US20200399222A1 - Picolinamides as fungicides - Google Patents

Picolinamides as fungicides Download PDF

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Publication number
US20200399222A1
US20200399222A1 US16/978,693 US201916978693A US2020399222A1 US 20200399222 A1 US20200399222 A1 US 20200399222A1 US 201916978693 A US201916978693 A US 201916978693A US 2020399222 A1 US2020399222 A1 US 2020399222A1
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United States
Prior art keywords
oil
hydrogen
compound according
alkyl
plant
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US16/978,693
Inventor
Brian A. Loy
Nicolaas Vermeulen
Brannon Sam
Kevin G. Meyer
Chenglin Yao
Nicholas R. Babij
Jeff Petkus
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Corteva Agriscience LLC
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Dow AgroSciences LLC
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Priority to US16/978,693 priority Critical patent/US20200399222A1/en
Publication of US20200399222A1 publication Critical patent/US20200399222A1/en
Assigned to CORTEVA AGRISCIENCE LLC reassignment CORTEVA AGRISCIENCE LLC CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: DOW AGROSCIENCES LLC
Assigned to CORTEVA AGRISCIENCE LLC reassignment CORTEVA AGRISCIENCE LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: VERMEULEN, NICOLAAS, SAM, BRANNON, LOY, BRIAN A, YAO, CHENGLIN, BABIJ, NICHOLAS R, MEYER, KEVIN G
Assigned to CORTEVA AGRISCIENCE LLC reassignment CORTEVA AGRISCIENCE LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: PETKUS, JEFF
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/04—Carbamic acid halides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
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    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
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    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
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    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/12—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, neither directly attached to a ring nor the nitrogen atom being a member of a heterocyclic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/18—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, directly attached to a heterocyclic or cycloaliphatic ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
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    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
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    • C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C211/03—Monoamines
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    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
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    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/28—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and containing rings
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    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/18—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
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    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
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    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
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    • C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D265/20—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 4
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Definitions

  • Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
  • the present disclosure relates to picolinamides and their use as fungicides.
  • the compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
  • X is hydrogen or C(O)R 4 ;
  • Y is hydrogen or C(O)R 4 ;
  • Z is N or N + ⁇ O ⁇ and W is O or S;
  • R 1 is hydrogen or alkyl, substituted with 0, 1 or multiple R 7 ;
  • R 2 is methyl
  • R 3 is chosen from alkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R 7 ;
  • R 4 is chosen from alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R 7 ;
  • R 5 is chosen from hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R 7 ;
  • R 6 is chosen from hydrogen, —C(O)R 8 , or —CH 2 OC(O)R 8 ;
  • R 7 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R 9 ;
  • R 8 is chosen from alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R 7 ;
  • R 9 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl;
  • R 10 is chosen from hydrogen or alkyl, each substituted with 0, 1 or multiple R 7 .
  • Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
  • Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.
  • alkyl refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
  • alkenyl refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.
  • aryl and “Ar” refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms.
  • heterocyclyl refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms
  • alkoxy refers to an —OR substituent.
  • acyloxy refers to an —OC(O)R substituent.
  • cyano refers to a —C ⁇ N substituent.
  • hydroxyl refers to a —OH substituent.
  • amino refers to an —N(R) 2 substituent.
  • arylalkoxy refers to —O(CH 2 ) n Ar where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.
  • haloalkoxy refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
  • haloalkyl refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • halogen refers to one or more halogen atoms, defined as F, Cl, Br, and I.
  • nitro refers to a —NO 2 substituent.
  • thioalkyl refers to a —SR substituent.
  • Formula (I) is read as also including salts or hydrates thereof.
  • Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, hydroiodide, trifluoroacetate, and trifluoromethane sulfonate.
  • Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.
  • composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
  • the compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds.
  • the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants.
  • the materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.
  • the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier.
  • Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment.
  • the formulations can be prepared according to procedures that are conventional in the agricultural chemical art.
  • the present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and used as a fungicide.
  • formulations are applied as aqueous suspensions or emulsions.
  • Such suspensions or emulsions may be produced from water-soluble, water-suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates.
  • any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.
  • Wettable powders which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants.
  • concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent.
  • the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like.
  • the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
  • Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate.
  • the compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers.
  • the concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions.
  • Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.
  • Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers.
  • nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene.
  • Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts.
  • Anionic emulsifiers include the oilsoluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated-polyglycol ether.
  • organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of
  • Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases.
  • Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds.
  • the formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
  • Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension.
  • Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above.
  • Other components such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.
  • the compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil.
  • Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance.
  • Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm.
  • a suitable solvent is a solvent in which the compound is substantially or completely soluble.
  • Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.
  • Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • a suitable dusty agricultural carrier such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • the formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism.
  • adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix.
  • the amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent.
  • Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%)+emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C 9 -C 11 alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C 12 -C 16 ) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium
  • the formulations may optionally include combinations that contain other pesticidal compounds.
  • additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds.
  • the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use.
  • the compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.
  • the compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases.
  • the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s).
  • Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, aminopyrifen, amisulbrom, antimycin, Ampelomyces quisqualis , azaconazole, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone,
  • the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests.
  • the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s).
  • Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, acynonapyr, afidopyropen, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfura
  • the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants.
  • the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s).
  • Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, beflubutamid-M,
  • Another embodiment of the present disclosure is a method for the control or prevention of fungal attack.
  • This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I.
  • the compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity.
  • the compounds may be useful both in a protectant and/or an eradicant fashion.
  • the compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.
  • the compounds have broad ranges of activity against fungal pathogens.
  • exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch ( Zymoseptoria tritici ), wheat brown rust ( Puccinia triticina ), wheat stripe rust ( Puccinia striiformis ), scab of apple ( Venturia inaequalis ), powdery mildew of grapevine ( Uncinula necator ), barley scald ( Rhynchosporium secalis ), blast of rice ( Magnaporthe grisea ), rust of soybean ( Phakopsora pachyrhizi ), glume blotch of wheat ( Parastagonospora nodorum ), powdery mildew of wheat ( Blumeria graminis f.
  • the exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.
  • the compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount.
  • disease-inhibiting and phytologically acceptable amount refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred.
  • concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like.
  • a suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m 2 ).
  • the compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.
  • Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R 3 is as previously defined can be prepared by the method shown in Scheme 1, step a.
  • Scheme 1, step a submission of racemic epoxide mixtures of Formulas 1.0-Rac and 1.4-Rac, to reaction with an organometallic nucleophile, such
  • aryl magnesium halide in the presence of a metal halide, such as copper iodide, in a polar, aprotic solvent, such as tetrahydrofuran (THF) or diethyl ether (Et 2 O), at a temperature of about ⁇ 78° C. to 55° C., affords racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R 3 is as previously defined, and shown in step a.
  • a metal halide such as copper iodide
  • a polar, aprotic solvent such as tetrahydrofuran (THF) or diethyl ether (Et 2 O)
  • Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R 3 is as previously defined can be separated into their individual enantiomers utilizing a lipase-catalyzed kinetic resolution described by Akita ( Tetrahedron: Asymmetry 2009, 20, 1286-1294) and outlined in Scheme 2, steps a and b. Subjection of racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R 3 is as previously defined, to Candida antarctica lipase B (CAL-B) in an
  • acetylating solvent such as vinyl acetate
  • acetylating solvent such as vinyl acetate
  • the mixtures can be purified via silica gel chromatography using a hexane-ethyl acetate mixture as the mobile phase giving the resolved secondary alcohols and acetates of Formulas 1.2-Abs, 1.5-Abs, 2.1-Abs and 2.3-Abs, wherein R 3 is as originally defined, and in high enantiomeric excess.
  • Compounds of Formula 3.2 may be prepared according to the method outlined in Scheme 3, step a.
  • Alcohols of Formula 3.0, wherein R 2 and R 3 , are as originally defined can be treated with compounds of Formula 3.1, wherein R 1 and R 10 are as originally defined, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as (CH 2 Cl 2 ) or THF to afford compounds of Formula 3.2, wherein R 1 , R 2 , R 3 , and R 10 , are as originally defined, as shown in step a.
  • a coupling reagent such as 3-(ethyliminomethyleneamino)-N,N-dimethylprop
  • Compounds of Formula 4.5 wherein R 1 , R 2 , R 3 , R 5 , and R 10 , are as originally defined, can be prepared according to the methods outlined in Scheme 4, steps a-d.
  • Compounds of Formula 3.2, wherein R 1 , R 2 , R 3 , and R 10 , are as originally defined, can be treated with an acid, such as a 4 Normal (N) solution of hydrogen chloride (HCl) in dioxane, in a halogenated solvent such as CH 2 Cl 2 to afford compounds of Formula 4.1, wherein R 1 , R 2 , R 3 , and R 10 , as shown in step a.
  • an acid such as a 4 Normal (N) solution of hydrogen chloride (HCl) in dioxane
  • a halogenated solvent such as CH 2 Cl 2
  • Compounds of Formula 4.2 wherein R 1 , R 2 , R 3 , and R 10 , are as originally defined, can be prepared by treating compounds of Formula 3.2, wherein R 1 , R 2 , R 3 , and R 10 , are as originally defined, with an acid, such as 2,2,2-trifluoroacetic acid, in a halogenated solvent such as CH 2 Cl 2 , as shown in step c.
  • an acid such as 2,2,2-trifluoroacetic acid
  • Compounds of Formula 5.1 wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined, can be prepared according to the method outlined in Scheme 5, steps a or b.
  • Compounds of Formula 4.5, wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined, can be treated with an appropriate alkyl halide, with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na 2 CO 3 ) or potassium carbonate (K 2 CO 3 ), in a solvent such as acetone, at a temperature of about 25° C. to about 50° C., as shown in step a.
  • a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na 2 CO 3 ) or potassium carbonate (K 2 CO 3 )
  • solvent such as acetone
  • Compounds of Formula 6.1 and 6.2, wherein R 1 , R 2 , R 3 , R 5 , R 6 , and R 10 , are as originally defined, can be prepared according to the method outlined in Scheme 6, steps a and b.
  • Compounds of Formula 4.5, wherein R 1 , R 2 , R 3 , R 5 , and R 10 , are as originally defined, can be treated with a thionating reagent such as phosphorus pentasulfide, an additive, such as hexamethyldisiloxane, optionally in a polar aprotic solvent such as acetonitrile (CH 3 CN), at a temperature of about 0° C. to 80° C.
  • a thionating reagent such as phosphorus pentasulfide
  • an additive such as hexamethyldisiloxane
  • a polar aprotic solvent such as acetonitrile (CH 3 CN)
  • Additives can include, but not limited to, aluminum oxide (Al 2 O 3 ); inorganic bases, such as potassium carbonate and sodium bicarbonate; organic bases, such as triethylamine, diethylaniline, pyridine and morpholine.
  • Al 2 O 3 aluminum oxide
  • inorganic bases such as potassium carbonate and sodium bicarbonate
  • organic bases such as triethylamine, diethylaniline, pyridine and morpholine.
  • Optional solvents can include, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons, such as hexane, cyclohexane or toluene; halogenated hydrocarbons, such as dichloromethane, 1,2-dichloroethane and chlorobenzene; ethers, such as diethyl ether, 1,4-dioxane, THE and 1,2-dimethoxyethane; and other polar aprotic solvents such as pyridine and hexamethylphosphoramide (HMPA).
  • aliphatic, alicyclic or aromatic hydrocarbons such as hexane, cyclohexane or toluene
  • halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chlorobenzene
  • ethers such as diethyl ether, 1,4-dioxane, THE and 1,2-dimethoxyethane
  • step b treatment of compounds of Formula 6.1, wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined, with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium carbonate (Na 2 CO 3 ) or potassium carbonate (K 2 CO 3 ), in a polar aprotic solvent, such as acetone, at a temperature of about 55° C., or by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, Et 3 N, DMAP, or mixtures thereof, in an optional aprotic solvent such as CH 2 Cl 2 , at a temperature of about 23° C., can afford compounds of Formula 6.2 wherein R 1 , R 2 , R 3 , R 5 , R 6 , and R 10 , are as originally defined.
  • a aprotic solvent such as CH 2 Cl 2
  • Compounds of Formula 7.1 wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined, can be prepared according to the method outlined in Scheme 7, step a.
  • Compounds of Formula 4.5, wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined, can be treated with a oxidizing reagent such as m-chloroperbenzoic acid (mCPBA) in a polar solvent such as CH 2 Cl 2 , at a temperature of about 0° C. to 50° C., to give compounds of Formula 7.1, wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as previously defined, and shown in a.
  • mCPBA m-chloroperbenzoic acid
  • MMPP magnesium monoperoxyphthalate hexahydrate
  • peroxyacetic acid peroxide-urea complex
  • oxone peroxyacetic acid
  • sodium perchlorate sodium perchlorate or dimethyl dioxirane
  • Compounds of Formula 8.1 wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined, can be prepared according to the method outlined in Scheme 8, step a.
  • Compounds of Formula 4.5, wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined can be treated with a diactivated carbonyl reagent such as triphosgene, with a base, such as pyridine, and in a polar solvent, such as CH 2 Cl 2 , at a temperature of about 0° C. to 50° C. to afford compounds of Formula 8.1, wherein R 1 , R 2 , R 3 , R 5 and R 10 , are as originally defined, as depicted in a.
  • Example 1A Preparation of racemic threo-3-(2,4-dimethylphenyl)butan-2-ol
  • Racemic trans-butene epoxide (1.3 g, 18.01 mmol) was slowly added dropwise followed by warming the reaction to room temperature and stirring overnight. The mixture was then cooled to 0° C. and slowly quenched by the addition of a saturated aqueous ammonium chloride (NH 4 Cl) solution. The mixture was filtered through a pad of Celite and the pad was rinsed thoroughly with ethyl acetate. The organic solution was washed with saturated NH 4 Cl solution and brine. The solution was dried (magnesium sulfate (MgSO 4 )), filtered and concentrated under reduced pressure.
  • MgSO 4 magnesium sulfate
  • Step 1 Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol and (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate
  • Example 5C Preparation of 4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate
  • Step 1 Preparation of (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
  • the reaction was cooled, diluted with CH 2 Cl 2 (10 mL) and quenched by the addition of saturated aqueous NaHCO 3 (10 mL). The layers were separated and the aqueous layer was extracted with CH 2 Cl 2 (3 ⁇ 10 mL). The combined organic layers were passed through a phase separator and concentrated to a yellow oil.
  • Example A Evaluation of Fungicidal Activity: Leaf Blotch of Wheat ( Zymoseptoria tritici ; Bayer Code SEPTTR)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. When disease symptoms were fully expressed on the 1 st leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.
  • Example B Evaluation of Fungicidal Activity: Wheat Brown Rust ( Puccinia triticina ; Synonym: Puccinia recondita f. sp. tritici ; Bayer Code PUCCRT)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22° C. with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
  • Example C Evaluation of Fungicidal Activity: Asian Soybean Rust ( Phakopsora pachyrhizi ; Bayer Code PHAKPA)
  • Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two week old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22° C. and 100% relative humidity then transferred to a growth room at 23° C. for disease to develop. Disease severity was assessed on the sprayed leaves.
  • Example D Evaluation of Fungicidal Activity: Tomato Early Blight ( Alternaria solani ; Bayer Code ALTESO)
  • Tomato plants (variety Outdoor Girl) were propagated in soil-less Metro mix, with each pot having one plant, and used when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Alternaria solani 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example E Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets ( Cercospora beticola ; Bayer Code CERCBE)
  • Sugar beet plants (variety HH88) were grown in soil-less Metro mix and trimmed regularly to maintain a uniform plant size prior to test. Plants were inoculated with a spore suspension 24 hr after fungicide treatments. Inoculated plants were kept in a dew chamber at 22° C. for 48 hr then incubated in a greenhouse set at 24° C. under a clear plastic hood with bottom ventilation until disease symptoms were fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example F Evaluation of Fungicidal Activity: Cucumber Anthracnose ( Glomerella lagenarium ; Anamorph: Colletotrichum lagenarium ; Bayer Code COLLLA)
  • Cucumber seedlings (variety Bush Pickle) were propagated in soil-less Metro mix, with each pot having one plant, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Colletotrichum lagenarium 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room set at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example G Evaluation of Fungicidal Activity: Wheat Glume Blotch ( Parastagonospora nodorum ; Bayer Code LEPTNO)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Parastagonospora nodorum 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
  • Example H Evaluation of Fungicidal Activity: Cucumber Downy Mildew ( Pseudoperonospora cubensis ; Bayer Code PSPECU)
  • Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metro mix, with one plant per pot, and used in the test when 12 to 14 days old. Plants were inoculated with a spore suspension 24 hr following fungicide treatments. Test plants were inoculated with an aqueous spore suspension of Pseudoperonospora cubensis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 24 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. until disease was fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example I Evaluation of Fungicidal Activity: Rice Blast ( Magnaporthe grisea; Anamorph: Pyricularia oryzae ; Bayer Code PYRIOR)
  • Rice seedlings (variety Japonica ) were propagated in soil-less Metro mix, with each pot having 8 to 14 plants, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Pyricularia oryzae 24 hr after fungicide treatments. After inoculation, the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example J Evaluation of Fungicidal Activity: Barley Scald ( Rhyncosporium secalis ; Bayer Code RHYNSE)
  • Barley seedlings (variety Harrington) were propagated in soil-less Metro mix, with each pot having 8 to 12 plants, and used in the test when first leaf was fully emerged.
  • Test plants were inoculated by an aqueous spore suspension of Rhyncosporium secalis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 20° C. with 100% relative humidity for 48 hr. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example K Evaluation of Fungicidal Activity: Grape Powdery Mildew ( Uncinula necator ; Bayer Code UNCINE)
  • Grape seedlings (variety Carignane) were grown in soil-less Metro mix, with one plant per pot, and used in the test when approximately 1 month old. Plants were inoculated 24 hr after fungicide treatment by shaking spores from infected leaves over test plants. Plants were maintained in a greenhouse set at 20° C. until disease was fully developed. Fungicide formulation, application and disease assessment on sprayed leaves followed the procedures as described in the Example A.
  • Example 1A Example 2 Example 3 Oil 2 Example 1A Example 2 Example 3 Oil 3 Example 1A Example 2 Example 3 Oil 4 Example 1A Example 2 Example 3 Oil 5 Example 1A Example 2 Example 3 Oil 6 Example 1A Example 2 Example 3 Oil 7 Example 1A Example 2 Example 3 Oil 8 Example 1A Example 2 Example 3 Oil 9 Example 1B Example 2 Example 3 Oil 10 Example 1B Example 2 Example 3 Oil 11 Example 1B Example 2 Example 3 Oil 12 Example 1B Example 2 Example 3 Oil 13 Example 1B Example 2 Example 3 Oil 14 Example 1B Example 2 Example 3 Oil 15 Example 1B Example 2 Example 3 Oil 16 Example 1B Example 2 Example 3 Oil 17 Example 1B Example 2 Example 3 Oil 18 Example 1B Example 2 Example 3 Oil 19 Example 1B Example 2 Example 3 Oil 20 Example 1B Example 2 Example 3 Oil 21 Example 1A Example 2 Example 3 Oil 22 Example 1A Example 2 Example 3 Oil 23 Example 1A Example 2 Example 3 Oil 24 Example 1A Example 2 Example 3 Oil 25 Example 1A Example 2 Example 3

Abstract

This disclosure relates to picolinamides of Formula I and their use as fungicides.
Figure US20200399222A1-20201224-C00001

Description

    CROSS REFERENCE TO RELATED APPLICATION
  • This is a national phase entry under 35 U.S.C. § 371 of international patent application PCT/US2019/021263, filed on Mar. 8, 2019 and published in English as international patent publication WO2019173665 on Sep. 12, 2019, which claims priority to the benefit of of U.S. Provisional Patent Application Ser. No. 62/640,424 filed Mar. 8, 2018 and U.S. Provisional Patent Application Ser. No. 62/640,434 filed Mar. 8, 2018 the disclosure of which is hereby incorporated by reference in its entirety.
    • BACKGROUND & SUMMARY
  • Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
  • The present disclosure relates to picolinamides and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
  • One embodiment of the present disclosure may include compounds of Formula I:
  • Figure US20200399222A1-20201224-C00002
  • wherein:
  • Q is
  • Figure US20200399222A1-20201224-C00003
  • X is hydrogen or C(O)R4;
  • Y is hydrogen or C(O)R4;
  • Z is N or N+→O− and W is O or S;
  • R1 is hydrogen or alkyl, substituted with 0, 1 or multiple R7;
  • R2 is methyl;
  • R3 is chosen from alkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R7;
  • R4 is chosen from alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R7;
  • R5 is chosen from hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R7;
  • R6 is chosen from hydrogen, —C(O)R8, or —CH2OC(O)R8;
  • R7 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R9;
  • R8 is chosen from alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R7;
  • R9 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl; and
  • R10 is chosen from hydrogen or alkyl, each substituted with 0, 1 or multiple R7.
  • Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
  • Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.
  • It will be understood by those skilled in the art that the following terms may include generic “R”-groups within their definitions, e.g., “the term alkoxy refers to an —OR substituent”. It is also understood that within the definitions for the following terms, these “R” groups are included for illustration purposes and should not be construed as limiting or being limited by substitutions about Formula I.
  • The term “alkyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
  • The term “alkenyl” refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.
  • The terms “aryl” and “Ar” refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms.
  • The term “heterocyclyl” refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms
  • The term “alkoxy” refers to an —OR substituent.
  • The term “acyloxy” refers to an —OC(O)R substituent.
  • The term “cyano” refers to a —C≡N substituent.
  • The term “hydroxyl” refers to a —OH substituent.
  • The term “amino” refers to an —N(R)2 substituent.
  • The term “arylalkoxy” refers to —O(CH2)nAr where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.
  • The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
  • The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.
  • The term “nitro” refers to a —NO2 substituent.
  • The term thioalkyl refers to a —SR substituent.
  • Throughout the disclosure, reference to the compounds of Formula I is read as also including all stereoisomers, for example diastereomers, enantiomers, and mixtures thereof. In another embodiment, Formula (I) is read as also including salts or hydrates thereof. Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, hydroiodide, trifluoroacetate, and trifluoromethane sulfonate.
  • It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.
  • Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.
  • Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
    • DETAILED DESCRIPTION
  • The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.
  • Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.
  • The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and used as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water-suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.
  • Wettable powders, which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
  • Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.
  • Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oilsoluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated-polyglycol ether.
  • Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
  • Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.
  • The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.
  • Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%)+emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9-C11 alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12-C16) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.
  • The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.
  • The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, aminopyrifen, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxide, copper octanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin, enestroburin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluindapyr, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxapiprolin, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), inpyrfluxam, iodocarb, ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isofetamide, isoflucypram, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxium-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb, mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl iodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl, oxathiapiprolin, oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenyl laurate, penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium hydroxyquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pydiflumetofen, pyrametostrobin, pyraoxystrobin, pyraclostrobin, pyraziflumid, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp., (RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide, 1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithiine 1,1,4,4-tetraoxide, 2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl, bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, climbazole, copper bis(3-phenylsalicylate), copper zinc chromate, coumoxystrobin, cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlobentiazox, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipymetitrone, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, enoxastrobin, ESBP, etaconazole, etem, ethirim, fenaminstrobin, fenaminosulf, fenapanil, fenitropan, fenpicoxamid, florylpicoxamid, flufenoxystrobin, fluopimomide, fluotrimazole, furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos, ICIA0858, ipfentrifluconazole, ipflufenoquin, isopamphos, isovaledione, mandestrobin, mebenil, mecarbinzid, mefentrifluconazole, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, metyltetraprole, milneb, mucochloric anhydride, myclozolin, N-3,5-dichlorophenyl-succinimide, N-3-nitrophenylitaconimide, natamycin, N-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyrapropoyne, pyridachlometyl, pyridinitril, pyrisoxazole, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, quinofumelin, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, triclopyricarb, triflumezopyrim, urbacid, zarilamid, and any combinations thereof.
  • Additionally, the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests. When used in conjunction with other pesticides, the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s). Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, acynonapyr, afidopyropen, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, benzpyrimoxan, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, broflanilide, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chloroprallethrin, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclaniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalodiamide, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicloromezotiaz, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, epsilon-metofluthrin, epsilon-momfluorothrin, esdepallethrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flometoquin, flonicamid, fluazaindolizine, flubendiamide, flucofuron, flucycloxuron, flucythrinate, fluensulfone, flufenerim, flufenoxuron, flufenprox, flufiprole, fluhexafon, flupyradifurone, flupyrimin, fluvalinate, fluxametamide, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, furathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptafluthrin, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isocycloseram, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kappa-bifenthrin, kappa-tefluthrin, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan, mercurous chloride, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene, methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, momfluorothrin, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxazosulfyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocssene II, precocene III, primidophos, profenofos, profluralin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pyflubumide, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyriminostrobin, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad, spiromesifen, spiropidion, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachlorantraniliprole, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, tetraniliprole, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tioxazafen, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumezopyrim, triflumuron, trimethacarb, triprene, tyclopyrazoflor, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos, and any combinations thereof.
  • Additionally, the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants. When used in conjunction with herbicides, the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s). Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, beflubutamid-M, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac, bixlozone, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole chlorprocarb, carfentrazone, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clacyfos, clethodim, cliodinate, clodinafop, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenquinotrione, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M, flazasulfuron, florasulam, florpyrauxifen, fluazifop, fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate, halauxifen, halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iofensulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lancotrione, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, napropamide-M, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiafenacil, tiocarbazil, tioclorim, tolpyralate, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr, tridiphane, trietazine, trifloxysulfuron, trifludimoxazin, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate, and xylachlor.
  • Another embodiment of the present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.
  • The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.
  • It will be understood by those skilled in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.
  • The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch (Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust (Puccinia striiformis), scab of apple (Venturia inaequalis), powdery mildew of grapevine (Uncinula necator), barley scald (Rhynchosporium secalis), blast of rice (Magnaporthe grisea), rust of soybean (Phakopsora pachyrhizi), glume blotch of wheat (Parastagonospora nodorum), powdery mildew of wheat (Blumeria graminis f. sp. tritici), powdery mildew of barley (Blumeria graminis f. sp. hordei), powdery mildew of cucurbits (Erysiphe cichoracearum), anthracnose of cucurbits (Glomerella lagenarium), leaf spot of beet (Cercospora beticola), early blight of tomato (Alternaria solani), and spot blotch of barley (Cochliobolus sativus). The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.
  • The compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount. The term “disease-inhibiting and phytologically acceptable amount” refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m2).
  • Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.
  • The compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.
    • General Schemes
  • The following schemes illustrate approaches to generating picolinamide compounds of Formula (I). The following descriptions and examples are provided for illustrative purposes and should not be construed as limiting in terms of substituents or substitution patterns.
  • Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, can be prepared by the method shown in Scheme 1, step a. Submission of racemic epoxide mixtures of Formulas 1.0-Rac and 1.4-Rac, to reaction with an organometallic nucleophile, such
  • Figure US20200399222A1-20201224-C00004
  • as an aryl magnesium halide, in the presence of a metal halide, such as copper iodide, in a polar, aprotic solvent, such as tetrahydrofuran (THF) or diethyl ether (Et2O), at a temperature of about −78° C. to 55° C., affords racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, and shown in step a.
  • Racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, can be separated into their individual enantiomers utilizing a lipase-catalyzed kinetic resolution described by Akita (Tetrahedron: Asymmetry 2009, 20, 1286-1294) and outlined in Scheme 2, steps a and b. Subjection of racemic mixtures of Formulas 1.2-Rac, 1.3-Rac and 1.5-Rac, 1.6-Rac, wherein R3 is as previously defined, to Candida antarctica lipase B (CAL-B) in an
  • Figure US20200399222A1-20201224-C00005
  • acetylating solvent, such as vinyl acetate, at a temperature of about 25° C. to about 60° C., affords the unreacted secondary alcohols of Formulas 1.2-Abs and 1.5-Abs, wherein R3 is as originally defined, and the acetylated compounds of Formulas 2.1-Abs and 2.3-Abs, wherein R3 is as originally defined. The mixtures can be purified via silica gel chromatography using a hexane-ethyl acetate mixture as the mobile phase giving the resolved secondary alcohols and acetates of Formulas 1.2-Abs, 1.5-Abs, 2.1-Abs and 2.3-Abs, wherein R3 is as originally defined, and in high enantiomeric excess. The lipase recognition of the secondary alcohol of 1.2-Rac, 1.3-Rac, 1.5-Rac and 1.6-Rac, wherein R3 is as originally defined, was similar to the empirical rule for the kinetic resolution of secondary alcohols (Bornscheuer and Kazlauskus, Hydrolases in Organic Synthesis; Wiley-VCH, 2006). Treatment of acetates of Formulas 2.1-Abs and 2.3-Abs, wherein R3 is as originally defined, with a carbonate base, such as potassium carbonate, in an alcoholic solvent, such as methanol, at a temperature of about 25° C. to about 60° C., affords the resolved secondary alcohols of Formulas 2.2-Abs and 2.4-Abs, wherein R3 is as originally defined.
  • Compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, may be prepared according to the method outlined in Scheme 3, step a. Alcohols of Formula 3.0, wherein R2 and R3, are as originally defined, can be treated with compounds of Formula 3.1, wherein R1 and R10 are as originally defined, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as (CH2Cl2) or THF to afford compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, as shown in step a.
  • Figure US20200399222A1-20201224-C00006
  • Compounds of Formula 4.5, wherein R1, R2, R3, R5, and R10, are as originally defined, can be prepared according to the methods outlined in Scheme 4, steps a-d. Compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, can be treated with an acid, such as a 4 Normal (N) solution of hydrogen chloride (HCl) in dioxane, in a halogenated solvent such as CH2Cl2 to afford compounds of Formula 4.1, wherein R1, R2, R3, and R10, as shown in step a. Compounds of Formula 4.2, wherein R1, R2, R3, and R10, are as originally defined, can be prepared by treating compounds of Formula 3.2, wherein R1, R2, R3, and R10, are as originally defined, with an acid, such as 2,2,2-trifluoroacetic acid, in a halogenated solvent such as CH2Cl2, as shown in step c. Compounds of Formulas 4.1 and 4.2, wherein R1, R2, R3, and R10, are as originally defined, can be treated with compounds of Formula 4.3, wherein R5 is as originally defined, in the presence of a base, such as diisopropylethylamine, and a peptide coupling reagent, such as benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) or O-(7-azabenzo-triazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU), in a halogenated solvent such as CH2Cl2, to afford compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, as shown in steps b and d.
  • Figure US20200399222A1-20201224-C00007
  • Compounds of Formula 5.1, wherein R1, R2, R3, R5 and R10, are as originally defined, can be prepared according to the method outlined in Scheme 5, steps a or b. Compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, can be treated with an appropriate alkyl halide, with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na2CO3) or potassium carbonate (K2CO3), in a solvent such as acetone, at a temperature of about 25° C. to about 50° C., as shown in step a. Or, alternatively, by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, triethylamine (NEt3), DMAP, or mixtures thereof, in an aprotic solvent, such as CH2Cl2, to afford compounds of Formula 5.1, wherein R1, R2, R3, R5, R6, and R10, are as originally defined, as shown in step b.
  • Figure US20200399222A1-20201224-C00008
  • Compounds of Formula 6.1 and 6.2, wherein R1, R2, R3, R5, R6, and R10, are as originally defined, can be prepared according to the method outlined in Scheme 6, steps a and b. Compounds of Formula 4.5, wherein R1, R2, R3, R5, and R10, are as originally defined, can be treated with a thionating reagent such as phosphorus pentasulfide, an additive, such as hexamethyldisiloxane, optionally in a polar aprotic solvent such as acetonitrile (CH3CN), at a temperature of about 0° C. to 80° C. to afford compounds of Formula 6.1, wherein R1, R2, R3, R5 and R10, are as originally defined, and shown in step a. It will be understood by those skilled in the art that compounds such as Formula 6.1 may also be prepared using other thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson's reagent, ammonium O,O′-diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent. Additives can include, but not limited to, aluminum oxide (Al2O3); inorganic bases, such as potassium carbonate and sodium bicarbonate; organic bases, such as triethylamine, diethylaniline, pyridine and morpholine. Optional solvents can include, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons, such as hexane, cyclohexane or toluene; halogenated hydrocarbons, such as dichloromethane, 1,2-dichloroethane and chlorobenzene; ethers, such as diethyl ether, 1,4-dioxane, THE and 1,2-dimethoxyethane; and other polar aprotic solvents such as pyridine and hexamethylphosphoramide (HMPA). In step b, treatment of compounds of Formula 6.1, wherein R1, R2, R3, R5 and R10, are as originally defined, with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium carbonate (Na2CO3) or potassium carbonate (K2CO3), in a polar aprotic solvent, such as acetone, at a temperature of about 55° C., or by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, Et3N, DMAP, or mixtures thereof, in an optional aprotic solvent such as CH2Cl2, at a temperature of about 23° C., can afford compounds of Formula 6.2 wherein R1, R2, R3, R5, R6, and R10, are as originally defined.
  • Figure US20200399222A1-20201224-C00009
  • Compounds of Formula 7.1, wherein R1, R2, R3, R5 and R10, are as originally defined, can be prepared according to the method outlined in Scheme 7, step a. Compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, can be treated with a oxidizing reagent such as m-chloroperbenzoic acid (mCPBA) in a polar solvent such as CH2Cl2, at a temperature of about 0° C. to 50° C., to give compounds of Formula 7.1, wherein R1, R2, R3, R5 and R10, are as previously defined, and shown in a. It will be understood by those skilled in the art that compounds of Formula 7.1, wherein R1, R2, R3, R5 and R10, are as originally defined, may also be prepared using other oxidizing agents, including, but not limited to: hydrogen peroxide, hydrogen
  • Figure US20200399222A1-20201224-C00010
  • peroxide-urea complex, magnesium monoperoxyphthalate hexahydrate (MMPP), peroxyacetic acid, oxone, sodium perchlorate or dimethyl dioxirane.
  • Compounds of Formula 8.1 wherein R1, R2, R3, R5 and R10, are as originally defined, can be prepared according to the method outlined in Scheme 8, step a. Compounds of Formula 4.5, wherein R1, R2, R3, R5 and R10, are as originally defined, can be treated with a diactivated carbonyl reagent such as triphosgene, with a base, such as pyridine, and in a polar solvent, such as CH2Cl2, at a temperature of about 0° C. to 50° C. to afford compounds of Formula 8.1, wherein R1, R2, R3, R5 and R10, are as originally defined, as depicted in a.
  • Figure US20200399222A1-20201224-C00011
    • EXAMPLES Example 1A: Preparation of racemic threo-3-(2,4-dimethylphenyl)butan-2-ol
  • Figure US20200399222A1-20201224-C00012
  • To a suspension of freshly activated magnesium metal shavings (1.14 g, 46.80 mmol) in anhydrous Et2O (20 mL) was added dropwise 1-bromo-2,4-dimethylbenzene (8 g, 43.20 mmol). The mixture was gently heated at slight reflux (36° C.) for 5 hours (hr). The resulting dark brown solution was added via syringe to a flask containing copper (I) iodide (4.12 g, 21.61 mmol) suspended in Et2O (50 mL) at −20° C. The dark yellow suspension was stirred for 15 minutes (min) at −20° C. and then cooled to −50° C. Racemic trans-butene epoxide (1.3 g, 18.01 mmol) was slowly added dropwise followed by warming the reaction to room temperature and stirring overnight. The mixture was then cooled to 0° C. and slowly quenched by the addition of a saturated aqueous ammonium chloride (NH4Cl) solution. The mixture was filtered through a pad of Celite and the pad was rinsed thoroughly with ethyl acetate. The organic solution was washed with saturated NH4Cl solution and brine. The solution was dried (magnesium sulfate (MgSO4)), filtered and concentrated under reduced pressure. The residue was purified via automated flash column chromatography (SiO2, 0-40% ethyl acetate/hexanes gradient) to give racemic threo-3-(2,4-dimethylphenyl)butan-2-ol as a yellow oil (813 mg, 25%): 1H NMR (500 MHz, CDCl3) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.94-3.82 (m, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.29 (d, J=7.7 Hz, 6H), 1.50 (d, J=3.9 Hz, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 139.99, 135.49, 135.38, 131.31, 126.81, 126.18, 71.92, 41.42, 21.25, 20.87, 19.85, 16.06; EIMS m/z 178.
    • Example 1B: Preparation of racemic erythro-3-(o-tolyl)butan-2-ol
  • Figure US20200399222A1-20201224-C00013
  • To a −20° C. suspension of copper(I) iodide (4.15 g, 21.60 mmol) in anhydrous Et2O (40 mL) was added 2-methylphenylmagnesium bromide (2.0 M in Et2O, 22.5 mL, 43.20 mmol) slowly dropwise. After stirring for 30 min, the orange suspension was cooled to −78° C., and racemic cis-butene epoxide (1.3 g, 18.01 mmol) was slowly added. The dry ice bath was removed and the mixture was allowed to slowly warm to ambient temperature and stirred overnight. The mixture was cooled with an ice bath to 0° C. and quenched slowly by the dropwise addition of a saturated aqueous NH4Cl solution. The mixture was warmed to room temperature and filtered through Celite, followed by rinsing the pad with ethyl acetate (EtOAc). The resulting filtrate was washed with saturated aqueous NH4Cl solution and brine. The solution was then dried (MgSO4) and concentrated under reduced pressure. The residue was purified automated flash column chromatography (SiO2, 0-30% ethyl acetate/hexanes gradient) to give racemic erythro-3-(o-tolyl)butan-2-ol (2.05 g, 69%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.34-7.01 (m, 4H), 3.92 (p, J=6.3 Hz, 1H), 3.01 (p, J=7.1 Hz, 1H), 2.36 (s, 3H), 1.47 (s, 1H), 1.28 (d, J=6.1 Hz, 3H), 1.19 (d, J=7.0 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 142.14, 136.84, 130.61, 126.49, 125.81, 72.33, 42.62, 20.47, 19.93, 17.88; EIMS m/z 164.
    • Example 1C: Preparation of racemic threo-3-phenylbutan-2-ol
  • Figure US20200399222A1-20201224-C00014
  • To a suspension of copper (I) iodide (1.86 g, 9.76 mmol) in ethyl ether (18.0 mL) was added dropwise phenyllithium (1.9 M in butyl ether, 10.3 mL, 19.53 mmol) at 0° C. under a nitrogen atmosphere. After stirring at 0° C. for 1 hr, racemic trans-2,3-dimethyloxirane (0.64 g, 8.88 mmol) was added dropwise followed by removal of the ice bath and warming to room temperature with stirring over 2 hr. The reaction mixture was quenched with water (20 mL), filtered through a pad of Celite, and extracted with ethyl ether (3×20 mL). The organics were passed through a phase separator and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-25% acetone/hexanes gradient) to furnish racemic threo-3-phenylbutan-2-ol (1.33 g, 8.85 mmol, 99%) as orange oil: 1H NMR (400 MHz, CDCl3) δ 7.38-7.12 (m, 5H), 3.91-3.84 (m, 1H), 2.80-2.68 (m, 1H), 1.43 (s, 1H), 1.33 (d, J=7.1 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H). The spectral data was consistent with those reported in the literature: Tetrahedron 1981, 37, 709-713.
    • Example 2: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol and (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol Step 1: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol and (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate
  • Figure US20200399222A1-20201224-C00015
  • A vial containing a solution of the racemic trans-3-(2,4-dimethylphenyl)butan-2-ol (800 mg, 4.49 mmol) dissolved in vinyl acetate (15 mL) was charged with beads of Novozym 435 Lipase (CAL-B, 1.6 g, 4.49 mmol). The vial was placed in an orbital shaker and was shaken at 200 rpm and heated at 55° C. for 7.5 hrs. The reaction was cooled and filtered through a frit disk with an EtOAc rinse. The eluent was concentrated under reduced pressure to give 906 mg of a crude yellow oil. The residue was purified via flash column chromatography (SiO2, 0-20% ethyl acetate/hexanes gradient) to afford (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate (clear oil, 466 mg, 47%) followed by (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol (clear yellow oil, 357 mg, 43%). Acetate: 1H NMR (500 MHz, CDCl3) δ 7.07 (d, J=7.7 Hz, 1H), 7.01-6.97 (m, 2H), 5.08 (dq, J=8.5, 6.3 Hz, 1H), 3.16-3.05 (m, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 2.06 (s, 3H), 1.21 (d, J=6.9 Hz, 3H), 1.06 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 170.80, 138.92, 135.56, 135.42, 131.22, 126.93, 126.33, 75.09, 39.48, 21.34, 20.89, 19.88, 18.34, 17.96; EIMS m/z 220. Alcohol: 1H NMR (500 MHz, CDCl3) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.88 (tt, J=9.2, 4.7 Hz, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 1.49 (d, J=3.5 Hz, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 140.00, 135.49, 135.38, 131.31, 126.82, 126.18, 71.92, 41.43, 21.25, 20.87, 19.85, 16.07; EIMS m/z 178. The enatiomeric ratio of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-ol was determined to be 96:4 by analysis via enatiomeric HPLC separation (210 nm wavelength).
    • Step 2: Preparation of (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol
  • Figure US20200399222A1-20201224-C00016
  • To a solution containing (2R,3R)-3-(2,4-dimethylphenyl)butan-2-yl acetate prepared above (458 mg, 2.08 mmol) dissolved in methanol (4.2 mL) was added potassium carbonate (431 mg, 3.12 mmol). The mixture was stirred at ambient temperature for 1.5 hr, then heated to 50° C. for 2 hr. The reaction was cooled and concentrated under reduced pressure. The residue was diluted with acetone and passed through a small plug of silica gel, washing the pad well with acetone. The solvent was concentrated in vacuo to give (2R,3R)-3-(2,4-dimethylphenyl)butan-2-ol (332 mg, 90%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.06 (d, J=8.5 Hz, 1H), 7.01-6.97 (m, 2H), 3.88 (p, J=6.3 Hz, 1H), 2.97 (p, J=6.9 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H), 1.49 (s, 1H), 1.28 (d, J=7.0 Hz, 3H), 1.11 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 140.00, 135.49, 135.38, 131.31, 126.82, 126.18, 71.92, 41.43, 21.26, 20.87, 19.85, 16.07; EIMS m/z 178. The enatiomeric ratio of the alcohol was determined to be 7:93 via analysis by enatiomeric HPLC.
    • Example 3: Preparation of (2S,3S)-3-phenylbutan-2-ol (tert-butoxycarbonyl)-L-alaninate
  • Figure US20200399222A1-20201224-C00017
  • To a solution of (2S,3S)-3-phenylbutan-2-ol (0.23 g, 1.53 mmol) dissolved in methylene chloride (7.7 mL) was added N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.59 g, 3.06 mmol) and N,N-dimethylpyridin-4-amine (19 mg, 0.15 mmol). The reaction mixture was purged with nitrogen, stirred over 16 hr, followed by concentration in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-20% ethyl acetate/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (tert-butoxycarbonyl)-L-alaninate (0.43 g, 1.34 mmol, 83% yield) as colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.35-7.25 (m, 2H), 7.27-7.15 (m, 3H), 5.12-5.01 (m, 2H), 4.35-4.26 (m, 1H), 2.95-2.83 (m, 1H), 1.45 (s, 9H), 1.37 (d, J=7.2 Hz, 3H), 1.29 (d, J=7.1 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 172.9, 155.0, 143.0, 128.5, 127.8, 126.7, 79.7, 76.1, 49.5, 45.1, 28.3, 18.9, 18.3, 17.5; IR (thin film) 3355, 2978, 2934, 1711, 1495, 1452, 1366, 1161, 1087, 1065, 701 cm−1.
    • Example 4: Preparation of (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate Step 1: Preparation of (2S,3S)-3-phenylbutan-2-yl-L-alaninate hydrochloride
  • Figure US20200399222A1-20201224-C00018
  • To neat (2S,3S)-3-phenylbutan-2-ol (tert-butoxycarbonyl)-L-alaninate (0.42 g, 1.31 mmol) was added dropwise a solution of HCl dissolved in dioxane (4 M, 3.3 mL, 13.07 mmol) under nitrogen. Upon stirring for 16 hr, the reaction mixture was concentrated in vacuo to afford crude (2S,3S)-3-phenylbutan-2-yl-L-alaninate hydrogen chloride as white solid, which was directly carried to the next step: HRMS-ESI (m/z) [M+H]+ calc'd for C13H20NO2, 222.1489; found, 222.1485.
    • Step 2: Preparation of (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate
  • Figure US20200399222A1-20201224-C00019
  • To a solution of (2S,3S)-3-phenylbutan-2-yl-L-alaninate hydrogen chloride, 3-hydroxy-4-methoxypicolinic acid (0.24 g, 1.44 mmol), and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (0.75 g, 1.44 mmol) dissolved in methylene chloride (6.5 mL) was added dropwise N,N-diisopropylethylamine (0.75 mL, 4.31 mmol) under nitrogen. Upon stirring for 16 hr, the reaction mixture was concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-45% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (0.46 g, 1.173 mmol, 90% yield) as colorless oil: 1H NMR (500 MHz, CDCl3) δ 12.16 (s, 1H), 8.50 (d, J=8.0 Hz, 1H), 8.01 (d, J=5.2 Hz, 1H), 7.32-7.27 (m, 2H), 7.24-7.16 (m, 3H), 6.88 (d, J=5.2 Hz, 1H), 5.11 (dq, J=7.7, 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H), 2.97-2.87 (m, 1H), 1.54 (d, J=7.2 Hz, 3H), 1.31 (d, J=7.0 Hz, 3H), 1.13 (d, J=6.3 Hz, 3H); IR (thin film) 2978, 2937, 1733, 1647, 1527, 1451, 1262, 1147, 701 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C2H25N2O5, 373.1758; found, 373.1752.
    • Example 5A: Preparation of (2S,3S)-3-phenylbutan-2-yl (3-acetoxy-4-methoxypicolinoyl)-L-alaninate
  • Figure US20200399222A1-20201224-C00020
  • To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (84 mg, 0.23 mmol) dissolved in pyridine (1.0 mL) was added dropwise acetic anhydride (0.25 mL, 2.65 mmol) under nitrogen. Upon stirring for 30 min, the reaction mixture was concentrated in vacuo, followed by azeotroping with toluene (10 mL). The crude residue was purified via automated flash column chromatography (SiO2, 0-40% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (3-acetoxy-4-methoxypicolinoyl)-L-alaninate (90 mg, 0.21 mmol, 91% yield) as colorless oil: 1H NMR (500 MHz, CDCl3) δ 8.56 (s, 1H), 8.34 (d, J=5.5 Hz, 1H), 7.32-7.27 (m, 2H), 7.24-7.16 (m, 3H), 7.01 (d, J=5.5 Hz, 1H), 5.09 (dq, J=7.7, 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.91 (s, 3H), 2.96-2.86 (m, 1H), 2.41 (s, 3H), 1.49 (d, J=7.2 Hz, 3H), 1.30 (d, J=7.0 Hz, 3H), 1.10 (d, J=6.3 Hz, 3H); IR (thin film) 3377, 2980, 2938, 1770, 1732, 1674, 1507, 1310, 1198, 1174, 702 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C22H27N2O6, 415.1864; found, 415.1859.
    • Example 5B: Preparation of (2S,3R)-3-(o-tolyl)butan-2-yl (3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate
  • Figure US20200399222A1-20201224-C00021
  • To a solution containing (2S,3R)-3-(o-tolyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate dissolved in 0.7 mL of acetone was added potassium carbonate (39 mg, 0.279 mmol) followed by bromomethyl acetate (27 μL, 0.279 mmol). The solution was heated at 50° C. for 1.5 hr. The reaction mixture was cooled and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-80% acetone/hexanes gradient) to afford (2S,3R)-3-(o-tolyl)butan-2-yl (3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate (63 mg, 93% yield) as a thick oil: 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J=5.4 Hz, 1H), 8.22 (t, J=7.4 Hz, 1H), 7.22-7.03 (m, 4H), 6.93 (d, J=5.4 Hz, 1H), 5.73 (dd, J=5.6, 1.8 Hz, 2H), 5.16 (dq, J=8.1, 6.3 Hz, 1H), 4.58-4.51 (m, 1H), 3.90 (s, 3H), 3.31-3.22 (m, 1H), 2.37 (s, 3H), 2.06 (s, 3H), 1.31 (d, J=6.2 Hz, 3H), 1.24 (d, J=7.0 Hz, 3H), 1.03 (d, J=7.2 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 172.26, 170.26, 162.87, 160.25, 145.68, 143.94, 142.57, 141.57, 136.03, 130.21, 126.16, 125.94, 109.49, 89.57, 75.57, 56.16, 48.08, 39.48, 20.87, 19.84, 17.92, 17.77, 17.05; HRMS-ESI (m/z) [M+H]+ calc'd for C24H30N2O7, 459.2126; found, 459.2121.
    • Example 5C: Preparation of 4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate
  • Figure US20200399222A1-20201224-C00022
  • To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (283.9 mg, 0.645 mmol) and N,N-dimethylpyridin-4-amine (15.75 mg, 0.129 mmol) was prepared in CH2Cl2 (2 mL). To this solution was added triethylamine (0.180 mL, 1.289 mmol) followed by isobutyryl chloride (0.102 mL, 0.967 mmol). The resultant clear reaction was stirred at ambient temperature overnight. The reaction was concentrated under reduced pressure to afford an orange oil under a stream of N2. The crude residue was purified via automated flash column chromatography (SiO2, 0-100% ethyl acetate/hexanes gradient) to afford 4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl)oxy)propan-2-yl)carbamoyl)pyridin-3-yl isobutyrate (252.3 mg, 0.494 mmol, 77% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J=7.4 Hz, 1H), 8.34 (d, J=5.4 Hz, 1H), 7.64 (dd, J=8.0, 1.3 Hz, 1H), 7.54-7.47 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.31 (t, J=7.5 Hz, 1H), 6.99 (d, J=5.4 Hz, 1H), 5.26-5.11 (m, 1H), 4.76 (p, J=7.3 Hz, 1H), 3.89 (s, 3H), 3.34 (p, J=6.6 Hz, 1H), 2.96 (hept, J=7.0 Hz, 1H), 1.54 (d, J=7.2 Hz, 3H), 1.36 (dd, J=7.0, 1.3 Hz, 6H), 1.28 (d, J=6.8 Hz, 3H), 1.10 (d, J=6.3 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ−58.25; IR (thin film) 3383, 2981, 1737, 1679, 1505, 1310, 1114, 1045, 732 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C25H3F3N2O6, 511.2050; found, 511.2048.
    • Example 6: Preparation of (2S,3S)-3-(2,4-dimethylphenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate Step 1: Preparation of (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
  • Figure US20200399222A1-20201224-C00023
  • To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (120.1 mg, 0.273 mmol) dissolved in acetonitrile (2.73 mL) was added phosphorus pentasulfide (121 mg, 0.545 mmol) followed by 1,1,1,3,3,3-hexamethyldisiloxane (291 μL, 1.363 mmol) added in one portion. The reaction was heated to 45° C. for 30 min. The reaction was cooled, diluted with CH2Cl2 (10 mL) and quenched by the addition of saturated aqueous NaHCO3 (10 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic layers were passed through a phase separator and concentrated to a yellow oil. The crude material was purified via automated flash column chromatography (SiO2, 0-50% acetone/hexanes gradient) to afford (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (104.7 mg, 0.229 mmol, 84% yield) as a yellow semisolid; 1H NMR (400 MHz, CDCl3) δ 12.93 (s, 1H), 10.74 (d, J=7.6 Hz, 1H), 8.00 (d, J=5.1 Hz, 1H), 7.73-7.59 (m, 1H), 7.51 (t, J=7.7 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 6.89 (d, J=5.1 Hz, 1H), 5.30-5.18 (m, 1H), 5.14 (p, J=7.2 Hz, 1H), 3.96 (s, 3H), 3.37 (p, J=6.8 Hz, 1H), 1.69 (dd, J=7.2, 3.2 Hz, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.14 (d, J=6.3 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ−58.23; IR (thin film) 3087, 2984, 1737, 1513, 1484, 1311, 1151, 1118, 800, 771 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C21H24F3N2O4S, 457.1403; found, 457.1399.
    • Step 2: Preparation of (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
  • Figure US20200399222A1-20201224-C00024
  • To a solution containing (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (53.9 mg, 0.118 mmol) and N,N-dimethylpyridin-4-amine (2.89 mg, 0.024 mmol) dissolved in CH2Cl2 (2 mL) was added triethylamine (0.041 mL, 0.295 mmol) followed by acetyl chloride (9.23 μL, 0.130 mmol). The resultant light orange reaction was stirred at ambient temperature for 18 hr. The reaction was concentrated under reduced pressure to afford an orange oil under a stream of N2. The crude residue was purified via automated flash column chromatography (SiO2, 0-50% acetone/hexanes gradient) to afford (2S,3S)-3-(2-(trifluoromethyl)phenyl)butan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (51.7 mg, 0.104 mmol, 88% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 9.96 (d, J=7.3 Hz, 1H), 8.34 (d, J=5.5 Hz, 1H), 7.71-7.59 (m, 1H), 7.59-7.47 (m, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.39-7.28 (m, 1H), 7.00 (d, J=5.5 Hz, 1H), 5.28-5.15 (m, 2H), 3.91 (s, 3H), 3.42-3.29 (m, 1H), 2.37 (s, 3H), 1.64 (d, J=7.2 Hz, 3H), 1.30 (d, J=6.8 Hz, 3H), 1.12 (d, J=6.3 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ−58.23; HRMS-ESI (m/z) [M+H]+ calc'd for C23H26F3N2O5S, 499.1509; found, 499.1508.
    • Example 7: Preparation of 3-hydroxy-4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-phenylbutan-2-yl)oxy)propan-2-yl)carbamoyl)pyridine 1-oxide
  • Figure US20200399222A1-20201224-C00025
  • To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (54 mg, 0.15 mmol) dissolved in methylene chloride (1.0 mL) was added m-CPBA (50 mg, 0.29 mmol). Upon stirring for 30 min at room temperature, the reaction mixture was concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-50% acetone/hexanes gradient) to afford 3-hydroxy-4-methoxy-2-(((S)-1-oxo-1-(((2S,3S)-3-phenylbutan-2-yl)oxy)propan-2-yl)carbamoyl)pyridine 1-oxide (51 mg, 0.13 mmol, 86% yield) as viscous, pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 14.39 (s, 1H), 12.82 (d, J=6.9 Hz, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.25-7.15 (m, 3H), 6.78 (d, J=7.2 Hz, 1H), 5.10 (dq, J=8.1, 6.3 Hz, 1H), 4.75-4.64 (m, 1H), 3.97 (s, 3H), 2.96-2.86 (m, 1H), 1.56 (d, J=7.2 Hz, 3H), 1.30 (d, J=6.9 Hz, 3H), 1.12 (d, J=6.2 Hz, 3H); IR (thin film) 2978, 2937, 1735, 1643, 1569, 1479, 1452, 1211, 1154, 729, 702 cm−1; HRMS-ESI (m/z) [M+H]+ calc'd for C20H25N2O6, 389.1707; found, 389.1703.
    • Example 8: Preparation of (2S,3S)-3-phenylbutan-2-yl (S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3(4H)-yl)propanoate
  • Figure US20200399222A1-20201224-C00026
  • To a solution containing (2S,3S)-3-phenylbutan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (54 mg, 0.15 mmol) and triphosgene (86 mg, 0.29 mmol) dissolved in methylene chloride (1.0 mL) was added pyridine (0.1 mL, 1.24 mmol). Upon stirring for 45 min, the reaction mixture was quenched with saturated sodium bicarbonate solution (5 mL) and extracted with methylene chloride (3×5 mL). The organics were passed through a phase separator and concentrated in vacuo. The crude residue was purified via automated flash column chromatography (SiO2, 0-40% acetone/hexanes gradient) to afford (2S,3S)-3-phenylbutan-2-yl (S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3(4H)-yl)propanoate (41 mg, 0.10 mmol, 67% yield) as an off-white foam: 1H NMR (500 MHz, CDCl3) δ 8.61 (d, J=5.3 Hz, 1H), 7.24-7.17 (m, 2H), 7.17-7.06 (m, 4H), 5.61 (q, J=7.1 Hz, 1H), 5.16-5.06 (m, 1H), 4.06 (s, 3H), 2.93-2.83 (m, 1H), 1.70 (d, J=7.1 Hz, 3H), 1.27 (d, J=7.1 Hz, 3H), 1.04 (d, J=6.3 Hz, 3H); IR (thin film) 2978, 2942, 1769, 1712, 1602, 1501, 1371, 1242, 1081, 702 cm1; HRMS-ESI (m/z) [M+H]+ calc'd for C21H23N2O6, 399.1551; found, 399.1549.
    • Example A: Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Zymoseptoria tritici; Bayer Code SEPTTR)
  • Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 110 ppm Triton X-100. The fungicide solutions were applied onto wheat seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling. All fungicides were evaluated using the aforementioned method for their activity vs. all target diseases, unless stated otherwise. Wheat leaf blotch and brown rust activity were also evaluated using track spray applications, in which case the fungicides were formulated as EC formulations, containing 0.1% Trycol 5941 in the spray solutions.
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. When disease symptoms were fully expressed on the 1st leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.
    • Example B: Evaluation of Fungicidal Activity: Wheat Brown Rust (Puccinia triticina; Synonym: Puccinia recondita f. sp. tritici; Bayer Code PUCCRT)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22° C. with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
    • Example C: Evaluation of Fungicidal Activity: Asian Soybean Rust (Phakopsora pachyrhizi; Bayer Code PHAKPA)
  • Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 0.011% Tween 20. The fungicide solutions were applied onto soybean seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling.
  • Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two week old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22° C. and 100% relative humidity then transferred to a growth room at 23° C. for disease to develop. Disease severity was assessed on the sprayed leaves.
    • Example D: Evaluation of Fungicidal Activity: Tomato Early Blight (Alternaria solani; Bayer Code ALTESO)
  • Tomato plants (variety Outdoor Girl) were propagated in soil-less Metro mix, with each pot having one plant, and used when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Alternaria solani 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example E: Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets (Cercospora beticola; Bayer Code CERCBE)
  • Sugar beet plants (variety HH88) were grown in soil-less Metro mix and trimmed regularly to maintain a uniform plant size prior to test. Plants were inoculated with a spore suspension 24 hr after fungicide treatments. Inoculated plants were kept in a dew chamber at 22° C. for 48 hr then incubated in a greenhouse set at 24° C. under a clear plastic hood with bottom ventilation until disease symptoms were fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example F: Evaluation of Fungicidal Activity: Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotrichum lagenarium; Bayer Code COLLLA)
  • Cucumber seedlings (variety Bush Pickle) were propagated in soil-less Metro mix, with each pot having one plant, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Colletotrichum lagenarium 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room set at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example G: Evaluation of Fungicidal Activity: Wheat Glume Blotch (Parastagonospora nodorum; Bayer Code LEPTNO)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Parastagonospora nodorum 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
    • Example H: Evaluation of Fungicidal Activity: Cucumber Downy Mildew (Pseudoperonospora cubensis; Bayer Code PSPECU)
  • Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metro mix, with one plant per pot, and used in the test when 12 to 14 days old. Plants were inoculated with a spore suspension 24 hr following fungicide treatments. Test plants were inoculated with an aqueous spore suspension of Pseudoperonospora cubensis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 24 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. until disease was fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example I: Evaluation of Fungicidal Activity: Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae; Bayer Code PYRIOR)
  • Rice seedlings (variety Japonica) were propagated in soil-less Metro mix, with each pot having 8 to 14 plants, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Pyricularia oryzae 24 hr after fungicide treatments. After inoculation, the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example J: Evaluation of Fungicidal Activity: Barley Scald (Rhyncosporium secalis; Bayer Code RHYNSE)
  • Barley seedlings (variety Harrington) were propagated in soil-less Metro mix, with each pot having 8 to 12 plants, and used in the test when first leaf was fully emerged. Test plants were inoculated by an aqueous spore suspension of Rhyncosporium secalis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 20° C. with 100% relative humidity for 48 hr. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example K: Evaluation of Fungicidal Activity: Grape Powdery Mildew (Uncinula necator; Bayer Code UNCINE)
  • Grape seedlings (variety Carignane) were grown in soil-less Metro mix, with one plant per pot, and used in the test when approximately 1 month old. Plants were inoculated 24 hr after fungicide treatment by shaking spores from infected leaves over test plants. Plants were maintained in a greenhouse set at 20° C. until disease was fully developed. Fungicide formulation, application and disease assessment on sprayed leaves followed the procedures as described in the Example A.
  • TABLE 1
    Compound Structure, Appearance, and Preparation Method
    As Prepared
    Cmpd. According
    No. Structure To Appearance
    1
    Figure US20200399222A1-20201224-C00027
         		Example 1A Example 2 Example 3 Oil
    2
    Figure US20200399222A1-20201224-C00028
         		Example 1A Example 2 Example 3 Oil
    3
    Figure US20200399222A1-20201224-C00029
         		Example 1A Example 2 Example 3 Oil
    4
    Figure US20200399222A1-20201224-C00030
         		Example 1A Example 2 Example 3 Oil
    5
    Figure US20200399222A1-20201224-C00031
         		Example 1A Example 2 Example 3 Oil
    6
    Figure US20200399222A1-20201224-C00032
         		Example 1A Example 2 Example 3 Oil
    7
    Figure US20200399222A1-20201224-C00033
         		Example 1A Example 2 Example 3 Oil
    8
    Figure US20200399222A1-20201224-C00034
         		Example 1A Example 2 Example 3 Oil
    9
    Figure US20200399222A1-20201224-C00035
         		Example 1B Example 2 Example 3 Oil
    10
    Figure US20200399222A1-20201224-C00036
         		Example 1B Example 2 Example 3 Oil
    11
    Figure US20200399222A1-20201224-C00037
         		Example 1B Example 2 Example 3 Oil
    12
    Figure US20200399222A1-20201224-C00038
         		Example 1B Example 2 Example 3 Oil
    13
    Figure US20200399222A1-20201224-C00039
         		Example 1B Example 2 Example 3 Oil
    14
    Figure US20200399222A1-20201224-C00040
         		Example 1B Example 2 Example 3 Oil
    15
    Figure US20200399222A1-20201224-C00041
         		Example 1B Example 2 Example 3 Oil
    16
    Figure US20200399222A1-20201224-C00042
         		Example 1B Example 2 Example 3 Oil
    17
    Figure US20200399222A1-20201224-C00043
         		Example 1B Example 2 Example 3 Oil
    18
    Figure US20200399222A1-20201224-C00044
         		Example 1B Example 2 Example 3 Oil
    19
    Figure US20200399222A1-20201224-C00045
         		Example 1B Example 2 Example 3 Oil
    20
    Figure US20200399222A1-20201224-C00046
         		Example 1B Example 2 Example 3 Oil
    21
    Figure US20200399222A1-20201224-C00047
         		Example 1A Example 2 Example 3 Oil
    22
    Figure US20200399222A1-20201224-C00048
         		Example 1A Example 2 Example 3 Oil
    23
    Figure US20200399222A1-20201224-C00049
         		Example 1A Example 2 Example 3 Oil
    24
    Figure US20200399222A1-20201224-C00050
         		Example 1A Example 2 Example 3 Oil
    25
    Figure US20200399222A1-20201224-C00051
         		Example 1A Example 2 Example 3 Oil
    26
    Figure US20200399222A1-20201224-C00052
         		Example 1A Example 2 Example 3 Oil
    27
    Figure US20200399222A1-20201224-C00053
         		Example 1A Example 2 Example 3 Oil
    28
    Figure US20200399222A1-20201224-C00054
         		Example 1A Example 2 Example 3 Oil
    29
    Figure US20200399222A1-20201224-C00055
         		Example 1B Example 2 Example 3 Oil
    30
    Figure US20200399222A1-20201224-C00056
         		Example 1B Example 2 Example 3 Oil
    31
    Figure US20200399222A1-20201224-C00057
         		Example 1B Example 2 Example 3 Oil
    32
    Figure US20200399222A1-20201224-C00058
         		Example 1B Example 2 Example 3 Oil
    33
    Figure US20200399222A1-20201224-C00059
         		Example 1B Example 2 Example 3 Oil
    34
    Figure US20200399222A1-20201224-C00060
         		Example 1B Example 2 Example 3 Oil
    35
    Figure US20200399222A1-20201224-C00061
         		Example 1B Example 2 Example 3 Oil
    36
    Figure US20200399222A1-20201224-C00062
         		Example 1B Example 2 Example 3 Oil
    37
    Figure US20200399222A1-20201224-C00063
         		Example 1B Example 2 Example 3 Oil
    38
    Figure US20200399222A1-20201224-C00064
         		Example 1B Example 2 Example 3 Oil
    39
    Figure US20200399222A1-20201224-C00065
         		Example 1B Example 2 Example 3 Oil
    40
    Figure US20200399222A1-20201224-C00066
         		Example 1B Example 2 Example 3 Oil
    41
    Figure US20200399222A1-20201224-C00067
         		Example 1A Example 2 Example 3 Light Yellow Oil
    42
    Figure US20200399222A1-20201224-C00068
         		Example 1A Example 2 Example 3 Clear Oil
    43
    Figure US20200399222A1-20201224-C00069
         		Example 1A Example 2 Example 3 Reddish Brown Oil
    44
    Figure US20200399222A1-20201224-C00070
         		Example 1A Example 2 Example 3 Orange Oil
    45
    Figure US20200399222A1-20201224-C00071
         		Example 1A Example 2 Example 3 Yellow Oil
    46
    Figure US20200399222A1-20201224-C00072
         		Example 1A Example 2 Example 3 Yellow Oil
    47
    Figure US20200399222A1-20201224-C00073
         		Example 1A Example 3 Clear, Colorless Oil
    48
    Figure US20200399222A1-20201224-C00074
         		Example 1A Example 3 Pale Yellow Oil
    49
    Figure US20200399222A1-20201224-C00075
         		Example 1A Example 2 Example 3 Clear, Colorless Oil
    50
    Figure US20200399222A1-20201224-C00076
         		Example 1A Example 2 Example 3 Pale Yellow Oil
    51
    Figure US20200399222A1-20201224-C00077
         		Example 1A Example 2 Example 3 Clear, Colorless Oil
    52
    Figure US20200399222A1-20201224-C00078
         		Example 1A Example 2 Example 3 Clear, Colorless Oil
    53
    Figure US20200399222A1-20201224-C00079
         		Example 1B Example 2 Example 3 Colorless Oil
    54
    Figure US20200399222A1-20201224-C00080
         		Example 1C Example 2 Example 3 Colorless Oil
    55
    Figure US20200399222A1-20201224-C00081
         		Example 1B Example 2 Example 3 Yellow Oil
    56
    Figure US20200399222A1-20201224-C00082
         		Example 1B Example 2 Example 3 Colorless Oil
    57
    Figure US20200399222A1-20201224-C00083
         		Example 1B Example 2 Example 3 Residue
    58
    Figure US20200399222A1-20201224-C00084
         		Example 4 Step 1 Oil
    59
    Figure US20200399222A1-20201224-C00085
         		Example 4 Step 1 Oil
    60
    Figure US20200399222A1-20201224-C00086
         		Example 4 Step 1 Oil
    61
    Figure US20200399222A1-20201224-C00087
         		Example 4 Step 1 Oil
    62
    Figure US20200399222A1-20201224-C00088
         		Example 4 Step 1 Oil
    63
    Figure US20200399222A1-20201224-C00089
         		Example 4 Step 1 Oil
    64
    Figure US20200399222A1-20201224-C00090
         		Example 4 Step 1 Oil
    65
    Figure US20200399222A1-20201224-C00091
         		Example 4 Step 1 Oil
    66
    Figure US20200399222A1-20201224-C00092
         		Example 4 Step 1 Oil
    67
    Figure US20200399222A1-20201224-C00093
         		Example 4 Step 1 Oil
    68
    Figure US20200399222A1-20201224-C00094
         		Example 4 Step 1 Oil
    69
    Figure US20200399222A1-20201224-C00095
         		Example 4 Step 1 Oil
    70
    Figure US20200399222A1-20201224-C00096
         		Example 4 Step 1 Oil
    71
    Figure US20200399222A1-20201224-C00097
         		Example 4 Step 1 Oil
    72
    Figure US20200399222A1-20201224-C00098
         		Example 4 Step 1 Oil
    73
    Figure US20200399222A1-20201224-C00099
         		Example 4 Step 1 Oil
    74
    Figure US20200399222A1-20201224-C00100
         		Example 4 Step 1 Oil
    75
    Figure US20200399222A1-20201224-C00101
         		Example 4 Step 1 Oil
    76
    Figure US20200399222A1-20201224-C00102
         		Example 4 Step 1 Oil
    77
    Figure US20200399222A1-20201224-C00103
         		Example 4 Step 1 Oil
    78
    Figure US20200399222A1-20201224-C00104
         		Example 4 Step 1 Oil
    79
    Figure US20200399222A1-20201224-C00105
         		Example 4 Step 1 Oil
    80
    Figure US20200399222A1-20201224-C00106
         		Example 4 Step 1 Oil
    81
    Figure US20200399222A1-20201224-C00107
         		Example 4 Step1 Oil
    82
    Figure US20200399222A1-20201224-C00108
         		Example 4 Step 1 Oil
    83
    Figure US20200399222A1-20201224-C00109
         		Example 4 Step 1 Oil
    84
    Figure US20200399222A1-20201224-C00110
         		Example 4 Step 1 Oil
    85
    Figure US20200399222A1-20201224-C00111
         		Example 4 Step 1 Oil
    86
    Figure US20200399222A1-20201224-C00112
         		Example 4 Step 1 Oil
    87
    Figure US20200399222A1-20201224-C00113
         		Example 4 Step 1 Oil
    88
    Figure US20200399222A1-20201224-C00114
         		Example 4 Step 1 Oil
    89
    Figure US20200399222A1-20201224-C00115
         		Example 4 Step 1 Oil
    90
    Figure US20200399222A1-20201224-C00116
         		Example 4 Step 1 Oil
    91
    Figure US20200399222A1-20201224-C00117
         		Example 4 Step 1 Oil
    92
    Figure US20200399222A1-20201224-C00118
         		Example 4 Step 1 Oil
    93
    Figure US20200399222A1-20201224-C00119
         		Example 4 Step 1 Oil
    94
    Figure US20200399222A1-20201224-C00120
         		Example 4 Step 1 Oil
    95
    Figure US20200399222A1-20201224-C00121
         		Example 4 Step 1 Oil
    96
    Figure US20200399222A1-20201224-C00122
         		Example 4 Step 1 Oil
    97
    Figure US20200399222A1-20201224-C00123
         		Example 4 Step 1 Oil
    98
    Figure US20200399222A1-20201224-C00124
         		Example 4 Step 1 Dark Yellow Oil
    99
    Figure US20200399222A1-20201224-C00125
         		Example 4 Step 1 Dark Yellow Oil
    100
    Figure US20200399222A1-20201224-C00126
         		Example 4 Step 1 Brown Semisolid
    101
    Figure US20200399222A1-20201224-C00127
         		Example 4 Step 1 Light Brown Semisolid
    102
    Figure US20200399222A1-20201224-C00128
         		Example 1A Example 2 Example 3 Example 4 Step 1 Pale Yellow Oil
    103
    Figure US20200399222A1-20201224-C00129
         		Example 4 Step 1 Orange Semisolid
    104
    Figure US20200399222A1-20201224-C00130
         		Example 4 Step 1 Orange Semisolid
    105
    Figure US20200399222A1-20201224-C00131
         		Example 1A Example 2 Example 3 Example 4 Step 1 White Semisolid
    106
    Figure US20200399222A1-20201224-C00132
         		Example 4 Step 1 White Semisolid
    107
    Figure US20200399222A1-20201224-C00133
         		Example 4 Step 1 Pale Yellow Oil
    108
    Figure US20200399222A1-20201224-C00134
         		Example 4 Step 1 White Semisolid
    109
    Figure US20200399222A1-20201224-C00135
         		Example 4 Step 1 Clear, Colorless Glass
    110
    Figure US20200399222A1-20201224-C00136
         		Example 4 Step 1 Clear, Colorless Oil
    111
    Figure US20200399222A1-20201224-C00137
         		Example 4 Step 1 Clear, Colorless Oil
    112
    Figure US20200399222A1-20201224-C00138
         		Example 4 Step 1 Colorless Oil
    113
    Figure US20200399222A1-20201224-C00139
         		Example 4 Step 1 White Solid
    114
    Figure US20200399222A1-20201224-C00140
         		Example 4 Step 1 Yellow Oil
    115
    Figure US20200399222A1-20201224-C00141
         		Example 4 Step 1 Colorless Oil
    116
    Figure US20200399222A1-20201224-C00142
         		Example 4 Step 2 Thick Clear Oil
    117
    Figure US20200399222A1-20201224-C00143
         		Example 4 Step 2 Thick Clear Oil
    118
    Figure US20200399222A1-20201224-C00144
         		Example 4 Step 2 White Solid
    119
    Figure US20200399222A1-20201224-C00145
         		Example 4 Step 2 White Solid
    120
    Figure US20200399222A1-20201224-C00146
         		Example 4 Step 2 Thick Oil
    121
    Figure US20200399222A1-20201224-C00147
         		Example 4 Step 2 Thick Oil
    122
    Figure US20200399222A1-20201224-C00148
         		Example 4 Step 2 Thick Oil
    123
    Figure US20200399222A1-20201224-C00149
         		Example 4 Step 2 White Solid
    124
    Figure US20200399222A1-20201224-C00150
         		Example 4 Step 2 Thick Oil
    125
    Figure US20200399222A1-20201224-C00151
         		Example 4 Step 2 Thick Oil
    126
    Figure US20200399222A1-20201224-C00152
         		Example 4 Step 2 White Solid
    127
    Figure US20200399222A1-20201224-C00153
         		Example 4 Step 2 Thick Oil
    128
    Figure US20200399222A1-20201224-C00154
         		Example 4 Step 2 White Solid
    129
    Figure US20200399222A1-20201224-C00155
         		Example 4 Step 2 Thick Oil
    130
    Figure US20200399222A1-20201224-C00156
         		Example 4 Step 2 White Solid
    131
    Figure US20200399222A1-20201224-C00157
         		Example 4 Step 2 Thick Oil
    132
    Figure US20200399222A1-20201224-C00158
         		Example 4 Step 2 Thick Oil
    133
    Figure US20200399222A1-20201224-C00159
         		Example 4 Step 2 Thick Oil
    134
    Figure US20200399222A1-20201224-C00160
         		Example 4 Step 2 Thick Oil
    135
    Figure US20200399222A1-20201224-C00161
         		Example 4 Step 2 Think Oil
    136
    Figure US20200399222A1-20201224-C00162
         		Example 4 Step 2 Thick Oil
    137
    Figure US20200399222A1-20201224-C00163
         		Example 4 Step 2 Thick Oil
    138
    Figure US20200399222A1-20201224-C00164
         		Example 4 Step 2 White Solid
    139
    Figure US20200399222A1-20201224-C00165
         		Example 4 Step 2 Thick Oil
    140
    Figure US20200399222A1-20201224-C00166
         		Example 4 Step 2 Thick Oil
    141
    Figure US20200399222A1-20201224-C00167
         		Example 4 Step 2 White Solid
    142
    Figure US20200399222A1-20201224-C00168
         		Example 4 Step 2 Thick Oil
    143
    Figure US20200399222A1-20201224-C00169
         		Example 4 Step 2 Thick Oil
    144
    Figure US20200399222A1-20201224-C00170
         		Example 4 Step 2 Thick Oil
    145
    Figure US20200399222A1-20201224-C00171
         		Example 4 Step 2 Think Oil
    146
    Figure US20200399222A1-20201224-C00172
         		Example 4 Step 2 Thick Oil
    147
    Figure US20200399222A1-20201224-C00173
         		Example 4 Step 2 Thick Oil
    148
    Figure US20200399222A1-20201224-C00174
         		Example 4 Step 2 Thick Oil
    149
    Figure US20200399222A1-20201224-C00175
         		Example 4 Step 2 Thick Oil
    150
    Figure US20200399222A1-20201224-C00176
         		Example 4 Step 2 Thick Oil
    151
    Figure US20200399222A1-20201224-C00177
         		Example 4 Step 2 Thick Oil
    152
    Figure US20200399222A1-20201224-C00178
         		Example 4 Step 2 Thick Oil
    153
    Figure US20200399222A1-20201224-C00179
         		Example 4 Step 2 White Solid
    154
    Figure US20200399222A1-20201224-C00180
         		Example 4 Step 2 Thick Oil
    155
    Figure US20200399222A1-20201224-C00181
         		Example 4 Step 2 White Solid
    156
    Figure US20200399222A1-20201224-C00182
         		Example 4 Step 2 Thick Oil
    157
    Figure US20200399222A1-20201224-C00183
         		Example 4 Step 2 Thick Oil
    158
    Figure US20200399222A1-20201224-C00184
         		Example 4 Step 2 Orange Oil
    159
    Figure US20200399222A1-20201224-C00185
         		Example 4 Step 2 Orange Oil
    160
    Figure US20200399222A1-20201224-C00186
         		Example 4 Step 2 Pale Yellow Oil
    161
    Figure US20200399222A1-20201224-C00187
         		Example 4 Step 2 Yellow Oil
    162
    Figure US20200399222A1-20201224-C00188
         		Example 4 Step 2 Yellow Oil
    163
    Figure US20200399222A1-20201224-C00189
         		Example 4 Step 2 Clear, Colorless Oil
    164
    Figure US20200399222A1-20201224-C00190
         		Example 4 Step 2 Yellow Oil
    165
    Figure US20200399222A1-20201224-C00191
         		Example 4 Step 2 Orange Oil
    166
    Figure US20200399222A1-20201224-C00192
         		Example 4 Step 2 Clear, Colorless Oil
    167
    Figure US20200399222A1-20201224-C00193
         		Example 4 Step 2 Yellow Oil
    168
    Figure US20200399222A1-20201224-C00194
         		Example 4 Step 2 Clear, Colorless Oil
    169
    Figure US20200399222A1-20201224-C00195
         		Example 4 Step 2 Yellow Oil
    170
    Figure US20200399222A1-20201224-C00196
         		Example 4 Step 2 Colorless Oil
    171
    Figure US20200399222A1-20201224-C00197
         		Example 4 Step 2 Colorless Oil
    172
    Figure US20200399222A1-20201224-C00198
         		Example 4 Step 2 Pale Yellow Oil
    173
    Figure US20200399222A1-20201224-C00199
         		Example 4 Step 2 Colorless Oil
    174
    Figure US20200399222A1-20201224-C00200
         		Example 4 Step 2 Clear Oil
    175
    Figure US20200399222A1-20201224-C00201
         		Example 4 Step 2 Colorless Foam
    176
    Figure US20200399222A1-20201224-C00202
         		Example 4 Step 2 Residue
    177
    Figure US20200399222A1-20201224-C00203
         		Example 5A Thick Oil
    178
    Figure US20200399222A1-20201224-C00204
         		Example 5A Thick Oil
    179
    Figure US20200399222A1-20201224-C00205
         		Example 5C Thick Oil
    180
    Figure US20200399222A1-20201224-C00206
         		Example 5C Thick Oil
    181
    Figure US20200399222A1-20201224-C00207
         		Example 5A Thick Oil
    182
    Figure US20200399222A1-20201224-C00208
         		Example 5A Thick Oil
    183
    Figure US20200399222A1-20201224-C00209
         		Example 5A Thick Oil
    184
    Figure US20200399222A1-20201224-C00210
         		Example 5A Thick Oil
    185
    Figure US20200399222A1-20201224-C00211
         		Example 5A Thick Oil
    186
    Figure US20200399222A1-20201224-C00212
         		Example 5A Thick Oil
    187
    Figure US20200399222A1-20201224-C00213
         		Example 5A Thick Oil
    188
    Figure US20200399222A1-20201224-C00214
         		Example 5A Thick Oil
    189
    Figure US20200399222A1-20201224-C00215
         		Example 5A Thick Oil
    190
    Figure US20200399222A1-20201224-C00216
         		Example 5A Thick Oil
    191
    Figure US20200399222A1-20201224-C00217
         		Example 5A Thick Oil
    192
    Figure US20200399222A1-20201224-C00218
         		Example 5A Thick Oil
    193
    Figure US20200399222A1-20201224-C00219
         		Example 5A Thick Oil
    194
    Figure US20200399222A1-20201224-C00220
         		Example 5A Thick Oil
    195
    Figure US20200399222A1-20201224-C00221
         		Example 5A Thick Oil
    196
    Figure US20200399222A1-20201224-C00222
         		Example 5C Thick Oil
    197
    Figure US20200399222A1-20201224-C00223
         		Example 5C Thick Oil
    198
    Figure US20200399222A1-20201224-C00224
         		Example 5C Thick Oil
    199
    Figure US20200399222A1-20201224-C00225
         		Example 5C Thick Oil
    200
    Figure US20200399222A1-20201224-C00226
         		Example 5C Thick Oil
    201
    Figure US20200399222A1-20201224-C00227
         		Example 5C Thick Oil
    202
    Figure US20200399222A1-20201224-C00228
         		Example 5C Thick Oil
    203
    Figure US20200399222A1-20201224-C00229
         		Example 5C Thick Oil
    204
    Figure US20200399222A1-20201224-C00230
         		Example 5C Thick Oil
    205
    Figure US20200399222A1-20201224-C00231
         		Example 5C Thick Oil
    206
    Figure US20200399222A1-20201224-C00232
         		Example 5C Thick Oil
    207
    Figure US20200399222A1-20201224-C00233
         		Example 5C Thick Oil
    208
    Figure US20200399222A1-20201224-C00234
         		Example 5C Thick Oil
    209
    Figure US20200399222A1-20201224-C00235
         		Example 5C Thick Oil
    210
    Figure US20200399222A1-20201224-C00236
         		Example 5C Thick Oil
    211
    Figure US20200399222A1-20201224-C00237
         		Example 5C Thick Oil
    212
    Figure US20200399222A1-20201224-C00238
         		Example 5C Thick Oil
    213
    Figure US20200399222A1-20201224-C00239
         		Example 5C Thick Oil
    214
    Figure US20200399222A1-20201224-C00240
         		Example 5C Thick Oil
    215
    Figure US20200399222A1-20201224-C00241
         		Example 5C Thick Oil
    216
    Figure US20200399222A1-20201224-C00242
         		Example 5C Thick Oil
    217
    Figure US20200399222A1-20201224-C00243
         		Example 5C Thick Oil
    218
    Figure US20200399222A1-20201224-C00244
         		Example 5C Thick Oil
    219
    Figure US20200399222A1-20201224-C00245
         		Example 5C Thick Oil
    220
    Figure US20200399222A1-20201224-C00246
         		Example 5A Thick Oil
    221
    Figure US20200399222A1-20201224-C00247
         		Example 5C Thick Oil
    222
    Figure US20200399222A1-20201224-C00248
         		Example 5C Thick Oil
    223
    Figure US20200399222A1-20201224-C00249
         		Example 5C Thick Oil
    224
    Figure US20200399222A1-20201224-C00250
         		Example 5C Thick Oil
    225
    Figure US20200399222A1-20201224-C00251
         		Example 5C Thick Oil
    226
    Figure US20200399222A1-20201224-C00252
         		Example 5C Thick Oil
    227
    Figure US20200399222A1-20201224-C00253
         		Example 5C Thick Oil
    228
    Figure US20200399222A1-20201224-C00254
         		Example 5C Thick Oil
    229
    Figure US20200399222A1-20201224-C00255
         		Example 5C Thick Oil
    230
    Figure US20200399222A1-20201224-C00256
         		Example 5C Thick Oil
    231
    Figure US20200399222A1-20201224-C00257
         		Example 5B Thick Oil
    232
    Figure US20200399222A1-20201224-C00258
         		Example 5B Thick Oil
    233
    Figure US20200399222A1-20201224-C00259
         		Example 5B Thick Oil
    234
    Figure US20200399222A1-20201224-C00260
         		Example 5C Yellow Oil
    235
    Figure US20200399222A1-20201224-C00261
         		Example 5C Pale Yellow Oil
    236
    Figure US20200399222A1-20201224-C00262
         		Example 5C Yellow Oil
    237
    Figure US20200399222A1-20201224-C00263
         		Example 5C Clear, Colorless Oil
    238
    Figure US20200399222A1-20201224-C00264
         		Example 5C Clear, Colorless Oil
    239
    Figure US20200399222A1-20201224-C00265
         		Example 5C Clear, Colorless Oil
    240
    Figure US20200399222A1-20201224-C00266
         		Example 5C Clear, Colorless Oil
    241
    Figure US20200399222A1-20201224-C00267
         		Example 5C Clear, Colorless Oil
    242
    Figure US20200399222A1-20201224-C00268
         		Example 5C Clear, Colorless Oil
    243
    Figure US20200399222A1-20201224-C00269
         		Example 5C Clear, Colorless Oil
    244
    Figure US20200399222A1-20201224-C00270
         		Example 5C Clear, Colorless Oil
    245
    Figure US20200399222A1-20201224-C00271
         		Example 5C Yellow Oil
    246
    Figure US20200399222A1-20201224-C00272
         		Example 5C Pale Yellow Oil
    247
    Figure US20200399222A1-20201224-C00273
         		Example 5C Clear, Colorless Oil
    248
    Figure US20200399222A1-20201224-C00274
         		Example 5C Clear, Colorless Oil
    249
    Figure US20200399222A1-20201224-C00275
         		Example 5C Clear, Colorless Oil
    250
    Figure US20200399222A1-20201224-C00276
         		Example 5C Clear, Colorless Oil
    251
    Figure US20200399222A1-20201224-C00277
         		Example 5C Clear, Colorless Oil
    252
    Figure US20200399222A1-20201224-C00278
         		Example 5C Clear, Colorless Oil
    253
    Figure US20200399222A1-20201224-C00279
         		Example 5C Clear, Colorless Oil
    254
    Figure US20200399222A1-20201224-C00280
         		Example 5C Clear, Colorless Oil
    255
    Figure US20200399222A1-20201224-C00281
         		Example 5C Clear, Colorless Oil
    256
    Figure US20200399222A1-20201224-C00282
         		Example 5C Clear, Colorless Oil
    257
    Figure US20200399222A1-20201224-C00283
         		Example 5A Colorless Oil
    258
    Figure US20200399222A1-20201224-C00284
         		Example 5A Colorless Oil
    259
    Figure US20200399222A1-20201224-C00285
         		Example 5A Pale Yellow Oil
    260
    Figure US20200399222A1-20201224-C00286
         		Example 5A Colorless Oil
    261
    Figure US20200399222A1-20201224-C00287
         		Example 8 Off-White Foam
    262
    Figure US20200399222A1-20201224-C00288
         		Example 8 Tan Foam
    263
    Figure US20200399222A1-20201224-C00289
         		Example 5A Clear Oil
    264
    Figure US20200399222A1-20201224-C00290
         		Example 5A Clear Oil
    265
    Figure US20200399222A1-20201224-C00291
         		Example 5C Clear Oil
    266
    Figure US20200399222A1-20201224-C00292
         		Example 5C Colorless Oil
    267
    Figure US20200399222A1-20201224-C00293
         		Example 6 Step 1 Yellow Semisolid
    268
    Figure US20200399222A1-20201224-C00294
         		Example 6 Step 1 Yellow Semisolid
    269
    Figure US20200399222A1-20201224-C00295
         		Example 6 Step 1 Orange Semisolid
    270
    Figure US20200399222A1-20201224-C00296
         		Example 6 Step 2 Yellow Oil
    271
    Figure US20200399222A1-20201224-C00297
         		Example 6 Step 2 Yellow Oil
    272
    Figure US20200399222A1-20201224-C00298
         		Example 6 Step 2 Yellow Oil
    273
    Figure US20200399222A1-20201224-C00299
         		Example 7 Yellow Oil
    274
    Figure US20200399222A1-20201224-C00300
         		Example 7 Pale Yellow Oil
    275
    Figure US20200399222A1-20201224-C00301
         		Example 7 Pale Yellow Oil
    276
    Figure US20200399222A1-20201224-C00302
         		Example 7 Pale Yellow Oil
    277
    Figure US20200399222A1-20201224-C00303
         		Example 7 Pale Yellow Oil
    278
    Figure US20200399222A1-20201224-C00304
         		Example 5C White Solid
    279
    Figure US20200399222A1-20201224-C00305
         		Example 5C White Solid
    280
    Figure US20200399222A1-20201224-C00306
         		Example 5C Yellow Oil
    281
    Figure US20200399222A1-20201224-C00307
         		Example 5C Clear Oil
    282
    Figure US20200399222A1-20201224-C00308
         		Example 5C White Solid
    284
    Figure US20200399222A1-20201224-C00309
         		Example 5C Thick Yellow Oil
    285
    Figure US20200399222A1-20201224-C00310
         		Example 5C Glassy Solid
    *Cmpd. No. - Compound Number
  • TABLE 2
    Analytical Data
    Melting
    Cmpd. Point IR
    No. (° C.) (cm−1) MASS SPEC NMR
    1 ESIMS m/z 362.3
    ([M + Na]+)
    2 ESIMS m/z 354.3
    ([M + H]+)
    3 ESIMS m/z 382.3
    ([M + H]+)
    4 ESIMS m/z 376.3
    ([M + Na]+)
    5 ESIMS m/z 362.3
    ([M + Na]+)
    6 ESIMS m/z 354.3
    ([M + H]+)
    7 ESIMS m/z 382.3
    ([M + H]+)
    8 ESIMS m/z 354.3
    ([M + H]+)
    9 ESIMS m/z 344.3
    ([M + Na]+)
    10 ESIMS m/z 336.5
    ([M + H]+)
    11 ESIMS m/z 364.3
    ([M + H]+)
    12 ESIMS m/z 336.2
    ([M + H]+)
    13 ESIMS m/z 348.2
    ([M + Na]+)
    14 ESIMS m/z 340.5
    ([M + H]+)
    15 ESIMS m/z 390.3
    ([M + Na]+)
    16 ESIMS m/z 340.2
    ([M + H]+)
    17 ESIMS m/z 374.3
    ([M + Na]+)
    18 ESIMS m/z 366.3
    ([M + H]+)
    19 ESIMS m/z 394.3
    ([M + H]+)
    20 ESIMS m/z 366.3
    ([M + H]+)
    21 ESIMS m/z 362.3
    ([M + Na]+)
    22 ESIMS m/z 376.3
    ([M + Na]+)
    23 ESIMS m/z 382.3
    ([M + H]+)
    24 ESIMS m/z 354.3
    ([M + H]+)
    25 ESIMS m/z 362.3
    ([M + Na]+)
    26 ESIMS m/z 376.3
    ([M + Na]+)
    27 ESIMS m/z 382.3
    ([M + H]+)
    28 ESIMS m/z 376.3
    ([M + Na]+)
    29 ESIMS m/z 344.3
    ([M + Na]+)
    30 ESIMS m/z 336.2
    ([M + H]+)
    31 ESIMS m/z 364.3
    ([M + H]+)
    32 ESIMS m/z 336.3
    ([M + H]+)
    33 ESIMS m/z 348.2
    ([M + Na]+)
    34 ESIMS m/z 340.3
    ([M + H]+)
    35 ESIMS m/z 368.3
    ([M + H]+)
    36 ESIMS m/z 340.3
    ([M + H]+)
    37 ESIMS m/z 374.3
    ([M + Na]+)
    38 ESIMS m/z 366.3
    ([M + H]+)
    39 ESIMS m/z 394.4
    ([M + H]+)
    40 ESIMS m/z 366.3
    ([M + H]+)
    41 ESIMS m/z 372.3
    ([M + Na]+)
    42 ESIMS m/z 372.3
    ([M + Na]+)
    43 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.64
    film) 3355, [M + Na]+ calcd for (dd, J = 7.8, 1.4 Hz, 1H), 7.52 (td, J =
    2981, 1711, C19H26F3NNaO4, 7.6, 1.3 Hz, 1H), 7.43 (d, J = 7.9 Hz,
    1310, 1150, 412.1706; found, 1H), 7.35-7.28 (m, 1H), 5.25-5.13
    1116, 1046, 412.1698 (m, 1H), 5.08 (d, J = 7.9 Hz, 1H), 4.42-
    770 cm−1 4.28 (m, 1H), 3.41-3.27 (m, 1H),
    1.46 (s, 9H), 1.43 (d, J = 7.2 Hz, 3H),
    1.27 (d, J = 6.8 Hz, 3H), 1.07 (d, J =
    6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.25.
    44 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.42
    film) 3362, [M + Na]+ calcd for (dd, J = 8.8, 5.4 Hz, 1H), 7.35 (dd, J =
    2982, 1711, C19H25F4NNaO4, 9.2, 2.8 Hz, 1H), 7.23 (td, J = 8.2, 2.8
    1499, 1314, 430.1612; found, Hz, 1H), 5.18-5.09 (m, 1H), 5.07 (d,
    1154, 1121, 430.1607 J = 7.6 Hz, 1H), 4.41-4.27 (m, 1H),
    1046, 909, 3.36-3.24 (m, 1H), 1.46 (s, 9H), 1.42
    879 cm−1 (d, J = 7.3 Hz, 3H), 1.26 (d, J = 6.8 Hz,
    3H), 1.08 (d, J = 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.81, −114.05.
    45 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.64
    film) 3364, [M + Na]+ calcd for (dd, J = 8.0, 1.3 Hz, 1H), 7.52 (td, J =
    2981, 1712, C19H26F3NNaO4, 7.6, 1.3 Hz, 1H), 7.43 (d, J = 7.8 Hz,
    1310, 1150, 412.1706; found, 1H), 7.32 (t, J = 7.6 Hz, 1H), 5.25-
    1116, 1046, 412.1699 5.13 (m, 1H), 5.04 (d, J = 7.8 Hz, 1H),
    770 cm−1 4.42-4.26 (m, 1H), 3.40-3.26 (m,
    1H), 1.46 (s, 9H), 1.41 (d, J = 7.3 Hz,
    3H), 1.29 (d, J = 6.7 Hz, 3H), 1.05 (d,
    J = 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.25.
    46 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.42
    film) 2981, [M + Na]+ calcd for (dd, J = 8.8, 5.3 Hz, 1H), 7.35 (dd, J =
    1711, 1498, C19H25F4NNaO4, 9.2, 2.8 Hz, 1H), 7.23 (td, J = 8.3, 2.9
    1314, 1154, 430.1612; found, Hz, 1H), 5.20-5.09 (m, 1H), 5.02 (d,
    1120, 1045, 430.1603 J = 7.8 Hz, 1H), 4.42-4.23 (m, 1H),
    909, 879, 3.29 (tt, J = 7.6, 6.0 Hz, 1H), 1.46 (s,
    739 cm−1 9H), 1.40 (d, J = 7.2 Hz, 3H), 1.28 (d, J
    = 6.8 Hz, 3H), 1.07 (d, J = 6.4 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.78,
    −58.80, −114.19.
    47 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.05-
    film) 3357, [M + NH4]+ calcd 6.91 (m, 3H), 5.58 (ddq, J = 10.5, 8.3,
    2977, 1713, for C20H35N2O4, 6.2 Hz, 1H), 5.11 (s, 1H), 4.42-4.28
    1500, 1452, 367.2587; found, (m, 1H), 3.49-3.33 (m, 1H), 2.44-
    1365, 1162, 367.2587 2.33 (m, 6H), 1.46 (d, J = 1.1 Hz, 9H),
    1055, 1006, 1.45-1.39 (m, 3H), 1.27 (dd, J = 7.1,
    769 cm−1 3.5 Hz, 3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H).
    48 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 6.70
    film) 3357, [M + Na]+ calcd for (ddd, J = 16.1, 9.4, 2.9 Hz, 2H), 5.53
    2978, 1712, C20H30FNNaO4, (ddq, J = 10.5, 8.6, 6.2 Hz, 1H), 5.11
    1366, 1162, 390.2051; found, (s, 1H), 4.41-4.26 (m, 1H), 3.44-
    1057, 1023, 390.2048 3.27 (m, 1H), 2.40 (d, J = 1.7 Hz, 3H),
    1006, 857 2.35 (s, 3H), 1.46 (s, 9H), 1.45-1.38
    cm−1 (m, 3H), 1.25 (dd, J = 7.2, 3.8 Hz, 3H),
    1.01 (dd, J = 7.6, 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.37, −118.44.
    49 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.04-
    film) 3361, [M + Na]+ calcd for 6.93 (m, 3H), 5.58 (ddq, J = 10.4, 8.3,
    2977, 1713, C20H31NNaO4, 6.2 Hz, 1H), 5.10 (d, J = 7.3 Hz, 1H),
    1365, 1162, 372.2145; found, 4.43-4.27 (m, 1H), 3.48-3.29 (m,
    1056, 1006, 372.2144 1H), 2.41 (d, J = 1.6 Hz, 3H), 2.37 (s,
    769 cm−1 3H), 1.46 (d, J = 1.1 Hz, 9H), 1.45-
    1.39 (m, 3H), 1.27 (dd, J = 7.1, 3.5 Hz,
    3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H).
    50 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 6.70
    film) 3359, [M + Na]+ calcd for (ddd, J = 16.2, 9.4, 2.9 Hz, 2H), 5.53
    2978, 1712, C20H30FNNaO4, (ddq, J = 10.5, 8.6, 6.2 Hz, 1H), 5.09
    1450, 1366, 390.2051; found, (s, 1H), 4.43-4.28 (m, 1H), 3.34 (dp,
    1163, 1057, 390.2050 J = 10.3, 6.9 Hz, 1H), 2.40 (d, J = 1.7
    1023, 1006, Hz, 3H), 2.35 (s, 3H), 1.46 (s, 9H),
    858, 732 1.45-1.36 (m, 3H), 1.26 (d, J = 3.8
    cm−1 Hz, 3H), 1.01 (dd, J = 7.6, 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.40, −118.46.
    51 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.03-
    film) 3356, [M + Na]+ calcd for 6.94 (m, 3H), 5.58 (ddq, J = 10.5, 8.3,
    2977, 1713, C20H31NNaO4, 6.2 Hz, 1H), 5.10 (d, J = 7.1 Hz, 1H),
    1500, 1452, 372.2145; found, 4.43-4.27 (m, 1H), 3.50-3.34 (m,
    1163, 1056, 372.2137 1H), 2.41 (d, J = 1.6 Hz, 3H), 2.37 (s,
    769 cm−1 3H), 1.46 (d, J = 1.1 Hz, 9H), 1.45-
    1.36 (m, 3H), 1.27 (dd, J = 7.2, 3.5 Hz,
    3H), 1.02 (dd, J = 7.7, 6.2 Hz, 3H).
    52 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 6.70
    film) 3358, [M + Na]+ calcd for (ddd, J = 16.0, 9.4, 2.9 Hz, 2H), 5.53
    2978, 1712, C20H30FNNaO4, (ddq, J = 10.5, 8.5, 6.2 Hz, 1H), 5.11
    1366, 1163, 390.2051; found, (s, 1H), 4.33 (q, J = 7.3 Hz, 1H), 3.35
    1058, 1023, 390.2051 (ddq, J = 13.0, 10.4, 7.1, 6.5 Hz, 1H),
    1006, 858, 2.40 (d, J = 1.8 Hz, 3H), 2.35 (s, 3H),
    733 cm−1 1.46 (s, 9H), 1.45-1.39 (m, 3H), 1.25
    (dd, J = 7.2, 3.8 Hz, 3H), 1.01 (dd, J =
    7.6, 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.39, −118.45.
    53 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 7.23-
    film) 3357, [M + Na]+ calcd for 7.12 (m, 2H), 6.96-6.79 (m, 2H), 5.24
    2977, 2936, C19H29NO5Na, (dq, J = 7.7, 6.3 Hz, 1H), 5.00 (d, J =
    2837, 1711, 374.1938; found, 6.6 Hz, 1H), 4.19-4.10 (m, 1H), 3.81
    1493, 1241, 374.1944 (s, 3H), 3.43 (p, J = 7.3 Hz, 1H), 1.42
    1161, 1052, (s, 9H), 1.25-1.20 (m, 6H), 0.99 (d, J =
    752 cm−1 7.1 Hz, 3H).
    54 IR (thin 1H NMR (400 MHz, CDCl3) δ 7.35-
    film) 3355, 7.25 (m, 2H), 7.27-7.15 (m, 3H),
    2978, 2934, 5.12-5.01 (m, 2H), 4.35-4.26 (m, 1H),
    1711, 1495, 2.95-2.83 (m, 1H), 1.45 (s, 9H), 1.37
    1452, 1366, (d, J = 7.2 Hz, 3H), 1.29 (d, J = 7.1 Hz,
    1161, 1087, 3H), 1.09 (d, J = 6.3 Hz, 3H).
    1065, 701 13C NMR (126 MHz, CDCl3) δ 172.9,
    cm−1 155.0, 143.0, 128.5, 127.8, 126.7, 79.7,
    76.1, 49.5, 45.1, 28.3, 18.9, 18.3, 17.5.
    55 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 6.64-
    film) 3365, [M + Na]+ calcd for 6.53 (m, 2H), 5.11-5.05 (m, 1H), 5.06-
    2977, 2933, C17H27NO4SNa, 4.95 (m, 1H), 4.35-4.26 (m, 1H),
    1712, 1500, 364.1553; found, 3.20-3.08 (m, 1H), 2.43 (d, J = 1.2
    1449, 1365, 364.1551 Hz, 3H), 1.45 (s, 9H), 1.38 (d, J = 7.2
    1161, 1065, Hz, 3H), 1.31 (d, J = 7.1 Hz, 3H), 1.16
    796 cm−1 (d, J = 6.3 Hz, 3H).
    56 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 7.08
    film) 3365, [M + Na]+ calcd for (dd, J = 8.5, 6.7 Hz, 1H), 6.65-6.53
    2978, 2937, C19H28FNO5Na, (m, 2H), 5.16-5.07 (m, 1H), 5.05 (d, J =
    1708, 1601, 392.1844; found, 7.6 Hz, 1H), 4.30-4.23 (m, 1H),
    1502, 1163, 392.1839 3.80 (s, 3H), 3.38-3.29 (m, 1H), 1.45
    1035, 952, (s, 9H), 1.35 (d, J = 7.2 Hz, 3H), 1.23
    834 cm−1 (d, J = 7.1 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H).
    57 1H NMR (300 MHz, CDCl3) δ 7.13-
    6.95 (m, 2H), 6.77-6.52 (m, 2H), 5.11
    (d, J = 7.8 Hz, 1H), 5.00 (dq, J = 8.2,
    6.2 Hz, 1H), 4.31 (t, J = 7.4 Hz, 1H),
    2.92 (s, 6H), 1.45 (s, 9H), 1.39 (d, J =
    7.2 Hz, 3H), 1.31-1.17 (m, 4H), 1.08
    (d, J = 6.3 Hz, 3H).
    13C NMR (75 MHz, CDCl3) δ 172.95,
    171.16, 155.04, 149.48, 130.86,
    128.41, 112.69, 60.40, 49.51, 44.14,
    40.70, 28.35, 18.93, 18.27, 17.82, 14.21.
    58 ESIMS m/z 240.2
    ([M + H]+)
    59 ESIMS m/z 240.2
    ([M + H]+)
    60 ESIMS m/z 222.2
    ([M + H]+)
    61 ESIMS m/z 248.9
    ([M + Na]+)
    62 ESIMS m/z 252.2
    ([M + H]+)
    63 ESIMS m/z 240.2
    ([M + H]+)
    64 ESIMS m/z 240.2
    ([M + H]+)
    65 ESIMS m/z 222.2
    ([M + H]+)
    66 ESIMS m/z 226.2
    ([M + H]+)
    67 ESIMS m/z 252.2
    ([M + H]+)
    68 ESIMS m/z 254.2
    ([M + H]+)
    69 ESIMS m/z 254.2
    ([M + H]+)
    70 ESIMS m/z 236.2
    ([M + H]+)
    71 ESIMS m/z 240.2
    ([M + H]+)
    72 ESIMS m/z 266.3
    ([M + H]+)
    73 ESIMS m/z 254.2
    ([M + H]+)
    74 ESIMS m/z 254.2
    ([M + H]+)
    75 ESIMS m/z 236.2
    ([M + H]+)
    76 ESIMS m/z 240.2
    ([M + H]+)
    77 ESIMS m/z 266.3
    ([M + H]+)
    78 ESIMS m/z 282.3
    ([M + H]+)
    79 ESIMS m/z 282.2
    ([M + H]+)
    80 ESIMS m/z 264.3
    ([M + H]+)
    81 ESIMS m/z 268.2
    ([M + H]+)
    82 ESIMS m/z 294.3
    ([M + H]+)
    83 ESIMS m/z 282.2
    ([M + H]+)
    84 ESIMS m/z 282.2
    ([M + H]+)
    85 ESIMS m/z 264.3
    ([M + H]+)
    86 ESIMS m/z 268.2
    ([M + H]+)
    87 ESIMS m/z 294.3
    ([M + H]+)
    88 ESIMS m/z 254.2
    ([M + H]+)
    89 ESIMS m/z 254.2
    ([M + H]+)
    90 ESIMS m/z 236.2
    ([M + H]+)
    91 ESIMS m/z 240.2
    ([M + H]+)
    92 ESIMS m/z 266.3
    ([M + H]+)
    93 ESIMS m/z 254.2
    ([M + H]+)
    94 ESIMS m/z 254.2
    ([M + H]+)
    95 ESIMS m/z 236.2
    ([M + H]+)
    96 ESIMS m/z 240.2
    ([M + H]+)
    97 ESIMS m/z 266.3
    ([M + H]+)
    98 ESIMS m/z 250.3
    ([M + H]+)
    99 ESIMS m/z 250.3
    ([M + H]+)
    100 ESIMS m/z 290.2
    ([M + H]+)
    101 ESIMS m/z 308.1
    ([M + H]+)
    102 ESIMS m/z 214.2
    ([M + H]+)
    103 ESIMS m/z 290.2
    ([M + H]+)
    104 ESIMS m/z 308.1
    ([M + H]+)
    105 ESIMS m/z 214.2
    ([M + H]+)
    106 ESIMS m/z 250.2
    ([M + H]+)
    107 ESIMS m/z 268.2
    ([M + H]+)
    108 ESIMS m/z 250.2
    ([M + H]+)
    109 ESIMS m/z 268.2
    ([M + H]+)
    110 ESIMS m/z 250.2
    ([M + H]+)
    111 ESIMS m/z 268.2
    ([M + H]+)
    112 HRMS-ESI (m/z)
    [M + H]+ calcd for
    C14H22NO3,
    252.1600; found,
    252.1443
    113 HRMS-ESI (m/z)
    [M + H]+ calcd for
    C13H20NO2,
    222.1489; found,
    222.1485
    114 IR (thin
    film) 2854,
    1740, 1233,
    1203, 1118,
    1078, 872,
    796 cm−1
    115 HRMS-ESI (m/z)
    [M + H]+ calcd for
    C14H21FNO3,
    270.1500; found,
    270.1501
    116 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.16
    [M + H]+ calcd for (s, 1H), 8.52 (d, J = 7.8 Hz, 1H), 8.00
    C22H29N2O5, (d, J = 5.2 Hz, 1H), 7.09-7.03 (m,
    401.2071; found, 1H), 7.00-6.94 (m, 2H), 6.88 (d, J =
    401.2067 5.1 Hz, 1H), 5.13 (dq, J = 8.4, 6.2 Hz,
    1H), 4.79-4.67 (m, 1H), 3.95 (s, 3H),
    3.16 (dq, J = 8.9, 7.0 Hz, 1H), 2.31 (s,
    3H), 2.28 (s, 3H), 1.57 (d, J = 7.2 Hz,
    3H), 1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J =
    6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.86,
    168.68, 155.38, 148.77, 140.50,
    138.63, 135.76, 135.33, 131.31,
    130.52, 126.97, 126.26, 109.44, 56.08,
    48.18, 39.45, 20.89, 19.87, 18.48,
    18.46, 17.56.
    117 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.17
    [M + H]+ calcd for (d, J = 0.6 Hz, 1H), 8.50 (d, J = 7.9 Hz,
    C22H29N2O5, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.10-
    401.2071; found, 7.02 (m, 1H), 6.97 (d, J = 6.9 Hz, 2H),
    401.2064 6.88 (d, J = 5.2 Hz, 1H), 5.16 (dq, J =
    8.4, 6.2 Hz, 1H), 4.77-4.68 (m, 1H),
    3.95 (s, 3H), 3.19-3.09 (m, 1H), 2.31
    (s, 3H), 2.27 (s, 3H), 1.54 (d, J = 7.2
    Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12
    (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.87,
    168.72, 155.38, 148.76, 140.50,
    138.60, 135.72, 135.36, 131.29,
    130.53, 127.00, 126.28, 109.44, 56.08,
    47.99, 39.42, 20.87, 19.88, 18.31,
    18.26, 17.65.
    118 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.04
    [M + H]+ calcd for (s, 1H), 8.46 (t, J = 5.8 Hz, 1H), 8.01
    C20H23FN2O5, (d, J = 5.2 Hz, 1H), 7.18-7.06 (m,
    391.1664; found, 1H), 6.93-6.79 (m, 3H), 5.15 (dq, J =
    391.1662 8.0, 6.3 Hz, 1H), 4.21 (dd, J = 5.7, 3.2
    Hz, 2H), 3.95 (s, 3H), 3.15 (p, J = 7.1
    Hz, 1H), 2.33 (s, 3H), 1.24 (d, J = 6.9
    Hz, 3H), 1.15 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.32,
    168.74, 161.97, 160.03, 155.39,
    148.70, 140.61, 137.91, 137.20,
    130.40, 127.85, 117.11, 116.95,
    113.07, 112.90, 109.54, 76.40, 56.10,
    41.03, 39.10, 20.00, 18.22, 17.42.
    119 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.01
    [M + H]+ calcd for (s, 1H), 8.34 (t, J = 5.8 Hz, 1H), 7.99
    C20H23FN2O5, (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 9.5,
    391.1664; found, 5.8 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H),
    391.1660 6.85-6.75 (m, 2H), 5.24-5.10 (m,
    1H), 4.23-3.92 (m, 5H), 3.23 (p, J =
    7.1 Hz, 1H), 2.33 (s, 3H), 1.25 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 169.19,
    168.38, 161.97, 160.02, 155.38,
    148.68, 140.55, 138.37, 136.63,
    130.36, 127.68, 116.81, 116.65,
    112.86, 112.70, 109.52, 75.82, 56.09,
    40.88, 38.65, 19.86, 17.20, 16.64.
    120 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.03
    [M + H]+ calcd for (s, 1H), 8.34 (t, J = 5.8 Hz, 1H), 7.99
    C20H24N2O5, (d, J = 5.2 Hz, 1H), 7.20 (dd, J = 7.6,
    373.1758; found, 1.3 Hz, 1H), 7.16-7.06 (m, 3H), 6.87
    373.1754 (d, J = 5.2 Hz, 1H), 5.24-5.17 (m,
    1H), 4.16-3.89 (m, 2H), 3.95 (s, 3H),
    3.29 (p, J = 7.1 Hz, 1H), 2.35 (s, 3H),
    1.27 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 169.15,
    168.40, 155.35, 148.66, 140.97,
    140.52, 136.10, 130.41, 130.27,
    126.30, 126.20, 126.14, 109.48, 75.92,
    56.08, 40.85, 39.18, 19.79, 17.18, 16.37.
    121 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.04
    [M + H]+ calcd for (s, 1H), 8.46 (t, J = 5.8 Hz, 1H), 8.01
    C19H21FN2O5, (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 8.6,
    377.1507; found, 5.5 Hz, 2H), 7.01-6.94 (m, 2H), 6.89
    377.1504 (d, J = 5.2 Hz, 1H), 5.16-5.05 (m,
    1H), 4.21 (dd, J = 5.8, 2.1 Hz, 2H),
    3.95 (s, 3H), 2.92 (p, J = 7.1 Hz, 1H),
    1.28 (d, J = 7.0 Hz, 3H), 1.12 (d, J =
    6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.33,
    168.65, 162.66, 160.72, 155.40,
    148.71, 140.61, 138.35, 130.40,
    129.27, 129.21, 115.36, 115.19,
    109.55, 76.35, 56.10, 44.12, 41.06,
    17.83, 17.27.
    122 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.06
    [M + H]+ calcd for (s, 1H), 8.47 (t, J = 5.8 Hz, 1H), 8.01
    C21H26N2O6, (d, J = 5.2 Hz, 1H), 7.08 (d, J = 8.4 Hz,
    403.1864; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.77-
    403.1835 6.66 (m, 2H), 5.15 (dq, J = 8.2, 6.3 Hz,
    1H), 4.22 (dd, J = 5.7, 2.0 Hz, 2H),
    3.95 (s, 3H), 3.77 (s, 3H), 3.18-3.07
    (m, 1H), 2.32 (s, 3H), 1.23 (d, J = 6.9
    Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.30,
    168.80, 157.71, 155.38, 148.69,
    140.60, 136.96, 133.70, 130.44,
    127.36, 115.97, 111.49, 109.52, 76.84,
    56.09, 55.12, 41.05, 39.03, 20.17,
    18.27, 17.59.
    123 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.04
    [M + H]+ calcd for (s, 1H), 8.46 (t, J = 5.8 Hz, 1H), 8.00
    C20H23FN2O5, (d, J = 5.2 Hz, 1H), 7.20-7.08 (m,
    391.1664; found, 1H), 6.93-6.80 (m, 3H), 5.15 (dq, J =
    391.1662 7.9, 6.3 Hz, 1H), 4.21 (dd, J = 5.7, 3.2
    Hz, 2H), 3.95 (s, 3H), 3.15 (p, J = 7.1
    Hz, 1H), 2.33 (s, 3H), 1.24 (d, J = 6.9
    Hz, 3H), 1.15 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.32,
    168.75, 161.97, 160.03, 155.39,
    148.70, 140.61, 137.91, 137.85,
    137.20, 137.17, 130.40, 127.85,
    127.78, 117.11, 116.95, 113.06,
    112.90, 109.54, 76.40, 56.10, 41.03,
    39.10, 19.99, 18.22, 17.42.
    124 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.01
    [M + H]+ calcd for (d, J = 0.6 Hz, 1H), 8.34 (t, J = 5.8 Hz,
    C20H23FN2O5, 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.15 (dd,
    391.1664; found, J = 9.5, 5.8 Hz, 1H), 6.88 (d, J = 5.2
    391.1661 Hz, 1H), 6.85-6.77 (m, 2H), 5.21-
    5.11 (m, 1H), 4.20-3.91 (m, 2H), 3.95
    (s, 3H), 3.23 (p, J = 7.1 Hz, 1H), 2.33
    (s, 3H), 1.30-1.20 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 169.19,
    168.38, 161.97, 160.02, 155.38,
    148.68, 140.55, 138.43, 136.66,
    130.36, 127.75, 127.68, 116.81,
    116.65, 112.86, 112.70, 109.52, 75.82,
    56.09, 40.88, 38.65, 19.85, 17.20, 16.64.
    125 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.03
    [M + H]+ calcd for (d, J = 0.6 Hz, 1H), 8.34 (t, J = 5.8 Hz,
    C20H24N2O5, 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.20 (dd,
    373.1758; found, J = 7.7, 1.3 Hz, 1H), 7.17-7.04 (m,
    373.1755 3H), 6.87 (d, J = 5.2 Hz, 1H), 5.25-
    5.16 (m, 1H), 4.12 (dd, J = 18.2, 5.9
    Hz, 1H), 3.95 (s, 3H), 3.98-3.89 (m,
    1H), 3.29 (p, J = 7.1 Hz, 1H), 2.35 (s,
    3H), 1.27 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 169.15,
    168.41, 155.35, 148.66, 140.97,
    140.52, 136.10, 130.41, 130.27,
    126.30, 126.14, 109.48, 75.92, 56.08,
    40.85, 39.18, 19.79, 17.18, 16.37.
    126 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.04
    [M + H]+ calcd for (s, 1H), 8.46 (t, J = 5.9 Hz, 1H), 8.01
    C19H21FN2O5, (d, J = 5.2 Hz, 1H), 7.22-7.08 (m,
    377.1507; found, 2H), 6.98 (t, J = 8.7 Hz, 2H), 6.89 (d,
    377.1507 J = 5.2 Hz, 1H), 5.16-5.01 (m, 1H),
    4.29-4.14 (m, 2H), 3.95 (s, 3H), 2.92
    (p, J = 7.1 Hz, 1H), 1.28 (d, J = 7.0 Hz,
    3H), 1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.33,
    168.65, 162.67, 160.72, 155.41,
    148.71, 140.61, 138.37, 130.40,
    129.27, 129.21, 115.36, 115.19,
    109.55, 76.36, 56.10, 44.12, 41.06,
    17.83, 17.27.
    127 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.06
    [M + H]+ calcd for (s, 1H), 8.47 (t, J = 5.7 Hz, 1H), 8.01
    C21H26N2O6, (d, J = 5.2 Hz, 1H), 7.08 (d, J = 8.4 Hz,
    403.1864; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.82-
    403.1853 6.66 (m, 2H), 5.15 (dq, J = 8.1, 6.3 Hz,
    1H), 4.29-4.15 (m, 2H), 3.95 (s, 3H),
    3.77 (s, 3H), 3.17-3.08 (m, 1H), 2.32
    (s, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.14
    (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.30,
    168.80, 157.71, 155.38, 148.69,
    140.60, 136.96, 133.70, 130.44,
    127.36, 115.97, 111.49, 109.52, 76.84,
    56.09, 55.12, 41.05, 39.03, 20.17,
    18.27, 17.59.
    128 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (d, J = 0.6 Hz, 1H), 8.49 (d, J = 7.9 Hz,
    C21H25FN2O5, 1H), 8.00 (d, J = 5.2 Hz, 1H), 7.18-
    405.1820; found, 7.05 (m, 1H), 6.93-6.79 (m, 3H), 5.11
    405.1819 (dq, J = 8.0, 6.3 Hz, 1H), 4.78-4.64
    (m, 1H), 3.95 (s, 3H), 3.23-3.09 (m,
    1H), 2.33 (s, 3H), 1.55 (d, J = 7.2 Hz,
    3H), 1.24 (d, J = 6.9 Hz, 3H), 1.14 (d,
    J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.79,
    168.69, 161.97, 160.03, 155.39,
    148.77, 140.51, 137.87, 137.81,
    137.33, 137.30, 130.47, 127.86,
    127.79, 117.10, 116.94, 113.02,
    112.85, 109.47, 76.32, 56.09, 48.13,
    39.16, 20.00, 18.42, 18.36, 17.33.
    129 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.09
    [M + H]+ calcd for (s, 1H), 8.35 (d, J = 7.9 Hz, 1H), 7.98
    C21H25FN2O5, (dd, J = 5.2, 3.6 Hz, 1H), 7.13 (dd, J =
    405.1820; found, 8.4, 5.8 Hz, 1H), 6.94-6.73 (m, 3H),
    405.1820 5.21-5.08 (m, 1H), 4.63-4.46 (m,
    1H), 3.94 (s, 2H), 3.27-3.15 (m, 1H).
    13C NMR (126 MHz, CDCl3) δ 171.55,
    168.59, 161.91, 159.97, 155.37,
    148.73, 140.44, 138.30, 137.15,
    130.43, 127.47, 116.73, 116.57,
    112.89, 112.73, 109.43, 75.74, 56.07,
    47.87, 38.98, 19.90, 17.79, 17.32.
    130 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.11
    [M + H]+ calcd for (s, 1H), 8.36 (d, J = 8.0 Hz, 1H), 7.97
    C21H26N2O5, (d, J = 5.2 Hz, 1H), 7.24-7.01 (m,
    387.1914; found, 4H), 6.86 (d, J = 5.2 Hz, 1H), 5.27-
    387.1911 5.12 (m, 1H), 4.59-4.47 (m, 1H), 3.94
    (s, 2H), 3.33-3.20 (m, 1H), 2.36 (s,
    3H), 1.32 (d, J = 6.3 Hz, 3H), 1.24 (d,
    J = 7.1 Hz, 3H), 1.08 (d, J = 7.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.58,
    168.54, 155.33, 148.71, 141.47,
    140.41, 135.95, 130.49, 130.22,
    126.20, 125.88, 109.39, 75.87, 56.06,
    47.85, 39.52, 19.83, 17.83, 17.74, 17.14.
    131 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.00
    C20H23FN2O5, (d, J = 5.2 Hz, 1H), 7.15 (dd, J = 8.6,
    391.1664; found, 5.4 Hz, 2H), 6.97 (t, J = 8.7 Hz, 2H),
    391.1662 6.88 (d, J = 5.2 Hz, 1H), 5.11-5.02
    (m, 1H), 4.71 (p, J = 7.3 Hz, 1H), 3.95
    (s, 3H), 2.92 (p, J = 7.1 Hz, 1H), 1.53
    (d, J = 7.2 Hz, 3H), 1.29 (d, J = 7.1 Hz,
    3H), 1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.67,
    168.69, 162.64, 160.70, 155.40,
    148.78, 140.51, 138.48, 130.46,
    129.26, 129.19, 115.32, 115.16,
    109.48, 76.31, 56.09, 48.12, 44.11,
    18.38, 17.95, 17.16.
    132 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.16
    [M + H]+ calcd for (s, 1H), 8.51 (d, J = 7.9 Hz, 1H), 8.00
    C22H28N2O6, (d, J = 5.2 Hz, 1H), 7.11-7.05 (m,
    417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.70 (d,
    417.2007 J = 6.7 Hz, 2H), 5.11 (dq, J = 8.3, 6.3
    Hz, 1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95
    (s, 3H), 3.77 (s, 3H), 3.18-3.06 (m,
    1H), 2.32 (s, 3H), 1.56 (d, J = 7.2 Hz,
    3H), 1.23 (d, J = 6.9 Hz, 3H), 1.14 (d,
    J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.85,
    168.67, 157.70, 155.38, 148.77,
    140.50, 136.91, 133.86, 130.52,
    127.36, 115.95, 111.48, 109.45, 56.08,
    55.13, 48.17, 39.11, 20.18, 18.46,
    17.57, 16.10.
    133 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.01
    C21H25FN2O5, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.4,
    405.1820; found, 5.8 Hz, 1H), 6.91-6.81 (m, 3H), 5.12
    405.1819 (dq, J = 8.1, 6.3 Hz, 1H), 4.72 (p, J =
    7.2 Hz, 1H), 3.95 (s, 3H), 3.20-3.10
    (m, 1H), 2.33 (s, 3H), 1.54 (d, J = 7.1
    Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12
    (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.81,
    168.74, 161.95, 160.01, 155.40,
    148.78, 140.51, 137.89, 137.83,
    137.29, 137.26, 130.48, 127.87,
    127.81, 117.08, 116.91, 113.06,
    112.90, 109.48, 76.19, 56.09, 47.96,
    39.12, 20.02, 18.24, 18.12, 17.47.
    134 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.12
    [M + H]+ calcd for (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.99
    C21H25FN2O5, (d, J = 5.2 Hz, 1H), 7.18-7.12 (m,
    405.1820; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.78 (t,
    405.1818 J = 8.2 Hz, 2H), 5.17-5.06 (m, 1H),
    4.64-4.51 (m, 1H), 3.95 (s, 3H), 3.23
    (p, J = 7.1 Hz, 1H), 2.33 (s, 3H), 1.38
    (d, J = 7.1 Hz, 3H), 1.26-1.20 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 171.29,
    168.55, 161.93, 159.99, 155.38,
    148.74, 140.44, 138.41, 138.35,
    136.73, 136.71, 130.43, 127.71,
    127.65, 116.77, 116.61, 112.81,
    112.64, 109.45, 75.62, 56.09, 47.82,
    38.64, 19.89, 19.88, 18.06, 17.22, 16.84.
    135 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.15
    [M + H]+ calcd for (s, 1H), 8.30 (d, J = 8.0 Hz, 1H), 7.99
    C21H26N2O5, (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.8,
    387.1914; found, 1.4 Hz, 1H), 7.15-7.00 (m, 3H), 6.87
    387.1915 (d, J = 5.2 Hz, 1H), 5.20-5.12 (m,
    1H), 4.59-4.50 (m, 1H), 3.95 (s, 3H),
    3.29 (p, J = 7.1 Hz, 1H), 2.36 (s, 3H),
    1.35 (d, J = 7.2 Hz, 3H), 1.29-1.22
    (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 171.30,
    168.54, 155.35, 148.73, 141.04,
    140.40, 136.09, 130.51, 130.26,
    126.23, 126.11, 109.40, 75.73, 56.08,
    47.88, 39.15, 19.83, 18.11, 17.16, 16.53.
    136 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (s, 1H), 8.46 (d, J = 7.7 Hz, 1H), 8.00
    C20H23FN2O5, (dd, J = 5.2, 2.2 Hz, 1H), 7.15 (ddd,
    391.1664; found, J = 9.9, 6.1, 3.4 Hz, 2H), 6.97 (td, J =
    391.1658 8.8, 2.6 Hz, 2H), 6.88 (dd, J = 5.4, 1.5
    Hz, 1H), 5.12-5.01 (m, 1H), 4.77-
    4.64 (m, 1H), 3.95 (s, 3H), 2.92 (p, J =
    7.1 Hz, 1H), 1.53 (d, J = 7.2 Hz, 3H),
    1.28 (d, J = 7.0 Hz, 3H), 1.09 (d, J =
    6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.72,
    168.76, 162.65, 160.70, 155.41,
    148.78, 140.51, 138.43, 138.40,
    130.47, 129.29, 129.23, 115.33,
    115.16, 109.48, 76.12, 56.09, 47.98,
    44.09, 18.20, 17.69, 17.30.
    137 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.17
    [M + H]+ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.01
    C22H28N2O6, (d, J = 5.2 Hz, 1H), 7.09 (d, J = 8.4 Hz,
    417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.76-
    417.2010 6.67 (m, 2H), 5.13 (dq, J = 8.3, 6.3 Hz,
    1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s,
    3H), 3.76 (s, 3H), 3.18-3.07 (m, 1H),
    2.32 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H),
    1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J =
    6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.86,
    168.72, 157.68, 155.38, 148.76,
    140.50, 136.94, 133.82, 130.53,
    127.37, 115.97, 111.47, 109.45, 76.65,
    56.08, 55.11, 47.99, 39.06, 20.19,
    18.31, 18.20, 17.68.
    139 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.12
    [M + H]+ calcd for (s, 1H), 8.38 (d, J = 9.3 Hz, 1H), 7.99
    C23H29FN2O5, (t, J = 5.1 Hz, 1H), 7.14 (dd, J = 8.5,
    433.2133; found, 5.9 Hz, 1H), 6.88 (dd, J = 7.6, 5.1 Hz,
    433.213 1H), 6.84-6.72 (m, 3H), 5.13 (dq, J =
    8.4, 6.3 Hz, 1H), 4.49 (td, J = 9.4, 4.9
    Hz, 1H), 3.94 (s, 3H), 3.20 (p, J = 7.4
    Hz, 1H), 2.33 (s, 3H), 1.94 (pd, J = 6.9,
    4.6 Hz, 1H), 1.29 (d, J = 6.3 Hz, 3H),
    1.21 (d, J = 7.1 Hz, 3H), 0.85 (d, J =
    6.9 Hz, 3H), 0.68 (d, J = 6.8 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.52,
    168.98, 161.96, 160.02, 155.39,
    148.70, 140.45, 138.31, 138.25,
    137.28, 137.25, 130.49, 127.46,
    127.40, 116.75, 116.59, 112.92,
    112.76, 109.42, 75.86, 56.97, 56.08,
    38.86, 31.12, 19.89, 19.12, 17.79,
    17.34, 17.02.
    140 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.38 (d,
    [M + H]+ calcd for J = 9.4 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    C23H30N2O5, 1H), 7.20 (d, J = 7.7 Hz, 1H), 7.16-
    415.2227; found, 7.08 (m, 1H), 7.08-7.03 (m, 2H), 6.86
    415.2222 (d, J = 5.2 Hz, 1H), 5.25-5.11 (m,
    1H), 4.49 (dd, J = 9.4, 4.5 Hz, 1H),
    3.94 (s, 3H), 3.37-3.18 (m, 1H), 2.34
    (s, 3H), 1.91 (pd, J = 6.9, 4.5 Hz, 1H),
    1.31 (d, J = 6.2 Hz, 3H), 1.23 (d, J =
    7.1 Hz, 3H), 0.82 (d, J = 6.8 Hz, 3H),
    0.64 (d, J = 6.8 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.54,
    168.94, 155.34, 148.67, 141.56,
    140.42, 135.94, 130.56, 130.25,
    126.23, 125.89, 109.37, 75.96, 56.90,
    56.07, 39.37, 31.11, 19.82, 19.14,
    17.78, 17.11, 16.98.
    141 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.16
    [M + H]+ calcd for (s, 1H), 8.48 (d, J = 9.4 Hz, 1H), 8.01
    C22H27FN2O5, (d, J = 5.2 Hz, 1H), 7.19-7.10 (m,
    419.1977; found, 2H), 6.94 (t, J = 8.7 Hz, 2H), 6.89 (d,
    419.1973 J = 5.2 Hz, 1H), 5.11-4.98 (m, 1H),
    4.64 (dd, J = 9.4, 4.8 Hz, 1H), 3.95 (s,
    3H), 2.92 (p, J = 7.1 Hz, 1H), 2.31 (pd,
    J = 6.9, 4.8 Hz, 1H), 1.29 (d, J = 7.0
    Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H), 1.03
    (d, J = 6.8 Hz, 3H), 0.95 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.57,
    169.05, 162.62, 160.67, 155.43,
    148.76, 140.52, 138.50, 130.50,
    129.23, 129.16, 115.29, 115.13,
    109.47, 77.27, 76.39, 57.25, 56.10,
    43.96, 31.33, 19.41, 18.04, 17.40, 17.07.
    142 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.18
    [M + H]+ calcd for (s, 1H), 8.52 (d, J = 9.4 Hz, 1H), 8.02
    C24H32N2O6, (d, J = 5.2 Hz, 1H), 7.06 (d, J = 8.4 Hz,
    445.2333; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.75-
    445.2314 6.63 (m, 2H), 5.08 (dq, J = 8.3, 6.2 Hz,
    1H), 4.66 (dd, J = 9.4, 4.8 Hz, 1H),
    3.95 (s, 3H), 3.76 (s, 3H), 3.19-3.06
    (m, 1H), 2.41-2.33 (m, 1H), 2.31 (s,
    3H), 1.23 (d, J = 6.9 Hz, 3H), 1.13 (d,
    J = 6.2 Hz, 3H), 1.05 (d, J = 6.9 Hz, 3H),
    0.98 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.79,
    169.06, 157.68, 155.40, 148.74,
    140.51, 136.87, 133.93, 130.56,
    127.33, 115.96, 111.46, 109.44, 76.90,
    57.29, 56.08, 55.12, 39.01, 31.37,
    20.17, 19.50, 18.52, 17.65, 17.40.
    143 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.18
    [M + H]+ calcd for (s, 1H), 8.50 (d, J = 9.2 Hz, 1H), 8.02
    C23H29FN2O5, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.5,
    433.2133; found, 5.7 Hz, 1H), 6.89 (d, J = 5.2 Hz, 1H),
    433.2142 6.87-6.82 (m, 2H), 5.12 (dq, J = 8.0,
    6.3 Hz, 1H), 4.63 (dd, J = 9.3, 5.1 Hz,
    1H), 3.95 (s, 3H), 3.15 (p, J = 7.1 Hz,
    1H), 2.41-2.25 (m, 4H), 1.24 (d, J =
    6.9 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H),
    1.03 (d, J = 6.9 Hz, 3H), 0.99 (d, J =
    6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.87,
    169.06, 161.95, 160.01, 155.41,
    148.74, 140.53, 137.86, 137.80,
    137.31, 137.28, 130.54, 127.91,
    117.05, 116.89, 113.06, 112.89,
    109.46, 76.09, 57.04, 56.09, 39.11,
    31.39, 20.00, 19.12, 18.25, 17.80, 17.41.
    144 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.16
    [M + H]+ calcd for (s, 1H), 8.32 (d, J = 9.2 Hz, 1H), 8.00
    C23H29FN2O5, (d, J = 5.2 Hz, 1H), 7.16 (dd, J = 8.4,
    433.2133; found, 5.8 Hz, 1H), 6.89 (d, J = 5.2 Hz, 1H),
    433.2139 6.78 (ddd, J = 9.8, 7.0, 4.1 Hz, 2H),
    5.17-5.05 (m, 1H), 4.48 (dd, J = 9.3,
    5.3 Hz, 1H), 3.96 (s, 3H), 3.22 (p, J =
    7.2 Hz, 1H), 2.33 (s, 3H), 2.18 (pd, J =
    6.9, 5.2 Hz, 1H), 1.28-1.19 (m, 6H),
    0.92 (d, J = 6.8 Hz, 3H), 0.86 (d, J =
    6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.29,
    168.86, 161.96, 160.02, 155.40,
    148.71, 140.46, 138.45, 138.39,
    136.79, 136.76, 130.49, 127.77,
    127.70, 116.77, 116.61, 112.79,
    112.63, 109.43, 75.66, 57.06, 56.09,
    38.58, 31.26, 19.91, 18.94, 17.61,
    17.30, 16.84.
    145 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.19
    [M + H]+ calcd for (s, 1H), 8.34 (d, J = 9.3 Hz, 1H), 8.00
    C23H30N2O5, (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.6,
    415.2227; found, 1.7 Hz, 1H), 7.14-7.05 (m, 2H), 7.02
    415.2224 (td, J = 7.2, 1.4 Hz, 1H), 6.88 (d, J =
    5.2 Hz, 1H), 5.20-5.12 (m, 1H), 4.48
    (dd, J = 9.3, 5.1 Hz, 1H), 3.95 (s, 3H),
    3.28 (p, J = 7.1 Hz, 1H), 2.36 (s, 3H),
    2.17 (pd, J = 6.9, 5.1 Hz, 1H), 1.29-
    1.22 (m, 6H), 0.90 (d, J = 6.8 Hz, 3H),
    0.84 (d, J = 6.8 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.28,
    168.84, 155.36, 148.69, 141.08,
    140.42, 136.11, 130.59, 130.28,
    126.23, 126.11, 109.39, 75.76, 57.06,
    56.08, 39.06, 31.33, 19.83, 18.93,
    17.59, 17.20, 16.50.
    146 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.17
    [M + H]+ calcd for (s, 1H), 8.50 (d, J = 8.9 Hz, 1H), 8.02
    C22H27FN2O5, (d, J = 5.2 Hz, 1H), 7.19-7.10 (m,
    419.1977; found, 3H), 7.00-6.93 (m, 2H), 6.89 (d, J =
    419.1974 5.2 Hz, 1H), 5.11-5.02 (m, 1H), 4.67-
    4.58 (m, 1H), 3.95 (s, 4H), 2.92 (p, J =
    7.1 Hz, 1H), 2.31 (pd, J = 6.9, 5.0
    Hz, 1H), 1.28 (d, J = 7.0 Hz, 3H), 1.10
    (d, J = 6.2 Hz, 3H), 1.02 (d, J = 6.9 Hz,
    3H), 0.99 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.76,
    169.06, 162.64, 160.70, 155.41,
    148.74, 140.53, 138.48, 130.53,
    129.28, 129.22, 115.33, 115.16,
    109.46, 76.11, 57.07, 56.09, 44.09,
    31.35, 19.09, 17.87, 17.82, 17.23.
    147 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.20
    [M + H]+ calcd for (s, 1H), 8.53 (d, J = 9.2 Hz, 1H), 8.02
    C24H32N2O6, (d, J = 5.2 Hz, 1H), 7.10 (d, J = 8.4 Hz,
    445.2333; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.75-
    445.2334 6.64 (m, 2H), 5.12 (dq, J = 8.2, 6.3 Hz,
    1H), 4.65 (dd, J = 9.2, 5.0 Hz, 1H),
    3.95 (s, 3H), 3.75 (s, 3H), 3.20-3.06
    (m, 1H), 2.32 (s, 4H), 1.23 (d, J = 6.9
    Hz, 3H), 1.13 (d, J = 6.2 Hz, 3H), 1.03
    (d, J = 6.9 Hz, 3H), 1.00 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.92,
    169.04, 157.67, 155.39, 148.73,
    140.52, 136.92, 133.85, 130.59,
    127.40, 116.00, 111.44, 109.43, 76.56,
    57.04, 56.08, 55.10, 39.05, 31.44,
    20.18, 19.13, 18.32, 17.80, 17.65.
    148 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (s, 1H), 8.47 (d, J = 7.9 Hz, 1H), 8.01
    C21H25FN2O5, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 9.5,
    405.1820; found, 5.8 Hz, 1H), 6.91-6.80 (m, 3H), 5.12
    405.1820 (dq, J = 8.1, 6.3 Hz, 1H), 4.72 (p, J =
    7.3 Hz, 1H), 3.95 (s, 3H), 3.21-3.10
    (m, 1H), 2.33 (s, 3H), 1.54 (d, J = 7.2
    Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.12
    (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.81,
    168.74, 161.95, 160.01, 155.40,
    148.78, 140.51, 137.89, 137.83,
    137.29, 137.26, 130.48, 127.87,
    127.81, 117.07, 116.91, 113.06,
    112.90, 109.48, 76.19, 56.09, 47.96,
    39.12, 20.01, 18.24, 18.13, 17.48.
    149 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.12
    [M + H]+ calcd for (s, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.99
    C21H25FN2O5, (d, J = 5.2 Hz, 1H), 7.22-7.09 (m,
    405.1820; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.83-
    405.1820 6.74 (m, 2H), 5.19-5.06 (m, 1H),
    4.62-4.50 (m, 1H), 3.95 (s, 3H), 3.31-
    3.17 (m, 1H), 2.33 (s, 3H), 1.38 (d, J =
    7.2 Hz, 3H), 1.27-1.18 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 171.29,
    168.55, 161.93, 159.99, 155.38,
    148.74, 140.44, 138.41, 138.35,
    136.73, 136.71, 130.43, 127.71,
    127.64, 116.77, 116.61, 112.80,
    112.64, 109.45, 75.62, 56.09, 47.82,
    38.64, 18.06, 17.22, 16.84.
    150 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.15
    [M + H]+ calcd for (s, 1H), 8.30 (d, J = 7.9 Hz, 1H), 7.99
    C21H26N2O5, (d, J = 5.2 Hz, 1H), 7.21 (dd, J = 7.8,
    387.1914; found, 1.4 Hz, 1H), 7.15-7.01 (m, 4H), 6.87
    387.1913 (d, J = 5.2 Hz, 1H), 5.23-5.08 (m,
    1H), 4.58-4.49 (m, 1H), 3.95 (s, 3H),
    3.28 (h, J = 7.3 Hz, 1H), 2.36 (s, 3H),
    1.35 (d, J = 7.2 Hz, 3H), 1.28-1.22
    (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 171.29,
    168.54, 155.35, 148.73, 141.04,
    140.40, 136.09, 130.51, 130.26,
    126.23, 126.11, 109.40, 75.73, 56.08,
    47.88, 39.15, 19.83, 18.11, 17.16, 16.53.
    151 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (d, J = 0.6 Hz, 1H), 8.46 (d, J = 7.9 Hz,
    C20H23FN2O5, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.16 (dd,
    391.1664; found, J = 8.7, 5.4 Hz, 2H), 6.97 (t, J = 8.7
    391.1658 Hz, 2H), 6.88 (d, J = 5.2 Hz, 1H), 5.07
    (dq, J = 7.4, 6.3 Hz, 1H), 4.79-4.64
    (m, 1H), 3.95 (s, 3H), 2.92 (p, J = 7.1
    Hz, 1H), 1.53 (d, J = 7.2 Hz, 3H), 1.28
    (d, J = 7.1 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.72,
    168.76, 162.65, 160.70, 155.40,
    148.78, 140.51, 138.43, 130.47,
    129.29, 129.23, 115.33, 115.16,
    109.48, 76.12, 56.09, 47.98, 44.09,
    18.19, 17.69, 17.30.
    152 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.17
    [M + H]+ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.01
    C22H28N2O6, (d, J = 5.2 Hz, 1H), 7.09 (d, J = 8.3 Hz,
    417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.78-
    417.2007 6.64 (m, 2H), 5.13 (dq, J = 8.4, 6.3 Hz,
    1H), 4.73 (p, J = 7.3 Hz, 1H), 3.95 (s,
    3H), 3.76 (s, 3H), 3.18-3.06 (m, 1H),
    2.32 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H),
    1.23 (d, J = 6.9 Hz, 3H), 1.12 (d, J =
    6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.86,
    168.72, 157.68, 155.38, 148.76,
    140.50, 136.94, 133.81, 130.53,
    127.37, 115.97, 111.47, 109.45, 76.65,
    56.08, 55.11, 47.99, 39.06, 20.19,
    18.30, 18.19, 17.68.
    153 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (s, 1H), 8.49 (d, J = 8.0 Hz, 1H), 8.00
    C21H25FN2O5, (d, J = 5.2 Hz, 1H), 7.17-7.08 (m,
    405.1820; found, 1H), 6.91-6.81 (m, 4H), 5.11 (dq, J =
    405.1818 8.1, 6.3 Hz, 1H), 4.72 (p, J = 7.3 Hz,
    1H), 3.95 (s, 3H), 3.20-3.10 (m, 1H),
    2.33 (s, 3H), 1.55 (d, J = 7.2 Hz, 3H),
    1.24 (d, J = 6.9 Hz, 3H), 1.14 (d, J =
    6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.80,
    168.69, 161.97, 160.03, 155.39,
    148.77, 140.51, 137.87, 137.81,
    137.33, 137.30, 130.47, 127.86,
    127.79, 117.10, 116.94, 113.02,
    112.86, 109.47, 76.33, 56.09, 48.13,
    39.16, 20.00, 18.41, 18.36, 17.33.
    154 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.09
    [M + H]+ calcd for (s, 1H), 8.35 (d, J = 8.0 Hz, 1H), 7.98
    C21H25FN2O5, (d, J = 5.2 Hz, 1H), 7.13 (dd, J = 8.4,
    405.1820; found, 5.8 Hz, 1H), 6.86 (d, J = 5.2 Hz, 1H),
    405.1816 6.80 (ddd, J = 9.5, 7.0, 4.1 Hz, 2H),
    5.14 (dq, J = 8.2, 6.2 Hz, 1H), 4.60-
    4.49 (m, 1H), 3.94 (s, 3H), 3.27-3.16
    (m, 1H), 2.34 (s, 3H), 1.30 (d, J = 6.3
    Hz, 3H), 1.22 (d, J = 7.1 Hz, 3H), 1.14
    (d, J = 7.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.55,
    168.59, 161.91, 159.97, 155.37,
    148.74, 140.44, 138.30, 138.24,
    137.15, 137.13, 130.43, 127.46,
    127.40, 116.74, 116.57, 112.90,
    112.73, 109.43, 75.74, 56.08, 47.87,
    38.98, 19.90, 19.89, 17.79, 17.32.
    155 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.11
    [M + H]+ calcd for (d, J = 0.6 Hz, 1H), 8.36 (d, J = 8.0 Hz,
    C21H26N2O5, 1H), 7.97 (d, J = 5.2 Hz, 1H), 7.19 (dd,
    387.1914; found, J = 7.5, 1.2 Hz, 1H), 7.12 (td, J = 7.8,
    387.1912 7.0, 2.4 Hz, 1H), 7.09-7.02 (m, 2H),
    6.86 (d, J = 5.2 Hz, 1H), 5.19 (dq, J =
    8.3, 6.2 Hz, 1H), 4.60-4.45 (m, 1H),
    3.94 (s, 3H), 3.33-3.20 (m, 1H), 2.36
    (s, 3H), 1.32 (d, J = 6.2 Hz, 3H), 1.24
    (d, J = 7.0 Hz, 3H), 1.08 (d, J = 7.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.58,
    168.54, 155.33, 148.71, 141.47,
    140.41, 135.95, 130.49, 130.22,
    126.20, 125.88, 109.39, 75.87, 56.06,
    47.85, 39.52, 19.83, 17.83, 17.74, 17.14.
    156 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.14
    [M + H]+ calcd for (s, 1H), 8.47 (d, J = 7.7 Hz, 1H), 8.00
    C20H23FN2O5, (d, J = 5.2 Hz, 1H), 7.21-7.10 (m,
    391.1664; found, 3H), 6.97 (td, J = 8.8, 2.6 Hz, 2H), 6.88
    391.1661 (dd, J = 5.3, 1.7 Hz, 1H), 5.12-5.01
    (m, 1H), 4.77-4.66 (m, 1H), 3.95 (d,
    J = 1.6 Hz, 4H), 2.92 (p, J = 7.1 Hz, 1H),
    1.53 (d, J = 7.2 Hz, 4H), 1.29 (d, J =
    7.0 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.67,
    168.69, 162.64, 160.70, 155.40,
    148.78, 140.51, 138.45, 130.46,
    129.26, 115.32, 115.16, 109.48, 76.31,
    56.09, 48.12, 44.11, 18.38, 17.95, 17.16.
    157 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.16
    [M + H]+ calcd for (s, 1H), 8.51 (d, J = 7.9 Hz, 1H), 8.00
    C22H28N2O6, (d, J = 5.2 Hz, 1H), 7.12-7.06 (m,
    417.2020; found, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.76-
    417.2006 6.67 (m, 2H), 5.11 (dq, J = 8.3, 6.3 Hz,
    1H), 4.72 (p, J = 7.3 Hz, 1H), 3.95 (s,
    3H), 3.77 (s, 3H), 3.19-3.07 (m, 1H),
    2.32 (s, 3H), 1.61-1.51 (m, 4H), 1.23
    (d, J = 6.9 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.86,
    168.68, 157.70, 155.38, 148.77,
    140.50, 136.91, 133.86, 130.51,
    127.36, 115.95, 111.48, 109.45, 56.08,
    55.13, 48.17, 39.11, 20.18, 18.46, 17.57.
    158 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.13
    film) 3369, [M + H]+ calcd for (s, 1H), 8.58-8.47 (m, 1H), 8.01 (d,
    2983, 1736, C21H24F3N2O5, J = 5.2 Hz, 1H), 7.68-7.61 (m, 1H),
    1649, 1528, 441.1632; found, 7.51 (td, J = 7.7, 1.2 Hz, 1H), 7.43 (d,
    1310, 1148, 441.1627 J = 7.7 Hz, 1H), 7.38-7.29 (m, 1H),
    1115, 770, 6.88 (d, J = 5.2 Hz, 1H), 5.29-5.15
    731 cm−1 (m, 1H), 4.82-4.71 (m, 1H), 3.95 (s,
    3H), 3.42-3.29 (m, 1H), 1.60 (d, J =
    7.2 Hz, 3H), 1.29 (d, J = 6.8 Hz, 3H),
    1.12 (d, J = 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.24.
    159 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.11
    film) 3370, [M + H]+ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.01
    2984, 1737, C21H23F4N2O5, (d, J = 5.2 Hz, 1H), 7.42 (dd, J = 8.8,
    1528, 1313, 459.1538; found, 5.3 Hz, 1H), 7.35 (dd, J = 9.2, 2.8 Hz,
    1151, 1118, 459.1535 1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H), 6.89
    1045, 908, (d, J = 5.2 Hz, 1H), 5.24-5.09 (m,
    799, 738 1H), 4.82-4.67 (m, 1H), 3.95 (s, 3H),
    cm−1 3.41-3.26 (m, 1H), 1.59 (d, J = 7.2
    Hz, 3H), 1.27 (d, J = 6.8 Hz, 3H), 1.12
    (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.78, −113.91.
    160 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.17
    film) 3369, [M + H]+ calcd for (s, 1H), 8.53 (d, J = 7.8 Hz, 1H), 7.99
    2944, 1732, C19H29N2O5, (d, J = 5.2 Hz, 1H), 6.87 (d, J = 5.2 Hz,
    1648, 1526, 365.2071; found, 1H), 5.11 (qd, J = 6.4, 3.1 Hz, 1H),
    1438, 1280, 365.2067 4.76-4.64 (m, 1H), 3.95 (s, 3H), 1.76
    1263, 1216, (dddd, J = 13.2, 10.4, 8.0, 6.4 Hz, 2H),
    1149, 1057, 1.69-1.52 (m, 6H), 1.52-1.43 (m,
    800 cm−1 1H), 1.43-1.35 (m, 1H), 1.24 (d, J =
    6.4 Hz, 3H), 1.19-0.98 (m, 3H), 0.98-
    0.89 (m, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.76,
    168.71, 155.39, 148.78, 140.46,
    130.58, 109.43, 74.81, 56.08, 48.23,
    43.31, 43.13, 31.22, 30.74, 25.15,
    24.98, 18.51, 17.78, 12.50.
    161 HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.15
    [M + H]+ calcd for (s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.01
    C21H24F3N2O5, (d, J = 5.2 Hz, 1H), 7.64 (dd, J = 7.9,
    441.1632; found, 1.3 Hz, 1H), 7.56-7.47 (m, 1H), 7.44
    441.1624 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.5 Hz,
    1H), 6.88 (d, J = 5.2 Hz, 1H), 5.27-
    5.17 (m, 1H), 4.83-4.68 (m, 1H), 3.95
    (s, 3H), 3.42-3.28 (m, 1H), 1.58 (d,
    J = 7.2 Hz, 3H), 1.30 (d, J = 6.8 Hz, 3H),
    1.10 (d, J = 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.24.
    162 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.12
    film) 2983, [M + H]+ calcd for (s, 1H), 8.46 (d, J = 7.9 Hz, 1H), 8.01
    1738, 1649, C21H23F4N2O5, (d, J = 5.2 Hz, 1H), 7.43 (dd, J = 8.8,
    1528, 1313, 459.1538; found, 5.3 Hz, 1H), 7.34 (dd, J = 9.2, 2.8 Hz,
    1152, 1119, 459.1530 1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H), 6.89
    1045, 909, (d, J = 5.2 Hz, 1H), 5.18 (p, J = 6.6 Hz,
    800, 732 1H), 4.79-4.69 (m, 1H), 3.95 (s, 3H),
    cm−1 3.31 (p, J = 7.1 Hz, 1H), 1.57 (d, J =
    7.2 Hz, 3H), 1.29 (d, J = 6.9 Hz, 3H),
    1.12 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.78, −114.01.
    163 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.18
    film) 3370, [M + H]+ calcd for (s, 1H), 8.52 (d, J = 7.8 Hz, 1H), 7.99
    2944, 1732, C19H29N2O5, (d, J = 5.2 Hz, 1H), 6.87 (d, J = 5.2 Hz,
    1649, 1526, 365.2071; found, 1H), 5.10 (qd, J = 6.4, 3.0 Hz, 1H),
    1438, 1263, 365.2068 4.74-4.64 (m, 1H), 3.95 (s, 3H), 1.83-
    1216, 1150, 1.65 (m, 3H), 1.65-1.52 (m, 6H),
    1058, 954, 1.52-1.34 (m, 2H), 1.23 (d, J = 6.4
    800, 731 Hz, 3H), 1.18-1.03 (m, 2H), 0.94 (d,
    cm−1 J = 6.9 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.75,
    168.76, 155.39, 148.79, 140.46,
    130.62, 109.44, 74.90, 56.08, 48.04,
    43.11, 42.95, 31.26, 30.67, 25.14,
    25.00, 18.33, 17.49, 12.53.
    164 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.17
    film) 3369, [M + H]+ calcd for (s, 1H), 8.58 (t, J = 7.7 Hz, 1H), 7.99
    2971, 1733, C22H29N2O5, (d, J = 5.2 Hz, 1H), 7.14-6.90 (m,
    1648, 1527, 401.2071; found, 3H), 6.87 (d, J = 5.3 Hz, 1H), 5.72-
    1438, 1263, 401.2072 5.58 (m, 1H), 4.86-4.71 (m, 1H), 3.93
    1149, 1057, (s, 3H), 3.44 (dp, J = 10.5, 7.1 Hz, 1H),
    801, 770, 2.42 (d, J = 1.7 Hz, 3H), 2.38 (s, 3H),
    730 cm−1 1.61 (dd, J = 14.3, 7.2 Hz, 3H), 1.29
    (dd, J = 7.1, 2.7 Hz, 3H), 1.10-0.95
    (m, 3H).
    165 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.15
    film) 3370, [M + H]+ calcd for (s, 1H), 8.69-8.42 (m, 1H), 8.00 (d,
    2975, 1734, C22H28FN2O5, J = 5.2 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H),
    1649, 1527, 419.1977; found, 6.70 (ddd, J = 14.6, 8.1, 2.5 Hz, 2H),
    1480, 1262, 419.1975 5.59 (ddq, J = 12.4, 10.7, 6.2 Hz, 1H),
    1148, 849, 4.76 (p, J = 7.2 Hz, 1H), 3.94 (d, J =
    799, 728 1.9 Hz, 3H), 3.38 (dp, J = 10.5, 7.0 Hz,
    cm−1 1H), 2.41 (d, J = 1.9 Hz, 3H), 2.36 (s,
    3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H),
    1.27 (dd, J = 7.1, 3.1 Hz, 3H), 1.04 (dt,
    J = 11.6, 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.25, −118.31.
    166 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.16
    film) 3369, [M + H]+ calcd for (d, J = 3.9 Hz, 1H), 8.56 (t, J = 7.7 Hz,
    2971, 1733, C22H29N2O5, 1H), 8.00 (d, J = 5.2 Hz, 1H), 7.07-
    1648, 1527, 401.2071; found, 6.90 (m, 3H), 6.88 (d, J = 5.2 Hz, 1H),
    1438, 1280, 401.2066 5.73-5.53 (m, 1H), 4.76 (pd, J = 7.2,
    1263, 1149, 1.1 Hz, 1H), 3.95 (s, 3H), 3.43 (dp, J =
    1056, 801, 10.5, 7.2 Hz, 1H), 2.42 (d, J = 1.9 Hz,
    770, 730 3H), 2.38 (s, 3H), 1.61 (dd, J = 14.3,
    cm−1 7.2 Hz, 3H), 1.29 (dd, J = 7.2, 2.3 Hz,
    3H), 1.06 (t, J = 6.0 Hz, 3H).
    167 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.15
    film) 3370, [M + H]+ calcd for (d, J = 3.3 Hz, 1H), 8.55 (t, J = 7.9 Hz,
    2976, 1734, C22H28FN2O5, 1H), 8.00 (d, J = 5.2 Hz, 1H), 6.88 (d,
    1649, 1527, 419.1977; found, J = 5.2 Hz, 1H), 6.70 (ddd, J = 15.1, 9.4,
    1480, 1263, 419.1971 2.6 Hz, 2H), 5.59 (ddq, J = 12.4, 10.5,
    1149, 849, 6.2 Hz, 1H), 4.76 (p, J = 7.3 Hz, 1H),
    800, 730 3.95 (s, 3H), 3.38 (dp, J = 10.5, 7.0 Hz,
    cm−1 1H), 2.41 (d, J = 1.9 Hz, 3H), 2.36 (s,
    3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H),
    1.27 (dd, J = 7.2, 2.9 Hz, 3H), 1.05 (t,
    J = 5.9 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.26, −118.27, −118.33.
    168 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.16
    film) 3370, [M + H]+ calcd for (d, J = 3.8 Hz, 1H), 8.56 (t, J = 7.6 Hz,
    2971, 1734, C22H29N2O5, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.05-
    1649, 1527, 401.2071; found, 6.91 (m, 3H), 6.88 (d, J = 5.2 Hz, 1H),
    1451, 1263, 401.2070 5.70-5.57 (m, 1H), 4.76 (pd, J = 7.1,
    1150, 801, 1.1 Hz, 1H), 3.95 (s, 3H), 3.43 (dp, J =
    770, 730 10.5, 7.2 Hz, 1H), 2.42 (d, J = 2.0 Hz,
    cm−1 3H), 2.38 (s, 3H), 1.61 (dd, J = 14.3,
    7.2 Hz, 3H), 1.29 (dd, J = 7.2, 2.1 Hz,
    3H), 1.06 (t, J = 6.0 Hz, 3H).
    169 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.15
    film) 3371, [M + H]+ calcd for (d, J = 3.3 Hz, 1H), 8.55 (t, J = 7.8 Hz,
    2976, 1734, C22H28FN2O5, 1H), 8.00 (d, J = 5.2 Hz, 1H), 6.88 (d,
    1649, 1527, 419.1977; found, J = 5.2 Hz, 1H), 6.70 (ddd, J = 17.0, 9.4,
    1480, 1280, 419.1971 2.8 Hz, 2H), 5.59 (ddq, J = 12.2, 10.8,
    1262, 1157, 6.2 Hz, 1H), 4.76 (p, J = 7.3 Hz, 1H),
    849, 800, 3.95 (s, 3H), 3.38 (dp, J = 10.4, 7.0 Hz,
    731 cm−1 1H), 2.41 (d, J = 2.2 Hz, 3H), 2.36 (s,
    3H), 1.61 (dd, J = 13.6, 7.2 Hz, 3H),
    1.27 (dd, J = 72, 2.8 Hz, 3H), 1.05 (t,
    J = 5.9 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.29, −118.36.
    170 HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.16
    [M + H]+ calcd for (s, 1H), 8.41 (d, J = 7.9 Hz, 1H), 7.97
    C21H27N2O6, (d, J = 5.2 Hz, 1H), 7.23-7.10 (m,
    403.1864; found, 2H), 6.92-6.78 (m, 3H), 5.31 (dq, J =
    403.1827 7.8, 6.3 Hz, 1H), 4.63-4.49 (m, 1H),
    3.93 (s, 3H), 3.81 (s, 3H), 3.49-3.39
    (m, 1H), 1.26 (d, J = 6.3 Hz, 3H), 1.23
    (d, J = 7.2 Hz, 3H), 1.16 (d, J = 7.2 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.5,
    168.6, 157.2, 155.3, 148.7, 140.4,
    131.1, 130.6, 128.1, 127.4, 120.5,
    110.5, 109.4, 75.1, 56.0, 55.4, 48.0,
    37.6, 17.9, 17.8, 16.6.
    171 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.16
    film) 2978, [M + H]+ calcd for (s, 1H), 8.50 (d, J = 8.0 Hz, 1H), 8.01
    2937, 1733, C20H25N2O5, (d, J = 5.2 Hz, 1H), 7.32-7.27 (m,
    1647, 1527, 373.1758; found, 2H), 7.24-7.16 (m, 3H), 6.88 (d, J =
    1451, 1262, 373.1752 5.2 Hz, 1H), 5.11 (dq, J = 1.1, 6.3 Hz,
    1147, 701 1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H),
    cm−1 2.97-2.87 (m, 1H), 1.54 (d, J = 1.2
    Hz, 3H), 1.31 (d, J = 7.0 Hz, 3H), 1.13
    (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.8,
    168.7, 155.3, 148.7, 142.9, 140.5,
    130.4, 128.5, 127.8, 126.8, 109.4, 76.5,
    56.1, 48.1, 44.9, 18.4, 18.2, 17.2.
    172 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.16
    film) 3368, [M + H]+ calcd for (s, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.00
    2978, 1937, C19H25N2O5S, (d, J = 5.2 Hz, 1H), 6.88 (d, J = 5.2 Hz,
    1734, 1648, 393.1479; found, 1H), 6.61 (d, J = 3.5 Hz, 1H), 6.55 (dq,
    1527, 1480, 393.1473 J = 3.5, 1.1 Hz, 1H), 5.10-5.01 (m,
    1438, 1262, 1H), 4.77-4.67 (m, 1H), 3.95 (s, 3H),
    797, 730 3.22-3.12 (m, 1H), 2.42 (d, J = 1.1
    cm−1 Hz, 3H), 1.55 (d, J = 7.1 Hz, 3H), 1.33
    (d, J = 7.0 Hz, 3H), 1.20 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.6,
    168.7, 155.3, 148.7, 143.3, 140.5,
    138.0, 130.5, 124.5, 124.1, 109.4, 76.1,
    56.1, 48.1, 40.1, 18.4, 17.8, 17.2, 15.3.
    173 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 12.19
    film) 3369, [M + H]+ calcd for (s, 1H), 8.49 (d, J = 7.9 Hz, 1H), 8.01
    2977, 2939, C21H26FN2O6, (d, J = 5.2 Hz, 1H), 7.13-7.06 (m,
    1733, 1649, 421.1769; found, 1H), 6.88 (d, J = 5.3 Hz, 1H), 6.62-
    1528, 1450, 421.1770 6.54 (m, 2H), 5.21-5.12 (m, 1H),
    1278, 1262, 4.73-4.63 (m, 1H), 3.95 (s, 3H), 3.79 (s,
    1149, 952 3H), 3.42-3.32 (m, 1H), 1.51 (d, J =
    cm−1 7.2 Hz, 3H), 1.24 (d, J = 7.0 Hz, 3H),
    1.14 (d, J = 6.3 Hz, 3H).
    19FNMR(471 MHz, CDCl3) δ
    −113.8-−113.9 (m).
    174 ESIMS m/z 387.3 1H NMR (400 MHz, CDCl3) δ 12.16
    [(M + H)+] (d, J = 4.9 Hz, 1H), 8.50 (d, J = 7.8 Hz,
    1H), 8.01 (dd, J = 5.2, 2.7 Hz, 1H),
    7.21-7.01 (m, 4H), 6.88 (dd, J = 5.3,
    1.9 Hz, 1H), 5.18 (dq, J = 8.3, 6.3 Hz,
    1H), 4.73 (p, J = 7.3 Hz, 1H), 3.95 (d,
    J = 1.6 Hz, 3H), 3.19 (dq, J = 9.0, 6.9
    Hz, 1H), 2.35 (s, 3H), 1.55 (d, J = 7.0
    Hz, 3H), 1.26 (dd, J = 6.9, 3.8 Hz, 3H),
    1.13 (dd, J = 9.0, 6.2 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.85,
    168.74, 155.41, 148.80, 141.65,
    140.49, 135.53, 130.54, 126.37,
    126.31, 126.29, 109.46, 56.07, 53.40,
    48.00, 39.74, 19.94, 18.28, 18.27,
    17.52, −0.01.
    175 1H NMR (400 MHz, CDCl3) δ 12.16
    (d, J = 0.6 Hz, 1H), 8.51 (d, J = 7.9 Hz,
    1H), 8.00 (d, J = 5.2 Hz, 1H), 7.22-
    7.02 (m, 5H), 6.88 (d, J = 5.2 Hz, 1H),
    5.16 (dq, J = 8.3, 6.2 Hz, 1H), 4.78-
    4.65 (m, 1H), 3.95 (s, 3H), 3.20 (dq,
    J = 8.3, 6.9 Hz, 1H), 2.35 (s, 3H), 1.56
    (d, J = 7.2 Hz, 3H), 1.26 (d, J = 6.9 Hz,
    3H), 1.15 (d, J = 6.3 Hz, 3H).
    176 ESIMS m/z 416 1H NMR (300 MHz, CDCl3) δ 12.18
    ([M + H]+) (s, 1H), 8.52 (d, J = 7.9 Hz, 1H), 8.00
    (d, J = 5.2 Hz, 1H), 7.13-7.01 (m,
    2H), 6.88 (d, J = 5.2 Hz, 1H), 6.67 (d,
    J = 8.5 Hz, 2H), 5.12-4.98 (m, 1H),
    4.72 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H),
    2.92 (s, 6H), 2.88-2.75 (m, 1H), 1.57
    (s, 3H), 1.26 (dd, J = 7.1, 4.0 Hz, 3H),
    1.11 (d, J = 6.2 Hz, 3H).
    13C NMR (75 MHz, CDCl3) δ 148.75,
    140.49, 130.54, 128.42, 112.68,
    109.42, 40.70, 18.33 (d, J = 22.8 Hz), 0.01.
    177 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.57 (s,
    [M + H]+ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.07 (d,
    C24H30N2O6, J = 8.6 Hz, 1H), 7.01 (d, J = 5.5 Hz, 1H),
    443.2177; found, 6.97 (d, J = 6.7 Hz, 2H), 5.12 (dq, J =
    443.2170 8.5, 6.3 Hz, 1H), 4.78-4.67 (m, 1H),
    3.91 (s, 3H), 3.19-3.09 (m, 1H), 2.41
    (s, 3H), 2.31 (s, 3H), 2.28 (s, 3H), 1.52
    (d, J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz,
    3H), 1.11 (d, J = 6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.41,
    168.96, 162.36, 159.42, 146.70,
    141.53, 138.75, 137.46, 135.67,
    135.33, 131.26, 126.95, 126.26,
    109.75, 76.48, 56.29, 48.16, 39.45,
    20.89, 20.78, 19.90, 18.76, 18.48, 17.67.
    178 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.57 (s,
    [M + H]+ calcd for 1H), 8.35 (d, J = 5.5 Hz, 1H), 7.07 (d,
    C24H30N2O6, J = 7.7 Hz, 1H), 7.01 (d, J = 5.5 Hz, 1H),
    443.2177; found, 6.98 (d, J = 7.4 Hz, 2H), 5.12 (dq, J =
    443.2172 8.5, 6.2 Hz, 1H), 4.72 (p, J = 7.2 Hz,
    1H), 3.91 (s, 3H), 3.18-3.09 (m, 1H),
    2.41 (s, 3H), 2.31 (s, 3H), 2.27 (s, 3H),
    1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J =
    6.9 Hz, 3H), 1.10 (d, J = 6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.41,
    168.97, 162.40, 159.43, 146.70,
    141.52, 138.72, 137.46, 135.64,
    135.37, 131.24, 126.98, 126.27,
    109.75, 76.37, 56.29, 48.04, 39.38,
    20.88, 20.78, 19.92, 18.59, 18.24, 17.73.
    179 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.51 (s,
    [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.09-
    C26H34N2O6, 7.04 (m, 1H), 7.02-6.94 (m, 3H), 5.11
    471.2490; found, (dq, J = 8.5, 6.2 Hz, 1H), 4.73 (p, J =
    471.2484 7.2 Hz, 1H), 3.89 (s, 3H), 3.19-3.09
    (m, 1H), 2.96 (p, J = 7.0 Hz, 1H), 2.31
    (s, 3H), 2.28 (s, 3H), 1.51 (d, J = 7.2
    Hz, 3H), 1.36 (dd, J = 7.0, 1.4 Hz, 5H),
    1.23 (d, J = 6.9 Hz, 3H), 1.11 (d, J =
    6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.73,
    172.50, 162.34, 159.40, 146.59,
    141.90, 138.78, 137.63, 135.66,
    135.33, 131.25, 126.95, 126.28,
    109.58, 76.41, 56.29, 48.13, 39.45,
    33.94, 20.89, 19.90, 18.80, 18.48, 17.66.
    180 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.50 (s,
    [M + H]+ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.07 (d,
    C26H34N2O6, J = 7.8 Hz, 1H), 7.03-6.93 (m, 3H),
    471.2490; found, 5.12 (dq, J = 8.5, 6.2 Hz, 1H), 4.72 (p,
    471.2490 J = 7.1 Hz, 1H), 3.89 (s, 3H), 3.20-
    3.09 (m, 1H), 2.96 (p, J = 7.0 Hz, 1H),
    2.31 (s, 3H), 2.27 (s, 3H), 1.49 (d, J =
    7.1 Hz, 3H), 1.37 (dd, J = 6.9, 2.0 Hz,
    6H), 1.22 (d, J = 6.9 Hz, 3H), 1.09 (d,
    J = 6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.74,
    172.50, 162.39, 159.41, 146.59,
    141.90, 138.76, 137.63, 135.63,
    135.37, 131.23, 126.98, 126.28,
    109.58, 76.29, 56.29, 48.03, 39.40,
    33.94, 20.88, 19.91, 18.81, 18.59,
    18.25, 17.74.
    181 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.37 (s,
    [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.17 (dd,
    C23H27FN2O6, J = 8.4, 5.9 Hz, 1H), 7.01 (d, J = 5.4
    447.1926; found, Hz, 1H), 6.84-6.75 (m, 2H), 5.10 (p,
    447.1923 J = 6.4 Hz, 1H), 4.57 (p, J = 7.2 Hz,
    1H), 3.91 (s, 3H), 3.22 (p, J = 7.0 Hz,
    1H), 2.40 (s, 2H), 2.33 (s, 3H), 1.34 (d,
    J = 7.1 Hz, 2H), 1.27-1.18 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 171.87,
    168.95, 162.24, 161.89, 159.95,
    159.44, 146.62, 141.38, 138.44,
    137.47, 136.77, 127.73, 116.74,
    116.58, 112.79, 112.62, 109.75, 75.32,
    56.29, 47.87, 38.50, 20.76, 19.89,
    18.40, 17.06, 16.72.
    182 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.53 (s,
    [M + H]+ calcd for 1H), 8.35 (d, J = 5.5 Hz, 1H), 7.22-
    C22H25FN2O6, 7.13 (m, 2H), 7.05-6.93 (m, 3H), 5.05
    433.1769; found, (h, J = 6.5 Hz, 1H), 4.71 (ddt, J = 14.7,
    433.1767 10.3, 5.3 Hz, 1H), 3.91 (s, 3H), 2.91 (p,
    J = 6.8 Hz, 1H), 2.41 (s, 3H), 1.48 (d,
    J = 7.2 Hz, 3H), 1.27 (d, J = 7.2 Hz, 3H),
    1.08 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.34,
    167.06, 160.68, 160.54, 158.74,
    157.59, 144.78, 139.51, 136.64,
    136.61, 135.58, 127.40, 127.34,
    113.37, 113.21, 107.93, 73.96, 54.42,
    46.14, 42.14, 18.85, 16.52, 15.76, 15.38.
    183 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    [M + H]+ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.09 (d,
    C24H30N2O7, J = 8.4 Hz, 1H), 7.02 (d, J = 5.5 Hz, 1H),
    459.2126; found, 6.75-6.66 (m, 2H), 5.15-5.05 (m,
    459.2096 1H), 4.72 (pd, J = 7.3, 1.5 Hz, 1H),
    3.92 (s, 3H), 3.76 (s, 3H), 3.16-3.07
    (m, 1H), 2.41 (s, 3H), 2.32 (s, 3H),
    1.50 (d, J = 7.2 Hz, 3H), 1.22 (d, J =
    6.8 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.45,
    167.03, 160.47, 157.55, 155.65,
    144.76, 139.57, 135.54, 135.02,
    132.00, 125.43, 113.97, 109.50,
    107.85, 74.52, 54.38, 53.17, 46.15,
    37.09, 18.83, 18.29, 16.63, 16.24, 15.80.
    184 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.52 (s,
    [M + H]+ calcd for 1H), 8.36 (d, J = 5.5 Hz, 1H), 7.11
    C25H31FN2O6, (ddd, J = 7.5, 5.9, 1.5 Hz, 1H), 7.02 (d,
    475.2239; found, J = 5.5 Hz, 1H), 6.83 (t, J = 8.1 Hz,
    475.2238 2H), 5.06 (dq, J = 8.1, 6.3 Hz, 1H),
    4.66 (dd, J = 9.4, 4.7 Hz, 1H), 3.92 (s,
    3H), 3.20-3.08 (m, 1H), 2.40 (s, 3H),
    2.32 (d, J = 2.3 Hz, 3H), 2.29 (td, J =
    6.9, 4.8 Hz, 1H), 1.23 (d, J = 6.9 Hz,
    3H), 1.11 (d, J = 6.2 Hz, 3H), 1.01 (d,
    J = 6.8 Hz, 3H), 0.93 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.24,
    168.92, 162.74, 161.89, 159.95,
    159.47, 146.68, 141.59, 137.81,
    137.76, 137.49, 127.86, 127.79,
    117.00, 116.83, 113.00, 112.83,
    109.75, 76.14, 57.17, 56.31, 39.04,
    31.46, 20.79, 20.00, 19.38, 18.45,
    17.47, 17.44.
    185 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.41 (s,
    [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.16 (dd,
    C25H31FN2O6, J = 9.0, 5.9 Hz, 1H), 7.01 (d, J = 5.4
    475.2239; found, Hz, 1H), 6.81 (t, J = 8.0 Hz, 2H), 5.15-
    475.2236 5.07 (m, 1H), 4.53 (dd, J = 9.5, 4.5
    Hz, 1H), 3.90 (s, 3H), 3.24-3.16 (m,
    1H), 2.38 (s, 3H), 2.34 (s, 3H), 1.88
    (td, J = 6.9, 4.5 Hz, 1H), 1.26 (d, J =
    6.2 Hz, 3H), 1.21 (d, J = 6.9 Hz, 3H),
    0.81 (d, J = 6.8 Hz, 3H), 0.63 (d, J =
    6.8 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.14,
    167.00, 160.78, 160.02, 158.08,
    157.53, 144.77, 139.62, 136.49,
    135.51, 135.45, 125.64, 125.57,
    114.82, 114.66, 110.95, 110.79,
    107.84, 73.69, 54.92, 54.40, 36.84,
    29.39, 18.86, 17.99, 17.09, 15.75,
    15.30, 15.12.
    186 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.43 (s,
    [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.24-
    C25H32N2O6, 7.19 (m, 1H), 7.09 (dddd, J = 29.3,
    457.2333; found, 14.6, 7.2, 2.9 Hz, 3H), 7.00 (d, J = 5.5
    457.2330 Hz, 1H), 5.14 (dq, J = 8.2, 6.2 Hz, 1H),
    4.53 (dd, J = 9.4, 4.3 Hz, 1H), 3.90 (s,
    3H), 3.26 (q, J = 7.4 Hz, 1H), 2.38 (s,
    3H), 2.36 (s, 3H), 1.91-1.78 (m, 1H),
    1.27 (d, J = 6.2 Hz, 3H), 1.25-1.20
    (m, 3H), 0.78 (d, J = 6.9 Hz, 3H), 0.58
    (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.16,
    166.97, 160.75, 157.48, 144.73,
    139.69, 135.46, 134.11, 128.31,
    124.26, 124.06, 107.75, 73.76, 54.85,
    54.36, 37.31, 29.36, 18.84, 17.91,
    17.07, 15.67, 15.06, 15.00.
    187 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.50 (d,
    [M + H]+ calcd for J = 9.8 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    C24H29FN2O6, 1H), 7.14 (dd, J = 8.6, 5.5 Hz, 2H),
    461.2082; found, 7.03 (d, J = 5.5 Hz, 1H), 6.94 (t, J =
    461.2082 8.7 Hz, 2H), 5.07-4.99 (m, 1H), 4.65
    (dd, J = 9.4, 4.7 Hz, 1H), 3.92 (s, 3H),
    2.93-2.86 (m, 1H), 2.40 (s, 3H), 2.26
    (pd, J = 6.8, 4.7 Hz, 1H), 1.28 (d, J =
    7.0 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H),
    0.99 (d, J = 6.9 Hz, 3H), 0.92 (d, J =
    6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.14,
    167.00, 160.80, 160.63, 158.69,
    157.57, 144.75, 139.63, 136.70,
    136.67, 135.57, 127.33, 127.27,
    113.31, 113.14, 107.86, 74.15, 55.24,
    54.40, 42.02, 29.52, 18.86, 17.37,
    16.09, 15.54, 15.21.
    188 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.53 (d,
    [M + H]+ calcd for J = 9.3 Hz, 1H), 8.36 (d, J = 5.5 Hz,
    C26H34N2O7, 1H), 7.07 (d, J = 9.5 Hz, 1H), 7.02 (d, J =
    487.2439; found, 5.5 Hz, 1H), 6.72-6.66 (m, 2H),
    487.2427 5.06 (dq, J = 8.5, 6.3 Hz, 1H), 4.67 (dd,
    J = 9.4, 4.6 Hz, 1H), 3.91 (s, 3H), 3.76
    (s, 3H), 3.15-3.06 (m, 1H), 2.40 (s,
    3H), 2.31 (m, 4H), 1.23 (d, J = 6.9 Hz,
    3H), 1.10 (d, J = 6.2 Hz, 3H), 1.02 (d,
    J = 6.8 Hz, 3H), 0.94 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.38,
    167.00, 160.80, 157.51, 155.65,
    144.76, 139.71, 135.53, 134.94,
    132.15, 125.41, 109.49, 107.80, 74.70,
    55.25, 54.37, 53.18, 37.08, 29.56,
    18.86, 18.27, 17.47, 16.60, 15.86, 15.53.
    189 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.61-
    [M + H]+ calcd for 8.47 (m, 1H), 8.36 (d, J = 5.4 Hz, 1H),
    C25H31FN2O6, 7.13 (dd, J = 9.6, 5.7 Hz, 1H), 7.02 (d,
    475.2239; found, J = 5.5 Hz, 1H), 6.88-6.79 (m, 2H),
    475.2238 5.09 (dq, J = 8.0, 6.3 Hz, 1H), 4.64 (dd,
    J = 9.1, 5.0 Hz, 1H), 3.92 (s, 3H), 3.13
    (p, J = 7.1 Hz, 1H), 2.41 (s, 3H), 2.33
    (s, 3H), 2.29 (qd, J = 7.0, 5.2 Hz, 1H),
    1.23 (d, J = 7.0 Hz, 3H), 1.12 (d, J =
    6.3 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H),
    0.96 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.44,
    167.00, 160.79, 159.96, 158.02,
    157.53, 144.78, 139.68, 135.91,
    135.53, 135.50, 125.99, 125.93,
    115.05, 114.89, 111.11, 110.95,
    107.83, 73.93, 55.11, 54.38, 37.14,
    29.57, 18.86, 18.10, 17.03, 16.32,
    16.00, 15.50.
    190 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.40 (s,
    [M + H]+ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.18 (dd,
    C25H31FN2O6, J = 9.5, 5.8 Hz, 1H), 7.02 (d, J = 5.5
    475.2239; found, Hz, 1H), 6.84-6.75 (m, 2H), 5.10 (p,
    475.2235 J = 6.4 Hz, 1H), 4.51 (dd, J = 9.2, 5.1
    Hz, 1H), 3.92 (s, 3H), 3.22 (p, J = 7.1
    Hz, 1H), 2.40 (s, 3H), 2.33 (s, 3H),
    2.15 (pd, J = 6.9, 5.0 Hz, 1H), 1.23 (d,
    J = 7.1 Hz, 3H), 1.21 (d, J = 6.3 Hz,
    3H), 0.88 (d, J = 6.9 Hz, 3H), 0.84 (d, J =
    6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.81,
    168.93, 162.52, 161.93, 159.99,
    159.45, 146.63, 141.52, 138.48,
    138.42, 137.46, 136.82, 136.79,
    127.88, 127.82, 116.75, 116.59,
    112.77, 112.61, 109.71, 75.30, 57.02,
    56.30, 38.43, 31.44, 20.78, 19.90,
    18.78, 17.72, 17.08, 16.67.
    191 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.42 (s,
    [M + H]+ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.23 (dd,
    C25H32N2O6, J = 7.8, 1.4 Hz, 1H), 7.15-7.03 (m,
    457.2333; found, 3H), 7.02 (d, J = 5.4 Hz, 1H), 5.13 (p,
    457.2331 J = 6.4 Hz, 1H), 4.53 (dd, J = 9.2, 4.9
    Hz, 1H), 3.91 (s, 3H), 3.28 (p, J = 7.1
    Hz, 1H), 2.40 (s, 3H), 2.36 (s, 3H),
    2.14 (pd, J = 6.9, 4.9 Hz, 1H), 1.26 (d,
    J = 7.2 Hz, 3H), 1.22 (d, J = 6.3 Hz,
    3H), 0.86 (d, J = 6.9 Hz, 3H), 0.81 (d,
    J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.77,
    168.93, 162.52, 159.43, 146.63,
    141.61, 141.09, 137.44, 136.15,
    130.25, 126.37, 126.20, 126.09,
    109.69, 75.37, 57.02, 56.29, 38.88,
    31.51, 20.79, 19.83, 18.77, 17.70,
    16.91, 16.26.
    192 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.58-
    [M + H]+ calcd for 8.45 (m, 1H), 8.36 (d, J = 5.5 Hz, 1H),
    C24H29FN2O6, 7.16 (ddd, J = 10.8, 6.6, 3.7 Hz, 2H),
    457.2333; found, 7.02 (d, J = 5.5 Hz, 1H), 7.01-6.94
    457.2331 (m, 2H), 5.10-4.99 (m, 1H), 4.63 (dd,
    J = 9.2, 5.0 Hz, 1H), 3.92 (s, 3H), 2.90
    (p, J = 7.1 Hz, 1H), 2.40 (d, J = 2.1 Hz,
    3H), 2.31-2.21 (m, 1H), 1.28 (d, J =
    7.0 Hz, 3H), 1.09 (d, J = 6.4 Hz, 3H),
    1.00-0.97 (m, 3H), 0.96 (d, J = 6.9
    Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.25,
    168.93, 162.72, 162.58, 160.64,
    159.46, 146.69, 141.58, 138.61,
    138.59, 137.46, 129.30, 129.23,
    115.28, 115.11, 109.76, 75.84, 57.06,
    56.31, 44.06, 31.47, 20.79, 18.93,
    17.96, 17.84, 17.26.
    193 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.62-
    [M + H]+ calcd for 8.50 (m, 1H), 8.36 (d, J = 5.4 Hz, 1H),
    C26H34N2O7, 7.10 (d, J = 8.4 Hz, 1H), 7.02 (d, J =
    487.2439; found, 5.5 Hz, 1H), 6.75-6.67 (m, 2H), 5.09
    487.2434 (dq, J = 8.4, 6.3 Hz, 1H), 4.65 (dd, J =
    9.1, 4.9 Hz, 1H), 3.91 (s, 3H), 3.75 (s,
    3H), 3.17-3.06 (m, 1H), 2.40 (s, 3H),
    2.32 (m, 4H), 1.22 (d, J = 6.9 Hz, 3H),
    1.11 (d, J = 6.2 Hz, 3H), 0.99 (d, J =
    6.8 Hz, 3H), 0.97 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.50,
    167.02, 160.80, 157.52, 155.67,
    144.82, 139.74, 135.53, 135.01,
    132.08, 125.49, 114.01, 109.51,
    107.84, 74.46, 55.12, 54.40, 53.18,
    37.11, 29.65, 18.89, 18.31, 17.06,
    16.41, 16.02, 15.83.
    194 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.45-
    [M + H]+ calcd for 8.36 (m, 1H), 8.33 (d, J = 5.5 Hz, 1H),
    C23H28N2O6, 7.25-7.17 (m, 1H), 7.17-7.03 (m,
    429.2020; found, 3H), 7.01 (d, J = 5.5 Hz, 1H), 5.18-
    429.2021 5.09 (m, 1H), 4.61-4.48 (m, 1H), 3.91
    (s, 3H), 3.28 (p, J = 7.3 Hz, 1H), 2.39
    (d, J = 5.8 Hz, 3H), 2.36 (s, 3H), 1.32
    (d, J = 7.2 Hz, 3H), 1.26 (d, J = 7.0 Hz,
    3H), 1.23 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 169.93,
    167.04, 160.36, 157.55, 144.72,
    139.53, 139.14, 135.53, 134.21,
    128.32, 124.37, 124.31, 107.85, 73.52,
    54.40, 46.07, 37.09, 18.84, 17.93,
    16.51, 15.05, 14.45.
    195 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.54 (d,
    [M + H]+ calcd for J = 7.4 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    C23H27FN2O6, 1H), 7.13 (dd, J = 9.5, 5.8 Hz, 1H),
    447.1926; found, 7.02 (d, J = 5.5 Hz, 1H), 6.88-6.81
    447.1922 (m, 2H), 5.09 (dq, J = 8.2, 6.3 Hz, 1H),
    4.72 (p, J = 7.3 Hz, 1H), 3.91 (s, 3H),
    3.20-3.09 (m, 1H), 2.41 (s, 3H), 2.33
    (s, 3H), 1.50 (d, J = 7.1 Hz, 3H), 1.23
    (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.39,
    167.02, 160.44, 159.98, 158.04,
    157.54, 144.76, 139.53, 135.94,
    135.88, 135.55, 135.49, 125.94,
    125.88, 115.11, 114.94, 111.06,
    110.90, 107.87, 74.14, 54.38, 46.21,
    37.21, 18.84, 18.08, 16.77, 16.43, 15.46.
    196 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.44 (s,
    [M + H]+ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.12
    C24H29FN2O6, (ddd, J = 9.3, 4.5, 2.0 Hz, 1H), 7.00 (d,
    461.2082; found, J = 5.5 Hz, 1H), 6.86 (dd, J = 9.0, 6.7
    461.2082 Hz, 2H), 5.12 (dq, J = 7.9, 6.3 Hz, 1H),
    4.18 (dd, J = 5.7, 2.8 Hz, 2H), 3.90 (s,
    3H), 3.14 (p, J = 7.1 Hz, 1H), 2.95 (p,
    J = 7.0 Hz, 1H), 2.32 (s, 3H), 1.37 (d,
    J = 7.0 Hz, 6H), 1.22 (d, J = 7.0 Hz, 3H),
    1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    169.37, 163.02, 161.95, 160.00,
    159.48, 146.62, 141.68, 137.91,
    137.73, 137.35, 137.32, 127.89,
    127.82, 117.05, 116.89, 113.04,
    112.87, 109.72, 76.09, 56.31, 41.38,
    39.11, 33.98, 20.01, 18.81, 18.22, 17.42.
    197 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.34 (d,
    [M + H]+ calcd for J = 5.0 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    C24H29FN2O6, 1H), 7.21-7.10 (m, 1H), 6.99 (d, J =
    461.2082; found, 5.4 Hz, 1H), 6.84-6.76 (m, 2H), 5.13
    461.2082 (p, J = 6.4 Hz, 1H), 4.17-3.92 (m,
    2H), 3.90-3.88 (s, 3H), 3.22 (p, J =
    7.1 Hz, 1H), 2.94 (p, J = 7.0 Hz, 1H),
    2.33 (s, 3H), 1.36 (d, J = 7.0 Hz, 6H),
    1.23 (dd, J = 6.7, 1.3 Hz, 6H).
    13C NMR (126 MHz, CDCl3) δ 174.69,
    169.03, 162.91, 161.95, 160.01,
    159.46, 146.58, 141.61, 138.48,
    137.71, 136.72, 136.69, 127.84,
    127.77, 116.78, 116.62, 112.83,
    112.67, 109.70, 75.49, 56.30, 41.22,
    38.58, 33.96, 19.87, 19.86, 18.80,
    17.11, 16.56.
    198 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.33 (m,
    [M + H]+ calcd for 2H), 7.21 (dd, J = 7.6, 1.5 Hz, 1H),
    C24H30N2O6, 7.10 (ttd, J = 14.3, 7.8, 7.3, 1.8 Hz,
    443.2177; found, 3H), 6.98 (d, J = 5.5 Hz, 1H), 5.17 (h,
    443.2174 J = 6.5 Hz, 1H), 4.14-3.90 (m, 2H),
    3.89 (s, 3H), 3.33-3.23 (m, 1H), 2.94
    (p, J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.36
    (d, J = 7.0 Hz, 6H), 1.28-1.19 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 174.69,
    169.05, 162.90, 159.44, 146.58,
    141.67, 141.02, 137.68, 136.17,
    130.25, 126.30, 126.27, 126.11,
    109.66, 75.58, 56.29, 41.22, 39.10,
    33.97, 19.80, 18.80, 18.75, 17.05, 16.24.
    199 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.44 (t,
    [M + H]+ calcd for J = 5.5 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C23H27FN2O6, 1H), 7.18-7.11 (m, 2H), 7.02-6.92
    447.1926; found, (m, 3H), 5.14-5.02 (m, 1H), 4.22-
    447.1926 4.13 (m, 2H), 3.90 (s, 3H), 3.02-2.84
    (m, 2H), 1.37 (d, J = 7.0 Hz, 6H), 1.30-
    1.23 (m, 3H), 1.09 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    169.27, 163.03, 162.63, 160.69,
    159.48, 146.62, 141.66, 138.52,
    137.74, 129.30, 129.23, 115.31,
    115.14, 109.73, 76.02, 56.31, 44.12,
    41.41, 33.98, 18.81, 17.81, 17.26.
    200 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.45 (t,
    [M + H]+ calcd for J = 5.4 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C25H32N2O7, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.00 (d,
    473.2282; found, J = 5.5 Hz, 1H), 6.77-6.67 (m, 2H),
    473.2275 5.12 (dq, J = 8.1, 6.2 Hz, 1H), 4.25-
    4.14 (m, 2H), 3.89 (s, 3H), 3.77 (s,
    3H), 3.16-3.05 (m, 1H), 2.96 (p, J =
    7.0 Hz, 1H), 2.31 (s, 3H), 1.37 (d, J =
    7.0 Hz, 6H), 1.22 (d, J = 7.0 Hz, 3H),
    1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    169.43, 163.02, 159.46, 157.66,
    146.63, 141.71, 137.71, 136.96,
    133.86, 127.39, 115.94, 111.46,
    109.70, 76.54, 56.30, 55.11, 41.41,
    39.04, 33.98, 20.18, 18.81, 18.27, 17.62.
    201 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.36 (s,
    [M + H]+ calcd for 1H), 8.31 (d, J = 5.4 Hz, 1H), 7.16
    C25H31FN2O6, (ddd, J = 13.0, 8.8, 6.0 Hz, 1H), 6.97
    475.2239; found, (d, J = 5.4 Hz, 1H), 6.81 (t, J = 7.8 Hz,
    475.2234 2H), 5.11 (dq, J = 8.3, 6.4 Hz, 1H),
    4.56 (p, J = 7.3 Hz, 1H), 3.88 (s, 3H),
    3.26-3.16 (m, 1H), 2.99-2.90 (m,
    1H), 2.34 (s, 3H), 1.35 (d, J = 6.9 Hz,
    6H), 1.27 (d, J = 6.3 Hz, 3H), 1.21 (d,
    J = 7.1 Hz, 3H), 1.08 (d, J = 7.1 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    172.20, 162.29, 161.91, 159.97,
    159.42, 146.55, 141.88, 138.36,
    138.30, 137.64, 137.22, 137.19,
    127.57, 127.50, 116.70, 116.54,
    112.85, 112.68, 109.58, 75.44, 56.28,
    47.83, 38.90, 33.93, 19.91, 18.80,
    18.20, 17.70, 17.22.
    202 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.35
    [M + H]+ calcd for (dd, J = 8.2, 5.5 Hz, 1H), 8.31 (d, J =
    C25H32N2O6, 5.4 Hz, 1H), 7.19 (dd, J = 7.7, 1.4 Hz,
    457.2333; found, 1H), 7.09 (ttd, J = 14.5, 7.2, 1.7 Hz,
    457.2331 3H), 6.97 (d, J = 5.4 Hz, 1H), 5.15 (dq,
    J = 7.7, 6.1 Hz, 1H), 4.60-4.45 (m,
    1H), 3.88 (s, 3H), 3.26 (dp, J = 14.7,
    7.2 Hz, 1H), 2.93 (p, J = 7.1 Hz, 1H),
    2.36 (s, 3H), 1.35 (d, J = 7.0 Hz, 6H),
    1.28 (d, J = 6.3 Hz, 3H), 1.24 (d, J =
    7.2 Hz, 3H), 1.01 (d, J = 7.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    172.25, 162.27, 159.39, 146.55,
    141.96, 141.54, 137.60, 136.03,
    130.21, 126.16, 125.98, 109.53, 77.28,
    75.56, 56.27, 47.84, 39.44, 33.93,
    19.84, 18.81, 18.14, 17.71, 17.01.
    203 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.46 (s,
    [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.15 (dd,
    C24H29FN2O6, J = 8.6, 5.5 Hz, 2H), 7.01-6.92 (m,
    461.2082; found, 3H), 5.09-5.00 (m, 1H), 4.71 (p, J =
    461.2082 7.3 Hz, 1H), 3.89 (s, 3H), 3.00-2.86
    (m, 2H), 1.47 (d, J = 7.1 Hz, 3H), 1.36
    (dd, J = 7.0, 1.3 Hz, 6H), 1.27 (d, J =
    7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    172.30, 162.61, 162.36, 160.67,
    159.46, 146.57, 141.90, 138.63,
    137.71, 129.29, 129.23, 115.27,
    115.10, 109.62, 75.96, 56.30, 48.10,
    44.13, 33.96, 18.81, 18.72, 17.93, 17.20.
    204 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.50 (d,
    [M + H]+ calcd for J = 9.7 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C26H34N2O7, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d,
    487.2439; found, J = 5.5 Hz, 1H), 6.76-6.66 (m, 2H),
    487.2431 5.08 (dq, J = 8.3, 6.2 Hz, 1H), 4.73 (p,
    J = 7.3 Hz, 1H), 3.89 (s, 3H), 3.77 (s,
    3H), 3.18-3.05 (m, 1H), 2.95 (p, J =
    7.0 Hz, 1H), 2.32 (s, 3H), 1.50 (d, J =
    7.2 Hz, 3H), 1.36 (dd, J = 7.0, 1.5 Hz,
    6H), 1.22 (d, J = 6.8 Hz, 3H), 1.11 (d,
    J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.70,
    172.48, 162.36, 159.43, 157.65,
    146.58, 141.96, 137.67, 136.91,
    134.03, 127.40, 115.92, 111.45,
    109.59, 76.46, 56.29, 55.12, 48.15,
    39.14, 33.95, 20.19, 18.81, 18.43, 17.63.
    205 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.51-
    [M + H]+ calcd for 8.39 (m, 1H), 8.34 (d, J = 5.3 Hz, 1H),
    C25H31FN2O6, 7.13 (dd, J = 9.4, 5.8 Hz, 1H), 6.99 (d,
    475.2239; found, J = 5.4 Hz, 1H), 6.87-6.81 (m, 2H),
    475.2239 5.09 (dq, J = 7.9, 6.2 Hz, 1H), 4.71 (p,
    J = 7.3 Hz, 1H), 3.89 (s, 3H), 3.13 (p,
    J = 7.1 Hz, 1H), 2.95 (p, J = 7.0 Hz, 1H),
    2.33 (s, 3H), 1.48 (d, J = 7.1 Hz, 3H),
    1.39-1.33 (m, 6H), 1.22 (d, J = 6.9
    Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    172.43, 162.41, 161.91, 159.97,
    159.46, 146.57, 141.90, 137.88,
    137.82, 137.47, 127.91, 127.85,
    117.01, 116.84, 113.03, 112.87,
    109.63, 75.88, 56.30, 48.01, 39.13,
    33.96, 20.02, 18.81, 18.50, 18.12, 17.48.
    206 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.35-
    [M + H]+ calcd for 8.27 (m, 2H), 7.22 (dd, J = 7.7, 1.4 Hz,
    C25H32N2O6, 1H), 7.17-7.03 (m, 3H), 6.98 (d, J =
    457.2333; found, 5.4 Hz, 1H), 5.14 (p, J = 6.5 Hz, 1H),
    457.2332 4.56 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H),
    3.28 (p, J = 7.0 Hz, 1H), 2.94 (p, J =
    7.0 Hz, 1H), 2.35 (s, 3H), 1.39-1.34
    (m, 6H), 1.31 (d, J = 7.2 Hz, 3H), 1.25
    (d, J = 7.1 Hz, 3H), 1.22 (d, J = 6.4 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.70,
    171.97, 162.25, 159.43, 146.50,
    141.92, 141.08, 137.66, 136.14,
    130.23, 126.33, 126.21, 126.09,
    109.55, 75.33, 56.29, 47.95, 39.03,
    33.95, 19.82, 18.81, 18.47, 16.96, 16.35.
    207 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.45 (s,
    [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.20-
    C24H29FN2O6, 7.12 (m, 2H), 7.02-6.94 (m, 3H), 5.10-
    461.2082; found, 4.99 (m, 1H), 4.70 (p, J = 7.3 Hz,
    461.2082 1H), 3.89 (s, 3H), 2.94 (ddt, J = 15.3,
    14.2, 7.1 Hz, 2H), 1.47 (d, J = 7.1 Hz,
    3H), 1.38-1.34 (m, 6H), 1.27 (d, J =
    6.9 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.72,
    172.36, 162.62, 162.44, 160.67,
    159.46, 146.57, 141.88, 138.58,
    137.70, 129.33, 129.26, 115.28,
    115.11, 109.63, 75.77, 56.30, 48.03,
    44.07, 33.96, 18.81, 18.46, 17.65, 17.30.
    208 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.49 (d,
    [M + H]+ calcd for J = 5.7 Hz, 1H), 8.34 (d, J = 5.5 Hz,
    C26H34N2O7, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d,
    487.2439; found, J = 5.4 Hz, 1H), 6.75-6.67 (m, 2H),
    487.2432 5.09 (dq, J = 8.2, 6.2 Hz, 1H), 4.72 (p,
    J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.76 (s,
    3H), 3.15-3.05 (m, 1H), 2.96 (p, J =
    7.0 Hz, 1H), 2.32 (s, 3H), 1.49 (d, J =
    7.2 Hz, 3H), 1.39-1.34 (m, 6H), 1.21
    (d, J = 6.9 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    172.49, 162.41, 159.44, 157.62,
    146.58, 141.96, 137.67, 136.95,
    134.00, 127.40, 115.94, 111.45,
    109.60, 76.36, 56.29, 55.10, 48.06,
    39.08, 33.96, 20.21, 18.82, 18.58,
    18.19, 17.74.
    209 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.44 (d,
    [M + H]+ calcd for J = 9.0 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    C27H35FN2O6, 1H), 7.16-7.08 (m, 1H), 6.99 (d, J =
    503.2552; found, 5.5 Hz, 1H), 6.82 (t, J = 7.9 Hz, 2H),
    503.2547 5.06 (dq, J = 8.0, 6.2 Hz, 1H), 4.66 (dd,
    J = 9.4, 4.8 Hz, 1H), 3.89 (s, 3H), 3.20-
    3.09 (m, 1H), 2.95 (p, J = 7.0 Hz,
    1H), 2.32 (s, 3H), 2.28 (qd, J = 7.0, 4.9
    Hz, 1H), 1.39-1.32 (m, 6H), 1.23 (d,
    J = 6.9 Hz, 3H), 1.11 (d, J = 6.2 Hz,
    3H), 1.01 (d, J = 6.8 Hz, 3H), 0.92 (d, J =
    6.8 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.67,
    171.34, 162.74, 161.92, 159.98,
    159.45, 146.56, 142.09, 137.82,
    137.67, 137.55, 127.90, 127.83,
    117.00, 116.83, 113.00, 112.84,
    109.59, 76.07, 57.14, 56.29, 39.10,
    33.94, 31.48, 19.99, 19.38, 18.82,
    18.47, 17.46.
    210 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.32 (m,
    [M + H]+ calcd for 2H), 7.16 (dd, J = 9.5, 5.7 Hz, 1H),
    C27H35FN2O7, 6.98 (d, J = 5.5 Hz, 1H), 6.83-6.76
    503.2552; found, (m, 2H), 5.10 (dq, J = 8.0, 6.3 Hz, 1H),
    503.2554 4.54 (dd, J = 9.4, 4.5 Hz, 1H), 3.88 (s,
    3H), 3.19 (p, J = 7.2 Hz, 1H), 2.93 (p,
    J = 7.0 Hz, 1H), 2.34 (s, 3H), 1.88 (pd,
    J = 6.9, 4.5 Hz, 1H), 1.34 (d, J = 7.0 Hz,
    6H), 1.25 (d, J = 6.3 Hz, 3H), 1.21 (d,
    J = 7.1 Hz, 3H), 0.81 (d, J = 6.9 Hz, 3H),
    0.63 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.66,
    171.16, 162.69, 161.96, 160.03,
    159.41, 146.55, 142.06, 138.40,
    138.34, 137.62, 137.32, 127.61,
    116.73, 116.57, 112.86, 112.70,
    109.54, 75.49, 56.79, 56.28, 38.77,
    33.92, 31.34, 19.89, 19.01, 18.82,
    17.63, 17.17, 17.05.
    211 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.38-
    [M + H]+ calcd for 8.27 (m, 2H), 7.21 (dd, J = 7.8, 1.3 Hz,
    C25H36N2O6, 1H), 7.09 (dddd, J = 23.7, 14.5, 7.3, 1.6
    485.2646; found, Hz, 3H), 6.97 (d, J = 5.5 Hz, 1H), 5.14
    485.2642 (dq, J = 6.8, 5.8, 5.3 Hz, 1H), 4.54 (dd,
    J = 9.5, 4.4 Hz, 1H), 3.88 (s, 3H), 3.26
    (dp, J = 14.6, 7.1 Hz, 1H), 2.93 (p, J =
    6.9 Hz, 1H), 2.36 (d, J = 3.7 Hz, 3H),
    1.85 (pd, J = 6.9, 4.4 Hz, 1H), 1.34 (d,
    J = 7.0 Hz, 6H), 1.27 (d, J = 6.3 Hz,
    3H), 1.23 (d, J = 7.1 Hz, 3H), 0.78 (d,
    J = 6.9 Hz, 3H), 0.58 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.65,
    171.20, 162.68, 159.38, 146.55,
    142.13, 141.63, 137.58, 136.06,
    130.25, 126.19, 126.05, 109.49, 75.58,
    56.75, 56.29, 39.27, 33.92, 31.33,
    19.82, 19.02, 18.81, 17.57, 17.02, 16.89.
    212 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.42 (d,
    [M + H]+ calcd for J = 9.0 Hz, 1H), 8.34 (d, J = 5.5 Hz,
    C26H33FN2O6, 1H), 7.14 (dd, J = 8.6, 5.5 Hz, 2H),
    489.2395; found, 7.00 (d, J = 5.5 Hz, 1H), 6.97-6.89
    489.2391 (m, 2H), 5.03 (p, J = 6.4 Hz, 1H), 4.65
    (dd, J = 9.4, 4.7 Hz, 1H), 3.89 (s, 3H),
    3.00-2.85 (m, 2H), 2.25 (pd, J = 6.9,
    4.7 Hz, 1H), 1.38-1.31 (m, 6H), 1.28
    (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    3H), 0.99 (d, J = 6.9 Hz, 3H), 0.91 (d,
    J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    171.17, 162.73, 162.59, 160.64,
    159.46, 146.56, 142.06, 138.69,
    137.69, 129.27, 129.21, 115.23,
    115.07, 109.60, 76.00, 57.13, 56.30,
    43.99, 33.94, 31.47, 19.30, 18.81,
    18.02, 17.49, 17.14.
    213 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.45 (d,
    [M + H]+ calcd for J = 8.6 Hz, 1H), 8.34 (d, J = 5.5 Hz,
    C28H38N2O7, 1H), 7.07 (d, J = 9.4 Hz, 1H), 6.99 (d,
    515.2752; found, J = 5.5 Hz, 1H), 6.72-6.65 (m, 2H),
    515.2737 5.06 (dq, J = 8.3, 6.2 Hz, 1H), 4.67 (dd,
    J = 9.3, 4.7 Hz, 1H), 3.89 (s, 3H), 3.76
    (s, 3H), 3.16-3.05 (m, 1H), 2.95 (p,
    J = 7.0 Hz, 1H), 2.35-2.25 (m, 3H),
    1.40-1.30 (m, 6H), 1.23 (d, J = 6.9
    Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H), 1.01
    (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.67,
    171.40, 162.75, 159.43, 157.63,
    146.57, 142.14, 137.65, 136.86,
    134.14, 127.37, 115.93, 111.45,
    109.57, 76.57, 60.39, 57.17, 56.29,
    55.12, 39.07, 33.94, 31.51, 20.18,
    19.40, 18.82, 18.54, 17.77, 17.48, 14.20.
    214 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.44 (d,
    [M + H]+ calcd for J = 9.1 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    C27H35FN2O6, 1H), 7.13 (dd, J = 9.6, 5.8 Hz, 1H),
    503.2552; found, 7.00 (d, J = 5.4 Hz, 1H), 6.88-6.78
    503.2549 (m, 2H), 5.09 (dq, J = 8.1, 6.3 Hz, 1H),
    4.63 (dd, J = 9.1, 5.2 Hz, 1H), 3.89 (s,
    3H), 3.13 (p, J = 7.1 Hz, 1H), 2.95 (p,
    J = 7.0 Hz, 1H), 2.32 (s, 3H), 2.26 (pd,
    J = 6.8, 4.9 Hz, 1H), 1.41-1.31 (m,
    6H), 1.23 (d, J = 6.9 Hz, 3H), 1.11 (d,
    J = 6.3 Hz, 3H), 0.99 (d, J = 7.0 Hz, 3H),
    0.96 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    171.48, 162.75, 161.91, 159.97,
    159.44, 146.59, 142.11, 137.84,
    137.64, 137.49, 127.88, 116.98,
    116.81, 113.04, 112.88, 109.58, 75.80,
    57.04, 56.29, 39.14, 33.95, 31.48,
    20.01, 19.00, 18.81, 18.26, 17.94, 17.46.
    215 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.38-
    [M + H]+ calcd for 8.28 (m, 2H), 7.25-7.20 (m, 1H), 7.16-
    C27H36N2O6, 7.02 (m, 3H), 6.99 (d, J = 5.4 Hz,
    485.2646; found, 1H), 5.13 (p, J = 6.4 Hz, 1H), 4.53 (dd,
    485.2643 J = 9.1, 4.9 Hz, 1H), 3.89 (s, 3H), 3.28
    (p, J = 7.1 Hz, 1H), 2.94 (h, J = 7.0 Hz,
    1H), 2.35 (s, 3H), 2.21-2.09 (m, 1H),
    1.35 (dd, J = 7.0, 1.2 Hz, 6H), 1.26 (d,
    J = 7.1 Hz, 3H), 1.21 (d, J = 6.2 Hz,
    3H), 0.86 (d, J = 6.9 Hz, 3H), 0.81 (d,
    J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    170.88, 162.55, 159.42, 146.51,
    142.10, 141.12, 137.63, 136.16,
    130.26, 126.41, 126.19, 126.09,
    109.52, 75.28, 57.01, 56.29, 38.91,
    33.94, 31.50, 19.81, 18.81, 17.71,
    16.90, 16.26.
    216 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.48-
    [M + H]+ calcd for 8.39 (m, 1H), 8.34 (d, J = 5.4 Hz, 1H),
    C26H33FN2O6, 7.19-7.11 (m, 2H), 7.03-6.90 (m,
    489.2395; found, 3H), 5.05 (m, 1H), 4.62 (dd, J = 9.1,
    489.2391 5.1 Hz, 1H), 3.89 (s, 3H), 2.92 (dp, J =
    26.1, 7.0 Hz, 2H), 2.25 (pd, J = 6.9, 4.2
    Hz, 1H), 1.38-1.32 (m, 6H), 1.27 (d,
    J = 7.1 Hz, 3H), 1.08 (d, J = 6.2 Hz,
    3H), 0.98 (d, J = 6.9 Hz, 3H), 0.95 (d,
    J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    171.37, 162.76, 162.61, 160.67,
    159.44, 146.59, 142.08, 138.67,
    137.64, 129.32, 129.26, 115.27,
    115.10, 109.59, 75.75, 57.06, 56.30,
    44.10, 33.95, 31.45, 18.97, 18.81,
    17.97, 17.84, 17.27.
    217 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.46 (d,
    [M + H]+ calcd for J = 9.0 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    C28H38N2O7, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.99 (d,
    515.2752; found, J = 5.5 Hz, 1H), 6.75-6.66 (m, 2H),
    515.2741 5.09 (dq, J = 8.3, 6.2 Hz, 1H), 4.65 (dd,
    J = 9.1, 5.0 Hz, 1H), 3.89 (s, 3H), 3.75
    (s, 3H), 3.16-3.04 (m, 1H), 2.95 (p,
    J = 7.0 Hz, 1H), 2.31 (s, 3H), 2.27 (qd,
    J = 6.9, 5.0 Hz, 1H), 1.39-1.32 (m,
    6H), 1.22 (d, J = 6.9 Hz, 3H), 1.10 (d,
    J = 6.3 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H),
    0.96 (d, J = 6.9 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    171.52, 162.73, 159.42, 157.61,
    146.60, 142.18, 137.62, 136.92,
    134.06, 127.42, 115.96, 111.44,
    109.55, 76.31, 57.04, 56.29, 55.10,
    39.09, 33.94, 31.54, 20.20, 19.00,
    18.82, 18.33, 17.94, 17.77.
    218 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.37-
    [M + H]+ calcd for 8.28 (m, 2H), 7.22-7.12 (m, 1H), 6.99
    C25H31FN2O6, (d, J = 5.5 Hz, 1H), 6.85-6.75 (m,
    475.2239; found, 2H), 5.16-5.05 (m, 1H), 4.57 (h, J =
    475.2236 7.4 Hz, 1H), 3.89 (s, 3H), 3.22 (pd, J =
    7.3, 4.6 Hz, 1H), 3.00-2.89 (m, 1H),
    2.33 (s, 3H), 1.39-1.30 (m, 9H), 1.22
    (dd, J = 9.8, 6.7 Hz, 6H).
    13C NMR (126 MHz, CDCl3) δ 174.70,
    171.98, 162.25, 161.93, 159.99,
    159.45, 146.51, 141.82, 138.46,
    137.69, 136.79, 136.76, 127.85,
    127.79, 116.74, 116.58, 112.79,
    112.62, 109.59, 75.24, 56.30, 47.88,
    38.53, 33.95, 19.88, 18.80, 18.41,
    17.05, 16.71.
    219 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.48 (d,
    [M + H]+ calcd for J = 6.9 Hz, 1H), 8.33 (d, J = 5.3 Hz,
    C25H31FN2O6, 1H), 7.13 (dd, J = 9.4, 5.8 Hz, 1H),
    475.2239; found, 6.99 (d, J = 5.5 Hz, 1H), 6.88-6.81
    475.2238 (m, 2H), 5.09 (dp, J = 8.1, 6.5 Hz, 1H),
    4.72 (p, J = 7.2 Hz, 1H), 3.89 (s, 3H),
    3.14 (p, J = 7.1 Hz, 1H), 2.95 (p, J =
    7.0 Hz, 1H), 2.33 (d, J = 2.4 Hz, 3H),
    1.49 (d, J = 7.1 Hz, 3H), 1.38-1.33
    (m, 6H), 1.23 (d, J = 6.9 Hz, 3H), 1.11
    (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    172.42, 162.36, 161.94, 159.99,
    159.45, 146.58, 141.91, 137.86,
    137.80, 137.69, 137.46, 127.91,
    127.84, 117.04, 116.87, 113.00,
    112.83, 109.62, 75.99, 56.30, 48.11,
    39.18, 33.96, 20.00, 19.99, 18.85,
    18.81, 18.36, 17.37.
    220 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    [M + H]+ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.09 (d,
    C24H30N2O7, J = 8.4 Hz, 1H), 7.02 (d, J = 5.5 Hz, 1H),
    459.2126; found, 6.77-6.67 (m, 2H), 5.10 (dq, J = 8.3,
    459.2103 6.3 Hz, 1H), 4.72 (tt, J = 8.8, 6.2 Hz,
    1H), 3.91 (s, 3H), 3.76 (s, 3H), 3.15-
    3.06 (m, 1H), 2.41 (s, 3H), 2.32 (s,
    3H), 1.50 (d, J = 7.2 Hz, 3H), 1.22 (d,
    J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 170.46,
    167.04, 160.48, 157.55, 155.66,
    144.77, 139.57, 135.54, 135.03,
    132.01, 125.44, 113.97, 109.50,
    107.87, 74.52, 54.39, 53.17, 46.15,
    37.09, 18.84, 18.30, 16.63, 16.25, 15.80.
    221 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.44 (t,
    [M + H]+ calcd for J = 5.4 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    C24H29FN2O6, 1H), 7.12 (ddd, J = 10.1, 6.2, 3.4 Hz,
    461.2082; found, 1H), 7.00 (d, J = 5.5 Hz, 1H), 6.90-
    461.2080 6.80 (m, 3H), 5.12 (dq, J = 7.7, 6.2 Hz,
    1H), 4.18 (dd, J = 5.4, 2.8 Hz, 2H),
    3.90 (s, 3H), 3.14 (p, J = 7.1 Hz, 1H),
    2.95 (p, J = 7.0 Hz, 1H), 2.32 (s, 3H),
    1.37 (d, J = 7.0 Hz, 6H), 1.22 (d, J =
    6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    169.37, 163.02, 161.95, 160.00,
    159.48, 146.63, 141.67, 137.91,
    137.85, 137.73, 137.32, 127.89,
    127.82, 117.05, 116.89, 113.04,
    112.87, 109.72, 76.09, 56.31, 41.38,
    39.11, 33.98, 20.00, 18.81, 18.71,
    18.22, 17.42.
    222 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.36-
    [M + H]+ calcd for 8.27 (m, 2H), 7.21 (dd, J = 7.7, 1.4 Hz,
    C24H30N2O6, 1H), 7.16-7.05 (m, 3H), 6.98 (d, J =
    443.2177; found, 5.5 Hz, 1H), 5.17 (h, J = 6.6 Hz, 1H),
    443.2176 4.13-3.89 (m, 2H), 3.89 (s, 3H), 3.28
    (p, J = 7.1 Hz, 1H), 2.94 (p, J = 7.0 Hz,
    1H), 2.35 (s, 3H), 1.36 (d, J = 7.0 Hz,
    6H), 1.28-1.22 (m, 6H).
    13C NMR (126 MHz, CDCl3) δ 174.69,
    169.05, 162.90, 159.44, 146.58,
    141.67, 141.02, 137.68, 136.17,
    130.25, 126.29, 126.27, 126.11,
    109.66, 75.58, 56.29, 41.22, 39.09,
    33.97, 19.80, 18.81, 17.05, 16.23.
    223 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.44 (t,
    [M + H]+ calcd for J = 5.5 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C23H27FN2O6, 1H), 7.18-7.11 (m, 2H), 7.03-6.92
    447.1926; found, (m, 3H), 5.14-5.01 (m, 1H), 4.17 (d,
    447.1923 J = 5.4 Hz, 2H), 3.90 (s, 3H), 3.00-2.86
    (m, 2H), 1.37 (d, J = 7.0 Hz, 6H), 1.27
    (d, J = 7.0 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.72,
    169.28, 163.04, 162.64, 160.69,
    159.48, 146.62, 141.66, 138.52,
    137.74, 129.30, 129.24, 115.31,
    115.14, 109.73, 76.02, 56.31, 44.12,
    41.41, 33.98, 18.81, 17.81, 17.26.
    224 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.45 (t,
    [M + H]+ calcd for J = 5.4 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C25H32N2O7, 1H), 7.08 (d, J = 8.5 Hz, 1H), 7.00 (d,
    473.2282; found, J = 5.5 Hz, 1H), 6.76-6.67 (m, 2H),
    473.2282 5.12 (dq, J = 8.3, 6.3 Hz, 1H), 4.24-
    4.14 (m, 2H), 3.89 (s, 3H), 3.77 (s,
    3H), 3.16-3.05 (m, 1H), 2.96 (p, J =
    7.0 Hz, 1H), 2.31 (s, 3H), 1.37 (d, J =
    7.0 Hz, 6H), 1.22 (d, J = 6.9 Hz, 3H),
    1.12 (d, J = 6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    169.43, 163.01, 159.46, 157.66,
    146.63, 141.71, 137.71, 136.96,
    133.86, 127.39, 115.94, 111.46,
    109.70, 76.54, 56.30, 55.11, 41.41,
    39.04, 33.98, 20.18, 18.81, 18.27, 17.62.
    225 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.39-
    [M + H]+ calcd for 8.28 (m, 2H), 7.24-7.17 (m, 1H), 7.16-
    C25H32N2O6, 7.02 (m, 3H), 6.98 (d, J = 5.5 Hz,
    457.2333; found, 1H), 5.14 (p, J = 6.6 Hz, 1H), 4.55 (dt,
    457.2327 J = 10.4, 7.4 Hz, 1H), 3.89 (s, 3H),
    3.28 (p, J = 7.1 Hz, 1H), 2.94 (p, J =
    6.9 Hz, 1H), 2.36 (d, J = 4.9 Hz, 3H),
    1.36 (dd, J = 7.0, 1.6 Hz, 6H), 1.31 (d,
    J = 7.1 Hz, 3H), 1.25 (d, J = 7.2 Hz,
    3H), 1.22 (d, J = 6.4 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.70,
    171.96, 162.25, 159.42, 146.50,
    141.92, 141.08, 137.65, 136.14,
    130.23, 126.33, 126.21, 126.09,
    109.55, 75.32, 56.29, 47.95, 39.03,
    33.95, 19.82, 18.80, 18.47, 16.95, 16.35.
    226 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.44 (s,
    [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.20-
    C24H29FN2O6, 7.12 (m, 2H), 7.02-6.93 (m, 3H), 5.07-
    461.2082; found, 4.97 (m, 1H), 4.70 (p, J = 7.2 Hz,
    461.2078 1H), 3.90 (s, 3H), 3.01-2.86 (m, 2H),
    1.47 (d, J = 7.1 Hz, 3H), 1.39-1.34
    (m, 6H), 1.27 (d, J = 7.0 Hz, 3H), 1.07
    (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.72,
    172.36, 162.62, 162.44, 160.67,
    159.46, 146.57, 141.88, 138.56,
    137.70, 129.33, 129.26, 115.28,
    115.11, 109.63, 75.77, 56.30, 48.03,
    44.07, 33.96, 18.81, 18.46, 17.65, 17.30.
    227 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.49 (d,
    [M + H]+ calcd for J = 8.6 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    C26H34N2O7, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d,
    487.2439; found, J = 5.4 Hz, 1H), 6.75-6.64 (m, 2H),
    487.2425 5.09 (dq, J = 8.3, 6.2 Hz, 1H), 4.72 (p,
    J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.76 (s,
    3H), 3.16-3.05 (m, 1H), 2.96 (p, J =
    7.0 Hz, 1H), 2.32 (s, 3H), 1.49 (d, J =
    7.1 Hz, 3H), 1.39-1.34 (m, 6H), 1.21
    (d, J = 6.8 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    172.49, 162.41, 159.44, 157.62,
    146.58, 141.97, 137.67, 136.95,
    134.01, 127.40, 115.94, 111.45,
    109.59, 76.36, 56.29, 55.11, 48.06,
    39.08, 33.96, 20.21, 18.82, 18.58,
    18.19, 17.74.
    228 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.40-
    [M + H]+ calcd for 8.33 (m, 1H), 8.31 (d, J = 5.4 Hz, 1H),
    C25H32N2O6, 7.22-7.15 (m, 1H), 7.15-7.03 (m,
    457.2333; found, 3H), 6.97 (d, J = 5.4 Hz, 1H), 5.15 (dq,
    457.2329 J = 8.0, 6.2 Hz, 1H), 4.61-4.47 (m,
    1H), 3.88 (s, 3H), 3.25 (p, J = 7.3 Hz,
    1H), 2.93 (p, J = 7.0 Hz, 1H), 2.36 (d,
    J = 3.5 Hz, 3H), 1.35 (d, J = 7.0 Hz, 6H),
    1.28 (d, J = 6.3 Hz, 3H), 1.24 (d, J =
    7.0 Hz, 3H), 1.01 (d, J = 7.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.68,
    172.25, 162.26, 159.39, 146.54,
    141.96, 141.54, 137.60, 136.03,
    130.21, 126.16, 125.98, 109.53, 75.56,
    56.27, 47.84, 39.43, 33.93, 19.84,
    18.80, 17.71, 17.01.
    229 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.46 (d,
    [M + H]+ calcd for J = 8.6 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C24H29FN2O6, 1H), 7.18-7.10 (m, 2H), 7.01-6.89
    461.2082; found, (m, 3H), 5.09-5.00 (m, 1H), 4.71 (p,
    461.2077 J = 7.3 Hz, 1H), 3.89 (d, J = 1.2 Hz, 3H),
    3.01-2.86 (m, 2H), 1.47 (dd, J = 7.2,
    1.8 Hz, 3H), 1.39-1.34 (m, 6H), 1.27
    (dd, J = 7.1, 1.6 Hz, 3H), 1.09 (d, J =
    6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    172.29, 162.61, 162.36, 160.66,
    159.46, 146.57, 141.89, 138.63,
    137.70, 129.33, 129.29, 129.26,
    115.27, 115.10, 109.63, 75.95, 56.30,
    48.10, 44.13, 33.96, 18.81, 18.71,
    17.93, 17.20.
    230 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.50 (d,
    [M + H]+ calcd for J = 8.7 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C26H34N2O7, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 (d,
    487.2439; found, J = 5.5 Hz, 1H), 6.77-6.66 (m, 2H),
    X487.2423 5.08 (dq, J = 8.3, 6.2 Hz, 1H), 4.73 (p,
    J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.77 (s,
    3H), 3.17-3.05 (m, 1H), 2.95 (p, J =
    7.0 Hz, 1H), 2.32 (s, 3H), 1.50 (d, J =
    7.2 Hz, 3H), 1.38-1.33 (m, 6H), 1.22
    (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 174.71,
    172.49, 162.36, 159.43, 157.65,
    146.58, 141.97, 137.67, 136.91,
    134.03, 127.40, 115.92, 111.45,
    109.59, 76.46, 56.29, 55.12, 48.15,
    39.14, 33.95, 20.19, 18.79, 18.43, 17.63.
    231 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.26 (d,
    [M + H]+ calcd for J = 5.4 Hz, 1H), 8.22 (t, J = 7.4 Hz,
    C24H30N2O7, 1H), 7.22-7.03 (m, 4H), 6.93 (d, J =
    459.2126; found, 5.4 Hz, 1H), 5.73 (dd, J = 5.6, 1.8 Hz,
    459.2121 2H), 5.16 (dq, J = 8.1, 6.3 Hz, 1H),
    4.58-4.51 (m, 1H), 3.90 (s, 3H), 3.31-
    3.22 (m, 1H), 2.37 (s, 3H), 2.06 (s,
    3H), 1.31 (d, J = 6.2 Hz, 3H), 1.24 (d,
    J = 7.0 Hz, 3H), 1.03 (d, J = 7.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.26,
    170.26, 162.87, 160.25, 145.68,
    143.94, 142.57, 141.57, 136.03,
    130.21, 126.16, 125.94, 109.49, 89.57,
    75.57, 56.16, 48.08, 39.48, 20.87,
    19.84, 17.92, 17.77, 17.05.
    232 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.33 (d,
    [M + H]+ calcd for J = 7.4 Hz, 1H), 8.29 (d, J = 5.3 Hz,
    C23H27FN2O7, 1H), 7.20-7.12 (m, 2H), 7.01-6.93
    463.1875; found, (m, 3H), 5.79-5.71 (m, 2H), 5.10-
    463.1870 5.00 (m, 1H), 4.73 (p, J = 7.2 Hz, 1H),
    3.92 (d, J = 2.0 Hz, 3H), 2.92 (p, J =
    7.1 Hz, 1H), 2.07 (d, J = 1.6 Hz, 3H),
    1.50 (d, J = 7.1 Hz, 3H), 1.29 (dd, J =
    7.0, 2.5 Hz, 3H), 1.08 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.37,
    170.29, 163.02, 162.63, 160.68,
    160.30, 145.74, 144.03, 142.51,
    138.55, 138.52, 129.32, 129.26,
    115.30, 115.13, 109.59, 89.58, 75.82,
    56.20, 48.22, 44.12, 20.88, 18.39,
    17.69, 17.39.
    233 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.38 (d,
    [M + H]+ calcd for J = 7.7 Hz, 1H), 8.29 (d, J = 5.3 Hz,
    C25H32N2O8, 1H), 7.09 (d, J = 8.3 Hz, 1H), 6.96 (d,
    489.2231; found, J = 5.3 Hz, 1H), 6.79-6.62 (m, 2H),
    489.2220 5.76 (d, J = 2.2 Hz, 2H), 5.17-5.05
    (m, 1H), 4.75 (p, J = 7.2 Hz, 1H), 3.92
    (s, 3H), 3.76 (s, 3H), 3.22-3.03 (m,
    1H), 2.32 (s, 3H), 2.07 (s, 3H), 1.52 (d,
    J = 7.2 Hz, 3H), 1.23 (d, J = 6.9 Hz,
    3H), 1.10 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.52,
    170.29, 162.99, 160.29, 157.63,
    145.74, 144.02, 142.57, 136.96,
    133.96, 127.39, 115.93, 111.48,
    109.55, 89.61, 76.42, 56.19, 55.11,
    48.23, 39.10, 20.88, 20.21, 18.51,
    18.21, 17.82.
    234 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.50 (d,
    film) 3383, [M + H]+ calcd for J = 7.4 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2981, 1737, C25H30F3N2O6, 1H), 7.64 (dd, J = 8.0, 1.3 Hz, 1H),
    1679, 1505, 511.2050; found, 7.54-7.47 (m, 1H), 7.44 (d, J = 7.8
    1310, 1114, 511.2048 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H), 6.99
    1045, 732 (d, J = 5.4 Hz, 1H), 5.26-5.11 (m,
    cm−1 1H), 4.76 (p, J = 7.3 Hz, 1H), 3.89 (s,
    3H), 3.34 (p, J = 6.6 Hz, 1H), 2.96
    (hept, J = 7.0 Hz, 1H), 1.54 (d, J = 7.2
    Hz, 3H), 1.36 (dd, J = 7.0, 1.3 Hz, 6H),
    1.28 (d, J = 6.8 Hz, 3H), 1.10 (d, J =
    6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.25.
    235 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.47 (d,
    film) 3383, [M + H]+ calcd for J = 8.1 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2982, 1761, C25H29F4N2O6, 1H), 7.42 (dd, J = 8.8, 5.4 Hz, 1H),
    1738, 1679, 529.1956; found, 7.34 (dd, J = 9.2, 2.8 Hz, 1H), 7.21 (td,
    1500, 1312, 529.1954 J = 8.3, 2.8 Hz, 1H), 7.00 (d, J = 5.5
    1119, 909, Hz, 1H), 5.13 (p, J = 6.5 Hz, 1H), 4.75
    732 cm−1 (dq, J = 9.3, 7.3 Hz, 1H), 3.89 (s, 3H),
    3.36-3.24 (m, 1H), 2.95 (hept, J = 7.0
    Hz, 1H), 1.53 (d, J = 7.2 Hz, 3H), 1.36
    (dd, J = 7.0, 1.5 Hz, 6H), 1.26 (d, J =
    6.8 Hz, 3H), 1.11 (d, J = 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.80, −114.13.
    236 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.53 (d,
    film) 3383, [M + H]+ calcd for J = 7.7 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    2943, 1763, C23H35N2O6, 1H), 6.98 (d, J = 5.4 Hz, 1H), 5.08 (qd,
    1733, 1678, 435.2490; found, J = 6.5, 3.0 Hz, 1H), 4.69 (dt, J = 7.9,
    1504, 1310, 435.2483 7.0 Hz, 1H), 3.89 (s, 3H), 3.02-2.87
    1210, 1090, (m, 1H), 1.74 (dddd, J = 19.4, 17.2,
    843, 731 9.8, 5.1 Hz, 3H), 1.67-1.51 (m, 4H),
    cm−1 1.48 (d, J = 7.1 Hz, 3H), 1.36 (d, J =
    7.0 Hz, 6H), 1.22 (d, J = 6.4 Hz, 3H),
    1.18-1.02 (m, 3H), 0.94 (d, J = 6.9
    Hz, 3H).
    237 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.52 (s,
    film) 3382, [M + H]+ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.04-
    2976, 1762, C26H34N2O6, 6.91 (m, 4H), 5.60 (dp, J = 10.5, 6.3
    1734, 1678, 471.2490; found, Hz, 1H), 4.84-4.67 (m, 1H), 3.89 (s,
    1504, 1210, 471.2488 3H), 3.42 (dp, J = 10.6, 7.1 Hz, 1H),
    1079, 730 2.95 (hept, J = 7.0 Hz, 1H), 2.41 (d, J =
    cm−1 2.5 Hz, 3H), 2.37 (s, 3H), 1.55 (dd, J =
    14.2, 7.1 Hz, 3H), 1.40-1.32 (m, 6H),
    1.28 (d, J = 7.1 Hz, 3H), 1.03 (dd, J =
    6.2, 3.0 Hz, 3H).
    238 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.52 (d,
    film) 3384, [M + H]+ calcd for J = 10.1 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2977, 1762, C26H34FN2O6, 1H), 6.99 (d, J = 5.4 Hz, 1H), 6.70
    1735, 1679, 489.2395; found, (ddd, J = 15.3, 9.4, 2.7 Hz, 2H), 5.56
    1505, 1211, 489.2399 (dp, J = 10.4, 6.3 Hz, 1H), 4.82-4.65
    1127, 861, (m, 1H), 3.89 (s, 3H), 3.43-3.20 (m,
    731 cm−1 1H), 2.95 (hept, J = 7.0 Hz, 1H), 2.40
    (d, J = 2.4 Hz, 3H), 2.35 (s, 3H), 1.54
    (dd, J = 13.5, 7.2 Hz, 3H), 1.36 (dd,
    J = 7.1, 1.6 Hz, 6H), 1.26 (dd, J = 7.2,
    1.0 Hz, 3H), 1.02 (dd, J = 62, 2.9 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.50 (d, J = 25.8 Hz).
    239 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.47 (d,
    film) 3383, [M + H]+ calcd for J = 7.8 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2982, 1762, C25H30F3N2O6, 1H), 7.67-7.60 (m, 1H), 7.54-7.45
    1739, 1681, 511.2050; found, (m, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.34-
    1505, 1311, 511.2052 7.27 (m, 1H), 6.99 (d, J = 5.5 Hz,
    1151, 1117, 1H), 5.25-5.14 (m, 1H), 4.81-4.69
    772 cm−1 (m, 1H), 3.89 (s, 3H), 3.40-3.25 (m,
    1H), 2.96 (hept, J = 7.0 Hz, 1H), 1.51
    (d, J = 7.1 Hz, 3H), 1.37 (dd, J = 7.0,
    1.8 Hz, 6H), 1.29 (d, J = 6.8 Hz, 3H),
    1.09 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.26.
    240 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.44 (d,
    film) 3383, [M + H]+ calcd for J = 7.8 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2982, 1761, C25H29F4N2O6, 1H), 7.42 (dd, J = 8.8, 5.4 Hz, 1H),
    1740, 1680, 529.1956; found, 7.33 (dd, J = 9.2, 2.8 Hz, 1H), 7.19 (td,
    1500, 1312, 529.1958 J = 8.3, 2.8 Hz, 1H), 7.00 (d, J = 5.4
    1120, 909, Hz, 1H), 5.14 (p, J = 6.5 Hz, 1H), 4.81-
    732 cm−1 4.67 (m, 1H), 3.90 (s, 3H), 3.36-
    3.22 (m, 1H), 2.96 (hept, J = 7.0 Hz,
    1H), 1.50 (d, J = 7.2 Hz, 3H), 1.37 (dd,
    J = 7.0, 1.9 Hz, 6H), 1.28 (d, J = 6.9
    Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.80, −114.24.
    241 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.52 (s,
    film) 3382, [M + H]+ calcd for 1H), 8.32 (d, J = 5.4 Hz, 1H), 6.98 (d,
    2944, 1764, C23H35N2O6, J = 5.4 Hz, 1H), 5.07 (qd, J = 6.5, 3.0
    1734, 1680, 435.2490; found, Hz, 1H), 4.73-4.62 (m, 1H), 3.89 (s,
    1504, 1210, 435.2491 3H), 2.95 (hept, J = 7.0 Hz, 1H), 1.85-
    1090, 1040, 1.61 (m, 2H), 1.61-1.50 (m, 2H), 1.47
    916, 843, (d, J = 7.1 Hz, 3H), 1.43-1.29 (m,
    732 cm−1 9H), 1.21 (d, J = 6.4 Hz, 3H), 1.17-
    1.01 (m, 3H), 0.93 (d, J = 6.9 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 174.69,
    172.36, 162.38, 159.45, 146.55,
    142.04, 137.69, 109.56, 74.50, 56.28,
    48.04, 43.14, 42.93, 33.98, 31.24,
    30.70, 25.13, 25.01, 18.82, 18.71,
    17.48, 12.50.
    242 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.49 (d,
    film) 3383, [M + H]+ calcd for J = 8.4 Hz, 1H), 8.34 (d, J = 5.5 Hz,
    2977, 1762, C26H34FN2O6, 1H), 6.99 (d, J = 5.5 Hz, 1H), 6.70
    1735, 1679, 489.2395; found, (ddd, J = 17.0, 9.4, 2.8 Hz, 2H), 5.57
    1504, 1210, 489.2399 (dq, J = 10.4, 6.4 Hz, 1H), 4.85-4.62
    1081, 914, (m, 1H), 3.89 (s, 3H), 3.36 (dp, J =
    861, 731 10.4, 7.1 Hz, 1H), 2.95 (hept, J = 7.0
    cm−1 Hz, 1H), 2.40 (s, 3H), 2.35 (s, 3H),
    1.52 (d, J = 7.2 Hz, 3H), 1.36 (dd, J =
    7.0, 1.9 Hz, 6H), 1.26 (dd, J = 7.2, 1.0
    Hz, 3H), 1.02 (d, J = 6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −118.53.
    243 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3383, [M + H]+ calcd for J = 12.1 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2977, 1763, C26H35N2O6, 1H), 7.04-6.94 (m, 4H), 5.60 (dp, J =
    1735, 1679, 471.2490; found, 10.4, 6.3 Hz, 1H), 4.75 (ddq, J = 14.6,
    1504, 1211, 471.2495 7.2, 3.5 Hz, 1H), 3.89 (s, 3H), 3.42 (dp,
    1080, 914, J = 10.6, 7.1 Hz, 1H), 2.96 (hept, J =
    731 cm−1 7.0 Hz, 1H), 2.41 (d, J = 2.5 Hz, 3H),
    2.38 (s, 3H), 1.55 (dd, J = 14.2, 7.1 Hz,
    3H), 1.36 (dd, J = 7.1, 1.7 Hz, 6H),
    1.28 (d, J = 7.1 Hz, 3H), 1.03 (dd, J =
    6.2, 2.9 Hz, 3H).
    244 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.49 (d,
    film) 3383, [M + H]+ calcd for J = 9.5 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2977, 1761, C26H34FN2O6, 1H), 6.99 (d, J = 5.5 Hz, 1H), 6.82-
    1735, 1678, 489.2395; found, 6.61 (m, 2H), 5.56 (dp, J = 10.4, 6.3
    1504, 1309, 489.2399 Hz, 1H), 4.75 (pd, J = 7.2, 4.4 Hz, 1H),
    1209, 1081, 3.89 (s, 3H), 3.36 (dp, J = 10.3, 7.0 Hz,
    1059, 731 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.40 (d,
    cm−1 J = 2.4 Hz, 3H), 2.35 (s, 3H), 1.54 (dd,
    J = 13.6, 7.2 Hz, 3H), 1.36 (dd, J = 7.0,
    1.8 Hz, 6H), 1.26 (dd, J = 7 2, 1.1 Hz,
    3H), 1.02 (dd, J = 62, 2.9 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.49 (d, J = 25.8 Hz).
    245 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.56 (d,
    film) 3379, [M + H]+ calcd for J = 7.5 Hz, 1H), 8.35 (d, J = 5.5 Hz,
    2986, 1771, C23H26F3N2O6, 1H), 7.64 (dd, J = 8.0, 1.4 Hz, 1H),
    1736, 1676, 473.1737; found, 7.55-7.46 (m, 1H), 7.43 (d, J = 7.8
    1508, 1310, 483.1733 Hz, 1H), 7.35-7.28 (m, 1H), 7.01 (d,
    1149, 1116, J = 5.5 Hz, 1H), 5.25-5.13 (m, 1H),
    1046, 732 4.81-4.70 (m, 1H), 3.91 (s, 3H), 3.43-
    cm−1 3.29 (m, 1H), 2.40 (s, 3H), 1.55 (d,
    J = 7.2 Hz, 3H), 1.28 (d, J = 6.8 Hz, 3H),
    1.10 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.25.
    246 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.61-
    film) 3379, [M + H]+ calcd for 8.44 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),
    2986, 1771, C23H25F4N2O6, 7.42 (dd, J = 8.8, 5.3 Hz, 1H), 7.34 (dd,
    1737, 1677, 501.1643; found, J = 9.2, 2.9 Hz, 1H), 7.21 (td, J = 8.2,
    1500, 1312, 501.1642 2.8 Hz, 1H), 7.02 (d, J = 5.5 Hz, 1H),
    1154, 1123, 5.19-5.07 (m, 1H), 4.82-4.69 (m,
    1045, 909, 1H), 3.91 (s, 3H), 3.37-3.23 (m, 1H),
    732 cm−1 2.41 (s, 3H), 1.54 (d, J = 7.2 Hz, 3H),
    1.27 (d, J = 6.8 Hz, 3H), 1.11 (d, J =
    62 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.80, −114.08.
    247 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.58 (s,
    film) 3379, [M + H]+ calcd for 1H), 8.33 (d, J = 5.5 Hz, 1H), 7.00 (d,
    2946, 1771, C21H31N2O6, J = 5.5 Hz, 1H), 5.09 (qd, J = 6.5, 3.0
    1732, 1676, 407.2177; found, Hz, 1H), 4.77-4.62 (m, 1H), 3.90 (s,
    1506, 1310, 407.2173 3H), 2.40 (s, 3H), 1.83-1.68 (m, 3H),
    1193, 1174, 1.59 (dddt, J = 19.6, 14.7, 7.5, 3.1 Hz,
    1060, 906, 4H), 1.49 (d, J = 7.2 Hz, 3H), 1.38
    731 cm−1 (dddd, J = 13.6, 9.7, 6.8, 3.0 Hz, 1H),
    1.22 (d, J = 6.5 Hz, 3H), 1.18-1.02
    (m, 2H), 0.95 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.30,
    168.88, 162.36, 159.48, 146.65,
    141.67, 137.52, 109.73, 74.49, 56.28,
    48.23, 43.34, 43.11, 31.23, 30.75,
    25.16, 24.98, 20.75, 18.87, 17.79, 12.49.
    248 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.59 (d,
    film) 3378, [M + H]+ calcd for J = 7.7 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    2980, 1770, C24H31N2O6, 1H), 7.07-6.91 (m, 4H), 5.67-5.55
    1733, 1676, 443.2177; found, (m, 1H), 4.85-4.70 (m, 1H), 3.91 (s,
    1506, 1310, 443.2176 3H), 3.42 (dp, J = 10.6, 7.1 Hz, 1H),
    1195, 1175, 2.41 (s, 3H), 1.56 (dd, J = 14.4, 7.1 Hz,
    1006, 907, 3H), 1.28 (d, J = 7.1 Hz, 3H), 1.04 (dd,
    730 cm−1 J = 6.2, 2.8 Hz, 3H).
    249 HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.57 (d,
    [M + H]+ calcd for J = 8.7 Hz, 1H), 8.35 (d, J = 5.5 Hz,
    C24H30FN2O6, 1H), 7.01 (d, J = 5.5 Hz, 1H), 6.70
    461.2082; found, (ddd, J = 15.2, 9.3, 2.5 Hz, 2H), 5.65-
    461.2080 5.47 (m, 1H), 4.81-4.64 (m, 1H), 3.91
    (s, 3H), 3.36 (dp, J = 10.5, 7.0 Hz, 1H),
    2.40 (s, 6H), 2.35 (s, 3H), 1.55 (dd, J =
    13.8, 7.2 Hz, 3H), 1.26 (d, J = 7.2 Hz,
    3H), 1.03 (dd, J = 6.2, 2.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −118.43.
    250 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3377, [M + H]+ calcd for J = 7.8 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2985, 1771, C23H26F3N2O6, 1H), 8.01 (d, J = 5.2 Hz, OH), 7.63 (dt,
    1737, 1677, 483.1737; found, J = 8.0, 1.7 Hz, 1H), 7.55-7.47 (m,
    1507, 1310, 483.1735 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.31 (dt,
    1149, 1116, J = 9.6, 4.2 Hz, 1H), 7.01 (d, J = 5.5
    771, 731 Hz, 1H), 5.28-5.12 (m, 1H), 4.75
    cm−1 (dqd, J = 8.4, 7.2, 1.3 Hz, 1H), 3.91 (s,
    3H), 3.41-3.28 (m, 1H), 2.41 (s, 3H),
    1.52 (d, J = 7.2 Hz, 3H), 1.29 (d, J =
    6.8 Hz, 3H), 1.13-1.05 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.25.
    251 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.50 (d,
    film) 2985, [M + H]+ calcd for J = 7.9 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    1771, 1738, C23H25F4N2O6, 1H), 7.43 (dd, J = 8.8, 5.3 Hz, 1H),
    1677, 1500, 501.1643; found, 7.34 (dd, J = 9.2, 2.8 Hz, 1H), 7.20 (td,
    1312, 1193, 501.1640 J = 8.2, 2.9 Hz, 1H), 7.02 (d, J = 5.5
    1154, 1122, Hz, 1H), 5.15 (h, J = 6.5 Hz, 1H), 4.74
    909, 732 (dq, J = 8.1, 7.1 Hz, 1H), 3.92 (s, 3H),
    cm−1 3.30 (p, J = 6.9 Hz, 1H), 2.41 (s, 3H),
    1.52 (d, J = 7.2 Hz, 3H), 1.28 (d, J =
    6.8 Hz, 3H), 1.11 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.80, −114.19.
    252 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.58 (s,
    film) 3382, [M + H]+ calcd for 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.00 (d,
    2947, 1771, C21H31N2O6, J = 5.4 Hz, 1H), 5.08 (qd, J = 6.4, 3.0
    1732, 1676, 407.2177; found, Hz, 1H), 4.75-4.63 (m, 1H), 3.91 (s,
    1505, 1310, 407.2176 3H), 2.40 (s, 3H), 1.85-1.63 (m, 4H),
    1199, 1174, 1.63-1.51 (m, 2H), 1.48 (d, J = 7.2
    1151, 1061, Hz, 3H), 1.45-1.32 (m, 2H), 1.21 (d,
    906, 731 J = 6.4 Hz, 3H), 1.17-1.00 (m, 2H),
    cm−1 0.94 (d, J = 6.9 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.27,
    168.90, 162.40, 159.48, 146.66,
    141.66, 137.53, 109.72, 74.58, 56.28,
    48.07, 43.13, 42.93, 31.25, 30.69,
    25.14, 25.01, 20.75, 18.69, 17.48, 12.50.
    253 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.59 (d,
    film) 3378, [M + H]+ calcd for J = 8.8 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    2979, 1770, C24H31N2O6, 1H), 7.08-6.92 (m, 4H), 5.66-5.55
    1733, 1676, 443.2177; found, (m, 1H), 4.76 (p, J = 7.3 Hz, 1H), 3.91
    1506, 1195, 443.2170 (s, 3H), 3.42 (dp, J = 10.5, 7.1 Hz, 1H),
    1175, 1006, 2.41 (d, J = 1.7 Hz, 6H), 2.38 (s, 3H),
    907, 730 1.54 (d, J = 7.1 Hz, 3H), 1.28 (d, J =
    cm−1 7.2 Hz, 3H), 1.03 (d, J = 6.2 Hz, 3H).
    254 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.55
    film) 3379, [M + H]+ calcd for (dd, J = 16.7, 7.9 Hz, 1H), 8.35 (d, J =
    2980, 1771, C24H30FN2O6, 5.4 Hz, 1H), 7.01 (d, J = 5.5 Hz, 1H),
    1733, 1676, 461.2082; found, 6.70 (ddd, J = 17.0, 9.3, 2.7 Hz, 2H),
    1507, 1174, 461.2082 5.57 (dq, J = 10.3, 6.1 Hz, 1H), 4.82-
    1130, 1007, 4.69 (m, 1H), 3.91 (s, 3H), 3.36 (dp,
    731 cm−1 J = 10.5, 6.9 Hz, 1H), 2.40 (d, J = 2.6
    Hz, 6H), 2.35 (s, 3H), 1.53 (d, J = 7.2
    Hz, 3H), 1.26 (d, J = 7.1 Hz, 3H), 1.02
    (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −118.49.
    255 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.64-
    film) 3380, [M + H]+ calcd for 8.52 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),
    2979, 1770, C24H31N2O6, 7.07-6.90 (m, 4H), 5.68-5.53 (m,
    1733, 1676, 443.2177; found, 1H), 4.86-4.68 (m, 1H), 3.91 (s, 3H),
    1506, 1310, 443.2176 3.42 (dp, J = 10.5, 7.1 Hz, 1H), 2.42-
    1195, 1175, 2.39 (m, 6H), 2.38 (s, 3H), 1.56 (dd,
    1006, 907, J = 14.5, 7.1 Hz, 3H), 1.28 (d, J = 7.1
    730 cm−1 Hz, 3H), 1.04 (dd, J = 6.2, 2.8 Hz, 3H).
    256 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.68-
    film) 3377, [M + H]+ calcd for 8.47 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),
    2981, 1771, C24H30FN2O6, 7.01 (d, J = 5.5 Hz, 1H), 6.70 (ddd, J =
    1734, 1676, 461.2082; found, 14.7, 9.4, 2.4 Hz, 2H), 5.66-5.48 (m,
    1507, 1310, 461.2084 1H), 4.75 (tdd, J = 8.8, 7.2, 5.7 Hz,
    1195, 1175, 1H), 3.91 (d, J = 1.6 Hz, 3H), 3.36 (dp,
    1007, 908, J = 10.5, 7.0 Hz, 1H), 2.40 (d, J = 2.8
    731 cm−1 Hz, 6H), 2.35 (s, 3H), 1.55 (dd, J =
    13.9, 7.2 Hz, 3H), 1.26 (d, J = 7.1 Hz,
    3H), 1.03 (dd, J = 62, 2.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.43, −118.49.
    257 HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 8.46 (d,
    [M + H]+ calcd for J = 7.4 Hz, 1H), 8.31 (d, J = 5.5 Hz,
    C23H29N2O7, 1H), 7.20-7.10 (m, 2H), 6.98 (d, J =
    445.1969; found, 5.5 Hz, 1H), 6.88-6.79 (m, 2H), 5.27
    445.1949 (dq, J = 7.7, 6.3 Hz, 1H), 4.61-4.51
    (m, 1H), 3.88 (s, 3H), 3.80 (s, 3H),
    3.49-3.41 (m, 1H), 2.38 (s, 3H), 1.24
    (d, J = 4.7 Hz, 3H), 1.22 (d, J = 3.8 Hz,
    3H), 1.11 (d, J = 7.2 Hz, 3H).
    13CNMR(101 MHz, CDCl3) δ 172.1,
    168.9, 162.3, 159.4, 157.2, 146.6,
    141.7, 137.5, 131.2, 128.1, 127.3,
    120.5, 110.5, 109.7, 74.9, 56.3, 55.4,
    48.0, 37.4, 20.7, 18.3, 17.8, 16.6.
    258 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    film) 3377, [M + H]+ calcd for 1H), 8.34 (d, J = 5.5 Hz, 1H), 7.32-
    2980, 2938, C22H27N2O6, 7.27 (m, 2H), 7.24-7.16 (m, 3H), 7.01
    1770, 1732, 415.1864; found, (d, J = 5.5 Hz, 1H), 5.09 (dq, J = 7.7,
    1674, 1507, 415.1859 6.3 Hz, 1H), 4.77-4.67 (m, 1H), 3.91
    1310, 1198, (s, 3H), 2.96-2.86 (m, 1H), 2.41 (s,
    1174, 702 3H), 1.49 (d, J = 12 Hz, 3H), 1.30 (d,
    cm−1 J = 7.0 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.3,
    169.0, 162.4, 159.4, 146.7, 143.0,
    141.5, 137.5, 128.4, 127.8, 126.7,
    109.7, 76.3, 56.3, 48.1, 45.0, 20.8,
    18.7, 18.2, 17.3.
    259 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    film) 3380, [M + H]+ calcd for 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.01 (d,
    2980, 2938, C21H27N2O6S, J = 5.5 Hz, 1H), 6.61 (d, J = 3.5 Hz, 1H),
    1770, 1734, 435.1584; found, 6.56 (dq, J = 3.4, 1.1 Hz, 1H), 5.07-
    1674, 1506, 435.1581 4.98 (m, 1H), 4.77-4.67 (m, 1H), 3.91
    1193, 1173, (s, 3H), 3.20-3.11 (m, 1H), 2.42 (d,
    1060, 800 J = 1.1 Hz, 3H), 2.40 (s, 3H), 1.49 (d,
    cm−1 J = 7.2 Hz, 3H), 1.32 (d, J = 7.0 Hz, 3H),
    1.17 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.2,
    169.0, 162.4, 159.4, 146.7, 143.5,
    141.5, 138.0, 137.5, 124.5, 124.1,
    109.7, 75.9, 56.3, 48.1, 40.2, 20.8,
    18.7, 18.0, 17.3, 15.3.
    260 IR (thin HRMS-ESI (wz) 1H NMR (500 MHz, CDCl3) δ 8.54 (s,
    film) 3381, [M + H]+ calcd for 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.14-
    2980, 2940, C23H28FN2O7, 7.06 (m, 1H), 7.01 (d, J = 5.5 Hz, 1H),
    1770, 1733, 463.1875; found, 6.62-6.51 (m, 2H), 5.18-5.08 (m,
    1675, 1502, 463.1874 1H), 4.72-4.62 (m, 1H), 3.92 (s, 3H),
    1193, 1175, 3.79 (s, 3H), 3.42-3.31 (m, 1H), 2.41
    1150, 731 (s, 3H), 1.46 (d, J = 7.2 Hz, 3H), 1.23
    cm−1 (d, J = 7.1 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H).
    19F NMR (471 MHz, CDCl3) δ
    −13.9-−14.0 (m).
    261 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.61 (d,
    film) 2978, [M + H]+ calcd for J = 5.3 Hz, 1H), 7.24-7.17 (m, 2H),
    2942, 1769, C21H23N2O6, 7.17-7.06 (m, 4H), 5.61 (q, J = 7.1
    1712, 1602, 399.1551; found, Hz, 1H), 5.16-5.06 (m, 1H), 4.06 (s,
    1501, 1371, 399.1549 3H), 2.93-2.83 (m, 1H), 1.70 (d, J =
    1242, 1081, 7.1 Hz, 3H), 1.27 (d, J = 7.1 Hz, 3H),
    702 cm−1 1.04 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 168.2,
    158.7, 154.2, 149.1, 145.8, 142.5,
    141.6, 131.5, 128.2, 128.0, 126.5,
    111.2, 76.5, 56.8, 51.6, 44.7, 17.5,
    17.2, 14.0.
    262 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.60 (d,
    film) 2942, [M + H]+ calcd for J = 5.2 Hz, 1H), 7.13 (d, J = 5.3 Hz,
    1769, 1713, C22H24FN2O7, 1H), 7.02 (dd, J = 8.5, 6.7 Hz, 1H),
    1602, 1501, 447.1562; found, 6.59-6.50 (m, 2H), 5.56 (q, J = 7.1
    1371, 1242, 447.1566 Hz, 1H), 5.15-5.06 (m, 1H), 4.05 (s,
    1080, 731 3H), 3.79 (s, 3H), 3.31-3.20 (m, 1H),
    cm−1 1.68 (d, J = 7.0 Hz, 3H), 1.18 (d, J =
    7.0 Hz, 3H), 1.16 (d, J = 6.3 Hz, 3H).
    19FNMR(471 MHz, CDCl3) δ −113.9.
    263 ESIMS m/z 427.2 1H NMR (400 MHz, CDCl3) δ 8.55 (d,
    [(M + H)+] J = 7.8 Hz, 1H), 8.35 (dd, J = 5.4, 2.9
    Hz, 1H), 7.23-7.05 (m, 4H), 7.01 (dd,
    J = 5.5, 2.2 Hz, 1H), 5.15 (dq, J = 8.7,
    6.2 Hz, 1H), 4.80-4.62 (m, 1H), 3.91
    (d, J = 1.7 Hz, 3H), 3.35-3.02 (m,
    1H), 2.41 (d, J = 1.8 Hz, 3H), 2.35 (s,
    3H), 1.50 (t, J = 6.8 Hz, 3H), 1.25 (dd,
    J = 6.9, 4.3 Hz, 3H), 1.11 (t, J = 5.9
    Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.39,
    168.89, 159.49, 146.67, 141.80,
    137.54, 135.55, 130.49, 126.39,
    126.30, 126.23, 109.75, 56.28, 48.19,
    48.09, 39.75, 20.74, 19.96, 18.56,
    18.48, 18.25, 17.58, 17.46, −0.01.
    264 ESIMS m/z 429.3 1H NMR (400 MHz, CDCl3) δ 8.55 (d,
    [(M + H)+] J = 7.6 Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H),
    7.23-6.93 (m, 5H), 5.14 (dq, J = 8.4,
    6.2 Hz, 1H), 4.73 (p, J = 7.2 Hz, 1H),
    3.91 (s, 3H), 3.19 (dq, J = 8.4, 6.9 Hz,
    1H), 2.40 (s, 3H), 2.35 (s, 3H), 1.51 (d,
    J = 7.1 Hz, 3H), 1.25 (d, J = 6.9 Hz, 3H),
    1.12 (d, J = 6.2 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.39,
    168.89, 162.39, 159.48, 146.67,
    141.81, 141.66, 137.54, 135.51,
    130.50, 126.39, 126.27, 126.26,
    109.74, 56.27, 48.19, 39.81, 20.74,
    19.94, 18.73, 18.48, 17.46.
    265 ESIMS m/z 457.5 1H NMR. (400 MHz, CDCl3) δ 8.49 (s,
    [(M + H)+] 1H), 8.34 (dd, J = 5.4, 2.9 Hz, 1H),
    7.22-7.06 (m, 4H), 6.99 (d, J = 5.4
    Hz, 1H), 5.24-5.04 (m, 1H), 4.79-
    4.64 (m, 1H), 3.89 (d, J = 1.7 Hz, 3H),
    3.18 (dq, J = 9.2, 6.9 Hz, 1H), 2.96 (p,
    J = 7.0 Hz, 1H), 2.35 (s, 3H), 1.49 (dd,
    J = 7.2, 5.9 Hz, 3H), 1.37 (dd, J = 7.0,
    1.7 Hz, 6H), 1.30-1.18 (m, 3H), 1.11
    (t, J = 6.2 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 174.68,
    172.48, 162.41, 159.47, 146.56,
    142.03, 141.83, 137.71, 135.55,
    130.48, 126.40, 126.29, 126.21,
    109.59, 56.28, 48.07, 39.77, 33.97,
    19.96, 18.81, 18.56, 18.26, 17.60, −0.01.
    266 ESIMS m/z 457.4 1H NMR (400 MHz, CDCl3) δ 8.49 (s,
    [(M + H)+] 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.23-
    7.05 (m, 4H), 6.99 (d, J = 5.5 Hz, 1H),
    5.12 (dt, J = 8.4, 6.2 Hz, 1H), 4.73(p,
    J = 7.2 Hz, 1H), 3.89 (s, 3H), 3.38-3.09
    (m, 1H), 2.95 (p, J = 7.0 Hz, 1H), 2.35
    (s, 3H), 1.50 (d, J = 7.1 Hz, 3H), 1.36
    (dd, J = 7.0, 1.1 Hz, 6H), 1.25 (d, J = 6.9
    Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.48,
    162.36, 159.46, 146.56, 142.03,
    141.84, 137.70, 135.51, 130.49,
    126.40, 126.27, 126.24, 109.58, 56.28,
    48.17, 39.81, 33.96, 19.94, 18.81,
    18.76, 18.48, 17.45.
    267 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.93
    film) 3087, [M + H]+ calcd for (s, 1H), 10.74 (d, J = 7.6 Hz, 1H), 8.00
    2984, 1737, C21H24F3N2O4S, (d, J = 5.1 Hz, 1H), 7.73-7.59 (m,
    1513, 1484, 457.1403; found, 1H), 7.51 (t, J = 7.7 Hz, 1H), 7.43 (d,
    1311, 1151, 457.1399 J = 7.8 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H),
    1118, 800, 6.89 (d, J = 5.1 Hz, 1H), 5.30-5.18
    771 cm−1 (m, 1H), 5.14 (p, J = 7.2 Hz, 1H), 3.96
    (s, 3H), 3.37 (p, J = 6.8 Hz, 1H), 1.69
    (dd, J = 7.2, 3.2 Hz, 3H), 1.30 (d, J =
    6.8 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.23.
    268 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.91
    film) 3086, [M + H]+ calcd for (s, 1H), 10.72 (d, J = 7.7 Hz, 1H), 8.00
    2984, 1735, C21H23F4N2O4S, (d, J = 5.1 Hz, 1H), 7.41 (dd, J = 8.7,
    1512, 1313, 475.1309; found, 5.3 Hz, 1H), 7.36 (dd, J = 9.1, 2.8 Hz,
    1279, 1153, 475.1308 1H), 7.22 (td, J = 8.2, 2.8 Hz, 1H), 6.90
    1120, 909, (d, J = 5.1 Hz, 1H), 5.16 (dp, J = 21.6,
    730 cm−1 6.9 Hz, 2H), 3.96 (s, 3H), 3.34 (p, J =
    7.2 Hz, 1H), 1.68 (d, J = 7.2 Hz, 3H),
    1.29 (d, J = 6.8 Hz, 3H), 1.14 (d, J =
    6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.77, −113.84.
    269 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 12.94
    film) 3128, [M + H]+ calcd for (d, J = 1.8 Hz, 1H), 10.76 (d, J = 7.9
    2947, 1735, C19H29N2O4S, Hz, 1H), 7.98 (dd, J = 5.1, 1.4 Hz, 1H),
    1511, 1479, 381.1843; found, 6.88 (d, J = 5.1 Hz, 1H), 5.19-5.00
    1280, 1200, 381.1840 (m, 2H), 3.95 (s, 3H), 1.85-1.69 (m,
    1151, 985, 2H), 1.68-1.32 (m, 7H), 1.30-1.20
    797 cm−1 (m, 4H), 1.20-1.01 (m, 3H), 0.96 (d,
    J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 188.94,
    171.20, 157.16, 149.30, 138.96,
    131.63, 109.05, 75.08, 56.26, 52.28,
    43.32, 43.13, 31.22, 30.75, 25.15,
    24.98, 17.81, 17.23, 12.49.
    270 HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 9.96 (d,
    [M + H]+ calcd for J = 7.3 Hz, 1H), 8.34 (d, J = 5.5 Hz,
    C23H26F3N2O5S, 1H), 7.71-7.59 (m, 1H), 7.59-7.47
    499.1509; found, (m, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.39-
    499.1508 7.28 (m, 1H), 7.00 (d, J = 5.5 Hz,
    1H), 5.28-5.15 (m, 2H), 3.91 (s, 3H),
    3.42-3.29 (m, 1H), 2.37 (s, 3H), 1.64
    (d, J = 7.2 Hz, 3H), 1.30 (d, J = 6.8 Hz,
    3H), 1.12 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.23.
    271 HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 9.95 (d,
    [M + H]+ calcd for J = 7.3 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    C23H25F4N2O5S, 1H), 7.42 (dd, J = 8.8, 5.3 Hz, 1H),
    517.1415; found, 7.35 (dd, J = 9.2, 2.8 Hz, 1H), 7.22 (td,
    517.1410 J = 8.2, 2.8 Hz, 1H), 7.00 (d, J = 5.5
    Hz, 1H), 5.35-5.03 (m, 2H), 3.91 (s,
    3H), 3.41-3.21 (m, 1H), 2.37 (s, 3H),
    1.64 (d, J = 7.1 Hz, 3H), 1.29 (d, J =
    6.8 Hz, 3H), 1.13 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.78, −113.98.
    272 HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 10.00
    [M + H]+ calcd for (d, J = 7.3 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    C21H31N2O5S, 1H), 6.99 (d, J = 5.4 Hz, 1H), 5.24-
    423.1948; found, 5.06 (m, 2H), 3.91 (s, 3H), 2.36 (s,
    423.1944 3H), 1.83-1.71 (m, 3H), 1.71-1.54
    (m, 6H), 1.50 (dtd, J = 14.3, 8.0, 3.3
    Hz, 1H), 1.39 (dqd, J = 9.7, 6.9, 3.0
    Hz, 1H), 1.25 (d, J = 6.5 Hz, 3H), 1.20-
    1.02 (m, 2H), 0.96 (dd, J = 6.9, 1.7
    Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 189.09,
    171.67, 168.57, 159.84, 146.29,
    145.12, 136.88, 109.21, 74.86, 56.41,
    53.04, 43.36, 43.13, 31.22, 30.75,
    25.17, 24.99, 21.27, 17.86, 17.08, 12.46.
    273 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 14.35
    film) 2984, [M + H]+ calcd for (s, 1H), 12.85 (d, J = 6.8 Hz, 1H), 7.91
    1739, 1571, C21H24F3N2O6, (d, J = 7.1 Hz, 1H), 7.64 (dd, J = 7.9,
    1480, 1310, 457.1581; found, 1.4 Hz, 1H), 7.51 (td, J = 1.6, 1.3 Hz,
    1150, 1117, 457.1583 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.32 (t,
    759 cm−1 J = 7.6 Hz, 1H), 6.79 (d, J = 7.2 Hz, 1H),
    5.28-5.14 (m, 1H), 4.73 (p, J = 7.1
    Hz, 1H), 3.97 (s, 3H), 3.35 (tt, J = 7.5,
    3.8 Hz, 1H), 1.62 (d, J = 7.2 Hz, 3H),
    1.29 (d, J = 6.8 Hz, 3H), 1.10 (d, J =
    6.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −58.22.
    274 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 14.33
    film) 2985, [M + H]+ calcd for (s, 1H), 12.85 (d, J = 6.9 Hz, 1H), 7.91
    1739, 1480, C21H23F4N2O6, (d, J = 7.2 Hz, 1H), 7.44 (dd, J = 8.8,
    1313, 1153, 475.1487; found, 5.4 Hz, 1H), 7.35 (dd, J = 9.2, 2.8 Hz,
    1123, 909, 475.1492 1H), 7.21 (td, J = 8.2, 2.8 Hz, 1H), 6.80
    738 cm−1 (d, J = 7.2 Hz, 1H), 5.23-5.09 (m,
    1H), 4.73 (p, J = 7.2 Hz, 1H), 3.98 (s,
    3H), 3.41-3.25 (m, 1H), 1.61 (d, J =
    7.2 Hz, 3H), 1.27 (d, J = 6.8 Hz, 3H),
    1.11 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ
    −58.77, −114.03.
    275 IR (thin HRMS-ESI (m/z) 1H NMR (400 MHz, CDCl3) δ 14.40
    film) 2945, [M + H]+ calcd for (s, 1H), 12.75 (d, J = 7.1 Hz, 1H), 7.91
    1733, 1569, C19H29N2O6, (d, J = 7.2 Hz, 1H), 6.79 (d, J = 7.2 Hz,
    1479, 1300, 381.2020; found, 1H), 5.10 (qd, J = 6.4, 3.0 Hz, 1H),
    1212, 1152, 381.2016 4.78-4.63 (m, 1H), 3.97 (s, 3H), 1.85-
    1029, 757 1.68 (m, 2H), 1.68-1.51 (m, 7H),
    cm−1 1.51-1.44 (m, 1H), 1.44-1.33 (m,
    1H), 1.24 (d, J = 6.4 Hz, 3H), 1.18-
    0.99 (m, 2H), 0.94 (d, J = 6.9 Hz, 3H).
    276 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 14.39
    film) 2978, [M + H]+ calcd for (s, 1H), 12.82 (d, J = 6.9 Hz, 1H), 7.89
    2937, 1735, C20H25N2O6, (d, J = 7.2 Hz, 1H), 7.32-7.25 (m,
    1643, 1569, 389.1707; found, 2H), 7.25-7.15 (m, 3H), 6.78 (d, J =
    1479, 1452, 389.1703 7.2 Hz 1H), 5.10 (dq, J = 8.1, 6.3 Hz,
    1211, 1154, 1H), 4.75-4.64 (m, 1H), 3.97 (s, 3H),
    729, 702 2.96-2.86 (m, 1H), 1.56 (d, J = 7.2
    cm−1 Hz, 3H), 1.30 (d, J = 6.9 Hz, 3H), 1.12
    (d, J = 6.2 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 171.1,
    165.5, 152.5, 149.3, 143.0, 131.0,
    128.4, 127.8, 126.7, 123.7, 107.6, 76.5,
    56.5, 48.9, 45.0, 18.2, 17.9, 17.4.
    277 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 14.42
    film) 2978, [M + H]+ calcd for (s, 1H), 12.80 (d, J = 7.1 Hz, 1H), 7.89
    2939, 1735, C21H26FN2O7, (d, J = 7.2 Hz, 1H), 7.11 (dd, J = 8.4,
    1570, 1502, 437.1719; found, 6.7 Hz, 1H), 6.78 (d, J = 7.1 Hz, 1H),
    1453, 1213, 437.1727 6.63-6.55 (m, 2H), 5.22-5.13 (m,
    1152, 1031, 1H), 4.72-4.61 (m, 1H), 3.98 (s, 3H),
    952, 731 3.80 (s, 3H), 3.38-3.29 (m, 1H), 1.51
    cm−1 (d, J = 7.2 Hz, 3H), 1.25 (d, J = 7.1 Hz,
    3H), 1.13 (d, J = 6.3 Hz, 3H).
    19F NMR (471 MHz, CDCl3) δ
    −113.9 (dt, J = 11.2, 7.3 Hz).
    278 87-88 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.53 (d,
    [M + H]+ calcd for J = 7.1 Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H),
    C24H30N2O6, 7.22-7.06 (m, 4H), 7.00 (d, J = 5.5 Hz,
    443.2177; found, 1H), 5.14 (dq, J = 8.4, 6.3 Hz, 1H), 4.78-
    443.2186 4.68 (m, 1H), 3.90 (s, 3H), 3.18 (dt,
    J = 8.4, 6.9 Hz, 1H), 2.74 (q, J = 7.5 Hz,
    2H), 2.35 (s, 3H), 1.51 (d, J = 7.1 Hz,
    3H), 1.28 (t, J = 7.5 Hz, 3H), 1.25 (d,
    J = 6.9 Hz, 3H), 1.12 (d, J = 6.3 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.43,
    172.35, 162.39, 159.50, 146.60, 141.81,
    141.71, 137.61, 135.51, 130.49, 126.38,
    126.27, 109.70, 76.30, 56.28, 48.16,
    39.78, 30.93, 27.28, 19.97, 18.77, 18.49,
    17.47, 8.81.
    279 88-91 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.52 (d,
    [M + H]+ calcd for J = 6.1 Hz, 1H), 8.33 (d, J = 5.4 Hz, 1H),
    C25H32N2O6, 7.21-7.06 (m, 4H), 6.99 (d, J = 5.5 Hz,
    457.2333; found, 1H), 5.14 (dq, J = 8.4, 6.2 Hz, 1H), 4.77-
    457.2343 4.69 (m, 1H), 3.89 (s, 3H), 3.18 (dq,
    J = 8.4, 6.9 Hz, 1H), 2.68 (t, J = 7.5 Hz,
    2H), 2.35 (s, 3H), 1.82 (h, J = 7.4 Hz,
    2H), 1.50 (d, J = 7.1 Hz, 3H), 1.25 (d,
    J = 6.8 Hz, 3H), 1.12 (d, J = 6.2 Hz, 3H),
    1.05 (t, J = 7.4 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.43,
    171.45, 162.37, 159.46, 146.60, 141.81,
    141.76, 137.58, 135.51, 130.49, 126.38,
    126.27, 109.67, 76.28, 56.25, 48.15,
    39.77, 35.79, 19.96, 18.77, 18.48, 18.15,
    17.46, 13.60.
    280 ESIMS m/z 471 1H NMR (400 MHz, CDCl3) δ 8.53 (s,
    ([M + H]+) 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.22-
    7.06 (m, 4H), 7.00 (d, J = 5.5 Hz, 1H),
    5.13 (dq, J = 8.3, 6.2 Hz, 1H), 4.85-
    4.67 (m, 1H), 3.90 (s, 3H), 3.18 (dq, J =
    8.4, 6.9 Hz, 1H), 2.80-2.67 (m, 2H),
    2.35 (s, 3H), 1.77 (p, J = 7.6 Hz, 2H),
    1.48 (dd, J = 17.8, 7.4 Hz, 5H), 1.25 (d,
    J = 6.9 Hz, 3H), 1.12 (d, J = 6.2 Hz,
    3H), 0.96 (t, J = 7.4 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.46,
    171.62, 162.40, 159.50, 146.61, 141.84,
    141.82, 137.63, 135.53, 130.51, 126.41,
    126.29, 126.27, 109.68, 56.26, 48.17,
    39.80, 33.67, 26.64, 22.22, 19.96, 18.77,
    18.49, 17.47, 13.77.
    281 ESIMS m/z 455.4 1H NMR (400 MHz, CDCl3) δ 8.52 (d,
    ([M + H]+) J = 8.0 Hz, 1H), 8.33 (d, J = 5.4 Hz, 1H),
    7.22-7.05 (m, 4H), 6.99 (d, J = 5.5 Hz,
    1H), 5.13 (dq, J = 8.3, 6.2 Hz, 1H), 4.82-
    4.68 (m, 1H), 3.90 (s, 3H), 3.19 (dq,
    J = 8.4, 6.9 Hz, 1H), 2.35 (s, 3H), 1.97 (tt,
    J = 8.0, 4.6 Hz, 1H), 1.51 (d, J = 7.2 Hz,
    3H), 1.32-1.21 (m, 5H), 1.12 (d, J =
    6.3 Hz, 3H), 1.07 (dq, J = 7.5, 4.0 Hz, 2H).
    13C NMR (101 MHz, CDCl3) δ 172.49,
    172.45, 162.36, 159.53, 146.61, 142.00,
    141.84, 137.50, 135.52, 130.51, 126.41,
    126.29, 126.26, 109.67, 60.39, 56.31,
    48.13, 39.80, 21.04, 19.96, 18.83, 18.49,
    17.47, 14.21, 13.03, 9.26.
    282 ESIMS m/z 491.4 1H NMR (400 MHz, CDCl3) δ 8.56 (d,
    ([M + H]+) J = 7.9 Hz, 1H), 8.40 (d, J = 5.5 Hz, 1H),
    8.32-8.17 (m, 2H), 7.67-7.57 (m,
    1H), 7.50 (dd, J = 8.3, 7.0 Hz, 2H), 7.20-
    7.08 (m, 4H), 7.06 (d, J = 5.5 Hz, 1H),
    5.11 (dq, J = 8.2, 6.2 Hz, 1H), 4.89-
    4.55 (m, 1H), 3.90 (s, 3H), 3.23-3.03
    (m, 1H), 2.34 (s, 3H), 1.47 (d, J = 7.2
    Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H), 1.08
    (d, J = 6.2 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.51,
    164.53, 162.25, 159.68, 146.82, 141.85,
    135.53, 133.47, 130.60, 130.50, 129.20,
    128.55, 126.40, 126.28, 126.25, 109.77,
    56.33, 48.08, 39.79, 19.95, 18.84, 18.47, 17.46.
    284 HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ 8.43 (d,
    [M + H]+ calcd for J = 7.8 Hz, 1H), 8.28 (d, J = 5.3 Hz, 1H),
    C26H34N2O7, 7.22-7.05 (m, 4H), 6.94 (d, J = 5.4 Hz,
    487.2439; found, 1H), 5.78 (q, J = 6.4 Hz, 2H), 5.15 (dq,
    487.2450 J = 8.5, 6.3 Hz, 1H), 4.75 (p, J = 7.2 Hz,
    1H), 3.89 (s, 3H), 3.25-3.15 (m, 1H),
    2.55 (p, J = 7.0 Hz, 1H), 2.35 (s, 3H),
    1.53 (d, J = 7.2 Hz, 3H), 1.26 (dd, J =
    7.1, 5.9 Hz, 3H), 1.14 (dd, J = 8.7, 6.6
    Hz, 9H).
    13C NMR (126 MHz, CDCl3) δ 176.26,
    172.52, 162.94, 160.27, 145.58, 144.25,
    142.19, 141.80, 135.51, 130.50, 126.37,
    126.26, 109.50, 89.96, 76.30, 56.13,
    48.38, 39.79, 33.86, 19.96, 18.69, 18.62,
    18.51, 17.51.
    285 ESIMS m/z 413 1H NMR (400 MHz, CDCl3) δ 8.60 (d,
    ([M + H]+) J = 5.3 Hz, 1H), 7.18 (d, J = 5.4 Hz, 1H),
    7.14 (dd, J = 3.8, 1.4 Hz, 2H), 7.08-
    6.99 (m, 2H), 5.60 (q, J = 7.1 Hz, 1H),
    5.18 (dq, J = 8.2, 6.2 Hz, 1H), 4.06 (s,
    3H), 3.14 (dq, J = 8.3, 6.9 Hz, 1H), 2.29
    (s, 3H), 1.71 (d, J = 7.0 Hz, 3H), 1.22 (d,
    J = 6.9 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 168.34,
    158.73, 154.19, 149.12, 145.79, 141.65,
    141.53, 135.54, 131.44, 130.30, 126.41,
    126.23, 126.11, 111.45, 56.84, 51.51,
    39.55, 20.00, 17.74, 17.71, 14.03.
    *Cmpd. No.—Compound Number
  • TABLE 3
    Biological Testing Rating Scale
    Rating Table for Fungal Pathogens
    % Control Rating
     >80 A
    ≤80 B
    Not Tested C
     ≤0 D
  • TABLE 4
    Biological Activity - PUCCRT and SEPTTR Disease
    Control in High Volume Applications
    HV activity at 100 ppm*
    *PUCCRT *SEPTTR
    *Cmpd. No. 1DP* 3DC* 1DP* 3DC*
    116 A A B A
    117 B B B B
    118 A A D B
    119 A B D B
    120 B B D B
    121 A A D B
    122 A A B B
    123 A B D B
    124 B D D B
    125 B D D B
    126 A B D B
    127 B B D B
    128 A A A A
    129 A B B B
    130 A A B B
    131 A A B B
    132 A A A B
    133 A B B B
    134 B B B B
    135 B B B B
    136 A B B B
    137 A B B B
    138 A A A B
    139 B D B B
    140 A B B B
    141 A B A B
    142 A A A B
    143 A D B B
    144 D B B B
    145 B B B B
    146 A B A B
    147 A B A B
    148 A B A B
    149 D D B B
    150 D B B B
    151 B D B B
    152 A B B B
    153 B B B B
    154 D D B B
    155 B B B B
    156 D B B B
    157 B D B B
    158 A A A B
    159 A A A A
    160 B A B B
    161 D D B B
    162 D D B B
    163 B B B B
    164 A A B A
    165 A A A A
    166 A A A A
    167 A A A A
    168 A A B A
    169 A A A A
    170 A A B B
    171 A A B B
    172 B A B B
    173 A B B B
    175 A A B B
    176 A B D B
    258 A A B B
    259 A A B D
    260 A B B B
    267 A B B B
    268 A B B B
    269 B A B B
    276 A B B B
    277 B D B B
    *Cmpd. No.—Compound Number
    *PUCCRT—Wheat Brown Rust (Puccinia triticina)
    *SEPTTR—Wheat Leaf Blotch (Zymoseptoria tritici)
    *1DP—1 Day Protectant
    *3DC—3 Day Curative
    *ppm—Parts Per Million
  • TABLE 5
    Biological Activity - PUCCRT and SEPTTR Disease
    Control in Low Volume Applications
    LV activity at 121.5 g/ha*
    *PUCCRT *SEPTTR
    *Cmpd No. 1DP* 3DC* 1DP* 3DC*
    177 A A A A
    178 B B B B
    179 A A B B
    180 B B B B
    234 B B B B
    235 B B A A
    236 B B B D
    237 B B B B
    238 A B A A
    239 D D B B
    240 D D B B
    241 D D B D
    242 A B A A
    243 B B B B
    244 A B A A
    245 A B A A
    246 A A A A
    247 B B B B
    248 A B B A
    249 A A A A
    250 D B B B
    251 B B B B
    252 D B D B
    253 A B B B
    254 A A A A
    255 A B B A
    256 A A A A
    257 B B B B
    258 B A B A
    259 B D B D
    260 D D B D
    261 B D B D
    262 D D B B
    263 B B B B
    264 A A B B
    265 B B B B
    266 B B B B
    275 B D D D
    231 A B B B
    232 A B D B
    233 A B B B
    270 B B B B
    271 B B B B
    272 B B B B
    273 B B B B
    274 B B B B
    276 B B B B
    277 D B B B
    *Cmpd. No.—Compound Number
    *PUCCRT—Wheat Brown Rust (Puccinia triticina)
    *SEPTTR—Wheat Leaf Blotch (Zymoseptoria tritici)
    *1DP—1 Day Protectant
    *3DC—3 Day Curative
    *g/ha—grams per hectare
  • TABLE 6
    Biological Activity - High Volume Disease Control at 25 ppm
    PHAKPA*
    *Cmpd. No. 1DP* 3DC*
    128 C A
    158 C B
    159 C A
    175 A A
    177 A A
    178 A B
    179 A A
    180 A B
    181 B D
    182 B B
    183 A B
    184 A A
    185 D D
    186 B B
    187 A D
    188 A B
    189 A B
    190 D D
    191 B B
    192 B D
    193 B D
    194 D D
    195 B D
    196 A B
    197 D D
    198 D D
    199 D D
    200 B B
    201 B B
    202 B D
    203 A B
    204 A A
    205 A B
    206 B D
    207 B D
    208 A D
    209 A A
    210 D D
    211 B D
    212 B B
    213 A B
    214 B B
    215 B B
    216 B D
    217 B D
    218 D B
    219 D D
    220 B B
    221 D D
    222 D D
    223 D D
    224 B D
    225 D D
    226 D B
    227 B D
    228 D D
    229 D D
    230 D D
    231 B D
    232 B D
    233 A B
    234 A A
    235 A A
    236 A D
    237 A A
    238 A A
    239 B B
    240 B B
    241 D D
    242 A A
    243 A A
    244 A A
    245 A A
    246 A A
    247 A B
    248 A A
    249 A A
    250 B B
    251 A B
    252 B B
    253 A A
    254 A A
    255 A A
    256 A A
    257 B D
    258 A A
    259 B B
    260 A B
    261 B B
    262 B B
    263 A B
    264 A A
    265 A A
    266 A A
    270 A B
    271 A A
    272 A B
    273 B B
    274 B B
    275 B B
    276 D B
    277 B B
    284 A A
    278 A A
    279 A A
    280 A A
    281 A A
    282 A A
    285 A A
    *Cmpd. No.—Compound Number
    *PHAKPA—Asian Soybean Rust (Phakopsora pachyrhizi)
    *1DP—1 Day Protectant
    *3DC—3 Day Curative
  • TABLE 7
    Biological Activity - Disease Control in 1DP* test at 100 ppm
    Cmpd. No.* ALTESO* CERCBE* COLLLA* LEPTNO*
    263 B B D B
    264 B A B A
    266 B B D A
    *Cmpd. No.—Compound Number
    *ALTESO—Tomato Early Blight (Alternaria solani)
    *CERCBE—Leaf Spot of Sugar Beets (Cercospora beticola)
    *COLLLA—Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotricum lagenarium)
    *LEPTNO—Wheat Glume Blotch (Parastagonospora nodorum)
  • TABLE 8
    Biological Activity - Disease Control in 1DP* Test at 100 ppm
    Cmpd. No.* PSPECU* PYRIOR* RHYNSE* UNCINE*
    263 B B B A
    264 B A B A
    266 D A B A
    *Cmpd. No.—Compound Number
    *PSPECU—Cucumber Downy Mildew (Pseudoperonospora cubensis)
    *PYRIOR—Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae)
    *RHYNSE—Barley Scald (Rhyncosporium secalis)
    *UNCINE—Grape Powdery Mildew (Uncinula necator)
    *1DP—1 Day Protectant

Claims (28)

What is claimed is:
1. A compound of Formula I
Figure US20200399222A1-20201224-C00311
wherein:
Q is
Figure US20200399222A1-20201224-C00312
X is hydrogen or C(O)R4;
Y is hydrogen or C(O)R4;
Z is N or N+→O− and W is O or S;
R1 is hydrogen or alkyl, substituted with 0, 1 or multiple R7;
R2 is methyl;
R3 is alkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R7;
R4 is alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R7;
R5 is hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R7;
R6 is hydrogen, —C(O)R8 or —CH2OC(O)R5;
R7 is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R9;
R8 is alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R7;
R9 is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl; and
R10 is hydrogen or alkyl, each substituted with 0, 1 or multiple R7.
2. The compound according to claim 1, wherein Q is
Figure US20200399222A1-20201224-C00313
and X and Y are hydrogen.
3. The compound according to claim 2, wherein R1 and R10 are independently chosen from hydrogen or alkyl.
4. The compound according to claim 2, wherein R3 is aryl, optionally substituted with 0, 1 or multiple R7.
5. The compound according to claim 2, wherein R1 and R10 are independently chosen from hydrogen or alkyl, and R3 is aryl, optionally substituted with 0, 1 or multiple R7.
6. The compound according to claim 1, wherein Q is
Figure US20200399222A1-20201224-C00314
and X is C(O)R4 and Y is hydrogen.
7. The compound according to claim 6, wherein R1 and R10 are independently chosen from hydrogen or alkyl.
8. The compound according to claim 6, wherein R3 is aryl, optionally substituted with 0, 1 or multiple R7.
9. The compound according to claim 6, wherein R1 and R10 are independently chosen from hydrogen or alkyl, and R3 is aryl, optionally substituted with 0, 1 or multiple R7.
10. The compound according to claim 1, wherein Q is
Figure US20200399222A1-20201224-C00315
wherein X is hydrogen.
11. The compound according to claim 10 wherein Z is N.
12. The compound according to claim 11 wherein W is O.
13. The compound according to claim 12, wherein R5 is alkoxy.
14. The compound according to claim 13, wherein R6 is hydrogen.
15. The compound according to claim 14, wherein R1 and R10 are independently chosen from hydrogen or alkyl.
16. The compound according to claim 14, wherein R3 is aryl, optionally substituted with 0, 1 or multiple R7.
17. The compound according to claim 14, wherein R1 and R10 are independently chosen from hydrogen or alkyl, and R3 is aryl, optionally substituted with 0, 1 or multiple R7.
18. The compound according to claim 13, wherein R6 is chosen from —C(O)R8 or —CH2OC(O)R5.
19. The compound according to claim 18, wherein R1 and R10 are independently chosen from hydrogen or alkyl.
20. The compound according to claim 18, wherein R3 is aryl, optionally substituted with 0, 1 or multiple R7.
21. The compound according to claim 18, wherein R1 and R10 are independently chosen from hydrogen or alkyl, and R3 is aryl, optionally substituted with 0, 1 or multiple R7.
22. An antifungal composition comprising any one of the compounds of claims 1-21.
23. The composition of claim 22 wherein the composition further comprises one or more fungicides, insecticides, nematocides, miticides, arthropodicides, bactericides and combinations thereof.
24. A composition for the control of a fungal pathogen including mixtures of at least one of the compounds of claims 1-21 and another pesticide including fungicides, insecticides, nematocides, miticides, arthropodicides, bactericides and combinations thereof.
25. The composition of any one of claim 24 wherein wherein the fungal pathogen is one of Leaf Blotch of Wheat (Zymoseptoria tritici), Wheat Brown Rust (Puccinia triticina), Stripe Rust (Puccinia striiformis), Scab of Apple (Venturia inaequalis), Blister Smut of Maize (Ustilago maydis), Powdery Mildew of Grapevine (Uncinula necator), Barley Scald (Rhynchosporium secalis), Blast of Rice (Pyricularia oryzae), Rust of Soybean (Phakopsora pachyrhizi), Glume Blotch of Wheat (Parastagonospora nodorum), Powdery Mildew of Wheat (Blumeria graminis f. sp. tritici), Powdery Mildew of Barley (Blumeria graminis f. sp. hordei), Powdery Mildew of Cucurbits (Erysiphe cichoracearum), Anthracnose of Cucurbits (Colletotrichum lagenarium), Leaf Spot of Beet (Cercospora beticola), Early Blight of Tomato (Alternaria solani), Cucumber Downy Mildew (Pseudoperonospora cubensis), and Net Blotch of Barley (Pyrenophora teres).
26. The composition of any one of claim 24 wherein the fungal pathogen is one of Leaf Blotch of Wheat (Zymoseptoria tritici), Wheat Brown Rust (Puccinia triticina), Barley Scald (Rhynchosporium secalis), Blast of Rice (Pyricularia oryzae), Rust of Soybean (Phakopsora pachyrhizi), Glume Blotch of Wheat (Parastagonospora nodorum), Anthracnose of Cucurbits (Colletotrichum lagenarium), Leaf Spot of Beet (Cercospora beticola), Powdery Mildew of Grapevine (Uncinula necator), Cucumber Downy Mildew (Pseudoperonospora cubensis), and Early Blight of Tomato (Alternaria solani).
27. A method for the control and prevention of fungal attack on a plant, the method including the step of:
applying a fungicidally effective amount of at least one of the compounds of any of claims 1-21 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, and foliage of the plant.
28. A method for the control and prevention of fungal attack on a plant, the method including the step of:
applying a fungicidally effective amount of at least one of the compositions of any of claims 22-23 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, and foliage of the plant.
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