5-membered ring-based molecules and their use as herbicides

Abstract

The present disclosure is directed to 5-member ring-based molecules having herbicidal activity. Methods of synthesizing these 5-member ring-based molecules, compositions comprising these 5-member ring-based molecules, and processes for using these molecules are also disclosed. These molecules may be used, for example, as herbicides to control undesirable vegetation.

Description

Docket No.210869-WO-SEC-1 5-MEMBERED RING-BASED MOLECULES AND THEIR USE AS HERBICIDES CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application No. 63 / 589,468, filed October 11, 2023, which is incorporated by reference herein in its entirety. FIELD

[0002] The present disclosure is directed to 5-member ring-based molecules having herbicidal activity. Methods of synthesizing these 5-member ring-based molecules, compositions comprising these 5-member ring-based molecules, and processes for using these molecules are also disclosed. These molecules may be used, for example, as herbicides to control undesirable vegetation. BACKGROUND

[0003] Many recurring problems in agriculture involve controlling the growth of undesirable vegetation. If it is not controlled, the undesirable vegetation can, for instance, negatively affect the growth of desirable vegetation, such as crops, lawns, pastures, gardens, and recreational areas. To help control undesirable vegetation, researchers have produced a variety of chemicals and chemical compositions effective in controlling such unwanted growth. However, there exists an ongoing need for new herbicides and methods to control the growth of undesirable vegetation in various locations. SUMMARY

[0004] Disclosed herein are 5-member ring-based molecules, that may be used as herbicides to control undesirable vegetation in various locations, such as croplands, lawns, pastures, gardens, and recreational areas. The molecules may include 5-member ring-based molecules which may be substituted with a fluorinated benzyl group and other groups, such as an amino acid or other derivatives thereof. The molecules may also include lactams or thiolactams, either of which may be substituted with a fluorinated benzyl group and other groups, such as an amino acid or other derivatives thereof.

[0005] In some aspects, the 5-member ring-based molecules are molecules of Formula (I):Docket No.210869-WO-SEC-1wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R2is selected from the group consisting of methyl and cyclopropyl; R3is selected from the group consisting of H, methyl, and methoxy; R4is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C3-C10)-cycloalkyl, (C4-C16)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)-alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C4-C16)-aryl, (C5-C18)-alkylaryl, (C1- C16)-heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C16)-alkoxy, (C4-C16)-arylalkoxy, (C1-C10)- alkylcyano, (C1-C16)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C10)-alkylthio-(C1-C10)-alkyl, (C0-C10)-alkylsulfonyl-R74, NR72R73, SiR75R76R77, (C1-C10)-alkyl-SiR75R76R77, R78R79C=N, (C1- C10)-alkyl-C(=O)QR70, aryl-(C1-C10)-alkyl-C(=O)QR70, heteroaryl-(C1-C10)-alkyl-C(=O)QR70, (C3-C10)-cycloalkyl-(C0-C10)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C10)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1-C10)-alkyl-C(=O)QR71, hydroxy-(C1-C10)-alkyl-C(=O)QR70, (C1-C10)-alkylthio- (C1-C10)-alkyl-C(=O)QR70, (C3-C16)-alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)-haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)-alkylaryl, (C1- C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-heterocycloalkyl, (C1-C10)-heterocycloaryl,(C1- C10)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C3-C8)-cycloalkyl-(C1-C10)-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R72R73N-sulfonyl, (C1-C10)-alkoxy-NR74-sulfonyl, and aryloxysulfonyl; Q is selected from the group consisting of O, S, and NR72;Docket No.210869-WO-SEC-1 R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl, (C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together may form a substituted or unsubstituted ring or an agriculturally-acceptable salt of the molecule of Formula (I).

[0006] In some aspects, the 5-member ring-based molecules are molecules of Formula (II):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R2is selected from the group consisting of methyl and cyclopropyl; R3is selected from the group consisting of H, methyl, and methoxy; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl-Docket No.210869-WO-SEC-1 C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)-haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)-alkylaryl, (C1- C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-alkylsulfonyl, (C4-C10)-arylsulfonyl, and R72R73N-sulfonyl; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring or an agriculturally-acceptable salt of the molecule of Formula (II).

[0007] In some aspects, the 5-member ring-based molecules are molecules of Formula (III):wherein X1, X2, Y, R1, R4, R5, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (III).

[0008] In some aspects, the 5-member ring-based molecules are molecules of Formula (IV):Docket No.210869-WO-SEC-1wherein X1, X2, Y, R1, R4, R5, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (IV).

[0009] In some aspects, the 5-member ring-based molecules are molecules of Formula (V):wherein X1, X2, Y, R1, R4, R5, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (V).

[0010] In some aspects, the 5-member ring-based molecules are molecules of Formula (VI):Docket No.210869-WO-SEC-1 wherein X1, X2, Y, R4, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (VI).

[0011] In some aspects, the 5-member ring-based molecules are molecules of Formula (VII):wherein X1, X2, Y, R4, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (VII).

[0012] In some aspects, the 5-member ring-based molecules are molecules of Formula (VIII):wherein X1, X2, Y, R4, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (VIII).

[0013] In some aspects, the 5-member ring-based molecules are molecules of Formula (IX):Docket No.210869-WO-SEC-1wherein X1, X2, Y, R4, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (IX).

[0014] In some aspects, the 5-member ring-based molecules are molecules of Formula (X):wherein X1, X2, Y, R4, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (X).

[0015] In some aspects, the 5-member ring-based molecules are molecules of Formula (XI):Docket No.210869-WO-SEC-1 wherein X1-X2, Y, R4, Q, and R70- R79are as defined for Formula (II) or an agriculturally-acceptable salt of the molecule of Formula (XI).

[0016] Various 5-member ring-based molecules included in the present disclosure, such as lactam-based or thiolactam-based molecules, have been found to exhibit herbicidal activity against various key species of undesirable vegetation.

[0017] The description below sets forth details of one or more aspects of the present disclosure. Other features, objects, and advantages will be apparent from the description and from the claims. DETAILED DESCRIPTION

[0018] The present disclosure includes molecules that may be used as herbicides to control undesirable vegetation in various locations, such as croplands, lawns, pastures, gardens, and recreational areas. These 5-member ring-based molecules, such as lactam-based or thiolactam- based molecules, may be substituted with fluorinated benzyl groups and other groups, such as amino acid groups or derivatives thereof. The present disclosure also includes methods for using the molecules for controlling undesirable vegetation. In some aspects, the undesirable vegetation is in row crops. In some aspects, the undesirable vegetation is in maize, soy, canola, cotton, pulses, sunflower, sugar beet, wheat, barley, rice, sorghum, millet, or oats. In some aspects, the molecules are graminicides used to control undesirable vegetation including grass-type species. 1. Definitions

[0019] Terms used herein will have their customary meaning in the art unless specified otherwise. The singular forms "a" and "the" include plural references unless stated otherwise. To the extent that the term "or" is employed (e.g., A or B) it is intended to mean "A or B or both." Thus, use of the term "or" herein is the inclusive and not the exclusive use.

[0020] As used herein, the terms “herbicide” and “herbicidal active ingredient” refer to an active ingredient that kills, controls, or otherwise adversely modifies the growth of vegetation, particularly undesirable vegetation such as weed species, when applied in an appropriate amount.

[0021] As used herein, the term “herbicidal effect” is an adversely modifying effect of an active ingredient on vegetation, including, for example, a deviation from natural growth or development, killing, regulation, desiccation, growth inhibition, growth reduction, andDocket No.210869-WO-SEC-1 retardation. The term "herbicidal activity" refers generally to herbicidal effects of an active ingredient.

[0022] As used herein, the term “herbicide resistance” refers to an inherited ability of an individual plant to survive an herbicide application that would kill a normal population of the same species of plant. Herbicide resistance in a plant species often arises due to the application of an herbicide on plants of that species in a specific location.

[0023] As used herein, the term “herbicide tolerance” refers to the inherent ability of a species of plants to survive and reproduce after herbicide treatment at a normal use rate. Herbicide tolerance is therefore a natural tolerance within the normal population of the plant species, rather than resistance selected for in that species by the application of an herbicide.

[0024] As used herein, a “composition” is a mixture comprising at least one herbicide, and also comprising other ingredients used to enhance the properties or effectiveness of the mixture in some way. The other ingredients may include, but are not limited to, diluents, surfactants, adjuvants, anti-foam agents, emulsifiers, colorants, dispersants, antifreeze agents, and other such ingredients.

[0025] As used herein, "applying" an herbicide or herbicidal composition refers to delivering it directly to the targeted vegetation or to the locus thereof or to the area where control of undesirable vegetation is desired. Methods of application include, but are not limited to, pre- emergently contacting soil or water, post-emergently contacting the undesirable vegetation, or contacting the area adjacent to the undesirable vegetation.

[0026] As used herein, the term “vegetation” can include, for instance, dormant seeds, germinating seeds, emerging seedlings, plants propagating from vegetative propagules, immature vegetation, and established vegetation.

[0027] As used herein, the term "crop" refers to desired vegetation, for instance, plants that are grown to provide food, shelter, pasture, erosion control, etc. Example crops include cereals, legumes, vegetables, orchard and timber trees, grapevines, etc. Preferably, herbicides or herbicidal compositions have zero or minimal herbicidal effect on crops.

[0028] As used herein, the term "undesirable vegetation" refers to vegetation that is not wanted in a given area, for instance, weed species. Herbicides or herbicidal compositions are used to control undesirable vegetation. Preferably, herbicides or herbicidal compositions have a large or complete herbicidal effect on undesirable vegetation.Docket No.210869-WO-SEC-1

[0029] As used herein, “alkyl” refers to straight-chained or branched saturated hydrocarbon moieties. Unless otherwise specified, C1-C16alkyl groups are intended. Examples include methyl, ethyl, propyl, 1-methyl-ethyl, butyl, 1-methyl-propyl, 2-methyl-propyl, 1,1-dimethyl-ethyl, pentyl, 1-methyl-butyl, 2-methyl-butyl, 3-methyl-butyl, 2,2-dimethyl-propyl, 1-ethyl-propyl, hexyl, 1,1-dimethyl-propyl, 1,2-dimethyl-propyl, 1-methyl-pentyl, 2-methyl-pentyl, 3-methyl- pentyl, 4-methyl-pentyl, 1,1-dimethyl-butyl, 1,2-dimethyl-butyl, 1,3-dimethyl-butyl, 2,2- dimethyl-butyl, 2,3-dimethyl-butyl, 3,3-dimethyl-butyl, 1-ethyl-butyl, 2-ethyl-butyl, 1,1,2- trimethyl-propyl, 1,2,2-trimethyl-propyl, 1-ethyl-1-methyl-propyl, and 1-ethyl-2-methyl-propyl.

[0030] As used herein, “cycloalkyl” refers to saturated hydrocarbon moieties arranged in a ring. As used herein, “alkylcycloalkyl” refers to cycloalkyl moities with alkyl substituents. Unless otherwise specified, C3-C16 cycloalkyl or alkylcycloalkyl groups are intended. Examples include cyclopropyl, cyclobutyl, methylcyclopropyl, 1,1-dimethylcyclopropyl, 1,2- dimethylcyclopropyl, cyclopentyl, 1-methylcyclobutyl, 2-methylcyclobutyl, 1,2- dimethylcyclobutyl, 1,3-dimethylcyclobutyl, 1-ethylcyclobutyl, cyclohexyl, 1,2- dimethylcyclobutyl, 1,3-dimethylcyclobutyl, 1-ethylcyclobutyl, 1-methylcyclopentyl, 2- methylcyclopentyl, cycloheptyl, 1-methylcyclohexyl, 2-methylcyclohexyl, 3-methylcyclohexyl, 1,1-dimethylcyclopentyl, 1,2-dimethylcyclopentyl, 1,3-dimethylcyclopentyl, 1,4- dimethylcyclopentyl, 2,3-dimethylcyclopentyl, 1-ethylcyclopentyl, 1,1,2-trimethylcyclobutyl, 1,2,3-trimethylcyclopentyl, 1-ethyl-1-methylcyclohexyl, cyclooctyl, 1-ethylcyclohexyl, 1,2- dimethylcyclohexyl, 1,3-dimethylcyclohexyl, and 1-ethylcyclohexyl.

[0031] As used herein, “polycycloalkyl” refers to saturated hydrocarbon moieties arranged in two or more rings sharing one or more carbon atoms. Polycycloalkyl groups may be fused- ring, spiro, or bridged-ring structures. Unless otherwise specified, C4-C16polycycloalkyl groups are intended. Examples include spiro[2.2]heptane, spiro[2.4]heptane, bicyclo[3.2.0]heptane, bicyclo[2.2.1]heptane (also called norbornane), bicyclo[3.3.0]octane, bicyclo[3.2.1]octane, bicyclo[4.4.0]decane (also called decalin). As used herein, “alkylpolycycloalkyl” refers to polycycloalkyl groups with alkyl substituents.

[0032] As used herein, “haloalkyl” refers to straight-chained or branched alkyl groups, in which the hydrogen atoms may be substituted partially or entirely with halogen atoms. Unless otherwise specified, C1-C16 groups are intended. Examples include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1- fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-Docket No.210869-WO-SEC-1 chloro-2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl.

[0033] As used herein, “alkenyl” refers to unsaturated straight-chained or branched hydrocarbon moieties containing a carbon-carbon double bond. Unless otherwise specified, C3- C16 alkenyl are intended. Alkenyl groups may contain more than one carbon-carbon double bond. Examples include ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2- propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1- butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1- methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2- dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1- hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl- 2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3- pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1- ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2- trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl, and 1-ethyl-2- methyl-2-propenyl. Vinyl refers to a group having the strutcture –CH=CH2; 1-propenyl refers to a group with the structure–CH=CH-CH3; and 2-propenyl refers to a group with the structure –CH2- CH=CH2.

[0034] As used herein, “alkylidene” refers to an unsaturated straight-chained or branched hydrocarbon moiety containing a carbon-carbon double bond of the wherein the double bond of the moiety is the bond to the rest of theR groups are independently H or C3-C12 alkyl groups.

[0035] As used herein, “alkynyl” represents unsaturated straight-chained or branched hydrocarbon moieties containing a carbon-carbon triple bond. Unless otherwise specified, C3- C16 alkynyl groups are intended. Alkynyl groups may contain more than one carbon-carbon tripleDocket No.210869-WO-SEC-1 bond. Examples include C2-C6-alkynyl, such as ethynyl, 1-propynyl, 2-propynyl (or propargyl), 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4- pentynyl, 3-methyl-1-butynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1,1- dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5- hexynyl, 3-methyl-1-pentynyl, 4-methyl-1-pentynyl, 1-methyl-2-pentynyl, 4-methyl-2-pentynyl, 1-methyl-3-pentynyl, 2-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 3-methyl- 4-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2- dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3- butynyl, and 1-ethyl-1-methyl-2-propynyl.

[0036] As used herein, “alkoxy” refers to a group of the formula R-O-, where R is alkyl as defined above. Unless otherwise specified, alkoxy groups wherein R is a C1-C10 alkyl group are intended. Examples include methoxy, ethoxy, propoxy, 1-methyl-ethoxy, butoxy, 1-methyl- propoxy, 2-methyl-propoxy, 1,1-dimethyl-ethoxy, pentoxy, 1-methyl-butyloxy, 2-methyl-butoxy, 3-methyl-butoxy, 2,2-dimethyl-propoxy, 1-ethyl-propoxy, hexoxy, 1,1-dimethyl-propoxy, 1,2- dimethyl-propoxy, 1-methyl-pentoxy, 2-methyl-pentoxy, 3-methyl-pentoxy, 4-methyl-pentoxy, 1,1-dimethyl-butoxy, 1,2-dimethyl-butoxy, 1,3-dimethyl-butoxy, 2,2-dimethyl-butoxy, 2,3- dimethyl-butoxy, 3,3-dimethyl-butoxy, 1-ethyl-butoxy, 2-ethyl-butoxy, 1,1,2-trimethyl-propoxy, 1,2,2-trimethyl-propoxy, 1-ethyl-1-methyl-propoxy, and 1-ethyl-2-methyl-propoxy.

[0037] As used herein, “alkylthio” refers to a group of the formula R-S- where R is alkyl as defined above. Unless otherwise specified, alkylthio groups wherein R is a C1-C10 alkyl group are intended. Examples include methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1- methyl-propylthio, 2-methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2- methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1- dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3- methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3- dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1- ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, 1-ethyl-1- methylpropylthio, and 1-ethyl-2-methylpropylthio.

[0038] As used herein, “heterocycloalkyl,” as well as derivative terms such as heteroalkylcycloalkyl or heterocycloalkoxy, refers to saturated hydrocarbon moieties arranged in a ring wherein one or more carbon atoms in the ring is substituted with a heteroatom, such as N, O, or S. Unless otherwise specified, C3-C16 heterocycloalkyl groups are intended.Docket No.210869-WO-SEC-1

[0039] As used herein, “aryl”, as well as derivative terms such as aryloxy, refers to a phenyl, indanyl or naphthyl group, with phenyl being preferred. The term heteroaryl, as well as derivative terms such as heteroaryloxy, refers to a 4-, 5-, or 6-membered aromatic ring containing one or more heteroatoms, viz., N, O or S; these aromatic and heteroaromatic rings may be fused to other aromatic and / or heteroaromatic systems.

[0040] As used herein, “alkylaryl”, as well as derivative terms such as arylalkoxy, refers to a C1-C16 alkyl group substituted with one or more phenyl, indanyl or naphthyl groups, with phenyl or benzyl substituents being preferred. For instance, C7-C16alkylaryl refers to a group wherein the total number of carbon atoms in the group is 7 to 16.

[0041] As used herein, “alkoxycarbonyl” refers to a group of the wherein R is alkyl.

[0042] As used herein “alkylsulfonyl” refers to a group of the formula , where R is alkyl.

[0043] As used herein, trialkylsilyl refers to a group of the formula –SiR3 wherein each R is independently a C1-C8 alkyl group (the trialkylsilyl group contains a total of 3 to 18 carbon atoms).

[0044] As used herein Me refers to a methyl group and OMe refers to a methoxy group.

[0045] As used herein, “substituted” refers to any of the moities defined above, such as “alkyl,” “alkenyl,” “cycloalkyl,” etc., which is substituted with one or more substituents selected from halogen, hydroxy, nitro, cyano, formyl, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6alkoxycarbonyl, C1-C6carbamoyl, hydroxycarbonyl, C1-C6alkylcarbonyl, aminocarbonyl, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied.

[0046] As used herein, the term halogen including derivative terms such as halo refers to fluorine, chlorine, bromine and iodine.

[0047] As used herein, agriculturally acceptable salts refer to salts that are approved for use in agricultural applications. Agriculturally acceptable salts of herbicides may be converted inDocket No.210869-WO-SEC-1 plants, water, or soil to the referenced herbicide, which, depending on the pH, may be in the dissociated or undissociated form. Exemplary agriculturally acceptable salts include but are not limited to: cationic alkali metals or alkali earth metals; ammonium ions; mono-, di-, tri-, or tetra- alkylammonium ions; mono-, di-, tri-, or tetra-alkylhydroxyammonium ions; and unsubstituted or substituted morpholinium ions.

[0048] As used herein, "active ingredient" or "ai" refers to a chemical compound or composition that has an effect on vegetation, for example, a herbicidal effect or a safening effect on the vegetation.

[0049] As used herein, "acid equivalent" or "ae" refers to the amount of the acid form of an active ingredient that is calculated from the amount of a salt or ester form of that active ingredient. For example, if the acid form of an active ingredient "Z" has a molecular weight of 100 Dalton, and the salt form of Z has a molecular weight of 130 Dalton, an application of 130 grams of active ingredient per hectare (g ai / ha) of the Z salt would be equal to applying 100 grams of acid equivalent per hectare (g ae / ha) of the acid form of Z: 130 g ai / ha Z salt * (100 Da Z acid / 130 Da Z salt) = 100 g ae / ha Z acid. 2. 5-member Ring-Based Molecules

[0050] Disclosed herein are 5-member ring-based molecules, such as lactam-based or thiolactam-based molecules, that may be used as herbicides to control undesirable vegetation in various locations, such as croplands, lawns, pastures, gardens, and recreational areas. The molecules include molecules that are substituted with fluorinated benzyl groups and amino acid groups, and derivatives thereof.

[0051] In some aspects, the 5-member ring-based molecules are molecules of Formula (I):Docket No.210869-WO-SEC-1 wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R2is selected from the group consisting of methyl and cyclopropyl; R3is selected from the group consisting of H, methyl, and methoxy; R4is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C3-C10)-cycloalkyl, (C4-C16)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6- C16)-alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C4-C16)-aryl, (C5-C18)-alkylaryl, (C1-C16)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C16)-alkoxy, (C4-C16)-arylalkoxy, (C1-C10)-alkylcyano, (C1-C16)-haloalkyl(C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C10)-alkylthio-(C1-C10)-alkyl, (C0-C10)- alkylsulfonyl-R74, NR72R73, SiR75R76R77, (C1-C10)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C10)-alkyl-C(=O)QR70, heteroaryl-(C1-C10)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C10)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C10)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C10)-alkyl-C(=O)QR71, hydroxy-(C1-C10)-alkyl-C(=O)QR70, (C1-C10)-alkylthio-(C1-C10)-alkyl- C(=O)QR70, (C3-C16)-alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)-haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)-alkylaryl, (C1- C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-heterocycloalkyl, (C1-C10)-heterocycloaryl,(C1- C10)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C3-C8)-cycloalkyl-(C1-C10)-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R72R73N-sulfonyl, (C1-C10)-alkoxy-NR74-sulfonyl, and aryloxysulfonyl; Q is selected from the group consisting of O, S, and NR72; R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl, (C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; andDocket No.210869-WO-SEC-1 R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together may form a substituted or unsubstituted ring or an agriculturally-acceptable salt of the molecule of Formula (I).

[0052] In some aspects, the 5-member ring-based molecules are molecules of Formula (II):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R2is selected from the group consisting of methyl and cyclopropyl; R3is selected from the group consisting of H, methyl, and methoxy; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof;Docket No.210869-WO-SEC-1 R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)-haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)-alkylaryl, (C1- C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-alkylsulfonyl, (C4-C10)-arylsulfonyl, and R72R73N-sulfonyl; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (II).

[0053] In some aspects, the 5-member ring-based molecules are molecules of Formula (III):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-alky, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)-Docket No.210869-WO-SEC-1 alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)-haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)-alkylaryl, (C1- C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-alkylsulfonyl, (C4-C10)-arylsulfonyl, and R72R73N-sulfonyl; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (III).

[0054] In some aspects, the 5-member ring-based molecules are molecules of Formula (IV):Docket No.210869-WO-SEC-1 wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl,(C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)-haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)-alkylaryl, (C1- C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-alkylsulfonyl, (C4-C10)-arylsulfonyl, and R72R73N-sulfonyl; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (IV).

[0055] In some aspects, the 5-member ring-based molecules are molecules of Formula (V):Docket No.210869-WO-SEC-1wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl,(C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)-haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)-alkylaryl, (C1- C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-alkylsulfonyl, (C4-C10)-arylsulfonyl, and R72R73N-sulfonyl; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring;Docket No.210869-WO-SEC-1 R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (V).

[0056] In some aspects, the 5-member ring-based molecules are molecules of Formula (VI):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl,(C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; Q is selected from the group consisting of O, S, and NR72,Docket No.210869-WO-SEC-1 R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (VI).

[0057] In some aspects, the 5-member ring-based molecules are molecules of Formula (VII):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl,(C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof;Docket No.210869-WO-SEC-1 Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (VII).

[0058] In some aspects, the 5-member ring-based molecules are molecules of Formula (VIII):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl,(C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1-Docket No.210869-WO-SEC-1 C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (VIII).

[0059] In some aspects, the 5-member ring-based molecules are molecules of Formula (IX):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl,(C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl-Docket No.210869-WO-SEC-1 C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (IX).

[0060] In some aspects, the 5-member ring-based molecules are molecules of Formula (X):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl,(C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)-Docket No.210869-WO-SEC-1 heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (X).

[0061] In some aspects, the 5-member ring-based molecules are molecules of Formula (XI):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S;Docket No.210869-WO-SEC-1 R4is selected from the group consisting of H, hydroxy, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3- C8)-alkynyl, (C3-C8)-cycloalkyl, (C4-C10)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C16)- alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C5-C12)-aryl, (C6-C18)-alkylaryl, (C1-C12)- heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C16)-arylalkoxy, (C1-C6)-alkylcyano, (C1-C8)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl- sulfonyl-R74, NR72R73, SiR75R76R77, (C1-C6)-alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl- C(=O)QR70, aryl-(C1-C6)-alkyl-C(=O)QR70, heteroaryl-(C1-C6)-alkyl-C(=O)QR70, (C3-C10)- cycloalkyl-(C0-C6)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C6)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1- C6)-alkyl-C(=O)QR71, hydroxy-(C1-C6)-alkyl-C(=O)QR70, (C1-C6)-alkylthio-(C1-C6)-alkyl- C(=O)QR70, (C3-C10)-alkylidene-amino-oxo, and salts thereof; Q is selected from the group consisting of O, S, and NR72, R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1- C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl,(C1-C16)-haloalkyl, (C1-C16)- arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1- C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together form a substituted or unsubstituted ring, or an agriculturally-acceptable salt of the molecule of Formula (XI).

[0062] The 5-member ring-based molecules of the present disclosure exist in specific chiral forms, as shown in the molecular structures shown throughout the present application. However, the 5-member ring-based molecules may also exist in different geometric or optical isomeric forms at other locations within each molecule. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. This disclosure covers all such chiral forms, isomers, and mixtures thereof, in all proportions.

[0063] Examples of 5-member ring-based molecules of the present disclosure are listed in Table 1 below. Analytical data and the method of preparation (see Section 3 below) are also given.Docket No.210869-WO-SEC-1 Table 1: Examples of 5-member ring-based molecules Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. Structure Mass NMR C orMethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)MethodDocket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .Docket No.210869-WO-SEC-1 Cmpd. Prep. NStructure Mass NMR (H , C or F)Method .3. Preparation of 5-member ring-based molecules

[0064] 5-member ring-based molecules of the present disclosure were prepared in accordance with the preparation methods given below.

[0065] Method 1: Preparation of Methyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.1)Docket No.210869-WO-SEC-1

[0066] In a round-bottomed flaskstir bar were added (S)-2-(1- (2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetic acid (1 equiv) and amine or ammonium chloride or ammonium trifluoroacetate (1 equiv) in dichloromethane (CH2Cl2, 0.1 M).3- (((Ethylimino) methylene)amino)-N,N-dimethylpropan-1-amine) hydrochloride (1.2 equiv), triethylamine (1.2 equiv), and N,N-dimethylpyridin-4-amine (1.2 equiv) were added sequentially. The reaction mixture was stirred at 20 °C for 18 hours (h) or until the reaction was complete. The reaction product was concentrated onto silica gel and purified by silica column chromatography. (1.405 g, 89% yield)

[0067] The following compounds were prepared in accordance to the procedure in Method 1:

[0068] Allyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.3)

[0069] The title compound was prepared and was isolated as a clear oil. (151.5 mg, 70% yield)

[0070] N-Propyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.9)Docket No.210869-WO-SEC-1

[0071] The title compound wasas a colorless oil. (220 mg, 72% yield)

[0072] Isopropyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.8)

[0073] The title compound was as a colorless oil. (220 mg, 72% yield)

[0074] Benzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.6)

[0075] The title compound was prepared and was isolated as a colorless oil. (474 mg, 88% yield)Docket No.210869-WO-SEC-1

[0076] Ethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.5)

[0077] The title compound wasas a colorless liquid). (421 mg, 91% yield)

[0078] Methyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- valinate (Compound No.323)

[0079] The title compound was prepared and was isolated as a colorless oil. (270.5 mg, 77% yield)

[0080] Prop-2-yn-1-yl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.4)Docket No.210869-WO-SEC-1

[0081] The title compound was prepared and was isolated as a yellow sticky oil. (154 mg, 72% yield)

[0082] Methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoate (Compound No.205)

[0083] The title compound wasas a clear oil. (527.8 mg, 85% yield)

[0084] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N- methyl-L-valinate (Compound No.24)

[0085] The title compound was prepared and was isolated as a clear oil. (567.1 mg, 86% yield)

[0086] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- leucinate (Compound No.22)Docket No.210869-WO-SEC-1

[0087] The title compound wasas a colorless solid. (60 mg, 22% yield)

[0088] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threoninate (Compound No.280)

[0089] The title compound was was as a clear oil. (523.7 mg, 85% yield)

[0090] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-ethyl- L-valinate (Compound No.27)Docket No.210869-WO-SEC-1

[0091] The title compound was prepared and was isolated as a clear oil. (542.2 mg, 84% yield)

[0092] Methyl N-(cyanomethyl)-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.26)

[0093] The title compound wasas a yellow oil. (197.2 mg, 40% yield)

[0094] Methyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoate (Compound No.350)

[0095] The title compound was prepared and was isolated as a yellow oil. (806.2 mg, 95% yield)

[0096] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-(prop- 2-yn-1-yl)-L-valinate (Compound No.31)Docket No.210869-WO-SEC-1

[0097] The title compound wasas a yellow oil. (285.6 mg, 64% yield)

[0098] Methyl N-allyl-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.29)

[0099] The title compound was was as a yellow oil. (237.8 mg, 67% yield)

[0100] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-(2- methoxy-2-oxoethyl)-L-valinate (Compound No.47)

[0101] The title compound was prepared and was isolated as a yellow oil. (328.6 mg, 35% yield)Docket No.210869-WO-SEC-1

[0102] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threoninate (Compound No.410)

[0103] The title compound wasas a clear oil. (328.3 mg, 77% yield)

[0104] 2-(Methylsulfonyl)ethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.55)

[0105] The title compound was prepared and was isolated as a white fluffy solid. (135 mg, 51% yield)

[0106] Furan-2-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.56)Docket No.210869-WO-SEC-1

[0107] The title compound was prepared and was isolated as a yellow oil. (35.9 mg, 15% yield)

[0108] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-(methylsulfonyl)butanamide (Compound No.65)

[0109] The title compound wasas an off white solid. (43 mg, 17% yield, melting point 52-54 °C)

[0110] (R)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-(methylsulfonyl)butanamide (Compound No.57)

[0111] The title compound was was as an off white solid. (40 mg, 16% yield, melting point 63-65 °C)

[0112] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N- (ethylsulfonyl)-3-methylbutanamide (Compound No.58)Docket No.210869-WO-SEC-1

[0113] The title compound wasas a white solid. (110 mg, 54% yield, melting point 73-75 °C)

[0114] (S)-N-(Cyclopropylsulfonyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin- 2-yl)acetamido)-3-methylbutanamide (Compound No.59)

[0115] The title compound was was as an off white solid. (120 mg, melting point 70-72 °C)

[0116] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(N- methoxysulfamoyl)-3-methylbutanamide (Compound No.64)

[0117] The title compound was prepared and was isolated as an off white solid. (167 mg, melting point 73-75 °C)Docket No.210869-WO-SEC-1

[0118] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(N- isopropylsulfamoyl)-3-methylbutanamide (Compound No.63)

[0119] The title compound wasas an off white solid. (107 mg, melting point 159-161 °C)

[0120] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-(phenylsulfonyl)butanamide (Compound No.62)

[0121] The title compound was was as a white solid. (83 mg, melting point 76-78 °C)

[0122] (S)-N-(tert-Butylsulfonyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.61)Docket No.210869-WO-SEC-1

[0123] The title compound was prepared and was isolated as an off white solid. (100 mg, melting point 121-123 °C)

[0124] (S)-N-((Cyclopropylmethyl)sulfonyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methylbutanamide (Compound No.60)

[0125] The title compound wasas an off white solid. (Compound No.63 mg, melting point 56-58 °C)

[0126] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonylglycinate (Compound No.283)

[0127] The title compound was prepared and was isolated as a white solid. (176.9 mg, 75% yield)

[0128] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threonyl-L-phenylalaninate (Compound No.412)Docket No.210869-WO-SEC-1

[0129] The title compound wasas a white solid. (249.6 mg, 87% yield)

[0130] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-(pyrrolidin-1-ylsulfonyl)butanamide (Compound No.68)

[0131] The title compound was was as an off white solid. (210 mg, melting point 73-75 °C)

[0132] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(N,N- dimethylsulfamoyl)-3-methylbutanamide (Compound No.67)

[0133] The title compound was prepared and was isolated as an off white solid. (119 mg, melting point 71-73 °C)Docket No.210869-WO-SEC-1

[0134] Phenyl ((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valyl)sulfamate (Compound No.66)

[0135] The title compoundas an off white solid. (180 mg, melting point 80-82 °C)

[0136] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threonylglycinate (Compound No.413)

[0137] The title compound was prepared and was isolated as a white solid. (382.1 mg, 79% yield)

[0138] 2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)-N-((S)-3-methyl-1-oxo-1- ((propan-2-ylideneamino)oxy)butan-2-yl)acetamide (Compound No.73)Docket No.210869-WO-SEC-1

[0139] The title compound was prepared and was isolated as a thick pale yellow oil. (344 mg, 71% yield)

[0140] S-Benzyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)- 3-methylbutanethioate (Compound No.72)

[0141] The title compound wasas a thick clear oil. (412 mg, 77% yield)

[0142] (2S,3R)-N-(Allyloxy)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)butanamide (Compound No.414)

[0143] The title compound was prepared and was isolated as a white semi solid. (147.9 mg, 61% yield)

[0144] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)-L-phenylalaninate (Compound No.353)Docket No.210869-WO-SEC-1

[0145] The title compound wasas a white solid. (220.7 mg, 71% yield)

[0146] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)glycinate (Compound No.352)

[0147] The title compound was prepared and was isolated as a white solid. (542.3 mg, 75% yield)

[0148] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N,N,3- trimethylbutanamide (Compound No.74)Docket No.210869-WO-SEC-1

[0149] The title compound was prepared and was isolated as a thick clear and colorless oil. (312 mg, 70% yield)

[0150] tert-Butyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.76)

[0151] The title compound wasas a colorless oil. (475 mg, 92% yield)

[0152] (S)-N-(Allyloxy)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanamide (Compound No.354)

[0153] The title compound was prepared and was isolated as a clear oil. (46.4 mg, 59% yield)

[0154] S-Benzyl (S)-3-methyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)butanethioate (Compound No.327)Docket No.210869-WO-SEC-1

[0155] The title compound was was as a thick clear and colorless oil. (269 mg, 78% yield)

[0156] S-Isopropyl (S)-2-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamido)-3-methylbutanethioate (Compound No.88)

[0157] The title compound was as a white crystalline solid. (29 mg, 7% yield)

[0158] S-Isopropyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.87)Docket No.210869-WO-SEC-1

[0159] The title compound was prepared and was isolated as a thick clear and colorless oil. (194 mg, 61% yield)

[0160] S-Isopropyl (S)-3-methyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)butanethioate (Compound No.328)

[0161] The title compound was as a white solid. (188 mg, 60% yield)

[0162] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoyl)-L-leucinate (Compound No.228)

[0163] The title compound was prepared and was isolated as an off white solid. (115 mg, melting point 91-93 °C)

[0164] S-(4-(Trifluoromethyl)benzyl) (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methylbutanethioate (Compound No.125)Docket No.210869-WO-SEC-1

[0165] The title compoundas a colorless thick semisolid. (239 mg, 59% yield)

[0166] S-(4-(Trifluoromethoxy)benzyl) (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methylbutanethioate (Compound No.128)

[0167] The title compound was prepared and was isolated as a thick clear and colorless oil. (336 mg, 79% yield)

[0168] S-(4-methylbenzyl) (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.129)Docket No.210869-WO-SEC-1

[0169] The title compound was prepared and was isolated as a thick clear and colorless oil. (225 mg, 60% yield)

[0170] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)-L-leucinate (Compound No.368)

[0171] The title compound wasas a white solid. (160 mg, melting point 144-146 °C)

[0172] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threonyl-L-valinate (Compound No.415)

[0173] The title compound was prepared and was isolated as a colorless liquid. (177 mg)

[0174] Methyl (S)-3-cyclopropyl-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methoxybutanamido)propanoate (Compound No.286)Docket No.210869-WO-SEC-1

[0175] The title compoundas an off white solid. (187 mg, melting point 125-127 °C)

[0176] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl-L-isoleucinate (Compound No.285)

[0177] The title compound was was as a colorless liquid. (194 mg)

[0178] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl-L-leucinate (Compound No.284)

[0179] The title compound was prepared and was isolated as a colorless liquid. (193 mg)Docket No.210869-WO-SEC-1

[0180] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threonyl-L-leucinate (Compound No.416)

[0181] The title compound wasas an off white gummy solid. (105 mg)

[0182] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threonyl-L-isoleucinate (Compound No.417)

[0183] The title compound was was as a colorless liquid. (149 mg)

[0184] Methyl (S)-3-cyclopropyl-2-((2S,3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)butanamido)propanoate (Compound No.418)Docket No.210869-WO-SEC-1

[0185] The title compound was prepared and was isolated as a colorless liquid. (208 mg)

[0186] Methyl (S)-3-cyclopropyl-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanamido)propanoate (Compound No.242)

[0187] The title compound wasas an off white solid. (191 mg, melting point 153-154 °C)

[0188] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)-L-alaninate (Compound No.373)

[0189] The title compound was prepared and was isolated as a white solid. (168 mg, melting point 106-108 °C)

[0190] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)-L-isoleucinate (Compound No.372)Docket No.210869-WO-SEC-1

[0191] The title compoundas a white solid. (190 mg, melting point 124-126 °C)

[0192] Methyl (S)-3-cyclopropyl-2-((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanamido)propanoate (Compound No.371)

[0193] The title compound was was as a white solid. (188 mg, melting point 122-124 °C)

[0194] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threonyl-L-alaninate (Compound No.420)

[0195] The title compound was prepared and was isolated as a colorless liquid. (171 mg)Docket No.210869-WO-SEC-1

[0196] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)-L-valinate (Compound No.370)

[0197] The title compoundas a white solid. (122 mg, melting point 153-155 °C)

[0198] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)-L-isoleucinate (Compound No.241)

[0199] The title compound was was as a colorless liquid. (222 mg)

[0200] Cyclopentyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.144)Docket No.210869-WO-SEC-1

[0201] The title compound was prepared and was isolated as a colorless oil. (226 mg, 88% yield)

[0202] Pyridazin-4-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.155)

[0203] The title compound wasas a brown oil. (193 mg, 50.8% yield)

[0204] Octyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.145)

[0205] The title compound was prepared and was isolated as a colorless oil. (220 mg, 69 % yield)

[0206] Pyridin-4-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (156)Docket No.210869-WO-SEC-1

[0207] The title compound wasas a brown oil. (226.07 mg, 69% yield)

[0208] Cyclopropylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.157)

[0209] The title compound was prepared and was isolated as a colorless oil. (110 mg, 33% yield)

[0210] Cyclobutylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.158)Docket No.210869-WO-SEC-1

[0211] The title compound was prepared and was isolated as a colorless oil. (171 mg, 50% yield)

[0212] S-Isobutyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.174)

[0213] The title compound was as a thick clear colorless oil. (218 mg, 64% yield)

[0214] S-Phenethyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.173)

[0215] The title compound was was as a thick clear colorless oil. (256 mg, 69% yield)

[0216] S-Cyclohexyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.172)Docket No.210869-WO-SEC-1

[0217] The title compound wasas a thick clear semisolid. (288 mg, 82% yield)

[0218] rac-2-((R)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)-N-((R)-3-methyl-1-(2- methyl-2-phenylhydrazineyl)-1-oxobutan-2-yl)acetamide (Compound No.171)

[0219] The title compound as a white crystalline solid. (289 mg, 78% yield)

[0220] Phenethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.167)Docket No.210869-WO-SEC-1

[0221] The title compound was prepared and was isolated as a colorless oil. (272 mg, 74% yield)

[0222] Cyclohexyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.166)

[0223] The title compound wasas a colorless oil. (284 mg, 81% yield)

[0224] Cyclobutyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.165)

[0225] The title compound was prepared and was isolated as a colorless oil. (260 mg, 79% yield)

[0226] (S)-sec-Butyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.164)Docket No.210869-WO-SEC-1

[0227] The title compound wasas a colorless oil. (170 mg, 51% yield)

[0228] (R)-sec-Butyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.163)

[0229] The title compound was was as a colorless oil. (74 mg, 22% yield)

[0230] 2-Methoxy-2-oxoethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.162)Docket No.210869-WO-SEC-1

[0231] The title compound was prepared and was isolated as a colorless oil. (163 mg, 47% yield)

[0232] 3,3-Dimethylbutyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.161)

[0233] The title compound wasas a colorless oil. (205 mg, 58% yield)

[0234] Cyclohexylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.160)

[0235] The title compound was prepared and was isolated as a colorless oil. (83 mg, 42% yield)

[0236] Cyclopentylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.159)Docket No.210869-WO-SEC-1

[0237] The title compound wasas a colorless oil. (191 mg, 54% yield)

[0238] N-((RS)-1-(2,2-Dimethylhydrazineyl)-3-methyl-1-oxobutan-2-yl)-2-((S)-5-oxo- 1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetamide (Compound No.334)

[0239] The title compound was prepared and was isolated as a white solid. (156 mg, 49.7% yield)

[0240] Methyl 2-(((RS)-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)valyl)thio)acetate (Compound No.175)Docket No.210869-WO-SEC-1

[0241] The title compound was prepared and was isolated as a thick clear and colorless oil. (277 mg, 80% yield)

[0242] (RS)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-(pyrrolidin-1-yl)butanamide (Compound No.176)

[0243] The title compound wasas a white solid. (101 mg, 30.5% yield)

[0244] S-(4-Methoxybenzyl) (RS)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.186)

[0245] The title compound was prepared and was isolated as a clear and colorless oil. (268 mg, 70.1% yield)

[0246] (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.188)Docket No.210869-WO-SEC-1

[0247] The title compound wasas a colorless glue. (98 mg, 25% yield)

[0248] (1S,2R,5S)-2-Isopropyl-5-methylcyclohexyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.187)

[0249] The title compound was prepared and was isolated as a colorless glue. (165 mg, 42% yield)

[0250] S-Benzyl (RS)-3-methyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)butanethioate (Compound No.454)Docket No.210869-WO-SEC-1

[0251] The title compound wasas a clear solid. (101 mg, 29% yield)

[0252] Benzyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetamido)propanoyl)-L-phenylalaninate (Compound No.395)

[0253] The title compound was prepared and was isolated as a white solid. (194.9 mg, 58% yield)

[0254] Benzyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoyl)-L-phenylalaninate (Compound No.260)Docket No.210869-WO-SEC-1

[0255] The title compound was prepared and was isolated as a white solid. (193.5 mg, 60% yield)

[0256] N-((S)-3-Methyl-1-oxo-1-((propan-2-ylideneamino)oxy)butan-2-yl)-2-((S)-5- oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetamide (Compound No.455)

[0257] The title compound was prepared and was isolated as a off white solid. (201mg, 63.4% yield)

[0258] N-((S)-3-Cyclopropyl-1-oxo-1-((propan-2-ylideneamino)oxy)propan-2-yl)-2- ((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamide (Compound No.452)

[0259] The title compound was was as a clear thick oil. (121 mg, 37% yield)

[0260] N-((S)-3-Cyclopropyl-1-oxo-1-((propan-2-ylideneamino)oxy)propan-2-yl)-2- ((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetamide (Compound No.456)Docket No.210869-WO-SEC-1

[0261] The title compound wasas a thick clear and colorless oil. (91 mg, 29% yield)

[0262] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl-L-alaninate (Compound No.310)

[0263] The title compound was was as an off white solid. (173 mg, melting point 133-135 °C)

[0264] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl-L-valinate (Compound No.308)

[0265] The title compound was prepared and was isolated as a colorless liquid. (129 mg)Docket No.210869-WO-SEC-1

[0266] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-D-allothreonyl-L-valinate (Compound No.307)

[0267] The title compound wasas an off white solid. (85 mg, melting point 145-147 °C)

[0268] Methyl N-(N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl)-O-methyl-L-threoninate (Compound No.305)

[0269] The title compound was was as a white solid. (182 mg, melting point 131-133 °C)

[0270] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-D-allothreonylglycinate (Compound No.312)Docket No.210869-WO-SEC-1

[0271] The title compound was prepared and was isolated as an off white solid. (65 mg, melting point 91-93 °C)

[0272] 2-(Methylsulfonyl)ethyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-O-methyl-L-threoninate (Compound No.313)

[0273] The title compoundas a colorless gummy solid. (97 mg)

[0274] 2-Methylbut-3-en-2-yl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.198)

[0275] The title compound was prepared and was isolated as a colorless oil. (219 mg, 64% yield)

[0276] But-3-yn-1-yl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.197)Docket No.210869-WO-SEC-1

[0277] The title compound as a colorless oil. (236.35 mg, 72% yield)

[0278] 2-((1S)-2-(2,3-Difluorobenzyl)-3-oxocyclopentyl)-N-((2S,3R)-3-methoxy-1-oxo- 1-((propan-2-ylideneamino)oxy)butan-2-yl)acetamide (Compound No.453)

[0279] The title compound wasas a pale yellow oil. (65 mg, 20% yield)

[0280] 2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)-N-((RS)-3-methyl-1-oxo-1- ((((E)-1,1,1-trifluoropropan-2-ylidene)amino)oxy)butan-2-yl)acetamide (Compound No. 451)Docket No.210869-WO-SEC-1

[0281] The title compound was prepared and was isolated as a clear colorless solid. (26 mg, 7% yield)

[0282] 2-(Methylsulfonyl)ethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.396)

[0283] The title compound was prepared and was isolated as a colorless liquid. (157 mg)

[0284] Furan-2-ylmethyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-threoninate (Compound No.429)

[0285] The title compound was was as a light brown liquid. (165 mg)

[0286] Furan-2-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.404)Docket No.210869-WO-SEC-1

[0287] The title compound was prepared and was isolated as an off white solid. (102 mg, melting point 101-103 °C)

[0288] Furan-2-ylmethyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-valinate (Compound No.342)

[0289] The title compoundas a brown liquid. (132 mg)

[0290] 2-(Methylsulfonyl)ethyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-valinate (Compound No.341)

[0291] The title compound was prepared and was isolated as a colorless gummy liquid. (201 mg)

[0292] 2-(Methylsulfonyl)ethyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-threoninate (Compound No.430)Docket No.210869-WO-SEC-1

[0293] The title compound wasas a yellow gummy liquid. (176 mg)

[0294] Methyl (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanamido)-3-(4-fluorophenyl)propanoate (Compound No.269)

[0295] The title compound was was as a white solid. (67.5 mg, 24% yield)

[0296] Methyl (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methoxybutanamido)-3-(4-fluorophenyl)propanoate (Compound No. 314)Docket No.210869-WO-SEC-1

[0297] The title compound was prepared and was isolated as a white solid. (161 mg, 57% yield)

[0298] Methyl (S)-3-(4-chlorophenyl)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanamido)propanoate (Compound No.270)

[0299] The title compound wasas a white solid. (437.4 mg, 49% yield)

[0300] Methyl (S)-3-(4-chlorophenyl)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methoxybutanamido)propanoate (Compound No.315)

[0301] The title compound was prepared and was isolated as a white solid. (596 mg, 58% yield)

[0302] Methyl (S)-3-(4-bromophenyl)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanamido)propanoate (Compound No.271)Docket No.210869-WO-SEC-1

[0303] The title compound wasas a white solid. (352 mg, 56% yield)

[0304] Methyl (S)-3-(4-bromophenyl)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methoxybutanamido)propanoate (Compound No.316)

[0305] The title compound was was as a white solid. (230 mg, 36% yield)

[0306] Methyl (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanamido)-3-(4-nitrophenyl)propanoate (Compound No.272)Docket No.210869-WO-SEC-1

[0307] The title compoundas a white solid. (286 mg, 49% yield)

[0308] Methyl (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methoxybutanamido)-3-(4-nitrophenyl)propanoate (Compound No.317)

[0309] The title compound was was as a white solid. (428.1 mg, 71% yield)

[0310] Methyl (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanamido)-3-(3-fluorophenyl)propanoate (Compound No.273)Docket No.210869-WO-SEC-1

[0311] The title compound wasas a white solid. (445 mg, 77% yield)

[0312] Methyl (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methoxybutanamido)-3-(3-fluorophenyl)propanoate (Compound No. 318)

[0313] The title compound was prepared and was isolated as a white solid. (442 mg, 76% yield)

[0314] Methyl (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanamido)-3-(2-fluorophenyl)propanoate (Compound No.274)Docket No.210869-WO-SEC-1

[0315] The title compound wasas a white solid. (435 mg, 75% yield)

[0316] Methyl (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methoxybutanamido)-3-(2-fluorophenyl)propanoate (Compound No. 319)

[0317] The title compound was was as a white solid. (410 mg, 71% yield)

[0318] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl-D-phenylalaninate (Compound No.320)Docket No.210869-WO-SEC-1

[0319] The title compound was prepared and was isolated as a white solid. (358 mg, 64% yield)

[0320] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoyl)-D-phenylalaninate (Compound No.275)

[0321] The title compound wasas a white solid. (280 mg, 51% yield)

[0322] Cyclopropyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.199)

[0323] The title compound was prepared and was isolated as a colorless oil. (240.59 mg, 75% yield)

[0324] 2-(adamantan-1-yl)ethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.202)Docket No.210869-WO-SEC-1

[0325] The title compound was prepared and was isolated as a white solid. (148 mg, 36% yield)

[0326] Adamantan-1-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.201)

[0327] The title compound was prepared and was isolated as a white solid. (132 mg, 33% yield)

[0328] Adamantan-1-yl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.200)

[0329] The title compound was prepared and was isolated as a white solid. (199 mg, 51% yield)Docket No.210869-WO-SEC-1

[0330] Methyl (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanamido)-3-(3,4-dihydroxyphenyl)propanoate (Compound No.276)

[0331] The title compound was was as a light brown solid. (146 mg, 12% yield)

[0332] S-(furan-2-ylmethyl) (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.131)

[0333] The title compound was prepared and was isolated as a pale yellow oil (288 mg, 78% yield)

[0334] S-(3,3,3-trifluoropropyl) (RS)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methylbutanethioate (Compound No.132)Docket No.210869-WO-SEC-1

[0335] The title compoundas a clear and colorless oil (268 mg, 74% yield)

[0336] S-benzyl (2S,3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl) pyrrolidin-2-yl) acetamido) butanethioate (Compound No.436)

[0337] The title compound was prepared and was isolated as a yellow liquid (350 mg, 66% yield).

[0338] Methyl 2-(((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valyl)thio)acetate (Compound 467)

[0339] The title compound was prepared and was isolated as a colorless viscous liquid (98% purity).Docket No.210869-WO-SEC-1

[0340] S-(3,3,3-trifluoropropyl) (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin- 2-yl)acetamido)-3-methylbutanethioate (Compound 468)

[0341] The title compound was was as a colorless viscous liquid (98% purity).

[0342] 2-(Methylsulfonyl)ethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound 483)

[0343] The title compound was prepared and was isolated as a clear oil (95% purity, 63% yield).

[0344] Phenethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin- 2-yl)acetamido)propanoate (Compound 484)Docket No.210869-WO-SEC-1

[0345] The title compound was prepared and was isolated as a clear oil (95% purity, 47% yield).

[0346] Cyclohexyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin- 2-yl)acetamido)propanoate (Compound 485)

[0347] The title compound was was as a clear oil (95% purity, 87% yield).

[0348] S-Benzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanethioate(Compound 495)

[0349] The title compound was prepared and was isolated as a pale yellow viscous liquid (99% purity).

[0350] S-(3,3,3-Trifluoropropyl) (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanethioate (Compound 497)Docket No.210869-WO-SEC-1

[0351] The title compound was prepared and was isolated as a yellow viscous liquid (99% purity).

[0352] S-Isopropyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanethioate (Compound 498)

[0353] The title compound was was as a pale yellow viscous liquid (99% purity).

[0354] Methyl 2-(((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin- 2-yl)acetamido)propanoyl)thio)acetate (Compound 499)

[0355] The title compound was prepared and was isolated as a yellow viscous liquid (99% purity).

[0356] Cyclopropylmethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound 514)Docket No.210869-WO-SEC-1

[0357] The title compound was prepared and was isolated as a white solid (90% purity).

[0358] Isopropyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound 515)

[0359] The title compound was was as a white solid (90% purity).

[0360] 2,2-Difluoroethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound 516)

[0361] The title compound was prepared and was isolated as a light yellow oil (90% purity).

[0362] Method 2: Preparation of Methyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valyl-L-phenylalaninate (Compound No.35)Docket No.210869-WO-SEC-1

[0363] In a round-bottomed flask charged with a magnetic stir bar were added compound tert-butyloxycarbonyl amine and HCl in 1,4-dioxane (4 M, 4 equiv). This is stirred for 2 hours, then the solvent and excess HCl removed in vacuo. The residue is reconstituted in CH2Cl2 (0.2 M) followed by the addition (S)-2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetic acid (1 equiv), ((Ethylimino) methylene)amino)-N,N-dimethylpropan-1-amine) hydrochloride (1.2 equiv), triethylamine (2 equiv), and N,N-dimethylpyridin-4-amine (1.2 equiv) sequentially. The reaction mixture was stirred at 20 °C for 18 hours (h) or until the reaction was complete. The reaction product was concentrated onto silica gel and purified by silica column chromatography. The title compound was isolated as a white solid. (347 mg, 64% yield)

[0364] The following compounds were prepared in accordance to the procedure in Method 2:

[0365] 2-Cyanoethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.36)

[0366] The title compound was prepared and was isolated as a clear sticky goo. (553.5 mg, 62% yield)

[0367] 2-Cyanoethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.214)Docket No.210869-WO-SEC-1

[0368] The title compound was prepared and was isolated as a clear sticky oil. (849.5 mg, 90% yield)

[0369] Methyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-valyl- L-phenylalaninate (Compound No.325)

[0370] The title compound was a white powder. (392 mg, 70% yield)

[0371] Methyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- valylglycinate (Compound No.326)

[0372] The title compound wap p d as a white powder. (392 mg, 84% yield)

[0373] Methyl 2-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamido)-2-methylpropanoate (Compound No.71)Docket No.210869-WO-SEC-1

[0374] The title compound wasas a white foam. (417 mg, 87% yield)

[0375] 2-cyanoethyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- valinate (Compound No.329)

[0376] The title compound was prepared and was isolated as a clear oil. (529.5 mg, 55% yield)

[0377] Methyl 3-((R*)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamido)propanoate (Compound No.126)

[0378] The title compound wasprepared and was isolated as a white solid. (81 mg, 35% yield)Docket No.210869-WO-SEC-1

[0379] Methyl 3-((R*)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamido)propanoate (Compound No.127)

[0380] The title compound wasas a white solid. (102 mg, 44% yield)

[0381] (R*)-N-Cyclohexyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.134)

[0382] The title compound was was as a white powder. (16 mg, 7% yield)

[0383] (R*)-N-Cyclohexyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.133)Docket No.210869-WO-SEC-1

[0384] The title compound was prepared and was isolated as a white powder. (24 mg, 10% yield)

[0385] 2-Cyanoethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.386)

[0386] The title compound was was as a clear goo. (299.3 mg, 71% yield)

[0387] 2-Cyanoethyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threoninate (Compound No.288)

[0388] The title compoundas a clear goo. (286.1 mg, 31% yield)

[0389] 2-Cyanoethyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threoninate (Compound No.421)Docket No.210869-WO-SEC-1

[0390] The title compound was a white semi solid. (361.4 mg, 38% yield)

[0391] tert-Butyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valylglycinate (Compound No.169)

[0392] The title compound was prepared and was isolated as a white powder. (182 mg, 36% yield)

[0393] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-(2-(methylamino)-2-oxoethyl)butanamide (Compound No.168)

[0394] The title compound was prepared and was isolated as a white solid. (371 mg, 80% yield)Docket No.210869-WO-SEC-1

[0395] 3,3,3-Trifluoropropyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.177)

[0396] The title compound wad as a clear oil. (556.5mg, 57% yield)

[0397] 3,3,3-trifluoropropyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-valinate (Compound No.335)

[0398] The title compound was prepared and was isolated as a clear oil. (661.3 mg, 64% yield)

[0399] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-D- phenylalaninate (Compound No.183)Docket No.210869-WO-SEC-1

[0400] The title compound was as a white powder. (496 mg, 92% yield)

[0401] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-D- valinate (Compound No.182)

[0402] The title compound was was as a white powder. (410 mg, 83% yield)

[0403] 3,3,3-Trifluoropropyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)valylvalinate (Compound No.336)Docket No.210869-WO-SEC-1

[0404] The title compound was prepared and was isolated as a white solid. (70.7 mg, 6% yield)

[0405] 3,3,3-Trifluoropropyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (259)

[0406] The title compound was a clear goo. (676.8 mg, 64% yield) 3,3,3-Trifluoropropyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.394)

[0408] The title compound was prepared and was isolated as a clear goo. (475.5 mg, 46% yield)

[0409] (Tetrahydrofuran-2-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin- 2-yl)acetyl)-L-valinate (Compound No.449)Docket No.210869-WO-SEC-1

[0410] The title compound as a light yellow resin. (55.51mg, 34% yield)

[0411] 2-Methoxyethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.450)

[0412] The title compounda yellow oil. (140.57 mg, 43% yield)

[0413] Methyl 1-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamido)cyclopropane-1-carboxylate (Compound No.203)Docket No.210869-WO-SEC-1

[0414] The title compound was prepared and was isolated as a white foam. (260 mg, 47% yield)

[0415] Isopropyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valylglycinate (Compound 457)was prepared and was isolated as a white solid. (26% yield)

[0417] Method 3: Preparation of N-(3-chlorobenzyl)-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methylbutanamide (Compound No. 99)

[0418] In a round-bottomed a stir bar were added compound tert-butyloxycarbonyl amine, CH2Cl2(0.5 M), and trifluoroacetic acid (9 equiv). This is stirred for 12 hours, then the volatiles removed in vacuo. The residue is reconstituted in CH2Cl2 (0.2 M) followed by the addition of (S)-2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetic acid (1 equiv), ((Ethylimino) methylene)amino)-N,N-dimethylpropan-1-amine) hydrochloride (1.2 equiv), triethylamine (5 equiv), and N,N-dimethylpyridin-4-amine (1.2 equiv) sequentially. The reaction mixture was stirred at 20 °C for 18 hours (h) or until the reaction was complete. The reaction product was concentrated onto silica gel and purified by silica column chromatography. The title compound was isolated as a white solid. (342mg, 66% yield)Docket No.210869-WO-SEC-1

[0419] The following compounds were prepared in accordance to the procedure in Method 3:

[0420] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(furan-2- ylmethyl)-3-methylbutanamide (Compound No.114)

[0421] The title compound was prepared and was isolated as an orange gum. (198 mg, 42% yield)

[0422] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- (3-phenylpropyl)butanamide (Compound No.113)

[0423] The title compound wap p as a tan solid. (174 mg, 34% yield)

[0424] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- propylbutanamide (Compound No.112)Docket No.210869-WO-SEC-1

[0425] The title compound wasas a white solid. (212 mg, 51% yield)

[0426] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-isobutyl- 3-methylbutanamide (Compound No.111)

[0427] The title compound wasd as a white solid. (189 mg, 44% yield)

[0428] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- octylbutanamide (Compound No.110)

[0429] The title compound wasprepared and was isolated as a white solid. (165 mg, 34% yield)Docket No.210869-WO-SEC-1

[0430] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(2- methoxyethyl)-3-methylbutanamide (Compound No.109)

[0431] The title compound wasas a white solid. (247 mg, 57% yield)

[0432] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(2-(2- methoxyethoxy)ethyl)-3-methylbutanamide (Compound No.108)

[0433] The title compound wased as a tan solid. (328 mg, 63% yield)

[0434] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- phenethylbutanamide (Compound No.107)Docket No.210869-WO-SEC-1

[0435] The title compound was prepared and was isolated as a tan solid. (268 mg, 54% yield)

[0436] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- (4-methylbenzyl)butanamide (Compound No.106)

[0437] The title compound was was as a tan solid. (33 mg, 47% yield)

[0438] Methyl 3-((2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methylbutanamido)methyl)benzoate (Compound No.105)

[0439] The title compound was prepared and was isolated as a white solid. (293 mg, 54% yield)

[0440] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(4- methoxybenzyl)-3-methylbutanamide (Compound No.104)Docket No.210869-WO-SEC-1

[0441] The title compound wasas a white solid. (210 mg, 41% yield)

[0442] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(4- fluorobenzyl)-3-methylbutanamide (Compound No.103)

[0443] The title compound wasas a white solid. (244 mg, 49% yield)

[0444] N-(4-Chlorobenzyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.102)

[0445] The title compound wasprepared and was isolated as a white solid. (188 mg, 36% yield)Docket No.210869-WO-SEC-1

[0446] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- (3,4,5-trifluorobenzyl)butanamide (Compound No.101)

[0447] The title compoundas a white solid. (247 mg, 44% yield)

[0448] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3- methoxybenzyl)-3-methylbutanamide (Compound No.100)

[0449] The title compound wasd as a white solid. (236 mg, 46% yield)

[0450] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-ethyl-3- methylbutanamide (Compound No.98)Docket No.210869-WO-SEC-1

[0451] The title compound was prepared and was isolated as a white solid. (230 mg, 57% yield)

[0452] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(4- fluorophenyl)-3-methylbutanamide (Compound No.115)

[0453] The title compound wasas a white solid. (244 mg, 52% yield)

[0454] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3,5- dimethoxyphenyl)-3-methylbutanamide (Compound No.116)

[0455] The title compound was prepared and was isolated as a white solid. (363 mg, 71% yield)

[0456] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3-fluoro- 5-methoxyphenyl)-3-methylbutanamide (Compound No.117)Docket No.210869-WO-SEC-1

[0457] The title compound wasas a white solid. (378 mg, 75% yield)

[0458] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- (3,4,5-trifluorophenyl)butanamide (Compound No.448)

[0459] The title compound was was as a white solid. (270 mg, 53% yield)

[0460] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- (2,4,6-trifluorophenyl)butanamide (Compound No.447)Docket No.210869-WO-SEC-1

[0461] The title compound was prepared and was isolated as a white solid. (392 mg, 77% yield)

[0462] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(4- methoxyphenyl)-3-methylbutanamide (Compound No.446)

[0463] The title compound was a white solid. (369 mg, 76% yield)

[0464] N-(4-Chlorophenyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.445)

[0465] The title compound was prepared and was isolated as a white solid. (386 mg, 77% yield)

[0466] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- (4-nitrophenyl)butanamide (Compound No.444)Docket No.210869-WO-SEC-1

[0467] The title compound wasas a yellow solid. (423 mg, 82% yield)

[0468] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- (4-(trifluoromethyl)phenyl)butanamide (Compound No.443)

[0469] The title compound wad as a white solid. (362 mg, 69% yield) Methyl 4-(2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methylbutanamido)benzoate (Compound No.442)Docket No.210869-WO-SEC-1

[0471] The title compound was prepared and was isolated as a white solid. (378 mg, 74% yield)

[0472] Methyl 3-(2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methylbutanamido)benzoate (Compound No.441)

[0473] The title compoundas a white solid. (401 mg, 78% yield)

[0474] N-(3-Chlorophenyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.124)

[0475] The title compound was was as a white solid. (414 mg, 85% yield)

[0476] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3- methoxyphenyl)-3-methylbutanamide (Compound No.123)Docket No.210869-WO-SEC-1

[0477] The title compound wasas a white solid. (378 mg, 78% yield)

[0478] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(2,4- difluorophenyl)-3-methylbutanamide (Compound No.122)

[0479] The title compound was was as a white solid. (450 mg, 92% yield)

[0480] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3,4- difluorophenyl)-3-methylbutanamide (Compound No.121)

[0481] The title compound was prepared and was isolated as a white solid. (396 mg, 81% yield)Docket No.210869-WO-SEC-1

[0482] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(4-fluoro- 3-methoxyphenyl)-3-methylbutanamide (Compound No.120)

[0483] The title compound wasas a white solid. (165 mg, 33% yield)

[0484] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3-fluoro- 4-methoxyphenyl)-3-methylbutanamide (Compound No.119)

[0485] The title compound was prepared and was isolated as a white solid. (302 mg, 60% yield)

[0486] 2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3,4- dimethoxyphenyl)-3-methylbutanamide (Compound No.118)Docket No.210869-WO-SEC-1

[0487] The title compound was prepared and was isolated as a white solid. (262 mg, 51% yield)

[0488] Method 4: Preparation of ethyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetyl)valinate (Compound No.330)

[0489] In a round-bottomed flstir bar was added (2-((S)-5-oxo- 1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)valine (1 equiv), amine, ammonium hydrochloride or trifluoroacetate, thiol, or alcohol nucleophile (1 equiv), 1- [Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate ((HATU), 1.2 equiv), and CH2Cl2(0.2 M). To this was added 4- methylmorpholine (3 equiv) and the reaction was allowed to stir at 22 °C for 16 hours (h) or until complete. The reaction is filtered through celite, concentrated, and purified by silica column chromatography. The title compound was isolated as an off-white solid. (146 mg, 43% yield, melting point 121-125 °C).

[0490] The following compounds were prepared in accordance to the procedure in Method 4:

[0491] 2-(Methylsulfonyl)ethyl 3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.388)Docket No.210869-WO-SEC-1

[0492] The title compound was a pale yellow sticky solid. (179 mg, 43% yield)

[0493] Ethyl 3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)propanoate (Compound No.387)

[0494] The title compound was was as a pale yellow liquid. (111 mg, 40% yield)

[0495] 2-(Methylsulfonyl)ethyl (3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)butanoate (Compound No.422)

[0496] The title compound was prepared and was isolated as a pale yellow sticky solid. (116 mg, 36% yield)Docket No.210869-WO-SEC-1

[0497] Allyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)valinate(Compound No.331)

[0498] The title compoundas a pale yellow solid. (180 mg, 51% yield)

[0499] 2-(Methylsulfonyl)ethyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)valinate (Compound No.332)

[0500] The title compound was prepared and was isolated as an off white gummy solid. (302 mg, 60% yield)

[0501] Benzyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)valinate (Compound No.333)Docket No.210869-WO-SEC-1

[0502] The title compound was prepared and was isolated as a pale brown gummy liquid. (200 mg, 50% yield)

[0503] Ethyl (3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)butanoate (Compound No.423)

[0504] The title compound wasas a pale yellow liquid. (192 mg, 59% yield)

[0505] S-Benzyl (2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methoxybutanethioate (Compound No.322)

[0506] The title compoundas a yellow liquid. (175 mg, 32% yield)

[0507] S-Isopropyl (2S,3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)butanethioate (Compound No.437)Docket No.210869-WO-SEC-1

[0508] The title compound was as a yellow liquid (273 mg).

[0509] Method 5: Preparation of 2-Cyanoethyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.14)

[0510] In a round-bottomed flask charged with a magnetic stir bar were added (2-((S)-1- (2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)valine (1 equiv) and alcohol, amine, ammonium, or thiol nucleophile (1-3 equiv) in dichloromethane (CH2Cl2, 0.1 M).3- (((Ethylimino) methylene)amino)-N,N-dimethylpropan-1-amine) hydrochloride (1.2 equiv), triethylamine (1.2 equiv), and N,N-dimethylpyridin-4-amine (1.2 equiv) were added sequentially. The reaction mixture was stirred at 20 °C for 18 hours (h) or until the reaction was complete. The reaction product was concentrated onto silica gel and purified by silica column chromatography. The title compound was prepared and was isolated as a pale yellow oil. (170.4 mg, 89% yield)

[0511] The following compounds were prepared in accordance to the procedure in Method 5:

[0512] 2,2,2-Trifluoroethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)valinate (Compound No.7)Docket No.210869-WO-SEC-1

[0513] The title compound was as a clear oil. (116.7 mg, 96% yield)

[0514] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- valylglycinate (Compound No.16)

[0515] The title compoundas a white solid. (368.4 mg, 80% yield)

[0516] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-D- valylglycinate (20)Docket No.210869-WO-SEC-1

[0517] The title compound was prepared and was isolated as a white solid. (54 mg, 10% yield)

[0518] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valylglycinate (Compound No.19)

[0519] The title compound wasas a white solid. (140 mg, 30% yield)

[0520] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-D-valyl-L- valinate (Compound No.18)

[0521] The title compound was prepared and was isolated as a white solid. (137.1 mg, 28% yield)

[0522] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- valinate (Compound No.17)Docket No.210869-WO-SEC-1

[0523] The title compounda viscous semisolid. (129.6 mg, 26% yield)

[0524] 2-(((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)methyl)-4-isopropyloxazol- 5(4H)-one (Compound No.54)

[0525] The title compound wasof nucleophile and was isolated as a colorless oil. (70 mg, 20% yield)

[0526] Method 6: Preparation of 2,2,2-Trifluoroethyl (2-((S)-1-(2,3-difluorobenzyl)- 5-oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.33)Docket No.210869-WO-SEC-1

[0527] In a flask charged with magnetic stir bar was added (2-((S)-1-(2,3-difluorobenzyl)- 5-oxopyrrolidin-2-yl)acetyl)-L-valine (1 equiv), cesium carbonate (1 equiv), acetonitrile (0.1 M), and alkyl sulfonate (1.5 equiv). This is stirred at 22 °C for 18 hours or until complete. The reaction is filtered through celite, the solvent is removed to load onto silica gel and purified by silica column chromatography. The title compound was isolated as a colorless oil. (155.7 mg, 67% yield)

[0528] The following compounds were prepared in accordance to the procedure in Method 6:

[0529] 2,2,2-Trifluoroethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (211)

[0530] The title compound was was as a light yellow goo. (336 mg, 70% yield)

[0531] Method 7: Preparation of Ethyl N-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-O-methyl-L-threoninate (293)

[0532] In a round-bottomed flask charged with magnetic stir bar was added N-(2-((S)-1- (2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O-methyl-L-threonine (1 equiv), potassium carbonate (1 equiv), N,N-dimethylformamide (0.2 M). This is stirrd for 5 minutes, then alkylDocket No.210869-WO-SEC-1 bromide or trifluoromethane sulfomnate (1 equiv). This is stirred at room temperature for 2-16 hours or until complete. The solvent is removed to load onto silica gel and purified by silica column chromatography. The title compound was isolated as a colorless oil. (192 mg)

[0533] The following compounds were prepared in accordance to the procedure in Method 7:

[0534] (Trimethylsilyl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.189)

[0535] The title compound was prepared and was isolated as an amber liquid. (107 mg)

[0536] 4-Methylbenzyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- O-methyl-L-threoninate (Compound No.299)

[0537] The title compound was prepared and was isolated as a colorless liquid. (151 mg)

[0538] 4-Bromobenzyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- O-methyl-L-threoninate (298)Docket No.210869-WO-SEC-1

[0539] The title compound as a colorless liquid. (147 mg)

[0540] 4-Nitrobenzyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threoninate (297)

[0541] The title compounda colorless liquid. (130 mg)

[0542] Allyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O-methyl- L-threoninate (296)

[0543] The title compound was prepared and was isolated as a colorless liquid. (134 mg)Docket No.210869-WO-SEC-1

[0544] Isopropyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threoninate (295)

[0545] The title compound wasas a colorless liquid. (92 mg)

[0546] Propyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threoninate (294)

[0547] The title compoundas a colorless liquid. (136 mg, 93% yield)

[0548] Benzyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threoninate (Compound No.300)Docket No.210869-WO-SEC-1

[0549] The title compound was prepared and was isolated as a colorless liquid. (171 mg)

[0550] 2,2,2-Trifluoroethyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-O-methyl-L-threoninate (Compound No.301)

[0551] The title compounda white gummy solid. (98 mg) Cyanomethyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threoninate (Compound No.302)

[0553] The title compound was prepared and was isolated as a colorless liquid. (153 mg)

[0554] Prop-2-yn-1-yl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- O-methyl-L-threoninate (Compound No.303)Docket No.210869-WO-SEC-1

[0555] The title compounds a colorless liquid. (117 mg)

[0556] Allyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-valinate (Compound No.339)

[0557] The title compound wad as a colorless liquid. (175 mg)

[0558] Prop-2-yn-1-yl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)- L-valinate (Compound No.338)

[0559] The title compound was prepared and was isolated as a colorless liquid. (177 mg)

[0560] Cyanomethyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- valinate (Compound No.337)Docket No.210869-WO-SEC-1

[0561] The title compound wasas a pale yellow liquid. (157 mg) Prop-2-yn-1-yl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.399)

[0563] The title compound was was as a colorless liquid. (132 mg)

[0564] Cyanomethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.398)

[0565] The title compound was prepared and was isolated as a colorless liquid. (173 mg)

[0566] 2,2,2-Trifluoroethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.397)Docket No.210869-WO-SEC-1

[0567] The title compound was a colorless liquid. (131 mg)

[0568] Prop-2-yn-1-yl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetyl)-L-threoninate (Compound No.427)

[0569] The title compound was as a colorless liquid. (169 mg)

[0570] Allyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)propanoate (Compound No.400)

[0571] The title compoundas a colorless liquid. (134 mg)

[0572] Benzyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threoninate (Compound No.428)Docket No.210869-WO-SEC-1

[0573] The title compound wa d as a colorless liquid. (159 mg)

[0574] Benzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)propanoate (Compound No.405)

[0575] The title compound wasd as a colorless liquid. (144 mg)

[0576] Allyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threoninate (Compound No.433)

[0577] The title compound was prepared and was isolated as a colorless liquid. (156 mg, 89% yield)

[0578] Cyanomethyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threoninate (Compound No.432)Docket No.210869-WO-SEC-1

[0579] The title compound wasas a yellow gummy liquid. (146 mg)

[0580] Benzyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- valinate (Compound No.343)

[0581] The title compound wasas a pale yellow liquid. (183 mg)

[0582] 2,2,2-Trifluoroethyl (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-valinate (Compound No.340)

[0583] The title compound was prepared and was isolated as a colorless liquid. (165 mg)Docket No.210869-WO-SEC-1

[0584] 2,2,2-Trifluoroethyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-threoninate (Compound No.431)

[0585] The title compound wasas an off white solid. (138 mg, melting point 120-122 °C)

[0586] Method 8: Preparation of 4-Nitrobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.11)

[0587] In a round-bottomed flask charged with magnetic stir bar was added (2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valine (1 equiv), potassium carbonate (2 equiv),is heated to 50 °C for 2 hours or until complete. The solvent is removed to load onto silica gel and purified by silica column chromatography. The title compound was isolated as a glassy solid. (100.4 mg, 98% yield)

[0588] The following compounds were prepared in accordance to the procedure in Method 8:

[0589] 4-Bromobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.12)Docket No.210869-WO-SEC-1

[0590] The title compound was prepared and was isolated as a colorless oil. (203.2 mg, 93% yield)

[0591] Cyanomethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.15)

[0592] The title compound wad as a yellow oil. (85 mg, 80% yield) 4-Nitrobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.209)Docket No.210869-WO-SEC-1

[0594] The title compound was prepared and was isolated as a colorless foam solid. (221.2 mg, 83% yield)

[0595] 4-Bromobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.208)

[0596] The title compound was prepared and was isolated as a colorless foam. (249.7 mg, 88% yield)

[0597] Benzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoate (Compound No.207)

[0598] The title compoundas a clear sticky oil. (171.1 mg, 69% yield)

[0599] Allyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoate (Compound No.210)Docket No.210869-WO-SEC-1

[0600] The title compound wasas a slightly yellow goo. (174 mg, 27% yield)

[0601] Prop-2-yn-1-yl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.212)

[0602] The title compoundas a clear sticky goo. (244.4 mg, 63% yield)

[0603] Cyanomethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.213)Docket No.210869-WO-SEC-1

[0604] The title compound was prepared and was isolated as a clear oil. (196 mg, 92% yield)

[0605] 3-Fluorobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.225)

[0606] The title compoundas a lightly yellow oil. (178.3 mg, 71% yield)

[0607] 3-(Trifluoromethyl)benzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)- 5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.224)

[0608] The title compound was prepared and was isolated as a clear oil. (181 mg, 65% yield)

[0609] 4-(Trifluoromethyl)benzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)- 5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.223)Docket No.210869-WO-SEC-1

[0610] The title compound was a clear oil. (172.4 mg, 62% yield)

[0611] Methyl 4-((((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoyl)oxy)methyl)benzoate (Compound No.222)

[0612] The title compound was prepared and was isolated as a clear oil. (160.6 mg, 59% yield)

[0613] 4-Fluorobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.221)

[0614] The title compound was prepared and was isolated as a clear oil. (210.7 mg, 84% yield)Docket No.210869-WO-SEC-1

[0615] 4-Chlorobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.220)

[0616] The title compound wasas a clear oil. (230.1 mg, 89% yield)

[0617] 4-Methylbenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.219)

[0618] The title compound wasas a clear oil. (157.4 mg, 63% yield)

[0619] 4-Cyanobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.218)Docket No.210869-WO-SEC-1

[0620] The title compound was prepared and was isolated as a white sticky solid. (244.2 mg, 96% yield)

[0621] 3-Chlorobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.226)

[0622] The title compound wasas a clear oil. (166.1 mg, 64% yield)

[0623] 3-Bromobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.227)

[0624] The title compound was prepared and was isolated as a clear oil. (200.6 mg, 71% yield)

[0625] Methyl 4-((((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valyl)oxy)methyl)benzoate (Compound No.97)Docket No.210869-WO-SEC-1

[0626] The title compound was prepared and was isolated as a clear oil. (170.6 mg, 64% yield)

[0627] 4-Cyanobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.96)

[0628] The title compound was prepared and was isolated as a white semi solid. (136.2 mg, 55% yield)

[0629] 4-Methoxybenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.95)Docket No.210869-WO-SEC-1

[0630] The title compound was prepared and was isolated as a clear oil. (77.4 mg, 27% yield)

[0631] 4-Methylbenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.94)

[0632] The title compound was as a clear oil. (168.8 mg, 69% yield) 4-Chlorobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.93)

[0634] The title compound was prepared and was isolated as a clear oil. (186 mg, 72% yield)

[0635] 4-Fluorobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.92)Docket No.210869-WO-SEC-1

[0636] The title compound wa d as a clear oil. (165.7 mg, 68%yield)

[0637] 2,4-Dimethylbenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.91)

[0638] The title compound was was as a clear oil. (179.7 mg, 72% yield)

[0639] 2,4,6-Trimethylbenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.90)

[0640] The title compoundas a clear oil. (159.4 mg, 62% yield)Docket No.210869-WO-SEC-1

[0641] 4-(Trifluoromethyl)benzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.89)

[0642] The title compounda clear oil. (189.4 mg, 70% yield)

[0643] Methyl 3-((((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoyl)oxy)methyl)benzoate (Compound No.239)

[0644] The title compound was prepared and was isolated as a clear oil. (199.8 mg, 73% yield)

[0645] 3-Cyanobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.238)Docket No.210869-WO-SEC-1

[0646] The title compound was was as a clear oil. (157.4 mg, 62% yield)

[0647] 3-Nitrobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.237)

[0648] The title compound was prepared and was isolated as a clear oil. (180.7 mg, 68% yield)

[0649] 3-Methoxybenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.236)Docket No.210869-WO-SEC-1

[0650] The title compound was prepared and was isolated as a clear oil. (212.5 mg, 83% yield)

[0651] 3-Methylbenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.235)

[0652] The title compoundas a clear oil. (190.6 mg, 76% yield)

[0653] Methyl 2-((((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoyl)oxy)methyl)benzoate (Compound No.234)

[0654] The title compoundas a clear oil. (194.5 mg, 70% yield)

[0655] 2-Cyanobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.233)Docket No.210869-WO-SEC-1

[0656] The title compound wasas a clear oil. (151.5 mg, 59% yield)

[0657] 2-Nitrobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.232)

[0658] The title compound was was as a clear oil. (118.9 mg, 45% yield)

[0659] 2-Methylbenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.231)

[0660] The title compound was prepared and was isolated as a yellow oil. (202.5 mg, 82% yield)Docket No.210869-WO-SEC-1

[0661] 2-Chlorobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.230)

[0662] The title compound wasas a clear oil. (180.1 mg, 70% yield)

[0663] 2-Fluorobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.229)

[0664] The title compound waas a clear oil. (159.4 mg, 64% yield)

[0665] 3-(Trifluoromethyl)benzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.367)Docket No.210869-WO-SEC-1

[0666] The title compound was was as a clear oil. (225.5 mg, 79% yield)

[0667] 3-Cyanobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.366)

[0668] The title compound was prepared and was isolated as a clear semisolid. (182.6 mg, 68% yield)

[0669] 3-Bromobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.365)Docket No.210869-WO-SEC-1

[0670] The title compound was prepared and was isolated as a clear oil. (241.6 mg, 83% yield)

[0671] 3-Chlorobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.364)

[0672] The title compound wasas a clear oil. (208.8 mg, 78% yield)

[0673] 3-Fluorobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.363)

[0674] The title compound was prepared and was isolated as a clear oil. (196.8 mg, 73% yield)

[0675] 4-(Trifluoromethyl)benzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.362)Docket No.210869-WO-SEC-1

[0676] The title compound wasas a clear oil. (234.7 mg, 82% yield)

[0677] Methyl 4-((((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoyl)oxy)methyl)benzoate (Compound No.361)

[0678] The title compound was prepared and was isolated as a clear oil. (206.8 mg, 72% yield) 4-Cyanobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound No.360)

[0680] The title compound was prepared and was isolated as a clear oil. (193.4 mg, 72% yield)Docket No.210869-WO-SEC-1

[0681] 4-Nitrobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound No.359)

[0682] The title compounda clear oil. (193.9 mg, 71% yield)

[0683] 4-Methylbenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound No.358)

[0684] The title compound was was as a clear oil. (215.1 mg, 84% yield)

[0685] 4-Chlorobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound No.357)Docket No.210869-WO-SEC-1

[0686] The title compound wasas a slightly yellow oil. (233.2 mg, 87% yield)

[0687] 4-Fluorobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.356)

[0688] The title compound was was as a clear oil. (213.8 mg, 84% yield)

[0689] 2-Fluorobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.378)

[0690] The title compound was prepared and was isolated as a clear goo. (210.8 mg, 81% yield)Docket No.210869-WO-SEC-1

[0691] Methyl 3-((((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoyl)oxy)methyl)benzoate (Compound No.377)

[0692] The title compound was was as a clear goo. (221.4 mg, 77% yield)

[0693] 3-Nitrobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound No.376)

[0694] The title compoundas a yellow goo. (230.4 mg, 84% yield)

[0695] 3-Methoxybenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound No.375)Docket No.210869-WO-SEC-1

[0696] The title compound waas a clear goo. (213.8 mg, 82% yield)

[0697] 3-Methylbenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.374)

[0698] The title compound was as a clear goo. (225.7 mg, 88% yield)

[0699] 2-Chlorobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.379)

[0700] The title compound was prepared and was isolated as a clear goo. (218.8 mg, 81% yield)Docket No.210869-WO-SEC-1

[0701] 2-Bromobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.380)

[0702] The title compoundas a clear oil. (237.1 mg, 81% yield)

[0703] 2-Methylbenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.381)

[0704] The title compound was was as a clear oil. (206 mg, 78% yield)

[0705] Thiazol-4-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.139)Docket No.210869-WO-SEC-1

[0706] The title compound was prepared and was isolated as a colorless oil. (114 mg, 78% yield)

[0707] (2-Methylthiazol-5-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.138)

[0708] The title compoundas a light yellow oil. (106 mg, 70% yield)

[0709] (2-Chlorothiazol-5-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.137)

[0710] The title compoundas a light orange oil. (94.5 mg, 44% yield)

[0711] 2,3-Dimethylbenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.385)Docket No.210869-WO-SEC-1

[0712] The title compound wasas a white solid. (199.8 mg, 76% yield)

[0713] Methyl 2-((((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoyl)oxy)methyl)benzoate (Compound No.384)

[0714] The title compound was was as a clear goo. (216.7 mg, 74% yield)

[0715] 2-Cyanobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.383)

[0716] The title compound was prepared and was isolated as a white semisolid. (204.9 mg, 76% yield)Docket No.210869-WO-SEC-1

[0717] 2-Nitrobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.382)

[0718] The title compound wasas a white semisolid. (220.1 mg, 78% yield)

[0719] Naphthalen-2-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.390)

[0720] The title compoundas a yellow semisolid. (17.4 mg, 5% yield)

[0721] Naphthalen-1-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.389)Docket No.210869-WO-SEC-1

[0722] The title compound was prepared and was isolated as a yellow solid. (136 mg, 43% yield)

[0723] (2-Chlorothiazol-4-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.140)

[0724] The title compounda colorless oil. (61.2 mg, 39% yield)

[0725] 3,5-Dimethylbenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.391)Docket No.210869-WO-SEC-1

[0726] The title compound was prepared and was isolated as a clear oil. (100 mg, 38% yield)

[0727] 2,4-Dimethylbenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.392)

[0728] The title compound was was as a clear oil. (83 mg, 31% yield)

[0729] 2,4,6-Trimethylbenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.393)

[0730] The title compoundas a clear oil. (57 mg, 19% yield)

[0731] Benzo[d]thiazol-2-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.154)Docket No.210869-WO-SEC-1

[0732] The title compound wa d as a colorless oil. (205 mg,64% yield)

[0733] (6-Methylpyridin-2-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin- 2-yl)acetyl)-L-valinate (Compound No.153)

[0734] The title compound wad as a colorless oil. (130 mg, 44% yield)

[0735] (2-Bromopyridin-4-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.152)

[0736] The title compound was prepared and was isolated as a light red oil. (250 mg, 75% yield)Docket No.210869-WO-SEC-1

[0737] Pyrazin-2-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.151)

[0738] The title compound wasas a brown oil. (160 mg, 56% yield)

[0739] (1-Methyl-1H-pyrazol-3-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.150)

[0740] The title compound was was as a colorless oil. (150 mg, 52% yield)

[0741] (6-Bromopyridin-2-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.149)Docket No.210869-WO-SEC-1

[0742] The title compound was prepared and was isolated as a colorless oil. (228 mg, 69% yield)

[0743] (6-Fluoropyridin-2-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.148)

[0744] The title compound wasas a light brown oil. (190 mg, 64% yield)

[0745] Pyridin-3-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.147)

[0746] The title compound wap p as a light brown oil. (135 mg, 48% yield)

[0747] Pyridin-2-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.146)Docket No.210869-WO-SEC-1

[0748] The title compound wasas a light brown oil. (140 mg, 49% yield)

[0749] (1H-Pyrazol-3-yl)methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.170)

[0750] The title compoundas a sticky glue. (152 mg, 50% yield)

[0751] Naphthalen-2-ylmethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.181)Docket No.210869-WO-SEC-1

[0752] The title compound was prepared and was isolated as a colorless glassy solid. (207 mg, 81% yield)

[0753] 3,4-Difluorobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- L-valinate (Compound No.180)

[0754] The title compound was was as a colorless gummy oil. (176 mg, 68% yield)

[0755] 2,3-Dimethylbenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.178)

[0756] The titlecolorless gummy oil. (243 mg, 98% yield)

[0757] Pyridin-2-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.252)Docket No.210869-WO-SEC-1

[0758] The title compound was a colorless oil. (118.86 mg, 61% yield)

[0759] Pyridin-3-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.253)

[0760] The title compoundas a colorless oil. (97.26 mg, 46% yield)

[0761] Pyrazin-2-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.258)

[0762] The title compound was prepared and was isolated as a light brown oil. (114.8 mg, 69% yield)Docket No.210869-WO-SEC-1

[0763] Benzo[d]thiazol-2-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)- 5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.257)

[0764] The title compound wasas a brown oil. (185.24 mg, 78% yield)

[0765] (1-Methyl-1H-pyrazol-4-yl)methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.256)

[0766] The title compound wad as a colorless oil. (85.52 mg, 40% yield)

[0767] (5-Bromopyridin-2-yl)methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.255)Docket No.210869-WO-SEC-1

[0768] The title compound was prepared and was isolated as a colorless oil. (136.28 mg, 55% yield)

[0769] Pyridin-4-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.254)

[0770] The title compound wad as a brown oil. (113.39 mg, 54% yield)

[0771] Quinolin-8-ylmethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.264)

[0772] The title compound was prepared and was isolated as a colorless oil. (110 mg, 45% yield)

[0773] (6-Bromopyridin-2-yl)methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.263)Docket No.210869-WO-SEC-1

[0774] The title compound waas a colorless oil. (125 mg, 48% yield)

[0775] (6-Bromoquinolin-8-yl)methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.262)

[0776] The title compound was was as a colorless oil. (120 mg, 42% yield)

[0777] (2-Bromopyridin-4-yl)methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.261)

[0778] The title compound was prepared and was isolated as a brown oil. (110.92 mg, 43% yield)Docket No.210869-WO-SEC-1

[0779] (6-Methylpyridin-2-yl)methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.277)

[0780] The title compound wad as a brown gum. (140 mg, 70% yield)

[0781] 4-bromobenzyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoate (Compound No.355)

[0782] The title compound was prepared and was isolated as a clear sticky goo. (294.7 mg, 81% yield)

[0783] 2-(Tert-butoxy)-2-oxoethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.464)Docket No.210869-WO-SEC-1

[0784] The title compound was prepared and was isolated as a colorless semisolid. (83% yield).

[0785] 2-Bromoallyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.466)

[0786] The title compound was was as a colorless oil. (90% purity, 71% yield).

[0787] 2-Bromobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.481)

[0788] The title compound was prepared and was isolated as a white foam. (95% purity).

[0789] 2-Cyanobenzyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.482)Docket No.210869-WO-SEC-1

[0790] The title compound was prepared and was isolated as a white foam. (95% purity).

[0791] 2-Bromobenzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.508)

[0792] The title compound was was as a colorless semisolid. (95% purity).

[0793] Method 9: Preparation of methyl (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valyl-L-alaninate (Compound No.34)

[0794] In a round-bottomed flask charged with magnetic stir bar was added (2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valine (1 equiv), amine, ammonium hydrochloride or trifluoroacetate, thiol, or alcohol nucleophile (1 equiv), 1- [Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate ((HATU), 1.2 equiv), and CH2Cl2(0.2 M). To this was added 4- methylmorpholine (3 equiv) and the reaction was allowed to stir at 22 °C for 16 hours (h) or until complete. The reaction is filtered through celite, concentrated, and purified by silica column chromatography. The title compound was isolated as a white solid. (100mg, 40% yield)Docket No.210869-WO-SEC-1

[0795] The following compounds were prepared in accordance to the procedure in Method 9:

[0796] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N- ethoxy-3-methylbutanamide (Compound No.38)

[0797] The title compound wad as an off white solid. (90 mg, melting point 163-165 °C)

[0798] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N- methoxy-3-methylbutanamide (Compound No.37)

[0799] The title compound was prepared and was isolated as an off white solid. (65 mg, melting point 133-135 °C)

[0800] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-propoxybutanamide (Compound No.39)Docket No.210869-WO-SEC-1

[0801] The title compound wa d as an off white solid. (84 mg,melting point 182-184 °C)

[0802] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N- isopropoxy-3-methylbutanamide (Compound No.40)

[0803] The title compound was was as an off white solid. (108 mg, melting point 167-169 °C)

[0804] (S)-N-(Allyloxy)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.41)

[0805] The title compound was prepared and was isolated as an off white solid. (130 mg, melting point 178-180 °C)Docket No.210869-WO-SEC-1

[0806] 2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)-N-((S)-3-methyl-1-(1,2- oxazinan-2-yl)-1-oxobutan-2-yl)acetamide (Compound No.46)

[0807] The title compound wasas a colorless liquid. (163 mg, melting point 140-142 °C)

[0808] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N- methoxy-N,3-dimethylbutanamide (Compound No.45)

[0809] The title compound was a colorless liquid. (116 mg, 52% yield)

[0810] (S)-N-(Benzyloxy)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.44)Docket No.210869-WO-SEC-1

[0811] The title compound wasas an off white solid. (110 mg, melting point 165-167 °C)

[0812] (S)-N-(tert-Butoxy)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.43)

[0813] The title compound was was as an off white solid. (72 mg, melting point 78-80 °C)

[0814] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N- isobutoxy-3-methylbutanamide (Compound No.42)

[0815] The title compound was prepared and was isolated as an off white solid. (100 mg, melting point 162-164 °C)Docket No.210869-WO-SEC-1

[0816] (2S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-((tetrahydro-2H-pyran-2-yl)oxy)butanamide (Compound No.48)

[0817] The title compound wasas an off white solid. (50 mg, melting point 69-71 °C)

[0818] (2R)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-((tetrahydro-2H-pyran-2-yl)oxy)butanamide (Compound No.49)

[0819] The title compound was was as an off white solid. (50 mg, melting point 70-72 °C)

[0820] Methyl (RS)-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)valyl- L-serinate (Compound No.53)Docket No.210869-WO-SEC-1

[0821] The title compound was prepared and was isolated as a white solid. (76 mg, 29% yield)

[0822] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- threoninate (Compound No.52)

[0823] The title compound wasas a white solid. (90 mg, 30% yield)

[0824] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoyl)glycinate (Compound No.216)

[0825] The titlewhite solid. (150.2 mg, 36% yield)

[0826] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoyl)-L-valinate (Compound No.215)Docket No.210869-WO-SEC-1

[0827] The title compouna slightly yellow solid. (107 mg, 20% yield)

[0828] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoyl)-L-phenylalaninate (217)

[0829] The title compound was prepared and was isolated as a white solid. (257 mg, 92% yield)

[0830] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl-L-phenylalaninate (282)Docket No.210869-WO-SEC-1

[0831] The title compounds a white solid. (177 mg, 63% yield)

[0832] N-(4-Chlorophenyl)-2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.86)

[0833] The title compound was was as a white solid. (346 mg, 71.97% yield, melting point 205-209 °C)

[0834] 2-(2-(1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N-(p- tolyl)butanamide (Compound No.85)Docket No.210869-WO-SEC-1

[0835] The title compound was prepared and was isolated as a white solid. (196 mg, 53% yield, melting point 206-210 °C)

[0836] 2-(2-(1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(3,4- difluorophenyl)-3-methylbutanamide (Compound No.84)

[0837] The title compound wasas an off white solid. (163 mg, 46% yield, melting point 161-165 °C)

[0838] 2-(2-(1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-N-(2- methoxyethyl)-3-methylbutanamide (Compound No.83)

[0839] The title compound was prepared and was isolated as a white solid. (159 mg, 46% yield, melting point 131-135 °C)

[0840] 2-(2-(1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N-(3- phenylpropyl)butanamide (Compound No.82)Docket No.210869-WO-SEC-1

[0841] The title compound was as a white solid. (204 mg, 46% yield, melting point 163-167 °C)

[0842] 2-(2-(1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N- phenethylbutanamide (Compound No.81)

[0843] The title compound wasas a white solid. (292 mg, 57% yield, melting point 157-161 °C)

[0844] N-Butyl-2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methylbutanamide (Compound No.80)

[0845] The title compound was prepared and was isolated as a white solid. (282 mg, 61% yield, melting point 178-182 °C)Docket No.210869-WO-SEC-1

[0846] 2-(2-(1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3-methyl-N-(4- methylbenzyl)butanamide (Compound No.79)

[0847] The title compound was prepared and was isolated as an off white solid. (181 mg, melting point 166-170 °C)

[0848] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methyl-N-(4-methylbenzyl)butanamide (Compound No.78)

[0849] The title compound was prepared and was isolated as a white solid. (281 mg, 55% yield, melting point 149-153 °C)

[0850] N-(4-Chlorobenzyl)-2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamide (Compound No.77)Docket No.210869-WO-SEC-1

[0851] The title compound was prepared and was isolated as an off white solid. (107 mg, 31% yield, melting point 95-99 °C)

[0852] Dimethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl- L-aspartate (Compound No.185)

[0853] The title compound was was as a white solid. (69 mg, 42% yield, melting point 16-167 °C)

[0854] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- tryptophanate (Compound No.196)Docket No.210869-WO-SEC-1

[0855] The title compound was prepared and was isolated as a pale yellow solid. (137 mg, 95% yield, melting point 89-91 °C)

[0856] Dimethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl- L-glutamate (Compound No.195)

[0857] The title compound was prepared and was isolated as a pale yellow gummy liquid. (123 mg, 72% yield)

[0858] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- glutaminate (Compound No.194)

[0859] The title compoundan off white solid. (26 mg, 26% yield, melting point 196-198 °C)

[0860] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- isoleucinate (Compound No.193)Docket No.210869-WO-SEC-1

[0861] The title compound was prepared and was isolated as a pale yellow gummy liquid. (124 mg, 77% yield)

[0862] Methyl N6-(tert-butoxycarbonyl)-N2-((2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valyl)-L-lysinate (Compound No.192)

[0863] The title compound was prepared and was isolated as a pale yellow gummy liquid. (133 mg, 67% yield)

[0864] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- methioninate (Compound No.191)Docket No.210869-WO-SEC-1

[0865] The title compoundas a pale yellow solid. (155 mg, 93% yield, melting point 144-146 °C)

[0866] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl-L- prolinate (Compound No.190)

[0867] The title compound was prepared and was isolated as a yellow gummy liquid. (126 mg, 80% yield)

[0868] S-Isopropyl 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methoxybutanethioate (Compound No.321)

[0869] The title compound wasas a yellow liquid. (27 mg)Docket No.210869-WO-SEC-1

[0870] S-Benzyl 3-cyclopropyl-2-(2-(5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)propanethioate (Compound No.408)

[0871] The title compound wasas a colorless liquid. (45 mg)

[0872] S-Isopropyl 3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanethioate (Compound No.278)

[0873] The title compound was was as a yellow liquid. (16 mg, 10% yield)

[0874] S-Isopropyl 3-cyclopropyl-2-(2-(5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)propanethioate (Compound No.409)Docket No.210869-WO-SEC-1

[0875] The title compound was prepared and was isolated as a white solid. (19 mg, melting point 122-124 °C)

[0876] S-Benzyl 3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanethioate (Compound No.279)

[0877] The title compound was prepared and was isolated as a yellow liquid. (70 mg)

[0878] Method 10: Preparation of (2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valine (Compound No.2)Docket No.210869-WO-SEC-1

[0879] In a round-bottomed flask charged with magnetic stir bar was added methyl (2- ((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valinate (1 equiv) and THF:H2O (0.2 M, 3:1). To this was added lithium hydroxide (2-5 equiv) and the reaction was stirred at room temperature for 16 hours. After this time the reaction was diluted to 0.05 M with H2O, the acidified to pH 1-4 with HCl. The reaction was extracted with EtOAc (3x), the combined organic layer washed with brine, and dried over Na2SO4. The solids are filtered off and solvent removed in vacuo to afford the product as a solid. The title compound was isolated as a white solid. (140 mg, 97% yield)

[0880] The following compounds were prepared in accordance to the procedure in Method 10:

[0881] (S)-3-Cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)propanoic acid (Compound No.206)

[0882] The title compound was was as a white solid. (312.7 mg, 96% yield)

[0883] N-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O-methyl-L- threonine (Compound No.281)Docket No.210869-WO-SEC-1

[0884] The title compound was prepared and was isolated as a white solid. (318.6 mg, 80% yield)

[0885] N-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-methyl-L- valine (Compound No.25)

[0886] The title compoundas a white solid. (287.7 mg, 82% yield)

[0887] N-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-ethyl-L-valine (Compound No.28)

[0888] The title compound was prepared and was isolated as a white solid. (224.8 mg, 73% yield)

[0889] N-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-(prop-2-yn-1- yl)-L-valine (Compound No.32)Docket No.210869-WO-SEC-1

[0890] The title compound wasas a white solid. (123.5 mg, 87% yield)

[0891] N-Allyl-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valine (Compound No.30)

[0892] The title compound was was as a white solid. (89.8 mg, 64% yield)

[0893] (S)-3-Cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)propanoic acid (Compound No.351)

[0894] The title compoundas a white solid. (510.5 mg, 89% yield)Docket No.210869-WO-SEC-1

[0895] N-(Carboxymethyl)-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valine (Compound No.51)

[0896] The title compound wasas a slightly yellow solid. (140.6 mg, 78% yield)

[0897] O-Methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- threonine (Compound No.411)

[0898] The title compounda white solid. (171.6 mg, 92% yield)

[0899] 2-((S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-3- methylbutanamido)-2-methylpropanoic acid (Compound No.75)Docket No.210869-WO-SEC-1

[0900] The title compound was a white powder. (153 mg, 62% yield)

[0901] (S)-3-Cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)-N- ethylacetamido)propanoic acid (Compound No.249)

[0902] The title compoundas a colorless liquid. (64 mg)

[0903] (S)-2-(N-Allyl-2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)- 3-cyclopropylpropanoic acid (Compound No.248)

[0904] The title compound was prepared and was isolated as an off white solid. (112 mg, melting point 120-121 °C)Docket No.210869-WO-SEC-1

[0905] (S)-3-Cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)-N- (prop-2-yn-1-yl)acetamido)propanoic acid (Compound No.266)

[0906] The title compound wasas a pale yellow liquid. (61 mg)

[0907] (S)-2-(N-(Carboxymethyl)-2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-cyclopropylpropanoic acid (Compound No.265)

[0908] The title compound was a pale yellow liquid. (57 mg)

[0909] N-(N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O-methyl- L-threonyl)-O-methyl-L-threonine (Compound No.304)Docket No.210869-WO-SEC-1

[0910] The title compound as a white solid. (139 mg)

[0911] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O-methyl-L- threonyl-L-valine (Compound No.306)

[0912] The title compound was prepared and was isolated as a white solid. (155 mg)

[0913] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O-methyl-L- threonyl-L-alanine (Compound No.309)

[0914] The title compound was prepared and was isolated as a white solid. (165 mg)Docket No.210869-WO-SEC-1

[0915] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O-methyl-L- threonylglycine (Compound No.311)

[0916] The title compound as an off white solid. (143 mg) Lithium (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valylglycinate (Compound No.70)

[0918] The title compound was prepared and isolated by filtration directly from the reaction mixture without dilution or acidification, and the solid washed with Et2O until dry, and was isolated as an off white solid. (89 mg).

[0919] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-valine (Compound No.324)Docket No.210869-WO-SEC-1

[0920] The title compound was isolated as a white solid. (452 mg, 88% yield)

[0921] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valylglycine (Compound No.69)

[0922] The title compound was prepared and was isolated as an off white solid. (150 mg)

[0923] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valyl- L-valinate (Compound No.21)Docket No.210869-WO-SEC-1

[0924] The title compound was prepared and was isolated as an off white solid. (666 mg, 66% yield)

[0925] Method 11: Preparation of methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)-N-ethylacetamido)propanoate (Compound No.251)

[0926] In a round-bottomed flaskstir bar was added (S)-2-(1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetic acid (1 equiv), anhydrous DMF (0.75 M), amine nucleophile (1.2 equiv), 2-chloro-1-methyl-pyridin-1-ium iodide (1.5 equiv), and N,N- Diisopropylethylamine (2.5 equiv). The reaction was allowed to stir at 22 °C for 16 hours (h) or until complete. The reaction was poured into ice cold water, then extracted with ethyl acetate. The combined organic layers were washed with water followed by brine, then dried over sodium sulfate. The solvent is filtered, then concentrated, and purified by silica column chromatography. The title compound was isolated as an off white solid. (56 mg, 41% yield, melting point 108-109 °C)

[0927] The following compounds were prepared in accordance to the procedure in Method 11:

[0928] Methyl (S)-2-(N-allyl-2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-cyclopropylpropanoate (Compound No.250)Docket No.210869-WO-SEC-1

[0929] The title compound was prepared and was isolated as an off white solid. (95 mg, melting point 68-69 °C)

[0930] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-(2- methoxy-2-oxoethyl)-O-methyl-L-threoninate (Compound No.289)

[0931] The title compound wasas a pale yellow liquid. (35 mg)

[0932] Methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)-N-(prop-2-yn-1-yl)acetamido)propanoate (Compound No.268)

[0933] The title compound was prepared and was isolated as a pale yellow liquid. (90 mg)

[0934] Methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)-N-(2-methoxy-2-oxoethyl)acetamido)propanoate (Compound No.267)Docket No.210869-WO-SEC-1

[0935] The title compound wasas a colorless liquid. (78 mg)

[0936] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-N-ethyl- O-methyl-L-threoninate (Compound No.292)

[0937] The title compoundas a pale yellow liquid. (93 mg) Methyl N-allyl-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)- O-methyl-L-threoninate (Compound No.291)

[0939] The title compound was prepared and was isolated as a colorless liquid. (76 mg)Docket No.210869-WO-SEC-1

[0940] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-N-(prop-2-yn-1-yl)-L-threoninate (Compound No.290)

[0941] The title compounda colorless liquid. (70 mg)

[0942] Methyl N-allyl-O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetyl)-L-threoninate (Compound No.426)

[0943] The title compound wad as a pale yellow liquid. (196 mg)

[0944] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-N-(prop-2-yn-1-yl)-L-threoninate (Compound No.425)Docket No.210869-WO-SEC-1

[0945] The title compound was prepared and was isolated as a pale yellow liquid. (93 mg)

[0946] Methyl N-(2-methoxy-2-oxoethyl)-O-methyl-N-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-threoninate (Compound No.424)

[0947] The title compound wasas a pale yellow liquid. (73 mg)

[0948] Methyl (S)-3-cyclopropyl-2-(N-(2-methoxy-2-oxoethyl)-2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetamido)propanoate (Compound No.403)

[0949] The title compoundas a pale yellow liquid. (119 mg)

[0950] Methyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)-N-(prop-2-yn-1-yl)acetamido)propanoate (Compound No.402)Docket No.210869-WO-SEC-1

[0951] The title compound was a pale yellow liquid. (135 mg)

[0952] Methyl (S)-2-(N-allyl-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetamido)-3-cyclopropylpropanoate (Compound No.401)

[0953] The title compoundas a pale yellow liquid. (137 mg)

[0954] Methyl N-(2-methoxy-2-oxoethyl)-N-(2-((S)-5-oxo-1-(2,3,5- trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-valinate (Compound No.346)Docket No.210869-WO-SEC-1

[0955] The title compound was prepared and was isolated as a pale yellow liquid. (127 mg)

[0956] Methyl N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-N- (prop-2-yn-1-yl)-L-valinate (Compound No.345)

[0957] The title compound wasas a pale yellow liquid. (112 mg)

[0958] Methyl N-allyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-valinate (Compound No.344)

[0959] The title compound was prepared and was isolated as a pale yellow liquid. (116 mg)

[0960] Method 12: Preparation of Methyl N-(cyanomethyl)-O-methyl-N-(2-((S)-5- oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L-threoninate (Compound No.434)Docket No.210869-WO-SEC-1

[0961] In a round-bottomed flask stir bar was added (S)-2-(5-oxo- 1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetic acid (1 equiv), pyridine (0.2 M), amine nucleophile (1.2 equiv). The reaction was cooled to 0 °C, then phosphoryl chloride (1.5 equiv) was added and the reaction allowed to warm to room temperature., and N,N- Diisopropylethylamine (2.5 equiv). The reaction was allowed to stir at 22 °C for 2 hours (h). The reaction was poured into ice cold 1N HCl, then extracted with ethyl acetate. The combined organic layers were washed with water followed by brine, then dried over sodium sulfate. The solvent is filtered, then concentrated, and purified by silica column chromatography. The title compound was isolated as a pale yellow liquid. (98 mg, 63% yield)

[0962] The following compounds were prepared in accordance to the procedure in Method 12:

[0963] Methyl (S)-2-(N-(cyanomethyl)-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)-3-cyclopropylpropanoate (Compound No.406)

[0964] The title compoundas a pale yellow liquid. (80 mg)

[0965] Methyl N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-N- (2,2,2-trifluoroethyl)-L-valinate (Compound No.347)Docket No.210869-WO-SEC-1

[0966] The title compound wasas a pale yellow liquid. (35 mg)

[0967] Methyl (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)-N-(2,2,2-trifluoroethyl)acetamido)propanoate (Compound No.407)

[0968] The title compoundas an off white solid. (71 mg, melting point 97-99 °C)

[0969] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-N-(2,2,2-trifluoroethyl)-L-threoninate (Compound No.435)

[0970] The title compound was prepared and was isolated as a pale yellow liquid. (35Docket No.210869-WO-SEC-1

[0971] Methyl N-(cyanomethyl)-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin- 2-yl)acetyl)-L-valinate (Compound No.348)

[0972] The title compound wasas a pale yellow liquid. (143 mg)

[0973] Method 13: Preparation of (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-N-hydroxy-3-methylbutanamide (Compound No.50)

[0974] To a solution of (S)-N- - - (2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl) acetamido)-3-methylbutanamide (0.2 g, 0.42 mmol) in methanol (5 mL), 10% Pd / C (0.02 g) was added. The reaction mixture was stirred under hydrogen balloon pressure for 2 h at 23 °C. The reaction mixture was filtered through celite and washed with methanol. The filtrate was concentrated to afford the title compound. (0.133 g, 82 %)

[0975] Method 14: Preparation of 1-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)-3-methylbutanamido)cyclopropane-1-carboxylic acid (Compound No.204)Docket No.210869-WO-SEC-1

[0976] A 2M aqueous solutionμL, 0.52 mmol, 2.0 equiv) was added to a stirred solution of methyl 1-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetamido)-3-methylbutanamido)cyclopropane-1-carboxylate (120 mg, 0.26 mmol, 1.0 equiv) in 2:1 methanol : tetrahydrofuran (3.0 mL) at 23 °C. The homogeneous colorless solution was stirred at 23 °C for 24 h. The reaction mixture was concentrated by rotary evaporation and the residue was diluted with 0.1M aqueous hydrochloric acid solution (50 mL) and extracted with ethyl acetate (6 x 25 mL). The combined organic layers were dried (sodium sulfate), gravity filtered, and concentrated by rotary evaporation. The title compound was isolated as a white powder. (115 mg, 99% yield).

[0977] The following compounds were prepared in accordance to the procedure in Method 14:

[0978] (S)-3-Cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2- yl)acetamido)propanoic acid (Compound No.488)

[0979] The title compound was prepared and was isolated as a white solid. (95% purity, 69% yield)

[0980] Method 15: Preparation of triisopropylsilyl (2-((S)-1-(2,3-difluorobenzyl)- 5-oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.179)Docket No.210869-WO-SEC-1

[0981] Imidazole (0.028 g, 0.407 (0.064 ml, 0.299 mmol) were sequentially added to a stirred mixture of (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valine (0.100 g, 0.271 mmol) in DMF (2.71 ml) at 23 °C.    The reaction solution was stirred at 23 °C for 1 h. The reaction was diluted with ethyl acetate (20 mL)^ washed throughly with water, and then dried with anhydrous MgSO4. The residue after concentration in vacuo was purified by flash silica gel chromatography (0% to 100% acetone in hexane), giving triisopropylsilyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L- valinate (93 mg, 0.168 mmol, 62.0 % yield) as a sticky oil.

[0982] The following compounds were prepared in accordance to the procedure in Method 15:

[0983] tert-Butyldiphenylsilyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.184)

[0984] The title compound was prepared and was isolated as a white solid. (121 mg, 70% yield)

[0985] Method 16: Preparation of Lithium (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.10)Docket No.210869-WO-SEC-1

[0986] In a 2-dram reaction vial charged with magnetic stir bar was added (2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valine (1.1 equiv) and lithium hydroxide (1 equiv) in 1:1 THF:Water mixture (0.125 M). The reaction was stirred at 20 °C for 20 hours (h) or until complete. The reaction was diluted with water and washed with ethyl acetate and then 3:1 ethyl acetate:heptane mixture. Aqueous layer was concentrated to remove water. The title compound was isolated as a white solid. (177.4 mg, 94% yield)

[0987] Method 17: Preparation of Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-N-methylvalinate (Compound No.23)

[0988] In a 25 mL reaction vial charged with magnetic stir bar was added methyl (2-((S)- 1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-L-valinate (1 equiv) in THF (0.2 M).1M Lithium bis(trimethylsilyl)amide in THF (1 equiv) added at 0 °C and stirred at 0 °C for 5 minutes. Iodomethane (2 equiv) was added and then the reaction was stirred at 20 °C for 48 hours (h) or until complete. The reaction was then quenched by adding MeOH, concentrated onto celite and purified by silica column chromatography. The title compound was isolated as a clear oil. (236 mg, 60% yield)

[0989] Method 18: Preparation of Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoyl)-L-tyrosinate (Compound No. 240)Docket No.210869-WO-SEC-1

[0990] To a solution of methyl - oxy) phenyl)-2-((S)-3- cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl) acetamido) propanamido) propanoate (1 equiv) in THF (0.6 M) at 0 °C, was added TBAF (1M in THF, 2 equiv), and stirred for 1 hour (h) or until complete at room temperature. Reaction mixture was diluted with ethyl acetate. Organic layer was washed with water, brine solution, dried over sodium sulfate and concentrated. The obtained crude compound was purified by silica column chromatography. The title compound was isolated as an off white solid. (0.12 g, 36 % yield)

[0991] The following compounds were prepared in accordance to the procedure in Method 18:

[0992] Methyl N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetyl)-O- methyl-L-threonyl-L-tyrosinate (Compound No.287)

[0993] The title compound was prepared and was isolated as an off white solid. (166 mg)

[0994] Methyl ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)propanoyl)-L-tyrosinate (Compound No.369)Docket No.210869-WO-SEC-1

[0995] The title compound as a white solid. (156 mg)

[0996] Methyl O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2- yl)acetyl)-L-threonyl-L-tyrosinate (Compound No.419)

[0997] The title compound was prepared and was isolated as an off white solid. (167 mg)

[0998] Method 19: Preparation of Tetramethylammonium (S)-3-cyclopropyl-2-(2- ((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No. 243)

[0999] In a 25 mL reaction vial charged with magnetic stir bar was added (S)-3- cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)-propanoic acid (1 equiv) in MeOH (0.5 M). Corresponding ammonium hydroxide or amine N-oxide (1 equiv)Docket No.210869-WO-SEC-1 was added via syringe. The reaction was stirred at 20 °C for 30 min or until completion. Crude reaction was concentrated to obtain the title compound as a slightly yellow goo. (347.6 mg, 73% yield)

[1000] The following compounds were prepared in accordance to the procedure in Method 19:

[1001] Tetraethylammonium (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.244)

[1002] The title compound was prepared and was isolated as a slightly yellow goo. (330.4 mg, 63% yield)

[1003] 2-Hydroxy-N,N,N-trimethylethan-1-aminium (S)-3-cyclopropyl-2-(2-((S)-1- (2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.245)

[1004] The title compound was prepared and was isolated as a slightly yellow goo. (361.2 mg, 71% yield)

[1005] N,N,N-Trimethylhydroxylammonium (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.246)Docket No.210869-WO-SEC-1

[1006] The title compound was prepared and was isolated as a clear goo. (162 mg, 69% yield)

[1007] 4-Hydroxy-4-methylmorpholin-4-ium (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (Compound No.247)

[1008] The title compound was prepared and was isolated as a clear goo. (167.6 mg, 64% yield)

[1009] Tetrabutylammonium (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.13)

[1010] The title compound was prepared and was isolated as a clear goo. (1.8 g, 99% yield)Docket No.210869-WO-SEC-1

[1011] Tetraethylammonium (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.135)

[1012] The title compound as a clear goo. (498 mg, 98% yield)

[1013] 2-Hydroxy-N,N,N-trimethylethan-1-aminium (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.136)

[1014] The title compound was prepared and was isolated as a clear goo. (472 mg, 98% yield)

[1015] Tetramethylammonium (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (Compound No.141)

[1016] The title compound was prepared and was isolated as a clear goo. (442 mg, 98% yield)Docket No.210869-WO-SEC-1

[1017] N,N,N-Trimethylhydroxylammonium (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.142)

[1018] The title compound as a clear goo. (222 mg, 98% yield)

[1019] 4-Hydroxy-4-methylmorpholin-4-ium (2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.143)

[1020] The title compound was prepared and was isolated as a clear goo. (243 mg, 98% yield).

[1021] Method 20: Preparation of Methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetamido)propanoate (Compound No.487)

[1022] In a round-bottomedstir bar were added methyl (S)- 3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (1.0 g, 2.5 mmol, 1.0 equiv), Lawesson's reagent (770 mg, 1.9 mmol, 0.75 eqiv) and tolueneDocket No.210869-WO-SEC-1 (25 mL). The resulting cloudy reaction mixture was stirred at 23 °C for 18 h and then heated to 40 °C and stirred for 24 h. The reaction mixture was concentrated onto silica gel and purified by silica column chromatography. The title compound was isolated as a colorless oil. (520 mg, 95% purity, 47% yield)

[1023] The following compounds were prepared in accordance to the procedure in Method 20:

[1024] Allyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetyl)-L-valinate (Compound No.458)

[1025] The title compound was prepared and was isolated as a pale yellow viscous liquid. (98% purity).

[1026] Benzyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.460)

[1027] The title compound was prepared and was isolated as a pale yellow viscous liquid. (90% purity).

[1028] S-Isopropyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.469)Docket No.210869-WO-SEC-1

[1029] The title compound as a white solid. (93% purity, m.p.110-112 °C).

[1030] S-Benzyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2- yl)acetamido)-3-methylbutanethioate (Compound No.470)

[1031] The title compound was prepared and was isolated as a white solid. (96% purity, m.p.127-129 °C).

[1032] Methyl 2-(((2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetyl)-L- valyl)thio)acetate (Compound No.471)

[1033] The title compound was prepared and was isolated as a white solid. (98% purity, m.p.59-61 °C).

[1034] S-(3,3,3-Trifluoropropyl) (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetamido)-3-methylbutanethioate (Compound No.472)Docket No.210869-WO-SEC-1

[1035] The title compoundas an off white solid. (98% purity, m.p.123-125 °C).

[1036] Allyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2- yl)acetamido)propanoate (Compound No.489)

[1037] The title compound was prepared and was isolated as a colorless viscous liquid. (99% purity).

[1038] Benzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin- 2-yl)acetamido)propanoate (Compound No.491)

[1039] The title compound was prepared and was isolated as a yellow viscous liquid. (96% purity).

[1040] S-Benzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetamido)propanethioate (Compound No.496)Docket No.210869-WO-SEC-1

[1041] The title compound as a white solid. (99% purity, m.p.108-110 °C).

[1042] S-Isopropyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetamido)propanethioate (Compound No.500)

[1043] The title compound was prepared and was isolated as an off white solid. (91% purity).

[1044] Methyl 2-(((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetamido)propanoyl)thio)acetate (Compound No.501)

[1045] The title compound was prepared and was isolated as a yellow viscous liquid. (99% purity).Docket No.210869-WO-SEC-1

[1046] S-(3,3,3-Trifluoropropyl) (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetamido)propanethioate (Compound No.502)

[1047] The title compound was was as a white solid. (98% purity).

[1048] Method 21: Preparation of Methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3- difluorobenzyl)-5-thioxopyrrolidin-2-yl)ethanethioamido)propanoate (Compound No. 486)

[1049] In a round-bottomed flaskstir bar were added methyl (S)- 3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetamido)propanoate (1.0 g, 2.5 mmol, 1.0 equiv), Lawesson's reagent (770 mg, 1.9 mmol, 0.75 eqiv) and toluene (25 mL). The resulting cloudy reaction mixture was stirred at 23 °C for 18 h and then heated to 40 °C and stirred for 24 h. The reaction mixture was concentrated onto silica gel and purified by silica column chromatography. The title compound was isolated as a colorless oil. (320 mg, 95% purity, 28% yield)

[1050] The following compounds were prepared in accordance to the procedure in Method 21:

[1051] Allyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)ethanethioyl)-L- valinate (Compound No.459)Docket No.210869-WO-SEC-1

[1052] The title compoundas a yellow viscous liquid. (98% purity).

[1053] S-Isopropyl (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2- yl)ethanethioamido)-3-methylbutanethioate (Compound No.473)

[1054] The title compound was prepared and was isolated as a yellow viscous liquid. (92% purity).

[1055] Benzyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)ethanethioyl)-L- valinate (Compound No.461)

[1056] The title compound was prepared and was isolated as a pale yellow viscous liquid. (99% purity).Docket No.210869-WO-SEC-1

[1057] Methyl 2-(((2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2- yl)ethanethioyl)-L-valyl)thio)acetate (Compound No.474)

[1058] The title compound as an off white solid. (85% purity, m.p.118-120 °C).

[1059] Allyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2- yl)ethanethioamido)propanoate (Compound No.490)

[1060] The title compound was prepared and was isolated as a yellow viscous liquid. (99% purity).

[1061] Benzyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin- 2-yl)ethanethioamido)propanoate (Compound No.492)

[1062] The title compound was prepared and was isolated as a pale yellow viscous liquid. (96% purity).Docket No.210869-WO-SEC-1

[1063] S-Isopropyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)ethanethioamido)propanethioate (Compound No.503)

[1064] The title compound was was as a pale brown viscous liquid. (98% purity).

[1065] S-(3,3,3-Trifluoropropyl) (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)ethanethioamido)propanethioate (Compound No.504)

[1066] The title compound was prepared and was isolated as a colorless viscous liquid. (98% purity).

[1067] Method 22, Step 1: Preparation of Methyl (S)-2-(1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetate

[1068] In a round-bottomed flask stir bar were added methyl 2- (1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2-yl)acetate (1.0 g, 3.5 mmol, 1.0 equiv), Lawesson'sDocket No.210869-WO-SEC-1 reagent (2.9 g, 7.1 mmol, 2.0 eqiv) and toluene (30 mL). The resulting cloudy reaction mixture was heated to 40 °C and stirred for 24 h. The reaction mixture was concentrated onto silica gel and purified by silica column chromatography. The title compound was isolated as a yellow oil. (1.0 g, 90% yield)

[1069] Method 22, Step 2: Preparation of (S)-2-(1-(2,3-Difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetic acid

[1070] In a round-bottomed flaskstir bar was added methyl (S)-2- (1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetate (950 mg, 3.2 mmol, 1.0 equiv) and 3:1 THF:H2O (16 mL). To this was added lithium hydroxide hydrate (91 mg, 3.8 mmol, 1.2 equiv) and the reaction was stirred at 23 °C for 2 h. The reaction mixture was concentrated by rotary evaporation. The residue was diluted with 1M HCl and extracted with EtOAc. The combined organic layers were dried over Na2SO4, gravity filtered, and concentrated by rotary evaporation. The title compound was isolated as an off-white solid. (850 mg, 93% yield)

[1071] Method 22, Step 3: Preparation of 2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)-N-((S)-3-methyl-1-oxo-1-((propan-2-ylideneamino)oxy)butan-2- yl)acetamide (Compound No.462)

[1072] To a stirred solution of - -5-thioxopyrrolidin-2- yl)acetic acid (180 mg, 0.63 mmol, 1.0 equiv), HATU (290 mg, 0.76 mmol, 1.2 equiv), and propan-2-one O-(L-valyl) oxime hydrochloride (200 mg, 0.95 mmol, 1.5 equiv) in dichloromethane (10 mL) was added N-methylmorpholine (0.28 mL, 2.5 mmol, 4.0 equiv). The reaction was stirred at 23 °C for 16 h. The reaction mixture was diluted with dichloromethaneDocket No.210869-WO-SEC-1 and washed with 1M HCl followed by water. The organic layer was dried over Na2SO4, gravity filtered, and concentrated by rotary evaporation. The reaction mixture was concentrated onto silica gel and purified by silica column chromatography. The title compound was isolated as a white solid. (170 mg, 98% purity, 60% yield, m.p.98-100 °C)

[1073] The following compounds were prepared in accordance to the procedure in Method 22:

[1074] 2-Cyanoethyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetyl)-L- valinate (Compound No.463)

[1075] The title compound was prepared and was isolated as a pale yellow viscous liquid. (92% purity).

[1076] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetyl)-L- valylglycinate (Compound No.475)

[1077] The title compound was prepared and was isolated as a white solid. (98% purity, m.p.180-182 °C).

[1078] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetyl)-L-valyl- L-leucinate (Compound No.476)Docket No.210869-WO-SEC-1

[1079] The title compound was as a white solid. (98% purity, m.p.81-83 °C).

[1080] Methyl (2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetyl)-L-valyl- L-isoleucinate (Compound No.477)

[1081] The title compound was prepared and was isolated as a white solid. (95% purity, m.p.213-215 °C).

[1082] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetamido)-N- methoxy-3-methylbutanamide (Compound No.478)

[1083] The title compound was prepared and was isolated as a white solid. (87% purity, m.p.198-200 °C).Docket No.210869-WO-SEC-1

[1084] (S)-2-(2-((S)-1-(2,3-Difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetamido)-N- isopropoxy-3-methylbutanamide (Compound No.479)

[1085] The title compound was as a white solid. (98% purity, m.p.48-50 °C).

[1086] 2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)-N-((S)-3-methyl-1-(1,2- oxazinan-2-yl)-1-oxobutan-2-yl)acetamide (Compound No.480)

[1087] The title compound was prepared and was isolated as an off white semisolid. (94% purity).

[1088] N-((S)-3-cyclopropyl-1-oxo-1-((propan-2-ylideneamino)oxy)propan-2-yl)-2- ((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin-2-yl)acetamide (Compound No.493)Docket No.210869-WO-SEC-1

[1089] The title compound was prepared and was isolated as an off white solid. (97% purity, m.p.108-110 °C).

[1090] 2-Cyanoethyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5- thioxopyrrolidin-2-yl)acetamido)propanoate (Compound No.494)

[1091] The title compound was was as an off white solid. (98% purity, m.p.128-130 °C).

[1092] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin- 2-yl)acetamido)propanoyl)glycinate (Compound No.505)

[1093] The title compound was prepared and was isolated as a white solid. (97% purity, m.p.79-81 °C).

[1094] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin- 2-yl)acetamido)propanoyl)-L-leucinate (Compound No.506)Docket No.210869-WO-SEC-1

[1095] The title compound was prepared and was isolated as a white solid. (98% purity, m.p.146-148 °C).

[1096] Methyl ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thioxopyrrolidin- 2-yl)acetamido)propanoyl)-L-isoleucinate (Compound No.507)

[1097] The title compound was was as a white solid. (98% purity, m.p.73-75 °C).

[1098] Methyl (2-((S)-5-thioxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- valyl-L-leucinate (Compound No.509)

[1099] The title compound was prepared and was isolated as a white solid. (97% purity, m.p.82-84 °C).

[1100] Methyl (2-((S)-5-thioxo-1-(2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetyl)-L- valyl-L-isoleucinate (Compound No.510)Docket No.210869-WO-SEC-1

[1101] The title compound was was as a white solid. (96% purity, m.p.123-125 °C).

[1102] (S)-N-Methoxy-3-methyl-2-(2-((S)-5-thioxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)butanamide (Compound No.511)

[1103] The title compound was prepared and was isolated as a white solid. (98% purity, m.p.210-212 °C).

[1104] (S)-N-Isopropoxy-3-methyl-2-(2-((S)-5-thioxo-1-(2,3,5-trifluorobenzyl)- pyrrolidin-2-yl)acetamido)butanamide (Compound No.512)

[1105] The title compound was prepared and was isolated as a white solid. (97% purity, m.p.78-80 °C).Docket No.210869-WO-SEC-1

[1106] N-((S)-3-methyl-1-(1,2-oxazinan-2-yl)-1-oxobutan-2-yl)-2-((S)-5-thioxo-1- (2,3,5-trifluorobenzyl)pyrrolidin-2-yl)acetamide (Compound No.513)

[1107] The title compound was as a white solid. (93% purity, m.p.168-170 °C).

[1108] Method 23: Preparation of 2-(((2-((S)-1-(2,3-difluorobenzyl)-5- oxopyrrolidin-2-yl)acetyl)-L-valyl)oxy)acetic acid (Compound No.465)

[1109] Trifluoroacetic acid 20 equiv) was added to a stirred solution of 2-(tert-butoxy)-2-oxoethyl (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidin-2- yl)acetyl)-L-valinate (250 mg, 0.52 mmol, 1.0 equiv) in dichloromethane (5.2 mL) at 23 °C. The homogeneous colorless solution was stirred at 23 °C for 24 h. The reaction mixture was concentrated by rotary evaporation and the residue was diluted with 0.1M aqueous hydrochloric acid solution (50 mL) and extracted with ethyl acetate (6 x 25 mL). The combined organic layers were dried (sodium sulfate), gravity filtered, and concentrated by rotary evaporation. The title compound was isolated as a white foam. (210 mg, 95% crude yield) 4. Compositions

[1110] The present disclosure also includes compositions containing the 5-member ring- based molecule herbicides disclosed herein. A composition is a mixture comprising at leastDocket No.210869-WO-SEC-1 one 5-member ring-based molecule herbicide and further comprising other additives, such as a carrier, used to enhance the properties or effectiveness of the mixture in some way. Exemplary additives include but are not limited to adjuvants, safeners, carriers, and combinations thereof. Compositions may be in various physical states, including but not limited to as solutions, emulsions, suspensions, granules, powders, and other such states. 1. Carriers

[1111] In some aspects, the additive includes a carrier. In some aspects, the additive includes a liquid or solid carrier. In some aspects, the additive includes an organic or inorganic carrier. Exemplary liquid carriers include, but are not limited to: water; petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; esters of monoalcohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy containing), such as 2-ethyl hexyl stearate, n-butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate and the like; esters of mono, di and polycarboxylic acids and the like; toluene; xylene; petroleum naphtha; crop oil; acetone; methyl ethyl ketone; cyclohexanone; trichloroethylene; perchloroethylene; ethyl acetate; amyl acetate; butyl acetate; propylene glycol monomethyl ether and diethylene glycol monomethyl ether; methyl alcohol; ethyl alcohol; isopropyl alcohol; amyl alcohol; ethylene glycol; propylene glycol; glycerin; N-methyl-2-pyrrolidinone; N;N-dimethyl alkylamides; dimethyl sulfoxide; and liquid fertilizers, as well as mixtures thereof. Exemplary solid carriers include, but are not limited to: silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground synthetic materials, pyrophyllite clay, attapulgus clay, kieselguhr, calcium carbonate, bentonite clay, Fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, cereal meal, tree bark meal, wood meal and nutshell meal, cellulose powders, and mixtures thereof. 2. Adjuvants

[1112] In some aspects, the additive includes an agriculturally acceptable adjuvant. Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifreeze agents, antifoam agents, compatibilizing agents, sequestering agents, neutralizing agents and buffers,Docket No.210869-WO-SEC-1 corrosion inhibitors, colorants, odorants, penetration aids, wetting agents, spreading agents, dispersing agents, thickening agents, freeze point depressants, antimicrobial agents, crop oil, adhesives (for instance, for use in seed formulations), surfactants, protective colloids, emulsifiers, tackifiers, and mixtures thereof.

[1113] Exemplary agriculturally acceptable adjuvants include, but are not limited to, crop oil concentrates (e.g., 85% mineral oil + 15% emulsifiers); nonylphenol ethoxylates; benzylcocoalkyldimethyl quaternary ammonium salts; blends of petroleum hydrocarbon, alkyl esters, organic acids, and anionic surfactants; C9-C11 alkylpolyglycoside; alkyl phosphates, such as tris(2-ethylhexyl) phosphate (TEHP); phosphate alcohol ethoxylates; natural primary alcohol (C12-C16) ethoxylate; di-sec-butylphenol EO-PO block copolymers; polysiloxane- methyl cap; nonylphenol ethoxylate+urea ammonium nitrates; emulsified methylated seed oils; tridecyl alcohol (synthetic) ethoxylates (e.g., 8 EO); tallow amine ethoxylates (e.g., 15 EO); and PEG(400) dioleate-99.

[1114] Exemplary surfactants (e.g., wetting agents, tackifiers, dispersants, emulsifiers) include, but are not limited to: the alkali metal salts, alkaline earth metal salts and ammonium salts of fatty acids or of aromatic sulfonic acids (e.g., lignosulfonic acids, phenolsulfonic acids, naphthalenesulfonic acids, and dibutylnaphthalenesulfonic acid); alkyl- and alkylarylsulfonates; alkyl sulfates, lauryl ether sulfates and fatty alcohol sulfates; salts of sulfated hexa-, hepta- and octadecanols; salts of fatty alcohol glycol ethers; condensates of sulfonated naphthalene and its derivatives with formaldehyde; condensates of naphthalene or of the naphthalene sulfonic acids with phenol and formaldehyde; polyoxyethylene octylphenol ether; ethoxylated isooctyl-, octyl- or nonylphenol, alkylphenyl or tributylphenyl polyglycol ether; alkyl aryl polyether alcohols; isotridecyl alcohol; fatty alcohol / ethylene oxide condensates; ethoxylated castor oil; polyoxyethylene alkyl ethers or polyoxypropylene alkyl ethers; lauryl alcohol polyglycol ether acetate; sorbitol esters; lignosulfite waste liquors and proteins; denatured proteins, polysaccharides (e.g., methylcellulose); hydrophobically modified starches; and polyvinyl alcohol, polycarboxylates, polyalkoxylates, polyvinyl amines, polyethyleneimine, polyvinylpyrrolidone, and copolymers thereof.

[1115] Exemplary thickeners include, but are not limited to, polysaccharides (e.g., xanthan gum), organic and inorganic sheet minerals, and mixtures thereof.Docket No.210869-WO-SEC-1

[1116] Exemplary antifoam agents include, but are not limited to, silicone emulsions, long-chain alcohols, fatty acids, fatty acid salts, organofluorine compounds, and mixtures thereof.

[1117] Exemplary antimicrobial agents include, but are not limited to, bactericides based on dichlorophen and benzyl alcohol hemiformal; isothiazolinone derivatives, such as alkylisothiazolinones and benzisothiazolinones; and mixtures thereof.

[1118] Exemplary antifreeze agents, include, but are not limited to ethylene glycol, propylene glycol, urea, glycerol, and mixtures thereof.

[1119] Exemplary colorants include, but are not limited to, the dyes known under the names Rhodamine B, pigment blue 15:4, pigment blue 15:3, pigment blue 15:2, pigment blue 15:1, pigment blue 80, pigment yellow 1, pigment yellow 13, pigment red 112, pigment red 48:2, pigment red 48:1, pigment red 57:1, pigment red 53:1, pigment orange 43, pigment orange 34, pigment orange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basic violet 10, basic violet 49, acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108, and mixtures thereof.

[1120] Exemplary adhesives include, but are not limited to, polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, tylose, and mixtures thereof. 3. Safeners

[1121] In some aspects, the additive is a safener. Safeners are compounds leading to better crop plant compatibility when applied with a herbicide. In some aspects, the safener itself is herbicidally active. In some aspects, the safener acts as an antidote or antagonist in the crop plants and can protect the crop plants from damage that might otherwise occur from an applied herbicide. Exemplary safeners include, but are not limited to, AD-67 (MON 4660), benoxacor, benthiocarb, brassinolide, cloquintocet, cloquintocet-mexyl, cyometrinil, cyprosulfamide, daimuron, dichlormid, dicyclonon, dietholate, dimepiperate, disulfoton, fenchlorazole, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, harpin proteins, isoxadifen-ethyl, jiecaowan, jiecaoxi, mefenpyr, mefenpyr-diethyl, mephenate, naphthalic anhydride, 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine, 4-(dichloroacetyl)-1-oxa-4- azaspiro [4.5]-decane, oxabetrinil, R29148, and N-phenyl-sulfonylbenzoic acid amides, agriculturally acceptable salts as well as thereof and, provided they have a carboxyl group, their agriculturally acceptable derivatives. In some aspects, the safener can be cloquintocet or an ester or salt thereof, such as cloquintocet-mexyl. In some aspects, the safener can be mefenpyrDocket No.210869-WO-SEC-1 or an ester or salt thereof, such as mefenpyr-diethyl. In some aspects, the safener is employed in rice, cereal, or maize. For example, mefenpyr or cloquintocet can be used to antagonize harmful effects of the compositions on rice, row crops, and cereals. 4. Physical States

[1122] In some aspects, the compositions comprising the 5-member ring-based molecule herbicide may be present in suspended, emulsified, dissolved, or solid form. Exemplary compositions include, but are not limited to, aqueous solutions, aqueous suspensions, aqueous dispersions, aqueous emulsions, aqueous microemulsions, aqueous suspo-emulsions, oil solutions, oil suspensions, oil dispersions, oil emulsions, oil microemulsions, oil suspo- emulsions, self-emulsifying formulations, gels, pastes, powders, dusts, granules, and materials for spreading.

[1123] In some aspects, the 5-member ring-based molecule herbicide is in an aqueous solution that can be diluted before use. In various aspects, the 5-member ring-based molecule herbicide may be provided as a high-strength formulation such as a concentrate. In some aspects, the concentrate is stable and retains potency during storage and shipping. In various aspects, the concentrate is a clear, homogeneous liquid that is stable at temperatures of 54 °C or greater. In some aspects, the concentrate does not exhibit any precipitation of solids at temperatures of 10 °C or higher. In some aspects, the concentrate does not exhibit separation, precipitation, or crystallization of any components at low temperatures. For example, the concentrate remains a clear solution at temperatures below 0 °C (e.g., below -5 °C, below -10 °C, below -15 °C). In some aspects, the concentrate exhibits a viscosity of less than 50 centipoise (50 megapascals), even at temperatures as low as 5 °C. In some aspects, the concentrate does not exhibit separation, precipitation, or crystallization of any components during storage for a period of 2 weeks or greater (e.g., 4 weeks, 6 weeks, 8 weeks, 3 months, 6 months, 9 months, or 12 months or greater).

[1124] In some aspects, emulsions, gels, pastes, or oil dispersions can be prepared by homogenizing the 5-member ring-based molecule herbicide in water with a wetting agent, tackifier, dispersant, or emulsifier. In some aspects, concentrates suitable for dilution with water can be prepared, comprising the 5-member ring-based molecule herbicide, a wetting agent, a tackifier, and a dispersant or emulsifier.Docket No.210869-WO-SEC-1

[1125] In some aspects, powders, materials for spreading, or dusts can be prepared by mixing or concomitant grinding the 5-member ring-based molecule herbicide and optionally other additives with a solid carrier.

[1126] In some aspects, granules (e.g., coated granules, impregnated granules and homogeneous granules) can be prepared by binding the 5-member ring-based molecule herbicide to solid carriers.

[1127] In some aspects, the compositions comprise, by total weight of the composition, from about 0.01% to about 99% of the 5-member ring-based molecule herbicide, including about 0.025%, 0.05%, 0.075%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 7.5%, 8%, 9%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5%, 50%, 52.5%, 55%, 57.5%, 60%, 62.5%, 65%, 67.5%, 70%, 72.5%, 75%, 77.5%, 80%, 82.5%, 85%, 87.5%, 90%, 92.5%, 95%, 97.5%, or 98% of the 5-member ring-based molecule herbicide by total weight of the composition, or within any range defined between any two of the forgoing values, such as between about 1% to about 97%, between about 10% to about 90%, between about 20% to about 45%, and about 25% to about 50% based on the total weight of the composition. Concentrates can be diluted with an inert carrier, such as water, prior to application. The diluted compositions applied to undesirable vegetation or the locus of undesirable vegetation can contain from 0.0006 to 8.0 weight percent (wt %) of the total amount of the 5-member ring-based molecule herbicide (e.g., from 0.001 to 5.0 wt %), based on the total weight of the diluted composition. 5. Methods of Use

[1128] The 5-member ring-based molecules disclosed herein can be formulated into compositions and applied in any known technique for applying herbicides. Exemplary application techniques include, but are not limited to, spraying, atomizing, dusting, sprinkling, spreading, or direct application. The method of application can vary depending on the intended purpose. In some aspects, the method of application can be chosen to ensure the finest possible distribution of the compositions disclosed herein.

[1129] In some aspects, a method of controlling undesirable vegetation which comprises contacting the vegetation or the locus thereof with or applying to the soil or water to prevent the emergence or growth of vegetation any of the compositions is disclosed herein.Docket No.210869-WO-SEC-1

[1130] The compositions containing a 5-member ring-based molecule disclosed herein can be applied pre-emergence (before the emergence of undesirable vegetation) or post- emergence (e.g., during and / or after emergence of the undesirable vegetation). In some aspects, the composition is applied postemergence to the undesirable vegetation.

[1131] When the compositions are used in crops, the compositions can be applied after seeding and before or after the emergence of the crop plants. In some aspects, the compositions disclosed herein show good crop tolerance even when the crop has already emerged and can be applied during or after the emergence of the crop plants. In some aspects, when the compositions are used in crops, the compositions can be applied before seeding of the crop plants.

[1132] In some aspects, the compositions disclosed herein are applied to vegetation or an area adjacent the vegetation or applying to soil or water to prevent the emergence or growth of vegetation by spraying (e.g., foliar spraying). In some aspects, the spraying techniques use, for example, water as carrier and spray volume rates of from 2 liters per hectare (L / ha) to 2000 L / ha (e.g., from 10–1000 L / ha or from 50–500 L / ha). In some aspects, the compositions disclosed herein are applied by the low-volume or the ultra-low-volume method, wherein the application is in the form of micro granules. In some aspects, wherein the compositions disclosed herein are less well tolerated by certain crop plants, the compositions can be applied with the aid of the spray apparatus in such a way that they come into little contact, if any, with the leaves of the sensitive crop plants while reaching the leaves of undesirable vegetation that grows underneath or on the bare soil (e.g., post-directed or lay-by). In some aspects, the compositions disclosed herein can be applied as dry compositions (e.g., granules, powders, or dusts).

[1133] In some aspects, wherein the undesirable vegetation is treated post-emergence, the compositions disclosed herein are applied by foliar application. In some aspects, herbicidal activity is exhibited by the compounds of the mixture when they are applied directly to the plant or to the locus of the plant at any stage of growth or before planting or emergence. The effect observed can depend upon the type of undesirable vegetation to be controlled, the stage of growth of the undesirable vegetation, the application parameters of dilution and spray drop size, the particle size of solid components, the environmental conditions at the time of use, the specific compound employed, the specific adjuvants and carriers employed, the soil type, and the like, as well as the amount of chemical applied. In some aspects, these and other factors can be adjusted to promote non-selective or selective herbicidal action.Docket No.210869-WO-SEC-1

[1134] The compositions and methods disclosed herein can be used to control undesirable vegetation in a variety of applications. The compositions and methods disclosed herein can be used for controlling undesirable vegetation in areas including, but not limited to, farmland, turfgrass, pastures, grasslands, rangelands, fallow land, rights-of-way, aquatic settings, tree and vine, wildlife management areas, or rangeland. In some aspects, the undesirable vegetation is controlled in a row crop. Exemplary crops include, but are not limited to, wheat, barley, triticale, rye, teff, oats, maize, cotton, soy, canola, pulses, sunflower, sugar beet, sorghum, rice, millet, sugarcane, and range land (e.g., pasture grasses). In some aspects, the compositions and methods disclosed herein can be used for controlling undesirable vegetation in maize, soy, canola, cotton, pulses, sunflower, sugar beet, wheat, barley, rice, sorghum, millet, oats, or combinations thereof. In some aspects, the compositions and methods disclosed herein can be used in industrial vegetation management (IVM) or for utility, pipeline, roadside, and railroad rights−of−way applications. In some aspects, the compositions and methods disclosed herein can also be used in forestry (e.g., for site preparation or for combating undesirable vegetation in plantation forests). In some aspects, the compositions and methods disclosed herein can be used to control undesirable vegetation in conservation reserve program lands (CRP), trees, vines, grasslands, and grasses grown for seeds. In some aspects, the compositions and methods disclosed herein can be used on lawns (e.g., residential, industrial, and institutional), golf courses, parks, cemeteries, athletic fields, and sod farms.

[1135] The compositions and methods disclosed herein can also be used in crop plants that are resistant to, for instance, herbicides, insecticides, fungicides, pathogens, insects, or combinations thereof. In some aspects, the compositions and methods disclosed herein can be used in crop plants that are resistant to one or more herbicides because of genetic engineering or breeding. In some aspects, the compositions and methods disclosed herein can be used in crop plants that are resistant to one or more pathogens such as plant pathogenic fungi owing to genetic engineering or breeding. In some aspects, the compositions and methods disclosed herein can be used in crop plants that are resistant to attack by insects owing to genetic engineering or breeding. Exemplary resistant crops include, but are not limited to, crops that are resistant to photosystem II inhibitors, or crop plants that, owing to introduction of the gene for Bacillus thuringiensis (or Bt) toxin by genetic modification, are resistant to attack by certain insects. In some aspects, the undesirable vegetation is controlled in crops that are tolerant to glyphosate, glufosinate, dicamba, phenoxy auxins, pyridyloxy auxins, aryloxyphenoxypropionates, ACCase inhibitors, synthetic auxin herbicide, HPPD inhibitors,Docket No.210869-WO-SEC-1 PROTOX inhibitors, triazines, and bromoxynil, where the tolerant crops possess single, multiple or stacked traits conferring tolerance to single or multiple chemistries and / or multiple modes of action. In some aspects, the undesirable vegetation can be controlled in a crop that is ACCase-tolerant, ALStolerant, or a combination thereof. In some aspects, the compositions described herein and other complementary herbicides are applied at the same time, either as a combination composition or as a tank mix, or as sequential applications. The compositions and methods may be used in controlling undesirable vegetation in crops possessing agronomic stress tolerance (including but not limited to drought, cold, heat, salt, water, nutrient, fertility, pH), pest tolerance (including but not limited to insects, fungi, and pathogens), and crop improvement traits (including but not limited to yield; protein, carbohydrate, or oil content; protein, carbohydrate, or oil composition; plant stature and plant architecture).

[1136] The compounds and compositions described herein may be used to control plant species described, but not limited to, weeds species found in Randall, R.P. (2017). A Global Compendium of Weeds.3rd Edition. Perth, Western Australia. In some aspects, the compositions disclosed herein can be used for controlling undesirable vegetation including grasses, broadleaf weeds, sedge weeds, and combinations thereof. In some aspects, the compositions disclosed herein can be used for controlling undesirable vegetation including, but not limited to, Acanthospermum species, Aegilops species, Agrostis species, Alopecurus species, Ambrosia species, Anthemis species, Apera species, Amaranthus species, Avena species, Brachiaria species, Bromus species, Chenopodium species, Cenchrus species, Cirsium species, Commelina species, Cyperus species, Datura species, Digitaria species, Echinochloa species, Eleusine species, Atriplex species, Brassica species, Convolvulus species, Conyza species, Cassia species, Euphorbia species, Geranium species, Galinsoga species, Ipomea species, Lamium species, Leptochloa species, Lolium species, Monochoria species, Malva species, Matricaria species, Panicum species, Phalaris species Polygonum species, Prosopis species, Rumex species, Setaria species, Sida species, Sisymbrium species, Solanum species, Sorghum species, Trifolium species, Xanthium species, Veronica species, and Viola species. In some aspects, the undesired vegetation includes blackgrass (Alopecurus myosuroides Huds.), wild oat (Avena fatua), barnyard grass (Echinochloa crus-galli) common chickweed (Stellaria media), velvetleaf (Abutilon theophrasti), hemp sesbania (Sesbania exaltata Cory), Anoda cristata, Bidens pilosa, Brassica kaber, shepherd’s purse (Capsella bursa-pastoris), cornflower (Centaurea cyanus or Cyanus segetum), hempnettle (Galeopsis tetrahit), cleavers (Galium aparine), common sunflower (Helianthus annuus), Desmodium tortuosum, Italian ryegrassDocket No.210869-WO-SEC-1 (Lolium multiflorum), kochia (Kochia scoparia), Medicago arabica, Mercurialis annua, Myosotis arvensis, common poppy (Papaver rhoeas), Raphanus raphanistrum, broad-leaf dock (Rumex obtusifolius), Russian thistle (Salsola kali), wild mustard (Sinapis arvensis), Sonchus arvensis, Thlaspi arvense, Tagetes minuta, Richardia brasiliensis, Plantago major, Plantago lanceolata, bird’seye speedwell (Veronica persica), pigweed (Amaranthus retroflexus), winter rape (Brassica napus), lambsquarters (Chenopodium album), Canadian thistle (Cirsium arvense), nutsedge (Cyperus esculentus), poinsettia (Euphorbia heterophylla), prickly lettuce (Lactuca serriola), purple deadnettle (Lamium purpureum), wild chamomile (Matricaria chamomilla), false chamomile (Matricaria inodora), field chamomile (Anthemis arvensis), common buckwheat (Fagopyrum esculentum), wild buckwheat (Polygonum convulvus), giant foxtail (Setaria faberi), green foxtail (Setaria viridis), yellow foxtail (Setaria pumila) common sorghum (Sorghum vulgare), wild pansy (Viola tricolor), or combinations thereof.

[1137] The compositions described herein can be used to control herbicide resistant or tolerant weeds. The methods employing the compositions described herein may also be employed to control herbicide resistant or tolerant weeds. Exemplary resistant or tolerant weeds include, but are not limited to, biotypes resistant or tolerant to acetolactate synthase (ALS) or acetohydroxy acid synthase (AHAS) inhibitors (e.g., imidazolinones, sulfonylureas, pyrimidinylthiobenzoates, triazolopyrimidines, sulfonylamino-carbonyltriazolinones), photosystem II inhibitors (e.g., phenylcarbamates, pyridazinones, triazines, triazinones, uracils, amides, ureas, benzothiadiazinones, nitriles, phenylpyridazines), acetyl CoA carboxylase (ACCase) inhibitors (e.g., aryloxyphenoxypropionates, cyclohexanediones, phenylpyrazolines), synthetic auxins (e.g., benzoic acids, phenoxycarboxylic acids, pyridine carboxylates, quinoline carboxylic acids), auxin transport inhibitors (e.g., phthalamates, semicarbazones), photosystem I inhibitors (e.g., bipyridyliums), 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase inhibitors (e.g., glyphosate), glutamine synthetase inhibitors (e.g., glufosinate, bilanafos), microtubule assembly inhibitors (e.g., benzamides, benzoic acids, dinitroanilines, phosphoramidates, pyridines), mitosis inhibitors (e.g., carbamates), very long chain fatty acid (VLCFA) inhibitors (e.g., acetamides, chloroacetamides, oxyacetamides, tetrazolinones), fatty acid and lipid synthesis inhibitors (e.g., phosphorodithioates, thiocarbamates, benzofuranes, chlorocarbonic acids), protoporphyrinogen oxidase (PROTOX) inhibitors (e.g., diphenylethers, N-phenylphthalimides, oxadiazoles, oxazolidinediones, phenylpyrazoles, pyrimidinediones, thiadiazoles, triazolinones), carotenoid biosynthesis inhibitors (e.g., clomazone, amitrole, aclonifen), phytoene desaturase (PDS) inhibitors (e.g., amides, anilidex, furanones,Docket No.210869-WO-SEC-1 phenoxybutan-amides, pyridiazinones, pyridines), 4-hydroxyphenyl-pyruvate-dioxygenase (HPPD) inhibitors (e.g., callistemones, isoxazoles, pyrazoles, triketones), cellulose biosynthesis inhibitors (e.g., nitriles, benzamides, quinclorac, triazolocarboxamides), herbicides with multiple modes of action such as quinclorac, and unclassified herbicides such as arylaminopropionic acids, difenzoquat, endothall, and organoarsenicals. Exemplary resistant or tolerant weeds include, but are not limited to, biotypes with resistance or tolerance to multiple herbicides, biotypes with resistance or tolerance to multiple chemical classes, biotypes with resistance or tolerance to multiple herbicide modes of action, and biotypes with multiple resistance or tolerance mechanisms (e.g., target site resistance or metabolic resistance). 6. Examples

[1138] By way of non-limiting illustration, examples of some aspects of the present disclosure are given below. Parts and percentages are on a per weight basis unless otherwise indicated. Example 1 – Pre-Emergent Application of Herbicides

[1139] This example was designed to evaluate the visual growth inhibition of representative weed species when the test herbicide was applied before the emergence (“pre- emergent” or “PRE”) of the sprouting weeds. The weed species tested were: Alopecurus myosuroides (blackgrass, ALOMY); Echinochloa crus-galli (barnyard grass, ECHCG); Setaria faberi (giant foxtail, SETFA); Avena fatua (wild oat, AVEFA); Avena sativa (common oat, AVESA); Ipomea hederacea (ivyleaf morningglory, IPOHE); and Helianthus annuus (sunflower, HELAN). Seeds of the desired test plant species were planted into 12.7 cm diameter round plastic pots containing a silt loam mineral soil.

[1140] Each herbicide molecule that was being tested was dissolved in a solvent mixture of acetone and DMSO (97:3 v / v) to form a herbicide solution. Each herbicide solution was further diluted with a mixture of deionized water, isopropanol, Agridex® crop oil concentrate (Helena Chemical Company, Collierville, Tennessee, USA), and Tergitol™ 15-S-7 surfactant (Dow Chemical Company, Midland, Michigan, USA) (78:20:2:0.02, v / v / v / v) to form a diluted herbicide compositon. The diluted herbicide composition was mixed vigorously and sonicated, if needed, to dissolve any solids. The diluted herbicide composition was diluted with additional deionized water to form the test composition. The concentration of each test composition was 0.338 grams of active ingredient per liter (gai / L), so that a 15-mL aliquot of the test composition would apply 4000 grams of active ingredient per hectare (gai / ha) of soilDocket No.210869-WO-SEC-1 surface. A 15-mL aliquot of each test composition was poured evenly over the soil containing the planted seeds, and an additional 15 mL of deionized water was poured evenly over the soil. The pots containing the treated seeds and soil were placed in a greenhouse with a photoperiod of approximately 16-hours / day. The greenhouse was maintained at 23 °C during the day (illuminated) hours and 22 °C during the night (dark) hours. The treated materials in the pots were kept moist during the test period by over-the-top irrigation. After 14 days, the conditions of the tested plants were compared with control plants by visual assessment and evaluated based on a scoring scale of 0 percent (no injury) to 100% (no emergence or complete plant death after emergence). The visual assessments of plant injury were made based on observed growth inhibition, growth reduction, discoloration, leaf deformity, and necrosis.

[1141] Table 2 presents the data from Example 1. Table 2: Visual Growth Inhibition (%) 14 Days After PRE Application Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEALOMY = blackgrass (Alopecurus myosuroides) AVEFA = wild oat (Avena fatua) AVESA = common oat (Avena sativa) ECHCG = barnyard grass (Echinochloa crus-galli) SETFA = giant foxtail (Setaria faberi) HELAN = sunflower (Helianthus annuus) IPOHE = ivy-leaf morning glory (Ipomoea hederacea) Example 2 – Post-Emergent Application of Herbicides

[1142] This example was designed to evaluate the visual growth inhibition of representative weed species when the test herbicide was applied after the emergence (“post- emergent” or “POST”) of the sprouting weeds. Plastic pots, each with a 64 cm2surface area, were filled with soil-less media planting mix containing Pro-Mix® BX (Premier TechDocket No.210869-WO-SEC-1 Horticulture, Quakertown, Pennsylvania, USA) and Profile® Greens Grade™ (Profile Products LLC, Buffalo Grove, Illinois, USA) at a pH of 5.2 to 6.2 and a minimum of 50% organic matter content. Seed of the desired test plant species were planted in the designated number of the prepared pots, according to the following planting schedule: Alopecurus myosuroides (blackgrass, ALOMY) was planted 14 days prior to herbicide application; Echinochloa crus-galli (barnyard grass, ECHCG), Setaria faberi (giant foxtail, SETFA), Avena fatua (wild oat, AVEFA), and Avena sativa (common oat, AVESA) were planted 11 days prior to herbicide application; Ipomea hederacea (ivyleaf morningglory, IPOHE) and Helianthus annuus (sunflower, HELAN) were planted 8 days prior to herbicide application. The pots containing the seeds were placed in a greenhouse with a photoperiod of approximately 16 hours / day. The greenhouse was maintained at 23 °C during the day (illuminated) hours and 22 °C during the night (dark) hours for the propagation periods indicated above. The pots were sub-irrigated as needed with water containing Jack’s Professional® 15-5-15 Ca-Mg LX fertilizer (JR Peters Inc., Allentown, Pennsylvania, USA).

[1143] Each herbicide molecule that was being tested was dissolved in a formulation solvent mixture containing deionized water, acetone, isopropanol, DMSO, Agridex® crop oil concentrate (Helena Chemical Company, Collierville, Tennessee, USA), and Tergitol™ 15-S-7 surfactant (Dow Chemical Company, Midland, Michigan, USA) (59:24:15:0.75:1.5:0.02, v / v / v / v / v / v) to form the test compositions. The test compositions were mixed vigorously and sonicated, if needed, to dissolve any solids. Each test composition was applied to all plant species at application rates of 4000 grams of active ingredient per hectare (gai / ha). The pots containing the treated plants were returned to the greenhouse. After 9-11 days, the conditions of the treated plants were compared with control plants by visual assessment and evaluated based on a scoring scale of 0 percent (no injury) to 100% (complete plant death). The visual assessments of plant injury were made based on observed growth inhibition, growth reduction, discoloration, leaf deformity, and necrosis.

[1144] Table 3 presents the data from Example 2. Table 3: Visual Growth Inhibition (%) 10 Days After POST Application Compd Rate ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEDocket No.210869-WO-SEC-1 Compd Rate No.(gai / ha)ALOMY AVEFA AVESA ECHCG SETFA HELAN IPOHEALOMY = blackgrass (Alopecurus myosuroides) AVEFA = wild oat (Avena fatua) AVESA = common oat (Avena sativa) ECHCG = barnyard grass (Echinochloa crus-galli) SETFA = giant foxtail (Setaria faberi) HELAN = sunflower (Helianthus annuus) IPOHE = ivy-leaf morning glory (Ipomoea hederacea) Example 3 – Post-Emergent Application of Herbicides

[1145] This example was designed to evaluate the visual growth inhibition of representative dicot weeds, monocot weeds, and crop plant species when the test herbicide was applied after the emergence (“post-emergent” or “POST”) of the sprouting plants. Plastic pots, each with a 64 cm2surface area, were filled with soil-less media planting mix containing Pro- Mix® BX (Premier Tech Horticulture, Quakertown, Pennsylvania, USA) and Profile® Greens Grade™ (Profile Products LLC, Buffalo Grove, Illinois, USA) at a pH of 5.2 to 6.2 and a minimum of 50% organic matter content. In some tests, the pots were treated with fungicide to help seed germination and healthy plant growth. Seeds of the desired test plant species were planted in the prepared pots, and placed in a greenhouse with a photoperiod of approximately 16 hours / day. The greenhouse was maintained at 23 °C during the day (illuminated) hours and 22 °C during the night (dark) hours for the propogation periods indicated above. The pots were sub-irrigated as needed with water containing Jack’s Professional® 15-5-15 Ca-Mg LX fertilizer (JR Peters Inc., Allentown, Pennsylvania, USA). The plants were grown for 7 to 36Docket No.210869-WO-SEC-1 days, until the plants reached the second or third true leaf stage, before treatment with each herbicide.

[1146] Each herbicide molecule that was being tested was dissolved in a solvent mixture of acetone and DMSO (97:3 v / v) to form a concentrated stock herbicide solution. The concentrated stock herbicide solution was mixed vigorously and sonicated, if needed, to dissolve any solids. Each concentrated stock herbicide solution was further diluted with a mixture of acetone, deionized water, isopropanol, DMSO, Agridex® crop oil concentrate (Helena Chemical Company, Collierville, Tennessee, USA), and Tergitol™ 15-S-7 surfactant (Dow Chemical Company, Midland, Michigan, USA) (48.5:39:10:1.5:0.02, v / v / v / v / v) to form the test compositions at the application rates noted in Table 4 below. Each test composition was applied to all of the tested plant species using an overhead track sprayer (Devries Manufacturing Company, Hollandale, Minnesota, USA) equipped with 8002E nozzles calibrated to deliver 187 L / ha of test composition over an application area of 0.503 m2at a spray height of 43 cm above the average plant canopy. Control or non-treated plants were sprayed in the same manner with either a solvent blank (control plants) or no treatment (non- treated plants). The pots containing the test plants were returned to the greenhouse and watered by sub-irrigation to prevent removal of the test compounds. After about 14 days, the conditions of the treated plants were compared with control plants by visual assessment and evaluated based on a scoring scale of 0 percent (no injury) to 100% (complete plant death). The visual assessments of plant injury were made based on observed growth inhibition, growth reduction, discoloration, leaf deformity, and necrosis.

[1147] Table 4 presents the data from Example 3.XMAE 0 0 0 5 5 0 0 0 0 0 0A045659530707055859055859080709050509055758ERAMA 0 001 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0LAEHC 0 0 0 00102 0 0 0 0 0 0 0 0 0 0 0 0 0 002EH OPI 0 002 5 502 0 002 0 002010103 00152 0 002)ah / ia 5g(25.15 025. 5 025. 5 025. 5 025 5.2 2321051321051321051321051532010.51532010.515320105.oN1 2 3 4 5 6 7ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 001 00101 0 0 0 0 001 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5g(2.152020.152020.1520250.152025252520.1520 . 5 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 105132105132105132105dp .mo8 901112 3 4 5oN 1 1 1 1CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152 252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 617181911 2 3 4oN 2 2 2 2CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 001 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5g(2.152020.152020.152020.152020.1525252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 526272829 0 1 2oN 2 3 3 3CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 002 0 001 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5g(2.152020.152020.152020.152020.1525252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 334353637 8 9 0oN 3 3 3 4CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 0 0 0 0 002)eata h / Ria 5 5 5 5 5 5g(2.152020.152020.152020.152020.1525252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 142434445 6 7 0oN 4 4 4 5CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152 252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 152535455 8 9 1oN 5 5 5 6CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 003 0 003 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5g(2.152020.152020.152020.152020.1525252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 263646667 8 9 0oN 6 6 6 7CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152 252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 172737576 7 8 9oN 7 7 7 7CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152 252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 081828384 6 7 9oN 8 8 8 8CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152 252200.15 0 . 5 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105132105dp .mo 091929394 5 6 7oN 9 9 9 9CERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.15202 20.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo 90oN 901020304 7 8C 1 1 1 1010101ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo9oN0112131415 6 7C 1 1 1 1 1111111ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo8oN1910212223 4 5C 1 1 1 1 1212121ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo6oN2728292132 5 6C 1 1 1 1 1313131ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 002 0 006 0 001e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 005 00101 0 0 0 0 0 0 0 0 0 0 003 0 003)eata h / Ria 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.25215200.1520 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 105132105dp .mo7oN3839314243 4 5C 1 1 1 1 1414141ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0010101e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 004 00104 0 003 0 002 0 003010202 0 0 0)eata h / Ria 5 5 5 5 5g(2.152020.152020.152020.1520250.1520252520.15200.15 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105dp .mo6oN47484940 1 2 3C 1 1 1 151515151ERAsdMeA 0 0 0 0 0 0 0 0 0 00102 0 0 0 0 0 0 0 003 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 002 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 003 0 0 0 00303 0 003 0 0 0 0 002 0 002 0 003)eata h / Ria 5 5 5 5 5g(2.152020.152020.152020.1520250.1520252520.15200.15 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105dp .mo4oN55565758 9 1 2C 1 1 1 151516161ERAsdMeA 0 005 0 0 0 0 001010105 00203 0 0 0 00202 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 002 00204 0 0 0 0 003 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5g(2.152020.152020.1520250.1520250.1525252200.15200.15 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105dp .mo3oN64656667 8 9 0C 1 1 1 161616171ERAsdMeA 0 002 0 0 0 0 003 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 003 0 003 0 0 0 0 001 0 003)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152 2200.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo1oN7273747576 7 8C 1 1 1 1 1717171ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 003 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo9oN7081838485 6 7C 1 1 1 1 1818181ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 001)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo8oN8980919293 5 6C 1 1 1 1 1919191ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo7oN9890010203 4 5C 1 1 2 2 2020202ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo6oN0708090011 2 3C 2 2 2 2 2121212ERAsdMeA 0 0 0 05103025202 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152 2200.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo4oN1516171819 0 1C 2 2 2 2 2122222ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo2oN2324252627 8 9C 2 2 2 2 2222222ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo0oN3132333435 6 7C 2 2 2 2 2323232ERAsdMeA 0 0 0 0 0 0050505030405 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152 2200.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo8oN3930414243 4 5C 2 2 2 2 2424242ERAsdMeA 0 003 0 003 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 007 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.15202 20.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo6oN4740525354 5 6C 2 2 2 2 2525252ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo7oN5859506162 3 4C 2 2 2 2 2626262ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo9oN6071727374 5 9C 2 2 2 2 2727272ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0020203030305 0 004 00203e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 031 0 0 0 0 0 0 0 0 0 0 003 0 0 0)eata h / Ria 5 5 5 5 5g(2.152020.152020.152020.1520250.1520252520.15200.15 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105dp .mo0oN81828384 5 6 7C 2 2 2 282828282ERAsdMeA 0 002 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 002 0 0 0 0 0 0 002)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152 2200.15200. 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 51305dp .mo8oN8394959697 8 9C 2 2 2 2 2929292ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 00202 00202 0 0 0 0 0 0 0 0 0 0 0 0 0 002 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152 2200.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo0oN0102030405 6 8C 3 3 3 3 3030303ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 006 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo9oN0011131416 7 8C 3 3 3 3 3131313ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 001 0 5 5 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo9oN1223242526 7 8C 3 3 3 3 3232323ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 001 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo9oN2233353637 8 9C 3 3 3 3 3333333ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 003 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 002 00101)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.15202 20.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo0oN4142434548 9 0C 3 3 3 3 3434353ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo1oN5253555657 8 9C 3 3 3 3 3535353ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo0oN6162636465 6 7C 3 3 3 3 3636363ERAsdMeA 00202030305 00203040203 0 003030303 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5g(2.152020.152020.1520250.1520250.1525252200.15200.15 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105dp .mo8oN69607172 3 4 5C 3 3 3 373737373ERAsdMeA 0 0 0 0 0 0 0 0 0 0 005 0 0 0 0 0 0 0 004 00305e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.15202 20.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo6oN7778797081 2 3C 3 3 3 3 3838383ERAsdMeA 0 0 0 0 0 0 0 0 0050656 00202 0 001 0 0 0 0 0 0e LW AtEoHC 0 0 0 0 0 0 0 0 0 00c0 0 0 0 0 0 0 3 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 003 0 006 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5g(2.152020.152020.152020.152020.1520250.25215200.1520 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 105132105dp .mo4oN8586898192 4 5C 3 3 3 3 3939393ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo6oN9798999001 2 4C 3 3 3 3 4040404ERAsdMeA 0 0 0 0 0 0 0 001 0 0 0 0 0 0 0 0 0 0 0 0020204e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 002 0 0 0 0 001 0 0 0 0 002 0 0 0)eata h / Ria 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.25215200.1520 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 105132105dp .mo5oN0800111213 4 5C 4 4 4 4 4141414ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 003 0 004 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 003 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.15202 20.15200. 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5132105dp .mo6oN1718191021 3 7C 4 4 4 4 4242424ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5g(25 5 5 5 5 5 5.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo8oN2920313233 4 6C 4 4 4 4 4343434ERAsdMeA 0 0 0 0 0 001010202 501 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 001010202010101 0 0 0 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5g(2.152020.152020.152020.1520250.1520252520.15200.15 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105dp .mo7oN38393041 2 3 4C 4 4 4 444444444ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 0 0 0 0 0 00201 0 0 0 0 0 0 0 0 0)eata h / Ria 5 5 5 5 5 5 5 5g(2.152020.152020.152020.152020.152020.152020.215200.15 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105dp .mo5oN4647484052 4 5C 4 4 4 4 4545454ERAsdMeA 0 0 0 0 001 0 0 0 0 0 0 0 0 0010101 0 0 0 0 0 0e LW AtEoHC 0 0 0 0 0 0 0 0 0 0 0 00 0 0c0 0 0 1 1 1 0 0 0 0 0 0iDEH OPI 0 0 0 0 0 0 0 004 0 004 0 003 0 002 0 002 00102)eata h / Ria 5 5 5 5g(2.152020.152020.1520250.1520250.1525252200.15200.15 0 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 32105132105dp .mo6oN5745850626960717C4 4 4 4 4 4 4ERAsdMeA 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0010101 0 0 0 0 0 0e LW AtEoHcC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0iDEH OPI 0 001 0 001 0 003 0 004 00303 0 004 0 0 5 0 0 0)eata h / Ria 5 5 5 5 5 5g(2.152020.152020.152020.152020.1520250.25215200.1520 . 5 03 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 1 5 3 105132105dp .mo2oN7348485868788809C4 4 4 4 4 4 4eeSGI 0 0 0 5 0 5 5 5 5 0 0 5 5 0 5WDt6 7 9 2 6 5 5 6 7 6 5 8 3 5 7ocYoM)nOoLMA085858575858575709080859085809)ameucbl)sAa a uxSrEe melf)s)sVA TNTNTNTNTNTNTNTNTNT deuid oredilNTNTNTNTNTNerat)haotpeio anor ru iuAcFeEhsu euo nseuV0 0 0 0 0 0 0 0r nmohhsgtn )aoy nas )irA580101580101580101580101570090e1pntapI Cnsu(( ysarr vitmsai ebeatm)aas urrat afEeRi h rr u au i aAdetM rnolA 0 0 0 0 0 0 0 0 0 0 0 0 0 001 gaigau A( tafnceegiirnl gqi esde avpolD( ateHn(in b e nA( mwevtA(ssa S(LeAv r roalgiAa(oss rg liaE itHc ewmnopttanaor batxC 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0asdolffaelmoor ogdmkcrcoe ftEmetsnu -modelimoalgr naHarg ets yvi c r=w c b= aligOtPI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 =o =anN= =E LE = =R AFAY= =SMAA h / )i =AHAA TLaatg EOEPHMEVEVOSLGFITEeN HI CA A A A DSah / Ria 5g(25 5 5 5.152020.2 2 215200.15200. 5 0 . 5 03 1 5 3 1 5 3 1 5132105132105dp .mo1oN929394969C4 4 4 4 4)illag-surc)sauol ph ac n )oani ci )x muhscs aviEa mts(rsBees( nica )av )istyaaral ylmuasmg on Gcit a adra (nir zacyra yeZeT( r (ne ertb taO( zani yo eheciab wsi= = =wrm=GCWA==X N MSKASYMHCSXERBL ZA GRTROEZDocket No.210869-WO-SEC-1

[1148] The molecules, compositions, and methods of the appended claims are not limited in scope by the specific molecules, compositions, and methods described herein, which are intended as illustrations of a few aspects of the claims and any molecules, compositions, and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the molecules, compositions, and methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative molecules, compositions, and method steps disclosed herein are specifically described, other combinations of the molecules, compositions, and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, molecules, compositions, or constituents may be explicitly mentioned herein; however, other combinations of steps, elements, molecules, compositions, and constituents are included, even though not explicitly stated. The term “comprising” and variations thereof as used herein is used synonymously with the term “including” and variations thereof and are open, non-limiting terms. Although the terms “comprising” and “including” have been used herein to describe various aspects, the terms “consisting essentially of” and “consisting of” can be used in place of “comprising” and “including” to provide for more specific aspects and are also disclosed. Other than in the examples, or where otherwise noted, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood to be construed in light of the number of significant digits and ordinary rounding approaches, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims.

Claims

Docket No.210869-WO-SEC-1 What is claimed is:

1. A 5-member ring-based molecule of Formula (I):wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R2is selected from the group consisting of methyl and cyclopropyl; R3is selected from the group consisting of H, methyl, and methoxy; R4is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C3-C16)- alkenyl, (C3-C16)-alkynyl, (C3-C10)-cycloalkyl, (C4-C16)-alkylcycloalkyl, (C5-C16)- polycycloalkyl, (C6-C16)-alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C4-C16)-aryl, (C5- C18)-alkylaryl, (C1-C16)-heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C16)-alkoxy, (C4-C16)- arylalkoxy, (C1-C10)-alkylcyano, (C1-C16)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1- C10)-alkylthio-(C1-C10)-alkyl, (C0-C10)-alkylsulfonyl-R74, NR72R73, SiR75R76R77, (C1-C10)- alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl-C(=O)QR70, aryl-(C1-C10)-alkyl-C(=O)QR70, heteroaryl-(C1-C10)-alkyl-C(=O)QR70, (C3-C10)-cycloalkyl-(C0-C10)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C10)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1-C10)-alkyl-C(=O)QR71, hydroxy- (C1-C10)-alkyl-C(=O)QR70, (C1-C10)-alkylthio-(C1-C10)-alkyl-C(=O)QR70, (C3-C16)- alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)- haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)- alkylaryl, (C1-C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-heterocycloalkyl, (C1-C10)- heterocycloaryl,(C1-C10)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C3-C8)-cycloalkyl-(C1-Docket No.210869-WO-SEC-1 C10)-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R72R73N-sulfonyl, (C1-C10)-alkoxy-NR74- sulfonyl, and aryloxysulfonyl; Q is selected from the group consisting of O, S, and NR72; R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1-C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl, (C1-C16)-haloalkyl, (C1- C16)-arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; and R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1-C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together may form a substituted or unsubstituted ring; or an agriculturally-acceptable salt of the molecule of Formula (I).

2. The molecule of claim 1, wherein R2is methyl and R3is methyl.

3. The molecule of claim 1, wherein R2is methyl and R3is methoxy.

4. The molecule of claim 1, wherein R2is cyclopropyl and R3is H.

5. The molecule of any one of claims 1-4, wherein R1is H.

6. The molecule of any one of claims 1-4, wherein R1is F.

7. The molecule of any one of claims 1-6, wherein R5is H.

8. The molecule of any one of claims 1-7, wherein X1and X2are O.

9. A herbicidal composition comprising a 5-member ring-based of Formula (I):Docket No.210869-WO-SEC-1 wherein: X1and X2are independently selected from the group consisting of O and S; Y is selected from the group consisting of O, NH, NR72; and S; R1is selected from the group consisting of H and F; R2is selected from the group consisting of methyl and cyclopropyl; R3is selected from the group consisting of H, methyl, and methoxy; R4is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C3-C16)- alkenyl, (C3-C16)-alkynyl, (C3-C10)-cycloalkyl, (C4-C16)-alkylcycloalkyl, (C5-C16)- polycycloalkyl, (C6-C16)-alkylpolycycloalkyl, (C3-C10)-heterocycloalkyl, (C4-C16)-aryl, (C5- C18)-alkylaryl, (C1-C16)-heteroaryl, (C4-C16)-alkylheteroaryl, (C1-C16)-alkoxy, (C4-C16)- arylalkoxy, (C1-C10)-alkylcyano, (C1-C16)-haloalkyl, (C1-C10)-alkoxy-(C1-C10)-alkyl, (C1- C10)-alkylthio-(C1-C10)-alkyl, (C0-C10)-alkylsulfonyl-R74, NR72R73, SiR75R76R77, (C1-C10)- alkyl-SiR75R76R77, R78R79C=N, (C1-C10)-alkyl-C(=O)QR70, aryl-(C1-C10)-alkyl-C(=O)QR70, heteroaryl-(C1-C10)-alkyl-C(=O)QR70, (C3-C10)-cycloalkyl-(C0-C10)-alkyl-C(=O)QR70, R70QC(=O)-(C1-C10)-alkyl-C(=O)QR71, R70QC(=O)Q-(C1-C10)-alkyl-C(=O)QR71, hydroxy- (C1-C10)-alkyl-C(=O)QR70, (C1-C10)-alkylthio-(C1-C10)-alkyl-C(=O)QR70, (C3-C16)- alkylidene-amino-oxo, and salts thereof; R5is selected from the group consisting of H, hydroxy, (C1-C16)-alkyl, (C1-C16)- haloalkyl, (C1-C10)-alkylcyano, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C4-C18)-aryl, (C5-C16)- alkylaryl, (C1-C10)-alkoxy, (C1-C16)-alkyl-C(=O)OR70, (C1-C10)-heterocycloalkyl, (C1-C10)- heterocycloaryl,(C1-C10)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C3-C8)-cycloalkyl-(C1- C10)-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R72R73N-sulfonyl, (C1-C10)-alkoxy-NR74- sulfonyl, and aryloxysulfonyl; Q is selected from the group consisting of O, S, and NR72; R70, R71, R72, R73, and R74are independently selected from the group consisting of H, (C1-C16)-alkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, (C5-C16)-alkylaryl, (C1-C16)-haloalkyl, (C1- C16)-arylalkoxy, NR78R79, and R72and R73together may form a substituted or unsubstituted ring; R75, R76, and R77are independently selected from the group consisting of (C1-C16)-alkyl and aryl; andDocket No.210869-WO-SEC-1 R78and R79are independently selected from the group consisting of H, (C1-C16)-alkyl, (C1-C16)-alkoxy, (C1-C16)-alkylaryl, (C1-C16)-haloalkyl, (C4-C16)-aryl, (C1-C16)-heteroaryl, and R78and R79together may form a substituted or unsubstituted ring; or an agriculturally-acceptable salt of the molecule of Formula (I); and an agriculturally-acceptable carrier.

10. The composition of claim 9, wherein R2is methyl and R3is methyl.

11. The composition of claim 9, wherein R2is methyl and R3is methoxy.

12. The composition of claim 9, wherein R2is cyclopropyl and R3is H.

13. The composition of any one of claims 9-12, wherein R1is H.

14. The composition of any one of claims 9-12, wherein R1is F.

15. The composition of any one of claims 9-14, wherein R5is H.

16. The composition of any one of claims 9-15, wherein X1and X2are O.

17. The composition of any one of claims 9-16, comprising an adjuvant.

18. The composition of any one of claims 9-17, comprising a safener.

19. The composition of any one of claims 9-18, wherein the composition is selected from the group consisting of aqueous solutions, aqueous suspensions, aqueous dispersions, aqueous emulsions, aqueous microemulsions, aqueous suspo-emulsions, oil solutions, oil suspensions, oil dispersions, oil emulsions, oil microemulsions, oil suspo-emulsions, self- emulsifying formulations, gels, pastes, powders, dusts, granules, and materials for spreading.

20. A method of controlling undesirable vegetation, comprising applying to the vegetation or an area adjacent the vegetation or applying to soil or agricultural surface water to limit the emergence or growth of vegetation a molecule of any one of claims 1-8 or a composition of any one of claims 9-19.

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