Molecules having certain pesticidal utilities, and intermediates, compositions, and processes related thereto

Abstract

To provide compounds having pesticidal utility against pests in phyla Nematoda, Arthropoda, and / or Mollusca, processes to produce such compounds and intermediates used in such processes, compositions containing such compounds, and processes of using such compounds against such pests.SOLUTION: There are provided compounds having the following formula.SELECTED DRAWING: None

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 875,079, filed on July 17, 2019 of the specification.

[0002] The present disclosure relates to the field of molecules having pesticidal utility against pests of the phyla Nematoda, Arthropoda, and Mollusca, to processes for generating such molecules and intermediates used in such processes, to compositions containing such molecules, and to processes for using such molecules against such pests. These molecules can be used, for example, as nematicides, acaricides, insecticides, acarid repellents, and mollusc repellents.

Background Art

[0003] "Many of the most dangerous human diseases are transmitted by vector insects" (Rivero, A. et al., Insect Control of Vector - Borne Di seases: When is Insect Resistance a Probl em? Public Library of Science Pathogens, 6 (8)(2010)). Historically, vector - borne diseases such as malaria, dengue, yellow fever, bubonic plague, and typhus exanthematicus have been the cause of more human diseases and deaths from the 1600s to the early 1900s than all other causes combined (Guble r D., Resurgent Vector - Borne Diseases as a Global Health Problem, Emerging Infecti ​​​​​​​ ous Diseases, Vol.4, No.3, July - September(1 998)). Currently, vector - borne diseases are responsible for approximately 17% of parasitic and infectious diseases worldwide and are estimated to infect approximately 250 million people globally with malaria, resulting in approximately 800,000 deaths annually , with approximately 85% of these deaths occurring in children under 5 years of age. Additionally, between 250,000 and 500,000 cases of dengue hemorrhagic fever occur annually (Matthews, G., Integrated Vector r Management: controlling vectors of malaria and other insect vector - borne diseases(2011)). The role of vector control in the prevention and control of infectious diseases is significant . However, resistance to insecticides (including multi - drug resistance to insecticides) has emerged in all insect species that are major vectors of human diseases (Rivero, A. et al.)

[0004] Annually, insects, plant pathogens, and weeds damage more than 40% of the total potential food production . Despite the application of pesticides and the use of various non - chemical controls such as crop rotation and biological control , this loss still occurs. If even a portion of this food could be saved, it could potentially be used to feed more than 3 billion malnourished people worldwide (Pimental, D., Pest Control in World Agriculture , Agricultural Sciences - Vol.II(2009)).

[0005]

[0005] Plant - parasitic nematodes are one of the most widespread pests and are often the most difficult and costly to control . Nematode - caused losses range from approximately 9% (in developed countries) to approximately 15 is estimated to be a developing country. However, in the United States, surveys of various crops in 35 states have shown that losses due to nematodes can exceed 25% (Nicol, J. et al., Current Nematode Threats to World Agriculture, Genomic and Molecular Genetics of Plant-Nematode Interactions (Eds. Jones, J. et al.), Chapter 2, (2011)). For snails and slugs, which are considered pests of lower economic importance than insects or nematodes, it should be noted that in certain regions, they can substantially reduce yields, have a profound impact on the quality of harvested products, and may even transmit diseases to humans, animals, and plants. Although only a few dozen species are major regional pests, a handful of species are important pests on a global scale. In particular, snails and slugs can affect a wide variety of agricultural and horticultural crops, such as arable crops, livestock crops, and fiber crops; vegetables; shrubs and fruit trees; herbs; and ornamental plants (Speiser, B., Molluscicides, Encyclopedia of Pest Management (2002)). l, J. et al., Current Nematode Threats to W orld Agriculture, Genomic and Molecular G enetics of Plant-Nematode Interactions (E ds. Jones, J. et al.), Chapter 2, (2011)).

[0006] are considered pests of lower economic importance than insects or nematodes but in certain regions, they can substantially reduce yields, have a profound impact on the quality of harvested products and may even transmit diseases to humans, animals, and plants. Although only a few dozen species are major regional pests, a handful of species are important pests on a global scale. In particular, they can affect a wide variety of agricultural and horticultural crops, such as arable crops livestock crops, and fiber crops; vegetables; shrubs and fruit trees; herbs; and ornamental plants (Speiser, B., Molluscicides, Encyclopedia of Pest Management (2002)). livestock crops, and fiber crops; vegetables; shrubs and fruit trees; herbs; and ornamental plants; ( Speiser, B., Molluscicides, Encyclopedia of Pest Management (2002)).

[0007] Termites cause damage to all types of private and public buildings, as well as agricultural and forest resources. In 2003, it was estimated that termites caused annual damage exceeding $20 billion worldwide (Su, N.Y., Overview of the global distribution and control of the global distribution and control of the Formosan subterranean termite,Sociobiolo gy 2003,41,177-192).

Summary of the Invention

Problems to be Solved by the Invention

[0008] Therefore, due to many reasons including the above reasons, there is a need for new pesticides .

Means for Solving the Problems

[0009] Definition The examples given in this definition are generally non-inclusive and should not be construed as limiting the molecules disclosed herein. Substituents should be understood to comply with chemical bonding rules and steric compatibility restrictions in relation to the specific molecule to which they are attached to .

[0010] "Alkenyl" means an acyclic unsaturated (at least one carbon-carbon double bond) consisting of carbon and hydrogen, a branched or unbranched substituent, for example, vinyl, allyl, butenyl, pentenyl and hexenyl

[0011] "Alkenyloxy" means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyl oxy, butenyloxy, pentenyloxy, hexenyloxy

[0012] "Alkoxy" means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy sy, propoxy, isopropoxy, butoxy, isobutoxy and tert-butoxy mean

[0013] "Alkyl" means an acyclic, saturated, branched or unbranched substituent consisting of carbon and hydrogen For example, it means methyl, ethyl, propyl, isopropyl, butyl, and tert-butyl. .

[0014] "Alkynyl" refers to an acyclic, unsaturated (with at least one carbon-carbon triple bond) substituent consisting of carbon and hydrogen, which can be branched or unbranched, such as ethynyl, propargyl, butynyl and pentynyl.

[0015] "Alkynyloxy" refers to an alkynyl further consisting of a carbon-oxygen single bond, such as pentyloxy, hexyloxy, heptyloxy, and octynyloxy.

[0016] "Aryl" refers to a cyclic aromatic substituent consisting of hydrogen and carbon, such as phenyl, naphthyl and biphenyl.

[0017] "Cycloalkenyl" refers to a monocyclic or polycyclic substituent consisting of carbon and hydrogen and being unsaturated (with at least one carbon-carbon double bond), such as cyclobutenyl, cyclopentenyl , cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl, tetrahydro naphthyl, hexahydronaphthyl, and octahydronaphthyl.

[0018] "Cycloalkenyloxy" refers to a cycloalkenyl further consisting of a carbon-oxygen single bond, such as cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo [2.2.2]octenyloxy.

[0019] "Cycloalkyl" refers to a monocyclic or polycyclic saturated substituent consisting of carbon and hydrogen, such as , cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2. 2] means octyl and decahydronaphthyl.

[0020] "Cycloalkoxy" further means a cycloalkyl consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy and bicyclo[2.2.2]octyloxy.

[0021] "Halo" means fluoro, chloro, bromo and iodo.

[0022] "Haloalkoxy" further means an alkoxy consisting of 1 to the maximum possible number of identical or different halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy , chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy and pentafluoroethoxy.

[0023] "Haloalkyl" further means an alkyl consisting of 1 to the maximum possible number of identical or different halos, for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloro methyl, trichloromethyl and 1,1,2,2-tetrafluoroethyl.

[0024] "Heterocyclyl" means a cyclic substituent that can be fully saturated, partially unsaturated or fully unsaturated, and its cyclic structure contains at least one carbon atom and at least one he tero atom, and the hetero atom is nitrogen, sulfur or oxygen. Examples of aromatic heterocyclyl include benzofuranyl, benzisothiazolyl, benzisoxazolyl, ben zoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, inda zolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl , etc. , isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrro ryl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thia zolyl, thienyl, triazinyl and triazolyl, but not limited to these. Examples of fully saturated heterocyclyl include piperazinyl, piperidinyl, morpho linyl, pyrrolidinyl, tetrahydrofuranyl and tetrahydropyranyl, but not limited to these. Examples of partially unsaturated heterocyclyl include 1,2,3,4 -tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1 H-pyrazolyl, 4,5-dihydro-isoxazolyl and 2,3-dihydro-[1,3, 4]-oxadiazolyl, but not limited to these.

BEST MODE FOR CARRYING OUT THE INVENTION

[0025] The structure of "Formula 1" or "Formula 1-A":

CHEMICAL FORMULA

[0026] In one embodiment, Ar 1 and Ar 2 are not ortho to each other (however, they can be meta or para , for example, in a 5-membered ring they are 1,3, and in a 6-membered ring they are 1,3 or 1 ,4).

[0027] In another embodiment, Ar 1 is substituted phenyl. This embodiment is Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl link and / or L's It can be used in combination with other embodiments.

[0028] In another embodiment, Ar 1 is a substituted phenyl having one or more substituents selected from C1-C6 haloalkyl and C1-C6 haloalkoxy This embodiment can be used in combination with other embodiments of Het , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L.

[0029] In another embodiment, Ar 1 is a substituted phenyl having one or more substituents selected from CN, SF5, CH3, CF3, SCF3, OCF3, OCH2CF3 and OC2F5. This embodiment can be used in combination with other embodiments of Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L.

[0030] In another embodiment, Ar 1 is a substituted phenyl having one or more substituents selected from CF3, OCF3 and OC2F5. This embodiment can be used in combination with other embodiments of Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L can be used in combination with

[0031] In another embodiment, Ar 1 is a substituted pyridyl. This embodiment is Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0032] In another embodiment, Ar 1 is a substituted pyridyl having one or more substituents selected from C1-C6 haloalkyl and C1-C6 haloalkoxy . This embodiment is Het , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0033] In another embodiment, Ar 1 is a substituted pyridinonyl. This embodiment is Het, A r 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0034] In another embodiment, Ar 1 is oxo, C1-C6 haloalkyl and C1-C6 halo It is a substituted pyridinonyl having one or more substituents selected from lucoxy. In this embodiment state, Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl ri nk and / or can be used in combination with other embodiments of L.

[0035] In another embodiment, Het is benzofuranyl, benzisothiazolyl, benzisox azolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, ph ranil, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyr midinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thia zolylinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperi dinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5 -dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl and 2,3-dihydro ro-[1,3,4]-oxadiazolyl selected from.

[0036] In another embodiment, Het is selected from one of Het-A to Het-M. This implementation form, Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R4 and Q 1 and R 2 and R 4 hydrocarbyl may be used in combination with the link and / or other embodiments of L.

Chemical formula

[0037] In another embodiment, Het is triazolyl. This embodiment is Ar 1 and Ar 2 and R 1 and R 2 and R 3 and R 4 and Q 1 and R 2 and R 4 hydrocarbyl link and / or other embodiments of L may be used in combination.

[0038] In another embodiment, Het is 1,2,4-triazolyl. This embodiment is A r 1 and Ar 2 and R 1 and R 2 and R 3 and R 4 and Q 1 and R 2 and R 4 hydrocarbyl link and / or may be used in combination with other embodiments of L.

[0039] In another embodiment, Het is 1,2,3-triazolyl. This embodiment is A r 1 and Ar 2 and R 1 and R 2 and R 3 and R 4 and Q 1 and R 2 and R 4 hydrocarbyl link and may be used in combination with other embodiments of L.

[0040] In another embodiment, Het is tetrazolyl. This embodiment is further illustrated by Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 Hydrocarbyl link and / or L other It may be used in combination with the embodiment of

[0041] In another embodiment, Het is 1,2,3,4-tetrazolyl. , Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 Hydrocarbyl Link and / or may be used in combination with other embodiments of L.

[0042] In another embodiment, Het is oxadiazolyl. This embodiment is further characterized in that Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 Hydrocarbyl link and / or L may be used in combination with other embodiments.

[0043] In another embodiment, Het is 1,3,4-oxadiazolyl. Ar 1 , Ar 2 , R 1 , R 2, R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0044] In another embodiment, Het is 1,2,4 - oxadiazolyl. This embodiment Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0045] In another embodiment, Het is thiadiazolyl. This embodiment, Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0046] In another embodiment, Het is 1,3,4 - thiadiazolyl. This embodiment Ar 1 , Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and or can be used in combination with other embodiments of L.

[0047] In another embodiment, Het is pyrazolyl. This embodiment can be used in combination with Ar 1 、Ar 2 、R 1 、R 2 、R 3 、R 4 、Q 1 、R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L can be used in combination.

[0048] In another embodiment, Het is imidazolyl. This embodiment can be used in combination with Ar 1 、Ar 2 、 R 1 、R 2 、R 3 、R 4 、Q 1 、R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L can be used in combination.

[0049] In another embodiment, Ar 2 is phenyl. This embodiment can be used in combination with Ar 1 、Het, R 1 、R 2 、R 3 、R 4 、Q 1 、R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L can be used in combination.

[0050] In another embodiment, Ar 2 is substituted phenyl. This embodiment can be used in combination with Ar 1 、Het 、R 1 、R 2 、R 3 、R 4 、Q 1 、R 2 and R 4The hydrocarbyl link and / or that of L can be used in combination with other embodiments.

[0051] In another embodiment, Ar 2 is a substituted phenyl having one or more substituents selected from C1-C6 alkyl. This embodiment is for Ar 1 , Het, R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 The hydrocarbyl link and / or other embodiments of L can be used in combination therewith.

[0052] In another embodiment, Ar 2 is a substituted phenyl having one or more substituents, and the substituents are H, F, Cl, Br, I, CN, OH, OCH3, OCH2OCH3, CHF2 , CF3, CH2CH3, CH(CH3)2 and CH3. This embodiment is 1 for Ar 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 The hydrocarbyl link and / or or other embodiments of L can be used in combination therewith.

[0053] In another embodiment, Ar 2 is a substituted pyridyl. This embodiment is 1 for Ar , Het 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 The hydrocarbyl link and / or that of L It can be used in combination with other embodiments.

[0054] In another embodiment, Ar 2 is a substituted pyridyl having one or more substituents selected from C1-C6 alkyl . This embodiment can be used in combination with other embodiments of Ar 1 , Het, R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L and can be used in combination.

[0055] In another embodiment, Ar 2 is a substituted phenyl having one or more substituents, and the substituent is CH3. This embodiment can be used in combination with other embodiments of Ar 1 , Het, R 1 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L and can be used in combination .

[0056] In another embodiment, R 1 is H. This embodiment can be used in combination with other embodiments of Ar 1 , Het, Ar 2 , R 2 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L and can be used in combination.

[0057] In another embodiment, R 2 is (J), H, C1-C6 alkyl, C1-C6 alkyl- O-C(=O)C1-C6 alkyl, C1-C6 alkyl-O-C(=O)N(RR y ) or (C1-C6 alkyl)S-(Het-1). This embodiment is for Ar 1 , He t, Ar 2 , R 1 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0058] In another embodiment, R 2 is (J), H, CH3, C1-C6 alkyl, CH2OC( =O)CH(CH3)2, CH2OC(=O)N(H)(C(=O)OCH2Ph) or CH2S(3,4,5-trimethoxy-2-tetrahydropyran). This embodiment is for Ar 1 , Het, Ar 2 , R 1 , R 3 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl li nkages and / or can be used in combination with other embodiments of L.

[0059] In another embodiment, R 3 is substituted phenyl. This embodiment is for Ar 1 , Het, Ar 2 , R 1 , R 2 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or can be used in combination with other embodiments of L.

[0060] In another embodiment, R 3 is a substituted phenyl, and the substituted phenyl is H, F, Cl , CN, OH, NO2, NH2, NHR x , NR x R y , C1-C6 alkyl, C3-C 6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, S(C1-C6 alkyl), S(C1-C6 haloalkyl), C1-C6 haloalkyl, (C1-C6 a lkyl)O(C1-C6 haloalkyl), (C1-C6 alkyl)O(C1-C6 alky l), (C1-C6 alkyl)S(C1-C6 haloalkyl), (C1-C6 alkyl) S(=O)(C1-C6 haloalkyl), (C1-C6 alkyl)S(=O)2(C1- C6 haloalkyl), (C1-C6 alkyl)S(C1-C6 alkyl), (C1-C6 alkyl)S(=O)(C1-C6 alkyl), (C1-C6 alkyl)S(=O)2( C1-C6 alkyl), C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), (Het-1) and phenyl, and has one or more substituents selected therefrom. This embodiment can be used in combination with the carbylline link and / or other embodiments of L, Ar 1 , Het, Ar 2 , R 1 , R 2 , R 4 , Q 1 , R 2 and R 4 hydro carbylline link and / or other embodiments of L.

[0061] In another embodiment, R 3 is a substituted phenyl, and the substituted phenyl is H, F, Cl , CN, NO2, NH2, NHCH3, NHCH2CH3, NHCH2CH2CH3, N (CH3)2, N(CH2CH3)2, N(CH2CH2CH3)2, N(CH3)C( =O)CH3, N(CH2CH3)C(=O)CH3, CH3, CH2CH3, CH2C H2CH3, CH2CH2CH2CH3, CF3, CHF2, CH2CF3, CF2CH 3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)(C2H5), OH, OCH3, OCH2CH3, OCH2CH2CH3, OCH2CF3, OCH2CH2C F3, OCH2CH2CH2CF3, CH(CH3)O(CH3), CH2OCH3, C H2OCH2CH3, CH2OCH2CF3, OCH(CH3)(CH2CH3), CH (CH3)O(CH2CH3), CH(CF3)O(CH3), CH(CH3)S(CH 3), C(=O)CH3, C(=O)OCH3, piperidinyl and phenyl selected from one or more substituents. This embodiment is Ar 1 , Het, Ar 2 , R 1 , R 2 , , R 4 , Q 1 , R 2 and R 4 hydrocarbyl link and / or combined with other embodiments of L can be used.

[0062] In another embodiment, R 3 is a substituted phenyl, the substituted phenyl has more than one substituent , and at least one pair of the substituents are not ortho to each other. This embodiment is A r 1 , Het, Ar 2 , R 1 , R 2 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl link It can be used in combination with / or other embodiments of L.

[0063] In another embodiment, R 3 is C1 - C6 alkylphenyl. This embodiment is for A r 1 , Het, Ar 2 , R 1 , R 2 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and It can be used in combination with / or other embodiments of L.

[0064] In another embodiment, R 3 is (Het - 1). This embodiment is for Ar 1 , Het, Ar 2 , R 1 , R 2 , R 4 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or L's other embodiments can be used in combination.

[0065] In another embodiment, R 4 is H. This embodiment is for Ar 1 , Het, Ar 2 , R 1 , R 2 , R 3 , Q 1 , R 2 and R 4 hydrocarbyl linkages and / or other embodiments of L can be used in combination.

[0066] In another embodiment, Q 1 is O. This embodiment is for Ar 1 , Het, Ar 2 , R 1 , R 2 , R3 , R 4 , R 2 and R 4 hydrocarbyl link and / or other embodiments of L may be used in combination with.

[0067] In another embodiment, Q 1 is S. This embodiment is Ar 1 , Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , R 2 and R 4 hydrocarbyl link and / or other embodiments of L may be used in combination with.

[0068] In another embodiment, R 2 and R 4 are hydrocarbyl links, and the hydrocarbyl link is substituted with oxo or C1-C6 alkyl. This embodiment is Ar 1 , He t, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 and / or may be used in combination with other embodiments of L used.

[0069] In another embodiment, R 2 and R 4 are hydrocarbyl links, and the hydrocarbyl link is CH2C(=O), C(C(OH)(CH3)2)C(=O), C(cyclop ropyl)C(=O), C(CH3)2C(=O), CFHC(=O), CBrHC(=O ), CH(CH3)C(=O), CH2CH2, CH2C(OH)(CH3), CH2C H2CH2, CH2CH2C(=O), CH2CH(CH3)CH2, N(CH3)C( =O), N(CH2CH3)C(=O), CH=C(CH3) or CH2CH(CH3) is. This embodiment is Ar 1 , Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 and / or can be used in combination with other embodiments of L.

[0070] In another embodiment, L is a bond, CH2, CH2CH2, CH2CH(CH3), CH2 C(CH3)2, CH2CH(CH2CH3), CH=CH, CH(CH3)CH2, C (CH3)2CH2, CHBrCH2, CH2C(cyclopropyl), CH(CH2CH 3)CH2, C(CH3)=CH, CH2CH2CH2, CH(CH3)CH(CH3) , CH2CH2CH2CH2, C≡CCH2CH2, cyclopropyl or cyclohexyl is. This embodiment is Ar 1 , Het, Ar 2 , R 1 , R 2 , R 3 , R 4 , Q 1 as well as to / or R 2 and R 4 can be used in combination with other embodiments of the hydrocarbyl link .

[0071] In one embodiment, compounds disclosed herein are also provided, where (A) Ar 1 is substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyridinonyl or is substituted pyrimidinyl, and the substituted phenyl, substituted pyridyl and substituted pyrimidinyl are independently H, CN, SF5, oxo, C1-C6 alkyl, C1-C6 alkoxy, S (C1-C6 haloalkyl), C1-C6 haloalkyl and C1-C6 haloalkoxy or has one or more substituents selected from: (B) Het is Het-A to Het-M

Chemical formula

[0072] In another embodiment, the compounds provided herein have the following formula ("Formula 2").

Chemical formula

[0073] In another embodiment, the compounds provided herein have a structure selected from the compounds listed in Table-1 and Tables 1A, 1B, 1C.

[0074] In another embodiment, the compounds provided herein have the structure of Formula 2 and are selected from the compounds listed in Table-1 and the group consisting of H1, H2, H3, H4, H6, H7, H8, H10, H11, H12, H13, H14, H15, H16, H17, H20 and H21.

[0075] In another embodiment, the compounds provided herein have the structure of Formula 3, 4 and / or 5 and are selected from the compounds listed in Tables 1A, 1B and / or 1C and the group consisting of J30, J34, J39 , J42, J49, J50, J60, J62, J66, J67, J72, J74, J81 , J87, J88, J90, J94, J97, J117, J119, J120, J123 ​​, J124, J139, J141, J165, J167, J168, J173, J174 , J178, J179, J180, J181, J182, J185, J186, J187 , J188, J189, J190, J194, J195, J197, J199, J200 , J203, J204, J205, J206, J214, J215, J220, J221 , J222, J226, J228, J229, J230, J232, J233, J234 , J236, J237, J240, J241, J244, J245, J249, J250 , J256, J262, J265, J267, J271, J274, J276, J280 , J281, J286, J289, J291, J297, J298, J299, J300 , consisting of J303, J304, J306, J308, J309, J310 and J311 selected from the group. In another embodiment, the provided compound is J30, J34, J39, J42, J49, J50, J60, J62, J66, J67, J72, J74, J81, J87, J88, J90, J94, J97, J117, J119, J120, J123, J124, J139, J141, J165, J167, J168, J173, J174, J178, J179, J180, J181, J182, J185, J186, J187, J188, J189, J190, J194, J195, J197, J199, J200, J203, J204, J205, J206, J214, J215, J220, J221, J222, J226, J228, J229, J230, J232, J233, J234, J236, J237, J240, J241, J244, J245, J249, J250, J256, J262, J265, J267, J271, J274, J276, J280, J281, J286, J289, J291, J297, J298, J299, J300, J303, J304, J306, J308, J309, J310, J311, J312, J314, J315, J16, J318, J319, J324, J325, J326, J 327, J328, J344, J350, J362, J363, J364, J365, J 366, J368, J510, J539, J570, J574, J645, J646, J 647, J648, J649, J650, J652, J653, J654, J655, J 656, J657, J659, J663, J684, J686, J716, J719, J 742, J745, J747, J751, J778, J779, 780, J781, J7 82, J783, J784, J785, J786, J787, J788, J789, J7 90, J791, J792, J793, J794, J795, J796, J797, J7 98 and selected from the group consisting of J799.

[0076] In another embodiment, the compounds provided herein are selected from the compounds listed in Table - 3 and have a structure selected.

[0077]

Table 1

[0078]

Table 2

[0079]

Table 3

[0080]

Table 4

[0081]

Table 5

[0082]

Table 6

[0083]

Table 7

[0084]

Table 8

[0085]

Table 9

[0086]

Table 10

[0087]

Table 11

[0088]

Table 12

[0089]

Table 13

[0090]

Table 14

[0091]

Table 15

[0092]

Table 16

[0093]

Table 17

[0094]

Table 18

[0095]

Table 19

[0096]

Table 20

[0097]

Table 21

[0098]

Table 22

[0099]

Table 23

[0100] In one embodiment, a process is also provided that includes applying a compound provided herein in an amount sufficient to control such pests at a location to control the pests. ​ 。

[0101] In a further embodiment, the pest is Spodoptera litura (BAW), Helicoverpa armigera (CL) or Aedes albopictus (YFM). 。

[0102] In another embodiment, the compounds provided herein have at least one 2 H or at least one 14 C.

[0103] In another embodiment, a composition is also provided that includes a compound provided herein and at least one other compound having insecticidal, herbicidal, acaricidal , nematicidal or fungicidal activity. 。

[0104] In another embodiment, a composition is also provided that includes a compound provided herein and seeds.

[0105] In another embodiment, a process is also provided that includes applying a compound provided herein to a genetically modified plant or genetically modified seed that has been genetically modified to express one or more specific traits. 。 。

[0106] In another embodiment, a process is also provided that includes orally administering or topically applying a compound provided herein to a non-human animal to control internal and / or external parasites. 。 。

[0107] Many of the molecules of Formula 1 can exist in two or more tautomeric 1 , R 2 or R 4 forms, such as when is H (see, for example, "Scheme TAU" below). For the sake of simplicity of the scheme, all molecules are shown as if they exist as a single tautomer. 。 。 All possible tautomeric forms are included within the scope of Formula 1, and no inference should be made regarding whether the molecule exists as the tautomeric form in which it is depicted.

Chemical formula

[0108] The molecule of Formula 1 generally has a molecular weight of from about 400 Daltons to about 1200 Daltons. However, generally, it is preferred when the molecular weight is from about 300 Daltons to about 1000 Daltons, and even more preferred when the molecular weight is from about 400 Daltons to about 750 Daltons.

[0109] Preparation of Thiobiuret The thiobiurets disclosed herein are prepared from the corresponding isocyanates, Ar 1 -Het- Ar 2 -L-NCO (1-2). Usually, those isocyanates are not isolated, but are instead formed in situ from suitable precursors and used directly in the preparation of the thiobiuret. One such suitable precursor is amine (1-1), which can be converted to an isocyanate by using one of several common reagents, such as phosgene, diphosgene, triphosgene or carbonyldiimidazole, in a mixed solvent system, such as dichloromethane and water or diethyl ether and water, in the presence of a base, such as sodium bicarbonate or triethylamine, at a temperature of from about -10 °C to about 50 °C (Scheme 1, Step a).

Chemical formula

[0110] Instead, the isocyanate is an acyl azide, Ar 1 -Het-Ar 2 -L-C(=O )N3 (1-4) (which is thus the corresponding carboxylic acid precursor Ar 1 -He t-Ar 2 -L-CO2H (1-3)) can also be generated via the Curtius rearrangement. The formation of the acyl azide (Scheme 1, step b) occurs either with ethyl chloroformate and sodium azide in the presence of an amine base, such as tri ethylamine, or by treating the acid with diphenylphosphoryl azide in the presence of an amine salt group, such as triethylamine. The acyl azide is then subjected to the Curtius rearrangement (which may need to be heat-induced in some cases) to afford the corresponding isocyanate (1-2). Depending on the properties of the particular acyl azide, this rearrangement can occur spontaneously at ambient temperature or may need to be heated to about 40 °C to about 100 °C in a suitable solvent, such as toluene or acetonitrile or an ether-based solvent, such as di xane or tetrahydrofuran. Aryl acetic acid azide compounds are known, but often, due to their reactivity, these are not isolated as pure solids. Thus, the acyl azide intermediate is not always fully characterized but the isocyanate can be generated simply by direct heating without characterization. The isocyanate, Ar -Het-Ar -L-NCO (1-2) is reacted with about 0.1 to about 2 equivalents of an inorganic base, such as cesium carbonate or sodium hydride, in the presence of N-arylthiourea

[0111] 1 -Het-Ar 2 -L-NCO(1-2) in the presence of about 0.1 to about 2 equivalents of an inorganic base, such as cesium carbonate or sodium hydride, in the presence of N-arylthiourea ​By directly treating with element (2-1), thiobiuret can be formed (2 -2, Scheme 2). The reaction is carried out at a temperature of about 0 °C to about 100 °C, preferably about 20 °C to about 80 °C in an aprotic solvent or solvent mixture selected from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloro ethane, dichloromethane or a mixture thereof, but it is preferred to use acetonitrile.

Chemical formula

[0112] The thiobiuret (2-2) generated in situ can be converted into various cyclization analogs without purification (Scheme 3), or they can be cyclized after isolation from the reaction medium. The cyclization reaction is carried out by treating with an α-haloester, such as methyl bromoacetate, to form a 2-imino-1,3-thiazolin- 4-one (3-1, step a) unsubstituted or mono- or di-substituted with R 5 , or by treating with an adjacent dihalide, such as 1-bromo -2-chloroethane or 1,2-dichloroethane, to form a 2-imino-1,3-thiazoline (3-2, step b) unsubstituted or mono-substituted with R 5 or R 6 , or by treating with an α-halo ketone, such as chloroacetone, to form a 2-imino-1, 3-thiazole (3-3, step c) unsubstituted with R 5 or R 6 , or by treating with 1,3-dihalopropane, such as 1-bromo-3-chloro-propane, to form a 2-imino-1,3-thiazoline unsubstituted or mono-substituted or unsubstituted or R 5 or R 6 mono-substituted or unsubstituted or R or unsubstituted or R 7 ​mono- or di-substituted 2-imino-1,3- can be achieved by forming thiazinane (3-4, step d). In the case of step a, it is preferable to use sodium acetate at a temperature in the range of about 20°C to about 70°C in a protic solvent such as ethanol or methanol. In the case of step b, it is preferable to use an inorganic base such as potassium carbonate at a temperature in the range of about 0°C to about 80°C in a solvent such as acetonitrile or (preferably) 2-butanone. For example, in a protic solvent such as ethanol or methanol, it is preferable to use sodium acetate at a temperature in the range of about 20°C to about 70°C. In the case of step b, in a solvent such as acetonitrile or (preferably) 2-butanone, it is preferable to use an inorganic base such as potassium carbonate at a temperature in the range of about 0°C to about 80°C. For example, in a solvent such as acetonitrile or (preferably) 2-butanone, it is preferable to use an inorganic base such as potassium carbonate at a temperature in the range of about 0°C to about 80°C. For example, potassium carbonate.

[0113] An alternative method (Scheme 3) for preparing analogs having the general structure 3-1' is described in Scheme 3a. The intermediate 4-imino-3-arylthiazolidinone-2-one (3-1a, step a) is reacted directly with an isocyanate (1-2) in the presence of about 0.1 to about 2 equivalents of an inorganic base such as cesium carbonate or sodium hydride to form a cyclic thiouret (3-1'). The reaction can be carried out at a temperature in the range of about 0°C to about 100°C, preferably about 20°C to about 80°C, in an aprotic solvent or a solvent mixture selected from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane or mixtures thereof, but it is preferable to use acetonitrile. The intermediate 4-imino-3-arylthiazolidinone-2-one (3-1a, step a) is reacted directly with an isocyanate (1-2) in the presence of about 0.1 to about 2 equivalents of an inorganic base such as cesium carbonate or sodium hydride to form a cyclic thiouret (3-1'). The reaction is carried out at a temperature in the range of about 0°C to about 100°C, preferably about 20°C to about 80°C, in an aprotic solvent or a solvent mixture selected from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane or mixtures thereof, but it is preferable to use acetonitrile. The reaction can be carried out at a temperature in the range of about 0°C to about 100°C, preferably about 20°C to about 80°C, in an aprotic solvent or a solvent mixture selected from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane or mixtures thereof, but it is preferable to use acetonitrile. The reaction can be carried out at a temperature in the range of about 0°C to about 100°C, preferably about 20°C to about 80°C, in an aprotic solvent or a solvent mixture selected from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane or mixtures thereof, but it is preferable to use acetonitrile. The reaction can be carried out at a temperature in the range of about 0°C to about 100°C, preferably about 20°C to about 80°C, in an aprotic solvent or a solvent mixture selected from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane or mixtures thereof, but it is preferable to use acetonitrile. The reaction can be carried out at a temperature in the range of about 0°C to about 100°C, preferably about 20°C to about 80°C, in an aprotic solvent or a solvent mixture selected from acetonitrile, acetone, toluene, tetrahydrofuran, 1,2-dichloroethane, dichloromethane or mixtures thereof, but it is preferable to use acetonitrile.

Chemical formula

[0114] Alternatively, 4-imino-3-arylthiazolidinone-2-one (3-1a) can be reacted with 4-nitrophenyl chloroformate (step b) to form the 4-nitrophenyl carbamate intermediate (3-2a). The reaction can be carried out in a polar aprotic solvent such as The reaction can be carried out in a polar aprotic solvent such as tetrahydrofuran. In tetrahydrofuran or dioxane and in the presence of about 0.1 to about 2 equivalents of an inorganic base, such as cesium carbonate or potassium carbonate, preferably at room temperature, an equimolar amount of an imine and a chloroformate salt are used. The reaction is carried out. Intermediate (3-2a) can be isolated by filtering from the inorganic salts and evaporating the solvent, or it can be used directly in step c. In step c, a primary or secondary alkylamine of Ar1-Het-Ar2-L-NHR (wherein R is each H or alkyl) is used to treat 3-2a, and a cyclic thioureido (3-1 ’) can be generated. Step c can also be carried out in the presence of about 0.1 to about 2 equivalents, preferably about 1 to about 1 (Here, R 1 is each H or alkyl) treating 3-2a with, a cyclic thioureido (3-1 ’) can be generated. Step c can also be carried out in the presence of about 0.1 to about 2 equivalents, preferably about 1 to about 1.2 equivalents of an inorganic base, such as cesium carbonate or potassium carbonate, and this is most conveniently carried out at room temperature, but can be carried out at a temperature of about 0 °C to about 100 °C.

Chemical formula

[0115] Alternatively, a primary or secondary alkylamine 3-3a of Ar1-Het-Ar2-L-NH R 1 (wherein R 1 is each H or alkyl) is preferably treated with about 1 to about 1.2 equivalents of an organic base, such as pyridine, in the presence of an activator, such as bis(2,5-dioxopyrrolidin-1-yl) carbonate, an organic base, such as N,N-diisopropylethylamine in the presence of triphosgene or in an aprotic solvent, such as dichloromethane, with 4-nitrophenyl carbonochloridate, an in situ activated amine (not shown ) can be generated, and this is an organic base, such as N,N-diisopropylethylamine When treated with phenyl carbonochloridate, an in situ activated amine (not shown ) can be generated, and this is an organic base, such as N,N-diisopropylethylamine With or without it, reacting with 4-imino-3-arylthiazolidin-2-one (3-1a ) gives the cyclic thiobiuret (3 -1’) as shown in step a, Scheme 3a’.

Chemical Structure

[0116] The thiobiuret (2-2) can also be converted into a novel S-alkylated analog as shown in Scheme 3b. For example, in a protic solvent such as ethanol, in the presence of a base, such as sodium acetate, at a temperature of about 0 °C to about 60 °C, reacting the thiobiuret 2-2 with an alkyl iodide gives (step a) the S-R 2 substituted product (3-1b). By varying the reaction conditions described in Scheme 3, step c, carefully controlling the reaction conditions so that the temperature does not exceed 20 °C. Under these conditions, 4-hydroxy-2-imino thiazolidine (3-2b, step b) can be isolated.

Chemical Structure

[0117] R 2 and R 4 are cyclized to form the analog of formula 1, 2-(R 5 )-4-(R 3 )-5-imino-1,2,4-thiadiazolidin-3-one (3-4c), which can be constructed as described in Scheme 3c. According to the procedure described by Kaugers et al. (J. Org. Chem. 199 2, 57, 1671), it can be prepared in one step by oxidation with sodium nitrite from the corresponding N -arylthiocarbazone to the N-aryl 3 -arylthiocarbazone and then by oxidation with sodium nitrite in one step.​​​ Treating amino 1,2,3,4-thiatriazole (3-1c) with an alkyl isocyanate to form 3-2c. In methanol at room temperature, treating 3-2c with a base, such as sodium methoxide (step b) cleaves the urea bond to form 2-(R 5 )-4-( R 3 )-5-imino-1,2,4-thiadiazolidin-3-one (3-3c). Subsequently, treating this imine with an isocyanate under conditions equivalent to those described in Scheme 3a, step a can generate 3-4c.

Chemical formula

[0118] Preparation of Triaryl Intermediates The molecule of formula 1 can be prepared by creating the Ar 1 -Het-Ar 2 of the triaryl intermediate and then coupling it with a suitable intermediate to form the desired compound. A variety of triaryl intermediates can be used to prepare the molecule of formula 1, provided that these triaryl intermediates contain a suitable functional group to which the desired functional group can be attached on Ar . Suitable functional groups include amino, nitro-derived amino, isocyanate , carboxyl, or halogen (preferably bromo or iodo). These triaryl intermediates can be prepared by the methods described in conventional chemical literature, including the international publication No. WO 2009 / 102736 by Crouse et al. (the entire disclosure of which is incorporated herein by reference). 2 .

[0119] The triaryl aldehyde used as a precursor in the preparation of the molecule of formula 1 is Cro prepared according to the procedure described in US Patent Application Publication No. 2012 / 0202688A1 by use Some of the above procedures require the use of the halo-aryl intermediate Ar 1 -Het-Ph-Br, which is a novel intermediate. These can be prepared as described in Scheme 4 3-(4-Bromophenyl)-1,2,4 -triazole (4-2, step a) is prepared in two steps from 4-bromobenzamide (4-1) under the above conditions (International Publication No. 200910273 6 pamphlet by Crouse et al.). This triazole can then be coupled with a halogenated aryl (R = C1-C 6 haloalkoxy), such as 4-trifluoromethoxyphenylbromobenzene, in a polar aprotic solvent, such as dimethylformamide, in the presence of cesium carbonate or potassium phosphate and can be catalyzed by a copper salt, such as copper(I) iodide, and a chelating agent, such as 8-hydroxyquin oline (both present in an amount of about 0.05 to about 0.25 equivalents) at a temperature in the range of about 80 °C to about 140 °C to form 1-aryl -3-(4-bromophenyl)triazole (4-4, step b).

Chemical formula

[0120] Another triaryl intermediate, Ar 1 -Het-Ar 2 (wherein Het is defined as one of Het-C ~Het-L) can be prepared as shown in Schemes 4A to 4H . ​ [Chemical formula]

[0121] Ar, which is a triaryl intermediate 1 -Het-Ar 2 (where Het is Het-D(1, 2,4-oxadiazole)) can be prepared according to Scheme 4A in a 4-step process. The first 2 steps (a and b) are applied from Baykov, S. et al . Tetrahedron Lett. 2016, 57, 2898 - 2900, where under thermal conditions, in ethanol, treatment with hydroxylamine converts benzonitrile, such as 3-fluoro-4-nitrobenzonitrile, to hydroxybenz imidamide, 4a-1. In the presence of a base, such as N,N-diisopropyleth lamine, reacting 4a-1 with benzoyl chloride in a solvent such as dichloromethane yields benzoyloxybenzimidamide 4a-2. The triaryl nitro intermediate (not shown, step c) can be obtained by treating 4a- 2 with tetrabutylammonium hydroxide (TBAH) in tetrahydrofuran (THF) (applying Otaka, H.; Ikeda, J.; Tanaka, D.; Tobe, M. Te trahedron Lett. 2014, 55, 979 - 981). The nitro group is reduced, as in step d, at 80 °C in an ethanol - water solvent mixture using standard reduction conditions with iron powder and ammonium chloride to obtain the triaryl intermediate 4a-3. [Chemical formula]

[0122] The triaryl intermediate Ar 1 -Het-Ar 2 (wherein Het is Het-E (reverse 1 ,2,4-oxadiazole)) can be prepared in a 3-step process according to Scheme 4B. In step a, under thermal conditions, in ethanol, by treating with hydroxylamine, benzonitrile, for example 4-(trifluoromethoxy ) benzonitrile is converted to hydroxybenzamidoxime, 4b-1. At high temperature (60 °C), in a solvent such as EtOAc, in the presence of a base such as pyridine, in the presence of an activator such as ) 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2 ,4,6-trioxide (T3P), reacting 4b-1 with benzoic acid gives the triaryl nitro intermediate 4b-2. This T3P-mediated cyclization is applied from August ine, J.K. et al. Tetrahedron 2009, 65, 9989-9 996. The nitro group on 4b-2 is reduced under standard reduction conditions with iron powder and ammonium chloride in an ethanol-aqueous solvent mixture at 80°C as in step c to obtain the triaryl intermediate 4b-3. ine, J.K. et al. Tetrahedron 2009, 65, 9989-9 996. The nitro group on 4b-2 is reduced under standard reduction conditions with iron powder and ammonium chloride in an ethanol-aqueous solvent mixture at 80°C as in step c to obtain the triaryl intermediate 4b-3.

Chemical Structure

[0123] The triaryl intermediate Ar 1 -Het-Ar 2 (wherein Het is Het-F (1, 3,4-oxadiazole)) can be prepared in a 2-step process according to Scheme 4C. In step a, at high temperature (60°C), in a solvent such as EtOAc, ​​​​Treatment with an activator such as T3P in the presence of a base such as pyridine converts benzohydrazide, for example 4-(trifluoromethoxy)benzohydrazide, to the triaryl nitro intermediate 4c-1. This T3P-mediated cyclization is applied from Augustine, J. K. et al. Tetrahedron 2009, 65, 9989-9996. The nitro group on 4c-1 is reduced using standard reduction conditions with iron powder and ammonium chloride in an ethanol-water solvent mixture at 80 °C as in step b to obtain the triaryl intermediate 4b-3. The triaryl nitro intermediate 4c-1 is obtained by treating benzohydrazide, for example 4-(trifluoromethoxy)benzohydrazide, with an activator such as T3P in the presence of a base such as pyridine. This T3P-mediated cyclization is applied from Augustine, J. K. et al. Tetrahedron 2009, 65, 9989-9996. The nitro group on 4c-1 is reduced using standard reduction conditions with iron powder and ammonium chloride in an ethanol-water solvent mixture at 80 °C as in step b to obtain the triaryl intermediate 4b-3.

Chemical Structure

[0124] The triaryl intermediate Ar-Het-Ar (where Het is Het-J(1,3,4-thiadiazole)) can be prepared in a 3-step process according to Scheme 4D. In step a, treatment with an activator such as T3P in the presence of a base such as pyridine in a solvent such as EtOAc at room temperature converts benzohydrazide, for example 4-(trifluoromethoxy)benzohydrazide, to benzoylbenzohydrazide 4d-1. 1 -Het-Ar 2 (where Het is Het-J(1, 3,4-thiadiazole)) can be prepared in a 3-step process according to Scheme 4D. In step a, treatment with an activator such as T3P in the presence of a base such as pyridine in a solvent such as EtOAc at room temperature converts benzohydrazide, for example 4-(trifluoromethoxy)benzohydrazide, to benzoylbenzohydrazide 4d-1. Treatment with an activator such as T3P in the presence of a base such as pyridine in a solvent such as EtOAc at room temperature converts benzohydrazide, for example 4-(trifluoromethoxy)benzohydrazide, to benzoylbenzohydrazide 4d-1. At high temperature (60 °C), reacting 4d-1 with Lawesson's reagent and T3P in the presence of a base such as pyridine in a solvent such as EtOAc gives a triaryl nitro intermediate (not shown, step b). This T3P-mediated cyclization is applied from Augustine, J. K. et al. Tetrahedron 2009, 65, 9989-9996. The nitro group is reduced as in step c at 80 °C with iron powder and ammonium chloride in an ethanol-water solvent mixture to obtain the triaryl intermediate Ar-Het-Ar (where Het is Het-J(1,3,4-thiadiazole)). This T3P-mediated cyclization is applied from Augustine, J. K. et al. Tetrahedron 2009, 65, 9989-9996. ugustine, J. K. et al. Tetrahedron 2009, 65, 9 989-9996. The nitro group is reduced as in step c at 80 °C with iron powder and ammonium chloride in an ethanol-water solvent mixture to obtain the triaryl intermediate Ar-Het-Ar (where Het is Het-J(1,3,4-thiadiazole)). Using standard reduction conditions with iron powder and ammonium chloride in a tanol - water solvent mixture for reduction, the triaryl intermediate 4d - 2 can be obtained. The triaryl intermediate Ar

Chemical formula

[0125] -Het-Ar 1 -Het-Ar 2 (where Het is Het - H (1, 2,3 - triazole)) can be prepared in a two - step process according to Scheme 4E. In step a, at high temperature (100 °C), in a solvent such as DMSO, a mixture of aniline, acetophenone, and 4 - methylbenzenesulfonohydrazide is treated with molecular iodine to obtain the corresponding Ar -Het - Ar nitro intermediate 4e - 1. 1 -Het - Ar 2 This procedure is applied from Chen, Z.; Yan, Q.; Liu, Z.; Zhang, Y. Chem Eur. J. 2014, 20, 17635 - 17639. The nitro group on 4e - 1 is reduced using standard reduction conditions with iron powder and ammonium chloride in an ethanol - water solvent mixture at 80 °C as in step b to obtain the triaryl intermediate 4e - 2.

Chemical formula

Chemical formula

[0126] The triaryl intermediate Ar 1 -Het - Ar 2 (where Het is Het - K (1, 3,4 - oxadiazole)) can be prepared in a two - step process according to Scheme 4F. In step a, at room temperature, in a solvent such as dichloromethane, a base, for example ​ For example, in the presence of pyridine, in the presence of copper(II) acetate, nitrophenyltetrazole, for example 5-(4-(nitrophenyl)-2H-tetrazole is reacted with a boronic acid, for example (4-(trifluoromethoxy)phenyl)boronic acid to obtain the corresponding Ar -Het-Ar 1 -Het-Ar 2 nitro intermediate 4f-1 can be obtained. This reaction is applied from Li, Y.; Gao, L.- X.; Han, F.-S. Chem. Commun. 2012, 48, 2719-272 1. The nitro group on 4f-1 is reduced using standard reduction conditions with iron powder and ammonium chloride in an ethanol -water solvent mixture at 80 °C as in step b to obtain the triaryl intermediate 4f-2.

Chemical formula

[0127] Triaryl precursor molecules, for example Ar 1 -Het-X 1 or X 1 -Het-Ar 2 (In the formula where X 1 is Br, Het is Het-G or Het-L (imidazole) or H et-C (triazole)) are described in Bouchet et al., Tetrahe dron 1979, 35, 1331-1338 and can be prepared via the method shown in Scheme 4G. In a solvent, for example N,N-dimethylformamide, in the presence of a base such as potassium carbonate, an aryl halide containing an activating group such as NO2, SF5 or SO2CF3 is substituted with imidazole or triazole to obtain the precursor The bulk molecules 4g-1, 4g-2, 4g-3 and 4g-4 are obtained and used in other reactions, triaryl intermediate, Ar 1 -Het-Ar 2 (wherein Het is Het-G or He t-L(imidazole) or Het-C(triazole)) can be obtained.

Chemical formula

[0128] Triaryl precursor molecules, such as Ar 1 -Het-X 1 or X 1 -Het-Ar 2 (Formula wherein X 1 is Br and Het is Het-C(triazole)) is prepared by applying Xia, N. ; Taillefer, M. Angew.Chem.Int.Ed. 2009, 48, 3 37 - 339 and can be prepared via the method shown in Scheme 4H. The halo genated aryl, such as 4h-1 or 4h-2, at high temperature (90 - 100 °C) in a solvent, such as N,N-dimethylformamide, in the presence of a base, such as cesium carbonate, in the presence of copper(II ) acetylacetonate and acetylacetone, reacts with bromotriazole to obtain the precursor molecules 4h-3 and 4h-4, which can be used in other reactions to obtain the triaryl intermediate, Ar -Het-Ar 1 -Het-Ar 2 (wherein Het is Het-C(tri azole)).

Chemical formula

[0129] Preparation of 1-atom linked intermediate The molecule of formula 1 (wherein L is a 1-carbon linker) can be prepared from the acid or amine intermediates described in Scheme 5 and Scheme 6 respectively. The acid precursor Ar -Het-Ar 1 -Het-Ar 2 -L-CO2H (unsubstituted or mono- or di-substituted with R 8 ) can be prepared as shown in Scheme 5. The boronic ester (5-2, step a) can be prepared from the halophenyl ester (5-1) using Miyaura conditions. The coupling of the boronic ester with the bromoheterocycle (5-3, step b) can be achieved at a temperature of about 50 °C to about 120 °C in a suitable solvent system, such as dioxane / water, in the presence of a base, such as sodium bicarbonate, potassium phosphate or cesium fluoride, using a palladium catalyst and a phosphine ligand to form the triaryl ester intermediate (5-4, step c). Among the palladium catalysts, tetrakis(triphenylphosphine)palladium(0 ) is preferred, but other well-known palladium catalysts can be used. The saponification of the ester can be achieved by using a strong base, such as sodium hydroxide or lithium hydroxide, in methanol or ethanol with or without tetrahydrofuran / water to provide the desired carboxylic acid (5 -5, step c). The amine precursor Ar -Het-Ar -L-NH2 (unsubstituted or mono- or di-substituted with R ) can be prepared as shown in Scheme 6. The halobenzylamine ) is preferred, but other well-known palladium catalysts can be used. The saponification of the ester can be achieved by using a strong base, such as sodium hydroxide or lithium hydroxide, in methanol or ethanol with or without tetrahydrofuran / water to provide the desired carboxylic acid (5 -5, step c). -5, step c).

Chemical formula

[0130] The amine precursor Ar 1 -Het-Ar 2 -L-NH2 (unsubstituted or mono- or di-substituted with R 8 ) can be prepared as shown in Scheme 6. The halobenzylamine ​​Compound (6-1) can be prepared using benzyl chloroformate in an aprotic solvent, such as dichloromethane, at a temperature of about -10 °C to about 10 °C in the presence of a base, such as triethylamine. to obtain benzylamine protected with N - carbobenzyloxy (Cbz) (6-2, step a).

Chemical formula

[0131] Alternatively, other N - protecting groups, such as tert - butoxycarbonyl (BOC) or 9 - fluorenylmethylcarbonyl (Fmoc), can be employed in step a using the same conditions as described above for Cbz. The boronic acid ester 6-3 protected with Cbz can be prepared using Miyaura conditions (step b). The coupling of the boronic acid ester with the bromoheterocycle (5-3) can be achieved using a palladium catalyst and a phosphine ligand in a suitable solvent system, such as dioxane / water, at a temperature of about 50 °C to about 120 °C in the presence of a base, such as sodium bicarbonate, potassium phosphate, or cesium fluoride, to form the N - protected aminoalkylphenyl intermediate (6-4, step c). The removal of the Cbz group is achieved under acidic conditions using a strong acid, such as hydrogen bromide, followed by free - basification with a base, such as sodium bicarbonate or sodium hydroxide, to provide the free amine precursor Ar - Het - Ar - L - NH2 (6-5, step d). The same method can be applied to compounds where L contains more than 1 carbon atom. 1 -Het - Ar 2 -L - NH2

[0132] Preparation of ethyl - linked intermediate The preparation of compounds in which L is a two-atom group is described in Schemes 7 to 9. At a temperature of about - 78 °C to about 20 °C, in the presence of a suitable base such as sodium hydride or n-butyllithium in an aprotic solvent such as tetrahydrofuran or diethyl ether, a reagent such as ethyl diethylphosphonoacetate or a Wittig reagent such as ethyl-2-(triphenylphosphoranylidene) propanoate) or an α-substituted acetate such as ethyl 2-fluoroacetate or ethyl 2-cyanoacetate is used for the condensation of an aldehyde (7 -1, R =H) (described in US Patent Application Publication No. 2012 / 0202688A1) 9 to prepare an unsubstituted or monosubstituted acrylic ester (7-2, step a) with R and R 9 and R 10 . The saponification of the obtained ester can be achieved by using a strong base such as sodium hydroxide in methanol or ethanol with or without tetrahydrofuran / water to provide a vinyl carboxylic acid (7-3, step b). In some cases, partial condensation of the aldehyde (7-1, R =H) can result in the isolation of an alcohol intermediate (7-4, step c), especially when R is electron-withdrawing . Substitution of this alcohol (step d) using a nucleophile such as Deoxo 9 -Fluor® and subsequent saponification (step e) as described above can produce a highly substituted ethyl 10 carboxylic acid (7-5) further substituted with R , where R is defined as R above. When a saturated linkage is preferred, a solvent such as dimethyl sulfoxide or tetrahydrofuran 11 is used. where R 11 is as defined for R 8 above. When a saturated linkage is preferred, a solvent such as dimethyl sulfoxide or tetrahydrofuran In the presence of an inorganic base such as sodium hydride in an aprotic polar solvent, trimethyl iodide using a sulfur ylide formed in situ from sulfonium such as, acrylic acid ester (7-2) with R 12 unsubstituted or mono- or di-substituted corresponding cyclopropane can be converted to (7-6, step f). Similarly, hydrogen gas and a palladium catalyst can be used to reduce the acrylic acid ester (7-2) to the parent alkane (7-8, step h). Both cyclopropane and alkane esters can be hydrolyzed under the above basic conditions to produce the free carboxylic acids 7-7 (step g) and 7-9 (step i), respectively .

[0133] In a similar manner, under the same conditions as above, a Wittig reagent such as ethyl diethylphosphonoacetate or ethyl 2-(triphenylphosphoranylidene)propanoate or an α-substituted alkyl ester such as ethyl 2-fluoroacetate or ethyl 2-cyanoacetate is used for the condensation of a ketone (7-1, R = alkyl) (described in International Publication No. WO 2011 / 01750 9 4A1 pamphlet) to produce an α-alkylalkylate ester 7-2 or an alcohol 7-4. Subsequent treatment of 7-2 or 7- 4 as described above for R 9 = H can result in the corresponding unsaturated (7-3) or saturated (7-5, 7-7, 7-9) carboxylic acids .

Chemical formula

[0134] Alternatively, a compound in which L is a 2-carbon linker is also prepared as shown in Scheme 8 It is possible. First, using the conditions described in Molander et al. Org. Lett. 2007, 9, pp 203 - 206, at a temperature of about 80 °C to about 120 °C, in the presence of a palladium catalyst such as palladium(II) acetate and a base such as cesium carbonate, bromoamide Ar -Het-Ar 1 -Br (8 - 1, step a) is coupled with potassium (2 - ((tert-butoxy 2 carbonyl)amino)ethyl)trifluoroborate, and as a result, the corresponding 2-(tert-butoxycarbonyl)amino)ethyl derivative 8 - 2 is formed. At a temperature of about 0 °C to about 50 °C, in an aprotic solvent such as dichloromethane or dioxane, this material is further treated with about 1 to about 5 equivalents of an acid such as trifluoroacetic acid or hydrogen chloride, resulting in cleavage of the tert-butoxycarbonyl group and formation of the trifluoroacetate salt of amine Ar -Het-Ar 1 -L-NH2 (8 - 3, step b). 2

Chemical formula

[0135] L is a 2-carbon atom mono- or disubstituted with R 9 where R is as defined above 9 and R is unsubstituted or mono-substituted with R where R is as defined above 10 and R is unsubstituted or mono-substituted with R 10 where R is as defined above The aminoalkyl precursor Ar 1 -Het-Ar 2 -L-NH2 can be prepared as shown in Scheme 9. X can be selected from Cl, Br, or I, and R and R 9 and R 1 0The unsubstituted halophenyl carbinols 9-1 are commercially available. 9 The mono- or di-substituted carbinol 9-1 is tetrahydrofuran at temperatures below about 0° C. The corresponding halophenylamines are reacted in ethereal solvents such as dihydrofuran or diethyl ether. acetate (9-I, step a) from Shin et al. Bioorg. Med. Ch em. Lett. 2008, 18, pp4424-4427 followed by reduction with a metal hydride such as lithium aluminum hydride. Both 9-I and 9-II can be prepared from diisobutylaluminum hydride. and subsequently reduced to the corresponding aldehyde using metal hydrides such as those described by Brimble et al. al. Org. Lett. 2012, 14, pp5820-5823 Further treatment with a Grignard reagent in a manner similar to that described above affords R 10 And further Carbinol 9-1 can be substituted with phthalimide under Mitsunobu conditions (step b or step c). Treatment with ethyl acetate can afford the N-phthalimide intermediate 9-2 (step d). The halide is converted to a boronic ester under Miyaura conditions to form a boronic ester. (9-3, step e) can be obtained by dissolving the cyclopentadiene in a mixture of dioxane / water at a temperature of about 50° C. to about 120° C. In the presence of a base such as sodium bicarbonate in a suitable solvent system, tetrakis(triphenyl Using palladium catalysts such as palladium(0)phosphine, boronic esters and bromine -heterocycle coupling can be carried out to give the N-phthalimide intermediate 9-4 ( Step f): Deprotection using hydrazine and methanol or other suitable solvent gives the amine 9-5 can be obtained (step g). [Chem.]

[0136] Alternatively, compounds in which L is a 2-atom linker can also be prepared as shown in Scheme 9a It can be achieved. At a temperature of about -78 °C to about 40 °C, in an aprotic solvent such as tetrahydrofuran or dichloromethane in the presence of a base such as sodium hydride or 1,8-diazabicycloundec-7-ene, methylenetriphenylphosphorane which can be prepared from methyltriphenylphosphonium iodide is used to achieve olefination of the aldehyde (7-1, R =H, step a) 9 =H, step a). This material (9-2a) can be further treated with a hydroboration reagent such as 9-borabicyclo(3.3.1)nonane in an aprotic solvent such as tetrahydrofuran and then oxidized using an oxidizing agent such as hydrogen peroxide to produce ethyl alcohol 9-3a (step b). The carbinol 9-3a can be treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 9-5a where R =H (step c). Deprotection using hydrazine and methanol or other suitable solvents can give the amine 9-6a (step f). In addition, oxidation to the corresponding aldehyde under Swern conditions followed by addition of a Grignard reagent as described above (Scheme 9) can further mono-substitute 9-3a with R where R 10 is as defined above (step d). The carbinol 9-4a can be further treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 9-5a which can be achieved (step c). Deprotection using hydrazine and methanol or other suitable solvents can give the amine 9-6a (step f). In addition, oxidation to the corresponding aldehyde under Swern conditions followed by addition of a Grignard reagent as described above (Scheme 9) can further mono-substitute 9-3a with R where R is as defined above (step d). The carbinol 9-4a can be further treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 9-5a 10 which can be achieved (step c). Deprotection using hydrazine and methanol or other suitable solvents can give the amine 9-6a (step f). In addition, oxidation to the corresponding aldehyde under Swern conditions 10 is as defined above (step d). The carbinol 9-4a can be further treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 9-5a which can be achieved (step c). Deprotection using hydrazine and methanol or other suitable solvents can give the amine 9-6a (step f). In addition, oxidation to the corresponding aldehyde under Swern conditions Cut (Step e). Deprotection using hydrazine and methanol or other suitable solvents gives amine 9-6a (Step f).

Chemical formula

[0137] Scheme 9b outlines an alternative route for constructing analogs where linker L is a 2-atom linker. The copper-catalyzed arylation of 2,4-pentane-2,4-dione using 8-1 (J.Am.Chem.Soc. 2010, 132, 8273.) gives the substituted acetone intermediate 9-1b (Step a). Reductive amination (Step b) using any of a variety of conditions well known to those skilled in the art can generate amine 9-2b, which can be converted to the target molecule using the conditions described above in Scheme 2. When the linker contains a chiral center as in the case of intermediate 9 -2b, these intermediates can be separated into their pure isomers either using a chiral column or by fractional crystallization of salts prepared from chiral acids such as (+)- and (-)-tartaric acid. -2b.

Chemical formula

[0138] The construction of analogs where the ethyl linker is part of a 6-membered ring can also be carried out starting from bromide 8-1. Coupling of 8-1 with 2-cyclohex-1 -enyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane under standard Suzuki coupling conditions (Scheme 9b, Step c) can afford alkene 9-3b. Epoxidation (Step d) using standard reagents such as meta-chloro peroxybenzoic acid and subsequent three ​ Acid-Catalyzed Rearrangement Using Indium Chloride (J. Org. Chem. 1998, 63, 821 2), ketone 9-5b can be generated. Reductive amination and conversion to the target molecule can be carried out using the conditions described above .

[0139] Preparation of Propyl-Linked Intermediates The preparation of compounds in which L is a 3-atom group is described in Schemes 10 and 11. L is a 3-carbon atom monosubstituted or disubstituted with R 9 as defined above, and R 9 is as defined above, and one of the R 10 is unsubstituted or monosubstituted with R 10 as defined above, and the aminoalkyl precursor Ar -Het-Ar 1 -L-NH2 can be prepared as shown in Scheme 10. When X is Br and R 2 and R are H, halophenylcarbinol 10-1 is commercially available. Rubinol 10-1 monosubstituted or disubstituted with R 9 and R 10 is prepared from the corresponding halophenyl acetate (10-I, step a) in an ethereal solvent such as tetrahydrofuran at a temperature of about 0 °C or lower, according to the method similar to that described by Shin et al .Bioorg. Med. Chem. Lett. 2008, 18, pp4424-442 9 7, followed by reduction using a metal hydride such as lithium aluminum hydride. Both 10-I and 10-II are reduced to the corresponding aldehyde using a metal hydride such as diisobutylaluminum hydride, followed by Brimble et al. Org. Lett. 2012, 14, pp5 . in an ethereal solvent such as tetrahydrofuran at a temperature of about 0 °C or lower, according to the method similar to that described by Shin et al .Bioorg. Med. Chem. Lett. 2008, 18, pp4424-442 7, followed by reduction using a metal hydride such as lithium aluminum hydride. Both 10-I and 10-II are reduced to the corresponding aldehyde using a metal hydride such as diisobutylaluminum hydride, followed by Brimble et al. Org. Lett. 2012, 14, pp5 . reduce to the corresponding aldehyde using a metal hydride such as diisobutylaluminum hydride, followed by Brimble et al. Org. Lett. 2012, 14, pp5 . In a manner similar to that described by 820-5823, with a Grignard reagent such as methylmagnesium bromide further treatment can be carried out to obtain a further mono-substituted product with R 10 (step b or step c). The carbinol 10-1 can be treated with phthalimide under Mitsunobu conditions to generate the N- phthalimide intermediate 10-2 (step d).

Chemical formula

[0140] The halide can be converted to a boronic acid ester under Miyaura conditions (10-3, step e). At a temperature of about 50 °C to about 120 °C, in the presence of a base such as sodium bicarbonate in a suitable solvent system such as dioxane / water, using a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0), a coupling of the boronic acid ester with a bromo-heterocyclic ring can be carried out to obtain the N-phthalimide intermediate 10-4 (step f). Deprotection using hydrazine and methanol or other suitable solvents can yield the amine 10-5 (step g). Alternatively, a compound in which L is a 3-atom linker can also be prepared as shown in Scheme 11.

Chemical formula

[0141] Instead, the bromide Ar -Het-Ar -Br (8-1) can be prepared in the presence of a palladium catalyst such as bis(triphenylphosphine)dichloropalladium(II), copper(I) iodide, and a base such as triethylamine at a temperature of about 50 °C to about 120 °C, where R 1 -Het-Ar 2 -Br (8-1) is unsubstituted or 10 mono-substituted with R, and in the formula R is unsubstituted or mono-substituted, and in the formula R10 is a suitable alkynyl alcohol as defined above (11 -1, which can be coupled with step a) to produce the corresponding alkynyl alcohol derivative 11-2 . The obtained carbinol 11-2 can be treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 11-3 (step b), and this can be converted to an amine using hydrazine and methanol or other suitable solvents (11-7, step e). The carbinol 11-2 can be reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an alkenyl or fully saturated alkyl carbinol 11-4 unsubstituted with R . Further, the carbinol 11-2 can be treated with a metal hydride such as lithium aluminum hydride to provide (E)-alkenyl carbinol 11-4 . Similarly, the carbinol 11-2 can be protected with a protecting group such as tert-butyldiphenylsilyl, treated with a hydrofunctionalization reagent such as Schwartz's reagent, and subsequently 10 electrophilic quenching can be carried out using elemental iodine or N-bromosuccinimide (NBS), etc. Instead, the carbinol 11-2 is mono- or di-substituted with R . Here, R is further used in a transition metal catalyst coupling reaction such as Suzuki or Negishi to prepare the carbinol 11-4 as defined above (step c), and can be treated with a metal exchange reaction reagent such as pinacol diboron. Following deprotection, the obtained carbinol 11-4 can be treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 11-5 (step d), and this can be converted to an amine using hydrazine and methanol or other suitable solvents (11-7, step e). The carbinol 11-2 can be reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an alkenyl or fully saturated alkyl carbinol 11-4 unsubstituted with R . Similarly, the carbinol 11-2 can be protected with a protecting group such as tert-butyldiphenylsilyl, treated with a hydrofunctionalization reagent such as Schwartz's reagent, and subsequently 9 electrophilic quenching can be carried out using elemental iodine or N-bromosuccinimide (NBS), etc. Instead, the carbinol 11-2 is mono- or di-substituted with R . Here, R 9 is as defined in the above (step c), and can be further used in a transition metal catalyst coupling reaction such as Suzuki or Negishi to prepare the carbinol 11-4, and can be treated with a metal exchange reaction reagent such as pinacol diboron. Following deprotection, the obtained carbinol 11-4 can be treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 11-5 (step d), and this can be converted to an amine using hydrazine and methanol or other suitable solvents . The obtained carbinol 11-4 can be treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 11-5 (step d), and this can be converted to an amine using hydrazine and methanol or other It can be converted to an amine using a suitable solvent (11-6, step e).

[0142] Preparation of Butyl-Linked Intermediate Compounds in which L is a 4-atom linker can be prepared as shown in Scheme 12 At a temperature of about 50 °C to about 120 °C, in the presence of a palladium catalyst such as bis(triphenylphosphine)dichloropalladium, copper(I) iodide, and a base such as triethylamine, bromide Ar -Het-Ar -Br(8-1) is coupled with a suitable alkynyl alcohol (12-1, step a) which is unsubstituted or mono-substituted with R 1 -Het-Ar 2 -Br(8-1) is coupled with a suitable alkynyl alcohol (12-1, step a) which is unsubstituted or mono-substituted with R 10 and is defined as above, and is mono-substituted or di-substituted with R9, where R R 10 is defined as above and is mono-substituted or di-substituted with R9, where R 9 is defined as above to produce the corresponding alkynyl alcohol derivative 12-2. The resulting carbinol 12-2 is treated with phthalimide under Mitsunobu conditions (step b) to produce the N-phthalimide intermediate 12-3, which can be converted to an amine using hydrazine and methanol or another suitable solvent (12-7, step e). Carbinol 12-2 is reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an unsubstituted alkenyl or fully saturated alkyl carbinol 12-4 (step c). The resulting carbinol 12-2 is treated with phthalimide under Mitsunobu conditions (step b) to produce the N-phthalimide intermediate 12-3, which can be converted to an amine using hydrazine and methanol or another suitable solvent (12-7, step e). The carbinol 12-2 can be reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an unsubstituted alkenyl or fully saturated alkyl carbinol 12-4 (step c). The resulting carbinol 12-2 is treated with phthalimide under Mitsunobu conditions (step b) to produce the N-phthalimide intermediate 12-3, which can be converted to an amine using hydrazine and methanol or another suitable solvent (12-7, step e). The carbinol 12-2 can be reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an unsubstituted alkenyl or fully saturated alkyl carbinol 12-4 (step c). The resulting carbinol 12-2 is treated with phthalimide under Mitsunobu conditions (step b) to produce the N-phthalimide intermediate 12-3, which can be converted to an amine using hydrazine and methanol or another suitable solvent (12-7, step e). The carbinol 12-2 can be reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an unsubstituted alkenyl or fully saturated alkyl carbinol 12-4 (step c). The resulting carbinol 12-2 is treated with phthalimide under Mitsunobu conditions (step b) to produce the N-phthalimide intermediate 12-3, which can be converted to an amine using hydrazine and methanol or another suitable solvent (12-7, step e). The carbinol 12-2 can be reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an unsubstituted alkenyl or fully saturated alkyl carbinol 12-4 (step c). The resulting carbinol 12-2 is treated with phthalimide under Mitsunobu conditions (step b) to produce the N-phthalimide intermediate 12-3, which can be converted to an amine using hydrazine and methanol or another suitable solvent (12-7, step e). The carbinol 12-2 can be reduced using a transition metal catalyst such as palladium under a hydrogen atmosphere to provide an unsubstituted alkenyl or fully saturated alkyl carbinol 12-4 (step c). 13 unsubstituted to provide an unsubstituted alkenyl or fully saturated alkyl carbinol 12-4 (step c). Furthermore, carbinol 12-2 can be treated with a metal hydride such as lithium aluminum hydride to provide (E)-alkenyl carbinol 12-4 (step c). Furthermore, carbinol 12-2 can be treated with a metal hydride such as lithium aluminum hydride to provide (E)-alkenyl carbinol 12-4 (step c). Furthermore, carbinol 12-2 can be treated with a metal hydride such as lithium aluminum hydride to provide (E)-alkenyl carbinol 12-4 (step c). is protected with a protecting group such as tert-butyldiphenylsilane, treated with a hydroalumination reagent such as Schwartz's reagent, and subsequently elemental iodine or can be electrophilically quenched using NBS or the like. Alternatively, the carbino l 2-2 is mono- or disubstituted with R 13 wherein R 13 is as defined for R 8 above in step (c), and the carbino l 12-4 is prepared for further use in a transition metal-catalyzed coupling reaction such as Suzuki or Negishi by treatment with a metal exchange reagent such as pinacol diboron. Following deprotection, the resulting carbino l 12-4 can be treated with phthalimide under Mitsunobu conditions to produce the N-phthalimide intermediate 12-5 (step d), which can be converted to an amine using hydrazine and methanol or another suitable solvent (1

Chemical formula

[0143] 2-Imino-1,3-thiazolin-4-one (3-1) can be further functionalized using various conditions. Treatment with Selectfluor® and 9-fluorenone in anhydrous acetonitrile (J. Am. Chem. Soc. 2013, 135, 17 494) can convert the molecule having formula 3-1 to the monofluoro analogue (13-1). Treatment with molecular bromine in an aprotic solvent such as dichloromethane at about 0 °C to about 30 °C (step b) can effect monobromination (13-2) on the thiazolinone ring. Di methyl

[0144] Preparation of substituted thiourets 2-Imino-1,3-thiazolin-4-one (3-1) can be further functionalized using various conditions. Treatment with Selectfluor® and 9-fluorenone in anhydrous acetonitrile (J. Am. Chem. Soc. 2013, 135, 17 494) can convert the molecule having formula 3-1 to the monofluoro analogue (13-1). Treatment with molecular bromine in an aprotic solvent such as dichloromethane at about 0 °C to about 30 °C (step b) can effect monobromination (13-2) on the thiazolinone ring. Di methyl

Chemical formula

[0145] Treatment with molecular bromine in an aprotic solvent such as dichloromethane at about 0 °C to about 30 °C (step b) can effect monobromination (13-2) on the thiazolinone ring. Di methyl In a polar aprotic solvent such as chloroformamide or tetrahydrofuran, at least 2 equivalents of an alkylating agent R 5 -I and a strong base such as sodium hydride or lithium diisopropylamide By alkylation (step c) using, a dialkylated product (13-3) can be Provided. Treatment with an inorganic salt such as a ketone or aldehyde and potassium carbonate or cesium carbonate Groups can result in the formation of carbinol (13-4). In the case of analogs of the compound of formula 3-1 where L is a -CH2C H2- group, in carbon tetrachloride at about 30 ° C to about 77 ° C N-bromosuccinimide and free radicals such as azobis(isobutyronitrile) Bromine can be incorporated into the ethyl linker by free radical bromination using an initiator, resulting in a monobrominated product (13-5).

[0146] The compounds of formula 1 disclosed herein can be synthesized using methods well known to those skilled in the art and the methods provided in the specification of US Patent Application Publication No. 20140274688A1 by Fischer Et al. and the pamphlet of International Publication No. 2016033025A1 by Baum et al., using known or commercially Available starting materials.

Examples

[0147] These examples are for illustrative purposes only and should not be construed as limiting the present disclosure to only the embodiments disclosed in these examples.

[0148] Starting materials, reagents and solvents obtained from commercial sources were used without further purification. Anhydrous solvents were purchased from Aldrich as Sure / Seal (trademark) and received It was used as it was. The melting point was obtained using a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMel t automatic melting point system from Stanford Research Systems and was not corrected. Examples using "room temperature (or rt)" were carried out in a laboratory where the temperature and humidity were controlled at a temperature in the range of about 20 °C to about 24 °C. Molecules are denoted by known names named according to the naming programs in ISIS Draw, ChemDraw or ACD Name Pro . When such programs are unable to name the molecule, the molecule is named using conventional naming rules. Unless otherwise specified, the units of the 1H 1 H NMR spectral data are in ppm (δ) and were recorded at 300, 400 or 600 MHz . 13 The units of the 13C NMR spectral data are in ppm (δ) and were recorded at 75, 1 00 or 150 MHz.

[0149] Example 1: Preparation of 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2 ,4-triazol-3-yl)phenyl)acetonitrile (C1) [Chemical formula] Into a reaction flask, (4-(cyanomethyl)phenyl)boronic acid (2.55 g, 15.8 mmol), 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1, 2,4-triazole (prepared as described in US Patent Application Publication No. 20140274688 A1 by Fischer et al., 3.9 g, 12.66 mmol) and sodium carbonate (2.68 g, 25.3 mmol) were added, followed by tetrakis(triphenylphosphine) ) Palladium(0) (Pd(PPh3)4; 0.731 g, 0.633 mmol) was added. The flask was emptied, back-filled with nitrogen (3×), and then dioxane (45 mL) and water (14.9 mL) were added. Subsequently, the reaction mixture was heated to 95 °C over 9 hours. The reaction mixture was cooled to room temperature (rt) and diluted with ethyl acetate (EtOAc) and water. The organic layer was separated, washed with brine, dried over Na2SO4, filtered, and concentrated to a yellow semi-solid. EtOAc was adhered to Celite (registered trademark) using the crude material. Purification by silica gel column chromatography eluting with a 0 - 50% EtOAc - hexane gradient over 20 minutes (min) gave the title compound as an off - white solid (3.92 g, 88%): 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.28 - 8.16 (m, 2H), 7.90 - 7 .74 (m, 2H), 7.50 - 7.43 (m, 2H), 7.43 - 7.35 (m, 2H ), 3.83 (s, 2H); 1 19F NMR (376 MHz, CDCl3) δ - 58. 02; ESIMS m / z 345 ([M + H] . 19 Example 2: Preparation of methyl 3 - cyano - 3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H - 1,2,4 - triazol - 3 - yl)phenyl)propanoate (C2) + .

[0150]

Chem.

[0151] Example 3: Preparation of 3-cyano-3-(4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)propanoic acid (C3) [Chemical Structure Diagram] Methyl 3-cyano-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propanoate (C2, 500 mg, 1.201 mmol) was suspended in methanol (5 mL), and 2N aqueous sodium hydroxide solution (NaOH; 0.721 mL, 1.44 mmol) was added. The clear reaction mixture was stirred overnight under nitrogen at rt. The reaction mixture was acidified with a few drops of 2N HCl. The solvent was removed under reduced pressure, and the residue was dried under high vacuum. The title compound was isolated as a white solid (480 mg, 97%): phenyl)propanoate (C2, 500 mg, 1.201 mmol) was suspended in methanol (5 mL), and 2N aqueous sodium hydroxide solution (NaOH; 0.721 mL, 1.44 mmol) was added. The clear reaction mixture was stirred overnight under nitrogen at rt. The reaction mixture was acidified with a few drops of 2N HCl. The solvent was removed under reduced pressure, and the residue was dried under high vacuum. The title compound was isolated as a white solid (480 mg, 97%): phenyl)propanoate (C2, 500 mg, 1.201 mmol) was suspended in methanol (5 mL), and 2N aqueous sodium hydroxide solution (NaOH; 0.721 mL, 1.44 mmol) was added. The clear reaction mixture was stirred overnight under nitrogen at rt. The reaction mixture was acidified with a few drops of 2N HCl. The solvent was removed under reduced pressure, and the residue was dried under high vacuum. The title compound was isolated as a white solid (480 mg, 97%): phenyl)propanoate (C2, 500 mg, 1.201 mmol) was suspended in methanol (5 mL), and 2N aqueous sodium hydroxide solution (NaOH; 0.721 mL, 1.44 mmol) was added. The clear reaction mixture was stirred overnight under nitrogen at rt. The reaction mixture was acidified with a few drops of 2N HCl. The solvent was removed under reduced pressure, and the residue was dried under high vacuum. The title compound was isolated as a white solid (480 mg, 97%): phenyl)propanoate (C2, 500 mg, 1.201 mmol) was suspended in methanol (5 mL), and 2N aqueous sodium hydroxide solution (NaOH; 0.721 mL, 1.44 mmol) was added. The clear reaction mixture was stirred overnight under nitrogen at rt. The reaction mixture was acidified with a few drops of 2N HCl. The solvent was removed under reduced pressure, and the residue was dried under high vacuum. The title compound was isolated as a white solid (480 mg, 97%): phenyl)propanoate (C2, 500 mg, 1.201 mmol) was suspended in methanol (5 mL), and 2N aqueous sodium hydroxide solution (NaOH; 0.721 mL, 1.44 mmol) was added. The clear reaction mixture was stirred overnight under nitrogen at rt. The reaction mixture was acidified with a few drops of 2N HCl. The solvent was removed under reduced pressure, and the residue was dried under high vacuum. The title compound was isolated as a white solid (480 mg, 97%): phenyl)propanoate (C2, 500 mg, 1.201 mmol) was suspended in methanol (5 mL), and 2N aqueous sodium hydroxide solution (NaOH; 0.721 mL, 1.44 mmol) was added. The clear reaction mixture was stirred overnight under nitrogen at rt. The reaction mixture was acidified with a few drops of 2N HCl. The solvent was removed under reduced pressure, and the residue was dried under high vacuum. The title compound was isolated as a white solid (480 mg, 97%): 1 H NMR (400 MHz, DMSO-d6) δ 12 .80 (s, 1H), 9.43 (s, 1H), 8.17 - 8.03 (m, 4H), 7.6 2 (dd, J = 8.8, 7.1 Hz, 4H), 4.56 (dd, J = 8.8, 5.9 Hz , 1H), 3.06 (dd, J = 16.8, 8.7 Hz, 1H), 2.92 (dd, J = 16.9, 6.0 Hz, 1H); 19 F NMR (376 MHz, DMSO-d6) δ -56.96; ESIMS m / z 403 ([M+H] + ).

[0152] Example 4: Preparation of 3-cyano-3-(4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)propionyl azide (C4) Preparation

Chemical Structure

[0153] In a vial, 3-cyano-3-(4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)propanoyl azide (C4 ; 50 mg, 0.117 mmol) and 3-(5-chloro-2-(trifluoromethyl) phenyl [Chemical formula] )-1H-1,2,4-triazol-3-yl)phenyl ; 50 mg, 0.117 mmol) and 3-(5-chloro-2-(trifluoromethyl) ​(Phenyl)-2-iminothiazolidin-4-one (C5; 41.4 mg, 0.14 mmol) was diluted with acetonitrile (3 mL) and heated to 75 °C over 30 minutes. The reaction mixture was cooled to rt and loaded onto silica. Purification by silica gel flash column chromatography using EtOAc - hexane:dichloromethane (DCM) (1:1)) gave the title compound as an off - white foam (24 mg, 28%).

[0154] Example 6: Preparation of 2,2,2 - trifluoro - 1 - (4 - methoxy - 2 - nitrophenyl)ethyl methanesulfonate (C6) [Chemical Structure Diagram] Step 1 - Preparation of 2,2,2 - trifluoro - 1 - (4 - methoxy - 2 - nitrophenyl)ethanol (C7): To 4 - methoxy - 2 - nitrobenzaldehyde (10 g, 55.2 mmol) in THF (100 mL) was added trimethyl(trifluoromethyl)silane (13 mL, 82.8 mmol) and cesium fluoride (CsF; 1.67 g, 11.0 mmol), and the reaction mixture was stirred under nitrogen at 0 °C for 3 hours. After 3 hours, concentrated hydrochloric acid (10 mL, 155 mmol) was added and the reaction mixture was stirred at rt for 30 minutes. The reaction mixture was diluted with water (100 mL) and extracted with DCM (2×100 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude title compound as a yellow oil, which was used without further purification in the next step (16 g): H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 2.8 Hz, 1H), 7.24 - 7.21 (m, 1H), 6.05 - 6.03 (m, 1H), 1 H NMR (400 MHz z, CDCl3) δ 7.83 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 2.8 Hz, 1H), 7.24 - 7.21 (m, 1H), 6.05 - 6.03 (m, 1H), ​​​​​​​​ 3.90 (s, 3H), 3.76 - 3.72 (m, 1H).

[0155] Step 2: Preparation of 2,2,2-trifluoro-1-(4-methoxy-2-nitrophenyl)ethyl methanesulfonate (C6) A solution of 2,2,2-trifluoro-1-(4-methoxy-2-nitrophenyl)ethan-1-ol (C7; 16 g, 63 .7 mmol) in DCM (160 mL) was added with diisopropylethylamine (DIPEA; 22 mL, 128 mmol), and the reaction mixture was cooled to 0 °C. Methanesulfonyl chloride (6.1 mL , 79.7 mmol) was added dropwise at 0 °C, and the reaction mixture was stirred at rt for 1 hour. The reaction mixture was diluted with water (100 mL) and extracted with DCM (2 × 50 mL). The organic layer was dried over anhydrous Na2 SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (100 - 200 mesh) eluting with 5 - 20% EtOAc in petroleum ether . The title compound was isolated as a red oil (8 g, 61%, over two steps): 1 H NMR (300 MHz, CDCl3) δ 7.78 (d, J = 8.7 Hz, 1H) 1 H NMR (300 MHz, CDCl3) δ 7.78 (d, J = 8.7 Hz, 1H) , 7.64 (d, J = 2.7 Hz, 1H), 7.29 - 7.26 (m, 1H), 6.97 - 6.95 (m, 1H), 3.92 (s, 3H), 3.12 (s, 3H).

[0156] Example 7: Preparation of 5-methoxy-2-(2,2,2-trifluoroethyl)aniline (C8) Preparation

Chemical Structure

[0157] The following compounds were prepared according to the procedures of Examples 6 and 7.

[0158] 5 - Methyl - 2 - (2,2,2 - trifluoroethyl)aniline (C9)

Chemical formula

[0159] Via previously reported conditions (U.S. Patent No. 9029560B2), all anilines were further converted to thiazolidinone intermediates.

[0160] Example 8: Preparation of 3 - (2 - (difluoromethyl)phenyl)-2 - iminothiazolidin - 4 - one (C10)​​

Chem.

[0161] The following compounds were prepared according to the procedure of Example 8.

[0162] 3-(2-(1,1-Difluoroethyl)phenyl)-2-iminothiazolidin-4-one in (C11)

Chem.

[0163] Example 9: 2-Chloro-N-(2-(difluoromethyl)phenyl)acetamide (C1 2) Preparation [ka] The title compound was synthesized using previously reported conditions (U.S. Pat. No. 9,029,560B2). was prepared and isolated as an oil (5.01 g, 86%): 1 H NMR (400MHz, C DCl3)δ 8.83(s,1H),8.13(d,J=8.2Hz,1H),7.5 7-7.49(m,1H),7.44(d,J=8.2Hz,1H),7.31-7.2 2(m,2H),6.69(t,J=54.8Hz,1H),4.23(s,2H);E IMS m / z 219.

[0164] The following compounds were prepared according to the procedure of Example 9.

[0165] 2-Chloro-N-(2-(1,1-difluoroethyl)phenyl)acetamide (C13 ) [ka] The title compound was isolated as a sticky oil which was carried forward without further manipulation (28 3mg, 44%): EIMS m / z 233.

[0166] Example 10: Preparation of 2-(difluoromethyl)aniline (C14) [ka] In a dry 1 L round-bottom flask under nitrogen, 1-(dichlorophenyl) fluoromethyl)-2-nitrobenzene (C15; 6.34 g, 36.6 mmol) and A solution of nickel(II) chloride (4.75 g, 36.6 mmol) was added to sodium borohydride. C. (2.77 g, 73.2 mmol) was added and the reaction mixture was stirred at 0.degree. C. for 3 h. The solution was filtered and concentrated under vacuum. The resulting residue was dissolved in DCM and washed with water. The organic layer was dried over Na2SO4 and concentrated under vacuum. The title compound was isolated as a brown oil (3.23 g, 52%): 1 H NMR (400 MHz, CDCl3) δ 7.29 - 7 .19 (m, 2H), 6.76 (m, 2H), 6.74 - 6.42 (m, 1H), 4.0 7 (s, 2H); EIMS m / z 143.

[0167] Example 11: Preparation of 1-(difluoromethyl)-2-nitrobenzene (C15)

Chemical formula

[0168] ​Example 12: Preparation of 2-(1,1-difluoroethyl)aniline (C16) [Chemical formula] In a dry 200 mL round-bottom flask, under a nitrogen atmosphere, in dry methanol (55.2 mL) A solution of sodium acetate (1.36 g, 16.6 mmol) and hydroxylamine hydrochloride (0. 768 g, 11.1 mmol) was added to 2-(1,1-difluoroethyl)-N-(di phenylmethylene)aniline (C17; 1.78 g, 5.52 mmol). The reaction mixture was stirred at 23 °C for 18 hours. The reaction mixture was concentrated under vacuum and diluted with DCM . The solution was washed with water. The organic layer was dried over Na2SO4 and concentrated under vacuum. Purification by flash chromatography eluting with a gradient of EtOAc in 0 - 20% hexane and subsequently a gradient of acetone in 0 - 20% hexane (silica gel, twice) gave the title compound as a yellow oil (265 mg, 15%): EIMS m / z 157. % of hexane in EtOAc gradient and subsequently 0 - 20% of hexane in acetone gradient elution (silica gel, twice) gave the title compound as a yellow oil (265 mg, 15%): EIMS m / z 157. yellow oil (265 mg, 15%): EIMS m / z 157.

[0169] Example 13: Preparation of 2-(1,1-difluoroethyl)-N-(diphenylmethylene)aniline (C17) [Chemical formula] In a dry 20 mL microwave vial, under a nitrogen atmosphere, 1-bromo-2-(1,1 -difluoroethyl)benzene (C18; 1.62 g, 7.33 mmol) was added to dry tolu ene (14.7 mL) containing sodium tert-butoxide (1.06 g, 11.0 mmo l), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3; 0 .336 g, 0.366 mmol), (oxybis(2,1-phenylene))bis(dif (0.395 g, 0.733 mmol) of phenylphosphine and diphenylmethanimine was added to a solution of (1.60 mL, 9.53 mmol). In a Biotage (registered trademark) microwave reactor, the reaction mixture was stirred at 100 °C for 3 hours. The reaction mixture was diluted with DCM and washed with water. The organic layer was dried over Na2SO4 and concentrated under vacuum. Purification by flash chromatography (silica gel) eluting with a gradient of EtOAc in hexane from 0 to 20% gave the title compound as an orange oil (1.78 g, 68%): 1 H N MR (500 MHz, CDCl3) δ 7.78 (d, J = 7.0 Hz, 1H), 7.5 3 - 7.44 (m, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.28 - 7.2 3 (m, 3H), 7.22 - 7.17 (m, 2H), 7.04 (t, J = 7.6 Hz, 1 H), 6.95 (t, J = 7.6 Hz, 1H), 6.33 - 6.27 (m, 1H), 2. 14 (t, J = 18.8 Hz, 3H); HRMS - ESI (m / z) [M + H] + C 21 H 17 F2N calculated value 321.1329; found 321.1333.

[0170] Example 14: Preparation of 1 - bromo - 2 - (1,1 - difluoroethyl)benzene (C18)

Chemical Structure

[0171] Example 15: Preparation of methyl 2-methyl-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)benzoate (C19)

Chemical formula

[0172] The following compounds were prepared according to the procedure of Example 15.

[0173] Methyl 2 - methyl - 4-(1-(4-(perfluoroethoxy)phenyl)-1H - 1, 2,4 - triazol - 3 - yl)benzoate (C20)

Chemical Structure

[0174] Methyl 2-methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1 ,2,4-triazol-3-yl)benzoate (C21)

Chemical formula

[0175] Methyl 3-methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1, 2,4-triazol-3-yl)benzoate (C22)

Chemical formula

[0176] Methyl 3-methyl-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1, 2,4-triazol-3-yl)benzoate (C23)

Chem.

[0177] Methyl 2-methoxy-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1 , 2,4-triazol-3-yl)benzoate (C24)

Chem.

[0178] Methyl 2-fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1H-1, (2,4-Triazol-3-yl)benzoate (C25)

Chem.

[0179] Methyl 2-methoxy-4-(1-(4-(trifluoromethyl)phenyl)-1H-1, (2,4-triazol-3-yl)benzoate (C26)

Chem.

[0180] Methyl 3-methyl-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2 ,4-triazol-3-yl)benzoate (C27)

Chem.

[0181] Example 16: Preparation of 2 - Methyl - 4-(1-(4-(trifluoromethyl)phenyl)-1H - 1,2,4 - triazol - 3 - yl)benzoic acid (C28)

Chemical Structure

[0182] The following compounds were prepared according to the procedure of Example 16.

[0183] 2-Methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)benzoic acid (C29)

Chemical Structure

[0184] 2-Methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2, 4-triazol-3-yl)benzoic acid (C30)

Chemical Structure

[0185] 3-Methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)benzoic acid (C31)

Chem.

[0186] 3-Methyl-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)benzoic acid (C32)

Chem.

[0187] 2-Methoxy-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2, 4-Triazol-3-yl)benzoic acid (C33)

Chem.

[0188] 2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4 -triazol-3-yl)benzoic acid (C34)

Chem.

[0189] 3-Methyl-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4- triazol-3-yl)benzoic acid (C35)

Chem.

[0190] Example 17: Preparation of 2 - methyl - 4-(1-(4-(trifluoromethyl)phenyl)-1H - 1,2,4 - triazol - 3 - yl)benzoyl azide (C36)

Chemical Structure

[0191] The following compounds were prepared according to the procedure of Example 17.

[0192] 2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4 -triazol-3-yl)benzoyl azide (C37)

Chemical Structure

[0193] 2-Methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)benzoyl azide (C38)

Chemical Structure

[0194] 2-Methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2, 4-triazol-3-yl)benzoyl azide (C39)

Chem.

[0195] 3-Methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)benzoyl azide (C40)

Chem.

[0196] 3-Methyl-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)benzoyl azide (C41)

Chemical formula

[0197] 2-Methoxy-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2, 4-triazol-3-yl)benzoyl azide (C42)

Chemical formula

[0198] 2-Methoxy-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4 -triazol-3-yl)benzoyl azide (C43)

Chem.

[0199] 3-Methyl-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4- triazol-3-yl)benzoyl azide (C44)

Chem.

[0200] Example 18: Preparation of 3-bromo-1-(3-(trifluoromethyl)phenyl)-1H-1,2 ,4-triazole (C45)

Chem.

[0201] The following compounds were prepared according to the procedure of Example 18.

[0202] 3-Bromo-1-(3-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C46) 3-Bromo-1-(3-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C46)

Chemical Structure

[0203] 3-Bromo-1-(p-tolyl)-1H-1,2,4-triazole (C47)

Chem.

[0204] 3-Bromo-1-(4-methoxyphenyl)-1H-1,2,4-triazole (C48 )

Chem.

[0205] Example 19. Preparation of 2-Fluoro-4-(1-(3-(trifluoromethyl)phenyl)-1H -1,2,4-triazol-3-yl)aniline (C49)

Chem.

[0206] The following compounds were prepared according to the procedure of Example 19.

[0207] 2 - Methyl - 4-(1-(3-(trifluoromethyl)phenyl)-1H - 1,2,4 - (Triazol-3-yl)aniline (C50) [Chemical formula] The title compound was prepared and isolated as a yellow solid (1.5 g, 53%): mp 135~ 140 °C; 1 H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.28 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.83 - 7.81( m, 4H), 6.70 (d, J = 8.4 Hz, 1H), 5.27 (br s, 2H) 2. 14 (s, 3H); 13 C NMR (101 MHz, DMSO-d6) δ 163.02 , 148.38, 143.25, 137.42, 131.07, 130.41, 128. 13, 125.07, 123.55, 122.62, 122.36, 120.78, 11 7.63, 115.27, 113.62, 17.44; 19 F NMR (376 MHz, DMSO-d6) -61.20; ESIMS m / z 319 ([M+H] + ).

[0208] 2-Fluoro-4-(1-(3-(trifluoromethoxy)phenyl)-1H-1,2, 4-triazol-3-yl)aniline (C51) [Chemical formula] The title compound was prepared and isolated as a pale yellow solid (1.7 g, 55%): mp 142 ~144 °C; 1 H NMR (300 MHz, DMSO-d6) δ 9.37 (s, 1H) , 7.99 (s, 1H), 7.96 (s, 1H), 7.73 - 7.62 (m, 3H), 7 .41 (d, J = 8.4 Hz, 1H), 6.86 (t, J = 8.8 Hz, 1H), 5.5 9 (br s, 2H); 13 C NMR (75 MHz, DMSO-d6) δ 161.9 5, 151.76, 148.99, 148.62, 143.53, 138.30, 138 .09, 131.73, 122.94, 119.48, 117.77, 115.92, 1 12.83, 112.56, 111.85; 19 F NMR (282 MHz, DMSO - d6) δ -56.81; ESIMS m / z 339 ([M + H] + ).

[0209] 2-Methyl-4-(1-(3-(trifluoromethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)aniline (C52)

Chem.

[0210] 2-Fluoro-4-(1-(p-tolyl)-1H-1,2,4-triazol-3-yl )aniline (C53)

Chem.

[0211] 2-Fluoro-4-(1-(4-methoxyphenyl)-1H-1,2,4-triazol -3-yl)aniline (C54)

Chemical formula

[0212] Example 20: Preparation of 2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)aniline (C55)

Chemical Structure

[0213] The following compounds were prepared according to the procedure of Example 20.

[0214] 2 - Methyl - 4-(1-(4-(trifluoromethoxy)phenyl)-1H - 1,2,4 -triazol - 3 - yl)aniline (C56)

Chemical formula

[0215] 2 - Chloro - 4-(1-(4-(trifluoromethoxy)phenyl)-1H - 1,2,4 -triazol - 3 - yl)aniline (C57)

Chemical formula

[0216] 2 - Ethyl - 4-(1-(4-(trifluoromethoxy)phenyl)-1H - 1,2,4 -triazol - 3 - yl)aniline (C58)

Chem.

[0217] 2 - Methoxy - 4-(1-(4-(trifluoromethoxy)phenyl)-1H - 1,2, 4 - triazol - 3 - yl)aniline (C59)

Chem.

[0218] 2 - Isopropyl - 4-(1-(4-(trifluoromethoxy)phenyl)-1H - 1, 2,4 - triazol - 3 - yl)aniline (C60)

Chemical Structure

[0219] 2 - Fluoro - 4-(1-(4-(trifluoromethyl)phenyl)-1H - 1,2,4 -Triazol-3-yl)aniline (C61)

Chem.

[0220] 2-Methyl-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4- triazol-3-yl)aniline (C62)

Chem.

[0221] 2-Chloro-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4- triazol-3-yl)aniline (C63)

Chem.

[0222] 2-Fluoro-4-(1-(4-(2,2,2-trifluoroethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)aniline (C64)

Chem.

[0223] 2-Fluoro-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2, (4 - Triazol - 3 - yl)aniline (C65)

Chem.

[0224] 2 - Fluoro - 4-(1-(4 - ((trifluoromethyl)thio)phenyl)-1H - 1 , 2,4 - triazol - 3 - yl)aniline (C66)

Chem.

[0225] 2 - Methyl - 4-(1-(4 - ((trifluoromethyl)thio)phenyl)-1H - 1, 2,4 - triazol - 3 - yl)aniline (C67) [Chemical formula] The title compound was prepared and isolated as a white solid (444 mg, 40%): 1 H NM R (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.50 (s, 1H), 7 .83 - 7.81 (m, 3H), 7.77 - 7.72 (m, 2H), 6.76 (d, J = 8.2 Hz, 1H), 3.83 (s, 2H), 2.25 (s, 3H); 19 F NMR ( 376 MHz, CDCl3) δ -42.47; ESIMS m / z 351 ([M + H + ).

[0226] 2-Chloro-4-(1-(4-((trifluoromethyl)thio)phenyl)-1H-1, 2,4-triazol-3-yl)aniline (C68) [Chemical formula] The title compound was prepared and isolated as a white solid (500 mg, 42%): 1 H NM R (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.12 (d, J = 1.9 Hz, 1H), 7.90 (dd, J = 8.3, 1.9 Hz, 1H), 7.86 - 7.74 (m, 4H), 6.85 (d, J = 8.4 Hz, 1H), 4.27 (s, 2H); 19 F NMR (376 MHz, CDCl3) δ -42.68; ESIMS m / z 371 ([M + H] + ).

[0227] 2-Fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2-yl)-1H -1,2,4-triazol-3-yl)aniline (C69) [Chemical formula]​ The title compound was prepared and isolated as a white solid (367 mg, 33%): 1 H NM R (400 MHz, CDCl3) δ 9.10 (s, 1H), 8.48 - 8.30 (m, 1H), 8.03 (dd, J = 8.9, 0.7 Hz, 1H), 7.91 - 7.69 (m, 3H), 6.86 (t, J = 8.5 Hz, 1H), 3.94 (s, 2H); 19 F NM R (376 MHz, CDCl3) δ -58.40, -135.35; HRMS-ESI (m / z) [M + H] + C 14 Calculated for C H9F4N5O 340.0816; found 340

[0228] 2-Methyl-4-(1-(5-(trifluoromethoxy)pyridin-2-yl)-1H- 1,2,4-triazol-3-yl)aniline (C70)

Chemical Structure

[0229] 2-Chloro-4-(1-(5-(trifluoromethoxy)pyridin-2-yl)-1H- 1,2,4-triazol-3-yl)aniline (C71)

Chemical formula

[0230] 2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H- 1,2,4-triazol-3-yl)aniline (C72)

Chemical formula

[0231] 2-Methyl-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-1 ,2,4-triazol-3-yl)aniline (C73)

Chemical formula

[0232] 2-Chloro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-1 ,2,4-triazol-3-yl)aniline (C74)

Chemical formula

[0233] 2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H- pyrazol-3-yl)aniline (C75)

Chem.

[0234] 2-Methyl-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-py razol-3-yl)aniline (C76)

Chem.

[0235] Example 21: 2-Bromo-4-(1-(4-(trifluoromethoxy)phenyl)-1H Preparation of (1,2,4-triazol-3-yl)aniline (C77) [ka] 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazo (3-yl)aniline (as described in International Publication No. 2009102736A1) (prepared as described above; 1.5 g, 4.68 mmol) was dissolved in acetonitrile (25 mL). The mixture was dissolved in water and N-bromosuccinimide (0.917 g, 5.15 mmol) was added. The mixture was stirred for 2 min and then poured into water. The reaction mixture was extracted with EtOAc. The organic extract was washed with brine, dried over Na2SO4 and concentrated. Loaded on algal earth. Silica gel chromatograph eluted with 0-25% acetone-hexane. Purification by HPLC afforded the title compound as a yellow solid (1.45 g, 77%): 1 H NMR(400MHz,CDCl3)δ 8.51(s,1H),8.28(d,J= 1.9 Hz, 1H), 7.94 (dd, J = 8.4, 1.9 Hz, 1H), 7.81 - 7 .75 (m, 2H), 7.41 - 7.35 (m, 2H), 6.84 (d, J = 8.3 Hz , 1H), 4.30 (s, 2H); ESIMS m / z 401 ([M + H] + ).

[0236] Example 22: Preparation of 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4 -triazol-3-yl)-2-(trifluoromethyl)aniline (C78)

Chemical Structure

[0237] The following compounds were prepared according to the procedure of Example 22.

[0238] 2,6-Dimethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1, 2,4-triazol-3-yl)aniline (C79)

Chemical formula

[0239] 2,6-Difluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1 , 2,4-triazol-3-yl)aniline (C80)

Chemical formula

[0240] 3-(3-(Methoxymethoxy)-4-nitrophenyl)-1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazole (C81)

Chem.

[0241] 2-Amino-5-(1-(5-(trifluoromethoxy)pyridin-2-yl)-1H- 1,2,4-triazol-3-yl)benzonitrile (C82)

Chem.

[0242] 4-(1-(5-(Trifluoromethoxy)pyridin-2-yl)-1H-1,2,4- triazol-3-yl)-2-(trifluoromethyl)aniline (C83)

Chem.

[0243] 2-(Trifluoromethyl)-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)aniline (C84)

Chem.

[0244] 4-(3-(4-Amino-3-fluorophenyl)-1H-1,2,4-triazol- 1-yl)benzonitrile (C85)

Chemical formula

[0245] Example 23: Preparation of 2-Amino-5-(1-(4-(trifluoromethoxy)phenyl)-1H -1,2,4-triazol-3-yl)benzonitrile (C86)

Chemical formula

[0246] Example 24: Preparation of 2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)aniline (C87)

Chemical Structure

[0247] Example 25: Preparation of 2 - methyl - 4 - (4,4,5,5 - tetramethyl - 1,3,2 - dioxaborolan - 2 - yl) aniline (C88) To a 250 mL round - bottom flask, 4 - bromo - 2 - methylaniline (5.0 g, 26.9 mmol), 4,4,4’,4’,5,5,5’,5’ - octamethyl - 2,2’ - bi( (1,3,2 - dioxaborolane) (8.96 g, 35.3 mmol), potassium acetate (5 .27 g, 53.7 mmol) and dioxane (90 mL) were added. The reaction mixture was degassed and filled with nitrogen (3×). [1,1’ - Bis(diphenylphosphino) ferrocene dichloropalladium(II) (0.98 g, 1.34 mmol) was added and the reaction mixture was stirred at 90 °C for 3 h. The reaction mixture was cooled, concentrated, and diluted with EtOAc and water . The mixture was extracted with EtOAc (3×). The organic extract was washed with brine, dried over anhydrous Na2 SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography gave the title compound as a pale yellow semi - solid (4.12 g, 63%): 1H NMR (4 1 00 MHz, CDCl3) δ 7.55 - 7.47 (m, 2H), 6.65 (d, J = 7 .7 Hz, 1H), 3.78 (s, 2H), 2.16 (s, 3H), 1.32 (s, 12 H); 13 ​​13C NMR (101 MHz, CDCl3) δ 147.62, 137.28, 134.17, 132.85, 129.58, 121.12, 116.34, 114.0 2, 110.09, 83.50, 83.26, 25.04, 24.85, 21.04, 1 7.19, 16.99, 14.21.

[0248] Example 26: Preparation of 2,6-difluoro-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)aniline (C89)

Chemical Structure

[0249] The following compounds were prepared according to the procedure of Example 26.

[0250] 2-(3-(Methoxymethoxy)-4-nitrophenyl)-4,4,5,5-tetramethyl -1,3,2-dioxaborolane (C90)

Chem.

[0251] Example 27: Preparation of 4-bromo-2-(methoxymethoxy)-1-nitrobenzene (C91) Preparation

Chem.

[0252] Example 28: Preparation of 4-(3-bromo-1H-1,2,4-triazol-1-yl)benzonitrile (C92)

Chemical Structure

[0253] Example 29: Preparation of 3-bromo-1-(4-(pentafluoro-λ 6 -sulfanyl)phenyl )-1H-1,2,4-triazole (C93)

Chemical Structure

[0254] The following compounds were prepared according to the procedure of Example 29.

[0255] 3 - Bromo - 1 - (4 - (trifluoromethoxy)phenyl)-1H - pyrazole (C9 H4)

Chemical Structure

[0256] 2 - (3 - Bromo - 1H - 1,2,4 - triazol - 1 - yl)-5 - (trifluoromethyl)pyridine (C9H5) N2BrF3)

Chemical Structure

[0257] 2-(3-Bromo-1H-pyrazol-1-yl)-5-(trifluoromethyl)pyridine (C96)

Chem.

[0258] 2-(3-Bromo-1H-pyrazol-1-yl)-5-(trifluoromethoxy)pyridine (C97)

Chem.

[0259] Example 30: (Z)-1-(3-(2-Ethyl-5-methylphenyl)-4-oxothia zolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethoxy phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J16 ) Preparation

Chemical Structure

[0260] The following compounds were prepared according to the procedure of Example 30.

[0261] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazoli din-2-ylidene)-3-(2-methyl-4-(1-(4-(perfluoroethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J2) The title compound was prepared and isolated as an orange solid (25 mg, 70%).

[0262] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolid in-2-ylidene)-3-(2-methoxy-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J3) The title compound was prepared and isolated as a dark brown oil (40 mg, 32%).

[0263] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolid in-2-ylidene)-3-(3-methyl-4-(1-(4-(trifluoromethyl)phe nyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J4) The title compound was prepared and isolated as a dark brown solid (150 mg, 55%).

[0264] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazoli din-2-ylidene)-3-(3-methyl-4-(1-(4-(trifluoromethyl)f (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J5) The title compound was prepared and isolated as a yellow solid (80 mg, 38%).

[0265] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J5) 2-ylidene)-3-(2-methoxy-4-(1-(4-(trifluoromethoxy )phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J6) The title compound was prepared and isolated as an orange solid (16 mg, 13%).

[0266] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J5) 2-ylidene)-3-(3-methyl-4-(1-(4-(perfluoroethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J7) The title compound was prepared and isolated as a yellow solid (23 mg, 21%).

[0267] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(trifluoromethyl) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J10) The title compound was prepared and isolated as a brown solid (19 mg, 11%).

[0268] (Z)-1-(3-(5-Methyl-2-propylphenyl)-4-oxothiazolidin-2-ylidene)-3-(3-methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J12) 2-ylidene)-3-(3-methyl-4-(1-(4-(perfluoroethoxy)phenyl yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J12) The title compound was prepared and isolated as an orange solid (70 mg, 31%).

[0269] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin -2-ylidene)-3-(2-methoxy-4-(1-(4-(trifluoromethyl)p henyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J13) The title compound was prepared and isolated as a yellowish brown solid (18 mg, 11%).

[0270] (Z)-1-(3-(2-Ethyl-5-methylphenyl)-4-oxothiazolidin-2 -ylidene)-3-(3-methyl-4-(1-(4-(perfluoroethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)urea (J14) The title compound was prepared and isolated as a red oil (47 mg, 22%).

[0271] (Z)-1-(3-(5-Methyl-2-propylphenyl)-4-oxothiazolidine- 2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethyl)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)urea (J15) The title compound was prepared and isolated as a yellowish brown solid (39 mg, 13%).

[0272] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazoli dine-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethyl)p henyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J18) The title compound was prepared and isolated as a yellowish brown solid (34 mg, 15%).

[0273] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- propylphenyl)-4-oxothiazolidin-2-ylidene)urea (J20) The title compound was prepared and isolated as an orange solid (60 mg, 26%).

[0274] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J21) The title compound was prepared and isolated as a yellowish brown solid (33 mg, 15%).

[0275] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazoli din-2-ylidene)-3-(3-methyl-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J22) The title compound was prepared and isolated as a yellow solid (36 mg, 15%).

[0276] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolid ine-2-ylidene)-3-(3-methyl-4-(1-(4-(trifluoromethoxy)p henyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J23) The title compound was prepared and isolated as a yellow solid (31 mg, 13%).

[0277] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolid (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J24) (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J24) The title compound was prepared and isolated as a yellowish brown solid (68 mg, 32%).

[0278] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J24) (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J24) (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J25) The title compound was prepared and isolated as a pink solid (86 mg, 39%).

[0279] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J28) (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J28) (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J28) The title compound was prepared and isolated as an orange solid (28 mg, 22%).

[0280] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J29) (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J29) (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(perfluoroethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J29) The title compound was prepared and isolated as an orange solid (29 mg, 21%).

[0281] Example 31: (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoro oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoro (Methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea Preparation of J1

Chemical formula

[0282] The following compounds were prepared according to the procedure of Example 31.

[0283] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazoli din-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethyl)f enyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J8) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazol in-4-one (C98) and isolated as a bright yellow solid (32 mg, 32% ).

[0284] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin -2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethyl)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)urea (J9) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazol in-4-one (as described in US Patent Application Publication No. 20140274688A1 ) and isolated as a bright yellow film (11 mg, 11%).

[0285] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J11) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazol in-4-one (C98) and isolated as a pale orange solid (72 mg, 74%).

[0286] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isoprop yl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J19) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazol Zin-4-one (prepared as described in US Patent Application Publication No. 20140274688A1 and isolated as a pale yellow solid (132 mg, 46%).

[0287] (Z)-1-(2-Fluoro-4-(1-(4-(perfluoroethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl 5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J26) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazol Zin-4-one (prepared as described in US Patent Application Publication No. 20140274688A1 and isolated as a white solid (32 mg, 18%).

[0288] (Z)-1-(2-Fluoro-4-(1-(4-(perfluoroethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl 5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J27) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazol Zin-4-one (C98) and isolated as a light purple solid (64 mg, 35% ).

[0289] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea ( J30) The title compound was prepared from 2-imino-3-(5-methyl-2-(trifluoromethyl)phenyl )Thiazolidin-4-one (prepared as described in WO 2017 / 040742 A1 pamphlet) and isolated as an orange foam (150 mg, 50%). And isolated as an orange foam (150 mg, 50%).

[0290] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2-yl lidene)urea (J31) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (prepared as described in WO 2017 / 040742 A1 pan phlet) and isolated as a yellow solid (181 mg, 5 8%).

[0291] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2- ylidene)urea (J35) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an orange foam (250 mg, 78%).

[0292] (Z)-1-(2-Chloro-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl (Z)-1-(2-Chloro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J37) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazole -4-one (C98) and isolated as an off-white solid (136 mg, 47 %).

[0293] (Z)-1-(2-Chloro-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J38) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazole -4-one (as described in US Patent Application Publication No. 20140274688A1 and isolated as an off-white solid (214 mg, 77%).

[0294] (Z)-1-(2-Chloro-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J 39) The title compound was prepared from 2-imino-3-(5-methyl-2-(trifluoromethyl)phenyl )thiazolidin-4-one (as described in International Publication No. 2017040742A1 and isolated as an off-white solid (174 mg, 62%).

[0295] (Z)-1-(2-Chloro-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (2,2,2-Trifluoroethoxy)phenyl)-4-oxothiazolidin-2-ylidene urea (J40) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (prepared as described in International Publication No. 2017040742A1 pamphlet) and isolated as an off-white solid (151 mg, 51%).

[0296] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -propylphenyl)-4-oxothiazolidin-2-ylidene)urea (J41) The title compound was prepared from 2-imino-3-(5-methyl-2-propylphenyl)thiazolidin -4-one (prepared as described in International Publication No. 2016033025A1 pamphlet) and isolated as an orange foam (58 mg, 20%).

[0297] (Z)-1-(3-(5-Chloro-2-(trifluoromethyl)phenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-chloro-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 42) The title compound was prepared from 3-(5-chloro-2-(trifluoromethyl)phenyl)-2-im nothiazolidin-4-one (C5) and isolated as an off-white solid (116 m g, 40%).

[0298] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- (1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methoxy- 2-propylphenyl)-4-oxothiazolidin-2-ylidene)urea (J43) The title compound was prepared from 2-imino-3-(5-methoxy-2-propylphenyl)thiazolidin -4-one (C113) and isolated as an off-white solid (135 mg, 69 %).

[0299] (Z)-1-(3-(2-butyl-5-methylphenyl)-4-oxothiazolidin-2 -ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)urea (J44) The title compound was prepared from 3-(2-butyl-5-methylphenyl)-2-iminothiazolidin -4-one (C114) and isolated as an orange foam (40 mg, 22% ).

[0300] (Z)-1-(3-(2-butyl-5-methoxyphenyl)-4-oxothiazolidin- 2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)urea (J45) The title compound was prepared from 3-(2-butyl-5-methoxyphenyl)-2-iminothiazolidin -4-one (C116) and isolated as an orange foam (80 mg, 42 %).

[0301] (Z)-1-(3-(5-chloro-2-isopropylphenyl)-4-oxothiazolidin -2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J46) The title compound was prepared from 3-(5-chloro-2-isopropylphenyl)-2-iminothiazole din-4-one (prepared as described in International Publication No. WO 2016 / 033025 A1) and isolated as a pale yellow solid (112 mg, 56%).

[0302] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isobutyl -5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J47) The title compound was prepared from 2-imino-3-(2-isobutyl-5-methylphenyl)thiazolidine -4-one (C122) and isolated as a pale yellow solid (101 mg, 51% ).

[0303] (Z)-1-(3-(2-(sec-Butyl)-5-methoxyphenyl)-4-oxoth iazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 48) The title compound was prepared from 3-(2-(sec-butyl)-5-methoxyphenyl)-2-imino thiazolidin-4-one (C123) and isolated as a pale yellow solid (120 mg, 63%).

[0304] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-meth oxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea ( J49) ​The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1) and isolated as a yellow solid (70 mg, 35%).

[0305] (Z)-1-(3-(2,5-Bis(trifluoromethyl)phenyl)-4-oxothia zolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J5 0) The title compound was prepared from 3-(2,5-bis(trifluoromethyl)phenyl)-2-iminoth iazolidin-4-one (C137) and isolated as a white solid (40 mg, 18%).

[0306] (Z)-1-(3-(2-(sec-Butoxy)-5-methylphenyl)-4-oxoth iazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 51) The title compound was prepared from 3-(2-(sec-butoxy)-5-methylphenyl)-2-imino thiazolidin-4-one (C146) and isolated as a bright yellow film (42 mg, 21%).

[0307] (Z)-1-(2-Fluoro-4-(1-(4-(perfluoroethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -propylphenyl)-4-oxothiazolidin-2-ylidene)urea (J52) ​The title compound was prepared from 2-imino-3-(5-methyl-2-propylphenyl)thiazolidin-4-one (prepared as described in WO 2016 / 033025 A1) and isolated as a white solid (20 mg, 11%).

[0308] (Z)-1-(3-(5-Methyl-2-propylphenyl)-4-oxothiazolidin- 2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J53) The title compound was prepared from 2-imino-3-(5-methyl-2-propylphenyl)thiazolidin-4-one (prepared as described in WO 2016 / 033025 A1) and isolated as an orange solid (64 mg, 34%).

[0309] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazolidin- 2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J54) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazolidin-4-one (C98) and isolated as an orange solid (135 mg, 71%).

[0310] (Z)-1-(3-(5-Methyl-2-(2,2,2-trifluoroethoxy)phenyl )-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-( trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J55) ​The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth xy)phenyl)thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040742 A1 ) and isolated as an off-white solid (144 mg, 71%).

[0311] (Z)-1-(3-(5-Methyl-2-(3,3,3-trifluoropropoxy)phenyl yl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl yl)urea (J56) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an orange solid (164 mg, 79%).

[0312] (Z)-1-(2-Fluoro-4-(1-(4-(2,2,2-trifluoroethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2 -isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J57) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)-thiazo lidin-4-one (prepared as described in U.S. Patent Application Publication No. 2014 / 0274688 A1 ) and isolated as an orange solid (68 mg, 73%).

[0313] (Z)-1-(2-Fluoro-4-(1-(4-(2,2,2-trifluoroethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2 -Isopropyl-5-methoxyphenyl)-4-oxothiazolidine-2-ylidene)urea (J58) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazole din-4-one (C98) and isolated as an orange solid (46 mg, 4 9%).

[0314] (Z)-1-(3-(2-Ethoxy-5-methylphenyl)-4-oxothiazolidine- 2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)urea (J59) The title compound was prepared from 3-(2-ethoxy-5-methylphenyl)-2-iminothiazolidine -4-one (prepared as described in WO 2017 / 040194 A1 pamphlet) and isolated as a yellow solid (70 mg, 76%).

[0315] (Z)-1-(3-(2-(1-Methoxyethyl)-5-methylphenyl)-4-oxo thiazolidine-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethoxy phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 60) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )thiazolidine-4-one (prepared as described in WO 2017 / 040194 A1 pamphlet) and isolated as a yellow solid (37 mg, 39%).

[0316] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1 ​(H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J61) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)-thia zolidin-4-one (as described in US Patent Application Publication No. 20140274688A1) and isolated as a pale orange solid (69 mg, 71%).

[0317] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-methoxy ethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J 62) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )thiazolidin-4-one (as described in International Publication No. 2017040194A1) and isolated as an orange solid (58 mg, 60%).

[0318] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea (J63) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (as described in International Publication No. 2017040742A1) and isolated as an off-white solid (81 mg, 7 8%). 8%)

[0319] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-yl lidene)urea (J64) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoro propoxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white solid (80 mg, 76%).

[0320] (Z)-1-(3-(2-(sec-Butyl)-5-methylphenyl)-4-oxothia zolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluorometh yl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J65 ) The title compound was prepared from 3-(2-(sec-butyl)-5-methylphenyl)-2-iminothi azolidin-4-one (C115) and isolated as an off-white solid (87 mg , 87%).

[0321] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(methoxy methyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J6 6) The title compound was prepared from 2-imino-3-(2-(methoxymethyl)-5-methylphenyl)thi azolidin-4-one (as described in WO 2017 / 040742A1 pamphlet) and ​Prepared from (prepared as described in International Publication No. 2017040742A1 Pamphlet) and isolated as a white solid (37 mg, 20%).

[0322] (Z)-1-(3-(2-(Methoxymethyl)-5-methylphenyl)-4-oxothia zolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethoxy phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J67 ) The title compound was prepared from 2-imino-3-(2-(methoxymethyl)-5-methylphenyl)thia zolidin-4-one (as described in International Publication No. 2017040742A1 Pamphlet) and isolated as a white solid (130 mg, 70%).

[0323] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea ( J68) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an orange solid (133 mg, 68%).

[0324] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J70) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli ​Zin-4-one (prepared as described in US Patent Application Publication No. 20140274688A1 ), and isolated as a yellow foam (37 mg, 41%).

[0325] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J71) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazol in-4-one (C98), and isolated as a bright yellow foam (46 mg, 48% ).

[0326] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(methoxymeth yl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J72 ) The title compound was prepared from 2-imino-3-(2-(methoxymethyl)-5-methylphenyl)th iazolidin-4-one (as described in International Publication No. 2017040742A1 pamphlet ), and isolated as a yellow foam (47 mg, 50%).

[0327] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-yl idene)urea (J73) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop (oxy)phenyl)thiazolidin-4-one (C99) and isolated as a yellow foam (45 mg, 43%).

[0328] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-methoxy ethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J 74) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040194 A1) and isolated as a yellow foam (31 mg, 32%).

[0329] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea (J75) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040742 A1) and isolated as a yellow foam (62 mg, 61 %).

[0330] (Z)-1-(3-(5-Cyano-2-isopropylphenyl)-4-oxothiazolidin ene-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy) ​​​​(Z)-1-(3-(5-Acetyl-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J76) The title compound was prepared from 3-(2-imino-4-oxothiazolidin-3-yl)-4-isopropylbenzonitrile (C108) and isolated as a yellowish brown solid (59 mg, 28%).

[0331] (Z)-1-(3-(5-Acetyl-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J77) The title compound was prepared from 3-(5-acetyl-2-isopropylphenyl)-2-iminothiazolidin-4-one (C109) and isolated as a white solid (31 mg, 32%).

[0332] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J83) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-iminothiazolidin-4-one (C126) and isolated as a yellow foam (41 mg, 43%).

[0333] (Z)-1-(3-(3-(Dimethylamino)phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J84) ​​​​​​​​​​​​​The title compound was prepared from 3-(3-(dimethylamino)phenyl)-2-iminothiazolidin- 4-one (C100) and isolated as an off-white solid (34 mg, 38%).

[0334] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl l-5-(methylamino)phenyl)-4-oxothiazolidin-2-ylidene)urea( J85) The title compound was prepared from 2-imino-3-(2-isopropyl-5-(methylamino)phenyl )thiazolidin-4-one hydrochloride (C150) and isolated as an off-white solid (37 mg, 20%).

[0335] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl lphenyl)-4-oxothiazolidin-2-ylidene)urea (J86) The title compound was prepared from 2-imino-3-(2-isopropylphenyl)thiazolidin-4-o ne (prepared as described in WO 2016 / 033025 A1) and isolated as a white solid (27 mg, 30%).

[0336] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-meth oxyethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J87) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)phenyl)thiazolid Prepared from N-4-one (C124) and isolated as a white foam (31 mg, 32%) 。

[0337] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-(me thylthio)ethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J88 ) The title compound was prepared from 2-imino-3-(2-(1-(methylthio)ethyl)phenyl)thia zolidin-4-one (C149) and isolated as a bright yellow solid (16 mg, 17%).

[0338] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-ox othiazolidin-2-ylidene)-3-(2-methoxy-4-(1-(4-(triflu romethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J89) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-im inothiazolidin-4-one (C126) and isolated as an off-white solid (6 2 mg, 65%).

[0339] (Z)-1-(2-Methoxy-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-meth oxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea ( J90) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )Thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1 and isolated as an off-white solid (56 mg, 60%).

[0340] (Z)-1-(2-Methoxy-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2- ylidene)urea (J91) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white foam (46 mg, 46%).

[0341] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methoxy- 2-(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2 -ylidene)urea (J92) The title compound was prepared from 2-imino-3-(5-methoxy-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C110) and isolated as an off-white solid (68 mg, 65%).

[0342] (Z)-1-(2-Isopropyl-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl -2-(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin- 2-ylidene)urea (J93) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop (oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white foam (147 mg, 74%).

[0343] (Z)-1-(2-Isopropyl-4-(1-(4-(trifluoromethoxy)phenyl ))-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1- methoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J94) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl ))thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040194A1 pamphlet) and isolated as a white, fluffy solid (76 mg, 41%).

[0344] (Z)-1-(2-Isopropyl-4-(1-(4-(trifluoromethoxy)phenyl ))-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isop ropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J99 )) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (prepared as described in U.S. Patent Application Publication No. US 2014 / 0274688A1 specification) and isolated as an off-white solid (113 mg, 61%).

[0345] (Z)-1-(2-Isopropyl-4-(1-(4-(trifluoromethoxy)phenyl ))-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isop ​​​(5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J1 00) The title compound was synthesized by 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazolyl Prepared from di-4-one (C98) and isolated as a pale orange solid (125 mg , 66%).

[0346] (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxo Sothiazolidine-2-ylidene)-3-(2-isopropyl-4-(1-(4-(trifluoromethyl) (fluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl Urea (J101) The title compound was synthesized by the reaction of 3-(5-(dimethylamino)-2-isopropylphenyl)-2-isopropyl Prepared from minothiazolidin-4-one (C126) and isolated as an off-white solid (1 27mg, 66%).

[0347] (Z)-1-(3-(5-(dimethylamino)-2-(3,3,3-trifluoropropionyl) 4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-phenyl)- (1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole- 3-I)phenyl)urea (J102) The title compound was synthesized by the reaction of 3-(5-(dimethylamino)-2-(3,3,3-trifluoropropanediol) Prepared from (2-(methoxy)phenyl)-2-iminothiazolidin-4-one (C101) and is gray-white It was isolated as a white foam (89 mg, 82%).

[0348] (Z)-1-(3-(5-cyano-2-(3,3,3-trifluoropropoxy)phenyl) (R)-4-oxothiazolidine-2-ylidene)-3-(2-fluoro-4-(1-(4 -(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl) phenyl)urea (J103) The title compound was prepared from 3-(2-imino-4-oxothiazolidin-3-yl)-4-(3, 3,3-trifluoropropoxy)benzonitrile (C111) and isolated as a bright yellow / orange range solid (48 mg, 46%).

[0349] Methyl (Z)-3-(2-(((2-fluoro-4-(1-(4-(trifluoromethoxy phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamoyl ))imino)-4-oxothiazolidin-3-yl)-4-isopropylbenzoate (J 104) The title compound was prepared from methyl 3-(2-imino-4-oxothiazolidin-3-yl)-4- isopropylbenzoate (C112) and isolated as a white solid (25 m g, 26%).

[0350] (Z)-1-(3-(5-(dimethylamino)-2-(3,3,3-trifluoropropo xy)phenyl)-4-oxothiazolidine-2-ylidene)-3-(2-fluoro-4 -(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole -3-yl)phenyl)urea (J105) The title compound was prepared from 3-(5-(dimethylamino)-2-(3,3,3-trifluoropropo xy)phenyl)-2-iminothiazolidin-4-one (C101) and isolated as a white solid (67 mg, 61%).

[0351] (Z)-1-(3-(5-(Dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-4-oxothiazolidine-2-ylidene)-3-(2-methoxy-4 -(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazole -3-yl)phenyl)urea (J109) The title compound was prepared from 3-(5-(dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-2-iminothiazolidin-4-one (C101) and isolated as a yellow solid (84 mg, 80%).

[0352] (Z)-1-(3-(5-(Dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-4-oxothiazolidine-2-ylidene)-3-(2-ethyl-4- (1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazole- 3-yl)phenyl)urea (J110) The title compound was prepared from 3-(5-(dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-2-iminothiazolidin-4-one (C101) and isolated as an off-white solid (47 mg, 45%).

[0353] (Z)-1-(3-(5-(Dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-4-oxothiazolidine-2-ylidene)-3-(2-isopropyl -4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triaz ole-3-yl)phenyl)urea (J111) The title compound was prepared from 3-(5-(dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-2-iminothiazolidin-4-one (C101) and isolated as a yellow Isolated as a solid content (82 mg, 79%).

[0354] (Z)-1-(3-(4-(Dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidine-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J112) The title compound was prepared from 3-(4-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C102) and isolated as an off-white solid content (6 2 mg, 64%).

[0355] (Z)-1-(3-(4-(dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidine-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea ([[]] J113) The title compound was prepared from 3-(4-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C102) and isolated as a light yellow foam (8 2 mg, 82%).

[0356] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-methoxy ethyl)-5-methylphenyl)-4-oxothiazolidine-2-ylidene)urea (J 119) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )(thiazolidin-4-one (described in International Publication No. WO2017040194A1 pamphlet) Prepared as described, and isolated as an off-white solid (75 mg, 47%).

[0357] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-meth oxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea( J120) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1), and isolated as an off-white solid (74 mg, 47%).

[0358] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2-yl idene)urea (J121) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (prepared as described in WO 2017 / 040742 A1), and isolated as an off-white solid (44 mg, 2 6%).

[0359] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea ​​Den) Urea (J122) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth xy)phenyl)thiazolidin-4-one (International Publication No. 2017040742A1 pan fret as described and isolated as an off-white solid (84 mg, 4 9%).

[0360] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolid ene-2-ylidene)urea (J123) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white foam (173 mg, 84%).

[0361] (Z)-1-(3-(2-(1-Ethoxyethyl)-5-methylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea ( J124) The title compound was prepared from 3-(2-(1-ethoxyethyl)-5-methylphenyl)-2-im nothiazolidin-4-one (C118) and isolated as an off-white solid (14 8 mg, 76%).

[0362] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- ​(1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -propoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J125) The title compound was prepared from 2-imino-3-(5-methyl-2-propoxyphenyl)thiazolidin -4-one (C119) and isolated as an off-white foam (166 mg, 88 %).

[0363] (Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin -2-ylidene)-3-(2-methyl-4-(1-(3-(trifluoromethyl)phenyl (1H-1,2,4-triazol-3-yl)phenyl)urea (J131) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (as described in US Patent Application Publication No. 20140274688A1 and isolated as an off-white solid (62 mg, 41%).

[0364] (Z)-1-(3-(2-isopropyl-5-methoxyphenyl)-4-oxothiazoli din-2-ylidene)-3-(2-methyl-4-(1-(3-(trifluoromethyl)phenyl (1H-1,2,4-triazol-3-yl)phenyl)urea (J132) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazoli din-4-one (C98) and isolated as an off-white solid (76 mg, 49% ).

[0365] (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(3-(trifluoro (Methyl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 133) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2- iminothiazolidin-4-one (C126) and isolated as an off-white solid (6 9 mg, 43%).

[0366] (Z)-1-(3-(5-Methyl-2-(3,3,3-trifluoropropoxy)phenyl yl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(3- (trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J134) (Z)-1-(3-(5-Methyl-2-(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J134) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white solid (84 mg, 50%).

[0367] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin ene-2-ylidene)-3-(2-methyl-4-(1-(3-(trifluoromethoxy)ph enyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J135) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)-thiazo lidene-4-one (prepared as described in US Patent Application Publication No. 20140274688A1) and isolated as an off-white solid (62 mg, 42%).

[0368] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazoli din-2-ylidene)-3-(2-methyl-4-(1-(3-(trifluoromethoxy) (phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J136) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazoli din-4-one (C98) and isolated as an off-white solid (120 mg, 79 %).

[0369] (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(3-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea( J137) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white solid (1 25 mg, 80%).

[0370] (Z)-1-(3-(5-methyl-2-(3,3,3-trifluoropropoxy)phenyl l)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(3- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J138) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white solid (73 mg, 44%).

[0371] (Z)-1-(3-(5-methyl-2-((2,2,2-trifluoroethoxy)methyl )phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1 -(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3- yl)phenyl)urea (J139) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid fraction (42 mg, 41%).

[0372] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J140) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)-thiazo lidin-4-one (as described in US Patent Application Publication No. 20140274688A1) and isolated as an off-white solid fraction (56 mg, 37%).

[0373] (Z)-1-(3-(2-(1-Ethoxyethyl)-5-methylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 141) The title compound was prepared from 3-(2-(1-ethoxyethyl)-5-methylphenyl)-2-im nothiazolidin-4-one (C118) and isolated as an off-white solid fraction (67 mg, 69%).

[0374] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethyl)phenyl)-1 (H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- ((3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-yl lidene)urea (J142) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white solid (60 mg, 36%).

[0375] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J143) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)-thiazo lidone-4-one (as described in US Patent Application Publication No. 20140274688A1) and isolated as a tan solid (94 mg, 63%).

[0376] (Z)-1-(2-Fluoro-4-(1-(4-methoxyphenyl)-1H-1,2,4 -triazol-3-yl)phenyl)-3-(3-(2-isopropyl-5-methylp henyl)-4-oxothiazolidin-2-ylidene)urea (J144) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)-thiazo lidone-4-one (as described in US Patent Application Publication No. 20140274688A1) and isolated as a tan solid (54 mg, 34%).

[0377] (Z)-1-(2-Fluoro-4-(1-(4-methoxyphenyl)-1H-1,2,4​​​ -Triazol-3-yl)phenyl)-3-(3-(2-Isopropyl-5-methoxy phenyl)-4-oxothiazolidin-2-ylidene)urea (J145) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazole din-4-one (C98) and isolated as an off-white solid (84 mg, 51% ).

[0378] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-methoxyphen yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J146) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white solid (1 02 mg, 61%).

[0379] (Z)-1-(2-Fluoro-4-(1-(4-methoxyphenyl)-1H-1,2,4 -triazol-3-yl)phenyl)-3-(3-(5-methyl-2-(3,3,3- trifluoropropoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea ( J147) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as a yellowish-brown solid (77 mg, 43%).

[0380] (Z)-1-(2-Fluoro-4-(1-(p-tolyl)-1H-1,2,4-triaz -ol-3-yl)phenyl)-3-(3-(2-isopropyl-5-methylphenyl)- (4-Oxothiazolidin-2-ylidene)urea (J148) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)-thiaz olidin-4-one (as described in US Patent Application Publication No. 20140274688A1) and isolated as an off-white solid (73 mg, 44%).

[0381] (Z)-1-(2-Fluoro-4-(1-(p-tolyl)-1H-1,2,4-triaz ol-3-yl)phenyl)-3-(3-(2-isopropyl-5-methoxyphenyl) -4-oxothiazolidin-2-ylidene)urea (J149) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazoli din-4-one (C98) and isolated as an off-white solid (74 mg, 44% ).

[0382] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-ox othiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(p-tolyl)-1 H-1,2,4-triazol-3-yl)phenyl)urea (J150) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-im inothiazolidin-4-one (C126) and isolated as an off-white solid (5 1 mg, 29%).

[0383] (Z)-1-(2-Fluoro-4-(1-(p-tolyl)-1H-1,2,4-triaz ol-3-yl)phenyl)-3-(3-(5-methyl-2-(3,3,3-triflu oropropoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea (J151) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as a yellowish brown solid (85 mg, 46%) .

[0384] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethyl)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J152) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)-thiazo lidin-4-one (C98) and isolated as an off-white solid (84 mg, 54 %).

[0385] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-ox othiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(3-(trifluoro methyl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea ( J153) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-im inothiazolidin-4-one (C126) and isolated as an off-white solid (9 5 mg, 60%).

[0386] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl yl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J154 ) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)-thiazole lysine-4-one (C98) and isolated as an off-white solid (74 mg, 49 %).

[0387] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(3-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J155) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white solid (1 00 mg, 64%).

[0388] (Z)-1-(2-Fluoro-4-(1-(3-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2- ylidene)urea (J156) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as a white solid (40 mg, 24%) .

[0389] (Z)-1-(3-(5-(Dimethylamino)-4-fluoro-2-isopropylphenyl yl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4 (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl) phenyl)urea (J162) The title compound was prepared from 3-(5-(dimethylamino)-4-fluoro-2-isopropylphenyl)-2-iminothiazolidin-4-one (C103) and isolated as an off-white solid (140 mg, 70%).

[0390] (Z)-1-(3-(2,5-Diisopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J164) The title compound was prepared from 3-(2,5-diisopropylphenyl)-2-iminothiazolidin-4-one (C104) and isolated as a white solid (68 mg, 68%).

[0391] (Z)-1-(2-Chloro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)urea (J166) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-iminothiazolidin-4-one (C126) and isolated as an off-white solid (26 mg, 27%).

[0392] (Z)-1-(3-(5-Methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J167) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid (73 mg, 69%).

[0393] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- ((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J168) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a white foam (65 mg, 62%).

[0394] (Z)-1-(3-(5-Ethoxy-2-propylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J169) The title compound was prepared from 3-(5-ethoxy-2-propylphenyl)-2-iminothiazolidin-4-one (C125) and isolated as a light yellow - orange solid (81 mg, 81%).

[0395] (Z)-1-(3-(2-(Ethoxymethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J180) (J1 80) ​​​​​​​​The title compound was prepared from 3-(2-(ethoxymethyl)-5-methylphenyl)-2-iminothi azolidin-4-one (C120) and isolated as a yellow foam (54 mg, 57%).

[0396] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -(2,2,2-trifluoro-1-methoxyethyl)phenyl)-4-oxothiazoli din-2-ylidene)urea (J181) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoro-1 -methoxyethyl)phenyl)thiazolidin-4-one (C121) and isolated as an off-white solid (101 mg, 98%).

[0397] (Z)-1-(3-(5-(Dimethylamino)-2-(trifluoromethyl)phenyl) -4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-( trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)ure (J182) The title compound was prepared from 3-(5-(dimethylamino)-2-(trifluoromethyl)phenyl )-2-iminothiazolidin-4-one (C127) and isolated as an off-white solid (76 mg, 75%).

[0398] (Z)-1-(3-(5-(Dimethylamino)-4-fluoro-2-isopropylphenyl l)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4 -(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)phenyl) Phenyl)urea (J183) The title compound was prepared from 3-(5-(dimethylamino)-4-fluoro-2-isopropylphen yl)-2-iminothiazolidin-4-one (C103) and isolated as an off-white solid (58 mg, 57%).

[0399] (Z)-1-(3-(5-(dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4 -(1-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol- 3-yl)phenyl)urea (J184) The title compound was prepared from 3-(5-(dimethylamino)-2-(3,3,3-trifluoroprop oxy)phenyl)-2-iminothiazolidin-4-one (C101) and isolated as an off-white solid (69 mg, 63%).

[0400] (Z)-1-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methoxy- 2-(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J185) The title compound was prepared from 2-imino-3-(5-methoxy-2-(trifluoromethyl)phenyl thiazolidin-4-one (C140) and isolated as a white oily solid ( 37 mg, 31%).

[0401] (Z)-1-(2-fluoro-4-(1-(4-((trifluoromethyl)thio)phenyl yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl ​​Ru-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothia zolidin-2-ylidene)urea (J186) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a yellow foam (88 mg, 85%).

[0402] (Z)-1-(2-Fluoro-4-(1-(4-((trifluoromethyl)thio)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1 -methoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene) urea (J187) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1 pamphlet) and isolated as an off-white foam (71 mg, 74%).

[0403] (Z)-1-(3-(5-Ethoxy-2-(trifluoromethyl)phenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J190) The title compound was prepared from 3-(5-ethoxy-2-(trifluoromethyl)phenyl)-2-imino thiazolidin-4-one (C141) and isolated as a yellowish brown solid (56 mg, 45%).

[0404] (Z)-1-(3-(5-Ethoxy-2-isopropylphenyl)-4-oxothiazoli (Z)-1-(3-(2-Fluoro-4-(1-(4-(trifluoromethoxy) )phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-2-iminothiazolidin-3-one (J191 ) The title compound was prepared from 3-(5-ethoxy-2-isopropylphenyl)-2-iminothiazolidin-4-one (C147) and isolated as a yellowish brown solid (76 mg, 6 0%).

[0405] (Z)-1-(3-(5-(Dimethylamino)-2-ethoxyphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 192) The title compound was prepared from 3-(5-ethoxy-2-isopropylphenyl)-2-iminothiazolidin-4-one (C147) and isolated as a bright orange solid (57 m g, 59%).

[0406] (Z)-1-(3-(5-(Dimethylamino)-2-(2,2,2-trifluoroethoxy phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4- (1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol- 3-yl)phenyl)urea (J193) The title compound was prepared from 3-(5-(dimethylamino)-2-(2,2,2-trifluoroethoxy phenyl)-2-iminothiazolidin-4-one (C129) and isolated as a bright orange solid (60 mg, 57%).

[0407] (Z)-1-(2-Chloro-4-(1-(4-(trifluoromethoxy)phenyl)-1​​​​ H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- ((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidine -2-ylidene)urea (J194) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth (oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a white foam (27 mg, 27%).

[0408] (Z)-1-(3-(2-(ethoxymethyl)-5-methylphenyl)-4-oxothia zolidine-2-ylidene)-3-(2-fluoro-4-(1-(4-((trifluoromethyl (thio)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J195) The title compound was prepared from 3-(2-(ethoxymethyl)-5-methylphenyl)-2-iminoth iazolidin-4-one (C120) and isolated as a yellow foam (40 mg, 43%).

[0409] (Z)-1-(3-(5-(dimethylamino)-2-propylphenyl)-4-oxothia zolidine-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethyl (oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 196) The title compound was prepared from 3-(5-(dimethylamino)-2-propylphenyl)-2-imino thiazolidin-4-one (C128) and isolated as a bright orange solid ([[]] 65 mg, 67%).

[0410] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-hydroxy -2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)urea (J19 7) The title compound was prepared from 3-(5-hydroxy-2-isopropylphenyl)-2-iminothia zolidin-4-one (C105) and isolated as a pale yellow - orange solid (6 mg, 6%).

[0411] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(4-oxo-3-(2 -(piperidin-1-yl)phenyl)thiazolidin-2-ylidene)urea (J198) The title compound was prepared from 2-imino-3-(2-(piperidin-1-yl)phenyl)thiazoli din-4-one (C106) and isolated as a pale yellow - orange solid (3 4 mg, 35%).

[0412] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methoxy- 2-(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2- ylidene)urea (J201) The title compound was prepared from 2-imino-3-(5-methoxy-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (C142) and isolated as an off - white solid (30 mg, 25%).

[0413] (Z)-1-(3-(4-Fluoro-2-isopropyl-5-methoxyphenyl)-4- oxothiazolidine-2-ylidene)-3-(2-fluoro-4-(1-(4-(trif luoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl) urea (J202) The title compound was prepared from 3-(4-fluoro-2-isopropyl-5-methoxyphenyl)-2 -iminothiazolidin-4-one (C143) and isolated as a white solid ([[]] 30 mg, 25%).

[0414] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-meth xyethyl)-4-methylphenyl)-4-oxothiazolidine-2-ylidene)urea([[]] J203) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-4-methylphenyl )-thiazolidin-4-one (C144) and isolated as a yellowish brown oily foam (35 mg, 29%).

[0415] (Z)-1-(3-(5-Methyl-2-((2,2,2-trifluoroethoxy)methyl )phenyl)-4-oxothiazolidine-2-ylidene)-3-(2-methyl-4-(1 -(4-((trifluoromethyl)thio)phenyl)-1H-1,2,4-triazole -3-yl)phenyl)urea (J204) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidine-4-one (C117) and isolated as an off-white sol id (56 mg, 55%).

[0416] (Z)-1-(3-(2-(Ethoxymethyl)-5-methylphenyl)-4-oxothia zolidin-2-ylidene)-3-(2-methyl-4-(1-(4-((trifluorometh yl)thio)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea( J205) The title compound was prepared from 3-(2-(ethoxymethyl)-5-methylphenyl)-2-iminothia zolidin-4-one (C120) and isolated as a yellow foam (60 mg, 64%).

[0417] (Z)-1-(3-(2-(Ethoxymethyl)-5-methylphenyl)-4-oxothia zolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoromethox y) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J20 6) The title compound was prepared from 3-(2-(ethoxymethyl)-5-methylphenyl)-2-iminothia zolidin-4-one (C120) and isolated as an orange foam (12 4 mg, 65%).

[0418] (Z)-1-(3-(2-Ethyl-5-methoxyphenyl)-4-oxothiazolidine- 2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J216) The title compound was prepared from 3-(2-ethyl-5-methoxyphenyl)-2-iminothiazolidine -4-one (C148) and isolated as an off-white solid (27 mg, 29%) .

[0419] (Z)-1-(2-Fluoro-4-(1-(4-((trifluoromethyl)thio)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl -2-(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidine- 2-ylidene)urea (J223) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040742 A1 pamphlet) and isolated as a white solid (45 mg, 46 %).

[0420] (Z)-1-(3-(2-Ethoxy-5-methylphenyl)-4-oxothiazolidine- 2-ylidene)-3-(2-fluoro-4-(1-(4-((trifluoromethyl)thio )phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J224 ) The title compound was prepared from 3-(2-ethoxy-5-methylphenyl)-2-iminothiazolidine -4-one (prepared as described in International Publication No. WO 2017 / 040194 A1 pamphlet) and isolated as a white solid (51 mg, 54%).

[0421] (Z)-1-(2-Fluoro-4-(1-(4-((trifluoromethyl)thio)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl -2-(4,4,4-trifluorobutoxy)phenyl)-4-oxothiazolidine- 2-ylidene)urea (J225) The title compound was prepared from 2-imino-3-(5-methyl-2-(4,4,4-trifluorobut Prepared from (Z)-1-(2-chloro-4-(1-(4-((trifluoromethyl)thio)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J226) as an off-white solid and isolated (52 mg, 51%).

[0422] (Z)-1-(2-chloro-4-(1-(4-((trifluoromethyl)thio)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl -2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiaz olidin-2-ylidene)urea (J226) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a white solid fraction (40 mg, 41%).

[0423] (Z)-1-(2-fluoro-4-(1-(4-((trifluoromethyl)thio)phenyl yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl yl-2-(2,2,2-trifluoro-1-methoxyethyl)phenyl)-4-oxothia zolidin-2-ylidene)urea (J229) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoro-1 -methoxyethyl)phenyl)thiazolidin-4-one (C121) and isolated as an off-white solid fraction (46 mg, 44%).

[0424] (Z)-1-(3-(2-(1-ethoxyethyl)-5-methylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-((trifluoro romethyl)thio)phenyl)-1H-1,2,4-triazol-3-yl)phenyl) urea (J230) The title compound was prepared from 3-(2-(1-ethoxyethyl)-5-methylphenyl)-2-iminothiazolidin-4-one (C118) and isolated as an off-white solid (70 mg, 72%).

[0425] (Z)-1-(2-chloro-4-(1-(4-((trifluoromethyl)thio)phenyl ))-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isop ropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J23 1) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (as prepared in US Patent Application Publication No. 20140274688A1 ) and isolated as a yellow solid (48 mg, 52%).

[0426] (Z)-1-(2-chloro-4-(1-(4-((trifluoromethyl)thio)phenyl ))-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1- methoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)ure a (J232) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. 2017040194A1 ) and isolated as a yellow solid (64 mg, 68%).

[0427] (Z)-1-(3-(2-(1-methoxyethyl)-5-methylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-((trifluoro ​(Methyl)thio)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea Urea (J233) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. 2017040194A1 pamphlet) and isolated as an off-white solid (58 mg, 60%).

[0428] (Z)-1-(2-chloro-4-(1-(4-(trifluoromethyl)phenyl)-1H -1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2-( (2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidine- 2-ylidene)urea (J234) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidine-4-one (C117) and isolated as a white solid fraction (36 mg, 35%).

[0429] (Z)-1-(2-chloro-4-(1-(4-(trifluoromethyl)phenyl)-1H -1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(dimethylamino no)-2-propylphenyl)-4-oxothiazolidine-2-ylidene)urea (J23 5) The title compound was prepared from 3-(5-(dimethylamino)-2-propylphenyl)-2-imino thiazolidine-4-one (C128) and isolated as a white solid fraction (32 mg , 33%).

[0430] (Z)-1-(2-fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2 ​-yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2- (1-methoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene ene)urea (J236) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (as described in International Publication No. WO2017040194A1 pamphlet and isolated as a white solid (47 mg, 50%).

[0431] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2 -yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5- methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxo thiazolidin-2-ylidene)urea (J237) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid (87 mg, 85%).

[0432] (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(5-(trifluoro methoxy)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J238) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white solid (7 9 mg, 82%).

[0433] ​ (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2 -yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2- isopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J239) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazol din-4-one (C98) and isolated as an off-white solid (65 mg, 69% ).

[0434] (Z)-1-(3-(2-(1-methoxyethyl)-5-methylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluorometh oxy)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl )urea (J240) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1 pamphlet ) and isolated as an off-white solid (52 mg, 55%).

[0435] (Z)-1-(3-(5-Methyl-2-((2,2,2-trifluoroethoxy)methyl )phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1 -(5-(trifluoromethoxy)pyridin-2-yl)-1H-1,2,4-triaz ol-3-yl)phenyl)urea (J241) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid Isolated as a solid (78 mg, 75%).

[0436] (Z)-1-(2-Chloro-4-(1-(5-(trifluoromethoxy)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-me thyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxoth iazolidin-2-ylidene)urea (J249) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid fraction (41 mg, 41%).

[0437] (Z)-1-(2-Chloro-4-(1-(5-(trifluoromethoxy)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-( 1-methoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene )urea (J250) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )(thiazolidin-4-one (as described in WO 2017 / 040194 A1 pamphlet and isolated as an off-white solid fraction (30 mg, 32%).

[0438] (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-ox othiazolidin-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluoro methoxy)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl yl)urea (J251) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-i Prepared from minothiazolidin-4-one (C126) and isolated as an off-white solid (5 5 mg, 57%).

[0439] (Z)-1-(3-(2-Isopropyl-5-methoxyphenyl)-4-oxothiazoli din-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluoromethoxy) pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)urea( J252) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazoli din-4-one (C98) and isolated as an off-white solid (59 mg, 62% ).

[0440] (Z)-1-(2-Chloro-4-(1-(5-(trifluoromethoxy)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-( dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-ylid ene)urea (J253) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white solid (5 1 mg, 54%).

[0441] (Z)-1-(3-(5-(dimethylamino)-2-propylphenyl)-4-oxoth iazolidin-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluoromethox y)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl) urea (J254) The title compound was prepared from 3-(5-(dimethylamino)-2-propylphenyl)-2-imino Prepared from thiazolidin-4-one (C128) and isolated as an off-white solid (60 m g, 62%).

[0442] (Z)-1-(3-(5-Methyl-2-(3,3,3-trifluoropropoxy)phenyl yl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1-(5- (trifluoromethoxy)pyridin-2-yl)-1H-1,2,4-triazol-3 -yl)phenyl)urea (J255) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoropro poxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white solid (82 mg, 79%).

[0443] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methoxy- 2-(1-methoxyethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J256) The title compound was prepared from 2-imino-3-(5-methoxy-2-(1-methoxyethyl)phenyl yl)thiazolidin-4-one (C145) and isolated as a yellowish-brown solid (3 0 mg, 31%).

[0444] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2 -yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5- methyl-2-(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea (J257) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white solid (79 mg, 77%).

[0445] (Z)-1-(3-(5-(Dimethylamino)-2-propylphenyl)-4-oxoth iazolidin-2-ylidene)-3-(2-fluoro-4-(1-(5-(trifluorometh oxy)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl )urea (J258) The title compound was prepared from 3-(5-(dimethylamino)-2-propylphenyl)-2-imino thiazolidin-4-one (C128) and isolated as an off-white solid (80 m g, 83%).

[0446] (Z)-1-(3-(5-(Dimethylamino)-4-fluoro-2-isopropylphen yl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(5 -(trifluoromethoxy)pyridin-2-yl)-1H-1,2,4-triazol- 3-yl)phenyl)urea (J261) The title compound was prepared from 3-(5-(dimethylamino)-4-fluoro-2-isopropylphen yl)-2-iminothiazolidin-4-one (C103) and isolated as an off-white solid (70 mg, 71%).

[0447] (Z)-1-(3-(5-(Dimethylamino)-2-(trifluoromethyl)phenyl) -4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(5-( trifluoromethoxy)pyridin-2-yl)-1H-1,2,4-triazol-3- ​(E)-1-(3-(5-(Dimethylamino)-2-(trifluoromethyl)phenyl )-2-iminothiazolidin-4-one (C127) to prepare the title compound, which was isolated as an off-white solid (63 mg, 63%).

[0448] (Z)-1-(3-(5-(Dimethylamino)-2-(2,2,2-trifluoroethoxy phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4- (1-(5-(Trifluoromethoxy)pyridin-2-yl)-1H-1,2,4-tri azol-3-yl)phenyl)urea (J263) The title compound was prepared from 3-(5-(dimethylamino)-2-(2,2,2-trifluoroethoxy phenyl)-2-iminothiazolidin-4-one (C129) and isolated as an off-white solid (56 mg, 53%).

[0449] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2 -yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2- isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea ( J270) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (prepared as described in U.S. Patent Application Publication No. 20140274688A1 ) and isolated as an off-white solid (49 mg, 53%).

[0450] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2 -yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-​​ Methyl-2-(trifluoromethyl)phenyl)-4-oxothiazolidine-2-ylidene urea (J271) The title compound was prepared from 2-imino-3-(5-methyl-2-(trifluoromethyl)phenyl thiazolidin-4-one (prepared as described in International Publication No. 2017040742A1 pamphlet and isolated as an off-white solid (54 mg, 56%).

[0451] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethoxy)pyridin-2 -yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5- methyl-2-propylphenyl)-4-oxothiazolidine-2-ylidene)urea (J2 72) The title compound was prepared from 2-imino-3-(5-methyl-2-propylphenyl)thiazolidine -4-one (prepared as described in International Publication No. 2016033025A1 pamphlet and isolated as an off-white solid (33 mg, 36%).

[0452] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-i sopropyl-5-methylphenyl)-4-oxothiazolidine-2-ylidene)urea (J 279) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli dine-4-one (prepared as described in U.S. Patent Application Publication No. 20140274688A1 specification and isolated as an off-white solid (47 mg, 50%).

[0453] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-( 1-methoxyethyl)-5-methylphenyl)-4-oxothiazolidine-2-ylidene )urea (J280) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040194 A1 pamphlet) and isolated as an off-white solid (54 mg, 56%).

[0454] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-me thyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxoth iazolidine-2-ylidene)urea (J281) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid (67 mg, 64%).

[0455] (Z)-1-(3-(5-(Dimethylamino)-2-propylphenyl)-4-oxoth iazolidine-2-ylidene)-3-(2-fluoro-4-(1-(5-(trifluorometh yl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl) urea (J282) The title compound was prepared from 3-(5-(dimethylamino)-2-propylphenyl)-2-imino thiazolidin-4-one (C128) and isolated as an off-white solid (66 m​ g, 67%).

[0456] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-i sopropyl-5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea( J283) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazol din-4-one (C98) and isolated as an off-white solid (70 mg, 72% ).

[0457] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolid in-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluoromethyl)pyr idin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J2 84) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazol din-4-one (as described in US Patent Application Publication No. 20140274688A1 and isolated as an off-white solid (84 mg, 86%).

[0458] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-ox othiazolidine-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluoro methyl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl )urea (J285) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-i Prepared from minothiazolidin-4-one (C126) and isolated as a white solid (70 mg, 70%).

[0459] (Z)-1-(3-(2-(1-methoxyethyl)-5-methylphenyl)-4-oxo Thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluoromethyl) ethyl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl Urea (J286) The title compound was synthesized by the reaction of 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidine-4-one (as described in the pamphlet of International Publication No. 2017040194A1) Prepared as described above) and isolated as a white solid (66 mg, 68%).

[0460] (Z)-1-(3-(2-isopropyl-5-methoxyphenyl)-4-oxothiazolidine Diphenyl ether)-3-(2-methyl-4-(1-(5-(trifluoromethyl)pyridin) Lysin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 292) The title compound was synthesized by 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazolyl Prepared from din-4-one (C98) and isolated as an off-white solid (66 mg, 68%) ).

[0461] (Z)-1-(3-(5-methyl-2-propylphenyl)-4-oxothiazolidine- 2-Ylidene)-3-(2-methyl-4-(1-(5-(trifluoromethyl)pyridine -2-yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J293 ) The title compound was synthesized by the reaction of 2-imino-3-(5-methyl-2-propylphenyl)thiazolidine -4-one (prepared as described in WO 2016 / 033025 A1) Prepared therefrom and isolated as a white solid (47 mg, 50%).

[0462] (Z)-1-(3-(5-(Dimethylamino)-2-propylphenyl)-4-oxothi azolidin-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluorometh yl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J294) The title compound was prepared from 3-(5-(dimethylamino)-2-propylphenyl)-2-imino thiazolidin-4-one (C128) and isolated as an off-white solid (67 m g, 67%).

[0463] (Z)-1-(2-Chloro-4-(1-(5-(trifluoromethyl)pyridin-2-yl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-iso propyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J2 95) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (prepared as described in US 2014 / 0274688 A1 ) and isolated as an off-white solid (22 mg, 23%).

[0464] (Z)-1-(2-Chloro-4-(1-(5-(trifluoromethyl)pyridin-2-yl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(di methylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene )urea (J296) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2- iminothiazolidin-4-one (C126) and isolated as an off-white solid (3 2 mg, 32%).

[0465] (Z)-1-(3-(5-Methyl-2-((2,2,2-trifluoroethoxy)methyl )phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1 -(5-(trifluoromethyl)pyridin-2-yl)-1H-1,2,4-triazol- 3-yl)phenyl)urea (J297) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid (37 mg, 35%).

[0466] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-( methoxymethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J298) The title compound was prepared from 2-imino-3-(2-(methoxymethyl)-5-methylphenyl)thi azolidin-4-one (prepared as described in WO 2017 / 040742 A1) and isolated as a yellow solid (29 mg, 31%).

[0467] (Z)-1-(3-(2-(ethoxymethyl)-5-methylphenyl)-4-oxothia zolidin-2-ylidene)-3-(2-fluoro-4-(1-(5-(trifluoromethyl (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-methoxyethyl)-4-methylphenyl)-4-oxothiazolidin-2-ylidene)urea Urea (J299) The title compound was prepared from 3-(2-(ethoxymethyl)-5-methylphenyl)-2-iminothiazolidin-4-one (C120) and isolated as a white solid (58 mg, 60%).

[0468] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-( 1-methoxyethyl)-4-methylphenyl)-4-oxothiazolidin-2-ylidene )urea (J300) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-4-methylphenyl )-thiazolidin-4-one (C144) and isolated as a white solid (56 mg, 58%).

[0469] (Z)-1-(2-Chloro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1 -methoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene )urea (J306) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1 pamphlet) and isolated as an off-white solid (42 mg, 44%).

[0470] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1 ​​​​(E)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazol-3-yl)phenyl)-3-(3-(5-methyl-2-(( -(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin -2-ylidene)urea (J307) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white solid (61 mg, 58%).

[0471] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-pyrazol-3-yl)phenyl)-3-(3-(5-methyl-2-(( (2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidin-2 -ylidene)urea (J308) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a white solid (66 mg, 63%).

[0472] (Z)-1-(2-Fluoro-4-(1-(5-(trifluoromethyl)pyridin-2- yl)-1H-pyrazol-3-yl)phenyl)-3-(3-(2-(1-methoxyeth yl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J30 9) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1 pamphlet) and isolated as a white solid (42 mg, 43%).

[0473] ​​​(Z)-1-(3-(5-Methyl-2-((2,2,2-trifluoroethoxy)methyl )phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-methyl-4-(1 -(5-(trifluoromethyl)pyridin-2-yl)-1H-pyrazol-3-yl) phenyl)urea (J310) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a white solid fraction (75 mg, 71%).

[0474] (Z)-1-(3-(2-(1-Methoxyethyl)-5-methylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(5-(trifluorometh yl)pyridin-2-yl)-1H-pyrazol-3-yl)phenyl)urea)(J31 1) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. WO2017040194A1 pamphlet) and isolated as a white solid fraction (78 mg, 81%).

[0475] Example 32: Preparation of (Z)-1-(3-(5-(diethylamino)-2-isopropylphenyl )-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)ph enyl)urea (J69)

Chemical formula

[0476] The following compounds were prepared according to the procedure of Example 32.

[0477] (Z)-1-(2,6 - Difluoro - 4-(1-(4-(trifluoromethoxy)phenyl yl)-1H - 1,2,4 - triazol - 3 - yl)phenyl)-3-(3-(2 - iso propyl - 5 - methylphenyl)-4 - oxothiazolidin - 2 - yliden)urea (J7 8) The title compound was prepared from 2 - imino - 3-(2 - isopropyl - 5 - methylphenyl)thiazoli din - 4 - one (prepared as described in US Patent Application Publication No. 20140274688A1 ) and isolated as a yellow powder (44 mg, 50%).

[0478] (Z)-1-(2,6 - Difluoro - 4-(1-(4-(trifluoromethoxy)phenyl yl)-1H - 1,2,4 - triazol - 3 - yl)phenyl)-3-(3-(5 - methyl ​Ru-2-(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidine- 2-ylidene)urea (J79) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (prepared as described in International Publication No. 2017040742A1 pamphlet ) and isolated as a yellow powder (58 mg, 60% ).

[0479] (Z)-1-(2,6-Difluoro-4-(1-(4-(trifluoromethoxy)phenyl yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl yl-2-(4,4,4-trifluorobutoxy)phenyl)-4-oxothiazolidine- 2-ylidene)urea (J80) The title compound was prepared from 2-imino-3-(5-methyl-2-(4,4,4-trifluorobut oxy)phenyl)thiazolidin-4-one (C107) and isolated as a yellow powder (51 mg, 51%).

[0480] (Z)-1-(2,6-Difluoro-4-(1-(4-(trifluoromethoxy)phenyl yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1 -methoxyethyl)-5-methylphenyl)-4-oxothiazolidine-2-ylidene) urea (J81) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. 2017040194A1 pamphlet ) and isolated as a yellow powder (49 mg, 54%).

[0481] (Z)-1-(2,6-Difluoro-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(di methylamino)-2-isopropylphenyl)-4-oxothiazolidine-2-ylidene )urea (J82) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-i mino-thiazolidin-4-one (C126) and isolated as a yellow powder (53 m g, 57%).

[0482] (Z)-1-(2,6-Dimethyl-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isop ropyl-5-methylphenyl)-4-oxothiazolidine-2-ylidene)urea (J95 ) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli dine-4-one (as described in US Patent Application Publication No. 20140274688A1 and isolated as a white powder (51 mg, 71%).

[0483] (Z)-1-(2,6-Dimethyl-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(di methylamino)-2-isopropylphenyl)-4-oxothiazolidine-2-ylidene) urea (J96) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-i mino-thiazolidin-4-one (C126) and isolated as an off-white powder (57 mg, 76%).

[0484] (Z)-1-(2,6-Dimethyl-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1- methoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J97) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040194A1) and isolated as a white powder (44 mg, 80%).

[0485] (Z)-1-(2,6-Dimethyl-4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J9 8) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazoli din-4-one (C98) and isolated as a white powder (47 mg, 85%).

[0486] (Z)-1-(3-(5-(Ethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea ( J106) The title compound was prepared from 3-(5-(ethylamino)-2-isopropylphenyl)-2-im nothiazolidin-4-one hydrochloride (C151) and isolated as a white solid ( 46 mg, 49%).

[0487] ​ (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-(propylamino)phenyl)-4-oxothiazolidin-2-ylidene)urea (J107) The title compound was prepared from 2-imino-3-(2-isopropyl-5-(propylamino)phenyl )thiazolidin-4-one hydrochloride (C152) and isolated as a white solid (62 mg, 64%).

[0488] (Z)-1-(3-(5-(dipropylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoro omethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J108) The title compound was prepared from 3-(5-(dipropylamino)-2-isopropylphenyl)-2- iminothiazolidin-4-one (C131) and isolated as a yellow powder (57 mg, 55%).

[0489] (Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin -2-ylidene)-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)-2-(trifluoromethyl)phenyl)urea (J114) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (as prepared in US Patent Application Publication No. 20140274688A1 and isolated as a yellow powder (39 mg, 33%).

[0490] (Z)-1-(3-(5-Methyl-2-(2,2,2-trifluoroethoxy)phenyl )-4-oxothiazolidine-2-ylidene)-3-(4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2-(trifluoro methyl)phenyl)urea (J115) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (as described in International Publication No. WO 2017 / 040742 A1 and isolated as a yellow powder (61 mg, 47% ).

[0491] (Z)-1-(3-(5-(Dimethylamino)-2-isopropylphenyl)-4-ox othiazolidine-2-ylidene)-3-(4-(1-(4-(trifluoromethoxy)ph enyl)-1H-1,2,4-triazol-3-yl)-2-(trifluoromethyl) phenyl)urea (J116) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-im inothiazolidin-4-one (C126) and isolated as a yellow powder (43 m g, 35%).

[0492] (Z)-1-(3-(2-(1-Methoxyethyl)-5-methylphenyl)-4-oxo thiazolidine-2-ylidene)-3-(4-(1-(4-(trifluoromethoxy)phenyl )-1H-1,2,4-triazol-3-yl)-2-(trifluoromethyl)phenyl )urea (J117) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-Thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1 pamphlet) and isolated as a yellow powder (40 mg, 33%). and isolated as a yellow powder (40 mg, 33%).

[0493] (Z)-1-(3-(5-(Dimethylamino)-2-(3,3,3-trifluoropropyl phenyl)-4-oxothiazolidin-2-ylidene)-3-(4-(1-(4- (Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)- 2-(Trifluoromethyl)phenyl)urea (J118) The title compound was prepared from 3-(5-(dimethylamino)-2-(3,3,3-trifluoropropyl phenyl)-2-iminothiazolidin-4-one (C101) and isolated as a yellow powder (85 mg, 62%).

[0494] (Z)-1-(3-(2-Isopropyl-5-(methylamino)phenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 126) The title compound was prepared from 2-imino-3-(2-isopropyl-5-(methylamino)phenyl )thiazolidin-4-one hydrochloride (C150) and isolated as an off-white solid (80 mg, 61%).

[0495] (Z)-1-(3-(5-(Ethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluorometh oxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J 127) The title compound was prepared from 3-(5-(ethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one hydrochloride (C151) and isolated as an off-white solid (68 mg, 51%).

[0496] (Z)-1-(3-(2-Isopropyl-5-(propylamino)phenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea( J128) The title compound was prepared from 2-imino-3-(2-isopropyl-5-(propylamino)phenyl thiazolidin-4-one hydrochloride (C152) and isolated as an off-white solid (95 mg, 70%).

[0497] (Z)-1-(3-(5-(Diethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea( J129) The title compound was prepared from 3-(5-(diethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C130) and isolated as an off-white solid (1 09 mg, 78%).

[0498] (Z)-1-(3-(5-(Dipropylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-methyl-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J130) The title compound was prepared from 3-(5-(dipropylamino)-2-isopropylphenyl)-2- iminothiazolidin-4-one (C131) and isolated as an off-white solid ([[]] 111 mg, 76%).

[0499] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-(methylamino)phenyl)-4-oxothiazolidin-2-ylidene)urea (J 157) The title compound was prepared from 2-imino-3-(2-isopropyl-5-(methylamino)phenyl )thiazolidin-4-one hydrochloride (C150) and isolated as an off-white solid (61 mg, 48%).

[0500] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(ethylamino no)-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)urea (J 158) The title compound was prepared from 3-(5-(ethylamino)-2-isopropylphenyl)-2-im inothiazolidin-4-one hydrochloride (C151) and isolated as an off-white solid (63 mg, 48%).

[0501] (Z)-1-(2-Ethyl-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-(propylamino)phenyl)-4-oxothiazolidin-2-ylidene)urea ( J159) The title compound was prepared from 2-imino-3-(2-isopropyl-5-(propylamino)phenyl )thiazolidin-4-one hydrochloride (C152) and isolated as an off-white solid (79 mg, 59%).

[0502] (Z)-1-(3-(5-(Diethylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-ethyl-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea( J160) The title compound was prepared from 3-(5-(diethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C130) and isolated as an off-white solid (7 5 mg, 55%).

[0503] (Z)-1-(3-(5-(Dipropylamino)-2-isopropylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-ethyl-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J161) The title compound was prepared from 3-(5-(dipropylamino)-2-isopropylphenyl)-2- imino thiazolidin-4-one (C131) and isolated as an off-white solid ([[]] 75 mg, 53%).

[0504] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)- 1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2 -nitrophenyl)-4-oxothiazolidin-2-ylidene)urea (J163) ​The title compound was prepared from 2-imino-3-(5-methyl-2-nitrophenyl)thiazolidin-4 -one (C136) and isolated as a yellow solid (400 mg, 73%).

[0505] (Z)-1-(3-(5-methyl-2-((2,2,2-trifluoroethoxy)methyl )phenyl)-4-oxothiazolidin-2-ylidene)-3-(4-(1-(4-(tr ifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)-2- (trifluoromethyl)phenyl)urea (J165) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a yellow solid fraction (50 mg, 27%).

[0506] (Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolid in-2-ylidene)-3-(2-(methoxymethoxy)-4-(1-(4-(trifluo romethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J170) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli dine-4-one (prepared as described in US Patent Application Publication No. 20140274688A1 ) and isolated as an off-white powder (192 mg, 74%).

[0507] (Z)-1-(2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5 -methyl-2-(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazoli (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J171) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (as described in International Publication No. WO 2017 / 040742 A1) and isolated as an off-white solid (178 mg, 64%).

[0508] (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J172) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white solid (2 40 mg, 89%).

[0509] (Z)-1-(2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5 -methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J173) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid (182 mg, 64%).

[0510] (Z)-1-(3-(2-(1-ethoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J174)(Z)-1-(3-(2-(1-ethoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J174)

[0510] (Z)-1-(3-(2-(1-ethoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-(methoxymethoxy)-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J174) (Z)-N-(3-(2-(((2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamoyl)imino)-4-oxothiazolidin-3-yl)-4-isopropylphenyl)-N-methylacetamide (J188) phenyl)urea (J174) The title compound was prepared from 3-(2-(1-ethoxyethyl)-5-methylphenyl)-2-iminothiazolidin-4-one (C118) and isolated as an off-white solid (23 3 mg, 86%).

[0511] (Z)-N-(3-(2-(((2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamoyl)imino)-4-oxothiazolidin-3-yl)-4-isopropylphenyl)-N-methylacetamide (J188) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamoyl )imino)-4-oxothiazolidin-3-yl)-4-isopropylphenyl)-N- methylacetamide (J188) The title compound was prepared from N-(3-(2-imino-4-oxothiazolidin-3-yl)-4- isopropylphenyl)-N-methylacetamide (C138) and isolated as an off-white semi-solid (118 mg, 75%).

[0512] (Z)-N-Ethyl-N-(3-(2-(((2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamoyl)imino)-4-oxothiazolidin-3-yl)-4-isopropylphenyl)acetamide (J189) phenyl)-1H-1,2,4-triazol-3-yl)phenyl) carbamoyl)imino)-4-oxothiazolidin-3-yl)-4-isopropylphenyl) phenyl)acetamide (J189) The title compound was prepared from N-ethyl-N-(3-(2-imino-4-oxothiazolidin-3- yl)-4-isopropylphenyl)acetamide (C139) and isolated as an off-white solid fraction (135 mg, 83%).

[0513] ​​(Z)-N-(4-Isopropyl-3-(2-(((2-methyl-4-(1-(4-(tr ifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl carbamoyl)imino)-4-oxothiazolidin-3-yl)phenyl)-N-me thylacetamide (J199) The title compound was prepared from N-(3-(2-imino-4-oxothiazolidin-3-yl)-4- isopropylphenyl)-N-methylacetamide (C138) and isolated as a white powder (35 mg, 35%).

[0514] (Z)-N-Ethyl-N-(4-isopropyl-3-(2-(((2-methyl-4-(1 -(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3- yl)phenyl)carbamoyl)imino)-4-oxothiazolidin-3-yl)phenyl yl)acetamide (J200) The title compound was prepared from N-ethyl-N-(3-(2-imino-4-oxothiazolidin-3- yl)-4-isopropylphenyl)acetamide (C139) and isolated as a white powder (44 mg, 43%).

[0515] (Z)-1-(2-(Difluoromethyl)-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2 -isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J211) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazo lidene-4-one (as described in US Patent Application Publication No. 20140274688A1 Prepared from (prepared as in International Publication No. 2017040742A1) and isolated as an off-white foam (58 mg, 37%).

[0516] (Z)-1-(2-(Difluoromethyl)-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5 -methyl-2-(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazoli din-2-ylidene)urea (J212) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth oxy)phenyl)thiazolidin-4-one (as described in International Publication No. 2017040742A1 and isolated as an off-white foam (49 mg, 2 9%).

[0517] (Z)-1-(2-(Difluoromethyl)-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5 -(dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-yl idene)urea (J213) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white foam (5 2 mg, 32%).

[0518] (Z)-1-(2-(Difluoromethyl)-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2 -(ethoxymethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene )urea (J214) The title compound was prepared from 3-(2-(ethoxymethyl)-5-methylphenyl)-2-iminothi azolidin-4-one (C120) and isolated as an off-white foam (50 mg , 31%).

[0519] (Z)-1-(2-(Difluoromethyl)-4-(1-(4-(trifluoromethoxy) phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5 -methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxo thiazolidin-2-ylidene)urea (J215) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white fo am (54 mg, 31%).

[0520] (Z)-1-(2-Bromo-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J217) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (as described in US Patent Application Publication No. 20140274688A1 and isolated as a yellow foamy powder (97 mg, 77%).

[0521] (Z)-1-(2-Bromo-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea Den) Urea (J218) The title compound was prepared from 2-imino-3-(5-methyl-2-(2,2,2-trifluoroeth xy)phenyl)thiazolidin-4-one (prepared as described in International Publication No. 2017040742A1 pamphlet and isolated as a yellow foam (70 mg, 51 %).

[0522] (Z)-1-(2-Bromo-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(dimethylamino -2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)urea( J219) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as a yellow foam (94 mg, 71%).

[0523] (Z)-1-(2-Bromo-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-methoxy ethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J 220) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl -thiazolidin-4-one (prepared as described in International Publication No. 2017040194A1 pamphlet and isolated as a yellow foam (56 mg, 43%).

[0524] (Z)-1-(2-Bromo-4-(1-(4-(trifluoromethoxy)phenyl)-1 (H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(ethoxymeth yl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J22 1) The title compound was prepared from 3-(2-(ethoxymethyl)-5-methylphenyl)-2-iminoth iazolidin-4-one (C120) and isolated as a yellow foam (93 mg, 72%).

[0525] (Z)-1-(2-Bromo-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- ((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidine -2-ylidene)urea (J222) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a yellow foam (107 mg, 77%).

[0526] (Z)-1-(4-(1-(4-Cyanophenyl)-1H-1,2,4-triazol- 3-yl)-2-fluorophenyl)-3-(3-(2-isopropyl-5-methylphen yl)-4-oxothiazolidin-2-ylidene)urea (J287) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli dine-4-one (as described in U.S. Patent Application Publication No. 20140274688A1 prepared) and isolated as a yellow powder (64 mg, 43%).

[0527] (Z)-1-(4-(1-(4-Cyanophenyl)-1H-1,2,4-triazol- (Z)-1-(4-(1-(4-cyanophenyl)-1H-1,2,4-triazol-3-yl)-2-fluorophenyl)-3-(3-(5-methyl-2-(3,3,3-trifluoro luoropropoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea (J 288) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as a yellow powder (114 mg, 68%).

[0528] (Z)-1-(4-(1-(4-cyanophenyl)-1H-1,2,4-triazol- 3-yl)-2-fluorophenyl)-3-(3-(5-methyl-2-((2,2,2- trifluoroethoxy)methyl)phenyl)-4-oxothiazolidin-2-ylidene) urea (J289) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as a yellow powder (36 mg, 22%).

[0529] (Z)-1-(4-(1-(4-cyanophenyl)-1H-1,2,4-triazol- 3-yl)-2-fluorophenyl)-3-(3-(5-(dimethylamino)-2-isopro pylphenyl)-4-oxothiazolidin-2-ylidene)urea (J290) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-im inothiazolidin-4-one (C126) and isolated as a yellow powder (116 mg, 74%).

[0530] (Z)-1-(4-(1-(4-cyanophenyl)-1H-1,2,4-triazol- 3-yl)-2-fluoro-phenyl)-3-(3-(2-(1-methoxyethyl)-5- methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J291) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in WO 2017 / 040194 A1 pamphlet) and isolated as a yellow powder (52 mg, 34%).

[0531] Example 33: Preparation of (Z)-1-(2-hydroxy-4-(1-(4-(trifluoromethoxy )phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-( 2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J175) [Chemical formula] (Z)-1-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin -2-ylidene)-3-(2-(methoxymethoxy)-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J170; 0.112 g, 0.171 mmol) was dissolved in THF (0.855 mL), and 10% aq HCl (0.520 mL, 1.711 mmol) was added. When the mixture was heated at 65 °C overnight, solids began to precipitate. The mixture was concentrated and directly loaded onto diatomaceous earth. Purification by silica gel chromatography eluting with 0-40% acetone-hexane gave the title compound as a yellow powder (0.028 g, 27%). The following compounds were prepared according to the procedure of Example 33.

[0532] ​​​​​​​

[0533] (Z)-1-(2-Hydroxy-4-(1-(4-(trifluoromethoxy)phenyl) -1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl- 2-(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidine-2- ylidene)urea (J176) The title compound was prepared from (Z)-1-(2-(methoxymethoxy)-4-(1-(4-(trif luoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl) -3-(3-(5-methyl-2-(2,2,2-trifluoroethoxy)phenyl)-4 -oxothiazolidine-2-ylidene)urea (J171) and isolated as an off-white powder (29 mg, 29%).

[0534] (Z)-1-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-ox othiazolidine-2-ylidene)-3-(2-hydroxy-4-(1-(4-(triflu oromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J177) The title compound was prepared from (Z)-1-(3-(5-(dimethylamino)-2-isopropylpheny l)-4-oxothiazolidine-2-ylidene)-3-(2-(methoxymethoxy)- 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J172) and isolated as an off-white powder (7 mg, 4.4%).

[0535] (Z)-1-(2-Hydroxy-4-(1-(4-(trifluoromethoxy)phenyl)(Z)-1-(2-Hydroxy-4-(1-(4-(trifluoromethoxy)phenyl) -1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl- 2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazoli din-2-ylidene)urea (J178) The title compound was prepared from (Z)-1-(2-(methoxymethoxy)-4-(1-(4-(trif luoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl) -3-(3-(5-methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J173) and isolated as an off-white powder (22 mg, 21%).

[0536] (Z)-1-(3-(2-(1-ethoxyethyl)-5-methylphenyl)-4-oxo thiazolidin-2-ylidene)-3-(2-hydroxy-4-(1-(4-(trifluoro methoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea ( J179) The title compound was prepared from (Z)-1-(3-(2-(1-ethoxyethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)-3-(2-(methoxymethoxy)-4 -(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J174) and isolated as an off-white powder (43 mg, 28%).

[0537] Example 34: (Z)-1-(5-chloro-3-(2-isopropyl-5-methylphenyl ))-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl) ​​​Preparation of (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J32) [Chemical formula] (Z)-1-(2-Fluoro-4-(1-(4-(trifluoromethoxy)phenyl) -1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopro pyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J19; 102 mg, 0.167 mmol) and 1-chloropyrrolidine-2,5-dione (26. 7 mg, 0.200 mmol) were placed in a vial, and DMF (1.70 mL) was added . The reaction mixture was stirred at 40 °C. When completed, the reaction mixture was washed with a mixture of methyl tert-butyl ether (MTBE; ca. 15 mL) and water (ca. 10 mL). The layers were separated , and the aqueous layer was extracted with DCM (10 mL). The combined organic layers were dried over Na2SO4, filtered, concentrated, and subsequently loaded onto a silica cartridge. Purification by flash chromatography (silica gel, 0 - 100% EtOAc-(1:1 hexane-DCM)) gave the title compound as an off-white foam (22 mg, 19%). (22 mg, 19%).

[0538] The following compounds were prepared according to the procedure of Example 34.

[0539] (Z)-1-(5-Chloro-3-(5-methyl-2-(2,2,2-trifluoroethoxy s) phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4- (1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol- 3-yl)phenyl)urea (J33) The title compound was obtained as an off-white foam from (Z)-1-(2-fluoro-4-(1-(4-(trifluoromethoxy (Z)-1-(5-Chloro-3-(5-methyl-2-(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J34) was prepared from (Z)-1-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2-(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J30) and isolated as an off-white foam (24 mg, 19%). (5-Methyl-2-(2,2,2-trifluoroethoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea (J31) and isolated as an off-white foam (20 mg, 14%). It was prepared from

[0540] (Z)-1-(5-Chloro-3-(5-methyl-2-(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J34) -4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4-(1-(4-( (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J34) The title compound was prepared from (Z)-1-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3- (5-Methyl-2-(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J30) and isolated as an off-white foam (24 mg, 19%) (5-Methyl-2-(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J30) It was prepared from )

[0541] (Z)-1-(5-Chloro-3-(5-methyl-2-(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-ylidene)-3-(2-fluoro-4 -(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J36) -(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)urea (J36) The title compound was prepared from (Z)-1-(2-fluoro-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3- (5-Methyl-2-(trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J30) and isolated as an off-white foam (24 mg, 19%) (5-Methyl-2-(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-ylidene)urea (J30) Prepared from (azolidine-2-ylidene)urea (J35) and isolated as a yellow foam (2 9 mg, 15%).

[0542] Example 35: (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2- isopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea( J227) Preparation

Chemical Structure

[0543]

[0544] The following compounds were prepared according to the procedure of Example 35.

[0544] ​(Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-(1-methoxy ethyl)-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J 228) The title compound was prepared from 2-imino-3-(2-(1-methoxyethyl)-5-methylphenyl )-thiazolidin-4-one (prepared as described in International Publication No. WO 2017 / 040194A1 pamphlet) and isolated as an orange foam (27 mg, 33%).

[0545] (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(dimethylamino )-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)urea ( J242) The title compound was prepared from 3-(5-(dimethylamino)-2-isopropylphenyl)-2-imino thiazolidin-4-one (C126) and isolated as an off-white solid (4 8 mg, 34%).

[0546] (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin-2-yl idene)urea (J243) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white powder (72 mg, 48%). ​​

[0547] (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- (trifluoromethyl)phenyl)-4-oxothiazolidin-2-ylidene)urea (J 244) The title compound was prepared from 2-imino-3-(5-methyl-2-(trifluoromethyl)phenyl )thiazolidin-4-one (prepared as described in International Publication No. 2017040742A1 pamphlet and isolated as an off-white solid (68 mg, 49%).

[0548] (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- ((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothiazolidine -2-ylidene)urea (J245) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroeth oxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white solid (71 mg, 47%).

[0549] (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-isopropyl -5-methoxyphenyl)-4-oxothiazolidin-2-ylidene)urea (J246) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methoxyphenyl)thiazoli din-4-one (C98) and isolated as an off-white solid (70 mg, 51% )。

[0550] (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(dimethylamino -2-propylphenyl)-4-oxothiazolidin-2-ylidene)urea (J2 47) The title compound was prepared from 3-(5-(dimethylamino)-2-propylphenyl)-2-imino thiazolidin-4-one (C128) and isolated as an off-white solid (65 m g, 46%).

[0551] (Z)-1-(2-Cyano-4-(1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-methyl-2- propylphenyl)-4-oxothiazolidin-2-ylidene)urea (J248) The title compound was prepared from 2-imino-3-(5-methyl-2-propylphenyl)thiazolidin -4-one (prepared as described in International Publication No. WO 2016 / 033025 A1) and isolated as an off-white powder (58 mg, 43%).

[0552] (Z)-1-(2-Cyano-4-(1-(5-(trifluoromethoxy)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(2-i sopropyl-5-methylphenyl)-4-oxothiazolidin-2-ylidene)urea (J 259) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (as described in U.S. Patent Application Publication No. US 2014 / 0274688 A1) Prepared from (prepared as described in US Patent Application Publication No. 20140274688A1) and isolated as a yellow semi-solid (70 mg, 78%).

[0553] (Z)-1-(3-(2-Isopropyl-5-methylphenyl)-4-oxothiazolidin -2-ylidene)-3-(4-(1-(5-(trifluoromethoxy)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)-2-(trifluoromethyl)ph enyl)urea (J260) The title compound was prepared from 2-imino-3-(2-isopropyl-5-methylphenyl)thiazoli din-4-one (as described in US Patent Application Publication No. 20140274688A1 and isolated as a yellow powder (70 mg, 82%).

[0554] (Z)-1-(2-Cyano-4-(1-(5-(trifluoromethoxy)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-me thyl-2-(3,3,3-trifluoropropoxy)phenyl)-4-oxothiazolidin -2-ylidene)urea (J264) The title compound was prepared from 2-imino-3-(5-methyl-2-(3,3,3-trifluoroprop oxy)phenyl)thiazolidin-4-one (C99) and isolated as an off-white powder (72 mg, 48%).

[0555] (Z)-1-(2-Cyano-4-(1-(5-(trifluoromethoxy)pyridin-2- yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-me thyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)-4-oxothi azolidin-2-ylidene)urea (J265) The title compound was prepared from 2-imino-3-(5-methyl-2-((2,2,2-trifluoroethoxy)methyl)phenyl)thiazolidin-4-one (C117) and isolated as an off-white powder (74 mg, 50%). (Z)-1-(2-cyano-4-(1-(5-(trifluoromethoxy)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-2-ylidene)urea (J266) (Z)-1-(2-cyano-4-(1-(5-(trifluoromethoxy)pyridin-2-yl)-1H-1,2,4-triazol-3-yl)phenyl)-3-(3-(5-(dimethylamino)-2-isopropylphenyl)-4-oxothiazolidin-...

Claims

1. The following formula ("Formula 2") 【Chemistry 1】 (In the formula, (A) Ar １ teeth, (1) furanyl, phenyl, pyridazinyl, pyridyl, pyridinonyl, pyrimidinyl, thienyl, or (2) a substituted furanyl, a substituted phenyl, a substituted pyridazinyl, a substituted pyridyl, a substituted pyridinonyl, a substituted pyrimidinyl, or a substituted thienyl is selected from The substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyridazinyl, substituted pyridinonyl, substituted pyrimidinyl and substituted thienyl are independently selected from F, Cl, Br, I, CN, OH, SH, SF ５ , NO ２ , oxo, thioxo, NR ｘ R ｙ , C １ ~C ８ Alkyl, C １ ~C ８ Haloalkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Halocycloalkyl, C ３ ~C ８ Cycloalkoxy, C ３ ~C ８ Halocycloalkoxy, C １ ~C ８ Alkoxy, C １ ~C ８ Haloalkoxy, C ２ ~C ８ Alkenyl, C ３ ~C ８ Cycloalkenyl, C ２ ~C ８ Haloalkenyl, C ２ ~C ８ Alkynyl, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), S(=O)(C １ ~C ８ alkyl), S(=O)(C １ ~C ８ haloalkyl), S(=O) ２ (C １ ~C ８ alkyl), S(=O) ２ (C １ ~C ８ haloalkyl), OSO ２ (C １ ~C ８ alkyl), OSO ２ (C １ ~C ８ haloalkyl), C(=O)NR ｘ R ｙ , (C １ ~C ８ alkyl)NR ｘ R ｙ , C(=O)(C １ ~C ８ alkyl), C(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ haloalkyl), C(=O)O(C １ ~C ８ haloalkyl), C(=O)(C ３ ~C ８ cycloalkyl), C(=O)O(C ３ ~C ８ cycloalkyl), C(=O)(C ２ ~C ８ alkenyl), C(=O)O(C ２ ~C ８ alkenyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)-O-phenyl, phenyl, phenoxy, Si(C １ ~C ８ Alkyl) ３ , SNR ｘ R ｙ , S(=O)NR ｘ R ｙ , S(=O) ２ N.R. ｘ R ｙ or (Het-1), Each alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkenyl, cycloalkenyl, haloalkenyl, alkynyl, phenyl, phenoxy and (Het-1) substituent is independently selected from F, Cl, Br, I, CN, OH, SH, SF ５ , NO ２ , oxo, thioxo, NR ｘ R ｙ , C １ ~C ８ Alkyl, C １ ~C ８ Haloalkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Halocycloalkyl, C ３ ~C ８ Cycloalkoxy, C ３ ~C ８ Halocycloalkoxy, C １ ~C ８ Alkoxy, C １ ~C ８ Haloalkoxy, C ２ ~C ８ Alkenyl, C ３ ~C ８ Cycloalkenyl, C ２ ~C ８ Haloalkenyl, C ２ ~C ８ Alkynyl, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), S(=O)(C １ ~C ８ alkyl), S(=O)(C １ ~C ８ haloalkyl), S(=O) ２ (C １ ~C ８ alkyl), S(=O) ２ (C １ ~C ８ haloalkyl), OSO ２ (C １ ~C ８ alkyl), OSO ２ (C １ ~C ８ haloalkyl), C(=O)NR ｘ R ｙ , (C １ ~C ８ alkyl)NR ｘ R ｙ , C(=O)(C １ ~C ８ alkyl), C(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ haloalkyl), C(=O)O(C １ ~C ８ haloalkyl), C(=O)(C ３ ~C ８ cycloalkyl), C(=O)O(C ３ ~C ８ cycloalkyl), C(=O)(C ２ ~C ８ alkenyl), C(=O)O(C ２ ~C ８ alkenyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)OC １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)-O-phenyl, phenyl, phenoxy, Si(C １ ~C ８ Alkyl) ３ , SNR ｘ R ｙ , S(=O)NR ｘ R ｙ , S(=O) ２ N.R. ｘ R ｙ or (Het-1); (B) Het is a 5- or 6-membered saturated or unsaturated heterocycle containing one or more heteroatoms independently selected from nitrogen, sulfur, or oxygen, and the heterocycle also independently is selected from F, Cl, Br, I, CN, OH, SH, NO ２ , oxo, thioxo, NR ｘ R ｙ , C １ ~C ８ Alkyl, C １ ~C ８ Haloalkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Halocycloalkyl, C ３ ~C ８ Cycloalkoxy, C ３ ~C ８ Halocycloalkoxy, C １ ~C ８ Alkoxy, C １ ~C ８ Haloalkoxy, C ２ ~C ８ Alkenyl, C ３ ~C ８ Cycloalkenyl, C ２ ~C ８ Haloalkenyl, C ２ ~C ８ Alkynyl, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), S(=O)(C １ ~C ８ alkyl), S(=O)(C １ ~C ８ haloalkyl), S(=O) ２ (C １ ~C ８ alkyl), S(=O) ２ (C １ ~C ８ haloalkyl), OSO ２ (C １ ~C ８ alkyl), OSO ２ (C １ ~C ８ haloalkyl), C(=O)NR ｘ R ｙ , (C １ ~C ８ alkyl)NR ｘ R ｙ , C(=O)(C １ ~C ８ alkyl), C(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ haloalkyl), C(=O)O(C １ ~C ８ haloalkyl), C(=O)(C ３ ~C ８ cycloalkyl), C(=O)O(C ３ ~C ８ cycloalkyl), C(=O)(C ２ ~C ８ alkenyl), C(=O)O(C ２ ~C ８ alkenyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)C(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)-O-phenyl, phenyl, phenoxy, Si(C １ ~C ８ Alkyl) ３ , SNR ｘ R ｙ , S(=O)NR ｘ R ｙ Or S(=O) ２ N.R. ｘ R ｙ Each alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkenyl, cycloalkenyl, haloalkenyl, alkynyl, phenyl, and phenoxy substituent is independently selected from F, Cl, Br, I, CN, OH, SH, NO ２ , oxo, thioxo, NR ｘ R ｙ , C １ ~C ８ Alkyl, C １ ~C ８ Haloalkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Halocycloalkyl, C ３ ~C ８ Cycloalkoxy, C ３ ~C ８ Halocycloalkoxy, C １ ~C ８ Alkoxy, C １ ~C ８ Haloalkoxy, C ２ ~C ８ Alkenyl, C ３ ~C ８ Cycloalkenyl, C ２ ~C ８ Haloalkenyl, C ２ ~C ８ Alkynyl, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), S(=O)(C １ ~C ８ alkyl), S(=O)(C １ ~C ８ haloalkyl), S(=O) ２ (C １ ~C ８ alkyl), S(=O) ２ (C １ ~C ８ haloalkyl), OSO ２ (C １ ~C ８ alkyl), OSO ２ (C １ ~C ８ haloalkyl), C(=O)C(=O)NR ｘ R ｙ , (C １ ~C ８ alkyl)NR ｘ R ｙ , C(=O)C(=O)(C １ ~C ８ alkyl), C(=O)O(C １ ~C ８ alkyl), C(=O)C(=O)(C １ ~C ８ haloalkyl), C(=O)O(C １ ~C ８ haloalkyl), C(=O)(C ３ ~C ８ cycloalkyl), C(=O)O(C ３ ~C ８ cycloalkyl), C(=O)(C ２ ~C ８ alkenyl), C(=O)O(C ２ ~C ８ alkenyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)-O-phenyl, phenyl, phenoxy, Si(C １ ~C ８ Alkyl) ３ , SNR ｘ R ｙ , S(=O)NR ｘ R ｙ Or S(=O) ２ N.R. ｘ R ｙ may be substituted with one or more substituents selected from (C) Ar ２ teeth, (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl. is selected from The substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl and substituted thienyl are independently selected from F, Cl, Br, I, CN, OH, SH, SF ５ , NO ２ , oxo, thioxo, NR ｘ R ｙ , C １ ~C ８ Alkyl, C １ ~C ８ Haloalkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Halocycloalkyl, C ３ ~C ８ Cycloalkoxy, C ３ ~C ８ Halocycloalkoxy, C １ ~C ８ Alkoxy, C １ ~C ８ Haloalkoxy, C ２ ~C ８ Alkenyl, C ３ ~C ８ Cycloalkenyl, C ２ ~C ８ Haloalkenyl, C ２ ~C ８ Alkynyl, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), S(=O)(C １ ~C ８ alkyl), S(=O)(C １ ~C ８ haloalkyl), S(=O) ２ (C １ ~C ８ alkyl), S(=O) ２ (C １ ~C ８ haloalkyl), OSO ２ (C １ ~C ８ alkyl), OSO ２ (C １ ~C ８ haloalkyl), C(=O)NR ｘ R ｙ , (C １ ~C ８ alkyl)NR ｘ R ｙ , C(=O)(C １ ~C ８ alkyl), C(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ haloalkyl), C(=O)O(C １ ~C ８ haloalkyl), C(=O)(C ３ ~C ８ cycloalkyl), C(=O)O(C ３ ~C ８ cycloalkyl), C(=O)(C ２ ~C ８ alkenyl), C(=O)O(C ２ ~C ８ alkenyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)-O-phenyl, phenyl, phenoxy, Si(C １ ~C ８ Alkyl) ３ , SNR ｘ R ｙ , S(=O)NR ｘ R ｙ , S(=O) ２ N.R. ｘ R ｙ or (Het-1), Each alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkenyl, cycloalkenyl, haloalkenyl, alkynyl, phenyl, phenoxy and (Het-1) substituent is independently selected from F, Cl, Br, I, CN, OH, SH, NO. ２ , oxo, thioxo, NR ｘ R ｙ , C １ ~C ８ Alkyl, C １ ~C ８ Haloalkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Halocycloalkyl, C ３ ~C ８ Cycloalkoxy, C ３ ~C ８ Halocycloalkoxy, C １ ~C ８ Alkoxy, C １ ~C ８ Haloalkoxy, C ２ ~C ８ Alkenyl, C ３ ~C ８ Cycloalkenyl, C ２ ~C ８ Haloalkenyl, C ２ ~C ８ Alkynyl, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), S(=O)(C １ ~C ８ alkyl), S(=O)(C １ ~C ８ haloalkyl), S(=O) ２ (C １ ~C ８ alkyl), S(=O) ２ (C １ ~C ８ haloalkyl), OSO ２ (C １ ~C ８ alkyl), OSO ２ (C １ ~C ８ haloalkyl), C(=O)NR ｘ R ｙ , (C １ ~C ８ alkyl)NR ｘ R ｙ , C(=O)(C １ ~C ８ alkyl), C(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ haloalkyl), C(=O)O(C １ ~C ８ haloalkyl), C(=O)(C ３ ~C ８ cycloalkyl), C(=O)O(C ３ ~C ８ cycloalkyl), C(=O)(C ２ ~C ８ alkenyl), C(=O)O(C ２ ~C ８ alkenyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)-O-phenyl, phenyl, phenoxy, Si(C １ ~C ８ Alkyl) ３ , SNR ｘ R ｙ , S(=O)NR ｘ R ｙ , S(=O) ２ N.R. ｘ R ｙ or (Het-1); (D) R ３ is a substitution C ３ ~C ８ Cycloalkyl, substituted phenyl, substituted (C １ ~C ８ alkyl)phenyl, substituted (C １ ~C ８ alkyl)-O-phenyl, substituted (C ２ ~C ８ alkenyl)-O-phenyl, substituted (Het-1), substituted (C １ ~C ８ alkyl)-(Het-1) or substituted (C １ ~C ８ alkyl)-O-(Het-1); The substitution C ３ ~C ８ Cycloalkyl, substituted phenyl, substituted (C １ ~C ８ alkyl)phenyl, substituted (C １ ~C ８ alkyl)-O-phenyl, substituted (C ２ ~C ８ alkenyl)-O-phenyl, substituted (Het-1), substituted (C １ ~C ８ alkyl)-(Het-1) or substituted (C １ ~C ８ alkyl)-O-(Het-1) is NR ｘ C(=O)(C １ ~C ８ alkyl), OH, SH, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), C １ ~C ８ Haloalkyl, (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C ３ ~C ８ cycloalkyl), unsubstituted (C １ ~C ８ Alkyl)O(C １ ~C ８ alkyl)phenyl, H, F, Cl, (C １ ~C ８ haloalkyl) and (C １ ~C ８ haloalkoxy) substituted with one or more of １ ~C ８ Alkyl)O(C １ ~C ８ alkyl)phenyl, (C １ ~C ８ Alkyl)O(C １ ~C ８ alkyl)benzothiazolyl, (C １ ~C ８ Alkyl)O(C １ ~C ８ alkyl)benzoxazolyl, (C １ ~C ８ Alkyl)O(C １ ~C ８ alkyl)thiophenyl, (C １ ~C ８ Alkyl)O(C １ ~C ８ alkyl)thienopyrazolyl, (C １ ~C ８ Alkyl)O(C １ ~C ８ haloalkyl), (C １ ~C ８ haloalkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ haloalkyl)O(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ haloalkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)(C １ ~C ８ alkyl), unsubstituted (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)pyridyl, F and (C １ ~C ８ haloalkyl) １ ~C ８ alkyl)phenyl or (C １ ~C ８ (alkyl)-O-phenyl; and The substitution C ３ ~C ８ Cycloalkyl, substituted phenyl, substituted (C １ ~C ８ alkyl)phenyl, substituted (C １ ~C ８ alkyl)-O-phenyl, substituted (C ２ ~C ８ alkenyl)-O-phenyl, substituted (Het-1), substituted (C １ ~C ８ alkyl)-(Het-1) or substituted (C １ ~C ８ alkyl)-O-(Het-1) is independently F, Cl, Br, I, CN, OH, SH, SF ５ , NO ２ , oxo, thioxo, NR ｘ R ｙ , C １ ~C ８ Alkyl, C １ ~C ８ Haloalkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Halocycloalkyl, C ３ ~C ８ Cycloalkoxy, C ３ ~C ８ Halocycloalkoxy, C １ ~C ８ Alkoxy, C １ ~C ８ Haloalkoxy, C ２ ~C ８ Alkenyl, C ３ ~C ８ Cycloalkenyl, C ２ ~C ８ Haloalkenyl, C ２ ~C ８ Alkynyl, S(C １ ~C ８ alkyl), S(C ３ ~C ８ Cycloalkyl), S(C １ ~C ８ haloalkyl), S(C ３ ~C ８ halocycloalkyl), S(=O)(C １ ~C ８ alkyl), S(=O)(C １ ~C ８ haloalkyl), S(=O) ２ (C １ ~C ８ alkyl), S(=O) ２ (C １ ~C ８ haloalkyl), OSO ２ (C １ ~C ８ alkyl), OSO ２ (C １ ~C ８ haloalkyl), C(=O)(C １ ~C ８ alkyl), C(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ haloalkyl), C(=O)O(C １ ~C ８ haloalkyl), C(=O)(C ３ ~C ８ cycloalkyl), C(=O)O(C ３ ~C ８ cycloalkyl), C(=O)(C ２ ~C ８ alkenyl), C(=O)O(C ２ ~C ８ alkenyl), (C １ ~C ８ Alkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ Alkyl), (C １ ~C ８ haloalkyl)O(C １ ~C ８ Alkyl), (C １ ~C ８ haloalkyl)O(C １ ~C ８ haloalkyl), (C １ ~C ８ Alkyl)S(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ Alkyl)S(=O) ２ (C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)OC(=O)O(C １ ~C ８ alkyl), C(=O)(C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)O(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)C(=O)(C １ ~C ８ Alkyl), (C １ ~C ８ alkyl)phenyl, (C １ ~C ８ alkyl)-O-phenyl, phenyl, phenoxy, Si(C １ ~C ８ Alkyl) ３ , SNR ｘ R ｙ , S(=O)NR ｘ R ｙ , S(=O) ２ N.R. ｘ R ｙ or (Het-1); (E) L is Ar ２ is a single bond connecting (F) each R 5 , R 6 and R 7 is selected from H, F, Cl, Br, I, CN, NO 2 , NR x R y , OH, SH, S(C 1 -C 6 alkyl), S(C 1 -C 6 haloalkyl), C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with OH, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, phenyl and oxo. A compound having the structure:

2. (A) Ar １ is a substituted phenyl, a substituted pyridyl, a substituted pyridazinyl, a substituted pyridinonyl, or a substituted pyrimidinyl, wherein the substituted phenyl, the substituted pyridyl, the substituted pyridazinyl, the substituted pyridinonyl, and the substituted pyrimidinyl are independently selected from CN, SF ５ , C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, S(C １ ~C ６ haloalkyl), C １ ~C ６ Haloalkyl and C １ ~C ６ having one or more substituents selected from haloalkoxy; (B) Het is any of the following Het-A to Het-M. 【Chemistry 2】 is selected from one of: (C) Ar ２ is phenyl, pyridyl, pyrimidinyl, substituted phenyl, substituted pyridyl or substituted pyrimidinyl, wherein the substituted phenyl, substituted pyridyl and substituted pyrimidinyl are independently F, Cl, Br, I, CN, NO ２ , N.R. ｘ R ｙ , O.H., C. １ ~C ６ Alkoxy, (C １ ~C ６ Alkyl)O(C １ ~C ６ Alkyl), C １ ~C ６ Haloalkyl and C １ ~C ６ having one or more substituents selected from alkyl; (D) R ３ is a substituted phenyl, said substituted phenyl being N(CH ３ )C(=O)CH ３ , N(CH ２ CH ３ )C(=O)CH ３ ,OH,SH,S(C １ ~C ６ alkyl), S(C １ ~C ６ haloalkyl), C １ ~C ６ Haloalkyl, (C １ ~C ６ Alkyl)S(C １ ~C ６ Alkyl), (C １ ~C ６ Alkyl)S(C １ ~C ６ haloalkyl), (C １ ~C ６ Alkyl)O(C １ ~C ６ haloalkyl), (C １ ~C ８ haloalkyl)O(C １ ~C ８ alkyl) or (C １ ~C ６ Alkyl)O(C １ ~C ６ alkyl); and The substituted phenyl is independently selected from F, Cl, Br, I, CN, NO ２ , N.R. ｘ R ｙ ,OH,SH,S(C １ ~C ６ alkyl), S(C １ ~C ６ haloalkyl), C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Cycloalkyl, C １ ~C ６ Halocycloalkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Haloalkoxy, phenyl, C(=O)(C １ ~C ６ alkyl), C(=O)O(C １ ~C ６ Alkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ alkyl) or (C １ ~C ８ Alkyl)O(C １ ~C ８ alkyl); each R 5 , R 6 and R 7 is selected from H, F, Cl, Br, I, CN, NO 2 , NR x R y , OH, SH, S(C 1 -C 6 alkyl), S(C 1 -C 6 haloalkyl), C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted with OH, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, phenyl and oxo; (E) L is Ar ２ is a single bond connecting to NH.

3. Table 1A, Table 1B and / or Table 1C below: 【Table 1-1】 【Table 1-2】 【Table 1-3】 【Table 1-4】 【Table 1-5】 【Table 1-6】 【Table 1-7】 【Table 1-8】 【Table 1-9】 【Table 1-10】 【Table 1-11】 【Table 1-12】 【Table 1-13】 【Table 1-14】 【Table 1-15】 【Table 1-16】 【Table 1-17】 【Table 1-18】 【Table 1-19】 【Table 1-20】 【Table 1-21】 【Table 1-22】 【Table 1-23】 【Table 1-24】 【Table 1-25】 【Table 1-26】 【Table 1-27】 【Table 1-28】 【Table 1-29】 【Table 1-30】 【Table 1-31】 【Table 1-32】 【Table 1-33】 2. The compound of claim 1 having a structure selected from the compounds listed in:

4. (A) Ar １ is a substituted phenyl, a substituted pyridyl, or a substituted pyrimidinyl, wherein the substituted phenyl, the substituted pyridyl, and the substituted pyrimidinyl are independently selected from CN, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, S(C １ ~C ６ haloalkyl), C １ ~C ６ Haloalkyl and C １ ~C ６ having one or more substituents selected from haloalkoxy; (B) Het is triazolyl or pyrazolyl; (C) Ar ２ is phenyl, pyridyl, pyrimidinyl, substituted phenyl, substituted pyridyl or substituted pyrimidinyl, wherein the substituted phenyl, substituted pyridyl and substituted pyrimidinyl are independently F, Cl, Br, I, CN, NO ２ , N.R. ｘ R ｙ , O.H., C. １ ~C ６ Alkoxy, (C １ ~C ６ Alkyl)O(C １ ~C ６ Alkyl), C １ ~C ６ Haloalkyl and C １ ~C ６ having one or more substituents selected from alkyl; (F) R ３ is a substituted phenyl, said substituted phenyl being N(CH ３ )C(=O)CH ３ , N(CH ２ CH ３ )C(=O)CH ３ ,OH,SH,S(C １ ~C ６ alkyl), S(C １ ~C ６ haloalkyl), C １ ~C ６ Haloalkyl, (C １ ~C ６ Alkyl)S(C １ ~C ６ Alkyl), (C １ ~C ６ Alkyl)S(C １ ~C ６ haloalkyl), (C １ ~C ６ Alkyl)O(C １ ~C ６ haloalkyl), (C １ ~C ８ haloalkyl)O(C １ ~C ８ alkyl) or (C １ ~C ６ Alkyl)O(C １ ~C ６ alkyl); and The substituted phenyl is independently selected from F, Cl, Br, I, CN, NO ２ , N.R. ｘ R ｙ ,OH,SH,S(C １ ~C ６ alkyl), S(C １ ~C ６ haloalkyl), C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Cycloalkyl, C １ ~C ６ Halocycloalkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Haloalkoxy, phenyl, C(=O)(C １ ~C ６ alkyl), C(=O)O(C １ ~C ６ Alkyl), (C １ ~C ８ Alkyl)S(C １ ~C ８ alkyl) or (C １ ~C ８ Alkyl)O(C １ ~C ８ alkyl); (J) Each R ５ , R ６ and R ７ are H, F, Cl, Br, I, CN, NO ２ , N.R. ｘ R ｙ ,OH,SH,S(C １ ~C ６ alkyl), S(C １ ~C ６ haloalkyl), C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Alkoxy, C １ ~C ６ Haloalkoxy, C ３ ~C ６ Cycloalkyl, C ３ ~C ６ selected from halocycloalkyl, phenyl and oxo; and (L) L is Ar ２ is a single bond connecting to NH.

5. J30, J34, J39, J42, J49, J50, J60, J62, J66, J67, J72, J74, J81, J87, J88, J90, J94, J97, J117, J119, J120, J123, J124, J13 9, J141, J165, J167, J168, J173, J174, J178, J179, J180, J181, J182, J185, J186, J187, J188, J189, J190, J194, J195, J197 , J199, J200, J203, J204, J205, J206, J214, J215, J220, J221, J222, J226, J228, J229, J230, J232, J233, J234, J236, J237, J240, J241, J244, J245, J249, J250, J256, J262, J265, J267, J271, J274, J276, J280, J281, J286, J289, J291, J297, J298, J 299, J300, J303, J304, J306, J308, J309, J310, J311, J312, J314, J315, J316, J318, J319, J324, J325, J326, J327, J328, J 344, J350, J362, J363, J364, J365, J366, J368, J510, J539, J570, J574, J645, J646, J647, J648, J649, J650, J652, J653, J6 54, J655, J656, J657, J659, J663, J684, J686, J716, J719, J742, J745, J747, J751, J778, J779, 780, J781, J782, J783, J784, J785, J786, J787, J788, J789, J790, J791, J792, J793, J794, J795, J796, J797, J798 and J799.

6. The following table: 【Table 2-1】 【Table 2-2】 【Table 2-3】 【Table 2-4】 【Table 2-5】 【Table 2-6】 【Table 2-7】 【Table 2-8】 【Table 2-9】 【Table 2-10】 【Table 2-11】 【Table 2-12】 【Table 2-13】 【Table 2-14】 【Table 2-15】 【Table 2-16】 【Table 2-17】 【Table 2-18】 【Table 2-19】 【Table 2-20】 A compound selected from the structures listed in:

7. 13. A non-therapeutic process for controlling pests comprising applying to a locus a compound of claim 1 in an amount sufficient to control said pests.

8. 8. A non-therapeutic process according to claim 7, wherein the pest is beet armyworm (BAW), corn looper (CL) or Aedes aegypti (YFM).

9. 13. A composition comprising a compound according to claim 1 and at least one other compound having insecticidal, herbicidal, acaricidal, nematicidal or fungicidal activity.

10. A composition comprising the compound of claim 1 and a seed.

11. 13. A process comprising applying a compound according to claim 1 to a genetically modified plant or a genetically modified seed that has been genetically modified to express one or more special traits.

12. 10. A compound according to claim 1 for use in controlling endoparasites and / or ectoparasites in non-human animals by oral or topical administration.

13. 10. A compound of formula 1 as defined in claim 1, its stereoisomer or its veterinarily acceptable salt for use in treating or protecting a non-human animal from infestation or infection by an invertebrate pest, comprising contacting said non-human animal with a pesticidally effective amount of at least one compound of formula 1 as defined in claim 1, its stereoisomer or its veterinarily acceptable salt.

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