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

Abstract

The present disclosure relates to 5-member ring-based molecules having herbicidal activity. Also disclosed are methods of synthesizing these 5-member ring-based molecules, compositions comprising these 5-member ring-based molecules, and processes for using these molecules. These molecules can be used, for example, as herbicides to control undesirable vegetation.

Description

Cross-references to related applications

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

[0002] This disclosure relates to 5-membered ring-based molecules with herbicidal activity. Methods for synthesizing these 5-membered ring-based molecules, compositions comprising these 5-membered ring-based molecules, and processes for using these molecules are also disclosed. These molecules can be used, for example, as herbicides to control unwanted vegetation. Background Technology

[0003] Many recurring problems in agriculture involve controlling the growth of unwanted vegetation. If left uncontrolled, unwanted vegetation can negatively impact the growth of desired vegetation, such as crops, lawns, pastures, gardens, and recreational areas. To help control unwanted vegetation, researchers have developed a variety of chemicals and chemical combinations that are effective in controlling this unwanted growth. However, there is a continuous need for new herbicides and methods to control the growth of unwanted vegetation in different locations. Summary of the Invention

[0004] This article discloses 5-membered ring-based molecules that can be used as herbicides to control unwanted vegetation in various locations, such as farmland, lawns, pastures, gardens, and recreational areas. These molecules may include 5-membered ring-based molecules that can be substituted with fluorinated benzyl groups and other groups, such as amino acids or other derivatives thereof. These molecules may also include lactams or thiolactams, either of which can be substituted with fluorinated benzyl groups and other groups, such as amino acids or other derivatives thereof.

[0005] In some respects, molecules based on a 5-membered ring are molecules with formula (I): Formula (I) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 2 Choose from the group consisting of: methyl and cyclopropyl; R 3 Choose from the group consisting of: H, methyl, and methoxy; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C16)-alkyl, (C3-C16)-alkenyl, (C3-C16)-alkynyl, (C3-C10)-cycloalkyl, (C4-C16)-alkylcycloalkyl, (C5-C16)-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C4-C 16 )-Aryl, (C5-C 18 )-alkylaryl, (C1-C 16 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C 16 )-alkoxy, (C4-C 16 )-arylalkoxy, (C1-C 10 )-alkylcyano, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C 10 )-alkylthio-(C1-C 10 )-alkyl, (C0-C 10 )-alkylsulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C) 10 )-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C 10 )-alkyl-C(=O)QR 70 heteroaryl-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C 10 )-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C 10 )-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C 10)-alkyl-C(=O)QR 71 hydroxyl-(C1-C) 10 )-alkyl-C(=O)QR 70 (C1-C) 10 )-alkylthio-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 16 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-Heterocyclic alkyl, (C1-C 10 )-Heterocyclic aryl, (C1-C 10 (C3-C8)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C1-C 10 )-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R 72 R 73 N-sulfonyl group, (C1-C 10 )-alkoxy-NR 74 -sulfonyl group and aryloxysulfonyl group; Q selects from the following groups: O, S, and NR. 72 ; R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they can form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (I).

[0006] In some respects, molecules based on a 5-membered ring are molecules with formula (II): Equation (II) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 2 Choose from the group consisting of: methyl and cyclopropyl; R 3 Choose from the group consisting of: H, methyl, and methoxy; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-alkylsulfonyl, (C4-C 10 )-arylsulfonyl, and R 72 R 73 N-sulfonyl group; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (II).

[0007] In some respects, molecules based on a 5-membered ring are molecules with formula (III): Equation (III) Where X 1 X 2 Y, R 1 R 4 R 5 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (III).

[0008] In some respects, molecules based on a 5-membered ring are molecules with formula (IV): Formula (IV) Where X 1 X 2 Y, R 1 R 4 R 5 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (IV).

[0009] In some respects, molecules based on a 5-membered ring are molecules with formula (V): Formula (V) Where X 1 X 2 Y, R 1 R 4 R 5 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (V).

[0010] In some respects, molecules based on a 5-membered ring are molecules with formula (VI): Formula (VI) Where X 1 X 2 Y, R 4 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (VI).

[0011] In some respects, molecules based on a 5-membered ring are molecules with formula (VII): Equation (VII) Where X 1 X 2 Y, R 4 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having molecules of formula (VII).

[0012] In some respects, molecules based on a 5-membered ring are molecules with formula (VIII): Formula (VIII) Where X 1 X 2 Y, R 4 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (VIII).

[0013] In some respects, molecules based on a 5-membered ring are molecules with formula (IX): Formula (IX) Where X 1 X 2 Y, R 4 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (IX).

[0014] In some respects, molecules based on a 5-membered ring are molecules with formula (X): Formula (X) Where X 1 X 2 Y, R 4 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (X).

[0015] In some respects, molecules based on a 5-membered ring are molecules with formula (XI): Formula (XI) Where X 1 -X 2 Y, R 4 Q and R 70 -R 79 As defined for equation (II) Or an agriculturally acceptable salt having a molecule of formula (XI).

[0016] Various five-membered ring-based molecules included in this disclosure, such as those based on lactams or thiolactams, have been found to exhibit herbicidal activity against a variety of key species in undesirable vegetation.

[0017] The following description sets forth details of one or more aspects of this disclosure. Other features, objectives, and advantages will become apparent from the specification and claims. Detailed Implementation

[0018] This disclosure includes molecules that can be used as herbicides to control unwanted vegetation in various locations, such as cultivated land, lawns, pastures, gardens, and recreational areas. These five-membered ring-based molecules (such as lactam-based or thiolactam-based molecules) can be substituted with fluorinated benzyl groups and other groups (such as amino acid groups or derivatives thereof). This disclosure also includes methods for using these molecules to control unwanted vegetation. In some aspects, the unwanted vegetation is present in cultivated crops. In some aspects, the unwanted vegetation is present in corn, soybean, canola, cotton, legumes, sunflower, sugar beet, wheat, barley, rice, sorghum, millet, or oats. In some aspects, the molecules are gramineous herbicides for controlling unwanted vegetation, including grassy species. 1. definition

[0019] Unless otherwise specified, the terms used herein will have their conventional meaning in the art. Unless otherwise stated, the singular forms “a” and “the” include a plural of indicators. With regard to the use of the term “or” (e.g., A or B), it is intended to mean “A or B or both”. Therefore, the use of the term “or” herein is inclusive and not exclusive.

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

[0021] As used herein, the term "herbicidal effect" refers to the adverse alteration of vegetation by an active ingredient, including, for example, deviation from natural growth or development, killing, regulating, drying, growth inhibition, weakening, and delaying. The term "herbicidal activity" generally refers to the herbicidal effect of the active ingredient.

[0022] As used herein, the term "herbicide resistance" refers to the genetic ability of an individual plant to survive the application of a herbicide that would kill a normal population of the same plant species. Herbicide resistance in a plant species typically arises from the application of a herbicide to that species at a specific location.

[0023] As used herein, the term "herbicide tolerance" refers to the inherent ability of a plant species to survive and reproduce after treatment with herbicides at normal application rates. Therefore, herbicide tolerance is the natural tolerance within a normal population of a plant species, rather than resistance selected in the species through herbicide application.

[0024] As used herein, a “composition” is a mixture that contains at least one herbicide and also contains other ingredients for enhancing the properties or effectiveness of the mixture in some way. Other ingredients may include, but are not limited to, diluents, surfactants, adjuvants, antifoaming agents, emulsifiers, colorants, dispersants, antifreeze agents, and other such ingredients.

[0025] As used herein, “application” of a herbicide or herbicidal composition means the direct delivery of it to the target vegetation or its location or to an area where unwanted vegetation is to be controlled. Methods of application include, but are not limited to, contact with soil or water before emergence, contact with unwanted vegetation after emergence, or contact with an area adjacent to unwanted vegetation.

[0026] As used herein, the term “vegetation” may include, for example, dormant seeds, germinating seeds, emerging seedlings, plants propagated from vegetative propagules, immature vegetation, and mature vegetation.

[0027] As used herein, the term "crop" refers to desired vegetation, such as plants that grow to provide food, shelter, pasture, erosion control, etc. Examples of crops include cereals, legumes, vegetables, orchards and timber trees, grapevines, etc. Preferably, the herbicide or herbicidal composition has zero or minimal herbicidal effect on the crop.

[0028] As used herein, the term "undesirable vegetation" refers to vegetation that is not desired in a given area, such as weed species. Herbicides or herbicidal compositions are used to control undesirable vegetation. Preferably, the herbicides or herbicidal compositions have a large or complete weeding effect on undesirable vegetation.

[0029] As used herein, "alkyl" refers to a straight-chain or branched saturated hydrocarbon moiety. Unless otherwise specified, it means C1-C2.16 Alkyl groups. 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 a saturated hydrocarbon moiety arranged in a ring. As used herein, “alkylcycloalkyl” refers to a cycloalkyl moiety having an alkyl substituent. Unless otherwise specified, it means C3-C16 cycloalkyl or alkylcycloalkyl group. 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 Cyclohexyl, 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 a saturated hydrocarbon moiety arranged in two or more rings sharing one or more carbon atoms. Polycycloalkyl groups can be fused rings, spirochetes, or bridged rings. Unless otherwise specified, it means C4-C. 16 Polycycloalkyl groups. Examples include spiro[2.2]heptane, spiro[2.4]heptane, bicyclo[3.2.0]heptane, bicyclo[2.2.1]heptane (also known as norbornane), bicyclo[3.3.0]octane, bicyclo[3.2.1]octane, and bicyclo[4.4.0]decane (also known as naphthane). As used herein, “alkyl polycycloalkyl” refers to a polycycloalkyl group having an alkyl substituent.

[0032] As used herein, “halogenated alkyl” refers to a straight-chain or branched alkyl group in which hydrogen atoms may be partially or completely replaced by halogen atoms. Unless otherwise specified, it means a C1-C16 group. 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-chloro-2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and 1,1,1-trifluoropropyl-2-yl.

[0033] As used herein, "alkenyl" refers to an unsaturated straight-chain or branched hydrocarbon moiety containing a carbon-carbon double bond. Unless otherwise specified, it means C3-C16 alkenyl. An alkenyl group may contain more than one carbon-carbon double bond. Examples include vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 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 The group comprises 1-ethyl-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 structure -CH=CH2; 1-propenyl refers to a group having the structure -CH=CH-CH3; and 2-propenyl refers to a group having the structure -CH2-CH=CH2.

[0034] As used herein, "alkylene" refers to a substance having the formula An unsaturated straight-chain or branched hydrocarbon moiety containing a carbon-carbon double bond, wherein the double bond of this moiety is bonded to the rest of the molecule, and the R group is independently H or C3-C. 12 Alkyl groups.

[0035] As used herein, “alkynyl” refers to an unsaturated straight-chain or branched hydrocarbon moiety containing a carbon-carbon triple bond. Unless otherwise specified, it means a C3-C16 alkynyl group. An alkynyl group may contain more than one carbon-carbon triple bond. Examples include C2-C6-ynyl groups, such as ethynyl, 1-propynyl, 2-propynyl (or propynyl), 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 having the formula RO-, where R is an alkyl group as defined above. Unless otherwise specified, it means that R is C1-C2. 10Alkyl groups of alkyl groups. Examples include methoxy, ethoxy, propoxy, 1-methyl-ethoxy, butoxy, 1-methyl-propoxy, 2-methyl-propoxy, 1,1-dimethyl-ethoxy, pentooxy, 1-methyl-butoxy, 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, “alkathioyl” refers to a group having the formula RS-, where R is an alkyl group as defined above. Unless otherwise specified, it means that R is C1-C2. 10 Alkyl thioyl groups. Examples include methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methyl-propylthio, 2-methyl-propylthio, 1,1-dimethylethylthio, pentylthio, 1-methyl-butylthio, 2-methyl-butylthio, 3-methyl-butylthio, 2,2-dimethyl-propylthio, 1-ethyl-propylthio, hexylthio, 1,1-dimethyl-propylthio, 1,2-dimethyl-propylthio, 1-methyl-pentylthio, 2-methyl-pentylthio, 3-methyl-ethyl-propylthio, 2-methyl-propylthio, 3-methyl-ethyl-propylthio, 2 ... 4-Methylpentylthio, 1,1-dimethylbutyrothio, 1,2-dimethylbutyrothio, 1,3-dimethylbutyrothio, 2,2-dimethylbutyrothio, 2,3-dimethylbutyrothio, 3,3-dimethylbutyrothio, 1-ethylbutyrothio, 2-ethylbutyrothio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, 1-ethyl-1-methylpropylthio, and 1-ethyl-2-methylpropylthio.

[0038] As used herein, "heterocyclic alkyl" and its derivatives (such as heteroalkylcycloalkyl or heterocyclic alkoxy) refer to a saturated hydrocarbon moiety arranged in a ring in which one or more carbon atoms in the ring are replaced by heteroatoms (such as N, O, or S). Unless otherwise specified, it means C3-C. 16 Heterocyclic alkyl groups.

[0039] As used herein, "aryl" and its derivatives (such as aryloxy) refer to a phenyl, indanyl, or naphthyl group, preferably phenyl. The term heteroaryl and its derivatives (such as heteroaryloxy) refer to a 4-, 5-, or 6-membered aromatic ring containing one or more heteroatoms (i.e., N, O, or S); these aromatic and heteroaromatic rings may be fused with other aromatic and / or heteroaromatic systems.

[0040] As used herein, "alkylaryl" and its derivatives (such as arylalkoxy) refer to a C1-C group substituted with one or more phenyl, indanyl, or naphthyl groups. 16 Alkyl groups, preferably phenyl or benzyl substituents. For example, C7-C 16 Alkyl aryl refers to a group in which the total number of carbon atoms is 7 to 16.

[0041] As used in this article, "alkoxycarbonyl" refers to a group having the following formula: The group, wherein R is an alkyl group.

[0042] As used herein, "alkylsulfonyl" refers to a group having the formula The group, wherein R is an alkyl group.

[0043] As used herein, trialkylsilyl means a group having 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 in this article, Me refers to the methyl group, and OMe refers to the methyl group.

[0045] As used herein, “substituted” means any part as defined above, such as “alkyl,” “alken,” “cycloalkyl,” etc., which is substituted by one or more substituents selected from the following: halogen, hydroxy, nitro, cyano, formyl, C1-C6 alkyl, C2-C6 alken, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkoxycarbonyl, C1-C6 carbamoyl, hydroxycarbonyl, C1-C6 alkylcarbonyl, aminocarbonyl, provided that these substituents are sterically compatible and satisfy the rules of chemical bonding and strain energy.

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

[0047] As used herein, agriculturally acceptable salts are salts approved for agricultural use. Agriculturally acceptable salts of herbicides can be converted into the herbicides mentioned in plants, water, or soil, and can be in dissociated or non-dissociated forms (depending on pH). Exemplary agriculturally acceptable salts include, but are not limited to: cationic alkali metals or alkaline 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 compound or composition that has an effect on vegetation (e.g., has a herbicidal or safety effect on vegetation).

[0049] As used herein, “acid equivalent” or “ae” refers to the amount of the acid form of the active ingredient calculated from the amount of the salt or ester form of the active ingredient. For example, if the acid form of active ingredient “Z” has a molecular weight of 100 Daltons and the salt form of Z has a molecular weight of 130 Daltons, then applying 130 grams of active ingredient per hectare (g ai / ha) of the salt of Z will be equivalent 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. Molecules based on 5-membered rings

[0050] This article discloses molecules based on five-membered rings, such as those based on lactams or thiolactams, which can be used as herbicides to control unwanted vegetation in various locations, such as farmland, lawns, pastures, gardens, and recreational areas. These molecules include those substituted with fluorinated benzyl groups and amino acid groups and their derivatives.

[0051] In some respects, molecules based on a 5-membered ring are molecules with formula (I): Formula (I) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 2 Choose from the group consisting of: methyl and cyclopropyl; R 3Choose from the group consisting of: H, methyl, and methoxy; R 4 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C3-C 10 )-cycloalkyl, (C4-C 16 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C4-C 16 )-Aryl, (C5-C 18 )-alkylaryl, (C1-C 16 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C 16 )-alkoxy, (C4-C 16 )-arylalkoxy, (C1-C 10 )-alkylcyano, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C 10 )-alkylthio-(C1-C 10 )-alkyl, (C0-C 10 )-alkylsulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C) 10 )-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C 10 )-alkyl-C(=O)QR 70 heteroaryl-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C 10 )-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C10 )-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C 10 )-alkyl-C(=O)QR 71 hydroxyl-(C1-C) 10 )-alkyl-C(=O)QR 70 (C1-C) 10 )-alkylthio-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 16 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-Heterocyclic alkyl, (C1-C 10 )-Heterocyclic aryl, (C1-C 10 (C3-C8)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C1-C 10 )-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R 72 R 73 N-sulfonyl group, (C1-C 10 )-alkoxy-NR 74 -sulfonyl group and aryloxysulfonyl group; Q selects from the following groups: O, S, and NR. 72 ; R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16)-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they can form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (I).

[0052] In some respects, molecules based on a 5-membered ring are molecules with formula (II): Equation (II) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 2 Choose from the group consisting of: methyl and cyclopropyl; R 3 Choose from the group consisting of: H, methyl, and methoxy; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16)-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-alkylsulfonyl, (C4-C 10 )-arylsulfonyl, and R 72 R 73 N-sulfonyl group; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (II).

[0053] In some respects, molecules based on a 5-membered ring are molecules with formula (III): Equation (III) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-alkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C)10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-alkylsulfonyl, (C4-C 10 )-arylsulfonyl, and R 72 R 73 N-sulfonyl group; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (III).

[0054] In some respects, molecules based on a 5-membered ring are molecules with formula (IV): Formula (IV) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16(C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-alkylsulfonyl, (C4-C10 )-arylsulfonyl, and R 72 R 73 N-sulfonyl group; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (IV).

[0055] In some respects, molecules based on a 5-membered ring are molecules with formula (V): Formula (V) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70(C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-alkylsulfonyl, (C4-C 10 )-arylsulfonyl, and R 72 R 73 N-sulfonyl group; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (V).

[0056] In some respects, molecules based on a 5-membered ring are molecules with formula (VI): Formula (VI) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (VI).

[0057] In some respects, molecules based on a 5-membered ring are molecules with formula (VII): Equation (VII) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16)-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having molecules of formula (VII).

[0058] In some respects, molecules based on a 5-membered ring are molecules with formula (VIII): Formula (VIII) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (VIII).

[0059] In some respects, molecules based on a 5-membered ring are molecules with formula (IX): Formula (IX) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10)-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (IX).

[0060] In some respects, molecules based on a 5-membered ring are molecules with formula (X): Formula (X) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70aryl-(C1-C6)-alkyl-C(=O)QR 70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C16 )-heteroaryl, and R 78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (X).

[0061] In some respects, molecules based on a 5-membered ring are molecules with formula (XI): Formula (XI) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 4 Choose from the group consisting of: H, hydroxyl, (C1-C8)-alkyl, (C3-C8)-alkenyl, (C3-C8)-ynyl, (C3-C8)-cycloalkyl, (C4-C 10 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C5-C 12 )-Aryl, (C6-C 18 )-alkylaryl, (C1-C 12 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C8)-alkoxy, (C5-C 16 (C1-C6)-arylalkoxy, (C1-C8)-alkylcyano, (C1-C8)-haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C0-C6)-alkyl-sulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C6)-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C6)-alkyl-C(=O)QR70 Heteroaryl-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C6)-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C6)-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C6)-alkyl-C(=O)QR 71 hydroxy-(C1-C6)-alkyl-C(=O)QR 70 (C1-C6)-alkylthio-(C1-C6)-alkyl-C(=O)QR 70 (C3-C) 10 )-alkylene-amino-oxo, and their salts; Q selects from the following groups: O, S, and NR. 72 , R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R78 and R 79 Together they form substituted or unsubstituted rings. Or an agriculturally acceptable salt having a molecule of formula (XI).

[0062] The 5-membered ring-based molecules of this disclosure exist in a specific chiral form, as shown in the molecular structures illustrated throughout this application. However, 5-membered ring-based molecules can also exist in different geometric or optical isomeric forms at other positions within each molecule. Those skilled in the art will understand that one stereoisomer can be more reactive than others. Individual stereoisomers can be obtained through known selective synthetic procedures, conventional synthetic procedures using resolved starting materials, or conventional resolution procedures. This disclosure covers all such chiral forms, isomers, and mixtures thereof in all proportions.

[0063] Examples of 5-membered ring-based molecules disclosed herein are listed in Table 1 below. Analytical data and preparation methods are also given (see Section 3 below). Table 1: Examples of molecules based on 5-membered rings 3. Preparation of molecules based on 5-membered rings

[0064] The 5-membered ring-based molecule of this disclosure was prepared according to the preparation method given below.

[0065] Method 1: Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine methyl ester (compound number 1)

[0066] In a round-bottom flask equipped with a magnetic stir bar, add (S)-2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetic acid (1 equivalent) and an amine or ammonium chloride or trifluoroacetate (1 equivalent) in dichloromethane (CH2Cl2, 0.1 M). Then add 3-((((ethylimino)methylene)amino)-N,N-dimethylpropyl-1-amine) hydrochloride (1.2 equivalent), triethylamine (1.2 equivalent), and N,N-dimethylpyridin-4-amine (1.2 equivalent) sequentially. Stir the reaction mixture at 20°C for 18 hours (h), or until the reaction is complete. Concentrate the reaction product onto silica gel and purify by silica column chromatography. (1.405 g, 89% yield)

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

[0068] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine allyl ester (Compound No. 3)

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

[0070] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine N-propyl ester (Compound No. 9)

[0071] The title compound was prepared and isolated as a colorless oil. (220 mg, 72% yield)

[0072] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine isopropyl ester (Compound No. 8)

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

[0074] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine benzyl ester (Compound No. 6)

[0075] The title compound was prepared and isolated as a colorless oil. (474 ​​mg, 88% yield)

[0076] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine ethyl ester (Compound No. 5)

[0077] The title compound was prepared and isolated as a colorless liquid. (421 mg, 91% yield)

[0078] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine methyl ester (compound number 323)

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

[0080] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine propion-2-yn-1-yl ester (Compound No. 4)

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

[0082] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)methyl propionate (Compound No. 205)

[0083] The title compound was prepared and isolated as a clear oil. (527.8 mg, 85% yield)

[0084] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-methyl-L-valine methyl ester (compound number 24)

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

[0086] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-leucine methyl ester (Compound No. 22)

[0087] The title compound was prepared and isolated as a colorless solid. (60 mg, 22% yield)

[0088] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine methyl ester (compound number 280)

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

[0090] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-ethyl-L-valine methyl ester (compound number 27)

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

[0092] N-(cyanomethyl)-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine methyl ester (compound number 26)

[0093] The title compound was prepared and isolated as a yellow oil. (197.2 mg, 40% yield)

[0094] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)methyl propionate (compound number 350)

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

[0096] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-(prop-2-yn-1-yl)-L-valine methyl ester (compound number 31)

[0097] The title compound was prepared and isolated as a yellow oil. (285.6 mg, 64% yield)

[0098] N-Allyl-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine methyl ester (Compound No. 29)

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

[0100] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-(2-methoxy-2-oxoethyl)-L-valine methyl ester (compound number 47)

[0101] The title compound was prepared and isolated as a yellow oil. (328.6 mg, 35% yield)

[0102] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine methyl ester (compound number 410)

[0103] The title compound was prepared and isolated as a clear oil. (328.3 mg, 77% yield)

[0104] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-(methanesulfonyl)ethyl ester (Compound No. 55)

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

[0106] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine furan-2-ylmethyl ester (Compound No. 56)

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

[0108] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(methylsulfonyl)butyramide (Compound No. 65)

[0109] The title compound was prepared and isolated as a grayish-white solid. (43 mg, 17% yield, melting point 52°C–54°C)

[0110] (R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(methanesulfonyl)butyramide (Compound No. 57)

[0111] The title compound was prepared and isolated as a grayish-white solid. (40 mg, 16% yield, melting point 63°C–65°C)

[0112] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(ethylsulfonyl)-3-methylbutyramide (Compound No. 58)

[0113] The title compound was prepared and isolated as a white solid. (110 mg, 54% yield, melting point 73°C–75°C)

[0114] (S)-N-(cyclopropylsulfonyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramide (Compound No. 59)

[0115] The title compound was prepared and isolated as a grayish-white solid. (120 mg, melting point 70°C-72°C)

[0116] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(N-methoxyaminosulfonyl)-3-methylbutyramide (Compound No. 64)

[0117] The title compound was prepared and isolated as a grayish-white solid. (167 mg, melting point 73°C-75°C)

[0118] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(N-isopropylaminosulfonyl)-3-methylbutyramide (Compound No. 63)

[0119] The title compound was prepared and isolated as a grayish-white solid. (107 mg, melting point 159°C–161°C)

[0120] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methyl-N-(phenylsulfonyl)butyramide (Compound No. 62)

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

[0122] (S)-N-(tert-butylsulfonyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 61)

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

[0124] (S)-N-((cyclopropylmethyl)sulfonyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 60)

[0125] The title compound was prepared and isolated as a grayish-white solid. (Compound number 63 mg, melting point 56°C–58°C)

[0126] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonylglycine methyl ester (compound number 283)

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

[0128] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonyl-L-phenylalanine methyl ester (compound number 412)

[0129] The title compound was prepared and isolated as a white solid. (249.6 mg, 87% yield)

[0130] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(pyrrolidone-1-ylsulfonyl)butyramide (Compound No. 68)

[0131] The title compound was prepared and isolated as a grayish-white solid. (210 mg, melting point 73°C-75°C)

[0132] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(N,N-dimethylaminosulfonyl)-3-methylbutyramide (Compound No. 67)

[0133] The title compound was prepared and isolated as a grayish-white solid. (119 mg, melting point 71°C-73°C)

[0134] ((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine)phenylaminosulfonate (compound number 66)

[0135] The title compound was prepared and isolated as a grayish-white solid. (180 mg, melting point 80°C-82°C)

[0136] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonylglycine methyl ester (compound number 413)

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

[0138] 2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)-N-((S)-3-methyl-1-oxo-1-((prop-2-imideamino)oxy)but-2-yl)acetamide (Compound No. 73)

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

[0140] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylthiobutyric acid S-benzyl ester (Compound No. 72)

[0141] The title compound was prepared and separated as 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)pyrrolidine-2-yl)acetamyl)butyramide (compound number 414)

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

[0144] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)-L-phenylalanine methyl ester (Compound No. 353)

[0145] The title compound was prepared and isolated as a white solid. (220.7 mg, 71% yield)

[0146] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)glycine methyl ester (compound number 352)

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

[0148] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N,N,3-trimethylbutyramide (Compound No. 74)

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

[0150] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine tert-butyl ester (Compound No. 76)

[0151] The title compound was prepared and isolated as a colorless oil. (475 mg, 92% yield)

[0152] (S)-N-(allyloxy)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionamide (Compound No. 354)

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

[0154] (S)-3-methyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)s-thiobutyric acid S-benzyl ester (compound number 327)

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

[0156] (S)-2-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutamido)-3-methylthiobutyric acid S-isopropyl ester (Compound No. 88)

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

[0158] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-isopropyl ester (Compound No. 87)

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

[0160] (S)-3-methyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)s-isopropyl thiobutyric acid (compound number 328)

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

[0162] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionyl)-L-leucine methyl ester (Compound No. 228)

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

[0164] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-(4-(trifluoromethyl)benzyl) ester (Compound No. 125)

[0165] The title compound was prepared and isolated as a colorless, viscous semi-solid. (239 mg, 59% yield)

[0166] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylthiobutyric acid S-(4-(trifluoromethoxy)benzyl) ester (Compound No. 128)

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

[0168] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-(4-methylbenzyl) ester (Compound No. 129)

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

[0170] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)-L-leucine methyl ester (Compound No. 368)

[0171] The title compound was prepared and isolated as a white solid. (160 mg, melting point 144°C–146°C)

[0172] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonyl-L-valine methyl ester (compound number 415)

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

[0174] (S)-3-cyclopropyl-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methoxybutamido)methyl propionate (compound number 286)

[0175] The title compound was prepared and isolated as a grayish-white solid. (187 mg, melting point 125°C-127°C)

[0176] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-isoleucine methyl ester (compound number 285)

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

[0178] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-leucine methyl ester (compound number 284)

[0179] The title compound was prepared and separated as a colorless liquid. (193 mg)

[0180] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonyl-L-leucine methyl ester (compound number 416)

[0181] The title compound was prepared and separated as a grayish-white viscous solid. (105 mg)

[0182] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonyl-L-isoleucine methyl ester (compound number 417)

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

[0184] (S)-3-cyclopropyl-2-((2S,3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)butamido)methyl propionate (compound number 418)

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

[0186] (S)-3-cyclopropyl-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionamido)methyl propionate (compound number 242)

[0187] The title compound was prepared and isolated as a grayish-white solid. (191 mg, melting point 153°C-154°C)

[0188] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)-L-alanine methyl ester (Compound No. 373)

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

[0190] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)-L-isoleucine methyl ester (Compound No. 372)

[0191] The title compound was prepared and isolated as a white solid. (190 mg, melting point 124°C–126°C)

[0192] (S)-3-cyclopropyl-2-((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propamido)methyl propionate (compound number 371)

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

[0194] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonyl-L-alanine methyl ester (compound number 420)

[0195] The title compound was prepared and separated as a colorless liquid. (171 mg)

[0196] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)-L-valine methyl ester (Compound No. 370)

[0197] The title compound was prepared and isolated as a white solid. (122 mg, melting point 153°C–155°C)

[0198] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)-L-isoleucine methyl ester (Compound No. 241)

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

[0200] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclopentyl ester (compound number 144)

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

[0202] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine pyridazine-4-ylmethyl ester (Compound No. 155)

[0203] The title compound was prepared and isolated as a brown oil. (193 mg, 50.8% yield)

[0204] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine octyl ester (Compound No. 145)

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

[0206] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine pyridin-4-yl methyl ester (156)

[0207] The title compound was prepared and isolated as a brown oil. (226.07 mg, 69% yield)

[0208] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclopropyl methyl ester (Compound No. 157)

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

[0210] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclobutyl methyl ester (Compound No. 158)

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

[0212] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-isobutyl ester (Compound No. 174)

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

[0214] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-phenylethyl ester (Compound No. 173)

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

[0216] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-cyclohexyl ester (Compound No. 172)

[0217] The title compound was prepared and isolated as a dense, clear semi-solid. (288 mg, 82% yield)

[0218] rac-2-((R)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)-N-((R)-3-methyl-1-(2-methyl-2-phenylhydrazyl)-1-oxobut-2-yl)acetamide (compound number 171)

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

[0220] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine phenethyl ester (compound number 167)

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

[0222] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclohexyl ester (compound number 166)

[0223] The title compound was prepared and isolated as a colorless oil. (284 mg, 81% yield)

[0224] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclobutyl ester (compound number 165)

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

[0226] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(S)-sec-butyl ester (Compound No. 164)

[0227] The title compound was prepared and isolated as a colorless oil. (170 mg, 51% yield)

[0228] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(R)-sec-butyl ester (Compound No. 163)

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

[0230] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-methoxy-2-oxoethyl ester (Compound No. 162)

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

[0232] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 3,3-dimethylbutyl ester (Compound No. 161)

[0233] The title compound was prepared and isolated as a colorless oil. (205 mg, 58% yield)

[0234] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclohexylmethyl ester (Compound No. 160)

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

[0236] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclopentylmethyl ester (compound number 159)

[0237] The title compound was prepared and isolated as a colorless oil. (191 mg, 54% yield)

[0238] N-((RS)-1-(2,2-dimethylhydrazine)-3-methyl-1-oxobut-2-yl)-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamide (compound number 334)

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

[0240] 2-(((RS)-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)valine)thio)methyl acetate (compound number 175)

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

[0242] (RS)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methyl-N-(pyrrolidine-1-yl)butyramide (Compound No. 176)

[0243] The title compound was prepared and isolated as a white solid. (101 mg, 30.5% yield)

[0244] (RS)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-(4-methoxybenzyl) ester (Compound No. 186)

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

[0246] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl ester (Compound No. 188)

[0247] The title compound was prepared and isolated as a colorless gel. (98 mg, 25% yield)

[0248] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(1S,2R,5S)-2-isopropyl-5-methylcyclohexyl ester (Compound No. 187)

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

[0250] (RS)-3-methyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)thiobutyric acid S-benzyl ester (Compound No. 454)

[0251] The title compound was prepared and isolated as a clear solid. (101 mg, 29% yield)

[0252] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionyl)-L-phenylalanine benzyl ester (Compound No. 395)

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

[0254] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionyl)-L-phenylalanine benzyl ester (Compound No. 260)

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

[0256] N-((S)-3-methyl-1-oxo-1-((prop-2-imideamino)oxy)but-2-yl)-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamide (compound number 455)

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

[0258] N-((S)-3-cyclopropyl-1-oxo-1-((propyl-2-imideamino)oxy)propyl-2-yl)-2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamide (compound number 452)

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

[0260] N-((S)-3-cyclopropyl-1-oxo-1-((propyl-2-imideamino)oxy)propyl-2-yl)-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamide (compound number 456)

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

[0262] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-alanine methyl ester (compound number 310)

[0263] The title compound was prepared and isolated as a grayish-white solid. (173 mg, melting point 133°C–135°C)

[0264] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-valine methyl ester (compound number 308)

[0265] The title compound was prepared and separated as a colorless liquid. (129 mg)

[0266] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-D-allothreoyl-L-valine methyl ester (compound number 307)

[0267] The title compound was prepared and isolated as a grayish-white solid. (85 mg, melting point 145°C-147°C)

[0268] N-(N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl)-O-methyl-L-threonine methyl ester (compound number 305)

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

[0270] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-D-allothreoylglycine methyl ester (compound number 312)

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

[0272] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetyl)-O-methyl-L-threonine 2-(methanesulfonyl)ethyl ester (compound number 313)

[0273] The title compound was prepared and isolated as a colorless, viscous solid. (97 mg)

[0274] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-methylbut-3-en-2-yl ester (Compound No. 198)

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

[0276] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine but-3-yne-1-yl ester (Compound No. 197)

[0277] The title compound was prepared and isolated 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-((propyl-2-imideamino)oxy)but-2-yl)acetamide (compound number 453)

[0279] The title compound was prepared and isolated as a pale yellow oil. (65 mg, 20% yield)

[0280] 2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)-N-((RS)-3-methyl-1-oxo-1-((((E)-1,1,1-trifluoroprop-2-ylidene)amino)oxy)but-2-yl)acetamide (compound number 451)

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

[0282] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionic acid 2-(methanesulfonyl)ethyl ester (compound number 396)

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

[0284] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine furan-2-yl methyl ester (compound number 429)

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

[0286] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)furan-2-ylmethyl propionate (Compound No. 404)

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

[0288] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine furan-2-yl methyl ester (compound number 342)

[0289] The title compound was prepared and separated as a brown liquid. (132 mg)

[0290] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine 2-(methanesulfonyl)ethyl ester (Compound No. 341)

[0291] The title compound was prepared and separated as a colorless, viscous liquid. (201 mg)

[0292] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine 2-(methanesulfonyl)ethyl ester (compound number 430)

[0293] The title compound was prepared and separated as a yellow, viscous liquid. (176 mg)

[0294] (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propamido)-3-(4-fluorophenyl)propionate (Compound No. 269)

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

[0296] (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxybutamido)-3-(4-fluorophenyl)propionate (compound number 314)

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

[0298] (S)-3-(4-chlorophenyl)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propamido)methyl propionate (compound number 270)

[0299] The title compound was prepared and isolated as a white solid. (437.4 mg, 49% yield)

[0300] (S)-3-(4-chlorophenyl)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxybutamido)methyl propionate (compound number 315)

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

[0302] (S)-3-(4-bromophenyl)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propamido)methyl propionate (compound number 271)

[0303] The title compound was prepared and isolated as a white solid. (352 mg, 56% yield)

[0304] (S)-3-(4-bromophenyl)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxybutamido)methyl propionate (compound number 316)

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

[0306] (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propamido)-3-(4-nitrophenyl)propionate (Compound No. 272)

[0307] The title compound was prepared and isolated as a white solid. (286 mg, 49% yield)

[0308] (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxybutamido)-3-(4-nitrophenyl)propionate (compound number 317)

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

[0310] (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propamido)-3-(3-fluorophenyl)propionate (Compound No. 273)

[0311] The title compound was prepared and isolated as a white solid. (445 mg, 77% yield)

[0312] (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxybutamido)-3-(3-fluorophenyl)propionate (compound number 318)

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

[0314] (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propamido)-3-(2-fluorophenyl)propionate (Compound No. 274)

[0315] The title compound was prepared and isolated as a white solid. (435 mg, 75% yield)

[0316] Methyl (S)-2-((2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxybutamido)-3-(2-fluorophenyl)propionate (Compound No. 319)

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

[0318] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-D-phenylalanine methyl ester (compound number 320)

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

[0320] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionyl)-D-phenylalanine methyl ester (Compound No. 275)

[0321] The title compound was prepared and isolated as a white solid. (280 mg, 51% yield)

[0322] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyclopropyl ester (Compound No. 199)

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

[0324] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-(adamantane-1-yl)ethyl ester (Compound No. 202)

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

[0326] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine adamantane-1-yl methyl ester (Compound No. 201)

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

[0328] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine adamantane-1-yl ester (Compound No. 200)

[0329] The title compound was prepared and isolated as a white solid. (199 mg, 51% yield)

[0330] (S)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propamido)-3-(3,4-dihydroxyphenyl)propionate (Compound No. 276)

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

[0332] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-(furan-2-ylmethyl) ester (Compound No. 131)

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

[0334] (RS)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-(3,3,3-trifluoropropyl) ester (Compound No. 132)

[0335] The title compound was prepared and isolated as a clear, colorless oil (268 mg, 74% yield).

[0336] (2S,3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)s-benzyl thiobutyric acid (compound number 436)

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

[0338] 2-(((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine)thio)methyl acetate (compound 467)

[0339] The title compound was prepared and separated as a colorless viscous liquid (98% purity).

[0340] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-(3,3,3-trifluoropropyl) ester (Compound 468)

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

[0342] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 2-(methanesulfonyl)ethyl ester (compound 483)

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

[0344] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)phenylethyl propionate (Compound 484)

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

[0346] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)cyclohexyl propionate (compound 485)

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

[0348] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)s-thiopropionic acid S-benzyl ester (Compound 495)

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

[0350] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)thiopropionic acid S-(3,3,3-trifluoropropyl) ester (compound 497)

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

[0352] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)thiopropionic acid S-isopropyl ester (Compound 498)

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

[0354] 2-(((S)-3-cyclopropyl-2-(2-(((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionyl)thio)methyl acetate (compound 499)

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

[0356] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)cyclopropyl methyl propionate (compound 514)

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

[0358] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)isopropyl propionate (compound 515)

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

[0360] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionic acid 2,2-difluoroethyl ester (compound 516)

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

[0362] Method 2:Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-phenylalanine methyl ester (compound number 35)

[0363] In a round-bottom flask equipped with a magnetic stir bar, the compound tert-butoxycarbonylamine in 1,4-dioxane (4 M, 4 equivalents) and HCl were added. The mixture was stirred for 2 hours, and then the solvent and excess HCl were removed under vacuum. The residue was reconstituted in CH₂Cl₂ (0.2 M), followed by the sequential addition of (S)-2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetic acid (1 equivalent), ((ethylimino)methylene)amino)-N,N-dimethylpropyl-1-amine)hydrochloride (1.2 equivalents), triethylamine (2 equivalents), and N,N-dimethylpyridin-4-amine (1.2 equivalents). 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 according to the procedure in Method 2:

[0365] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-cyanoethyl ester (Compound No. 36)

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

[0367] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)cyanoethyl propionate (Compound No. 214)

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

[0369] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine-L-phenylalanine methyl ester (Compound No. 325)

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

[0371] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine-glycine methyl ester (compound number 326)

[0372] The title compound was prepared and isolated as a white powder. (392 mg, 84% yield)

[0373] 2-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramidoyl)-2-methylpropionate (Compound No. 71)

[0374] The title compound was prepared and separated as a white foam. (417 mg, 87% yield)

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

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

[0377] 3-((R 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramidoyl)methyl propionate (compound number 126)

[0378] The title compound was prepared and isolated as a white solid. (81 mg, 35% yield)

[0379] 3-((R Methyl propionate (Compound No. 127)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramidoyl)propionate

[0380] The title compound was prepared and isolated as a white solid. (102 mg, 44% yield)

[0381] (R )-N-cyclohexyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramide (Compound No. 134)

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

[0383] (R )-N-cyclohexyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramide (Compound No. 133)

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

[0385] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)cyanoethyl propionate (Compound No. 386)

[0386] The title compound was prepared and isolated as a clear, viscous substance. (299.3 mg, 71% yield)

[0387] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine 2-cyanoethyl ester (Compound No. 288)

[0388] The title compound was prepared and isolated as a clear, viscous substance. (286.1 mg, 31% yield)

[0389] O-Methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine 2-cyanoethyl ester (Compound No. 421)

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

[0391] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-glycine tert-butyl ester (compound number 169)

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

[0393] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(2-(methylamino)-2-oxoethyl)butyramide (Compound No. 168)

[0394] The title compound was prepared and isolated as a white solid. (371 mg, 80% yield)

[0395] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 3,3,3-trifluoropropyl ester (Compound No. 177)

[0396] The title compound was prepared and isolated as a clear oil. (556.5 mg, 57% yield)

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

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

[0399] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-D-phenylalanine methyl ester (Compound No. 183)

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

[0401] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-D-valine methyl ester (Compound No. 182)

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

[0403] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)valine valine 3,3,3-trifluoropropyl ester (compound number 336)

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

[0405] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionic acid 3,3,3-trifluoropropyl ester (259)

[0406] The title compound was prepared and isolated as a clear, viscous substance. (676.8 mg, 64% yield)

[0407] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionic acid 3,3,3-trifluoropropyl ester (compound number 394)

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

[0409] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (tetrahydrofuran-2-yl)methyl ester (compound number 449)

[0410] The title compound was prepared and separated from the sample using a pale yellow resin. (55.51 mg, 34% yield)

[0411] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-methoxyethyl ester (Compound No. 450)

[0412] The title compound was prepared and isolated as a yellow oil. (140.57 mg, 43% yield)

[0413] 1-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramidoyl)cyclopropane-1-carboxylic acid methyl ester (compound number 203)

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

[0415] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-glycine isopropyl ester (compound 457)

[0416] The title compound was prepared and isolated as a white solid. (26% yield)

[0417] Method 3: Preparation of N-(3-chlorobenzyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (compound number 99)

[0418] In a round-bottom flask equipped with a magnetic stir bar, the compound tert-butoxycarbonylamine, CH₂Cl₂ (0.5 M), and trifluoroacetic acid (9 equivalents) were added. The mixture was stirred for 12 hours, followed by vacuum removal of volatiles. The residue was reconstituted in CH₂Cl₂ (0.2 M), and then (S)-2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetic acid (1 equivalent), ((ethylimino)methylene)amino)-N,N-dimethylpropyl-1-amine)hydrochloride (1.2 equivalents), triethylamine (5 equivalents), and N,N-dimethylpyridin-4-amine (1.2 equivalents) were added sequentially. The reaction mixture was stirred at 20°C for 18 hours, or until complete. The product was concentrated onto silica gel and purified by silica column chromatography. The title compound was isolated as a white solid (342 mg, 66% yield).

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

[0420] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(furan-2-ylmethyl)-3-methylbutyramide (Compound No. 114)

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

[0422] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(3-phenylpropyl)butyramide (Compound No. 113)

[0423] The title compound was prepared and isolated as a brownish-red solid. (174 mg, 34% yield)

[0424] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methyl-N-propylbutyramide (Compound No. 112)

[0425] The title compound was prepared and isolated as a white solid. (212 mg, 51% yield)

[0426] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-isobutyl-3-methylbutyramide (Compound No. 111)

[0427] The title compound was prepared and isolated as a white solid. (189 mg, 44% yield)

[0428] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-octylbutyramide (Compound No. 110)

[0429] The title compound was prepared and isolated as a white solid. (165 mg, 34% yield)

[0430] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(2-methoxyethyl)-3-methylbutyramide (Compound No. 109)

[0431] The title compound was prepared and isolated as a white solid. (247 mg, 57% yield)

[0432] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(2-(2-methoxyethoxy)ethyl)-3-methylbutyramide (Compound No. 108)

[0433] The title compound was prepared and isolated as a brownish-red solid. (328 mg, 63% yield)

[0434] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methyl-N-phenethylbutyramide (Compound No. 107)

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

[0436] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(4-methylbenzyl)butyramide (Compound No. 106)

[0437] The title compound was prepared and isolated as a brownish-red solid. (33 mg, 47% yield)

[0438] 3-((2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramido)methyl)methyl benzoate (compound number 105)

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

[0440] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(4-methoxybenzyl)-3-methylbutyramide (Compound No. 104)

[0441] The title compound was prepared and isolated as a white solid. (210 mg, 41% yield)

[0442] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(4-fluorobenzyl)-3-methylbutyramide (Compound No. 103)

[0443] The title compound was prepared and isolated as a white solid. (244 mg, 49% yield)

[0444] N-(4-chlorobenzyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 102)

[0445] The title compound was prepared and isolated as a white solid. (188 mg, 36% yield)

[0446] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(3,4,5-trifluorobenzyl)butyramide (Compound No. 101)

[0447] The title compound was prepared and isolated as a white solid. (247 mg, 44% yield)

[0448] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(3-methoxybenzyl)-3-methylbutyramide (Compound No. 100)

[0449] The title compound was prepared and isolated as a white solid. (236 mg, 46% yield)

[0450] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-ethyl-3-methylbutyramide (Compound No. 98)

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

[0452] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(4-fluorophenyl)-3-methylbutyramide (Compound No. 115)

[0453] The title compound was prepared and isolated as a white solid. (244 mg, 52% yield)

[0454] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(3,5-dimethoxyphenyl)-3-methylbutyramide (Compound No. 116)

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

[0456] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(3-fluoro-5-methoxyphenyl)-3-methylbutyramide (Compound No. 117)

[0457] The title compound was prepared and isolated as a white solid. (378 mg, 75% yield)

[0458] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(3,4,5-trifluorophenyl)butyramide (Compound No. 448)

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

[0460] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(2,4,6-trifluorophenyl)butyramide (Compound No. 447)

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

[0462] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(4-methoxyphenyl)-3-methylbutyramide (Compound No. 446)

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

[0464] N-(4-chlorophenyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 445)

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

[0466] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(4-nitrophenyl)butyramide (Compound No. 444)

[0467] The title compound was prepared and isolated as a yellow solid. (423 mg, 82% yield)

[0468] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(4-(trifluoromethyl)phenyl)butyramide (Compound No. 443)

[0469] The title compound was prepared and isolated as a white solid. (362 mg, 69% yield)

[0470] 4-(2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramidoyl)methyl benzoate (compound number 442)

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

[0472] Methyl 3-(2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramidoyl)benzoate (compound number 441)

[0473] The title compound was prepared and isolated as a white solid. (401 mg, 78% yield)

[0474] N-(3-chlorophenyl)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 124)

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

[0476] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(3-methoxyphenyl)-3-methylbutyramide (Compound No. 123)

[0477] The title compound was prepared and isolated as a white solid. (378 mg, 78% yield)

[0478] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(2,4-difluorophenyl)-3-methylbutyramide (Compound No. 122)

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

[0480] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(3,4-difluorophenyl)-3-methylbutyramide (Compound No. 121)

[0481] The title compound was prepared and isolated as a white solid. (396 mg, 81% yield)

[0482] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(4-fluoro-3-methoxyphenyl)-3-methylbutyramide (Compound No. 120)

[0483] The title compound was prepared and isolated as a white solid. (165 mg, 33% yield)

[0484] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(3-fluoro-4-methoxyphenyl)-3-methylbutyramide (Compound No. 119)

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

[0486] 2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-(3,4-dimethoxyphenyl)-3-methylbutyramide (Compound No. 118)

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

[0488] Method 4: Preparation of (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetyl)valine ethyl ester (compound number 330)

[0489] Add (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)valine (1 equivalent), amine, ammonium hydrochloride or ammonium trifluoroacetate, thiol or alcohol nucleophile (1 equivalent), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate ((HATU), 1.2 equivalent) and CH2Cl2 (0.2 M) to a round-bottom flask equipped with a magnetic stir bar. Add 4-methylmorpholine (3 equivalents) and stir the reaction mixture at 22°C for 16 hours (h) or until complete. Filter the reaction mixture through diatomaceous earth, concentrate, and purify by silica column chromatography. Separate the title compound as a grayish-white solid (146 mg, 43% yield, melting point 121°C–125°C).

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

[0491] 3-Cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionic acid 2-(methanesulfonyl)ethyl ester (Compound No. 388)

[0492] The title compound was prepared and isolated as a pale yellow viscous solid. (179 mg, 43% yield)

[0493] 3-Cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)ethyl propionate (Compound No. 387)

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

[0495] (3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)butyric acid 2-(methanesulfonyl)ethyl ester (compound number 422)

[0496] The title compound was prepared and isolated as a pale yellow viscous solid. (116 mg, 36% yield)

[0497] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)valine allyl ester (compound number 331)

[0498] The title compound was prepared and isolated as a pale yellow solid. (180 mg, 51% yield)

[0499] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)valine 2-(methanesulfonyl)ethyl ester (compound number 332)

[0500] The title compound was prepared and isolated as a grayish-white viscous solid. (302 mg, 60% yield)

[0501] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)valine benzyl ester (compound number 333)

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

[0503] (3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)ethyl butyrate (compound number 423)

[0504] The title compound was prepared and separated as a pale yellow liquid. (192 mg, 59% yield)

[0505] (2S,3R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxythiobutyric acid S-benzyl ester (Compound No. 322)

[0506] The title compound was prepared and separated as a yellow liquid. (175 mg, 32% yield)

[0507] (2S,3R)-3-methoxy-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)thiobutyric acid S-isopropyl ester (compound number 437)

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

[0509] Method 5: Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-cyanoethyl ester (compound number 14)

[0510] In a round-bottom flask equipped with a magnetic stir bar, add (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)valine (1 equivalent) and an alcohol, amine, ammonium, or thiol nucleophile (1-3 equivalents) in dichloromethane (CH₂Cl₂, 0.1 M). Then add 3-((((ethylimino)methylene)amino)-N,N-dimethylpropyl-1-amine) hydrochloride (1.2 equivalents), triethylamine (1.2 equivalents), and N,N-dimethylpyridin-4-amine (1.2 equivalents) sequentially. Stir the reaction mixture at 20°C for 18 hours, or until the reaction is complete. Concentrate the reaction product onto silica gel and purify by silica column chromatography. Prepare the title compound as a pale yellow oil. (170.4 mg, 89% yield)

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

[0512] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)valine 2,2,2-trifluoroethyl ester (Compound No. 7)

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

[0514] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-valine-glycine methyl ester (compound number 16)

[0515] The title compound was prepared and isolated as a white solid. (368.4 mg, 80% yield)

[0516] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-D-valine-glycine methyl ester (20)

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

[0518] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-glycine methyl ester (compound number 19)

[0519] The title compound was prepared and isolated as a white solid. (140 mg, 30% yield)

[0520] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-D-valine-L-valine methyl ester (Compound No. 18)

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

[0522] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-valine methyl ester (Compound No. 17)

[0523] The title compound was prepared and isolated as a viscous semi-solid. (129.6 mg, 26% yield)

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

[0525] The title compound was prepared in the absence of a nucleophile and isolated as a colorless oil. (70 mg, 20% yield)

[0526] Method 6: Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2,2,2-trifluoroethyl ester (compound number 33)

[0527] Add (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (1 equivalent), cesium carbonate (1 equivalent), acetonitrile (0.1 M), and alkyl sulfonate (1.5 equivalent) to a flask equipped with a magnetic stir bar. Stir at 22°C for 18 hours, or until complete. Filter the reaction mixture through diatomaceous earth to remove the solvent before loading onto silica gel and purifying by silica column chromatography. The title compound is isolated as a colorless oil (155.7 mg, 67% yield).

[0528] Prepare the following compounds according to the procedure in Method 6:

[0529] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionic acid 2,2,2-trifluoroethyl ester (211)

[0530] The title compound was prepared and isolated as a pale yellow viscous substance. (336 mg, 70% yield)

[0531] Method 7: Preparation of N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine ethyl ester (293)

[0532] Add N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine (1 equivalent), potassium carbonate (1 equivalent), and N,N-dimethylformamide (0.2 M) to a round-bottom flask equipped with a magnetic stir bar. Stir for 5 minutes, then add alkyl bromide or trifluoromethanesulfonate (1 equivalent). Stir at room temperature for 2–16 hours, or until complete. Remove the solvent to load onto silica gel and purify by silica column chromatography. The title compound is isolated as a colorless oil. (192 mg)

[0533] Prepare the following compounds according to the procedure in Method 7:

[0534] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (trimethylsilyl) methyl ester (compound number 189)

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

[0536] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine 4-methyl benzyl ester (Compound No. 299)

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

[0538] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine 4-bromobenzyl ester (298)

[0539] The title compound was prepared and separated as a colorless liquid. (147 mg)

[0540] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine 4-nitrobenzyl ester (297)

[0541] The title compound was prepared and separated as a colorless liquid. (130 mg)

[0542] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine allyl ester (296)

[0543] The title compound was prepared and isolated as a colorless liquid. (134 mg)

[0544] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine isopropyl ester (295)

[0545] The title compound was prepared and separated as a colorless liquid. (92 mg)

[0546] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine propyl ester (294)

[0547] The title compound was prepared and isolated as a colorless liquid. (136 mg, 93% yield)

[0548] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine benzyl ester (Compound No. 300)

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

[0550] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetyl)-O-methyl-L-threonine 2,2,2-trifluoroethyl ester (compound number 301)

[0551] The title compound was prepared and separated as a white, viscous solid. (98 mg)

[0552] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine cyanomethyl ester (compound number 302)

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

[0554] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine prop-2-yn-1-yl ester (Compound No. 303)

[0555] The title compound was prepared and isolated as a colorless liquid. (117 mg)

[0556] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine allyl ester (compound number 339)

[0557] The title compound was prepared and isolated as a colorless liquid. (175 mg)

[0558] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine prop-2-yn-1-yl ester (Compound No. 338)

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

[0560] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine cyanomethyl ester (compound number 337)

[0561] The title compound was prepared and separated as a pale yellow liquid. (157 mg)

[0562] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionate prop-2-yn-1-yl ester (compound number 399)

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

[0564] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)cyanomethyl propionate (Compound No. 398)

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

[0566] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionic acid 2,2,2-trifluoroethyl ester (compound number 397)

[0567] The title compound was prepared and isolated as a colorless liquid. (131 mg)

[0568] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine prop-2-yn-1-yl ester (compound number 427)

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

[0570] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)allyl propionate (compound number 400)

[0571] The title compound was prepared and isolated as a colorless liquid. (134 mg)

[0572] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine benzyl ester (compound number 428)

[0573] The title compound was prepared and isolated as a colorless liquid. (159 mg)

[0574] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)benzyl propionate (Compound No. 405)

[0575] The title compound was prepared and isolated as a colorless liquid. (144 mg)

[0576] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine allyl ester (compound number 433)

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

[0578] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine cyanomethyl ester (compound number 432)

[0579] The title compound was prepared and separated as a yellow, viscous liquid. (146 mg)

[0580] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine benzyl ester (compound number 343)

[0581] The title compound was prepared and separated as a pale yellow liquid. (183 mg)

[0582] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine 2,2,2-trifluoroethyl ester (Compound No. 340)

[0583] The title compound was prepared and separated as a colorless liquid. (165 mg)

[0584] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine 2,2,2-trifluoroethyl ester (compound number 431)

[0585] The title compound was prepared and isolated as a grayish-white solid. (138 mg, melting point 120°C-122°C)

[0586] Method 8: Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-nitrobenzyl ester (compound number 11)

[0587] Add (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (1 equivalent), potassium carbonate (2 equivalents), acetone (0.1–0.2 M), and an alkyl halide (1 equivalent) to a round-bottom flask equipped with a magnetic stir bar. Heat to 50°C for 2 hours, or until complete. Remove the solvent to load onto silica gel and purify by silica column chromatography. The title compound is isolated as a glassy solid. (100.4 mg, 98% yield)

[0588] Prepare the following compounds according to the procedure in Method 8:

[0589] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-bromobenzyl ester (Compound No. 12)

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

[0591] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine cyanomethyl ester (Compound No. 15)

[0592] The title compound was prepared and isolated as a yellow oil. (85 mg, 80% yield)

[0593] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 4-nitrobenzyl ester (Compound No. 209)

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

[0595] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 4-bromobenzyl ester (Compound No. 208)

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

[0597] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)benzyl propionate (Compound No. 207)

[0598] The title compound was prepared and isolated as a clear, viscous oil. (171.1 mg, 69% yield)

[0599] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)allyl propionate (compound number 210)

[0600] The title compound was prepared and isolated as a pale yellow viscous substance. (174 mg, 27% yield)

[0601] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionate-2-yn-1-yl ester (Compound No. 212)

[0602] The title compound was prepared and isolated as a clear, viscous substance. (244.4 mg, 63% yield)

[0603] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)cyanomethyl propionate (Compound No. 213)

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

[0605] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 3-fluorobenzyl ester (Compound No. 225)

[0606] The title compound was prepared and isolated as a pale yellow oil. (178.3 mg, 71% yield)

[0607] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 3-(trifluoromethyl)benzyl ester (Compound No. 224)

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

[0609] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionic acid 4-(trifluoromethyl)benzyl ester (Compound No. 223)

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

[0611] 4-((((S)-3-cyclopropyl-2-(2-(((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionyl)oxy)methyl)benzoate (compound number 222)

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

[0613] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 4-fluorobenzyl ester (compound number 221)

[0614] The title compound was prepared and isolated as a clear oil. (210.7 mg, 84% yield)

[0615] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)chlorobenzyl propionate (Compound No. 220)

[0616] The title compound was prepared and isolated as a clear oil. (230.1 mg, 89% yield)

[0617] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)4-methylbenzyl propionate (Compound No. 219)

[0618] The title compound was prepared and isolated as a clear oil. (157.4 mg, 63% yield)

[0619] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)cyanobenzyl propionate (Compound No. 218)

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

[0621] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)chlorobenzyl propionate (Compound No. 226)

[0622] The title compound was prepared and isolated as a clear oil. (166.1 mg, 64% yield)

[0623] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 3-bromobenzyl ester (Compound No. 227)

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

[0625] 4-((((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine)oxy)methyl)benzoate (compound number 97)

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

[0627] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-cyanobenzyl ester (Compound No. 96)

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

[0629] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-methoxybenzyl ester (Compound No. 95)

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

[0631] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-methylbenzyl ester (Compound No. 94)

[0632] The title compound was prepared and isolated as a clear oil. (168.8 mg, 69% yield)

[0633] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-chlorobenzyl ester (Compound No. 93)

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

[0635] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-fluorobenzyl ester (Compound No. 92)

[0636] The title compound was prepared and isolated as a clear oil. (165.7 mg, 68% yield)

[0637] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2,4-dimethyl benzyl ester (Compound No. 91)

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

[0639] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2,4,6-trimethylbenzyl ester (Compound No. 90)

[0640] The title compound was prepared and isolated as a clear oil. (159.4 mg, 62% yield)

[0641] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-(trifluoromethyl)benzyl ester (Compound No. 89)

[0642] The title compound was prepared and isolated as a clear oil. (189.4 mg, 70% yield)

[0643] 3-((((S)-3-cyclopropyl-2-(2-(((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionyl)oxy)methyl)benzoate (compound number 239)

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

[0645] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)cyanobenzyl propionate (Compound No. 238)

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

[0647] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 3-nitrobenzyl ester (Compound No. 237)

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

[0649] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionic acid 3-methoxybenzyl ester (compound number 236)

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

[0651] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)methylbenzyl propionate (Compound No. 235)

[0652] The title compound was prepared and isolated as a clear oil. (190.6 mg, 76% yield)

[0653] 2-((((S)-3-cyclopropyl-2-(2-(((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionyl)oxy)methyl)benzoate (compound number 234)

[0654] The title compound was prepared and isolated as a clear oil. (194.5 mg, 70% yield)

[0655] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)cyanobenzyl propionate (Compound No. 233)

[0656] The title compound was prepared and isolated as a clear oil. (151.5 mg, 59% yield)

[0657] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 2-nitrobenzyl ester (Compound No. 232)

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

[0659] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)methylbenzyl propionate (compound number 231)

[0660] The title compound was prepared and isolated as a yellow oil. (202.5 mg, 82% yield)

[0661] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)chlorobenzyl propionate (Compound No. 230)

[0662] The title compound was prepared and isolated as a clear oil. (180.1 mg, 70% yield)

[0663] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 2-fluorobenzyl ester (Compound No. 229)

[0664] The title compound was prepared and isolated as a clear oil. (159.4 mg, 64% yield)

[0665] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionic acid 3-(trifluoromethyl)benzyl ester (compound number 367)

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

[0667] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)cyanobenzyl propionate (compound number 366)

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

[0669] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionate 3-bromobenzyl ester (Compound No. 365)

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

[0671] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)chlorobenzyl propionate (Compound No. 364)

[0672] The title compound was prepared and isolated as a clear oil. (208.8 mg, 78% yield)

[0673] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionate 3-fluorobenzyl ester (compound number 363)

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

[0675] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionic acid 4-(trifluoromethyl)benzyl ester (compound number 362)

[0676] The title compound was prepared and isolated as a clear oil. (234.7 mg, 82% yield)

[0677] 4-((((S)-3-cyclopropyl-2-(2-(((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionyl)oxy)methyl)methyl)benzoate (compound number 361)

[0678] The title compound was prepared and isolated as a clear oil. (206.8 mg, 72% yield)

[0679] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)cyanobenzyl propionate (compound number 360)

[0680] The title compound was prepared and isolated as a clear oil. (193.4 mg, 72% yield)

[0681] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionic acid 4-nitrobenzyl ester (compound number 359)

[0682] The title compound was prepared and isolated as a clear oil. (193.9 mg, 71% yield)

[0683] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)4-methylbenzyl propionate (Compound No. 358)

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

[0685] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)chlorobenzyl propionate (compound number 357)

[0686] The title compound was prepared and isolated as a pale yellow oil. (233.2 mg, 87% yield)

[0687] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionate 4-fluorobenzyl ester (compound number 356)

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

[0689] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionate 2-fluorobenzyl ester (Compound No. 378)

[0690] The title compound was prepared and isolated as a clear, viscous substance. (210.8 mg, 81% yield)

[0691] 3-((((S)-3-cyclopropyl-2-(2-(((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionyl)oxy)methyl)benzoate (compound number 377)

[0692] The title compound was prepared and isolated as a clear, viscous substance. (221.4 mg, 77% yield)

[0693] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionate 3-nitrobenzyl ester (compound number 376)

[0694] The title compound was prepared and isolated as a yellow, viscous substance. (230.4 mg, 84% yield)

[0695] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionic acid 3-methoxybenzyl ester (compound number 375)

[0696] The title compound was prepared and isolated as a clear, viscous substance. (213.8 mg, 82% yield)

[0697] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)methyl benzyl propionate (compound number 374)

[0698] The title compound was prepared and isolated as a clear, viscous substance. (225.7 mg, 88% yield)

[0699] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)chlorobenzyl propionate (Compound No. 379)

[0700] The title compound was prepared and isolated as a clear, viscous substance. (218.8 mg, 81% yield)

[0701] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionate 2-bromobenzyl ester (Compound No. 380)

[0702] The title compound was prepared and isolated as a clear oil. (237.1 mg, 81% yield)

[0703] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)methyl benzyl propionate (compound number 381)

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

[0705] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine thiazolyl-4-ylmethyl ester (Compound No. 139)

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

[0707] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (2-methylthiazolyl-5-yl)methyl ester (compound number 138)

[0708] The title compound was prepared and isolated as a pale yellow oil. (106 mg, 70% yield)

[0709] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(2-chlorothiazol-5-yl)methyl ester (compound number 137)

[0710] The title compound was prepared and isolated as a light orange oil. (94.5 mg, 44% yield)

[0711] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionic acid 2,3-dimethyl benzyl ester (compound number 385)

[0712] The title compound was prepared and isolated as a white solid. (199.8 mg, 76% yield)

[0713] 2-((((S)-3-cyclopropyl-2-(2-(((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionyl)oxy)methyl)methyl)benzoate (compound number 384)

[0714] The title compound was prepared and isolated as a clear, viscous substance. (216.7 mg, 74% yield)

[0715] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)cyanobenzyl propionate (Compound No. 383)

[0716] The title compound was prepared and isolated as a white semi-solid. (204.9 mg, 76% yield)

[0717] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionic acid 2-nitrobenzyl ester (compound number 382)

[0718] The title compound was prepared and isolated as a white semi-solid. (220.1 mg, 78% yield)

[0719] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)naphthalene-2-ylmethyl propionate (Compound No. 390)

[0720] The title compound was prepared and isolated as a yellow semi-solid. (17.4 mg, 5% yield)

[0721] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)naphthalene-1-yl methyl propionate (compound number 389)

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

[0723] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(2-chlorothiazol-4-yl)methyl ester (compound number 140)

[0724] The title compound was prepared and isolated as a colorless oil. (61.2 mg, 39% yield)

[0725] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionic acid 3,5-dimethyl benzyl ester (compound number 391)

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

[0727] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionic acid 2,4-dimethyl benzyl ester (compound number 392)

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

[0729] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)propionic acid 2,4,6-trimethylbenzyl ester (compound number 393)

[0730] The title compound was prepared and isolated as a clear oil. (57 mg, 19% yield)

[0731] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine benzo[d]thiazol-2-ylmethyl ester (Compound No. 154)

[0732] The title compound was prepared and isolated as a colorless oil. (205 mg, 64% yield)

[0733] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (6-methylpyridin-2-yl)methyl ester (compound number 153)

[0734] The title compound was prepared and isolated as a colorless oil. (130 mg, 44% yield)

[0735] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(2-bromopyridin-4-yl)methyl ester (Compound No. 152)

[0736] The title compound was prepared and isolated as a light red oil. (250 mg, 75% yield)

[0737] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine pyrazin-2-yl methyl ester (Compound No. 151)

[0738] The title compound was prepared and isolated as a brown oil. (160 mg, 56% yield)

[0739] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (1-methyl-1H-pyrazole-3-yl)methyl ester (compound number 150)

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

[0741] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(6-bromopyridin-2-yl)methyl ester (compound number 149)

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

[0743] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(6-fluoropyridin-2-yl)methyl ester (compound number 148)

[0744] The title compound was prepared and isolated as a light brown oil. (190 mg, 64% yield)

[0745] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine pyridine-3-yl methyl ester (Compound No. 147)

[0746] The title compound was prepared and isolated as a light brown oil. (135 mg, 48% yield)

[0747] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine pyridine-2-yl methyl ester (Compound No. 146)

[0748] The title compound was prepared and isolated as a light brown oil. (140 mg, 49% yield)

[0749] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine(1H-pyrazole-3-yl)methyl ester (Compound No. 170)

[0750] The title compound was prepared and isolated as a viscous gel. (152 mg, 50% yield)

[0751] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine naphthyl-2-yl methyl ester (Compound No. 181)

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

[0753] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 3,4-difluorobenzyl ester (Compound No. 180)

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

[0755] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2,3-dimethyl benzyl ester (Compound No. 178)

[0756] The title compound was prepared and isolated as a colorless, viscous oil. (243 mg, 98% yield)

[0757] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)pyridin-2-ylmethyl propionate (Compound No. 252)

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

[0759] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)pyridine-3-ylmethyl propionate (Compound No. 253)

[0760] The title compound was prepared and isolated as a colorless oil. (97.26 mg, 46% yield)

[0761] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)pyrazin-2-ylmethyl propionate (Compound No. 258)

[0762] The title compound was prepared and isolated as a light brown oil. (114.8 mg, 69% yield)

[0763] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate benzo[d]thiazolyl-2-methyl ester (compound number 257)

[0764] The title compound was prepared and isolated as a brown oil. (185.24 mg, 78% yield)

[0765] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionic acid (1-methyl-1H-pyrazole-4-yl)methyl ester (compound number 256)

[0766] The title compound was prepared and isolated as a colorless oil. (85.52 mg, 40% yield)

[0767] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate (5-bromopyridin-2-yl)methyl ester (compound number 255)

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

[0769] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)pyridin-4-ylmethyl propionate (Compound No. 254)

[0770] The title compound was prepared and isolated as a brown oil. (113.39 mg, 54% yield)

[0771] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)quinoline-8-ylmethyl propionate (Compound No. 264)

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

[0773] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate (6-bromopyridin-2-yl)methyl ester (compound number 263)

[0774] The title compound was prepared and isolated as a colorless oil. (125 mg, 48% yield)

[0775] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate (6-bromoquinoline-8-yl)methyl ester (compound number 262)

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

[0777] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate (2-bromopyridin-4-yl)methyl ester (compound number 261)

[0778] The title compound was prepared and isolated as a brown oil. (110.92 mg, 43% yield)

[0779] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate (6-methylpyridin-2-yl)methyl ester (compound number 277)

[0780] The title compound was prepared and isolated as a brown gel. (140 mg, 70% yield)

[0781] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionate 4-bromobenzyl ester (Compound No. 355)

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

[0783] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-(tert-butoxy)-2-oxoethyl ester (Compound No. 464)

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

[0785] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-bromoallyl ester (Compound No. 466)

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

[0787] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-bromobenzyl ester (Compound No. 481)

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

[0789] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-cyanobenzyl ester (Compound No. 482)

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

[0791] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionate 2-bromobenzyl ester (Compound No. 508)

[0792] The title compound was prepared and isolated as a colorless semi-solid (95% purity).

[0793] Method 9: Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-alanine methyl ester (compound number 34)

[0794] Add (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (1 equivalent), amine, ammonium hydrochloride or ammonium trifluoroacetate, thiol or alcohol nucleophile (1 equivalent), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate ((HATU), 1.2 equivalent), and CH2Cl2 (0.2 M) to a round-bottom flask equipped with a magnetic stir bar. Add 4-methylmorpholine (3 equivalents) and stir the reaction mixture at 22°C for 16 hours (h) or until complete. Filter the reaction mixture through diatomaceous earth, concentrate, and purify by silica column chromatography. The title compound is isolated as a white solid. (100 mg, 40% yield)

[0795] Prepare the following compounds according to the procedure in Method 9:

[0796] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-ethoxy-3-methylbutyramide (Compound No. 38)

[0797] The title compound was prepared and isolated as a grayish-white solid. (90 mg, melting point 163°C-165°C)

[0798] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-methoxy-3-methylbutyramide (Compound No. 37)

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

[0800] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methyl-N-propoxybutyramide (Compound No. 39)

[0801] The title compound was prepared and isolated as a grayish-white solid. (84 mg, melting point 182°C-184°C)

[0802] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-isopropoxy-3-methylbutyramide (Compound No. 40)

[0803] The title compound was prepared and isolated as a grayish-white solid. (108 mg, melting point 167°C-169°C)

[0804] (S)-N-(allyloxy)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 41)

[0805] The title compound was prepared and isolated as a grayish-white solid. (130 mg, melting point 178°C-180°C)

[0806] 2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)-N-((S)-3-methyl-1-(1,2-oxazahexane-2-yl)-1-oxobut-2-yl)acetamide (Compound No. 46)

[0807] The title compound was prepared and isolated as a colorless liquid. (163 mg, melting point 140°C–142°C)

[0808] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-methoxy-N,3-dimethylbutyramide (Compound No. 45)

[0809] The title compound was prepared and isolated as a colorless liquid. (116 mg, 52% yield)

[0810] (S)-N-(benzyloxy)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramide (Compound No. 44)

[0811] The title compound was prepared and isolated as a grayish-white solid. (110 mg, melting point 165°C-167°C)

[0812] (S)-N-(tert-butoxy)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 43)

[0813] The title compound was prepared and isolated as a grayish-white solid. (72 mg, melting point 78°C-80°C)

[0814] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-N-isobutoxy-3-methylbutyramide (Compound No. 42)

[0815] The title compound was prepared and isolated as a grayish-white solid. (100 mg, melting point 162°C-164°C)

[0816] (2S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-((tetrahydro-2H-pyran-2-yl)oxy)butyramide (Compound No. 48)

[0817] The title compound was prepared and isolated as a grayish-white solid. (50 mg, melting point 69°C-71°C)

[0818] (2R)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-((tetrahydro-2H-pyran-2-yl)oxy)butyramide (compound number 49)

[0819] The title compound was prepared and isolated as a grayish-white solid. (50 mg, melting point 70°C-72°C)

[0820] (RS)-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)valine-L-serine methyl ester (Compound No. 53)

[0821] The title compound was prepared and isolated as a white solid. (76 mg, 29% yield)

[0822] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-threonine methyl ester (Compound No. 52)

[0823] The title compound was prepared and isolated as a white solid. (90 mg, 30% yield)

[0824] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionyl)glycine methyl ester (compound number 216)

[0825] The title compound was prepared and isolated as a white solid. (150.2 mg, 36% yield)

[0826] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionyl)-L-valine methyl ester (Compound No. 215)

[0827] The title compound was prepared and isolated as a pale yellow solid. (107 mg, 20% yield)

[0828] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionyl)-L-phenylalanine methyl ester (217)

[0829] The title compound was prepared and isolated as a white solid. (257 mg, 92% yield)

[0830] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-phenylalanine methyl ester (282)

[0831] The title compound was prepared and isolated as a white solid. (177 mg, 63% yield)

[0832] N-(4-chlorophenyl)-2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramide (Compound No. 86)

[0833] The title compound was prepared and isolated as a white solid. (346 mg, 71.97% yield, melting point 205°C–209°C)

[0834] 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(p-tolyl)butyramide (Compound No. 85)

[0835] The title compound was prepared and isolated as a white solid. (196 mg, 53% yield, melting point 206°C–210°C)

[0836] 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(3,4-difluorophenyl)-3-methylbutyramide (Compound No. 84)

[0837] The title compound was prepared and isolated as a grayish-white solid. (163 mg, 46% yield, melting point 161°C–165°C)

[0838] 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-(2-methoxyethyl)-3-methylbutyramide (Compound No. 83)

[0839] The title compound was prepared and isolated as a white solid. (159 mg, 46% yield, melting point 131°C–135°C)

[0840] 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(3-phenylpropyl)butyramide (Compound No. 82)

[0841] The title compound was prepared and isolated as a white solid. (204 mg, 46% yield, melting point 163°C–167°C)

[0842] 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methyl-N-phenethylbutyramide (Compound No. 81)

[0843] The title compound was prepared and isolated as a white solid. (292 mg, 57% yield, melting point 157°C–161°C)

[0844] N-Butyl-2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methylbutyramide (Compound No. 80)

[0845] The title compound was prepared and isolated as a white solid. (282 mg, 61% yield, melting point 178°C–182°C)

[0846] 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(4-methylbenzyl)butyramide (Compound No. 79)

[0847] The title compound was prepared and isolated as a grayish-white solid. (181 mg, 49% yield, melting point 166°C–170°C)

[0848] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-methyl-N-(4-methylbenzyl)butyramide (Compound No. 78)

[0849] The title compound was prepared and isolated as a white solid. (281 mg, 55% yield, melting point 149°C–153°C)

[0850] N-(4-chlorobenzyl)-2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (Compound No. 77)

[0851] The title compound was prepared and isolated as a grayish-white solid. (107 mg, 31% yield, melting point 95°C–99°C)

[0852] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-aspartic acid dimethyl ester (compound number 185)

[0853] The title compound was prepared and isolated as a white solid. (69 mg, 42% yield, melting point 16°C–167°C)

[0854] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-tryptophan methyl ester (Compound No. 196)

[0855] The title compound was prepared and isolated as a pale yellow solid. (137 mg, 95% yield, melting point 89°C–91°C)

[0856] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-glutamic acid dimethyl ester (compound number 195)

[0857] The title compound was prepared and separated as a pale yellow viscous liquid. (123 mg, 72% yield)

[0858] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-glutamine methyl ester (Compound No. 194)

[0859] The title compound was prepared and isolated as a grayish-white solid. (26 mg, 26% yield, melting point 196°C–198°C)

[0860] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-isoleucine methyl ester (compound number 193)

[0861] The title compound was prepared and separated as a pale yellow viscous liquid. (124 mg, 77% yield)

[0862] N 6 -(tert-butoxycarbonyl)-N 2 -((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine)-L-lysine methyl ester (compound number 192)

[0863] The title compound was prepared and separated as a pale yellow viscous liquid. (133 mg, 67% yield)

[0864] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-methionine methyl ester (Compound No. 191)

[0865] The title compound was prepared and isolated as a pale yellow solid. (155 mg, 93% yield, melting point 144°C–146°C)

[0866] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-proline methyl ester (Compound No. 190)

[0867] The title compound was prepared and separated as a yellow, viscous liquid. (126 mg, 80% yield)

[0868] 2-(2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methoxythiobutyric acid S-isopropyl ester (Compound No. 321)

[0869] The title compound was prepared and separated as a yellow liquid. (27 mg)

[0870] 3-Cyclopropyl-2-(2-(5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)thiopropionic acid S-benzyl ester (Compound No. 408)

[0871] The title compound was prepared and separated as a colorless liquid. (45 mg)

[0872] 3-Cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)thiopropionic acid S-isopropyl ester (Compound No. 278)

[0873] The title compound was prepared and separated as a yellow liquid. (16 mg, 10% yield)

[0874] 3-Cyclopropyl-2-(2-(5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)thiopropionic acid S-isopropyl ester (Compound No. 409)

[0875] The title compound was prepared and isolated as a white solid. (19 mg, melting point 122°C–124°C)

[0876] 3-Cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)thiopropionic acid S-benzyl ester (Compound No. 279)

[0877] The title compound was prepared and separated as a yellow liquid. (70 mg)

[0878] Method 10: Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (compound number 2)

[0879] In a round-bottom flask equipped with a magnetic stir bar, methyl 2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (1 equivalent) and THF:H₂O (0.2 M, 3:1) were added. Lithium hydroxide (2-5 equivalents) was added, and the reaction mixture was stirred at room temperature for 16 hours. Afterward, the reaction mixture was diluted to 0.05 M with H₂O and acidified to pH 1-4 with HCl. The reaction mixture was extracted with EtOAc (3x), and the combined organic layers were washed with brine and dried over Na₂SO₄. The solid was filtered off, and the solvent was removed under vacuum to give the product as a solid. The title compound was isolated as a white solid. (140 mg, 97% yield)

[0880] The following compounds were prepared according to the procedure in method 10:

[0881] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionic acid (compound number 206)

[0882] The title compound was prepared and isolated as a white solid. (312.7 mg, 96% yield)

[0883] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine (Compound No. 281)

[0884] The title compound was prepared and isolated as a white solid. (318.6 mg, 80% yield)

[0885] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-methyl-L-valine (Compound No. 25)

[0886] The title compound was prepared and isolated as a white solid. (287.7 mg, 82% yield)

[0887] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-ethyl-L-valine (Compound No. 28)

[0888] The title compound was prepared and isolated as a white solid. (224.8 mg, 73% yield)

[0889] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-(prop-2-yn-1-yl)-L-valine (Compound No. 32)

[0890] The title compound was prepared and isolated as a white solid. (123.5 mg, 87% yield)

[0891] N-Allyl-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (Compound No. 30)

[0892] The title compound was prepared and isolated as a white solid. (89.8 mg, 64% yield)

[0893] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidone-2-yl)acetamyl)propionic acid (compound number 351)

[0894] The title compound was prepared and isolated as a white solid. (510.5 mg, 89% yield)

[0895] N-(carboxymethyl)-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetyl)-L-valine (Compound No. 51)

[0896] The title compound was prepared and isolated as a pale yellow solid. (140.6 mg, 78% yield)

[0897] O-Methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine (Compound No. 411)

[0898] The title compound was prepared and isolated as a white solid. (171.6 mg, 92% yield)

[0899] 2-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramyl)-2-methylpropionic acid (Compound No. 75)

[0900] The title compound was prepared and isolated as a white powder. (153 mg, 62% yield)

[0901] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)-N-ethylacetamido)propionic acid (compound number 249)

[0902] The title compound was prepared and separated as a colorless liquid. (64 mg)

[0903] (S)-2-(N-allyl-2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-cyclopropylpropionic acid (compound number 248)

[0904] The title compound was prepared and isolated as a grayish-white solid. (112 mg, melting point 120°C-121°C)

[0905] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)-N-(prop-2-yn-1-yl)acetamyl)propionic acid (compound number 266)

[0906] The title compound was prepared and separated as a pale yellow liquid. (61 mg)

[0907] (S)-2-(N-(carboxymethyl)-2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-cyclopropylpropionic acid (compound number 265)

[0908] The title compound was prepared and separated as a pale yellow liquid. (57 mg)

[0909] N-(N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl)-O-methyl-L-threonine (Compound No. 304)

[0910] The title compound was prepared and isolated as a white solid. (139 mg)

[0911] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-valine (Compound No. 306)

[0912] The title compound was prepared and isolated as a white solid. (155 mg)

[0913] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-alanine (Compound No. 309)

[0914] The title compound was prepared and isolated as a white solid. (165 mg)

[0915] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetyl)-O-methyl-L-threonylglycine (Compound No. 311)

[0916] The title compound was prepared and isolated as a grayish-white solid. (143 mg)

[0917] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valinelglycine lithium (compound number 70)

[0918] The title compound was prepared and separated directly from the reaction mixture by filtration without dilution or acidification, and the solid was washed with Et2O until dry, and separated as a grayish-white solid (89 mg).

[0919] (2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine (Compound No. 324)

[0920] The title compound was prepared and isolated as a white solid. (452 ​​mg, 88% yield)

[0921] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine glycine (Compound No. 69)

[0922] The title compound was prepared and isolated as a grayish-white solid. (150 mg)

[0923] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine-L-valine methyl ester (Compound No. 21)

[0924] The title compound was prepared and isolated as a grayish-white solid. (666 mg, 66% yield)

[0925] Method 11: Preparation of methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)-N-ethylacetamido)propionate (compound number 251)

[0926] Add (S)-2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetic acid (1 equivalent), anhydrous DMF (0.75 M), an amine nucleophile (1.2 equivalent), 2-chloro-1-methylpyridin-1-onium iodide (1.5 equivalent), and N,N-diisopropylethylamine (2.5 equivalent) to a round-bottom flask equipped with a magnetic stir bar. Stir the reaction mixture at 22°C for 16 hours (h), or until complete. Pour the reaction mixture into ice-cold water and extract with ethyl acetate. Wash the combined organic layers with water, followed by brine, and dry over sodium sulfate. Filter the solvent, concentrate, and purify by silica column chromatography. The title compound is isolated as a grayish-white solid. (56 mg, 41% yield, melting point 108°C–109°C)

[0927] The following compounds were prepared according to the procedure in method 11:

[0928] (S)-2-(N-allyl-2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-3-cyclopropylpropionate (Compound No. 250)

[0929] The title compound was prepared and isolated as a grayish-white solid. (95 mg, melting point 68°C-69°C)

[0930] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-(2-methoxy-2-oxoethyl)-O-methyl-L-threonine methyl ester (compound number 289)

[0931] The title compound was prepared and separated as a pale yellow liquid. (35 mg)

[0932] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)-N-(prop-2-yn-1-yl)acetamyl)methyl propionate (compound number 268)

[0933] The title compound was prepared and separated as a pale yellow liquid. (90 mg)

[0934] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)-N-(2-methoxy-2-oxoethyl)acetamyl)methyl propionate (compound number 267)

[0935] The title compound was prepared and separated as a colorless liquid. (78 mg)

[0936] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-ethyl-O-methyl-L-threonine methyl ester (compound number 292)

[0937] The title compound was prepared and separated as a pale yellow liquid. (93 mg)

[0938] N-Allyl-N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonine methyl ester (Compound No. 291)

[0939] The title compound was prepared and separated as a colorless liquid. (76 mg)

[0940] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-N-(prop-2-yn-1-yl)-L-threonine methyl ester (compound number 290)

[0941] The title compound was prepared and separated as a colorless liquid. (70 mg)

[0942] N-Allyl-O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine methyl ester (Compound No. 426)

[0943] The title compound was prepared and separated as a pale yellow liquid. (196 mg)

[0944] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-N-(prop-2-yn-1-yl)-L-threonine methyl ester (compound number 425)

[0945] The title compound was prepared and separated as a pale yellow liquid. (93 mg)

[0946] N-(2-methoxy-2-oxoethyl)-O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine methyl ester (compound number 424)

[0947] The title compound was prepared and separated as a pale yellow liquid. (73 mg)

[0948] (S)-3-cyclopropyl-2-(N-(2-methoxy-2-oxoethyl)-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)methyl propionate (compound number 403)

[0949] The title compound was prepared and separated as a pale yellow liquid. (119 mg)

[0950] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)-N-(prop-2-yn-1-yl)acetamyl)methyl propionate (compound number 402)

[0951] The title compound was prepared and separated as a pale yellow liquid. (135 mg)

[0952] (S)-2-(N-allyl-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamyl)-3-cyclopropylpropionate (Compound No. 401)

[0953] The title compound was prepared and separated as a pale yellow liquid. (137 mg)

[0954] N-(2-methoxy-2-oxoethyl)-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine methyl ester (compound number 346)

[0955] The title compound was prepared and separated as a pale yellow liquid. (127 mg)

[0956] N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-N-(prop-2-yn-1-yl)-L-valine methyl ester (compound number 345)

[0957] The title compound was prepared and separated as a pale yellow liquid. (112 mg)

[0958] N-Allyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine methyl ester (Compound No. 344)

[0959] The title compound was prepared and separated as a pale yellow liquid. (116 mg)

[0960] Method 12: Preparation of N-(cyanomethyl)-O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonine methyl ester (compound number 434)

[0961] In a round-bottom flask equipped with a magnetic stir bar, add (S)-2-(5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetic acid (1 equivalent), pyridine (0.2 M), and an amine nucleophile (1.2 equivalent). Cool the reaction mixture to 0°C, then add phosphorus oxychloride (1.5 equivalent), and warm the mixture to room temperature, then add N,N-diisopropylethylamine (2.5 equivalent). Stir the mixture at 22°C for 2 hours (h). Pour the mixture into ice-cold 1N HCl and extract with ethyl acetate. Wash the combined organic layers with water, then with brine, and dry over sodium sulfate. Filter the solvent, concentrate, and purify by silica column chromatography. The title compound, a pale yellow liquid, is isolated. (98 mg, 63% yield)

[0962] The following compounds were prepared according to the procedure in Method 12:

[0963] (S)-2-(N-(cyanomethyl)-2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)-3-cyclopropylpropionate (Compound No. 406)

[0964] The title compound was prepared and separated as a pale yellow liquid. (80 mg)

[0965] N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-N-(2,2,2-trifluoroethyl)-L-valine methyl ester (compound number 347)

[0966] The title compound was prepared and separated as a pale yellow liquid. (35 mg)

[0967] (S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)-N-(2,2,2-trifluoroethyl)acetamyl)methyl propionate (compound number 407)

[0968] The title compound was prepared and isolated as a grayish-white solid. (71 mg, melting point 97°C-99°C)

[0969] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-N-(2,2,2-trifluoroethyl)-L-threonine methyl ester (compound number 435)

[0970] The title compound was prepared and separated as a pale yellow liquid. (35 mg)

[0971] N-(cyanomethyl)-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine methyl ester (compound number 348)

[0972] The title compound was prepared and separated as a pale yellow liquid. (143 mg)

[0973] Method 13: Preparation of (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)-N-hydroxy-3-methylbutyramide (compound number 50)

[0974] 10% Pd / C (0.02 g) was added to a solution of (S)-N-(benzyloxy)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutyramide (0.2 g, 0.42 mmol) in methanol (5 mL). The reaction mixture was stirred at 23°C for 2 h under hydrogen balloon pressure. The reaction mixture was filtered through diatomaceous earth and washed with methanol. The filtrate was concentrated to give the title compound (0.133 g, 82%).

[0975] Method 14: Preparation of 1-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutamido)cyclopropane-1-carboxylic acid (compound number 204)

[0976] A 2M aqueous solution of sodium hydroxide (260 µL, 0.52 mmol, 2.0 equivalent) was added at 23°C to a stirred solution of methyl 1-((S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-3-methylbutamido)cyclopropane-1-carboxylate (120 mg, 0.26 mmol, 1.0 equivalent) in a 2:1 methanol:tetrahydrofuran (3.0 mL). 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 (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 according to the procedure in method 14:

[0978] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidone-2-yl)acetamyl)propionic acid (compound number 488)

[0979] The title compound was prepared and isolated as a white solid. (95% purity, 69% yield)

[0980] Method 15: Preparation of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine triisopropylsilyl ester (compound number 179)

[0981] Imidazole (0.028 g, 0.407 mmol) and triisopropylchlorosilane (0.064 mL, 0.299 mmol) were added sequentially to a stirred mixture of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-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 reactants were diluted with ethyl acetate (20 mL), washed thoroughly with water, and dried over anhydrous MgSO4. The residue after vacuum concentration was purified by rapid silica gel chromatography (0% to 100% acetone in hexane) to give (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine triisopropylsilyl ester (93 mg, 0.168 mmol, 62.0% yield) as a viscous oil.

[0982] The following compounds were prepared according to the procedure in Method 15:

[0983] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine tert-butyldiphenylsilyl ester (Compound No. 184)

[0984] The title compound was prepared and isolated as a white solid. (121 mg, 70% yield)

[0985] Method 16: Preparation of lithium (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine (compound number 10)

[0986] Add (1.1 equivalents) of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine and lithium hydroxide (1 equivalent) in a 1:1 THF:water mixture (0.125 M) to a 2-dram reaction flask equipped with a magnetic stir bar. Stir the reaction mixture at 20°C for 20 h, or until complete. Dilute the reaction mixture with water and wash with ethyl acetate, then with a 3:1 ethyl acetate:heptane mixture. Concentrate the aqueous layer to remove water. Separate the title compound as a white solid. (177.4 mg, 94% yield)

[0987] Method 17:Preparation of N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-N-methylvaline methyl ester (compound number 23)

[0988] Add (1 equivalent) of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine methyl ester in THF (0.2 M) to a 25 mL reaction vial equipped with a magnetic stir bar. Add 1 M of bis(trimethylsilyl)amide lithium in THF (1 equivalent) at 0°C and stir for 5 min at 0°C. Add iodomethane (2 equivalents), and then stir the reaction mixture at 20°C for 48 h, or until complete. The reaction mixture was then quenched by adding MeOH, concentrated onto diatomaceous earth, and purified by silica column chromatography. The title compound was isolated as a clear oil. (236 mg, 60% yield)

[0989] Method 18: Preparation of ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionyl)-L-tyrosine methyl ester (compound number 240)

[0990] TBAF (1 M in THF, 2 equivalents) was added to a solution of methyl (S)-3-(4-((tert-butyldimethylsilyl)oxy)phenyl)-2-((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propamido)propionate (1 equivalent) in THF (0.6 M) at 0°C, and stirred for 1 hour (h) at room temperature, or until complete. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and saline solution, dried over sodium sulfate, and concentrated. The obtained crude compound was purified by silica gel column chromatography. The title compound was isolated as a grayish-white solid. (0.12 g, 36% yield)

[0991] The following compounds were prepared according to the procedure in Method 18:

[0992] N-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-O-methyl-L-threonyl-L-tyrosine methyl ester (compound number 287)

[0993] The title compound was prepared and isolated as a grayish-white solid. (166 mg)

[0994] ((S)-3-cyclopropyl-2-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)propionyl)-L-tyrosine methyl ester (Compound No. 369)

[0995] The title compound was prepared and isolated as a white solid. (156 mg)

[0996] O-methyl-N-(2-((S)-5-oxo-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-threonyl-L-tyrosine methyl ester (compound number 419)

[0997] The title compound was prepared and isolated as a grayish-white solid. (167 mg)

[0998] Method 19: Preparation of (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)tetramethylammonium propionate (compound number 243)

[0999] Add (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)-propionic acid (1 equivalent) to MeOH (0.5 M) in a 25 mL reaction flask equipped with a magnetic stir bar. Add the corresponding ammonium hydroxide or N-amine oxide (1 equivalent) via syringe. Stir the reaction mixture at 20°C for 30 min, or until complete. Concentrate the crude reaction mixture to obtain the title compound as a pale yellow viscous substance. (347.6 mg, 73% yield)

[1000] Prepare the following compounds according to the procedure in Method 19:

[1001] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)tetraethylammonium propionate (Compound No. 244)

[1002] The title compound was prepared and isolated as a pale yellow viscous substance. (330.4 mg, 63% yield)

[1003] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionic acid 2-hydroxy-N,N,N-trimethylethyl-1-ammonium (Compound No. 245)

[1004] The title compound was prepared and isolated as a pale yellow viscous substance. (361.2 mg, 71% yield)

[1005] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidone-2-yl)acetamyl)propionic acid N,N,N-trimethylhydroxyammonium (compound number 246)

[1006] The title compound was prepared and isolated as a clear, viscous substance. (162 mg, 69% yield)

[1007] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionic acid 4-hydroxy-4-methylmorpholine-4-onium (Compound No. 247)

[1008] The title compound was prepared and isolated as a clear, viscous substance. (167.6 mg, 64% yield)

[1009] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine tetrabutylammonium (Compound No. 13)

[1010] The title compound was prepared and isolated as a clear, viscous substance. (1.8 g, 99% yield)

[1011] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine tetraethylammonium (Compound No. 135)

[1012] The title compound was prepared and isolated as a clear, viscous substance. (498 mg, 98% yield)

[1013] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-hydroxy-N,N,N-trimethylethyl-1-ammonium (Compound No. 136)

[1014] The title compound was prepared and isolated as a clear, viscous substance. (472 mg, 98% yield)

[1015] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine tetramethylammonium (Compound No. 141)

[1016] The title compound was prepared and isolated as a clear, viscous substance. (442 mg, 98% yield)

[1017] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine N,N,N-trimethylhydroxyammonium (Compound No. 142)

[1018] The title compound was prepared and isolated as a clear, viscous substance. (222 mg, 98% yield)

[1019] (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 4-hydroxy-4-methylmorpholine-4-onium (Compound No. 143)

[1020] The title compound was prepared and isolated as a clear, viscous substance (243 mg, 98% yield).

[1021] Method 20: Preparation of methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)propionate (compound number 487)

[1022] In a round-bottom flask equipped with a magnetic stir bar, methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionate (1.0 g, 2.5 mmol, 1.0 equivalent), Lawson's reagent (770 mg, 1.9 mmol, 0.75 equivalent), and toluene (25 mL) were added. The resulting turbid 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 according to the procedure in method 20:

[1024] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetyl)-L-valine allyl ester (compound number 458)

[1025] The title compound was prepared and separated as a pale yellow viscous liquid (98% purity).

[1026] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetyl)-L-valine benzyl ester (Compound No. 460)

[1027] The title compound was prepared and separated as a pale yellow viscous liquid (90% purity).

[1028] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-isopropyl ester (Compound No. 469)

[1029] Prepare the title compound and isolate it as a white solid. (93% purity, mp 110°C-112°C).

[1030] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-benzyl ester (Compound No. 470)

[1031] Prepare the title compound and isolate it as a white solid. (96% purity, mp 127°C-129°C).

[1032] 2-(((2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetyl)-L-valine)thio)methyl acetate (compound number 471)

[1033] Prepare the title compound and isolate it as a white solid. (98% purity, mp 59°C-61°C).

[1034] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)-3-methylthiobutyric acid S-(3,3,3-trifluoropropyl) ester (Compound No. 472)

[1035] The title compound was prepared and isolated as a grayish-white solid. (98% purity, mp 123°C-125°C).

[1036] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)allyl propionate (compound number 489)

[1037] The title compound was prepared and separated as a colorless, viscous liquid (99% purity).

[1038] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)benzyl propionate (Compound No. 491)

[1039] The title compound was prepared and separated as a yellow, viscous liquid (96% purity).

[1040] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidone-2-yl)acetamyl)s-benzyl thiopropionic acid (compound number 496)

[1041] Prepare the title compound and isolate it as a white solid. (99% purity, mp 108°C-110°C).

[1042] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidone-2-yl)acetamyl)s-isopropyl thiopropionic acid (compound number 500)

[1043] The title compound was prepared and separated as a grayish-white solid (91% purity).

[1044] 2-(((S)-3-cyclopropyl-2-(2-(((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)propionyl)thio)methyl acetate (compound number 501)

[1045] The title compound was prepared and separated as a yellow, viscous liquid (99% purity).

[1046] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidone-2-yl)acetamyl)thiopropionic acid S-(3,3,3-trifluoropropyl) ester (compound number 502)

[1047] The title compound was prepared and separated as a white solid (98% purity).

[1048] Method 21: Preparation of methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetamido)propionate (compound number 486)

[1049] In a round-bottom flask equipped with a magnetic stir bar, methyl (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetamyl)propionate (1.0 g, 2.5 mmol, 1.0 equivalent), Lawson's reagent (770 mg, 1.9 mmol, 0.75 equivalent), and toluene (25 mL) were added. The resulting turbid 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 according to the procedure in method 21:

[1051] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetyl)-L-valine allyl ester (compound number 459)

[1052] The title compound was prepared and separated as a yellow, viscous liquid (98% purity).

[1053] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetamido)-3-methylthiobutyric acid S-isopropyl ester (Compound No. 473)

[1054] The title compound was prepared and separated as a yellow viscous liquid (92% purity).

[1055] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetyl)-L-valine benzyl ester (compound number 461)

[1056] The title compound was prepared and separated as a pale yellow viscous liquid (99% purity).

[1057] 2-(((2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetyl)-L-valine)thio)methyl acetate (compound number 474)

[1058] The title compound was prepared and isolated as a grayish-white solid. (85% purity, mp 118°C-120°C).

[1059] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetamido)allyl propionate (Compound No. 490)

[1060] The title compound was prepared and separated as a yellow, viscous liquid (99% purity).

[1061] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetamido)benzyl propionate (Compound No. 492)

[1062] The title compound was prepared and separated as a pale yellow viscous liquid (96% purity).

[1063] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetamido)s-isopropyl thiopropionic acid (compound number 503)

[1064] The title compound was prepared and separated as a pale brown viscous liquid (98% purity).

[1065] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)thioacetamido)thiopropionic acid S-(3,3,3-trifluoropropyl) ester (compound number 504)

[1066] The title compound was prepared and separated as a colorless, viscous liquid (98% purity).

[1067] Method 22, Step 1: Preparation of (S)-2-(1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)methyl acetate

[1068] In a round-bottom flask equipped with a magnetic stir bar, methyl 2-(1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetate (1.0 g, 3.5 mmol, 1.0 equivalent), Lawson's reagent (2.9 g, 7.1 mmol, 2.0 equivalent), and toluene (30 mL) were added. The resulting turbid 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-thiopyrrolidine-2-yl)acetic acid

[1070] In a round-bottom flask equipped with a magnetic stir bar, (S)-2-(1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)methyl acetate (950 mg, 3.2 mmol, 1.0 equivalent) and 3:1 THF:H₂O (16 mL) were added. Lithium hydroxide monohydrate (91 mg, 3.8 mmol, 1.2 equivalent) was added, and the reaction mixture was stirred at 23°C for 2 h. The reaction mixture was concentrated by rotary evaporation. The residue was diluted with 1 M HCl and extracted with EtOAc. The combined organic layers were dried over Na₂SO₄, filtered by gravity, and concentrated by rotary evaporation. The title compound was isolated as a grayish-white solid (850 mg, 93% yield).

[1071] Method 22, Step 3: Preparation of 2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidone-2-yl)-N-((S)-3-methyl-1-oxo-1-((prop-2-imideamino)oxy)but-2-yl)acetamide (compound number 462)

[1072] N-methylmorpholine (0.28 mL, 2.5 mmol, 4.0 equivalents) was added to a stirred solution of (S)-2-(1-(2,3-difluorobenzyl)-5-thiopyrrolidone-2-yl)acetic acid (180 mg, 0.63 mmol, 1.0 equivalents), HATU (290 mg, 0.76 mmol, 1.2 equivalents), and propyl-2-one O-(L-valinel)oxime hydrochloride (200 mg, 0.95 mmol, 1.5 equivalents) in dichloromethane (10 mL). The reaction mixture was stirred at 23°C for 16 h. The reaction mixture was diluted with dichloromethane and washed with 1 M HCl, followed by washing with water. The organic layer was dried over Na₂SO₄, filtered by gravity, 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. (170mg, 98% purity, 60% yield, mp 98°C-100°C)

[1073] The following compounds were prepared according to the procedure in method 22:

[1074] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetyl)-L-valine 2-cyanoethyl ester (Compound No. 463)

[1075] The title compound was prepared and separated as a pale yellow viscous liquid (92% purity).

[1076] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetyl)-L-valine-glycine methyl ester (compound number 475)

[1077] Prepare the title compound and isolate it as a white solid. (98% purity, mp 180°C-182°C).

[1078] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetyl)-L-valine-L-leucine methyl ester (compound number 476)

[1079] Prepare the title compound and isolate it as a white solid. (98% purity, mp 81°C-83°C).

[1080] (2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetyl)-L-valine-L-isoleucine methyl ester (compound number 477)

[1081] Prepare the title compound and isolate it as a white solid. (95% purity, mp 213°C-215°C).

[1082] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)-N-methoxy-3-methylbutyramide (Compound No. 478)

[1083] Prepare the title compound and isolate it as a white solid. (87% purity, mp 198°C–200°C).

[1084] (S)-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)-N-isopropoxy-3-methylbutyramide (Compound No. 479)

[1085] Prepare the title compound and isolate it as a white solid. (98% purity, mp 48°C-50°C).

[1086] 2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)-N-((S)-3-methyl-1-(1,2-oxazahexane-2-yl)-1-oxobut-2-yl)acetamide (compound number 480)

[1087] The title compound was prepared and separated as a grayish-white semi-solid (94% purity).

[1088] N-((S)-3-cyclopropyl-1-oxo-1-((propyl-2-imideamino)oxy)propyl-2-yl)-2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamide (compound number 493)

[1089] The title compound was prepared and isolated as a grayish-white solid (97% purity, mp 108°C-110°C).

[1090] (S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidone-2-yl)acetamyl)cyanoethyl propionate (Compound No. 494)

[1091] The title compound was prepared and isolated as a grayish-white solid (98% purity, mp 128°C-130°C).

[1092] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)propionyl)glycine methyl ester (Compound No. 505)

[1093] Prepare the title compound and isolate it as a white solid. (97% purity, mp 79°C-81°C).

[1094] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)propionyl)-L-leucine methyl ester (Compound No. 506)

[1095] Prepare the title compound and isolate it as a white solid. (98% purity, mp 146°C-148°C).

[1096] ((S)-3-cyclopropyl-2-(2-((S)-1-(2,3-difluorobenzyl)-5-thiopyrrolidine-2-yl)acetamyl)propionyl)-L-isoleucine methyl ester (Compound No. 507)

[1097] Prepare the title compound and isolate it as a white solid. (98% purity, mp 73°C–75°C).

[1098] (2-((S)-5-thio-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine-L-leucine methyl ester (compound number 509)

[1099] Prepare the title compound and isolate it as a white solid. (97% purity, mp 82°C–84°C).

[1100] (2-((S)-5-thio-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetyl)-L-valine-L-isoleucine methyl ester (compound number 510)

[1101] Prepare the title compound and isolate it as a white solid. (96% purity, mp 123°C-125°C).

[1102] (S)-N-methoxy-3-methyl-2-(2-((S)-5-thio-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)butyramide (compound number 511)

[1103] Prepare the title compound and isolate it as a white solid. (98% purity, mp 210°C-212°C).

[1104] (S)-N-isopropoxy-3-methyl-2-(2-((S)-5-thio-1-(2,3,5-trifluorobenzyl)-pyrrolidine-2-yl)acetamyl)butyramide (compound number 512)

[1105] Prepare the title compound and isolate it as a white solid. (97% purity, mp 78°C-80°C).

[1106] N-((S)-3-methyl-1-(1,2-oxazahexane-2-yl)-1-oxobut-2-yl)-2-((S)-5-thio-1-(2,3,5-trifluorobenzyl)pyrrolidine-2-yl)acetamide (compound number 513)

[1107] Prepare the title compound and isolate it as a white solid. (93% purity, mp 168°C-170°C).

[1108] Method 23: Preparation of 2-(((2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine)oxy)acetic acid (compound number 465)

[1109] Trifluoroacetic acid (TFA) (800 µL, 10 mmol, 20 equivalents) was added to a stirred solution of (2-((S)-1-(2,3-difluorobenzyl)-5-oxopyrrolidine-2-yl)acetyl)-L-valine 2-(tert-butoxy)-2-oxoethyl ester (250 mg, 0.52 mmol, 1.0 equivalents) in dichloromethane (5.2 mL). 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 0.1 M hydrochloric acid aqueous 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, present as a white foam, was isolated. (210 mg, 95% crude yield) 4. Composition

[1110] This disclosure also includes compositions containing the 5-membered ring-based molecular herbicides disclosed herein. A composition is a mixture comprising at least one 5-membered ring-based molecular herbicide and further comprising other additives, such as carriers, for enhancing the properties or effectiveness of the mixture in a certain way. Exemplary additives include, but are not limited to, adjuvants, safeners, carriers, and combinations thereof. The composition may be in a variety of physical states, including but not limited to, as a solution, emulsion, suspension, granules, powder, and other such states. 1. Carrier

[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, paraffin oil, etc.; vegetable oils, such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil, etc.; esters of the above vegetable oils; esters of monohydric or dihydric, trihydric or other lower polyols (containing 4-6 hydroxyl groups), such as 2-ethylhexyl stearate, n-butyl oleate, isopropyl myristate, propylene glycol dioleate, etc. Dioctyl succinate, dibutyl adipate, dioctyl phthalate, etc.; esters of monocarboxylic acids, dicarboxylic acids and polycarboxylic acids, etc.; toluene; xylene; 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; methanol; ethanol; isopropanol; pentanol; ethylene glycol; propylene glycol; glycerol; N-methyl-2-pyrrolidone; N;N-dimethylalkylamide; dimethyl sulfoxide; and liquid fertilizers, and mixtures thereof. Exemplary solid carriers include, but are not limited to: silica, silica gel, silicates, talc, kaolin, limestone, lime, chalk, red basalt, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground synthetic materials, pyrophyllite clay, attapulgite clay, diatomaceous earth, calcium carbonate, bentonite, bleaching clay, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell powder, lignin, ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, cereal flour, bark powder, wood flour and nut shell powder, cellulose powder, and mixtures thereof. 2. adjuvants

[1112] In some respects, additives include agriculturally acceptable adjuvants. Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifreeze agents, defoamers, compatibilizers, multivalent chelating agents, neutralizers and buffers, corrosion inhibitors, colorants, flavor enhancers, penetration aids, wetting agents, spreading agents, dispersants, thickeners, freezing point inhibitors, antimicrobial agents, crop oils, binders (e.g., used in seed formulations), surfactants, protective colloids, emulsifiers, thickeners, and mixtures thereof.

[1113] Exemplary agriculturally acceptable adjuvants include, but are not limited to, crop oil concentrates (e.g., 85% mineral oil + 15% emulsifier); nonylphenol ethoxylates; benzyl cocoa alkyl dimethyl quaternary ammonium salts; blends of petroleum hydrocarbons, alkyl esters, organic acids, and anionic surfactants; C9-C 11 Alkyl polyglycosides; alkyl phosphate esters, such as tris(2-ethylhexyl) phosphate (TEHP); phosphate ester alcohol ethoxylates; natural primary alcohols (C 12 -C16 Ethoxylated compounds; di-sec-butylphenol EO-PO block copolymers; methyl-terminated polysiloxanes; nonylphenol ethoxylated compounds + urea ammonium nitrate; emulsified methylated seed oils; tridecyl alcohol (synthetic) ethoxylated compounds (e.g., 8 EO); tallow amine ethoxylated compounds (e.g., 15 EO); and PEG(400) dioleate-99.

[1114] Exemplary surfactants (e.g., wetting agents, thickeners, dispersants, emulsifiers) include, but are not limited to: alkali metal salts, alkaline earth metal salts, and ammonium salts of fatty acids or aromatic sulfonic acids (e.g., lignin sulfonic acid, phenol sulfonic acid, naphthalene sulfonic acid, and dibutylnaphthalene sulfonic acid); alkyl- and alkylaryl sulfonates; alkyl sulfates, lauryl ether sulfates, and fatty alcohol sulfates; salts of sulfated hexadecyl alcohol, heptadecanol, and octadecyl alcohol; salts of fatty alcohol glycol ethers; condensates of sulfonated naphthalene and its derivatives with formaldehyde; condensates of naphthalene or naphthalene sulfonic acid with phenol and formaldehyde; and polyoxyethylene octylphenol ether. ; ethoxylated isooctyl-, octyl-, or nonylphenol, alkylphenyl or tributylphenyl polyglycol ethers; alkylaryl polyether alcohols; isotretinoin; fatty alcohol / ethylene oxide condensates; ethoxylated castor oil; polyoxyethylene alkyl ethers or polyoxypropylene alkyl ethers; lauryl glycol polyglycol ether acetate; sorbitol esters; lignin sulfite waste and proteins; denatured proteins, polysaccharides (e.g., methylcellulose); hydrophobically modified starch; and polyvinyl alcohol, polycarboxylates, polyalkoxylated compounds, polyethyleneamine, polyethyleneimine, polyvinylpyrrolidone, and copolymers thereof.

[1115] Exemplary thickeners include, but are not limited to, polysaccharides (e.g., xanthan gum), organic and inorganic flake minerals, and mixtures thereof.

[1116] Exemplary defoamers 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 dichlorophenol and benzyl alcohol hemiacetal; 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, glycerin, and mixtures thereof.

[1119] Exemplary colorants include, but are not limited to, dyes known by the name 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. safety agent

[1121] In some respects, additives are safeners. A safener is a compound that, when applied in conjunction with a herbicide, results in better crop-plant compatibility. In some respects, a safener itself has herbicidal activity. In some respects, a safener acts as an antidote or antagonist in the crop plant and can protect the crop plant from additional damage that may occur due to the applied herbicide. Exemplary safeners include, but are not limited to, AD-67 (MON 4660), chlorpyrifos, chlorpyrifos, blasinolide, cloquintocet, chlorpyrifos nitrile, cyclopropanesulfonamide, chlorpyrifos, dichloropropenesulfonamide, dicyclonon, dietholate, piperazine, ethoxyphos, chlorpyrifos, chlorpyrifos-ethyl, chlorpyrifos-ethyl, chlorpyrifos-ethyl, fluroxypyr, chlorpyrifos-oxazol, hypersensitive protein, chlorpyrifos-ethyl, jiecaowan, and chlorpyrifos-ethyl. (jiecaoxi), pyrazoloxalic acid, pyrazoloxalic acid-diethyl, mephenate, naphthalenecarboxylic anhydride, 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine, 4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane, pyrazoloxil, R29148 and N-phenyl-sulfonylbenzoic acid amide, and their agriculturally acceptable salts and their agriculturally acceptable derivatives (provided they have a carboxyl group). In some aspects, the safener may be quinoxyacetic acid or its esters or salts, such as pyrazoloxalic acid. In some aspects, the safener may be pyrazoloxalic acid or its esters or salts, such as pyrazoloxalic acid-diethyl. In some aspects, the safener is used in rice, cereals, or corn. For example, pyrazoloxalic acid or quinoxyacetic acid can be used to antagonize the harmful effects of the composition on rice, cultivated crops, and cereals. 4. physical state

[1122] In some aspects, compositions comprising 5-membered ring-based molecular herbicides can be present in suspension, emulsion, dissolved, or solid form. Exemplary compositions include, but are not limited to, aqueous solutions, aqueous suspensions, aqueous dispersions, aqueous emulsions, aqueous microemulsions, aqueous suspension emulsions, oil solutions, oil suspensions, oil dispersions, oil emulsions, oil microemulsions, oil suspension emulsions, self-emulsifying formulations, gels, pastes, powders, granules, and broadcasting materials.

[1123] In some respects, 5-membered ring-based molecular herbicides are available in aqueous solutions that can be diluted before use. In other respects, 5-membered ring-based molecular herbicides can be supplied as high-concentration formulations (such as concentrates). In some respects, the concentrates are stable and retain their potency during storage and transport. In various respects, the concentrates are clear, homogeneous liquids that are stable at temperatures of 54°C or higher. In some respects, the concentrates do not exhibit any solid precipitation at temperatures of 10°C or higher. In some respects, the concentrates do not exhibit any separation, precipitation, or crystallization of components at low temperatures. For example, the concentrates remain clear solutions at temperatures below 0°C (e.g., below -5°C, below -10°C, below -15°C). In some respects, even at temperatures as low as 5°C, the concentrates exhibit a viscosity of less than 50 centipoise (50 MPa). In some respects, the concentrate did not exhibit any separation, precipitation, or crystallization of components during storage periods of 2 weeks or longer (e.g., 4 weeks, 6 weeks, 8 weeks, 3 months, 6 months, 9 months, or 12 months or longer).

[1124] In some respects, emulsions, gels, pastes, or oil dispersions can be prepared by homogenizing a 5-membered ring-based molecular herbicide in water using a wetting agent, thickener, dispersant, or emulsifier. In some respects, concentrates suitable for dilution with water can be prepared, comprising a 5-membered ring-based molecular herbicide, a wetting agent, a thickener, and a dispersant or emulsifier.

[1125] In some respects, powders, broadcast materials, or granules can be prepared by mixing or simultaneously grinding a 5-membered ring-based molecular herbicide with optional other additives and a solid carrier.

[1126] In some respects, particles (e.g., coated particles, impregnated particles, and homogenized particles) can be prepared by combining 5-membered ring-based molecular herbicides with solid carriers.

[1127] In some aspects, the composition comprises about 0.01% to about 99% of a 5-membered ring-based molecular herbicide by weight of the total composition, comprising 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% by weight of the total composition. %, 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%, or within any range defined between any two of the foregoing values, such as a 5-membered ring-based molecular herbicide based on the total weight of the composition between about 1% and about 97%, between about 10% and about 90%, between about 20% and about 45%, and between about 25% and about 50%. The concentrate may be diluted with an inert carrier (such as water) before application. Based on the total weight of the diluted composition, the diluted composition applied to undesirable vegetation or sites of undesirable vegetation may contain a total amount of 0.0006 to 8.0 wt% of a 5-membered ring-based molecular herbicide (e.g., 0.001 to 5.0 wt%). 5. How to use

[1128] The 5-membered ring-based molecules disclosed herein can be formulated into compositions and applied using any known technique for applying herbicides. Exemplary application techniques include, but are not limited to, spraying, atomizing, dusting, sprinkling, broadcasting, or direct application. Application methods can vary depending on the intended purpose. In some aspects, the application method can be selected to ensure the optimal possible distribution of the compositions disclosed herein.

[1129] In some respects, this document discloses a method for controlling undesirable vegetation, which includes contacting the vegetation or its site with any composition or applying any composition to soil or water to prevent the germination or growth of the vegetation.

[1130] The compositions disclosed herein, containing molecules based on 5-membered rings, can be applied pre-emergence (before the emergence of undesirable vegetation) or post-emergence (e.g., during and / or after the emergence of undesirable vegetation). In some aspects, the compositions are applied to undesirable vegetation post-emergence.

[1131] When the compositions are used on crops, they can be applied after sowing and before or after crop emergence. In some aspects, the compositions disclosed herein exhibit good crop tolerance even when the crop has already emerged and can be applied during or after crop emergence. In some aspects, when the compositions are used on crops, they can be applied before crop sowing.

[1132] In some aspects, the compositions disclosed herein are applied by spraying (e.g., foliar spraying) to vegetation or areas adjacent to vegetation, or to soil or water, to prevent germination or growth of vegetation. In some aspects, the spraying technique uses, for example, water as a carrier and a spray volume ratio of 2 liters / ha (L / ha) to 2000 L / ha (e.g., 10-1000 L / ha or 50-500 L / ha). In some aspects, the compositions disclosed herein are applied by low-volume or ultra-low-volume methods, wherein the application is in the form of microparticles. In some aspects, where certain crop plants are not well tolerant of the compositions disclosed herein, these compositions can be applied by means of spraying equipment in a manner that allows them to reach the leaves of undesired vegetation growing at the bottom or in bare soil with minimal contact (if any) with the leaves of sensitive crop plants (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 concentrates).

[1133] In some respects, where the undesirable vegetation is treated post-emergence, the compositions disclosed herein are applied via foliar application. In some respects, the compounds of the mixture exhibit herbicidal activity when applied directly to the plant or the site of the plant at any stage of growth or before planting or emergence. The observed effects may depend on the type of undesirable vegetation to be controlled, the growth stage of the undesirable vegetation, application parameters such as dilution and spray droplet size, particle size of the solid components, environmental conditions at the time of application, the specific compound used, the specific adjuvants and carriers used, soil type, etc., and the amount of chemical applied. In some respects, these and other factors can be modulated to promote non-selective or selective herbicidal action.

[1134] The compositions and methods disclosed herein can be used to control unwanted vegetation in a variety of applications. These compositions and methods can be used to control unwanted vegetation in areas including, but not limited to, farmland, turf, pasture, grassland, grazing land, fallow land, roadsides, aquatic environments, trees and vines, wildlife management areas, or pasture. In some aspects, unwanted vegetation is controlled in cultivated crops. Exemplary crops include, but are not limited to, wheat, barley, triticale, rye, teff, oats, corn, cotton, soybean, canola, legumes, sunflower, sugar beet, sorghum, rice, millet, sugarcane, and pasture (e.g., forage grass). In some aspects, the compositions and methods disclosed herein can be used to control unwanted vegetation in corn, soybean, canola, cotton, legumes, sunflower, sugar beet, wheat, barley, rice, sorghum, millet, oats, or combinations thereof. In some aspects, the compositions and methods disclosed herein can be used for industrial vegetation management (IVM) or for applications in public utilities, pipelines, roadsides, and railway embankments. In some aspects, the compositions and methods disclosed herein can also be used in woodlands (e.g., for site preparation or to combat unwanted vegetation in plantations). In some aspects, the compositions and methods disclosed herein can be used to control unwanted vegetation in conservation fallow 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 public institutions), golf courses, parks, cemeteries, sports fields, and turf farms.

[1135] The compositions and methods disclosed herein can also be used in crop plants resistant to, for example, herbicides, insecticides, fungicides, pathogens, insects, or combinations thereof. In some aspects, the compositions and methods disclosed herein can be used in crop plants resistant to one or more herbicides due to genetic engineering or breeding. In some aspects, the compositions and methods disclosed herein can be used in crop plants resistant to one or more pathogens, such as plant pathogenic fungi, due to genetic engineering or breeding. In some aspects, the compositions and methods disclosed herein can be used in crop plants resistant to insect infestation due to genetic engineering or breeding. Exemplary resistant crops include, but are not limited to, crops resistant to photosystem II inhibitors, or crop plants resistant to certain insect infestations due to the introduction of Bacillus thuringiensis (or Bt) toxin genes through genetic modification. In some respects, undesirable vegetation can be controlled in crops tolerant to glyphosate, glufosinate, dicamba, phenoxy auxin, pyridoxine auxin, aryloxyphenoxypropionate, ACC enzyme inhibitors, synthetic auxin herbicides, HPPD inhibitors, PROTOX inhibitors, triazine, and bromobenzonitrile, wherein the tolerant crops possess a single trait, multiple trait, or superimposed trait conferring tolerance to one or more chemicals and / or multiple modes of action. In some respects, undesirable vegetation can be controlled in crops tolerant to ACC enzymes, ALS, or combinations thereof. In some respects, the compositions described herein and other complementary herbicides are applied simultaneously or sequentially as a combined composition or tank mix. These compositions and methods can be used to control undesirable vegetation in crops that have agronomic stress tolerance (including but not limited to drought, cold, high temperature, salinity, water, nutrients, 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 height, and plant structure).

[1136] The compounds and compositions described herein can be used to control the plant species described, which are not limited to Randall, RP (2017). A Global Compendium of Weeds. 3rd Edition, Perth, Western Australia.Weed species found in Australia. In some aspects, the compositions disclosed herein can be used to control undesirable vegetation, including grasses, broadleaf weeds, sedges, and combinations thereof. In some aspects, the compositions disclosed herein can be used to control undesirable vegetation, including but not limited to species of the genera *Acanthospermum*, *Aegilops*, *Agrostis*, *Alopecurus*, *Ambrosia*, *Anthemis*, *Apera*, *Amaranthus*, *Avena*, *Brachiaria*, and *Brachiaria*. Species of the genera *Bromus*, *Chenopodium*, *Cenchrus*, *Cirsium*, *Commelina*, *Cyperus*, *Datura*, *Digitaria*, *Echinochloa*, *Eleusine*, *Atriplex*, *Brassica*, and *Convolvulus*. Species of the genera *Conyza*, *Cassia*, *Euphorbia*, *Geranium*, *Galinsoga*, *Ipomea*, *Lamium*, *Leptochloa*, *Lolium*, *Monochoria*, *Malva*, *Matricaria*, and *Panicum*. Species include those from the genera *Phalaris*, *Polygonum*, *Prosopis*, *Rumex*, *Setaria*, *Sida*, *Sisymbrium*, *Solanum*, *Sorghum*, *Trifolium*, *Xanthium*, *Veronica*, and *Viola*. In some respects, undesirable vegetation includes black grass (*Alopecurus aequalis*), wild oats (*Avena fatua*), barnyard grass (*Echinochloa crus-galli*), and *Stellaria*.media, Abutilontheophrasti, Sesbania exaltata Cory, Anoda cristata, Bidens pilosa, Brassica kaber, Capsella bursa-pastoris, Centaurea cyanus or Cyanus segetum, Galeopsis tetrahit, Galium aparine, Helianthus annuus, Desmodium tortuosum, Lolium multiflorum, Kochia scoparia, Medicago arabica, Mercurialis annua, Myosotis Arvensis), Poppy (Papaverrhoeas), Wild Mustard (Raphanus raphanistrum), Broad-leaf Rumex (Rumex obtusifolius), Russian Thistle (Salsola kali), Wild Mustard (Sinapis arvensis), Sonchus arvensis, Thlaspi arvense, Tagetes minuta, Richardia brasiliensis, Plantago lanceolata, Veronica persica, Amaranthus retroflexus, Winter Rapeseed (Brassicanapus), Chenopodium album), Canada thistle (Cirsium arvense), Cyperus esculentus (Cyperus esculentus), Poinsettia (Euphorbia heterophylla), Lactuca serriola (Lactuca serriola), Lamium purpureum (Lamium purpureum), Matricaria*Chamomilla*, *Matricaria inodora*, *Anthemis arvensis*, common buckwheat (*Fagopyrum esculentum*), wild buckwheat (*Polygonum convulvus*), foxtail millet (*Setaria faberi*), green foxtail millet (*Setaria viridis*), golden foxtail millet (*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. Methods using the compositions described herein can also be used to control herbicide-resistant or tolerant weeds. Exemplary resistant or tolerant weeds include, but are not limited to, inhibitors of acetolactate synthase (ALS) or acetylhydroxy acid synthase (AHAS) inhibitors (e.g., imidazolinone, sulfonylurea, pyrimidinylthiobenzoate, triazolidine, sulfonylamino-carbonyltriazolone), photosystem II inhibitors (e.g., phenylcarbamate, pyridazinone, triazine, triazinone, uracil, amide, urea, benzothiadiazinone, nitrile, phenylpyridazine), acetyl-CoA carboxylase (ACCase) inhibitors (e.g., aryloxyphenoxypropionate, cyclohexanedione, phenylpyrazoline), and synthetic growth inhibitors. Auxin inhibitors (e.g., benzoic acid, phenoxycarboxylic acid, carboxypyridine, quinolinecarboxylic acid), auxin transport inhibitors (e.g., o-benzoamide formate, hemicarbazone), photosystem I inhibitors (e.g., bipyridinium), 5-enolpyruvate-shikimate-3-phosphate (EPSP) synthase inhibitors (e.g., glyphosate), glutamine synthase inhibitors (e.g., glufosinate, dialamidophos), microtubule assembly inhibitors (e.g., benzamide, benzoic acid, dinitroaniline, aminophosphate, pyridine), mitosis inhibitors (e.g., carbamates), very long chain fatty acids (VLCFs) A) Inhibitors (e.g., acetamide, chloroacetamide, oxyacetamide, tetrazolinone), fatty acid and lipid synthesis inhibitors (e.g., dithiophosphates, thiocarbamates, benzofuran, chlorocarbonate), protoporphyrinogen oxidase (PROTOX) inhibitors (e.g., diphenyl ether, N-phenylphthalimide, oxadiazole, oxazolidinone, phenylpyrazole, pyrimidinedione, thiadiazole, triazolone), carotenoid biosynthesis inhibitors (e.g., isoxaflutole, glyphosate, bensulfuron-methyl), phytorepinephrine dehydrogenase (PDS) inhibitors (e.g., amides, aniline pastes) Biotypes of resistant or tolerant weeds include, but are not limited to, biotypes resistant or tolerant to multiple herbicides, biotypes resistant or tolerant to multiple chemical classes, biotypes resistant or tolerant to multiple herbicides, biotypes resistant or tolerant to multiple herbicides, and biotypes with multiple resistance or tolerance mechanisms (e.g., target site resistance or metabolic resistance). Examples of resistant or tolerant weeds include, but are not limited to, biotypes resistant or tolerant to multiple herbicides, biotypes resistant or tolerant to multiple chemical classes, biotypes resistant or tolerant to multiple herbicides, and biotypes with multiple resistance or tolerance mechanisms (e.g., target site resistance or metabolic resistance). 6. Example

[1138] Examples of some aspects of this disclosure are given below by way of non-limitation. Unless otherwise specified, parts and percentages are on a per-weight basis. Example 1 - Pre-emergence application of herbicides

[1139] This example was designed to evaluate the visual growth inhibition of representative weed species when a test herbicide was applied before emergence (“pre-emergence” or “PRE”) of germinating weeds. The weed species tested were: large spike alopecuroides (ALOMY); barnyard grass (ECHCG); large foxtail grass (SETFA); wild oats (AVEFA); common oats (AVESA); split-leaved morning glory (IPOHE); and sunflower (HELAN). Seeds of the desired test plant species were planted in 12.7 cm diameter round plastic pots containing silty loam mineral soil.

[1140] Each herbicide molecule 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, Agriculturex® 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 composition. The diluted herbicide compositions were vigorously mixed and sonicated (if necessary) to dissolve any solids. The diluted herbicide compositions were then diluted with additional deionized water to form the test composition. Each test composition was prepared at a concentration of 0.338 g active ingredient per liter (gai / L), such that 15-mL aliquots of the test compositions were applied to a soil surface containing 4000 g active ingredient per hectare (gai / ha). 15-mL aliquots of each test composition were evenly poured onto the soil containing the planted seeds, and an additional 15 mL of deionized water was evenly poured onto the soil. 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 daytime (illuminated) hours and 22°C during nighttime (dark) hours. The treated material in the pots was kept moist by top irrigation during the test period. After 14 days, the condition of the test plants was visually assessed and compared to control plants, evaluated on a scale of 0% (no damage) to 100% (no emergence or complete death of plants after emergence). Visual assessment of plant damage was based on observed growth inhibition, reduced growth, discoloration, leaf deformity, and necrosis.

[1141] Table 2 presents the data from Example 1. Table 2: Visually observed growth inhibition (%) 14 days after PRE application gai / ha = g ai / ha NT = Not Tested ALOMY = Alopecurus myosuroides AVEFA = Avena fatua AVESA = Avena sativa ECHCG = Echinochloa crusgalli SETFA = Setaria faberi HELAN = Helianthus annuus IPOHE = Ipomoea hederacea Example 2 - Post-Emergence 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 emergence of germinated weeds ("post-emergence" or "POST"). To plastic pots (each with 64 cm 2The soilless growing medium mixture, containing Pro-Mix® BX (Premier Tech Horticulture, Quakertown, Pennsylvania, USA) and Profile® Greens Grade™ (Profile Products LLC, Buffalo Grove, Illinois, USA), is filled with soilless growing medium containing Pro-Mix® BX (Premier Tech Horticulture, Quakertown, Pennsylvania, USA) and Profile® Greens Grade™ (Profile Products LLC, Buffalo Grove, Illinois, USA) with a pH of 5.2 to 6.2 and a minimum organic matter content of 50%. Sow seeds of the desired test plant species in the specified number of prepared pots according to the following planting schedule: Sow Alomy (black grass) 14 days before herbicide application; sow ECHCG, SETFA, AVEFA, and AVESA (common oats) 11 days before herbicide application; sow Ipohea (hedrinleaf morning glory) and HELAN (sunflower) 8 days before herbicide application. Place the pots containing seeds in a greenhouse with a photoperiod of approximately 16 hours / day. For the propagation periods indicated above, maintain the greenhouse at 23°C during daytime (illuminated) hours and 22°C during nighttime (dark) hours. Irrigate the pot with water containing Jack's Professional® 15-5-15 Ca-Mg LX fertilizer (JR Peters Inc., Allentown, Pennsylvania, USA) as needed.

[1143] Each herbicide molecule being tested was dissolved in a formulated solvent mixture containing deionized water, acetone, isopropyl alcohol, 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 a test composition. The test compositions were vigorously mixed and sonicated (if necessary) to dissolve any solids. Each test composition was applied to all plant species at an application rate 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 condition of the treated plants was compared to the control plants by visual assessment and evaluated based on a scoring scale of 0% (no damage) to 100% (complete plant death). Visual assessment of plant injury was based on observed growth inhibition, growth reduction, discoloration, leaf malformation, and necrosis.

[1144] Table 3 presents the data from Example 2. Table 3: Visual growth inhibition (%) 10 days after POST application gai / ha = grams of active ingredient per hectare NT = Not tested ALOMY = Alopecurus myosuroides AVEFA = Avena fatua AVESA = Avena sativa ECHCG = Echinochloa crus - galli SETFA = Setaria viridis HELAN = Helianthus annuus IPOHE = Ipomoea hederacea Example 3 - POST application of herbicides

[1145] This example was designed to evaluate the visual growth inhibition of representative dicotyledonous weed, monocotyledonous weed, and crop plant species when the test herbicides were applied after emergence of the germinated plants (“post - emergence” or “POST”). To plastic pots (each having 64 cm 2The soilless growing medium mixture (surface area) was filled with Pro-Mix® BX (Premier Tech Horticulture, Quakertown, Pennsylvania, USA) and Profile® Greens Grade™ (Profile Products LLC, Buffalo Grove, Illinois, USA) with a pH of 5.2 to 6.2 and a minimum organic matter content of 50%. In some tests, the pots were treated with a fungicide to aid 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. For the propagation period indicated above, the greenhouse was maintained at 23°C during daytime (illuminated) hours and 22°C during nighttime (dark) hours. Irrigate the pots with water containing Jack's Professional® 15-5-15 Ca-Mg LX fertilizer (JR Peters Inc., Allentown, Pennsylvania, USA) as needed. Allow the plants to grow for 7 to 36 days, until they reach their second or third true leaf stage, then treat with each herbicide.

[1146] Each herbicide molecule 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 vigorously mixed and sonicated (if necessary) 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 Chemicals, Collierville, TN, USA) and Tergitol™ 15-S-7 surfactant (Dow Chemical Company, Midland, MIC, USA) (48.5:39:10:1.5:0.02, v / v / v / v / v) to form the test composition, according to the application ratios described in Table 4 below. Each test composition was applied to all test plant species using an elevated track sprayer equipped with an 8002E nozzle (Devries Manufacturing Company, Hollandale, Minnesota, USA). The nozzle was calibrated to a spray height of 0.503 m above the average plant canopy height of 43 cm.2 The test composition was delivered at a concentration of 187 L / ha over the application area. Control or untreated plants were sprayed with the solvent blank (control plants) or untreated (untreated plants) in the same manner. Pots containing the test plants were returned to the greenhouse and watered with subsurface irrigation to prevent removal of the test compound. After approximately 14 days, the condition of the treated plants was visually assessed against the control plants, evaluated on a scale of 0% (no damage) to 100% (complete plant death). Visual assessment of plant damage was based on observed growth inhibition, reduced growth, discoloration, leaf deformity, and necrosis.

[1147] Table 4 presents the data from Example 3.

[1148] The molecules, compositions, and methods described in the appended claims are not limited to the specific molecules, compositions, and methods described herein (which are intended to illustrate several aspects of the claims), and any functionally equivalent molecules, compositions, and methods are intended to fall within the scope of these claims. Various modifications to these molecules, compositions, and methods, in addition to those shown and described herein, are also intended to fall within the scope of the appended claims. Furthermore, although only certain representative molecules, compositions, and method steps disclosed herein are specifically described, other combinations of molecules, compositions, and method steps are intended to fall within the scope of the appended claims, even if not specifically stated otherwise. Therefore, combinations of steps, elements, molecules, compositions, or elements may be expressly referred to herein; however, other combinations of steps, elements, molecules, compositions, and elements are included even if not expressly stated otherwise. The term "comprising" and its variations are used synonymously with the term "including" and its variations as used herein and are open-ended and non-restrictive terms. Although the terms “comprising” and “including” have been used herein to describe various aspects, the terms “consistently composed of” and “comprises of” may also be used in place of “comprising” and “including” to provide more specific aspects and are also disclosed. Except where indicated by example or elsewhere, all figures used in the specification and claims to indicate amounts of ingredients, reaction conditions, etc., should be understood to be interpreted according to the number of significant figures and ordinary rounding methods, and not to attempt to limit the application of the doctrine of equivalence to the scope of the claims.

Claims

1. A molecule based on a 5-membered ring having formula (I): Formula (I) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 2 Choose from the group consisting of: methyl and cyclopropyl; R 3 Choose from the group consisting of: H, methyl, and methoxy; R 4 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C3-C 10 )-cycloalkyl, (C4-C 16 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C4-C 16 )-Aryl, (C5-C 18 )-alkylaryl, (C1-C 16 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C 16 )-alkoxy, (C4-C 16 )-arylalkoxy, (C1-C 10 )-alkylcyano, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C 10 )-alkylthio-(C1-C 10 )-alkyl, (C0-C 10 )-alkylsulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C) 10 )-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C 10 )-alkyl-C(=O)QR 70 heteroaryl-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C 10 )-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C 10 )-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C 10 )-alkyl-C(=O)QR 71 hydroxyl-(C1-C) 10 )-alkyl-C(=O)QR 70 (C1-C) 10 )-alkylthio-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 16 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-Heterocyclic alkyl, (C1-C 10 )-Heterocyclic aryl, (C1-C 10 (C3-C8)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C1-C 10 )-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R 72 R 73 N-sulfonyl group, (C1-C 10 )-alkoxy-NR 74 -sulfonyl group and aryloxysulfonyl group; Q selects from the following groups: O, S, and NR. 72 ; R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they can form substituted or unsubstituted rings; Or an agriculturally acceptable salt having the molecule of formula (I).

2. The molecule of claim 1, wherein R 2 It is methyl, and R 3 It is a methyl group.

3. The molecule of claim 1, wherein R 2 It is methyl, and R 3 It is a methoxy group.

4. The molecule of claim 1, wherein R 2 It is cyclopropyl, and R 3 It is H.

5. The molecule according to any one of claims 1-4, wherein R 1 It is H.

6. The molecule according to any one of claims 1-4, wherein R 1 It is F.

7. The molecule according to any one of claims 1-6, wherein R 5 It is H.

8. The molecule according to any one of claims 1-7, wherein X 1 and X 2 It is O.

9. A herbicidal composition comprising a molecule having a 5-membered ring based form of formula (I): Formula (I) in: X 1 and X 2 Choose independently from the following groups: O and S; Y is selected from the following groups: O, NH, NR 72 ; and S; R 1 Choose from the following groups: H and F; R 2 Choose from the group consisting of: methyl and cyclopropyl; R 3 Choose from the group consisting of: H, methyl, and methoxy; R 4 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C3-C 10 )-cycloalkyl, (C4-C 16 )-alkylcycloalkyl, (C5-C 16 )-polycycloalkyl, (C6-C 16 )-alkyl polycycloalkyl, (C3-C 10 )-Heterocyclic alkyl, (C4-C 16 )-Aryl, (C5-C 18 )-alkylaryl, (C1-C 16 )-Heteroaryl, (C4-C 16 )-alkylheteroaryl, (C1-C 16 )-alkoxy, (C4-C 16 )-arylalkoxy, (C1-C 10 )-alkylcyano, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkoxy-(C1-C 10 )-alkyl, (C1-C 10 )-alkylthio-(C1-C 10 )-alkyl, (C0-C 10 )-alkylsulfonyl-R 74 NR 72 R 73 SiR 75 R 76 R 77 (C1-C) 10 )-alkyl-SiR 75 R 76 R 77 R 78 R 79 C=N、(C1-C 10 )-alkyl-C(=O)QR 70 aryl-(C1-C 10 )-alkyl-C(=O)QR 70 heteroaryl-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 10 )-cycloalkyl-(C0-C 10 )-alkyl-C(=O)QR 70 R 70 QC(=O)-(C1-C 10 )-alkyl-C(=O)QR 71 R 70 QC(=O)Q-(C1-C 10 )-alkyl-C(=O)QR 71 hydroxyl-(C1-C) 10 )-alkyl-C(=O)QR 70 (C1-C) 10 )-alkylthio-(C1-C 10 )-alkyl-C(=O)QR 70 (C3-C) 16 )-alkylene-amino-oxo, and their salts; R 5 Choose from the following groups: H, hydroxyl, (C1-C) 16 )-alkyl, (C1-C 16 )-Haloalkyl, (C1-C 10 )-alkylcyano, (C3-C 16 )-Alkenyl, (C3-C 16 )-Alynyl group, (C4-C 18 )-Aryl, (C5-C 16 )-alkylaryl, (C1-C 10 )-alkoxy, (C1-C 16 )-alkyl-C(=O)OR 70 (C1-C) 10 )-Heterocyclic alkyl, (C1-C 10 )-Heterocyclic aryl, (C1-C 10 (C3-C8)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C1-C 10 )-alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, R 72 R 73 N-sulfonyl group, (C1-C 10 )-alkoxy-NR 74 -sulfonyl group and aryloxysulfonyl group; Q selects from the following groups: O, S, and NR. 72 ; R 70 R 71 R 72 R 73 and R 74 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C4-C 16 )-Aryl, (C1-C 16 )-Heteroaryl, (C5-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C1-C 16 )-Arylalkoxy, NR 78 R 79 And R 72 and R 73 Together they can form substituted or unsubstituted rings; R 75 R 76 and R 77 Choose independently the following groups: (C1-C 16 )-alkyl and aryl; and R 78 and R 79 Independently select from the following groups: H, (C1-C 16 )-alkyl, (C1-C 16 )-alkoxy, (C1-C 16 )-alkylaryl, (C1-C 16 )-Haloalkyl, (C4-C 16 )-Aryl, (C1-C 16 )-heteroaryl, and R 78 and R 79 Together they can form substituted or unsubstituted rings; Or an agriculturally acceptable salt having the molecule of formula (I); as well as An agriculturally acceptable carrier.

10. The composition of claim 9, wherein R 2 It is methyl, and R 3 It is a methyl group.

11. The composition of claim 9, wherein R 2 It is methyl, and R 3 It is a methoxy group.

12. The composition of claim 9, wherein R 2 It is cyclopropyl, and R 3 It is H.

13. The composition according to any one of claims 9-12, wherein R 1 It is H.

14. The composition according to any one of claims 9-12, wherein R 1 It is F.

15. The composition according to any one of claims 9-14, wherein R 5 It is H.

16. The composition according to any one of claims 9-15, wherein X 1 and X 2 It is O.

17. The composition according to any one of claims 9-16, wherein it comprises an auxiliary agent.

18. The composition according to any one of claims 9-17, wherein it comprises a safety agent.

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 suspension emulsions, oil solutions, oil suspensions, oil dispersions, oil emulsions, oil microemulsions, oil suspension emulsions, self-emulsifying formulations, gels, pastes, powders, granules, particles, and spreading materials.

20. A method for controlling unwanted vegetation, the method comprising applying a molecule as described in any one of claims 1-8 or a composition as described in any one of claims 9-19 to the vegetation or an area adjacent to the vegetation, or to soil or agricultural surface water to limit the emergence or growth of the vegetation.

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