bayer Cropscience Aktiengesellschaft Preparation of piperidine-4-carbothioamide
US10160707B2 (en) 2014-06-11 2018-12-25 Bayer Cropscience Aktiengesellschaft Process for preparing 3-chloro-2-vinylphenol
US10104891B2 (en) 2014-08-13 2018-10-23 Sds Biotech K.K. Fused 11-membered compounds and agricultural/horticultural fungicides containing them
KR20170036104A (en) 2014-08-13 2017-03-31 가부시키가이샤 에스디에스 바이오텍크 Condensed 11-member ring compound and agriculture and horticultural fungicide comprising same
US9980487B2 (en) 2014-08-13 2018-05-29 Sds Biotech K.K. Fused 11-membered compounds and agricultural/horticultural fungicides containing them
US10047080B2 (en) 2015-01-15 2018-08-14 Idorsia Pharmaceuticals Ltd. (R)-2-methyl-piperazine derivatives as CXCR3 receptor modulators
US10053457B2 (en) 2015-01-15 2018-08-21 Idorsia Pharmaceuticals Ltd. Hydroxyalkyl-piperazine derivatives as CXCR3 receptor modulators
US10093626B2 (en) 2015-03-05 2018-10-09 Bayer Cropscience Aktiengesellschaft Process for preparing piperidine-4-carbothioamide hydrochloride
US10189799B2 (en) 2015-03-05 2019-01-29 Bayer Cropscience Aktiengesellschaft Process for preparing substituted phenylisoxazoline derivatives
US10604495B2 (en) 2015-03-05 2020-03-31 Bayer Cropscience Aktiengesellschaft Process for preparing substituted phenylisoxazoline derivatives
WO2016202761A1 (en) 2015-06-17 2016-12-22 Bayer Cropscience Aktiengesellschaft Active compound combinations
KR20180105718A (en) 2016-02-08 2018-09-28 가부시키가이샤 에스디에스 바이오텍크 Bactericidal composition
US11903387B2 (en) 2016-02-08 2024-02-20 Gowan Company, L.L.C. Fungicidal composition
WO2017138069A1 (en) 2016-02-08 2017-08-17 株式会社エス・ディー・エス バイオテック Germicidal composition
US11274076B2 (en) 2016-02-08 2022-03-15 Gowan Company, L.L.C. Process for preparing 1, 2-benzenedimethanol compound
WO2018193387A1 (en) 2017-04-19 2018-10-25 Pi Industries Ltd. Heterocyclic compounds with microbiocidal properties
WO2019048989A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungicidal heterocyclic compounds
WO2019048988A1 (en) 2017-09-08 2019-03-14 Pi Industries Ltd. Novel fungidal heterocyclic compounds
WO2021028421A1 (en) 2019-08-13 2021-02-18 Bayer Aktiengesellschaft Substituted (2-heteroaryloxyphenyl)isoxazolines and salts thereof and their use as herbicidal active substances
WO2022130188A1 (en) 2020-12-15 2022-06-23 Pi Industries Ltd. Agrochemical composition comprising piperidine thiazole compounds
WO2022243810A1 (en) 2021-05-15 2022-11-24 Pi Industries Ltd. Novel agrochemical composition comprising piperidine thiazole compounds

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