Novel benzimidazolon derivative compounds as autotaxin inhibitors

Abstract

This invention relates to a novel benzimidazolon derivative compound as an autotaxin inhibitor.

Description

[Technical Field]

[0001] This application claims priority under Korean Patent Application No. 10-2023-0043118, filed on March 31, 2023, and all content disclosed in the documents of the said Korean Patent Application is incorporated herein by reference.

[0002] This invention relates to novel compounds as autotaxin inhibitors. Specifically, this invention relates to novel benzimidazolon derivative compounds as autotaxin inhibitors. [Background technology]

[0003] Autotaxin (ATX), also known as ectonucleotide pyrophosphatase / phosphodiesterase 2 or lysophospholipase D, is an enzyme responsible for increasing lysophosphatidic acid (LPA). It is a secreted enzyme that plays a crucial role in converting lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a vital signaling molecule. Lysophosphatidic acid (LPA) is a bioactive lipid that exerts its biological activity by transmitting signals via specific G protein-bound receptors (LPA1-6), influencing the migration, proliferation, and survival of various cell types. Because plasma lysophosphatidic acid (LPA) levels are associated with autotaxin (ATX) activity, autotaxin is an important source of extracellular lysophosphatidic acid (LPA).

[0004] In particular, recent studies have shown that while lysophosphatidic acid (LPA) is involved in various physiological activities, in cancer patients, excessive LPA produced by the action of autotaxin promotes the growth, migration, metastasis, invasion, and colony formation of cancer cells. Specifically, in cancer cells of patients with cancers such as renal cell carcinoma, highly metastatic ovarian and breast cancer, thyroid carcinoma, Hodgkin lymphoma, neuroblastoma, invasive glioblastoma multiforme, prostate cancer, and skin cancer (melanomas), autotaxin is excessively produced and secreted. The secreted autotaxin converts LPC into LPA, and the amount of LPA produced is approximately 40 times that of healthy individuals, which has been reported to promote the growth, metastasis, and invasion of various cancer cells.

[0005] Furthermore, LPA produced by autotaxin binds to receptors present in cells, inducing angiogenesis and sclerosis. It is known that the concentrations of LPA and LPA receptors are elevated in a variety of diseases, including fibrotic diseases, proliferative disorders, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, skin diseases, and diseases associated with abnormal angiogenesis.

[0006] Therefore, inhibitors targeting autotaxin, an enzyme involved in the production of lysophosphatidic acid (LPA), are expected to have the potential to treat a variety of diseases, including cancer and fibrosis. However, conventional autotaxin inhibitors have problems such as low exposure in the body, making them less effective, or reduced autotaxin inhibitory activity due to competition with lysophosphatidylcholine (LPC), a substrate of the autotaxin enzyme. Therefore, there is a need to develop novel autotaxin inhibitors that exhibit excellent inhibitory activity and high exposure in the body. [Overview of the project] [Problems that the invention aims to solve]

[0007] One object of the present invention is to provide a novel compound having autotaxin inhibitory activity.

[0008] Another object of the present invention is to provide compounds useful for the prevention or treatment of autotaxin-mediated diseases. [Means for solving the problem]

[0009] To achieve the above objective, one aspect of the present invention provides a compound having the chemical structure of the following chemical formula 1, or a pharmaceutically acceptable salt thereof.

[0010] [ka]

[0011] To achieve the above objectives, another aspect of the present invention provides a pharmaceutical composition comprising the compound of chemical formula 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. [Effects of the Invention]

[0012] The compound according to the present invention has excellent efficacy in suppressing the activity of autotaxin, an enzyme involved in the production of lysophosphatidic acid, and can therefore be usefully used as an active ingredient in pharmaceutical compositions for the prevention or treatment of autotaxin-mediated diseases.

[0013] However, the effects of the present invention are not limited to those mentioned above, and further effects not mentioned can be clearly understood by those skilled in the art from the following description. [Modes for carrying out the invention]

[0014] First, we define the terms used in this invention.

[0015] In this invention, the following terms have the meanings set forth below unless otherwise indicated. Any undefined terms have the meanings understood in the art.

[0016] Throughout the specification, "including" a component means, unless otherwise stated, that it may include other components rather than excluding them.

[0017] In the structural formulas herein, the symbol "-" may indicate a single bond, and the symbol "=" may indicate a double bond. These symbols may be omitted, or they may be shown when necessary, such as to identify the bonded atom or bond position.

[0018] In this invention, "halogen" refers to fluoro(F), chlorine(Cl), bromine(Br), and iodine(I).

[0019] In this invention, "alkyl" refers to an aliphatic hydrocarbon group that does not contain a double or triple bond, and unless otherwise specified, may have 1 to 20, 1 to 19, 1 to 18, 1 to 17, 1 to 16, 1 to 15, 1 to 14, 1 to 13, 1 to 12, 1 to 11, 1 to 10 carbon atoms, for example, 1 to 6 carbon atoms, and especially 1 to 4 carbon atoms, and may be linear or branched. Specific examples of the alkyl groups include methyl group, ethyl group, propyl group, n-propyl group, isopropyl group, butyl group, n-butyl group, isobutyl group, tert-butyl group, sec-butyl group, 1-methylbutyl group, 1-ethylbutyl group, pentyl group, n-pentyl group, isopentyl group, neopentyl group, tert-pentyl group, hexyl group, n-hexyl group, 1-methylpentyl group, 2-methylpentyl group, 4-methyl-2-pentyl group, 3,3-dimethyl Examples of but not limited to these include butyl group, 2-ethylbutyl group, heptyl group, n-heptyl group, 1-methylhexyl group, octyl group, n-octyl group, tert-octyl group, 1-methylheptyl group, 2-ethylhexyl group, 2-propylpentyl group, n-nonyl group, 2,2-dimethylheptyl group, 1-ethylpropyl group, 1,1-dimethylpropyl group, isohexyl group, 4-methylhexyl group, 5-methylhexyl group, and benzyl group.

[0020] In this invention, "alkenyl" refers to an aliphatic hydrocarbon group containing at least one double bond, and unless otherwise specified, may have 2 to 20, 2 to 19, 2 to 18, 2 to 17, 2 to 16, 2 to 15, 2 to 14, 2 to 13, 2 to 12, 2 to 11, 2 to 10 carbon atoms, for example, 2 to 6 carbon atoms, and particularly 2 to 4 carbon atoms, and may be linear or branched. Specific examples of the aforementioned alkenyl groups include, but are not limited to, vinyl group, 1-propenyl group, isopropenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 3-methyl-1-butenyl group, 1,3-butadienyl group, allyl group, 1-phenylvinyl-1-yl group, 2-phenylvinyl-1-yl group, 2,2-diphenylvinyl-1-yl group, 2-phenyl-2-(naphthyl-1-yl)vinyl-1-yl group, 2,2-bis(diphenyl-1-yl)vinyl-1-yl group, stilbenyl group, and styrenyl group.

[0021] In this invention, "alkynyl" refers to an aliphatic hydrocarbon group containing at least one triple bond, and unless otherwise specified, may have 2 to 20, 2 to 19, 2 to 18, 2 to 17, 2 to 16, 2 to 15, 2 to 14, 2 to 13, 2 to 12, 2 to 11, 2 to 10 carbon atoms, for example, 2 to 6 carbon atoms, and particularly 2 to 4 carbon atoms, and may be linear or branched. Specific examples of the alkynyl group include, but are not limited to, ethynyl, propynyl, butynyl, pentynyl, and hexynyl groups.

[0022] In this invention, "cycloalkyl" refers to a cyclic aliphatic hydrocarbon group that does not contain a double or triple bond, and unless otherwise specified, may have 3 to 30, 3 to 28, 3 to 26, 3 to 24, 3 to 22, 3 to 20, 3 to 18, 3 to 16, 3 to 14, 3 to 12, 3 to 10 carbon atoms, for example, 3 to 8 carbon atoms, and especially 3 to 6 carbon atoms, and may be monocyclic or polycyclic. The polycyclic group means a group in which a cycloalkyl group is immediately linked or fused with another ring group, where the other ring group may be a cycloalkyl group, but may also be another type of ring group, such as a heterocycloalkyl group, an aryl group, a heteroaryl group, etc. Specific examples of the aforementioned cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, 3-methylcyclopentyl, 2,3-dimethylcyclopentyl, cyclohexyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 2,3-dimethylcyclohexyl, 3,4,5-trimethylcyclohexyl, 4-tert-butylcyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.2]nonyl; bicyclo[4.4.0]decyl; and bicyclo[4.1.0]heptyl.

[0023] The term "cycloalkenyl" as used in this invention refers to a cyclic aliphatic hydrocarbon group containing at least one double bond, which, unless otherwise specified, may have 3 to 30, 3 to 28, 3 to 26, 3 to 24, 3 to 22, 3 to 20, 3 to 18, 3 to 16, 3 to 14, 3 to 12, or 3 to 10 carbon atoms, for example, 3 to 8 carbon atoms, and particularly 3 to 6 carbon atoms, and may be monocyclic or polycyclic. The polycyclic group means a group in which the cycloalkenyl group is immediately linked or fused with another ring group, where the other ring group may be a cycloalkyl group, but may also be other types of ring groups, such as a heterocycloalkyl group, an aryl group, or a heteroaryl group. Specific examples of the cycloalkenyl group include, but are not limited to, cyclopentenyl, cyclohexenyl, cyclopenta-1,3-dienyl, cycloheptenyl, cyclooctenyl, and cycloocta-1,4-dienyl groups.

[0024] In this invention, "aryl" refers to an aromatic hydrocarbon group, which, unless otherwise specified, may have 6 to 30, 6 to 28, 6 to 26, 6 to 24, 6 to 22, 6 to 20, 6 to 18, 6 to 16, 6 to 14 carbon atoms, for example, 6 to 12 carbon atoms, and may be monocyclic or polycyclic. Polycyclic means a group in which an aryl group is immediately linked or fused with another ring group, where the other ring group may be an aryl group, but may also be other types of ring groups, such as a cycloalkyl group, a heterocycloalkyl group, a heteroaryl group, etc. Furthermore, the aryl group may include a spiro group. Specific examples of the aforementioned aryl group include, but are not limited to, phenyl, biphenyl, triphenyl, naphthyl, anthryl, chrysenyl, phenantrenyl, perilenyl, fluoranthenyl, triphenylenyl, phenalenyl, pyrenyl, tetracenyl, pentacenyl, fluorenyl, indenyl, acenaphthirenyl, benzofluorenyl, spirobifluorenyl, 2,3-dihydro-1H-indenyl, and their fused ring groups.

[0025] In this invention, "heterocycloalkyl," "heterocycloalkenyl," and "heteroaryl" refer to compounds in which at least one atom constituting the ring of the aforementioned cycloalkyl, cycloalkenyl, and aryl is substituted with a heteroatom such as O, S, Se, N, or Si.

[0026] In this invention, "substitution" means that a hydrogen atom bonded to a carbon atom in the structure is replaced by another substituent. The position of substitution is not limited to any position where a hydrogen atom can be substituted, i.e., any position where a substituent can be substituted. If substitution occurs at two or more positions, the two or more substituents may be the same or different.

[0027] In this invention, "pharmaceutically acceptable" means that, when used in a normal medicinal dosage, it is available for use in animals, more specifically in humans, while avoiding significant toxic effects, and is therefore eligible for, preferably approved by, a federal or state regulatory body, or is listed in, the United States Pharmacopeia, or otherwise recognized as a common pharmacopoeia.

[0028] In this invention, "pharmaceutically acceptable salt" means a salt of the compound of the present invention that is pharmaceutically acceptable and has the preferred biological or pharmacological activity of the parent compound. Examples of these salts are not limited to those listed here, but include acid addition salts formed from inorganic acids [e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, etc.], and acetic acid, oxalic acid, tartari acid, succinic acid, malic acid, fumaric acid, maleic acid, ascorbic acid, trifluoroacetic acid, benzoic acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalene sulfonic acid, naphthalene disulfonic acid The compounds include salts formed from organic acids such as polygalacturonic acid. The compounds may also be administered as pharmaceutically acceptable quaternary salts known to those skilled in the art, particularly including chlorides, bromides, iodides, -O-alkyls, toluenesulfonates, methylsulfonates, sulfonates, phosphates, or carboxylates (e.g., benzoates, succinates, acetates, glycoates, maleates, malates, fumarates, citrates, tartarates, ascorbates, cinnamoates, mandeloates, and diphenylacetates). The compounds of the chemical formula of the present invention may include not only pharmaceutically acceptable salts but also any salts, hydrates, and solvates that can be produced by conventional methods.

[0029] In this invention, "hydrate" means a compound or salt thereof of the present invention that contains a stoichiometric or non-stoichiometric amount of water bonded by non-covalent intermolecular forces.

[0030] In this invention, "solvate" means a compound or salt thereof of the present invention that contains a stoichiometric or non-stoichiometric amount of solvent bonded by non-covalent intermolecular forces. Preferred solvents include volatile, non-toxic, and / or solvents suitable for administration to humans.

[0031] In this invention, "prodrug" refers to a substance that is transformed into a parent drug in vivo. This means a compound of the present invention that can be hydrolyzed, oxidized, and subjected to other reactions under biological conditions (in vitro or intra vivo) to produce an active compound, particularly the compound of the present invention. Examples of prodrugs include, but are not limited to, compounds containing a biohydrolyzable moiety that are biohydrolyzed to produce the compound of the present invention, such as biohydrolyzable amides, biohydrolyzable esters, biohydrolyzable carbamates, biohydrolyzable carbonates, biohydrolyzable ureides, and biohydrolyzable phosphate analogs. Such prodrugs include compounds readily available based on various known literature.

[0032] In this invention, "isomer" refers to a compound or salt thereof of the present invention that has the same chemical or molecular formula but is structurally or sterically different. Such isomers include structural isomers such as tautomers, stereoisomers such as R or S isomers having an asymmetric carbon center, geometric isomers (trans, cis), and enantiomers. Furthermore, all of these isomers and mixtures thereof are also included in the scope of this invention.

[0033] In this invention, "pharmaceutically acceptable carrier" refers to a diluent, adjuvant, additive, or carrier administered with the compound of the present invention.

[0034] In this invention, "prevention" means reducing the risk of acquiring a disease or disability (i.e., preventing the progression of one or more clinical symptoms of a disease in a subject who is exposed to the disease, susceptible to the disease but has not yet contracted it, or whose symptoms of the disease have not yet appeared).

[0035] In this invention, "treatment" means improving a disease or disorder (i.e., preventing or reducing the progression of the disease or one or more clinical symptoms of the disease), improving one or more physical parameters that the subject cannot recognize, or regulating a disease or disorder physically (e.g., stabilizing unrecognizable symptoms) or mentally (e.g., stabilizing physical parameters), or both.

[0036] The present invention will be described in detail below.

[0037] 1. Novel benzimidazolon derivative compounds One aspect of the present invention provides a compound having the chemical structure of the following chemical formula 1, or a pharmaceutically acceptable salt, isomer, solvate, hydrate, or prodrug thereof.

[0038] [ka]

[0039] In the above chemical formula 1, Q1 and Q2 may each be independently selected from the group consisting of carbon and nitrogen.

[0040] In the above chemical formula 1, X1 and X2 may each be independently selected from the group consisting of hydrogen; halogen; substituted or unsubstituted alkyl; substituted or unsubstituted cycloalkyl; and substituted or unsubstituted alkoxy. Specifically, X1 and X2 may each be independently selected from the group consisting of hydrogen; halogen; halogen-substituted or unsubstituted alkyl; halogen-substituted or unsubstituted cycloalkyl; and halogen-substituted or unsubstituted alkoxy. For example, X1 and X2 may each be independently selected from the group consisting of hydrogen; halogen; halogen-substituted or unsubstituted alkyl; unsubstituted cycloalkyl; and halogen-substituted alkoxy. In particular, X1 and X2 may each be independently selected from the group consisting of hydrogen; halogen; halogen-substituted or unsubstituted C1-C3 alkyl; unsubstituted C3-C6 cycloalkyl; and halogen-substituted C1-C3 alkoxy.

[0041] In the above chemical formula 1, A may be an aryl or a heteroaryl. For example, A may be any one selected from the group consisting of monocyclic or polycyclic aryls and monocyclic or polycyclic heteroaryls. Specifically, A may be any one selected from the group consisting of phenyl, benzodioxolyl, pyridinyl, pyrimidinyl, pyrazolyl, dihydroindenyl, isoindolinyl, benzothiazolyl, dihydroisobenzofuranyl, and dihydrobenzooxazinyl. In particular, A is phenyl; benzo[d][1,3]dioxolyl; pyridin-2-yl; pyridin-3-yl; pyrimidin-5-yl; 1H-pyrazol-4-yl; 2,3-dihydro-1H-inden-5-yl; isoindoline It may be any one selected from the group consisting of -5-yl (isoindolin-5-yl); benzo[d]thiazol-2-yl; 1,3-dihydroisobenzofuran-5-yl; and 3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl.

[0042] In the above chemical formula 1, X3, X4, and X5 may each be independently selected from the group consisting of hydrogen; halogen; hydroxyl; oxo; carboxyl; substituted or unsubstituted alkoxy; substituted or unsubstituted thio; substituted or unsubstituted amino; substituted or unsubstituted carbamoyl; substituted or unsubstituted sulfonyl; substituted or unsubstituted alkyl; substituted or unsubstituted cycloalkyl; substituted or unsubstituted tricycloalkyl; substituted or unsubstituted heterocycloalkyl; substituted or unsubstituted oxoheterocycloalkyl; substituted or unsubstituted heterobicycloalkyl; substituted or unsubstituted cycloalkenyl; substituted or unsubstituted heterocycloalkenyl; substituted or unsubstituted oxazabicycloalkyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; substituted or unsubstituted heterocycloalkylcarbonyl; and substituted or unsubstituted heterobicycloalkylcarbonyl. Specifically, X3, X4, and X5 are each independently hydrogen; halogen; hydroxy; oxo; carboxy; substituted or unsubstituted alkoxy; alkylthio; substituted or unsubstituted amino; substituted or unsubstituted carbamoyl; substituted or unsubstituted sulfonyl; substituted or unsubstituted alkyl; substituted or unsubstituted cycloalkyl; substituted or unsubstituted tricycloalkyl; substituted or unsubstituted morpholino; substituted or unsubstituted pyrrolidinyl; substituted or unsubstituted azetidinyl; substituted or unsubstituted This includes unsubstituted piperazinyl; substituted or unsubstituted piperidinyl; substituted or unsubstituted oxazepanyl; substituted or unsubstituted oxetanyl; substituted or unsubstituted tetrahydrofuranyl; substituted or unsubstituted tetrahydropyranyl; substituted or unsubstituted oxopiperidinyl; substituted or unsubstituted oxoxazolidinyl;Substituted or unsubstituted oxooxazaspiroalkanyl; substituted or unsubstituted azaspiroalkanyl; substituted or unsubstituted oxazazaspiroalkanyl; substituted or unsubstituted diazaspiroalkanyl; substituted or unsubstituted cycloalkenyl; substituted or unsubstituted dihydropyranyl; substituted or unsubstituted dihydrofuranyl; substituted or unsubstituted oxazabicycloalkyl; substituted or unsubstituted phenyl; substituted or unsubstituted oxadiazolyl It may be any one selected from the group consisting of (oxadiazolyl); substituted or unsubstituted pyrazol; substituted or unsubstituted pyrrolidinecarbonyl; substituted or unsubstituted piperazinecarbonyl; substituted or unsubstituted piperidinecarbonyl; substituted or unsubstituted morpholinecarbonyl; substituted or unsubstituted azetidinecarbonyl; and substituted or unsubstituted oxaazaspiroalkanecarbonyl. The functional groups substituted in X3, X4, and X5 are, independently, halogen; hydroxy; alkoxy; alkoxycarbonyl; sulfonyl; alkylsulfonyl; haloalkylsulfonyl; oxo; alkyl; haloalkyl; hydroxyalkyl; cycloalkyl; halocycloalkyl; heterocycloalkyl; alkyloxoheterocycloalkyl; aryl; heteroaryl; haloalkylheteroaryl; acetyl; alkylcarbonyl; haloalkylcarbonyl; cycloalkylcarbonyl; halocycloalkylcarbonyl; heterocycloalkylcarbonyl; haloheterocycloalkylcarbonyl; hydroxyheterocycloalkylcarbonyl; alkylheterocycloalkylcarbonyl; alkylamino; cycloalkylamino;X3, X4, and X5 may be substituted with at least one selected from the group consisting of cycloalkylalkylamino and alkylaminocarbonyl. For example, each of X3, X4, and X5 may independently be hydrogen; halogen; hydroxy; oxo; carboxy; methoxy; ethoxy; propoxy; isopropoxy; cyclobutylmethoxy; cyclopropylmethoxy; methylthio; dimethylamino; isobutyrylamido; methylsulfonamide; (2,2,2-trifluoroethyl)sulfonamide; methylcarbamoyl; dimethylcarbamoyl ;(2,2,2-trifluoroethyl)carbamoyl; methylsulfonyl; morpholinosulfonyl; piperidin-1-ylsulfonyl; pyrrolidine-1-ylsulfonyl; N,N-dimethylsulfamoyl; N-cyclopropylsulfamoyl; N-(cyclobutylmethyl)sulfamoyl; methyl; propyl; isopropyl; tert-butyl; butyl; 2-hydroxypropan-2-yl; trifluoromethyl; 2,2,2-trifluoroethyl;2-hydroxy-2-methylpropyl; 2-fluoro-2-methylpropyl; 1-hydroxy-2-methylpropan-2-yl; 1-fluoro-2-methylpropan-2-yl; (2-oxopyrrolidin-1-yl)methyl; ((3-(trifluoromethyl)-1H-pyrazol-4-yl)methyl(((3-(trifluoromethyl)-1H-pyrazol-4-yl)methyl);(4-(trifluoromethyl)-1H-imidazol-1-yl)methyl((4-(trifluoromethyl)-1H-imidazol-1-yl)methyl);(3-methyl-2-oxo-imidazolin-1-yl)methyl((3-methyl-2-oxo-imidazolin-1-yl)methyl);Oxetane-3-ylmethyl(o xetan-3-ylmethyl; 2-(dimethylamino)-2-oxoethyl; 2-oxo-2-(pyrrolidin-1-yl)ethyl; morpholinomethyl; 2-morpholino-2-oxoethyl; 2-(4,4-difluoropiperidine-1-yl)-2-oxoethyl peridin-1-yl)-2-oxoethyl; 2-(3-hydroxyazetidin-1-yl)-2-oxoethyl; 2-(2-methylmorpholino)-2-oxoethyl; 2-(3-methylmorpholino)-2-oxoethyl; cyclopropylmethyl;Cyclobutylmethyl; cyclopropyl; 1-(hydroxymethyl)cyclopropyl; 1-(hydroxymethyl)cyclobutyl; 1-hydroxycyclobutyl; cyclohexyl; (3r,5r,7r)-adamantan-1-yl; morpholino; 3-methyloxetan-3-yl; 3-hydroxyoxetan-3-yl; tetrahydro-2H-pyran-4-yl; tetrahydrofuran-3-yl; 2-oxo-piperidine-1-yl in-1-yl); pyrrolidine-1-yl; 3-hydroxyazetidin-1-yl; 3,3-difluoroazetidin-1-yl; 3,3-difluoropyrrolidin-1-yl; 4-methylpiperazin-1-yl; 4,4-difluoropiperidine- 1-yl(4,4-difluoropiperidin-1-yl); 4-(cyclopropanecarbonyl)piperazin-1-yl(4-(cyclopropanecarbonyl)piperazin-1-yl); 4-(cyclobutanecarbonyl)piperazin-1-yl(4-(cyclobutanecarbonyl)piperazin-1-yl); 4-(isopropoxycarbonyl)piperazin-1-yl(4-(isopropoxycarbonyl)piperazin-1-yl);4-(4,4-difluorocyclohexane-1-carbonyl)piperazin-1-yl; 1-(oxetan-3-yl)piperidine-4-yl; 1-(cyclopropanecarbonyl)piperidine-4-yl; 1-(cyclobutanecarbonyl)piperidine- 4-yl(1-(cyclobutanecarbonyl)piperidin-4-yl); 1-propionylpiperidin-4-yl(1-propionylpiperidin-4-yl); 4-propionylpiperazin-1-yl(4-propionylpiperazin-1-yl); 3,6-dihydro-2H-pyran-4-yl(3,6-dihydro-2H-pyran-4-yl); 2,5-dihydrofuran-3-yl(2,5-dihydrofuran-3-yl); 2-azaspiro[3.3]he Butan-2-yl (2-azaspiro[3.3]heptan-2-yl); 7-oxa-2-azaspiro[3.5]nonan-2-yl (7-oxa-2-azaspiro[3.5]nonan-2-yl); 2-oxa-6-azaspiro[3.3]heptan-6-yl (2-oxa-6-azaspiro[3.3]heptan-6-yl); 2-oxa-5-azabicyclo[2.2.1]heptan-5-yl (2-oxa-5-azabicyclo[2.2.1]heptan-5-yl); 8-oxa-3-az Bicyclo[3.2.1]octan-3-yl; 1,4-oxazepan-4-yl; 7-acetyl-2,7-diazaspiro[3.5]nonan-2-yl; 7-(tert-butoxycarbonyl)-2,7-diazaspiro[3.5]nonan-2-yl azaspiro[3.5]nonan-2-yl); 4,4-dimethyl-2-oxo-oxazolidin-3-yl; 5-oxo-6-oxa-4-azaspiro[2.4]heptan-4-yl; cyclohexen-1-yl; 4-methyl-cyclohexen-1-yl;4',4'-dimethylcyclohexen-1-yl; phenyl; chlorophenyl; 5-cyclopropyl-1,3,4-oxadiazol-2-yl; 5-cyclopentyl-1,3,4-oxadiazol-2-yl; 5-cyclohexyl-1,3 ,4-oxadiazol-2-yl(5-cyclohexyl-1,3,4-oxadiazol-2-yl);5-cycloheptyl-1,3,4-oxadiazol-2-yl(5-cycloheptyl-1,3,4-oxadiazol-2-yl);5-(tetrahydro-2H-pyran-4-yl)-1,3,4-oxadiazol-2-yl(5-(tetrahydro-2H-pyran-4-yl)-1,3,4-oxadiazol-2-yl);5-(4,4-difluorocyclohexyl)-1,3 ,4-Oxadiazol-2-yl (5-(4,4-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl); 1-Propyl-1H-pyrazol-4-yl (1-propyl-1H-pyrazol-4-yl); Piperidine-1-carbonyl (piperidine-1-carbonyl); Morpholine-4-carbonyl (morpholine-4-carbonyl); 3-Methylmorpholino-4-carbonyl (3-methylmorpholino-4-carbonyl) Pyrrolidine-1-carbonyl; azetidine-1-carbonyl; 3-hydroxyazetidine-1-carbonyl; 3,3-difluoroazetidine-1-carbonyl; 3-methoxypyrrolidine-1-carbonyl3,3-difluoropyrrolidine-1-carbonyl; 4-methylpiperazine-1-carbonyl; 4-hydroxypiperidine-1-carbonyl; 4-methoxypiperidine-1-carbonyl; 4,4-diph It may be any one selected from the group consisting of 4,4-difluoropiperidine-1-carbonyl; 7-oxa-2-azaspiro[3.5]nonane-2-carbonyl; and 2-oxa-6-azaspiro[3.3]heptane-6-carbonyl.

[0043] In the above chemical formula 1, n may be an integer between 0 and 3. Specifically, n may be an integer between 0 and 2, for example, n may be 0 or 1.

[0044] In the above chemical formula 1, R1 and R2 are each independently one selected from the group consisting of hydrogen; a substituted or unsubstituted alkyl group; and a substituted or unsubstituted cycloalkyl group; or R1 and R2 may be linked to each other to form a substituted or unsubstituted hydrocarbon ring. Specifically, R1 and R2 are each independently hydrogen; or a substituted or unsubstituted alkyl group; or R1 and R2 may be linked to each other to form one selected from the group consisting of a substituted or unsubstituted cycloalkyl group; a substituted or unsubstituted heterocycloalkyl group; a substituted or unsubstituted aryl group; and a substituted or unsubstituted heterocycloaryl group. For example, R1 and R2 are each independently hydrogen; or a substituted or unsubstituted C1-C6 alkyl group; or R1 and R2 may be linked to each other to form a substituted or unsubstituted cycloalkyl group. In particular, R1 and R2 may each be independently hydrogen or methyl, or R1 and R2 may be linked together to form a cycloalkyl group having 3 to 6 carbon atoms.

[0045] In the above chemical formula 1, B may be an aryl or a heteroaryl. Specifically, B may be phenyl or a heteroaryl comprising at least one selected from the group consisting of N and O. For example, B may be phenyl, pyridine, oxazole, or isoxazole.

[0046] In the above chemical formula 1, X6 and X7 may each be independently selected from the group consisting of hydrogen; halogen; hydroxyl; oxo; substituted or unsubstituted alkoxy; substituted or unsubstituted amino; substituted or unsubstituted alkyl; and substituted or unsubstituted cycloalkyl. Specifically, X6 and X7 may each be independently selected from the group consisting of hydrogen; halogen; hydroxyl; oxo; and substituted or unsubstituted alkyl. For example, X6 and X7 may each be independently hydrogen or halogen.

[0047] On the other hand, unless otherwise specified, the functional groups substituted in X1, X2, X6, X7, R1, and R2 may be substituted with at least one selected from the group consisting of halogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl, heterocycloalkyl, -OR3, -(CO)-R3, -(CO)-OR3, alkylamino, and oxo. Here, R3 may be hydrogen or alkyl.

[0048] In particular, the IUPAC names of specific examples of compounds having the chemical structure of chemical formula 1 may be those shown in Table 1 below, but are not limited to these.

[0049] [Table 1]

[0050] [Table 2]

[0051] [Table 3]

[0052] [Table 4]

[0053] Table 5

[0054] Table 6

[0055] Table 7

[0056] Table 8

[0057] Table 9

[0058] Table 10

[0059] Table 11

[0060] Table 12

[0061] Table 13

[0062] Table 14

[0063] Table 15

[0064] Table 16

[0065] Table 17

[0066] Table 18

[0067] Table 19

[0068] Table 20

[0069] Table 21

[0070] Table 22

[0071] Table 23

[0072] Table 24

[0073] Table 25

[0074] Table 26

[0075] Table 27

[0076] Table 28

[0077] Table 29

[0078] Table 30

[0079] Table 31

[0080] Table 32

[0081] Table 33

[0082] Table 34

[0083] Table 35

[0084] [Table 36]

[0085] [Table 37]

[0086] [Table 38]

[0087] [Table 39]

[0088] [Table 40]

[0089] [Table 41]

[0090] [Table 42]

[0091] The compound of the present invention having the chemical structure of Chemical Formula 1 inhibits the enzymatic activity of autotaxin. In specific experimental examples of the present invention, it was confirmed that the compound having the chemical structure of Chemical Formula 1 of the present invention is effective as a so-called "autotaxin inhibitor" that inhibits the enzymatic activity of autotaxin. Therefore, the compound having the chemical structure of Chemical Formula 1 of the present invention, or its pharmaceutically acceptable salts, isomers, solvates, hydrates, or prodrugs, can be used as active ingredients in pharmaceutical compositions for the prevention or treatment of diseases related to the enzymatic activity of autotaxin.

[0092] 2. Applications of novel benzimidazolon derivative compounds Another aspect of the present invention provides a pharmaceutical composition comprising a compound having the chemical structure of chemical formula 1, or a pharmaceutically acceptable salt, isomer, solvate, hydrate, or prodrug thereof, as an active ingredient.

[0093] As described above, the compound having the chemical structure of chemical formula 1 has activity as an autotaxin inhibitor that suppresses the expression and activity of autotaxin. Therefore, the pharmaceutical composition of the present invention can be used for the prevention or treatment of autotaxin-mediated diseases, so-called autotaxin-mediated diseases.

[0094] In particular, the autotaxin-mediated diseases mentioned above may be diseases caused by the overexpression or overactivation of autotaxins.

[0095] In one example, the autotaxin-mediated disease may be a cell proliferation disorder or fibrosis.

[0096] The aforementioned cell proliferation disorders include, but are not limited to, cancerous hyperproliferative disorders (e.g., cancers of the brain, lung, squamous epithelial cells, bladder, stomach, pancreas, breast, head, neck, kidney, liver, ovaries, prostate, colorectal, colon, epidermis, esophagus, testicles, gynecological, or thyroid; acute myeloid leukemia, multiple myeloma, mesothelioma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), neuroblastoma, and acute lymphoblastic leukemia (ALL)); noncancerous hyperproliferative disorders (e.g., benign hyperplasia of the skin (e.g., psoriasis), restenosis, and benign prostatic hyperplasia (BPH)); and diseases relating to angiogenesis or neoangiogenesis (e.g., tumor neoangiogenesis, hemangioma, glioma, melanoma, Kaposi's sarcoma, and cancers of the ovaries, breast, lung, pancreas, prostate, colon, and epidermis). Cell proliferation disorders further include primary and metastatic cancers. In particular, the cell proliferation disorders include pseudomyxoma, intrahepatic cholangiocarcinoma, hepatoblastoma, liver cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, oropharyngeal-tonsil cancer (HPV-related), oropharyngeal-hypopharyngeal cancer (HPV-unrelated), mycosis fungoides, basal cell carcinoma, ovarian epithelial carcinoma, ovarian germ cell tumor, male breast cancer, brain tumor, pituitary adenoma, gallbladder and biliary tract cancer, gallbladder cancer, biliary tract cancer, Colon cancer, chronic myeloid leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, diffuse large B-cell lymphoma, ampulla carcinoma of Vater, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, nasal and paranasal sinus cancer, non-Hodgkin lymphoma, tongue cancer, astrocytoma, pediatric and adolescent brain tumors, pediatric and adolescent lymphoma, pediatric and adolescent leukemia, small intestine cancer, meningioma, esophageal cancer, neuroblastoma, renal pelvis cancer, This includes, but is not limited to, kidney cancer, heart cancer, duodenal cancer, malignant soft tissue tumors, malignant bone tumors, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye tumors, vulvar cancer, ureteral cancer, urethral cancer, cancer of unknown primary origin, gastric lymphoma, gastric cancer, gastric carcinoid, gastrointestinal stromal tumors, Wilms' tumor, breast cancer, sarcoma, penile cancer, gestational trophoblastic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone tumors, metastatic brain tumors, mediastinal cancer, rectal neuroendocrine tumors, rectal cancer, vaginal cancer, spinal cord tumors, acoustic neuroma, pancreatic cancer, salivary gland cancer, Paget's disease, squamous cell carcinoma, lung adenocarcinoma, lung cancer, lung squamous cell carcinoma, skin cancer, anal cancer, rhabdomyosarcoma, laryngeal cancer, thymic cancer, etc.

[0097] Furthermore, the aforementioned fibrosis includes diseases such as cystic fibrosis, idiopathic pulmonary fibrosis, hepatic fibrosis, renal fibrosis, scleroderma, radiation-induced fibrosis, Peyronie's disease, scarring, and other diseases in which excessive fibrosis contributes to the disease pathology. Furthermore, the fibrosis is selected from the group consisting of mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive nodular fibrosis, nephrogenic systemic fibrosis, Crohn's disease, keloids, systemic sclerosis, articular fibrosis, Dupuytren's contracture, adhesive capsulitis, pancreatic fibrosis, intestinal fibrosis, hepatic fibrosis, pulmonary fibrosis, renal fibrosis, cardiac fibrosis, fibrostenosis, cystic fibrosis, idiopathic pulmonary fibrosis, radiation-induced fibrosis, Peyronie's disease, and cutaneous sclerosis, or respiratory diseases, abnormal wound healing and recovery, scarring, hypertrophic scarring / keloids, postoperative scarring, cardiac arrest, and excessive or extrusion deposition of fibrous material are associated with all pathological conditions related to disease, injury, transplantation, or surgery. In further embodiments, fibrosis is selected from the group consisting of hepatic fibrosis, pulmonary fibrosis, renal fibrosis, cardiac fibrosis, scarring, and cutaneous sclerosis. Alternatively, fibrosis may be selected from the group consisting of myelofibrosis, systemic sclerosis, hepatic fibrosis, pulmonary fibrosis, renal fibrosis, cardiac fibrosis, and radiation-induced fibrosis. For example, renal fibrosis may include, without limitation, diabetic nephropathy, vesicoureteral reflux, tubulointerstitial renal fibrosis, focal segmental glomerulosclerosis, and glomerulonephritis including membranous glomerulonephritis, or glomerulonephritis, IgA nephropathy, and interstitial capillary glomerulonephritis. For example, hepatic fibrosis can lead to cirrhosis and is associated with related conditions such as chronic viral hepatitis, non-alcoholic fatty liver disease (NAFLD), alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH), primary biliary cirrhosis (PBC), biliary cirrhosis, and autoimmune hepatitis. Furthermore, the fibrosis can be selected from keloids, scars, ocular scars, hypertrophic scars, sclerosis cutaneously, Dupuytren's contracture, and Péronie's disease. For example, hypertrophic scars can result from burns. Specifically, hypertrophic scars can result from external injuries. In yet another embodiment, hypertrophic scars can result from surgical procedures.In one embodiment, keloids are caused by external injury. In yet another embodiment, keloids are caused by surgical procedures. In yet another embodiment, keloids are the result of skin injury caused by acne, burns, chickenpox, ear piercing, scratching, surgical cuts, or vaccination sites.

[0098] In other realizations, the autotaxin-mediated disease may be, but is not limited to, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, skin diseases, and diseases related to abnormal angiogenesis.

[0099] The pharmaceutical composition of the present invention may further contain a pharmaceutically acceptable carrier or additive.

[0100] The active ingredient of the present invention may be administered alone or in mixture with a convenient carrier, and the dosage form may be a single-dose or repeated-dose form. The pharmaceutical composition may be a solid or liquid preparation. Examples of solid preparations include, but are not limited to, powders, granules, tablets, capsules, and suppositories. Solid preparations may contain, but are not limited to, carriers, flavoring agents, binders, preservatives, disintegrants, lubricants, and fillers. Examples of liquid preparations include, but are not limited to, solutions such as water and propylene glycol solutions, suspensions, and emulsions, and may be manufactured by adding appropriate coloring agents, flavoring agents, stabilizers, thickeners, etc. For example, a powder can be manufactured by simply mixing the active ingredient of the present invention with a pharmaceutically acceptable carrier such as lactose, starch, or microcrystalline cellulose. The granules can be produced by mixing the active ingredient of the present invention, a pharmaceutically acceptable appropriate carrier, and a pharmaceutically acceptable appropriate binder such as polyvinylpyrrolidone or hydroxypropylcellulose, and then by a wet granulation method using a solvent such as water, ethanol, or isopropanol, or by a dry granulation method using compressive force. Tablets can be produced by mixing the granules with a pharmaceutically acceptable appropriate lubricant such as magnesium stearate, and then compressing them using a tablet press.

[0101] The pharmaceutical composition of the present invention may be administered as an oral preparation, an injection (e.g., intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection, implant), an inhalation preparation, an intranasal preparation, a vaginal preparation, a rectal preparation, a sublingual preparation, a transdermal preparation, a topical preparation, etc., depending on the disease to be treated and the condition of the subject, but is not limited to these. Depending on the route of administration, it can be formulated into an appropriate administration unit dosage form containing a commonly used, non-toxic, and pharmaceutically acceptable carrier, excipient, and vehicle.

[0102] The pharmaceutical composition of the present invention may be administered daily at a dose of approximately 0.0001 mg / kg to approximately 10 g / kg, or at a daily dose of approximately 0.001 mg / kg to approximately 1 g / kg. However, the dosage varies depending on the degree of purity of the mixture, the patient's condition (age, sex, weight, etc.), the severity of the condition being treated, etc. If necessary, for convenience, the total daily dose may be divided into multiple doses throughout the day.

[0103] In another aspect, the present invention provides a method for treating autotaxin-mediated diseases, such as cytoproliferative disorders and fibrosis, comprising administering a therapeutically effective amount of a compound having the chemical structure of chemical formula 1, or a pharmaceutically acceptable salt, isomer, solvate, hydrate, or prodrug thereof, to a subject.

[0104] In another aspect, the present invention provides a method for inhibiting autotaxin activity, comprising administering a therapeutically effective amount of a compound having the chemical structure of chemical formula 1, or a pharmaceutically acceptable salt, isomer, solvate, hydrate, or prodrug thereof, to a target. [Examples]

[0105] The present invention will be described in detail below with reference to manufacturing examples, embodiments, and experimental examples.

[0106] However, the following manufacturing examples, embodiments, and experimental examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following manufacturing examples, embodiments, and experimental examples.

[0107] [Manufacturing example] Manufacturing Example 1: Preparation of 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate The title compound was obtained through the following steps A, B, and C.

[0108] Step A: Preparation of 3-(((4-chloro-2-nitrophenyl)amino)methyl)benzoate methyl ester 3-(aminomethyl)methyl benzoate (17 g, 103 mmol), K2CO3 (28.4 g, 206 mmol), and 4-chloro-1-fluoro-2-nitrobenzene (18 g, 103 mmol) were mixed with 150 mL of DMF, and then the mixture was packed with nitrogen gas. After stirring at room temperature for 2 hours, the reaction was completed. EtOAC and water were added to separate the organic layer, which was then dried over anhydrous MgSO4. The filtrate was distilled under reduced pressure and purified by MPLC to obtain the title compound (20 g, 61% yield). 1 H NMR (500 MHz, CDCl3) δ 8.45 (brs, 1H), 8.23 ​​(s, 1H), 8.02 (m, 2H), 7.55 (m, 1H), 7.48 (m, 1H), 7.34 (m, 1H), 6.75 (d, 1H), 4.62 (d, 2H), 3.95 (s, 3H)

[0109] Step B: Preparation of 3-(((2-amino-4-chlorophenyl)amino)methyl)benzoate methyl ester To the methyl 3-(((4-chloro-2-nitrophenyl)amino)methyl)benzoate (0.35 g, 1.09 mmol) and iron (274 mg, 4.91 mmol) obtained in step A, 1 mL of EtOH and 3 mL of water were added. 0.6 mL of acetic acid was added to the reaction solution and the mixture was stirred at 100°C for 3 hours. Once the reaction was complete, the mixture was diluted with ELISA at room temperature, based with 5 M aqueous NaOH solution, and the solid was removed with Celite. The organic layer was then washed with water and separated. The filtrate was dried over anhydrous MgSO4 and distilled under reduced pressure to obtain the title compound (0.32 g, 99% yield). 1 H NMR (500 MHz, CDCl3) δ 8.09 (brs, 1H), 7.98 (d, 1H), 7.59 (d, 1H), 7.45 (t, 1H), 7.28 (m, 2H)6.75 (m, 2H), 6.53 (d, 1H), 4.37 (s, 2H), 3.95 (s, 3H)

[0110] Step C: Preparation of 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester To the 3-(((2-amino-4-chlorophenyl)amino)methyl)benzoate methyl ester (367 mg, 1.26 mmol) and CDI (408 mg, 2.52 mmol) obtained in step B, 15 mL of THF was added and the mixture was stirred at 70°C for 12 hours. After the reaction was completed, the filtrate was distilled under reduced pressure and purified by MPLC to obtain the title compound (240 mg, 60% yield). 1 H NMR (500 MHz, CDCl3) δ 8.31 (brs, 1H), 8.00 (m, 2H), 7.51 (d, 1H), 7.43 (t, 1H), 7.10 (s, 1H), 7.00 (d, 1H), 6.74 (d, 1H), .5.11 (s, 2H), 3.93 (s, 3H)

[0111] Manufacturing Example 2: Preparation of 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester The title compound was obtained through the following steps A, B, and C.

[0112] Step A: Preparation of 3-(((4-chloro-2-nitrophenyl)amino)methyl)-2-fluorobenzoate methyl ester Using methyl 3-(aminomethyl)-2-fluorobenzoate (2.2 g, 12.01 mmol) and 4-chloro-1-fluoro-2-nitrobenzene, the title compound (2.53 g, 68% yield) was obtained by the same method as in step A of Production Example 1. 1 H NMR (500 MHz, CDCl3) δ 8.45 (brs, 1H), 8.23 ​​(s, 1H), 8.02 (m, 2H), 7.55 (m, 1H), 7.48 (m, 1H), 7.34 (m, 1H), 6.75 (d, 1H), 4.62 (d, 2H), 3.95 (s, 3H)

[0113] Step B: Preparation of 3-(((2-amino-4-chlorophenyl)amino)methyl)-2-fluorobenzoate methyl ester Using the 3-(((4-chloro-2-nitrophenyl)amino)methyl)-2-fluorobenzoate methyl ester (2.5 g, 7.38 mmol) obtained in step A, the title compound (2.36 g, 99% yield) was obtained by the same method as in step B of production example 1. 1 H NMR (500 MHz, CDCl3) δ 7.87 (t, 1H), 7.70 (m, 1H), 7.53 (m, 2H), 7.18 (t, 1H), 6.73 (m, 1H), 6.51 (m, 1H), 4.43 (s, 2H), 3.97 (s, 3H).

[0114] Step C: Preparation of 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester Using the 3-(((2-amino-4-chlorophenyl)amino)methyl)-2-fluorobenzoate methyl ester (2.36 g, 6.97 mmol) obtained in step B, the title compound (0.66 g, 28% yield) was obtained by the same method as in step C of production example 1. 1 H NMR (500 MHz, CDCl3) δ 8.95 (brs, 1H), 7.90 (t, 1H), 7.51 (t, 1H), 7.18 (t, 1H), 7.12 (m, 1H), 7.05 (d, 1H), 6.90 (d, 1H), 5.17 (s, 2H), 3.97 (s, 2H)

[0115] Manufacturing Example 3: Preparation of 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate The title compound (97 mg, 9% yield) was obtained using 3-(1-aminocyclopropyl)methyl benzoate (575 mg, 12.01 mmol) and 4-chloro-1-fluoro-2-nitrobenzene by the same method as in steps A, B, and C of Preparation Example 1. 1H NMR (500 MHz, CDCl3) δ 10.67 (brs, 1H), 7.85 (m, 2H), 7.34 (m, 2H), 7.13 (s, 1H), 7.03 (s, 2H), 3.90 (s, 3H), 1.73 (s, 4H)

[0116] Manufacturing Example 4: Preparation of 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester The title compound was obtained through the following steps A and B.

[0117] Step A: Preparation of methyl 3-(1-aminocyclopropyl)-2-fluorobenzoate 5.4 g, 30 mmol of methyl 3-cyano-2-fluorobenzoate was mixed with 150 mL of Et2O and 9.82 mL, 33 mmol of Ti(O-Pr)4. After cooling to -78°C, ethylmagnesium bromide (3 M Et2O solution) was slowly added. After stirring at room temperature for 1 hour, BF3-OEt2 (6.37 mL, 60 mmol) was added, and the mixture was stirred at room temperature for another 1 hour. 90 mL of 1 N aqueous hydrochloric acid was added to the reaction mixture, and it was washed with Et2O. The aqueous layer was separated, based with 2.5 M aqueous NaOH, and extracted with Et2O. The organic layer was dried over anhydrous Na2SO4, the solid was filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (3.1 g, 49% yield). 1 H NMR (500 MHz, CDCl3) δ 7.81 (m, 1H), 6.51 (m, 1H), 7.14 (m, 1H), 3.96 (s, 3H), 2.00 (brs, 2H), 1.05 (m, 2H), 0.92 (m, 2H)

[0118] Step B: Preparation of 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester Using methyl 3-(1-aminocyclopropyl)-2-fluorobenzoate (2.2 g, 10.51 mmol) obtained in the previous Step A and 4-chloro-1-fluoro-2-nitrobenzene, the title compound (278 mg, 7% yield) was obtained in the same manner as Steps A, B, and C of Production Example 1. 1 H NMR (500 MHz, CDCl3) δ 8.39 (brs, 1H), 8.09 (t, 1H), 8.56 (t, 1H), 7.44 (d, 1H), 7.20 (t, 1H), 7.11 (d, 1H), 7.03 (s, 1H), 3.93 (s, 3H), 1.65 (m, 4H)

[0119] Production Example 5: Production of 6-chloro-1-phenyl-1,3-dihydro-2H-benzo[d]imidazol-2-one The title compound was obtained through the following Steps A, B, and C.

[0120] Step A: Production of 5-chloro-2-nitro-N-phenylaniline 4-Chloro-2-fluoro-1-nitrobenzene (877.70 mg, 5.00 mmol), aniline (1.37 mL, 15.00 mmol), and potassium carbonate (1.72 g, 12.50 mmol) were dissolved in dimethyl sulfoxide and stirred at 50 °C. After the reaction was completed, water was added, and the mixture was extracted with ethyl acetate to separate the organic layer, which was then dried over anhydrous Na2SO4. The solid was filtered, and the filtrate was distilled under reduced pressure and then purified by MPLC to obtain the title compound (1.23 g, 99% yield). 1 H NMR (400 MHz, CDCl3) δ 9.55 (s, 1H), 8.17 (m 1H), 7.45 (m, 2H), 7.28 (m, 3H), 7.14 (m, 1H), 6.72 (m, 1H)

[0121] Step B: 5-Chloro-N 1 - Preparation of phenylbenzene-1,2-diamine Using the 5-chloro-2-nitro-N-phenylaniline (500.00 mg, 2.01 mmol) obtained in step A, the title compound (436.00 mg, 99% yield) was obtained by the same method as in step B of production example 1. 1 H NMR (500 MHz, CDCl3) δ 7.25 (m, 2H), 7.12 (s, 1H), 6.94 (d, 2H), 6.90 (t, 1H), 6.80 (d, 2H), 6.72 (d, 1H), 5.17 (s, 1H), 3.71 (s, 2H)

[0122] Step C: Preparation of 6-chloro-1-phenyl-1,3-dihydro-2H-benzo[d]imidazole-2-one 5-chloro-N obtained in step B above 1 Using phenylbenzene-1,2-diamine (437.36 mg, 2.00 mmol), the title compound (445.90 mg, 91% yield) was obtained by the same method as in step C of Production Example 1. 1 H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 7.59 (t, 2H), 7.53 (d, 2H), 7.47 (t, 1H), 7.09 (d, 1H), 7.05 (d, 2H)

[0123] Manufacturing Example 6: Preparation of methyl 3-(aminomethyl)-5-fluorobenzoate 3-(bromomethyl)-5-fluorobenzoate methyl ester (1.08 g, 4.37 mmol) was mixed with 15 mL of DMF and sodium azide (0.34 g, 5.25 mmol) and stirred at 70°C for 1 hour. After the reaction was complete, water and Et2O were added to separate the organic layer. The organic layer was concentrated under reduced pressure, and 15 mL of MeOH and 15 mL of DCM were added, followed by the addition of 10 wt% Pd / C (0.40 g) and stirring under hydrogen pressure. After the reaction was complete, the solid was filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (0.61 g, 76% yield). 1H-NMR (400 MHz, DMSO-d6) δ7.80 (d, 1H), 7.50 (2H), 3.87 (s, 3H), 3.86 (s, 1H), 3.76 (s, 1H)

[0124] Manufacturing Example 7: Production of 6-chloro-1-(6-propoxypyridine-3-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained by following the steps A, B, C, D, and E below.

[0125] Step A: Production of 5-nitro-2-propoxypyridine 18 mL of MTBE was added to 1-propanol (0.934 mL, 12.4 mmol), then cooled to 0°C, and KOtBu (1.39 g, 12.4 mmol) and 2-fluoro-5-nitropyridine (1.61 g, 11.3 mmol) were added. After the reaction was completed, water was added to separate the organic layer, which was then dried over anhydrous Na2SO4. The solid was filtered, and the filtrate was purified by vacuum distillation and MPLC to obtain the title compound (1.57 g, 76% yield). 1 H NMR (400 MHz, CDCl3) δ 9.07 (d, 1H), 8.34 (dd, 1H), 6.81 (d, 1H), 4.38 (t, 2H), 1.82 (m, 2H), 1.04 (t, 3H)

[0126] Step B: Preparation of 6-propoxypyridine-3-amine To the 5-nitro-2-propoxypyridine (1.57 g, 8.62 mmol) obtained in step A, 15 mL each of THF, EtOH, and water were added, followed by the addition of iron (3.37 g, 60 mmol) and ammonium chloride (3.23 g, 60 mmol), and the mixture was stirred under reflux for 2 hours. After the reaction was completed, the mixture was diluted with water and siRNA, and the solid was removed by celite. After separating the organic layer, it was dried over anhydrous Na2SO4 to obtain the title compound (1.28 g, 98% yield). 1H NMR (400 MHz, CDCl3) δ 7.65 (d, 1H), 7.03 (dd, 1H), 6.60 (d, 1H), 4.14 (t, 2H), 3.35 (brs, 2H), 1.76 (m, 2H), 1.00 (t, 3H)

[0127] Step C: Preparation of N-(5-chloro-2-nitrophenyl)-6-propoxypyridine-3-amine To the 6-propoxypyridine-3-amine (1.28 g, 8.41 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (1.62 g, 9.25 mmol) obtained in step B, 28 mL of AN and K2CO3 (2.30 g, 19.3 mmol) were added, and the mixture was stirred at 80°C for 3 days. After filtering the solid, the filtrate was purified by MPLC to obtain the title compound (1.05 g, 40% yield). 1 H NMR (400 MHz, CDCl3) δ 9.33 (brs, 1H), 8.16 (d, 1H), 8.10 (d, 1H), 7.50 (dd, 1H), 6.84 (2H), 6.72 (dd, 1H), 4.29 (t, 2H), 1.82 (m, 2H), 1.05 (t, 3H)

[0128] Step D: Preparation of 6-chloro-1-(6-propoxypyridine-3-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-6-propoxypyridine-3-amine (1.05 g, 3.41 mmol) obtained in step C, the title compound (0.70 g, 68% yield) was obtained by the same method as in step B of production example 7 and step C of production example 3. 1 H NMR (400 MHz, CDCl3) δ 8.92 (brs, 1H), 8.30 (d, 1H), 7.70 (dd, 1H), 7.09 (d, 1H), 7.03 (d, 1H), 6.93 (d, 1H), 6.90 (d, 1H), 4.32 (t, 2H), 1.83 (m, 2H), 1.06 (t, 3H)

[0129] Manufacturing Example 8: Production of 6-chloro-1-(4-(dimethylamino)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A and B.

[0130] Step A:N 1 -(3-chloro-2-fluoro-6-nitrophenyl)-N 4 、N 4 Production of dimethylbenzene-1,4-diamine N 1 , N 1 Dimethylbenzene-1,4-diamine (2.60 g, 19.1 mmol) was mixed with 19 mL of DMF, 1-chloro-2,3-difluoro-4-nitrobenzene (3.70 g, 19.1 mmol), and K2CO3 (5.28 g, 38.2 mmol), and the mixture was stirred at 70°C for 2 hours. After the reaction was complete, cold water was added, and the resulting solid was dried to obtain the title compound (5.92 g, 99% yield). 1 H NMR (400 MHz, DMSO-d6) δ 8.86 (brs, 1H), 7.90 (dd, 1H), 7.10 (dd, 1H), 6.94 (d, 2H), 6.66 (d, 2H), 2.86 (s, 6H)

[0131] Step B: Preparation of 6-chloro-1-(4-(dimethylamino)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one N obtained in step A 1 -(3-chloro-2-fluoro-6-nitrophenyl)-N 4 , N 4 Using -dimethylbenzene-1,4-diamine (2.60 g, 8.39 mmol), 5-chloro-N is produced in the same manner as in step B of Production Example 7. 1-(4-(dimethylamino)phenyl)-6-fluorobenzene-1,2-diamine was obtained. 200 mL of DCM was added to this, and the mixture was cooled to 0°C. DIPEA (8.34 mL, 47.8 mmol) and triphosgene (5.67 g, 19.1 mmol) were added in sequence. After 30 minutes, water was added and the organic layer was separated. The organic layer was dried over anhydrous Na2SO4 and purified by MPLC to obtain the title compound (3.25 g, 56% yield). 1 H NMR (400 MHz, DMSO-d6) δ 11.42 (brs, 1H), 7.26 (d, 2H), 7.16 (dd, 1H), 6.89 (dd, 1H), 6.82 (m, 2H), 2.97 (s, 6H)

[0132] Manufacturing Example 9: Production of 6-chloro-1-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, and C.

[0133] Step A: Preparation of 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-amine 4-Nitro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole (1.44 g, 7.30 mmol) was mixed with 50 mL of EtOH, and then the mixture was packed with nitrogen gas. 10 wt% Pd-C (0.777 g, 0.730 mmol) was added, and the mixture was stirred under hydrogen pressure. After the reaction was complete, the solid was filtered, and the filtrate was purified by MPLC to obtain the title compound (1.17 g, 96% yield). 1 H NMR (400 MHz, CDCl3) δ 7.17 (s, 1H), 7.06 (s, 1H), 4.22 (m, 1H), 4.08 (m, 2H), 3.51 (m, 2H), 2.90 (brs, 2H), 2.01 (4H)

[0134] Step B: Preparation of N-(5-chloro-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-amine Using 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-amine (1.17 g, 7.00 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (1.35 g, 7.70 mmol) obtained in step A, the title compound (0.65 g, 26% yield) was obtained by the same method as in step C of Production Example 7. 1 H NMR (500 MHz, CDCl3) δ 9.09 (brs, 1H), 8.13 (d, 1H), 7.53 (s, 1H), 7.49 (s, 1H), 6.97 (d, 1H), 6.70 (dd, 1H), 4.40 (m, 1H), 4.14 (m, 2H), 3.57 (m, 2H), 2.10 (m, 4H)

[0135] Step C: Preparation of 6-chloro-1-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-amine (0.65 g, 2.01 mmol) obtained in step B, the title compound (0.29 g, 45% yield) was obtained by the same method as in step B of production example 7 and step B of production example 8. 1 H NMR (400 MHz, CDCl3) δ 9.00 (brs, 1H), 7.83 (s, 1H), 7.78 (s, 1H), 7.08 (2H), 7.01 (d, 1H), 4.40 (m, 1H), 4.14 (m, 2H), 3.58 (m, 2H), 2.18 (m, 4H)

[0136] Manufacturing Example 10: Production of N-(5-chloro-2-nitrophenyl)-1H-pyrazole-4-amine The title compound was obtained through the following steps A, B, and C.

[0137] Step A: Preparation of 4-nitro-1H-pyrazole-1-carboxylate tert-butyl ester 4-nitro-1H-pyrazole (15.0 g, 133 mmol) was dissolved in 200 mL of DCM, and then dimethylaminopyridine (1.62 g, 13.2 mmol) and BOC2O (30.4 g, 139 mmol) were added. After stirring at room temperature for 1 hour, 0.5 N hydrochloric acid aqueous solution was added. The organic layer was separated, dried over Na2SO4, and the solid was removed to obtain the title compound (28.3 g, 100% yield). 1 H NMR (400 MHz, CDCl3) δ 8.79 (s, 1H), 8.22 (s, 1H), 1.69 (s, 9H)

[0138] Step B: Preparation of 4-amino-1H-pyrazole-1-carboxylate tert-butyl ester Using the 4-nitro-1H-pyrazole-1-carboxylate tert-butyl ester (10.8 g, 50.7 mmol) obtained in step A, the title compound (8.73 g, 94% yield) was obtained by the same method as in step A of production example 9. 1 H NMR (400 MHz, CDCl3) δ 7.55 (s, 1H), 7.41 (s, 1H), 3.12 (brs, 2H), 1.63 (s, 9H)

[0139] Step C: Preparation of N-(5-chloro-2-nitrophenyl)-1H-pyrazole-4-amine Using the 4-amino-1H-pyrazole-1-carboxylate tert-butyl ester (4.00 g, 21.8 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (3.83 g, 21.8 mmol) obtained in step B, the title compound (1.00 g, 19% yield) was obtained by the same method as in step A of production example 8. 1 H NMR (400 MHz, CDCl3) δ 9.14 (brs, 1H), 8.17 (d, 1H), 8.15 (s, 1H), 7.76 (s, 1H), 6.99 (d, 1H), 6.76 (dd, 1H), 1.67 (s, 9H)

[0140] Manufacturing Example 11: Preparation of 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, C, and D.

[0141] Step A: Production of 4-(4-nitrophenyl)morpholine 17 mL of morpholine was added to 1-fluoro-4-nitrobenzene (5.0 g, 35.4 mmol), and the mixture was stirred at 80°C for 4 hours. The reaction mixture was poured into 400 mL of cold water, and the resulting solid was filtered to obtain the title compound (7.38 g, 99% yield). 1 H NMR (400 MHz, DMSO-d6) δ 8.08 (d, 2H), 7.04 (d, 2H), 3.83 (m, 4H), 3.41 (m, 4H)

[0142] Step B: Production of 4-morpholinoaniline Using the 4-(4-nitrophenyl)morpholine (7.38 g, 35.40 mmol) obtained in step A, the title compound (6.22 g, 98% yield) was obtained by the same method as in step B of production example 7. 1 H NMR (500 MHz, DMSO-d6) δ 6.68 (d, 2H), 6.59 (d, 2H), 4.57 (brs, 2H), 3.67 (m, 4H), 2.86 (m, 4H)

[0143] Step C: Preparation of 3-chloro-2-fluoro-N-(4-morpholinophenyl)-6-nitroaniline Using 4-morpholinoaniline (1.38 g, 7.75 mmol) and 1-chloro-2,3-difluoro-4-nitrobenzene (1.50 g, 7.75 mmol) obtained in step B, the title compound (2.57 g, 94% yield) was obtained by the same method as in step A of production example 8. 1H NMR (400 MHz, DMSO-d6) δ 8.33 (brs, 1H), 7.90 (dd, 1H), 7.18 (dd, 1H), 6.95 (d, 2H), 6.87 (d, 2H), 3.73 (m, 4H), 3.03 (m, 4H)

[0144] Step D: Preparation of 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using 3-chloro-2-fluoro-N-(4-morpholinophenyl)-6-nitroaniline (2.57 g, 7.31 mmol) obtained in step C, the title compound (1.18 g, 46% yield) was obtained by the same method as in step B of production example 8. 1 H NMR (400 MHz, DMSO-d6) δ 11.45 (s, 1H), 7.33 (d, 2H), 7.18 (dd, 1H), 7.04 (d, 2H), 6.90 (dd, 1H), 3.77 (m, 4H), 3.18 (m, 4H)

[0145] Manufacturing Example 12: Production of 6-chloro-1-(1-propyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, and C.

[0146] Step A: Preparation of 1-propyl-1H-pyrazole-4-amine 4-bromo-1-propyl-1H-pyrazole (1.00 g, 5.29 mmol), K2CO3 (1.09 g, 7.93 mmol), and acetamide (0.63 g, 10.6 mmol) were mixed with 5.3 mL of n-butanol, and the mixture was then filled with nitrogen gas. DMEDA (0.074 mL, 0.69 mmol) and CuI (0.131 g, 0.688 mmol) were added, and the mixture was stirred at 100°C for 16 hours. After the reaction was complete, the solid was removed using Celite. The filtrate was concentrated, and 13 mL of EtOH and aqueous hydrochloric acid (0.87 mL, 10.6 mmol) were added, and the mixture was stirred at 70°C for 3 days. After the reaction was complete, the mixture was concentrated under reduced pressure, the filtrate was neutralized with 1N aqueous NaOH, and extracted with siRNA. After separating the organic layer, it was dried over anhydrous Na2SO4 to obtain the title compound (0.39 g, 59% yield). 1 H NMR (400 MHz, DMSO-d6) δ 7.01 (s, 1H), 6.88 (s, 1H), 4.00 (brs, 2H), 3.85 (t, 2H), 1.67 (m, 2H), 0.81 (t, 3H)

[0147] Step B: Preparation of N-(5-chloro-2-nitrophenyl)-1-propyl-1H-pyrazole-4-amine Using the 1-propyl-1H-pyrazole-4-amine (0.39 g, 3.12 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (0.57 g, 3.27 mmol) obtained in step A, the title compound (0.41 g, 46% yield) was obtained by the same method as in step C of Production Example 7. 1 H NMR (500 MHz, CDCl3) δ 9.08 (brs, 1H), 8.13 (d, 1H), 7.50 (s, 1H), 7.44 (s, 1H), 6.97 (d, 1H), 6.69 (dd, 1H), 4.00 (t, 2H), 1.83 (m, 2H), 0.88 (t, 3H)

[0148] Step C: Preparation of 6-chloro-1-(1-propyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-1-propyl-1H-pyrazole-4-amine (0.41 g, 1.5 mmol) obtained in step B, the title compound (0.077 g, 18% yield) was obtained by the same method as in step B of production example 7 and the same method as in step C of production example 3. 1 H NMR (400 MHz, CDCl3) δ 8.90 (brs, 1H), 7.78 (s, 1H), 7.76 (s, 1H), 7.08 (2H), 7.02 (d, 1H), 4.16 (t, 2H), 1.98 (m, 2H), 1.00 (t, 3H)

[0149] Manufacturing Example 13: Preparation of 6-chloro-7-fluoro-1-(1-propyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A and B.

[0150] Step A: Preparation of N-(3-chloro-2-fluoro-6-nitrophenyl)-1-propyl-1H-pyrazole-4-amine Using 1-propyl-1H-pyrazole-4-amine (0.32 g, 2.58 mmol) and 1-chloro-2,3-difluoro-4-nitrobenzene (0.50 g, 2.58 mmol) obtained in step A of the above-mentioned Production Example 12, the title compound (0.25 g, 33% yield) was obtained by the same method as in step A of the above-mentioned Production Example 8. 1 H NMR (400 MHz, CDCl3) δ 8.92 (brs, 1H), 7.97 (dd, 1H), 7.42 (s, 1H), 7.34 (s, 1H), 6.82 (dd, 1H), 4.06 (q, 2H), 1.88 (m, 2H), 0.93 (t, 3H)

[0151] Step B: Preparation of 6-chloro-7-fluoro-1-(1-propyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(3-chloro-2-fluoro-6-nitrophenyl)-1-propyl-1H-pyrazole-4-amine (0.25 g, 0.84 mmol) obtained in step A, the title compound (0.14 g, 58% yield) was obtained by the same method as in step B of production example 7 and the same method as in step C of production example 3. 1 H NMR (400 MHz, CDCl3) δ 9.23 (brs, 1H), 7.71 (2H), 7.11 (m, 1H), 6.85 (d, 1H), 4.14 (t, 2H), 1.95 (m, 2H), 0.98 (t, 3H)

[0152] Manufacturing Example 14: Preparation of 1-(4-(6-chloro-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)azetidine-3-yl acetate The title compound was obtained by following the steps A, B, C, D, and E below.

[0153] Step A: Production of 1-(4-nitrophenyl)azetidine-3-ol Azethidine-3-ol hydrochloride (1.97 g, 17.9 mmol) and (4-nitrophenyl)boronic acid (3.0 g, 17.9 mmol) were mixed with 180 mL of DCM, 10 mL of TEA, and Cu(OAc)2 (3.26 g, 17.9 mmol), and the mixture was stirred at room temperature for 2 days. After concentrating the reaction mixture under reduced pressure, it was purified by MPLC to obtain the title compound (0.58 g, 16% yield). 1 H NMR (400 MHz, CDCl3) δ 8.11 (d, 2H), 6.33 (d, 2H), 4.87 (m, 1H), 4.31 (m, 2H), 3.90 (m, 2H), 2.16 (d, 1H)

[0154] Step B: Production of 1-(4-aminophenyl)azetidine-3-ol Using the 1-(4-nitrophenyl)azetidine-3-ol (0.58 g, 2.99 mmol) obtained in step A, the title compound (0.49 g, 99% yield) was obtained by the same method as in step B of production example 7. 1 H NMR (400 MHz, CDCl3) δ 6.64 (d, 2H), 6.38 (d, 2H), 4.70 (m, 1H), 4.11 (t, 2H), 3.67 (m, 2H), 3.38 (brs, 2H)

[0155] Step C: Production of 1-(4-((3-chloro-2-fluoro-6-nitrophenyl)amino)phenyl)azetidine-3-ol Using 1-(4-aminophenyl)azetidine-3-ol (0.493 g, 3 mmol) and 1-chloro-2,3-difluoro-4-nitrobenzene (0.581 g, 3.00 mmol) obtained in step B, the title compound (0.77 g, 76% yield) was obtained by the same method as in step A of production example 8. 1 H NMR (400 MHz, CDCl3) δ 9.10 (brs, 1H), 7.96 (dd, 1H), 6.98 (m, 2H), 6.81 (dd, 1H), 7.44 (d, 2H), 4.77 (m, 1H), 4.19 (m, 2H), 3.68 (m, 2H), 2.04 (d, 1H)

[0156] Step D: Preparation of 1-(4-((3-chloro-2-fluoro-6-nitrophenyl)amino)phenyl)azetidine-3-yl acetate To the 1-(4-((3-chloro-2-fluoro-6-nitrophenyl)amino)phenyl)azetidine-3-ol (0.77 g, 2.28 mmol) obtained in step C, 9 mL of DMSO and KOtBu (0.256 g, 2.28 mmol) were added and the mixture was stirred at room temperature for 30 minutes. 4.5 mL of siRNA was added and the mixture was stirred at room temperature for 16 hours. After adding water and siRNA to the reaction mixture, the organic layer was separated and dried over anhydrous Na2SO4. This was purified by MPLC to obtain the title compound (0.367 g, 42% yield). 1 H-NMR (400 MHz, CDCl3) δ9.08 (brs, 1H), 7.96 (dd, 1H), 7.00 (d, 2H), 6.82 (dd, 1H), 6.45 (d, 2H), 5.31 (m, 1H), 4.25 (m, 2H), 3.83 (m, 2H), 2.11 (s, 3H)

[0157] Step E: Preparation of 1-(4-(6-chloro-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)azetidine-3-yl acetate Using the 1-(4-((3-chloro-2-fluoro-6-nitrophenyl)amino)phenyl)azetidine-3-yl acetate (0.38 g, 1.00 mmol) obtained in step D, the title compound (0.21 g, 56% yield) was obtained by the same method as in step B of production example 8. 1 H-NMR (400 MHz, CDCl3) δ9.14 (brs, 1H), 7.30 (m, 2H), 7.08 (dd, 1H), 6.81 (dd, 1H), 6.55 (d, 2H), 5.34 (m, 1H), 4.30 (m, 2H), 3.88 (m, 2H), 2.12 (s, 3H)

[0158] Manufacturing Example 15: Preparation of 3-((5-chloro-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate The title compound was obtained through the following steps A and B.

[0159] Step A: Preparation of 3-(((4-chloro-2-fluoro-6-nitrophenyl)amino)methyl)benzoate methyl ester Using 5-chloro-1,2-difluoro-3-nitrobenzene (0.726 g, 3.75 mmol) and methyl 3-(aminomethyl)benzoate (0.62 g, 3.75 mmol), the title compound (0.88 g, 69% yield) was obtained by the same method as in step A of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ8.11 (brs, 1H), 8.00 (3H), 7.51 (dd, 1H), 7.46 (t, 1H), 7.20 (dd, 1H), 4.77 (m, 2H), 3.96 (s, 3H)

[0160] Step B: Preparation of 3-((5-chloro-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using the 3-(((4-chloro-2-fluoro-6-nitrophenyl)amino)methyl)methyl benzoate ester (0.42 g, 1.24 mmol) obtained in step A, the title compound (0.075 g, 18% yield) was obtained by the same method as in step B of production example 8. 1 H-NMR (500 MHz, MeOH-d4) δ7.93 (2H), 7.54 (m, 1H), 7.44 (m, 1H), 6.94 (m, 1H), 6.90 (m, 1H), 5.18 (s, 2H), 3.88 (s, 3H)

[0161] Manufacturing Example 16: Production of 1-(4-((5-chloro-2-nitrophenyl)amino)phenyl)piperidine-2-one The title compound was obtained through the following steps A and B.

[0162] Step A: Preparation of 1-(4-aminophenyl)piperidine-2-one 4-bromoaniline (0.97 g, 5.6 mmol), piperidine-2-one (0.40 g, 4.0 mmol), CuI (38 mg, 0.20 mmol), K2CO3 (1.1 g, 8.1 mmol), and DMEDA (36 mg, 0.40 mmol) were mixed with 4 mL of toluene, and then the mixture was packed with nitrogen gas. The reaction mixture was stirred at 110 °C for 16 hours, and the solid was removed by Celite. The filtrate was purified by MPLC to obtain the title compound (0.21 g, 27% yield). 1 H-NMR (400 MHz, CDCl3) δ7.00 (d, 2H), 6.68 (d, 2H), 3.66 (brs, 2H), 3.57 (m, 2H), 2.53 (m, 2H), 1.92 (m, 4H)

[0163] Step B: Preparation of 1-(4-((5-chloro-2-nitrophenyl)amino)phenyl)piperidine-2-one Using 1-(4-aminophenyl)piperidine-2-one (0.21 g, 1.1 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (0.19 g, 1.1 mmol) obtained in step A, the title compound (0.12 g, 32% yield) was obtained by the same method as in step A of production example 8. 1 H-NMR (400 MHz, CDCl3) δ9.52 (brs, 1H), 8.16 (d, 1H), 7.35 (d, 2H), 7.30 (d, 2H), 7.22 (m, 1H), 6.72 (dd, 1H), 3.69 (m, 2H), 2.59 (m, 2H), 1.98 (m, 4H)

[0164] Manufacturing Example 17: Production of 6-cyclopropyl-1-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, and C.

[0165] Step A: Preparation of 4-cyclopropyl-2-fluoro-1-nitrobenzene 4-bromo-2-fluoro-1-nitrobenzene (1.00 g, 4.55 mmol) and cyclopropylboronic acid (0.586 g, 6.82 mmol) were mixed with 12 mL of in 1,4-dioxane and 3 mL of water, and then the mixture was packed with nitrogen gas. Na2CO3 (1.44 g, 13.6 mmol) and PdCl2(dppf)-CH2Cl2 (0.371 g, 0.455 mmol) were added to the mixture, and the mixture was stirred at 80°C for 16 hours. After the reaction was completed, the solid was filtered through Celite, and the filtrate was purified by MPLC to obtain the title compound (0.52 g, 2.87 mmol, 63% yield). 1 H-NMR (400 MHz, CDCl3) δ7.97 (t, 1H), 6.94 (dd, 1H), 6.90 (dd, 1H), 1.96 (m, 1H), 1.18 (m, 2H), 0.83 (m, 2H)

[0166] Step B: Preparation of N-(5-cyclopropyl-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-amine Using 4-cyclopropyl-2-fluoro-1-nitrobenzene (0.26 g, 1.43 mmol) obtained in step A above and 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-amine (0.24 g, 1.43 mmol) obtained in step A of production example 9, the title compound (0.147 g, 31% yield) was obtained by the same method as in step A of production example 8 above. 1 H-NMR (400 MHz, DMSO-d6) δ9.21 (m, 1H), 8.00 (2H), 7.57 (m, 1H), 6.78 (m, 1H), 6.40 (dd, 1H), 4.41 (m, 1H), 3.97 (m, 2H), 3.50 (m, 2H), 1.90 (5H), 1.00 (m, 2H), 0.71 (m, 2H)

[0167] Step C: Preparation of 6-cyclopropyl-1-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-cyclopropyl-2-nitrophenyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-amine (0.14 g, 0.43 mmol) obtained in step B, the title compound (0.078 g, 56% yield) was obtained by the same method as in step B of production example 7 and step C of production example 3. 1 H-NMR (400 MHz, CDCl3) δ7.20 (brs, 1H), 7.86 (s, 1H), 7.80 (s, 1H), 7.00 (d, 1H), 6 / 86 (dd, 1H), 6.82 (d, 1H), 4.40 (m, 1H), 4.14 (m, 2H), 3.59 (m, 2H), 2.18 (m, 4H), 1.93 (m, 1H), 0.95 (m, 2H), 0.64 (m, 2H)

[0168] Manufacturing Example 18: Production of 6-chloro-1-(1-isopropyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A and B.

[0169] Step A: Preparation of N-(5-chloro-2-nitrophenyl)-1-isopropyl-1H-pyrazole-4-amine N-(5-chloro-2-nitrophenyl)-1H-pyrazole-4-amine (250.0 mg, 1.05 mmol) obtained in the above-mentioned Production Example 10 was dissolved in DMF, and 2-iodopropane (214.0 mg, 1.26 mmol) and K2CO3 (290.0 mg, 2.10 mmol) were added, and the mixture was stirred at 70°C. After the reaction was completed, the solid was filtered, and the filtrate was distilled under reduced pressure and purified by MPLC to obtain the title compound (195.0 mg, 67% yield). 1 H NMR (500 MHz, CDCl3) δ 7.47 (s, 1H), 7.43 (s, 1H), 6.48 (d, 1H), 6.39 (d, 1H), 6.17 (s, 1H), 4.49 (m, 1H), 3.85 (br s, 1H), 1.54 (d, 6H)

[0170] Step B: Preparation of 6-chloro-1-(1-isopropyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-1-isopropyl-1H-pyrazole-4-amine (195.0 mg, 0.695 mmol) obtained in step A, the title compound (15.6 mg, 8% yield) was obtained by the same method as in step B of production example 7 and step C of production example 1. 1 H NMR (500 MHz, CDCl3) δ10.52 (m, 1H) 7.80 (s, 1H), 7.77 (s, 1H), 7.08 (m, 3H), 4.60 (m, 1H), 1.60 (d, 6H)

[0171] Manufacturing Example 19: Production of 6-chloro-1-(1-(cyclopropylmethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, and C.

[0172] Step A: Preparation of N-(5-chloro-2-nitrophenyl)-1-(cyclopropylmethyl)-1H-pyrazole-4-amine N-(5-chloro-2-nitrophenyl)-1H-pyrazole-4-amine (250.0 mg, 1.05 mmol) obtained in the above-mentioned Production Example 10 was dissolved in DMF, (bromomethyl)cyclopropane (170.0 mg, 1.26 mmol) and K2CO3 (290.0 mg, 2.10 mmol) were added, and the mixture was stirred at 70°C. After the reaction was completed, the solid was filtered, and the filtrate was distilled under reduced pressure and purified by MPLC to obtain the title compound (205.0 mg, 67% yield).

[0173] Step B: Preparation of 6-chloro-1-(1-(cyclopropylmethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-1-(cyclopropylmethyl)-1H-pyrazole-4-amine (205.0 mg, 0.70 mmol) obtained in step A, the title compound (55.3 mg, 13% yield) was obtained by the same method as in step B of production example 7 and step C of production example 1. 1 H NMR (500 MHz, CDCl3) δ9.02 (m, 1H), 7.90 (s, 1H), 7.77 (s, 1H), 7.09 (d, 2H), 7.03 (m, 1H), 4.07 (d, 2H), 1.36 (m, 1H), 0.72 (m, 2H), 0.45 (m, 2H)

[0174] Manufacturing Example 20: Production of 6-chloro-1-(1-(cyclobutylmethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A and B.

[0175] Step A: Preparation of N-(5-chloro-2-nitrophenyl)-1-(cyclobutylmethyl)-1H-pyrazole-4-amine N-(5-chloro-2-nitrophenyl)-1H-pyrazole-4-amine (250.0 mg, 1.05 mmol) obtained in the above-mentioned Production Example 10 was dissolved in DMF, (bromomethyl)cyclobutane (187.0 mg, 1.26 mmol) and K2CO3 (290.0 mg, 2.10 mmol) were added, and the mixture was stirred at 70°C. After the reaction was completed, the solid was filtered, and the filtrate was distilled under reduced pressure and purified by MPLC to obtain the title compound (232.0 mg, 72% yield). 1 H NMR (500 MHz, CDCl3) δ 7.46 (s, 1H), 7.38 (s, 1H), 6.50 (d, 1H), 6.42 (d, 1H), 6.17 (s, 1H), 4.14 (d, 2H), 2.86 (m, 1H), 1.96-1.78 (m, 6H)

[0176] Step B: Preparation of 6-chloro-1-(1-(cyclobutylmethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-1-(cyclobutylmethyl)-1H-pyrazole-4-amine (232 mg, 0.76 mmol) obtained in step A, the title compound (10.0 mg, 5% yield) was obtained by the same method as in step B of production example 7 and step C of production example 1. 1 H NMR (500 MHz, CDCl3) δ10.49 (br s, 1H), 7.75 (s, 2H), 7.08 (m, 3H), 4.22 (d, 2H), 2.93 (m, 1H), 2.17 (m, 2H), 2.00 (m, 4H)

[0177] Manufacturing Example 21: Production of 4-((5-chloro-2-nitrophenyl)amino)benzoic acid The title compound was obtained through the following steps A and B.

[0178] Step A: Preparation of 4-((5-chloro-2-nitrophenyl)amino) tert-butyl ester benzoate 4-Tert-butyl aminobenzoate (1.2 g, 6.27 mmol) was dissolved in DMF and cooled to 0°C. NaH (273.0 mg, 6.84 mmol) was slowly added, and the mixture was stirred for 30 minutes. Then, 4-chloro-2-fluoro-1-nitrobenzene (1.0 g, 5.70 mmol) was added at 0°C, and the mixture was stirred while increasing the temperature to room temperature. After the reaction was complete, water was slowly added while stirring at 0°C, and the organic layer was extracted with siRNA and saturated aqueous solution of NH4Cl, and dried over Na2SO4. The solid was filtered, and the filtrate was purified by vacuum distillation and MPLC to obtain the title compound (670.0 mg, 34% yield). 1 H NMR (500 MHz, CDCl3) δ 9.57 (s, 1H), 8.18 (m, 1H), 8.06 (d, 2H), 7.31 (m, 3H), 6.82 (d, 1H), 1.61 (s, 9H)

[0179] Step B: Production of 4-((5-chloro-2-nitrophenyl)amino)benzoic acid The 4-((5-chloro-2-nitrophenyl)amino)benzoate tert-butyl ester (670.0 mg, 1.92 mmol) obtained in step A was dissolved in 20 mL of DCM, and 8 mL of TFA was slowly added, followed by stirring. After the reaction was completed, the solvent and reactants were removed by vacuum distillation to obtain the title compound (559.0 mg, 99% yield).

[0180] Manufacturing Example 22: Production of 6-chloro-1-(4-(piperidine-1-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, and C.

[0181] Step A: Production of (4-((5-chloro-2-nitrophenyl)amino)phenyl)(piperidine-1-yl)methanone 4-((5-chloro-2-nitrophenyl)amino)benzoic acid (146.3 mg, 0.50 mmol) and piperidine (54 μL, 0.55 mmol) obtained in the above-mentioned Production Example 21 were dissolved in DMF and cooled to 0°C. HATU (228.0 mg, 0.60 mmol) and DIPEA (262.0 μL, 1.50 mmol) were added, and the mixture was stirred while increasing the temperature to room temperature. After the reaction was completed, ice was added and the mixture was stirred. The resulting solid was filtered and washed with cold water. The obtained solid was vacuum-dried to obtain the title compound (170.6 mg, 94% yield). 1 H NMR (500 MHz, CDCl3) δ 9.55 (s, 1H), 8.18 (t, 1H), 7.49 (s, 2H), 7.31 (m, 3H), 6.78 (m, 1H), 3.72-3.42 (m, 4H), 1.72-1.55 (m, 6H)

[0182] Step B: Production of (4-((2-amino-5-chlorophenyl)amino)phenyl)(piperidine-1-yl)methanone Using the (4-((5-chloro-2-nitrophenyl)amino)phenyl)(piperidine-1-yl)methanone (170.6 mg, 0.47 mmol) obtained in step A, the title compound (154.1 mg, 99% yield) was obtained by the same method as in step B of production example 7.

[0183] Step C: Preparation of 6-chloro-1-(4-(piperidine-1-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The (4-((2-amino-5-chlorophenyl)amino)phenyl)(piperidine-1-yl)methanone (154.1 mg, 0.46 mmol) obtained in step B above was dissolved in THF, then CDI (162.0 mg, 1.00 mmol) was added and the mixture was stirred at 70°C. After the reaction was completed, the mixture was cooled to room temperature, water and SiO were added to separate the organic layer, and it was dried over Na2SO4. The solid was filtered, and the filtrate was distilled under reduced pressure to obtain a mixture of the title compounds.

[0184] Manufacturing Example 23: Production of 6-chloro-1-(4-(morpholine-4-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A and B.

[0185] Step A: Production of (4-((5-chloro-2-nitrophenyl)amino)phenyl)(morpholino)methanone Using 4-((5-chloro-2-nitrophenyl)amino)benzoic acid (146.3 mg, 0.50 mmol) and morpholine (47.9 mg, 0.55 mmol) obtained in Production Example 21, the title compound (169.4 mg, 93% yield) was obtained by the same method as in step A of Production Example 22. 1 H NMR (500 MHz, CDCl3) δ 9.54 (s, 1H), 8.18 (d, 1H), 7.52 (d, 2H), 7.33 (m, 3H), 6.80 (d, 1H), 3.80-3.50 (m, 8H)

[0186] Step B: Preparation of 6-chloro-1-(4-(morpholine-4-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the (4-((5-chloro-2-nitrophenyl)amino)phenyl)(morpholino)methanone (169.4 mg, 0.47 mmol) obtained in step A, a mixture of the title compound was obtained by the same method as in steps B and C of production example 22.

[0187] Manufacturing Example 24: Production of 6-chloro-1-(4-(pyrrolidine-1-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A and B.

[0188] Step A: Production of (4-((5-chloro-2-nitrophenyl)amino)phenyl)(pyrrolidine-1-yl)methanone Using 4-((5-chloro-2-nitrophenyl)amino)benzoic acid (146.3 mg, 0.50 mmol) and pyrrolidine (39.1 mg, 0.55 mmol) obtained in the above-mentioned Production Example 21, the title compound (171.5 mg, 99% yield) was obtained by the same method as in step A of the above-mentioned Production Example 22. 1H NMR (400 MHz, CDCl3) δ 9.55 (s, 1H), 8.18 (d, 1H), 7.63 (d, 2H), 7.31 (d, 2H), 7.24 (s, 1H), 6.79 (d, 1H), 3.68 (m, 2H), 3.51 (m, 2H), 1.99 (m, 4H)

[0189] Step B: Preparation of 6-chloro-1-(4-(pyrrolidine-1-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the (4-((5-chloro-2-nitrophenyl)amino)phenyl)(pyrrolidin-1-yl)methanone (171.5 mg, 0.50 mmol) obtained in step A, a mixture of the title compound was obtained by the same method as in steps B and C of production example 22.

[0190] Manufacturing Example 25: Production of 4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid The title compound was obtained through the following steps A and B.

[0191] Step A: Preparation of 3-((3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (1.0 g, 3.16 mmol) obtained in the above-mentioned Production Example 1, (4-(tert-butoxycarbonyl)phenyl)boronic acid (1.4 g, 6.31 mmol), and copper(II) acetate (1.7 g, 9.47 mmol) were dissolved in DCM (30 mL). Then, TEA (1.3 mL, 9.47 mmol) was added and the mixture was stirred at room temperature. After the reaction was completed, a saturated K2CO3 solution (1 mL) was added and the mixture was stirred further for 20 minutes. The reaction solution was then filtered through Celite®, and the filtrate was extracted with water and SiO to separate the organic layer, which was then dried over Na2SO4. The solid was filtered, and the filtrate was purified by vacuum distillation and then MPLC to obtain the title compound (745.0 mg, 48% yield). 1H NMR (500 MHz, CDCl3) δ 8.18 (d, 2H), 8.05 (s, 1H), 7.99 (d, 1H), 7.65 (d, 2H), 7.57 (d, 1H), 7.45 (t, 1H), 7.13 (s, 1H), 7.05 (d, 1H), 6.83 (d, 1H), 5.16 (s, 2H), 3.91 (s, 3H), 1.62 (s, 9H)

[0192] Step B: Preparation of 4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid The 3-((3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (745.0 mg, 1.5 mmol) obtained in step A above was dissolved in 20 mL of DCM, and then 8 mL of TFA was slowly added and the mixture was stirred. After the reaction was completed, the solvent and reactants were removed by vacuum distillation to obtain the title compound (619.4 mg, 95% yield). 1 H NMR (500 MHz, DMSO-d6) δ8.14 (d, 2H), 8.01 (s, 1H), 7.89 (d, 1H), 7.64 (d, 2H), 7.66 (d, 1H), 7.51 (t, 1H), 7.29 (d, 1H), 7.19 (m, 2H), 5.23 (s, 2H), 3.84 (s, 3H)

[0193] Manufacturing Example 26: Production of 6-chloro-1-(2-morpholinopyrimidine-5-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, C, and D.

[0194] Step A: Production of 4-(5-nitropyrimidine-2-yl)morpholine 2-chloro-5-nitropyrimidine (3.00 g, 18.8 mmol) was mixed with 38 mL of AN and morpholine (3.60 mL, 41.4 mmol), and the mixture was stirred at room temperature for 1 hour. After removing the solid, the filtrate was concentrated. HCl and aqueous hydrochloric acid were added to the filtrate, and the organic layer was separated and dried over anhydrous Na2SO4 to obtain the title compound (2.65 g, 67% yield). 1 H-NMR (400 MHz, CDCl3) δ9.07 (s, 2H), 4.00 (m, 4H), 3.78 (m, 4H)

[0195] Step B: Preparation of 2-morpholinopyrimidine-5-amine Using the 4-(5-nitropyrimidine-2-yl)morpholine (2.65 g, 12.6 mmol) obtained in step A, the title compound (2.27 g, 99% yield) was obtained by the same method as in step A of production example 9. 1 H-NMR (400 MHz, CDCl3) δ7.99 (s, 2H), 3.77 (m, 4H), 3.64 (m, 4H)

[0196] Step C: Preparation of N-(5-chloro-2-nitrophenyl)-2-morpholinopyrimidine-5-amine To the 2-morpholinopyrimidine-5-amine (0.50 g, 2.77 mmol) obtained in step B, 4-chloro-2-fluoro-1-nitrobenzene (0.97 g, 5.55 mmol) and 14 mL of DMF were added, and the mixture was cooled to 0°C. KOtBu (0.31 g, 2.77 mmol) was then added. The reaction mixture was stirred under reflux for 3 days, and then an aqueous solution of ammonium chloride was added. The resulting solid was filtered and separated by MPLC to obtain the title compound (0.21 g, 22% yield). 1 H-NMR (400 MHz, DMSO-d6) δ9.37 (brs, 1H), 8.348 (s, 2H), 8.14 (d, 1H), 6.86 (dd, 1H), 6.80 (d, 1H), 3.73 (m, 4H), 3.68 (m, 4H)

[0197] Step D: Preparation of 6-chloro-1-(2-morpholinopyrimidine-5-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-2-morpholinopyrimidine-5-amine (0.21 g, 0.625 mmol) obtained in step C, the title compound (0.045 g, 22% yield) was obtained by the same method as in step B of production example 8. 1 H-NMR (400 MHz, MeOH-d4) δ8.46 (s, 2H), 7.11 (dd, 1H), 7.08 (dd, 1H), 6.95 (d, 1H), 3.86 (m, 4H), 3.75 (m, 4H)

[0198] Manufacturing Example 27: Production of 5-chloro-1-(4-(dimethylamino)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one

[0199] Step A:N 1 -(4-chloro-2-fluoro-6-nitrophenyl)-N 4 、N 4 Production of dimethylbenzene-1,4-diamine 5-Chloro-1,2-difluoro-3-nitrobenzene (0.710 g, 3.67 mmol) and N 1 , N 1 The title compound (1.08 g, 95% yield) was obtained using dimethylbenzene-1,4-diamine (0.50 g, 3.67 mmol) by the same method as in step A of Preparation Example 8. 1 H-NMR (400 MHz, CDCl3) δ8.94 (brs, 1H), 8.01 (d, 1H), 7.21 (dd, 1H), 6.99 (d, 2H), 6.67 (d, 2H), 2.93 (s, 6H)

[0200] Step B: Preparation of 5-chloro-1-(4-(dimethylamino)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one N obtained in step A 1 -(4-chloro-2-fluoro-6-nitrophenyl)-N 4 , N 4The title compound (0.50 g, 47% yield) was obtained using dimethylbenzene-1,4-diamine (1.08 g, 3.49 mmol) by the same method as in step B of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ11.48 (brs, 1H), 8.24 (m, 1H), 7.28 (m, 1H), 7.00 (d, 2H), 6.78 (d, 2H), 3.03 (s, 6H)

[0201] Manufacturing Example 28: Production of 6-chloro-1-(4-(4,4-difluoropiperidine-1-yl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, and C.

[0202] Step A: Production of 4-(4,4-difluoropiperidine-1-yl)aniline The title compound (6.25 g, 83% yield) was obtained using 1-fluoro-4-nitrobenzene (5.00 g, 35.4 mmol) and 4,4-difluoropiperidine hydrochloride (5.58 g, 35.4 mmol) in the same manner as in step A of Preparation Example 1 and step B of Preparation Example 7. 1 H-NMR (500 MHz, DMSO-d6) δ6.73 (d, 2H), 6.50 (d, 2H), 4.62 (brs, 2H), 3.02 (m, 4H), 2.05 (m, 4H)

[0203] Step B: Preparation of 5-chloro-N-(4-(4,4-difluoropiperidine-1-yl)phenyl)-2-nitroaniline Using 4-(4,4-difluoropiperidine-1-yl)aniline (1.00 g, 4.71 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (0.827 g, 4.71 mmol) obtained in step A, the title compound (1.52 g, 88% yield) was obtained by the same method as in step A of Production Example 1. 1H-NMR (400 MHz, DMSO-d6) δ 9.46 (d, 1H), 8.13 (d, 1H), 7.21 (d, 2H), 7.10 (d, 2H), 6.85 (dd, 1H), 6.80 (dd, 1H), 3.47 (m, 4H), 2.06 (m, 4H)

[0204] Step C: Preparation of 6-chloro-1-(4-(4,4-difluoropiperidine-1-yl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using 5-chloro-N-(4-(4,4-difluoropiperidine-1-yl)phenyl)-2-nitroaniline (1.52 g, 4.13 mmol) obtained in step B, the title compound (1.04 g, 69% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, DMSO-d6) δ 11.22 (brs, 1H), 7.34 (d, 2H), 7.15 (d, 2H), 7.05 (2H), 6.84 (d, 1H), 3.43 (m, 4H), 2.08 (m, 4H)

[0205] Manufacturing Example 29: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperazine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate hydrochloride The title compound was obtained by following steps A, B, C, D, and E below.

[0206] Step A: Preparation of 4-(4-aminophenyl)piperazine-1-carboxylate tert-butyl ester The title compound (1.60 g, 51% yield) was obtained using 1-fluoro-4-nitrobenzene (1.59 g, 11.3 mmol) and piperazine-1-carboxylate tert-butyl ester (2.10 g, 11.3 mmol) in the same manner as in step A of Preparation Example 1 and step B of Preparation Example 7. 1 H-NMR (400 MHz, DMSO-d6) δ6.70 (d, 2H), 6.49 (d, 2H), 4.61 (brs, 2H), 3.41 (m, 4H), 2.82 (m, 4H), 1.41 (s, 9H)

[0207] Step B: Preparation of 4-(4-((5-chloro-2-nitrophenyl)amino)phenyl)piperazine-1-carboxylate tert-butyl ester Using the 4-(4-aminophenyl)piperazine-1-carboxylate tert-butyl ester (1.60 g, 5.77 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (1.01 g, 5.77 mmol) obtained in step A, the title compound (2.35 g, 94% yield) was obtained by the same method as in step A of Production Example 1. 1 H-NMR (400 MHz, DMSO-d6) δ 9.46 (brs, 1H), 8.13 (d, 1H), 7.20 (d, 2H), 7.04 (d, 2H), 6.82 (dd, 1H), 6.80 (m, 1H), 3.48 (m, 4H), 3.14 (m, 4H), 1.42 (s, 9H)

[0208] Step C: Preparation of 4-(4-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperazine-1-carboxylate tert-butyl ester Using the 4-(4-((5-chloro-2-nitrophenyl)amino)phenyl)piperazine-1-carboxylate tert-butyl ester (2.35 g, 5.34 mmol) obtained in step B, the title compound (1.0 g, 43% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, DMSO-d6) δ 11.22 (brs, 1H), 7.34 (d, 2H), 7.10 (d, 2H), 7.06 (2H), 6.83 (d, 1H), 3.48 (m, 4H), 3.19 (m, 4H), 1.43 (s, 9H)

[0209] Step D: Preparation of 4-(4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperazine-1-carboxylate tert-butyl ester Using 4-(4-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)phenyl)piperazine-1-carboxylic acid tert-butyl ester (1.0 g, 2.33 mmol) obtained in the previous step C and methyl 3-(bromomethyl)benzoate (0.53 g, 2.33 mmol), the title compound (1.05 g, 78% yield) was obtained in the same manner as in step C of Production Example 7. 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.97 (dd, 1H), 7.55 (dd, 1H), 7.43 (d, 1H), 7.40 (d, 2H), 7.05 (d, 2H), 6.99 (m, 2H), 6.79 (d, 1H), 5.15 (s, 2H), 3.92 (s, 3H), 3.62 (m, 4H), 3.22 (m, 4H), 1.50 (s, 9H)

[0210] Step E: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperazine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate hydrochloride To 4-(4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)phenyl)piperazine-1-carboxylic acid tert-butyl ester (1.05 g, 1.82 mmol) obtained in the previous step D, 6 mL of DCM and 1.8 mL of hydrochloric acid (4M EtOAc solution) were added, and then stirred at room temperature for 1 hour. After concentrating the reaction solution under reduced pressure, ethyl ester was added, and the resulting solid was filtered to obtain the title compound (0.94 g, 99% yield). 1 H-NMR (400 MHz, DMSO-d6) δ 8.91 (brs, 2H), 8.00 (d, 1H), 7.88 (dd, 1H), 7.67 (dd, 1H), 7.52 (t, 1H), 7.45 (d, 2H), 7.24 (d, 1H), 7.18 (3H), 6.91 (d, 1H), 5.21 (s, 2H), 3.85 (s, 3H), 3.45 (m, 4H), 3.26 (m, 4H)

[0211] Manufacturing Example 30: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate hydrochloride The title compound was obtained by following steps A, B, C, and D below.

[0212] Step A: Preparation of 4-(4-((5-chloro-2-nitrophenyl)amino)phenyl)piperidine-1-carboxylate tert-butyl ester The title compound (1.65 g, 67% yield) was obtained using 4-(4-aminophenyl)piperidine-1-carboxylate tert-butyl ester (1.57 g, 5.70 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (1.00 g, 5.70 mmol) by the same method as in step A of Preparation Example 1. 1 H-NMR (400 MHz, CDCl3) δ9.15 (brs, 1H), 8.15 (d, 1H), 7.28 (d, 2H), 7.21 (d, 2H), 7.12 (d, 1H), 6.70 (dd, 1H), 4.28 (m, 2H), 2.83 (m, 2H), 2.70 (m, 1H), 1.85 (m, 2H), 1.65 (m, 2H), 1.49 (s, 9H)

[0213] Step B: Preparation of 4-(4-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperidine-1-carboxylate tert-butyl ester Using the 4-(4-((5-chloro-2-nitrophenyl)amino)phenyl)piperidine-1-carboxylate tert-butyl ester (1.65 g, 3.81 mmol) obtained in step A, the title compound (0.65 g, 40% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ8.79 (brs, 1H), 7.45 (d, 2H), 7.38 (2H), 7.07 (d, 1H), 7.02 (2H), 4.28 (m, 2H), 2.83 (m, 2H), 2.73 (m, 1H), 1.88 (m, 2H), 1.65 (m, 2H), 1.50 (s, 9H)

[0214] Step C: Preparation of 4-(4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperidine-1-carboxylate tert-butyl ester Using the 4-(4-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperidine-1-carboxylate tert-butyl ester (0.65 g, 1.52 mmol) and 3-(bromomethyl)benzoate methyl ester (0.35 g, 1.52 mmol) obtained in step B, the title compound (0.70 g, 80% yield) was obtained by the same method as in step C of Production Example 7. 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.98 (dd, 1H), 7.57 (dd, 1H), 7.47 (d, 2H), 7.42 (t, 1H), 7.38 (d, 2H), 7.07 (d, 1H), 7.02 (dd, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 4.29 (m, 2H), 3.91 (s, 3H), 2.83 (m, 2H), 2.73 (m, 1H), 1.87 (m, 2H), 1.66 (m, 2H), 1.50 (s, 9H)

[0215] Step D: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl hydrochloride To the 4-(4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperidine-1-carboxylic acid tert-butyl ester (0.70 g, 1.21 mmol) obtained in step C, 3 mL of DCM and 1.21 mL of hydrochloric acid (4 M ELISA solution) were added, and the mixture was stirred at room temperature for 1 hour. After concentrating the reaction mixture under reduced pressure, diethyl ester was added, and the resulting solid was dried to obtain the title compound (0.48 g, 76% yield). 1H-NMR (400 MHz, DMSO-d6) δ8.90 (brs, 2H), 8.01 (d, 1H), 7.89 (dd, 1H), 7.66 (dd, 1H), 7.57 (d, 2H), 7.52 (t, 1H), 7.455 (d, 2H), 7.27 (d, 1H), 7.16 (dd, 1H), 7.03 (d, 1H), 5.23 (s, 2H), 3.85 (s, 3H), 3.33 (m, 2H), 3.03 (m, 2H), 2.97 (m, 1H), 1.98 (m, 2H), 1.90 (m, 2H)

[0216] Manufacturing Example 31: Preparation of 6-chloro-1-(4-(3,6-dihydro-2H-pyran-4-yl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained by following steps A, B, and C below.

[0217] Step A: Preparation of 4-(4-nitrophenyl)-3,6-dihydro-2H-pyran 4-bromo-1-nitrobenzene (200 mg, 1.0 mmol) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (230 mg, 1.1 mmol) were mixed with 3 mL of 1,4-dioxane and 3 mL of 1 M aqueous sodium carbonate solution. After packing with nitrogen, a catalytic amount of Pd(PPh3)4 was added, and the mixture was stirred under reflux for 16 hours. After the reaction was completed, the solid was removed by Celite, and the filtrate was purified by MPLC to obtain the title compound (185 mg, 91% yield). 1 H-NMR (500 MHz, CDCl3) δ 8.22 (d, 2H), 7.55 (d, 2H), 6.36 (s, 1H), 4.39 (s, 2H), 3.98 (t, 2H), 2.57 (s, 2H)

[0218] Step B: Production of 4-(3,6-dihydro-2H-pyran-4-yl)aniline Using 4-(4-nitrophenyl)-3,6-dihydro-2H-pyran (180 mg, 0.88 mmol) obtained in Step A above, the title compound (138 mg, 90% yield) was obtained in the same manner as in Step B of Production Example 7.

[0219] Step C: Preparation of 6-chloro-1-(4-(3,6-dihydro-2H-pyran-4-yl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using 4-(3,6-dihydro-2H-pyran-4-yl)aniline (138 mg, 0.78 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (138 mg, 0.78 mmol) obtained in Step B above, the title compound (65 mg, 26% yield) was obtained via the same method as in Step A of Production Example 1, Step B of Production Example 7, and Step B of Production Example 8. 1 H-NMR (500 MHz, CDCl3) δ 8.18 (d, 1H), 7.50 (d, 2H), 7.26 (d, 2H), 7.19 (s, 1H), 6.75 (d, 1H), 6.20 (s, 1H), 4.38 (m, 2H), 3.98 (m, 2H), 2.57 (m, 2H)

[0220] Production Example 32: Preparation of 6-chloro-1-(4-(3,3-difluoropyrrolidin-1-yl)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazol-2-one The title compound was obtained via the following Steps A, B, C, and D.

[0221] Step A: Production of 3,3-difluoro-1-(4-nitrophenyl)pyrrolidine Using 1-fluoro-4-nitrobenzene (3.0 g, 21.3 mmol) and 3,3-difluoropyrrolidine hydrochloride (3.05 g, 21.26 mmol), the title compound (4.28 g, 88% yield) was obtained in the same manner as in Step A of Production Example 1. 1 H-NMR (400 MHz, DMSO-d6) δ 8.10 (d, 2H), 6.70 (d, 2H), 3.89 (t, 2H), 3.65 (t, 2H), 2.57 (m, 2H)

[0222] Step B: Preparation of 4-(3,3-difluoropyrrolidine-1-yl)aniline Using the 3,3-difluoro-1-(4-nitrophenyl)pyrrolidine (4.28 g, 18.8 mmol) obtained in step A, the title compound (2.17 g, 58% yield) was obtained by the same method as in step B of production example 7. 1 H-NMR (400 MHz, DMSO-d6) δ6.51 (d, 2H), 6.44 (d, 2H), 4.43 (brs, 2H), 3.50 (t, 2H), 3.30 (t, 2H), 2.45 (m, 2H)

[0223] Step C: Preparation of 3-chloro-N-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-2-fluoro-6-nitroaniline Using 4-(3,3-difluoropyrrolidine-1-yl)aniline (1.0 g, 5.04 mmol) and 1-chloro-2,3-difluoro-4-nitrobenzene (0.98 g, 5.04 mmol) obtained in step B, the title compound (0.87 g, 48% yield) was obtained by the same method as in step A of Production Example 1. 1 H-NMR (400 MHz, CDCl3) δ9.10 (brs, 1H), 7.97 (dd, 1H), 7.03 (d, 2H), 6.83 (dd, 1H), 6.52 (d, 2H), 3.68 (t, 2H), 3.53 (t, 2H), 2.50 (m, 2H)

[0224] Step D: Preparation of 6-chloro-1-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one Using 3-chloro-N-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-2-fluoro-6-nitroaniline (0.87 g, 2.34 mmol) obtained in step C, the title compound (0.48 g, 56% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1H-NMR (400 MHz, CDCl3) δ8.21 (brs, 1H), 7.32 (d, 2H), 7.09 (dd, 1H), 6.81 (dd, 1H), 6.63 (d, 2H), 3.73 (t, 2H), 3.58 (t, 2H), 2.52 (m, 2H)

[0225] Manufacturing Example 33: Production of 6-bromo-2,2-dimethyl-2,3-dihydro-1H-idden-1-one 6-bromo-2,3-dihydro-1H-inden-1-one (1.0 g, 4.74 mmol) was mixed with 31 mL of THF and iodomethane (0.74 mL, 11.8 mmol), then cooled to 0°C, and NaH (0.46 g, 11.3 mmol, 55 wt% in mineral oil) was added. After stirring at room temperature for 1 hour, saturated aqueous solution of ammonium chloride was added, and the mixture was extracted with siRNA. The organic layer was separated and purified by MPLC to obtain the title compound (0.81 g, 71% yield). 1 H-NMR (400 MHz, CDCl3) δ 7.88 (dd, 1H), 7.59 (dd, 1H), 7.31 (d, 1H), 2.94 (s, 2H), 1.24 (s, 6H)

[0226] Manufacturing Example 34: Production of 5-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-one The title compound (1.06 g, 94% yield) was obtained using 5-bromo-2,3-dihydro-1H-inden-1-one (1.0 g, 4.74 mmol) by the same method as in Preparation Example 33. 1 H-NMR (400 MHz, CDCl3) δ7.62 (2H), 7.52 (dd, 1H), 2.98 (s, 2H), 1.23 (s, 6H)

[0227] Manufacturing Example 35: Production of 6-chloro-1-(2-methyl-1-oxoisoindridine-5-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A and B.

[0228] Step A: Preparation of 5-((5-chloro-2-nitrophenyl)amino)-2-methylisoindoline-1-one 5-amino-2-methylisoindorin-1-one (1.0g, 6.17 mmol) with 61 mL of THF and KO t After adding Bu (0.69 g, 6.17 mmol), the mixture was stirred at 70°C for 30 minutes. 4-chloro-2-fluoro-1-nitrobenzene (1.62 g, 9.25 mmol) was added to the reaction mixture, and the mixture was stirred at 70°C for 16 hours. After adding water to the reaction mixture, the mixture was extracted with siRNA, and the organic layer was purified by MPLC to obtain the title compound (0.307 g, 15% yield). 1 H-NMR (400 MHz, DMSO-d6) δ 9.60 (brs, 1H), 8.18 (d, 1H), 7.90 (dd, 1H), 7.30 (2H), 7.24 (d, 1H), 6.82 (dd, 1H), 4.42 (s, 2H), 3.22 (s, 3H)

[0229] Step B: Preparation of 6-chloro-1-(2-methyl-1-oxoisoindridine-5-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using 5-((5-chloro-2-nitrophenyl)amino)-2-methylisoindorin-1-one (0.307 g, 0.97 mmol) obtained in step A, the title compound (0.29 g, 96% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, DMSO-d6) δ 11.41 (brs, 1H), 7.82 (d, 1H), 7.79 (d, 1H), 7.64 (dd, 1H), 7.10 (3H), 4.55 (s, 2H), 3.11 (s, 3H)

[0230] Manufacturing Example 36: Preparation of 3-(2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)ethyl)methyl benzoate The title compound was obtained through the following steps A, B, C, and D.

[0231] Step A: Production of methyl 3-(cyanomethyl)benzoate 3-(bromomethyl)methyl benzoate (2.00 g, 8.73 mmol) was mixed with 8 mL of DMSO and KCN (0.60 g, 9.17 mmol), and the mixture was stirred at room temperature for 16 hours. After adding water and Et2O to the reaction mixture, the organic layer was separated and purified by MPLC to obtain the title compound (0.78 g, 51% yield). 1 H-NMR (400 MHz, CDCl3) δ8.01 (2H), 7.56 (m, 1H), 7.49 (m, 1H), 3.93 (s, 3H), 3.81 (s, 2H)

[0232] Step B: Preparation of methyl 3-(2-aminoethyl)benzoate Using the methyl 3-(cyanomethyl)benzoate ester (0.70 g, 4.0 mmol) obtained in step A, the title compound (0.71 g, 99% yield) was obtained with reference to WO2016 / 165014. 1 H-NMR (400 MHz, DMSO-d6) δ7.83 (2H), 7.81 (brs, 2H), 7.55 (m, 1H), 7.52 (m, 1H), 3.86 (s, 3H), 3.07 (m, 2H), 2.95 (t, 2H)

[0233] Step C: Preparation of 3-(2-((4-chloro-2-nitrophenyl)amino)ethyl)methyl benzoate Using the methyl 3-(2-aminoethyl)benzoate (0.70 g, 4.0 mmol) and 4-chloro-1-fluoro-2-nitrobenzene (0.70 g, 7.0 mmol) obtained in step B, the title compound (0.24 g, 18% yield) was obtained by the same method as in step A of Production Example 1. 1 H-NMR (400 MHz, CDCl3) δ8.16 (d, 1H), 8.04 (m, 1H), 7.93 (2H), 7.43 (2H), 7.30 (dd, 1H), 6.82 (d, 1H), 3.92 (s, 3H), 3.58 (m, 2H), 3.07 (t, 2H)

[0234] Step D: Preparation of 3-(2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)ethyl)methyl benzoate Using the 3-(2-((4-chloro-2-nitrophenyl)amino)ethyl)methyl benzoate (0.24 g, 0.71 mmol) obtained in step C, the title compound (0.10 g, 42% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ9.52 (brs, 1H), 7.88 (2H), 7.37 (2H), 7.09 (d, 1H), 7.00 (dd, 1H), 6.72 (dd, 1H), 4.11 (t, 2H), 3.91 (s, 3H), 3.10 (t, 2H)

[0235] Manufacturing Example 37: Preparation of 2-(4-bromophenyl)-N,N-dimethylacetamide To 2-(4-bromophenyl)acetic acid (1.0 g, 4.65 mmol), 15 mL of DCM, dimethylamine hydrochloride (0.46 g, 5.58 mmol), EDC-HCl (0.98 g, 5.12 mmol), HOBt (0.78 g, 5.12 mmol), and DIPEA (2.03 mL, 11.6 mmol) were added, and the mixture was stirred at room temperature for 16 hours. After adding water to the reaction mixture, the organic layer was separated and purified by MPLC to obtain the title compound (1.13 g, 99% yield). 1 H-NMR (400 MHz, CDCl3) δ7.44 (dd, 2H), 7.13 (dd, 2H), 3.66 (s, 2H), 3.00 (s, 3H), 2.97 (s, 3H)

[0236] Manufacturing Example 38: Production of 1-(4-bromophenyl)azetidine-3-ol (4-bromophenyl)boronic acid (0.30 g, 1.49 mmol) was mixed with 15 mL of DCM, Cu(OAc)2 (0.54 g, 3.0 mol), and TEA (1.25 mL, 9 mmol), and the mixture was stirred at room temperature for 16 hours. After removing the solid with Celite, the filtrate was purified by MPLC to obtain the title compound (0.11 g, 31% yield). 1 H-NMR (400 MHz, CDCl3) δ7.28 (d, 2H), 6.33 (d, 2H), 4.76 (m, 1H), 4.15 (t, 2H), 3.65 (m, 2H), 2.08 (m, 1H)

[0237] Manufacturing Example 39: Manufacturing of 6-(4-bromophenyl)-2-oxa-6-azaspiro[3.3]heptane The title compound (0.062 g, 24% yield) was obtained using (4-bromophenyl)boronic acid (0.223 g, 1.11 mmol) and 2-oxa-6-azaspiro[3.3]heptane (0.10 g, 1 mmol) by the same method as in Preparation Example 38. 1 H-NMR (400 MHz, CDCl3) δ7.29 (dd, 2H), 6.32 (dd, 2H), 4.83 (s, 4H), 3.99 (s, 4H)

[0238] Manufacturing Example 40: Manufacturing of 2-(4-bromophenyl)-7-oxa-2-azaspiro[3.5]nonane The title compound (0.15 g, 22% yield) was obtained using (4-bromophenyl)boronic acid (0.50 g, 2.49 mmol) and 7-oxa-2-azaspiro[3.5]nonane hydrochloride (0.49 g, 2.74 mmol) by the same method as in Preparation Example 38. 1 H-NMR (500 MHz, CDCl3) δ7.28 (m, 2H), 6.31 (m, 2H), 3.67 (m, 4H), 3.62 (s, 4H), 1.83 (m, 4H)

[0239] Manufacturing Example 41: Production of 3-(2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)propan-2-yl)benzonitrile The title compound was obtained by following the steps A, B, C, D, and E below.

[0240] Step A: Preparation of (2-(3-bromophenyl)propan-2-yl)carboxylate tert-butyl ester 2-(3-bromophenyl)propan-2-amine hydrochloride (1.0 g, 4.0 mmol) was mixed with 40 mL of THF, BOC2O (1.0 mL, 4.4 mmol), DIPEA (1.7 mL, 10 mmol), and a catalytic amount of DMAP, and the mixture was stirred at room temperature for 16 hours. The solid was filtered, and the filtrate was purified by MPLC to obtain the title compound (1.2 g, 99% yield).

[0241] Step B: Preparation of (2-(3-cyanophenyl)propan-2-yl)carboxylate tert-butyl ester To the (2-(3-bromophenyl)propan-2-yl) carboxylate tert-butyl ester (0.45 g, 1.8 mmol) obtained in step A, 6 mL of DMF, Zn(CN)2 (0.13 g, 0.85 mmol), and Pd(PPh3)4 (0.21 g, 0.18 mmol) were added, and the mixture was stirred at 100°C for 16 hours. SiO2 was added to the reaction mixture, and it was washed with aqueous ammonia. The organic layer was separated and purified by MPLC to obtain the title compound (0.20 g, 42% yield). 1 H-NMR (400 MHz, CDCl3) δ7.68 (d, 1H), 7.64 (dd, 1H), 7.51 (dd, 1H), 7.43 (t, 1H), 5.06 (m, 1H), 1.51 (s, 6H), 1.39-1.10 (9H)

[0242] Step C: Manufacturing of 3-(2-aminopropan-2-yl)benzonitrile hydrochloride To the (2-(3-cyanophenyl)propan-2-yl) carboxylate tert-butyl ester (0.31 g, 1.2 mmol) obtained in step B, 1.2 mL of DCM and 1.2 mL of HCl (4.0 M HCl solution) were added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain the title compound (0.20 g, 85% yield). 1 H-NMR (400 MHz, DMSO-d6) δ8.76 (brs, 3H), 7.05 (d, 1H), 7.92 (dd, 1H), 7.86 (dd, 1H), 7.61 (t, 1H), 1.65 (s, 6H)

[0243] Step D: Preparation of 3-(2-((4-chloro-2-nitrophenyl)amino)propan-2-yl)benzonitrile Using 3-(2-aminopropan-2-yl)benzonitrile hydrochloride (0.20 g, 1 mmol) and 4-chloro-1-fluoro-2-nitrobenzene (0.18 g, 1 mmol) obtained in step C, the title compound (0.20 g, 62% yield) was obtained by the same method as in step A of Production Example 1. 1 H-NMR (400 MHz, CDCl3) δ8.61 (brs, 1H), 8.20 (d, 1H), 7.72 (m, 1H), 7.66 (m, 1H), 7.58 (m, 1H), 7.48 (t, 1H), 7.07 (dd, 1H), 6.13 (d, 1H), 1.78 (s, 6H)

[0244] Step E: Preparation of 3-(2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)propan-2-yl)benzonitrile Using the 3-(2-((4-chloro-2-nitrophenyl)amino)propan-2-yl)benzonitrile (0.20 g, 0.63 mmol) obtained in step D, the title compound (0.12 g, 64% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ8.23 (brs, 1H), 7.64 (d, 1H), 7.58 (2H), 7.47 (t, 1H), 7.00 (d, 1H), 6.74 (dd, 1H), 6.10 (dd, 1H), 2.08 (s, 6H)

[0245] Manufacturing Example 42: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperazine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl hydrochloride The title compound was obtained through the following steps A and B.

[0246] Step A: Preparation of 4-(4-(6-chloro-3-(2-fluoro-3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperazine-1-carboxylate tert-butyl ester Using 4-(4-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperazine-1-carboxylate tert-butyl ester (0.52 g, 1.21 mmol) and 3-(bromomethyl)-2-fluorobenzoate methyl ester (0.30 g, 1.21 mmol) obtained in step C of Preparation Example 29, the title compound (0.72 g, 99% yield) was obtained by the same method as in step A of Preparation Example 1. 1 H-NMR (400 MHz, CDCl3) δ 7.88 (t, 1H), 7.61 (t, 1H), 7.37 (d, 2H), 7.17 (t, 1H), 7.06 (3H), 7.00 (d, 1H), 6.96 (dd, 1H), 5.19 (s, 2H), 3.94 (s, 3H), 3.61 (m, 4H), 3.21 (m, 4H), 1.49 (s, 9H)

[0247] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperazin-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl hydrochloride To the 4-(4-(6-chloro-3-(2-fluoro-3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)piperazine-1-carboxylic acid tert-butyl ester (0.71 g, 1.2 mmol) obtained in step A, 4 mL of DCM and 1.2 mL of hydrochloric acid (4.0 M HCl solution) were added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated under reduced pressure to obtain the title compound (0.55 g, 86% yield). 1 H-NMR (400 MHz, DMSO-d6) δ8.86 (brs, 2H), 7.83 (td, 1H), 7.58 (td, 1H), 7.43 (d, 2H), 7.30 (t, 1H), 7.24 (m, 1H), 7.18 (3H), 6.91 (d, 1H), 5.22 (s, 2H), 3.86 (s, 3H), 3.45 (m, 4H), 3.27 (m, 4H)

[0248] Manufacturing Example 43: Preparation of 3-((5-chloro-4-fluoro-2-oxo-3-(4-(piperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl hydrochloride Using 4-(4-aminophenyl)piperidine-1-carboxylate tert-butyl ester (1.00 g, 3.62 mmol), 1-chloro-2,3-difluoro-4-nitrobenzene (0.70 g, 3.62 mmol), and 3-(bromomethyl)-2-fluorobenzoate methyl ester, the title compound (0.27 g, 13% yield) was obtained by the same method as in Preparation Example 30. 1 H-NMR (400 MHz, DMSO-d6) δ 8.74 (m, 1H), 8.55 (m, 1H), 7.83 (td, 1H), 7.61 (td, 1H), 7.52 (dd, 2H), 7.38 (d, 2H), 7.30 (2H), 7.13 (d, 1H), 5.24 (s, 2H), 3.86 (s, 3H), 3.40 (m, 2H), 3.04 (m, 2H), 2.95 (m, 1H), 2.02 (m, 2H), 1.87 (m, 2H)

[0249] Manufacturing Example 44: Preparation of 6-chloro-1-(6-(3,3-difluoropyrrolinidine-1-yl)pyridine-3-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound was obtained through the following steps A, B, C, and D.

[0250] Step A: Preparation of 2-(3,3-difluoropyrrolidine-1-yl)-5-nitropyridine The title compound (1.84 g, 91% yield) was obtained using 2-fluoro-5-nitropyridine (1.26 g, 8.87 mmol) and 3,3-difluoropyrrolidine hydrochloride (1.40 g, 9.47 mmol) by the same method as in step A of Preparation Example 1. 1H-NMR (400 MHz, DMSO-d6) δ9.01 (d, 1H), 8.30 (dd, 1H), 6.68 (m, 1H), 4.01 (t, 2H), 3.79 (m, 2H), 2.60 (m, 2H)

[0251] Step B: Preparation of 6-(3,3-difluoropyrrolidine-1-yl)pyridine-3-amine Using 2-(3,3-difluoropyrrolidine-1-yl)-5-nitropyridine (1.84 g, 8.03 mmol) obtained in step A, the title compound (1.58 g, 99% yield) was obtained by the same method as in step A of production example 9. 1 H-NMR (400 MHz, CDCl3) δ7.77 (d, 1H), 7.01 (dd, 1H), 6.28 (d, 1H) 3.78 (t, 2H), 3.60 (t, 2H), 3.27 (brs, 2H), 2.48 (m, 2H)

[0252] Step C: Preparation of N-(5-chloro-2-nitrophenyl)-6-(3,3-difluoropyrrolidine-1-yl)pyridine-3-amine 2-bromo-4-chloronitrobenzene (1.30 g, 5.52 mmol) and 6-(3,3-difluoropyrrolidine-1-yl)pyridine-3-amine (1.0 g, 5.0 mmol) obtained in step B were mixed with 34 mL of toluene and BINAP (0.38 g, 0.60 mmol), and then the mixture was packed with nitrogen gas. Cs2CO3 (2.62 g, 8.0 mmol) and Pd2(dba)3 (0.46 g, 0.50 mmol) were added to the mixture, and the mixture was stirred at 100°C for 16 hours. The solid was removed by Celite, and the filtrate was purified by MPLC to obtain the title compound (1.11 g, 63% yield). 1 H-NMR (400 MHz, CDCl3) δ9.30 (brs, 1H), 8.17 (d, 1H), 8.12 (dd, 1H), 7.41 (dd, 1H), 6.80 (d, 1H), 6.69 (dd, 1H), 6.45 (dd, 1H), 3.90 (t, 2H), 3.74 (t, 2H), 2.54 (m, 2H)

[0253] Step D: Preparation of 6-chloro-1-(6-(3,3-difluoropyrrolinidine-1-yl)pyridine-3-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-6-(3,3-difluoropyrrolinidine-1-yl)pyridine-3-amine (1.12 g, 3.16 mmol) obtained in step C, the title compound (0.48 g, 43% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, DMSO-d6) δ11.28 (brs, 1H), 8.22 (d, 1H), 7.70 (dd, 1H), 7.07 (2H), 6.82 (d, 1H), 6.71 (dd, 1H), 3.90 (t, 2H), 3.67 (t, 2H), 2.56 (m, 2H)

[0254] Manufacturing Example 45: Preparation of 3-(4-(dimethylamino)phenyl)-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-one The title compound was obtained through the following steps A and B.

[0255] Step A:N 1 、N 1 -dimethyl-N 4 Preparation of (6-methyl-3-nitropyridine-2-yl)benzene-1,4-diamine 2-Fluoro-6-methyl-3-nitropyridine (0.50 g, 3.2 mmol) and N 1 , N 1 The title compound (0.77 g, 88% yield) was obtained using dimethylbenzene-1,4-diamine (0.44 g, 3.2 mmol) by the same method as in step A of Preparation Example 1. 1 H-NMR (400 MHz, CDCl3) δ10.15 (brs, 1H), 8.37 (d, 1H), 7.53 (d, 2H), 6.76 (d, 2H), 6.58 (dd, 1H), 2.97 (s, 6H), 2.48 (s, 3H)

[0256] Step B: Preparation of 3-(4-(dimethylamino)phenyl)-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridine-2-one N obtained in step A1 , N 1 -dimethyl-N 4 The title compound (0.20 g, 26% yield) was obtained using -(6-methyl-3-nitropyridine-2-yl)benzene-1,4-diamine (0.77 g, 2.83 mmol) by the same method as in step B of Preparation Example 7 and step B of Preparation Example 8. 1 H-NMR (400 MHz, CDCl3) δ8.07 (d, 1H), 7.52 (brs, 1H), 7.42 (dd, 2H), 7.00 (dd, 1H), 6.89 (dd, 2H), 3.05 (s, 6H), 2.50 (s, 3H)

[0257] Manufacturing Example 46: Preparation of 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclobutyl)methyl benzoate The title compound was obtained by following the steps A, B, C, D, and E below.

[0258] Step A: Production of 3-(1-((tert-butoxycarbonyl)amino)cyclobutyl)benzoic acid 196 mg, 0.60 mmol of tert-butyl (1-(3-bromophenyl)cyclobutyl) carbamate was dissolved in 3 mL of DMF. Oxalic acid (81.03 mg, 0.90 mmol), acetic anhydride (92 mg, 0.90 mmol), Pd(OAc)2 (1.35 mg, 6 µl), and Xantphos (3.47 mg, 6 µl) were added, followed by DIPEA (116 mg, 0.90 mmol). The mixture was then filled with nitrogen gas and stirred at 100°C for 5 hours. After the reaction was complete, the mixture was diluted with siRNA and water, and the organic layer was separated by adding 1 mL of 1 N HCl. The organic layer was dried over anhydrous Na₂SO₄ and purified by MPLC to obtain the title compound (138 mg, 79% yield). 1H NMR (500 MHz, CDCl3) δ8.16 (s, 1H), 7.99 (d, 1H), 7.69 (br s, 1H), 7.46 (t, 1H), 2.61 (m, 2H), 2.51 (m, 2H), 2.15 (m, 1H), 1.92 (m,1H), 1.38 (m, 9H)

[0259] Step B: Preparation of 3-(1-((tert-butoxycarbonyl)amino)cyclobutyl)methyl benzoate The 3-(1-((tert-butoxycarbonyl)amino)cyclobutyl)benzoic acid (135 mg, 0.463 mmol) obtained in step A above was dissolved in 1 mL of DMF, Na2CO3 (98 mg, 0.927 mmol) was added, and then iodomethane (43.5 μL, 0.695 mmol) was added to the reaction solution and stirred at 40°C. After the reaction was completed, siRNA and water were added to separate the organic layer, which was dried over anhydrous MgSO4. The filtrate was distilled under reduced pressure and purified by MPLC to obtain the title compound (20 mg, 61% yield). 1 H NMR (500 MHz, CDCl3) δ8.08 (m, 1H), 7.91 (m, 1H), 7.64 (br s, 1H), 7.42 (m, 1H), 5.19 (s, 1H), 3.91 (s, 3H), 2.54 (m, 4H), 2.12 (m, 1H), 1.87 (m, 1H), 1.51 (m, 9H)

[0260] Step C: Preparation of methyl 3-(1-aminocyclobutyl)benzoate The 3-(1-((tert-butoxycarbonyl)amino)cyclobutyl)methyl benzoate (125 mg, 0.409 mmol) obtained in step B was dissolved in 20 mL of DCM, 8 mL of TFA was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was completed, the TFA and solvent were removed by vacuum distillation, and the process proceeded to the next step without further purification.

[0261] Step D: Preparation of 3-(1-((4-chloro-2-nitrophenyl)amino)cyclobutyl)methyl benzoate Using 4-chloro-1-fluoro-2-nitrobenzene and 3-(1-aminocyclobutyl)methyl benzoate obtained in step C, the title compound (77.1 mg, 52% yield) was obtained by the same method as in step A of Production Example 1. 1 H NMR (500 MHz, CDCl3) δ8.75 (s, 1H), 8.18 (s, 2H), 7.95 (d, 1H), 7.63 (d, 1H), 7.43 (t, 1H), 7.10 (d, 1H), 6.16 (d, 1H), 3.93 (s, 3H), 2.78 (m, 2H), 2.54 (m, 2H), 2.24 (m, 2H)

[0262] Step E: Preparation of 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclobutyl)methyl benzoate Using the 3-(1-((4-chloro-2-nitrophenyl)amino)cyclobutyl)methyl benzoate obtained in step D, the title compound (26.9 mg, 36% yield) was obtained sequentially by the same method as in steps B and C of Production Example 1. 1 H NMR (500 MHz, CDCl3) δ10.39 (s, 1H), 8.35 (s, 1H), 7.95 (d, 1H), 7.80 (d, 1H), 7.43 (t, 1H), 7.08 (s, 1H), 6.94 (d, 1H), 6.81 (d, 1H), 3.91 (s, 3H), 3.20 (m, 2H), 3.02 (m, 2H), 2.07 (m, 2H)

[0263] Manufacturing Example 47: Preparation of 3-(2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)propan-2-yl)methyl benzoate The title compound was obtained by following the steps A, B, C, D, and E below.

[0264] Step A: Production of 3-(2-((tert-butoxycarbonyl)amino)propan-2-yl)benzoic acid The title compound (139 mg, 20% yield) was obtained using tert-butyl(2-(3-bromophenyl)propan-2-yl)carbamate (785 mg, 2.50 mmol) by the same method as in step A of Production Example 46. 1 H NMR (500 MHz, CDCl3) δ8.14 (s, 1H), 7.98 (d, 1H), 7.66 (d, 1H), 7.45 (t, 1H), 1.65 (s, 6H), 1.40 (m, 9H)

[0265] Step B: Preparation of 3-(2-((tert-butoxycarbonyl)amino)propan-2-yl)methyl benzoate Using the 3-(2-((tert-butoxycarbonyl)amino)propan-2-yl)benzoic acid obtained in step A, the title compound (145 mg, 99% yield) was obtained by the same method as in step B of production example 46. 1 H NMR (500 MHz, CDCl3) δ8.07 (s, 1H), 7.90 (d, 1H), 7.60 (d, 1H), 7.40 (t, 1H), 4.99 (br s, 1H), 3.90 (s, 3H), 1.63 (s, 6H), 1.39 (m, 9H)

[0266] Step C: Preparation of methyl 3-(2-aminopropan-2-yl)benzoate Using the 3-(2-((tert-butoxycarbonyl)amino)propan-2-yl)methyl benzoate obtained in step B, the title compound was obtained by the same method as in step C of Production Example 46, and the process proceeded to the next step without further purification.

[0267] Step D: Preparation of 3-(2-((4-chloro-2-nitrophenyl)amino)propan-2-yl)methyl benzoate Using 4-chloro-1-fluoro-2-nitrobenzene and methyl 3-(2-aminopropan-2-yl)benzoate obtained in step C, the title compound (41.6 mg, 24% yield) was obtained by the same method as in step A of Production Example 1.

[0268] Step E: Preparation of 3-(2-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)propan-2-yl)methyl benzoate Using the methyl 3-(2-((4-chloro-2-nitrophenyl)amino)propan-2-yl)benzoate obtained in step D, the title compound (23.0 mg, 58% yield) was obtained sequentially by the same method as in steps B and C of Production Example 1. 1 H NMR (500 MHz, CDCl3) δ9.73 (s, 1H), 8.07 (s, 1H), 7.98 (d, 1H), 7.52 (d, 1H), 7.43 (t, 1H), 7.01 (s, 1H), 6.67 (d, 1H), 6.04 (d, 1H), 3.92 (s, 3H), 2.10 (s, 6H)

[0269] Manufacturing Example 48: Preparation of 3-((6-chloro-2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridine-3-yl)methyl)benzoate The title compound was obtained through the following steps A and B.

[0270] Step A: Preparation of 3-(((5-chloro-3-nitropyridine-2-yl)aminomethyl)methyl benzoate 775 mg, 4.69 mmol of 3-(aminomethyl)methyl benzoate was dissolved in THF and cooled to 0°C. 222 mg, 5.54 mmol of NaH was slowly added, and the mixture was stirred for 30 minutes. Then, 753 mg, 4.27 mmol of 5-chloro-2-fluoro-3-nitropyridine was added at 0°C, and the mixture was stirred while increasing the temperature to room temperature. After the reaction was complete, water was slowly added while stirring at 0°C, and the organic layer was extracted with pharmaceutically acceptable aqueous solutions of siRNA and NH4Cl. The mixture was then dried over Na2SO4. The solid was filtered, and the filtrate was purified by vacuum distillation and MPLC to obtain the title compound (448 mg, 33% yield). 1 H-NMR (500 MHz, CDCl3) δ8.55 (brs, 1H), 8.45 (s, 1H), 8.39 (s, 1H), 8.04 (s, 1H), 7.98 (d, 1H), 7.56 (d, 1H), 7.44 (s, 1H), 4.98 (d, 2H), 3.93 (s, 3H).

[0271] Step B: Preparation of 3-((6-chloro-2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridine-3-yl)methyl)benzoate methyl ester Using the 3-(((5-chloro-3-nitropyridine-2-yl)amino)methyl)methyl benzoate (110 mg, 0.34 mmol) obtained in step A, the title compound (45 mg, 41% yield) was obtained by the same method as in step B of production example 8. 1 H-NMR (500 MHz, CDCl3) δ10.01 (brs, 1H), 8.15 (s, 1H), 8.05 (s, 1H), 7.97 (d, 1H), 7.67 (d, 1H), 7.42 (t, 1H), 7.36 (s, 1H), 5.21 (d, 2H), 3.92 (s, 3H).

[0272] Manufacturing Example 49: Preparation of 3-(1-(2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate The title compound was obtained through the following steps A and B.

[0273] Step A: Preparation of 3-(1-((2-nitro-4-(trifluoromethyl)phenyl)amino)cyclopropyl)methyl benzoate The title compound (0.86 g, 94% yield) was obtained using 1-fluoro-2-nitro-4-(trifluoromethyl)benzene (0.50 g, 2.39 mmol) and the hydrochloride salt of 3-(1-aminocyclopropyl)benzoate methyl ester (0.60 g, 2.63 mmol) in the same manner as in step A of Production Example 1. 1 H-NMR (400 MHz, CDCl3) δ8.82 (brs, 1H), 7.50 (d, 1H), 7.88 (m, 1H), 7.76 (d, 1H), 7.51 (dd, 1H), 7.30 (2H), 7.04 (dd, 1H), 3.91 (s, 3H), 1.58 (m, 2H), 1.44 (m, 2H)

[0274] Step B: Preparation of 3-(1-(2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using the 3-(1-((2-nitro-4-(trifluoromethyl)phenyl)amino)cyclopropyl)methyl benzoate (0.85 g, 2.23 mmol) obtained in step A, the title compound (0.29 g, 35% yield) was obtained by the same method as in step B of Production Example 7 and step B of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ9.75 (brs, 1H), 7.89 (dd, 1H), 7.30 (d, 1H), 7.35 (4H), 7.23 (dd, 1H), 3.89 (s, 3H), 1.72 (m, 4H)

[0275] Manufacturing Example 50: Preparation of 3-(1-(2-oxo-5-(trifluoromethoxy)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate The title compound was obtained through the following steps A and B.

[0276] Step A: Preparation of 3-(1-((2-nitro-4-(trifluoromethoxy)phenyl)amino)cyclopropyl)methyl benzoate The title compound (0.86 g, 97% yield) was obtained using 1-fluoro-2-nitro-4-(trifluoromethoxy)benzene (0.50 g, 2.22 mmol) and methyl 3-(1-aminocyclopropyl)benzoate hydrochloride (0.55 g, 2.44 mmol) by the same method as in step A of Preparation Example 1. 1 H-NMR (400 MHz, CDCl3) δ8.62 (brs, 1H), 8.10 (dd, 1H), 7.88 (m, 1H), 7.76 (d, 1H), 7.40 (2H), 7.21 (dd, 1H), 6.96 (dd, 1H), 3.90 (s, 3H), 1.55 (m, 2H), 1.42 (m, 2H)

[0277] Step B: Preparation of 3-(1-(2-oxo-5-(trifluoromethoxy)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using the 3-(1-((2-nitro-4-(trifluoromethoxy)phenyl)amino)cyclopropyl)methyl benzoate (0.85 g, 2.14 mmol) obtained in step A, the title compound (0.21 g, 25% yield) was obtained by the same method as in step B of production example 7 and step B of production example 8. 1 H-NMR (400 MHz, CDCl3) δ8.81 (brs, 1H), 7.89 (dd, 1H), 7.81 (d, 1H), 7.38 (2H), 7.10 (d, 1H), 7.00 (d, 1H), 6.95 (dd, 1H), 3.89 (s, 3H), 1.69 (m, 4H)

[0278] Production Example 51: Production of 4-(4-bromophenyl)-1,4-oxazepane The title compound was obtained through the following steps A and B.

[0279] Step A: Production of 4-(1,4-oxazepan-4-yl)aniline The title compound (0.32 g, 23% yield) was obtained using 1-fluoro-4-nitrobenzene (1.02 g, 7.23 mmol) and 1,4-oxazepane hydrochloride (0.10 g, 7.25 mmol) by the same method as in step B of Preparation Example 1 and step B of Preparation Example 7. 1 H-NMR (400 MHz, DMSO-d6) δ6.50 (m, 4H), 4.36 (brs, 2H), 3.66 (t, 2H), 3.55 (t, 2H), 3.41 (t, 4H), 1.86 (m, 2H)

[0280] Step B: Production of 4-(4-bromophenyl)-1,4-oxazepane To the 4-(1,4-oxazepan-4-yl)aniline (0.32 g, 1.66 mmol) obtained in step A, 3.3 mL of 48% bromate solution was added, and the mixture was cooled to 0°C. 4 mL of NaNO2 solution (5 mmol) was slowly added to the mixture, and the mixture was stirred at room temperature for 15 minutes. After the reaction mixture cooled to 0°C, CuBr (0.36 g, 2.50 mmol) was added, and the mixture was stirred under reflux at 100°C for 2 hours. After the reaction mixture cooled to room temperature, NaOH solution and HCl were added for extraction, and the organic layer was purified by MPLC to obtain the title compound (0.14 g, 33% yield). 1 H-NMR (400 MHz, CDCl3) δ7.27 (d, 2H), 6.58 (d, 2H), 3.81 (m, 2H), 3.67 (m, 2H), 3.58 (m, 4H), 2.01 (m, 2H)

[0281] Manufacturing Example 52: Manufacturing of 2-(4-bromophenyl)-2-azaspiro[3.3]heptane 1,4-Dibromobenzene (0.50 g, 2.12 mmol), 2-Azaspiro[3.3]heptane hydrochloride (0.31 g, 2.33 mmol), and BINAP (0.13 g, 0.21 mmol) were mixed with 10 mL of toluene, and then the mixture was filled with nitrogen gas. Pd2(dba)3 (0.10 g, 0.11 mmol) and Cs2CO3 (1.52 g, 4.66 mmol) were added to the mixture, and the mixture was stirred at 85°C for 16 hours. After the reaction mixture was cooled to room temperature, the solid was removed by Celite, and the filtrate was purified by MPLC to obtain the title compound (0.28 g, 52% yield). 1 H-NMR (400 MHz, DMSO-d6) δ7.27 (d, 2H), 6.35 (d, 2H), 3.74 (s, 4H), 2.15 (t, 4H), 1.81 (m, 2H)

[0282] Manufacturing Example 53: Preparation of 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound (3.10 g, 48% yield) was obtained using 4-morpholinoaniline (3.50 g, 19.6 mmol) and 1-chloro-2,3-difluoro-4-nitrobenzene (3.80 g, 19.6 mmol) by the same method as in step A of Preparation Example 1, step B of Preparation Example 7, and step B of Preparation Example 8. 1 H-NMR (400 MHz, DMSO-d6) δ11.41 (s, 1H), 7.32 (m, 2H), 7.17 (dd, 1H), 7.03 (d, 2H), 6.90 (dd, 1H), 3.77 (m, 4H), 3.18 (m, 4H)

[0283] Manufacturing Example 54: Preparation of 6-chloro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one The title compound (7.2 g, 98% yield) was obtained using 4-morpholinoaniline (4.00 g, 22.4 mmol) and 4-chloro-2-fluoro-1-nitrobenzene (3.94 g, 22.4 mmol) by the same method as in step A of Preparation Example 1, step B of Preparation Example 7, and step B of Preparation Example 8. 1 H-NMR (400 MHz, DMSO-d6) δ11.22 (brs, 1H), 7.35 (d, 2H), 7.06 (4H), 6.82 (d, 1H), 3.77 (m, 4H), 3.18 (m, 4H)

[0284] Manufacturing Example 55: Preparation of 5-(bromomethyl)isoxazole-3-carboxylate methyl ester 5-methylisoxazole-3-carboxylate methyl ester (2.0 g, 14.1 mmol) was mixed with 70 mL of CCl4, N-bromosuccinimide (3.28 g, 18.4 mmol), and azobisbutyronitrile (0.23 g, 1.41 mmol), and the mixture was stirred at 70°C for 16 hours. After removing the solid by filtration, the filtrate was purified by MPLC to obtain the title compound (1.5 g, 48% yield). 1H-NMR (400 MHz, CDCl3) δ6.75 (s, 1H), 4.51 (s, 2H), 4.00 (s, 3H)

[0285] Manufacturing Example 56: Preparation of 2-(bromomethyl)oxazole-4-carboxylate methyl ester Using 2-methyloxazole-4-carboxylate methyl ester (2.0 g, 14.1 mmol), the title compound (1.14 g, 36% yield) was obtained by the same method as in Preparation Example 55. 1 H-NMR (400 MHz, CDCl3) δ8.25 (s, 1H), 4.48 (s, 2H), 3.93 (s, 3H)

[0286] Manufacturing Example 57: Preparation of ethyl 5-(bromomethyl)-2,3-difluorobenzoate The title compound was obtained through the following steps A and B.

[0287] Step A: Preparation of 2,3-difluoro-5-methylbenzoate ethyl ester 2,3-difluoro-5-methylbenzoic acid (2.0 g, 11.6 mmol) was mixed with 23 mL of EtOH and a catalytic amount of sulfuric acid, and the mixture was stirred under reflux for 16 hours. The reaction mixture was poured into ice water, and the resulting solid was dried to obtain the title compound (2.0 g, 86% yield). 1 H-NMR (400 MHz, CDCl3) δ7.47 (m, 1H), 7.15 (m, 1H), 4.40 (q, 2H), 2.34 (s, 3H), 1.41 (t, 3H)

[0288] Step B: Preparation of ethyl 5-(bromomethyl)-2,3-difluorobenzoate Using the 2,3-difluoro-5-methylbenzoate ethyl ester (2.0 g, 9.99 mmol) obtained in step A, the title compound (1.34 g, 48% yield) was obtained by the same method as in Production Example 55. 1H-NMR (400 MHz, CDCl3) δ7.72 (m, 1H), 7.41 (m, 1H), 4.43 (s, 2H), 4.41 (q, 2H), 1.41 (t, 3H)

[0289] Manufacturing Example 58: Preparation of ethyl 3-(bromomethyl)-2,6-difluorobenzoate The title compound was obtained through the following steps A and B.

[0290] Step A: Preparation of 2,6-difluoro-3-methylbenzoate ethyl ester 2,6-difluoro-3-methylbenzoic acid (2.0 g, 11.6 mmol) was mixed with 23 mL of EtOH and a catalytic amount of sulfuric acid, and the mixture was stirred under reflux for 16 hours. The reaction mixture was poured into ice water, and the resulting solid was dried to obtain the title compound (1.80 g, 77% yield). 1 H-NMR (500 MHz, CDCl3) δ7.26 (m, 1H), 6.86 (m, 1H), 4.44 (q, 2H), 2.27 (s, 3H), 1.41 (t, 3H)

[0291] Step B: Preparation of ethyl 3-(bromomethyl)-2,6-difluorobenzoate Using the ethyl 2,6-difluoro-3-methylbenzoate (1.80 g, 9.0 mmol) obtained in step A, the title compound (0.56 g, 22% yield) was obtained by the same method as in production example 55. 1 H-NMR (500 MHz, CDCl3) δ7.48 (m, 1H), 6.92 (m, 1H), 4.47 (s, 2H), 4.43 (q, 2H), 1.40 (t, 3H)

[0292] Manufacturing Example 59: Preparation of 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-5-fluorobenzoate ethyl ester The title compound was obtained through the following steps A and B.

[0293] Step A: Preparation of 3-(1-aminocyclopropyl)-5-fluorobenzoate ethyl hydrochloride 5.0 g, 25.9 mmol of ethyl 3-cyano-5-fluorobenzoate was mixed with 100 mL of Et2O and 20 mL of THF, then cooled to -78°C. Ti(OiPr)4 (10 mL, 34 mmol) and EtMgBr (3.0 M Et2O solution, 20 mL, 60 mmol) were slowly added. The reaction mixture was stirred at room temperature for 1 hour, then cooled to 0°C. BF3-Et2O (6.6 mL, 52 mmol) was slowly added, and the mixture was stirred at room temperature for 1 hour. After the reaction was complete, a 3 M aqueous HCl solution was slowly added, and the organic layer was extracted with HCl. The organic layer was concentrated, and HCl (4 M HCl solution) was added. The resulting solid was dried to obtain the title compound (2.6 g, 38% yield). 1 H-NMR (500 MHz, CDCl3) δ 9.06 (brs, 3H), 7.89 (d, 1H), 7.66 (dd, 1H), 7.47 (dd, 1H), 4.36 (q, 2H), 1.68 (m, 4H), 1.38 (t, 3H)

[0294] Step B: Preparation of 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-5-fluorobenzoate ethyl ester Using the 3-(1-aminocyclopropyl)-5-fluorobenzoate ethyl hydrochloride (1.62 g, 6.2 mmol) and 4-chloro-1-fluoro-2-nitrobenzene (1.0 g, 5.7 mmol) obtained in step A, the title compound (0.12 g, 6% yield) was obtained by the same method as in step A of Production Example 1, step B of Production Example 7, and step B of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ9.38 (brs, 1H), 7.56 (m, 2H), 7.14 (d, 1H), 7.04 (3H), 4.37 (q, 2H), 1.72 (4H), 1.38 (t, 3H)

[0295] Manufacturing Example 60: Preparation of 3-(4-bromophenyl)-8-oxa-3-azabicyclo[3.2.1]octane The title compound (0.11 g, 14% yield) was obtained using (4-bromophenyl)boronic acid (0.66 g, 3.29 mmol) and 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (0.44 g, 3 mmol) in the same manner as in Preparation Example 38. 1 H-NMR (400 MHz, CDCl3) δ7.33 (d, 2H), 6.67 (d, 2H), 4.48 (m, 2H), 3.27 (m, 2H), 2.98 (m, 2H), 1.95 (4H)

[0296] Production Example 61: Production of 1-(4-bromophenyl)-3,3-difluoroazetidine The title compound (0.42 g, 80% yield) was obtained using 1,4-dibromobenzene (0.50 g, 2.12 mmol) and 3,3-difluoroazetidine hydrochloride (0.31 g, 2.33 mmol) by the same method as in Preparation Example 52. 1 H-NMR (400 MHz, DMSO-d6) δ7.38 (d, 2H), 6.53 (d, 2H), 4.25 (t, 4H)

[0297] Manufacturing Example 62: Preparation of 1-(4-bromophenyl)-4,4-difluoropiperidine The title compound (0.075 g, 18% yield) was obtained using (4-bromophenyl)boronic acid (0.30 g, 1.50 mmol) and 4,4-difluoropiperidine (0.22 g, 1.8 mmol) by the same method as in Preparation Example 38. 1 H-NMR (400 MHz, CDCl3) δ7.36 (d, 2H), 6.82 (d, 2H), 3.32 (m, 4H), 2.08 (m, 4H)

[0298] Preparation Example 63: Preparation of 2-(4-bromophenyl)-2,7-diazaspiro[3.5]nonane-7-carboxylate tert-butyl ester The title compound (1.70 g, 70% yield) was obtained using 1,4-dibromobenzene (1.50 g, 6.36 mmol) and the hydrochloride salt of 2,6-diazaspiro[3.5]nonane-7-carboxylate tert-butyl ester (1.84 g, 7.00 mmol) in the same manner as in Preparation Example 52. 1 H-NMR (400 MHz, CDCl3) δ7.28 (d, 2H), 6.31 (d, 2H), 3.59 (s, 4H), 3.39 (m, 4H), 1.75 (m, 4H), 1.46 (s, 9H)

[0299] Manufacturing Example 64: Production of 2-(4-bromophenyl)-1-(3-hydroxyazetidine-1-yl)ethane-1-one 2-(4-bromophenyl)acetic acid (200 mg, 0.93 mmol) and 3-hydroxyazetidine hydrochloride (122 mg, 1.2 mmol) were mixed with 2 mL of DMF, HATU (390 mg, 1.02 mmol), and TEA (0.26 mL, 1.86 mmol), and the mixture was stirred at room temperature for 16 hours. After adding water to the reaction mixture, it was extracted with pharmaceutically acceptable substances and purified by MPLC to obtain the title compound (150 mg, 60% yield). 1 H-NMR (500 MHz, CDCl3) δ7.46 (d, 2H), 7.16 (d, 2H), 4.65 (m, 1H), 4.32 (t, 1H), 4.25 (t, 1H), 4.00 (dd, 1H), 3.88 (dd, 1H), 3.43 (s, 2H), 2.59 (s, 1H)

[0300] Manufacturing Example 65: Preparation of 2-(4-bromophenyl)-1-(4,4-difluoropiperidine-1-yl)ethane-1-one The title compound (102 mg, 69% yield) was obtained using 2-(4-bromophenyl)acetic acid (100 mg, 0.46 mmol) and 4,4-difluoropiperidine (67 mg, 0.56 mmol) by the same method as in Preparation Example 64. 1H-NMR (500 MHz, CDCl3) δ7.48 (d, 2H), 7.14 (d, 2H), 3.76 (m, 2H), 3.72 (s, 2H), 3.55 (m, 2H), 1.96 (m, 2H), 1.79 (m, 2H)

[0301] Manufacturing Example 66: Production of (S)-2-(4-bromophenyl)-1-(3-methylmorpholino)ethane-1-one The title compound (160 mg, 58% yield) was obtained using 2-(4-bromophenyl)acetic acid (200 mg, 0.93 mmol) and (S)-3-morpholine (113 mg, 1.11 mmol) by the same method as in Preparation Example 64. 1 H-NMR (500 MHz, CDCl3) δ7.47 (d, 2H), 7.14 (m, 2H), 4.31 (m, 1H), 3.86 (m, 2H), 3.66 (s, 2H), 3.60 (m, 1H), 3.41 (m, 2H), 3.30 (m, 1H), 1.27 (d, 3H)

[0302] Manufacturing Example 67: Production of (R)-2-(4-bromophenyl)-1-(3-methylmorpholino)ethane-1-one The title compound (160 mg, 58% yield) was obtained using 2-(4-bromophenyl)acetic acid (200 mg, 0.93 mmol) and (R)-3-morpholine (113 mg, 1.11 mmol) by the same method as in Preparation Example 64. 1 H-NMR (500 MHz, CDCl3) δ7.47 (d, 2H), 7.14 (m, 2H), 4.30 (m, 1H), 3.86 (m, 2H), 3.66 (s, 2H), 3.62 (m, 1H), 3.38 (m, 2H), 3.31 (m, 1H), 1.27 (d, 3H)

[0303] Manufacturing Example 68: Production of (R)-2-(4-bromophenyl)-1-(2-methylmorpholino)ethane-1-one The title compound (162 mg, 58% yield) was obtained using 2-(4-bromophenyl)acetic acid (200 mg, 0.93 mmol) and (R)-2-morpholine (113 mg, 1.11 mmol) by the same method as in Preparation Example 64. 1 H-NMR (500 MHz, CDCl3) δ7.47 (d, 2H), 7.14 (d, 2H), 4.45 (dd, 1H), 3.82 (dd, 1H), 3.68 (s, 2H), 3.61 (t, 1H), 3.47 (m, 1H), 3.33 (m, 1H), 3.19 (m, 1H), 2.85 (m, 1H), 2.82 (s, 3H), 1.16 (3H)

[0304] Manufacturing Example 69: Production of (S)-2-(4-bromophenyl)-1-(2-methylmorpholino)ethane-1-one The title compound (134 mg, 48% yield) was obtained using 2-(4-bromophenyl)acetic acid (200 mg, 0.93 mmol) and (S)-2-morpholine (113 mg, 1.11 mmol) by the same method as in Preparation Example 64. 1 H-NMR (500 MHz, CDCl3) δ7.47 (d, 2H), 7.14 (d, 2H), 4.45 (dd, 1H), 3.82 (dd, 1H), 3.68 (s, 2H), 3.61 (t, 1H), 3.47 (m, 1H), 3.33 (m, 1H), 3.19 (m, 1H), 2.85 (m, 1H), 2.82 (s, 3H), 1.16 (3H)

[0305] Manufacturing Example 70: Preparation of 4-bromo-N,N-dimethylbenzenesulfonamide 4-bromobenzenesulfonyl chloride (200 mg, 0.78 mmol) was mixed with 15 mL of THF, dimethylamine (0.79 mL, 1.56 mmol), and DIPEA (0.28 mL, 1.56 mmol), and the mixture was stirred at room temperature. After the reaction was complete, the solution was washed with water, and the organic layer was dried to obtain the title compound (196 mg, 95% yield). 1H-NMR (500 MHz, CDCl3) δδ 7.71 (d, 2H), 7.67 (d, 2H), 2.73 (s, 6H)

[0306] Manufacturing Example 71: Preparation of 4-bromo-N-cyclopropylbenzenesulfonamide The title compound (244 mg, 90% yield) was obtained using 4-bromobenzenesulfonyl chloride (250 mg, 0.98 mmol) and cyclopropanamine (112 mg, 2.0 mmol) by the same method as in Preparation Example 70. 1 H-NMR (500 MHz, CDCl3) δ7.80 (d, 2H), 7.70 (d, 2H), 4.85 (brs, 1H), 2.28 (m, 1H), 0.64 (m, 2H), 0.63 (m, 2H)

[0307] Manufacturing Example 72: Preparation of 4-((4-bromophenyl)sulfonyl)morpholine The title compound (273 mg, 91% yield) was obtained using 4-bromobenzenesulfonyl chloride (250 mg, 0.98 mmol) and morpholine (0.34 mL, 2.0 mmol) by the same method as in Preparation Example 70. 1 H-NMR (500 MHz, CDCl3) δ7.73 (d, 2H), 7.64 (d, 2H), 3.77 (m, 4H), 3.02 (m, 4H)

[0308] Manufacturing Example 73: Preparation of 4-bromo-N-(cyclobutylmethyl)benzenesulfonamide The title compound (140 mg, 78% yield) was obtained using 4-bromobenzenesulfonyl chloride (150 mg, 0.59 mmol) and cyclobutylmethanamine (75 mg, 0.88 mmol) by the same method as in Preparation Example 70. 1H-NMR (500 MHz, CDCl3) δ7.74 (d, 2H), 7.68 (d, 2H), 4.41 (t, 1H), 2.99 (t, 2H), 2.42 (m, 1H), 2.03 (m, 1H), 1.91 (m, 1H), 1.87 (m, 1H), 1.62 (m, 2H)

[0309] Manufacturing Example 74: Manufacturing of 1-((4-bromophenyl)sulfonyl)piperidine The title compound (149 mg, 83% yield) was obtained using 4-bromobenzenesulfonyl chloride (150 mg, 0.59 mmol) and piperidine (100 mg, 1.17 mmol) by the same method as in Preparation Example 70. 1 H-NMR (500 MHz, CDCl3) δ7.69 (d, 2H), 7.64 (d, 2H), 3.00 (m, 4H), 1.66 (m, 4H), 1.45 (m, 2H)

[0310] Manufacturing Example 75: Production of 1-((4-bromophenyl)sulfonyl)pyrrolidine The title compound (114 mg, 67% yield) was obtained using 4-bromobenzenesulfonyl chloride (150 mg, 0.59 mmol) and pyrrolidine (62.6 mg, 0.88 mmol) by the same method as in Preparation Example 70. 1 H-NMR (500 MHz, CDCl3) δ7.72 (d, 2H), 7.69 (d, 2H), 3.26 (m, 4H), 1.80 (m, 4H)

[0311] Manufacturing Example 76: Preparation of 3-(1-(6-chloro-2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridine-3-yl)cyclopropyl)methyl benzoate The title compound was obtained through the following steps A and B.

[0312] Step A: Preparation of 3-(1-((5-chloro-3-nitropyridine-2-yl)amino)cyclopropyl)methyl benzoate The title compound (2.34 g, 84% yield) was obtained using 5-chloro-2-fluoro-3-nitropyridine (1.56 g, 8.86 mmol) and methyl 3-(1-aminocyclopropyl)benzoate (1.54 g, 8.05 mmol) by the same method as in step A of Preparation Example 1. 1 H-NMR (500 MHz, CDCl3) δ8.55 (brs, 1H), 8.45 (s, 1H), 8.39 (s, 1H), 8.04 (s, 1H), 7.98 (d, 1H), 7.56 (d, 1H), 7.44 (t, 1H), 3.93 (s, 3H), 1.74 (m, 4H).

[0313] Step B: Preparation of 3-(1-(2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using the 3-(1-((5-chloro-3-nitropyridine-2-yl)amino)cyclopropyl)methyl benzoate (2.32 g, 6.68 mmol) obtained in step A, the title compound (0.90 g, 39% yield) was obtained by the same method as in step B of production example 7 and step B of production example 8. 1 H-NMR (500 MHz, CDCl3) δ8.15 (s, 1H), 8.05 (s, 1H), 7.97 (d, 1H), 7.67 (d, 1H), 7.42 (t, 1H), 7.36 (m, 1H), 3.89 (s, 3H), 1.72 (m, 4H).

[0314] Manufacturing Example 77: Preparation of 3-(1-(6-chloro-2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridine-3-yl)cyclopropyl)-2-fluorobenzoate methyl ester The title compound (0.26 g, 32% yield) was obtained using 5-chloro-2-fluoro-3-nitropyridine (0.40 g, 2.28 mmol) and methyl 3-(1-aminocyclopropyl)-2-fluorobenzoate (0.43 g, 2.07 mmol) by the same method as in step A of Preparation Example 1, step B of Preparation Example 7, and step B of Preparation Example 8. 1 H-NMR (500 MHz, CDCl3) δ10.10 (brs, 1H), 8.10 (s, 1H), 7.98 (t, 1H), 7.84 (t, 1H), 7.35 (s, 1H), 7.16 (t, 1H), 3.90 (s, 3H), 1.73 (m, 4H).

[0315] Manufacturing Example 78: Preparation of 3-(1-(6-chloro-2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridine-3-yl)cyclopropyl)-5-fluorobenzoate methyl ester The title compound was obtained through the following steps A and B.

[0316] Step A: Preparation of methyl 3-(1-aminocyclopropyl)-5-fluorobenzoate Using methyl 3-cyano-5-fluorobenzoate (12.0 g, 67.0 mmol), the title compound (4.5 g, 32% yield) was obtained by the same method as in steps A and B of Preparation Example 4. 1 H-NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.51 (m, 1H), 7.19 (m, 1H), 3.91 (s, 3H), 1.69 (s, 2H), 1.14 (m, 2H), 1.03 (m, 2H)

[0317] Step B: Preparation of 3-(1-(6-chloro-2-oxo-1,2-dihydro-3H-imidazo[4,5-b]pyridine-3-yl)cyclopropyl)-5-fluorobenzoate methyl ester Using 5-chloro-2-fluoro-3-nitropyridine (1.8 g, 8.6 mmol) and 3-(1-aminocyclopropyl)-5-fluorobenzoate methyl ester (1.6 g, 9.5 mmol) obtained in step A, the title compound (1.1 g, 81% yield) was obtained by the same method as in step A of Production Example 1, step B of Production Example 7, and step B of Production Example 8. 1 H-NMR (400 MHz, CDCl3) δ 8.02 (d, 1H), 7.74 (m, 1H), 7.52 (m, 1H), 7.32 (d, 1H), 7.19 (m, 1H), 3.86 (s, 3H), 1.70 (m, 4H)

[0318] [Examples] Example 1: Production of 3-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0319] Step A: Preparation of 3-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (30 mg, 0.095 mmol) obtained in step C of the above-mentioned Production Example 1 was mixed with 1.5 mL of DCM, followed by the addition of phenylboronic acid (23 mg, 0.189 mmol), cupric acetate (48 mg, 0.265 mmol), and TEA (0.04 mL, 0.284 mmol). After the reaction was completed, saturated aqueous solution of K2CO3 was added and the mixture was stirred for 20 minutes. The precipitate was removed by Celite, and the organic layer extracted with RINKAN was washed with water. The separated organic layer was dried over anhydrous MgSO4, and after vacuum distillation, it was purified by chromatography to obtain the title compound (27 mg, 72% yield). 1 H NMR (500 MHz, CDCl3) δ 8.08 (brs, 1H), 8.01 (d, 1H), 7.58 (m, 5H), 7.45 (m, 2H), 7.10 (s, 1H), 7.04 (d, 1H), 6.84 (d, 1H), 5.19 (s, 2H), 3.94 (s, 3H).

[0320] Step B: Production of 3-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid To the 3-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (14 mg, 0.035 mmol) obtained in step A, 1.5 mL of a mixed solution of THF / MeOH / water (7 / 2 / 1) was added. LiOH (1.7 mg, 0.070 mmol) was added, and the mixture was stirred at room temperature for 12 hours. Once the reaction was complete, the solution was diluted with SiO2. The aqueous solution obtained by extraction with 1 N sodium hydroxide solution was adjusted to pH 3 with 1 N hydrochloric acid solution and then extracted with SiO2. The separated organic layer was dried over anhydrous MgSO4, and after vacuum distillation, it was purified by chromatography to obtain the title compound (13 mg, 98% yield). 1 H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H), 8.03 (d, 1H), 7.61 (d, 1H), 7.54 (m, 4H), 7.44 (m, 2H), 7.08 (d, 1H), 7.03 (dd, 1H), 6.82 (d, 1H), 5.18 (s, 2H)

[0321] Example 2: Production of 3-((5-chloro-2-oxo-3-(4-propylphenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0322] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-propylphenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1 was mixed with 6 mL of DCM, followed by the addition of (4-propylphenyl)boronic acid (104 mg, 0.631 mmol), cupric acetate (172 mg, 0.947 mmol), and TEA (0.132 mL, 0.947 mmol). After the reaction was completed, saturated aqueous solution of K2CO3 was added and the mixture was stirred for 20 minutes. The solid was then removed by Celite. After washing the filtrate with water, the organic layer was separated and dried over Na2SO4. The solid was filtered, and the filtrate was purified by vacuum distillation and then MPLC to obtain the title compound (120 mg, 87% yield). MS [M+H] = 435 (M+1) 1H NMR (500 MHz, CD3OD) δ 8.08 (s, 1H), 8.00 (d, 1H), 7.59 (d, 1H), 7.45 (d, 3H), 7.38 (d, 2H), 7.08 (s, 1H), 7.03 (d, 1H), 6.82 (d, 1H), 5.18 (s, 2H), 3.94 (s, 3H), 2.68 (t, 2H), 1.72 (m, 2H), 1.02 (t, 3H)

[0323] Step B: Production of 3-((5-chloro-2-oxo-3-(4-propylphenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid To the 3-((5-chloro-2-oxo-3-(4-propylphenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (120 mg, 0.276 mmol) obtained in step A, 2 mL of THF and 1 N LiOH (2 mL, 2.00 mmol) were added. After stirring at room temperature for 16 hours, 1 N hydrochloric acid aqueous solution was added. The organic layer was separated and dried over Na2SO4. After removing the solid, the filtrate was distilled under reduced pressure to obtain the title compound (110 mg, 95% yield). MS [M+H] = 421 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ7.93 (s, 1H), 7.82 (d, 1H), 7.58 (d, 1H), 7.45 (m, 3H), 7.36 (d, 2H), 7.22 (d, 1H), 7.11 (dd, 1H), 6.96 (d, 1H), 5.17 (s, 2H), 2.60 (t, 2H), 1.61 (td, 2H), 0.90 (t, 3H)

[0324] Example 3: Production of 3-((5-chloro-3-(4-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0325] Step A: Preparation of 3-((5-chloro-3-(4-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.070 g, 0.22 mmol) and (4-fluorophenyl)boronic acid (0.062 g, 0.44 mmol) obtained in the above-mentioned Production Example 1, the title compound (0.090 g, 99% yield) was obtained by the same method as in step A of Example 2. 1 H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.98 (m, 1H), 7.58-7.50 (3H), 7.43 (t, 1H), 7.26 (m, 2H), 7.06-7.02 (2H), 6.82 (d, 1H), 5.16 (s, 2H), 3.92 (s, 3H)

[0326] Step B: Production of 3-((5-chloro-3-(4-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.090 g, 0.22 mmol) obtained in step A, the title compound (0.020 g, 23% yield) was obtained by the same method as in step B of Example 2. 1 H NMR (500 MHz, CDCl3) δ 8.10 (s, 1H), 8.04 (dd, 1H), 7.61 (d, 1H), 7.52 (m, 2H), 7.46 (t, 1H), 7.23 (2H), 7.04 (2H), 6.84 (dd, 1H), 5.18 (s, 2H)

[0327] Example 4: Production of 3-((5-chloro-2-oxo-3-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0328] Step A: Preparation of methyl 3-((5-chloro-2-oxo-3-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and (4-(trifluoromethyl)phenyl)boronic acid (120 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (105 mg, 72% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 461 (M+1) 1 H NMR (400 MHz, CD3OD) δδ 8.04 (s, 1H), 7.97 (d, 1H), 7.82 (d, 2H), 7.72 (d, 2H), 7.55 (d, 1H), 7.42 (t, 1H), 7.12 (s, 1H), 7.06 (d, 1H), 6.83 (d, 1H), 5.15 (s, 2H), 3.90 (s, 3H)

[0329] Step B: Production of 3-((5-chloro-2-oxo-3-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (105 mg, 0.228 mmol) obtained in step A, the title compound (90 mg, 88% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 447 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ7.94 (d, 2H), 7.91 (s, 1H), 7.85 (s, 1H), 7.82 (d, 2H), 7.60 (d, 1H), 7.45 (t, 1H), 7.26 (d, 1H), 7.20 (d, 1H), 7.16 (dd, 1H), 5.19 (s, 2H)

[0330] Example 5: Production of 3-((5-chloro-3-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0331] Step A: Preparation of 3-((5-chloro-3-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and (4-methoxyphenyl)boronic acid (96 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (73 mg, 55% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 423 (M+1) 1 H NMR (400 MHz, CD3OD) δδ8.04 (s, 1H), 7.96 (d, 1H), 7.55 (d, 1H), 7.42 (m, 3H), 7.05 (d, 2H), 7.00 (d, 2H), 6.78 (d, 1H), 5.14 (s, 2H), 3.90 (s, 3H), 3.86 (s, 3H)

[0332] Step B: Preparation of 3-((5-chloro-3-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-methoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (73 mg, 0.173 mmol) obtained in step A, the title compound (62 mg, 88% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 409 (M+1) 1H NMR (400 MHz, DMSO-D6) δ7.93 (s, 1H), 7.82 (dt, 1H), 7.58 (d, 1H), 7.45 (m, 3H), 7.20 (d, 1H), 7.09 (m, 3H), 6.89 (d, 1H), 5.16 (s, 2H), 3.79 (s, 3H)

[0333] Example 6: Preparation of 3-((3-([1,1'-biphenyl]-3-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0334] Step A: Preparation of 3-((3-([1,1'-biphenyl]-3-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and [1,1'-biphenyl]-3-ylboronic acid (125 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (65 mg, 44% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 469 (M+1) 1 H NMR (400 MHz, CD3OD) δ8.06 (s, 1H), 7.97 (d, 1H), 7.75 (m, 1H), 7.63 (m, 4H), 7.57 (d, 1H), 7.45 (m, 5H), 7.11 (d, 1H), 7.02 (dd, 1H), 6.81 (d, 1H), 5.17 (s, 2H), 3.90 (s, 3H)

[0335] Step B: Preparation of 3-((3-([1,1'-biphenyl]-3-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((3-([1,1'-biphenyl]-3-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (65 mg, 0.139 mmol) obtained in step A, the title compound (62 mg, 98% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 455 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ7.96 (s, 1H), 7.83 (m, 2H), 7.75 (dt, 1H), 7.70 (m, 2H), 7.65 (t, 1H), 7.60 (d, 1H), 7.55 (dt, 1H), 7.45 (m, 3H), 7.37 (m, 1H), 7.24 (d, 1H), 7.14 (dd, 1H), 7.07 (d, 1H), 5.19 (s, 2H)

[0336] Example 7: Production of 3-((5-chloro-3-(4'-chloro-[1,1'-biphenyl]-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0337] Step A: Preparation of 3-((5-chloro-3-(4'-chloro-[1,1'-biphenyl]-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and (4'-chloro-[1,1'-biphenyl]-4-yl)boronic acid (147 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (66 mg, 42% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 504 (M+1) 1H NMR (400 MHz, CD3OD) δ8.05 (s, 1H), 7.97 (d, 1H), 7.72 (d, 2H), 7.61 (d, 2H), 7.55 (t, 3H), 7.44 (t, 3H), 7.13 (d, 1H), 7.02 (dd, 1H), 6.82 (d, 1H), 5.16 (s, 2H), 3.91 (s, 3H)

[0338] Step B: Preparation of 3-((5-chloro-3-(4'-chloro-[1,1'-biphenyl]-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the methyl 3-((5-chloro-3-(4'-chloro-[1,1'-biphenyl]-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (66 mg, 0.131 mmol) obtained in step A, the title compound (55 mg, 86% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 490 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ7.95 (s, 1H), 7.84 (m, 3H), 7.75 (dd, 2H), 7.66 (dd, 2H), 7.59 (d, 1H), 7.53 (dd, 2H), 7.45 (t, 1H), 7.24 (d, 1H), 7.14 (dd, 1H), 7.08 (d, 1H), 5.19 (s, 2H)

[0339] Example 8: Production of 3-((5-chloro-2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0340] Step A: Preparation of 3-((5-chloro-2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and p-trilboronic acid (86 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (86 mg, 67% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 407 (M+1) 1 H NMR (400 MHz, CD3OD) δδ8.07 (s, 1H), 8.00 (d, 1H), 7.58 (d, 1H), 7.44 (m, 3H), 7.37 (m, 2H), 7.06 (s, 1H), 7.03 (d, 1H), 6.82 (d, 1H), 5.18 (s, 2H), 3.94 (s, 3H), 2.46 (s, 3H)

[0341] Step B: Preparation of 3-((5-chloro-2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (86 mg, 0.211 mmol) obtained in step A, the title compound (83 mg, 100% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 393 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ7.98 (s, 1H), 7.87 (d, 1H), 7.63 (d, 1H), 7.50 (d, 1H), 7.46 (d, 2H), 7.40 (d, 2H), 7.26 (d, 1H), 7.16 (d, 1H), 6.98 (s, 1H), 5.21 (s, 2H), 2.42 (d, 3H)

[0342] Example 9: Production of 3-((3-(benzo[d][1,3]dioxol-5-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0343] Step A: Preparation of 3-((3-(benzo[d][1,3]dioxol-5-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and benzo[d][1,3]dioxol-5-ylboronic acid (105 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (58 mg, 42% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 437 (M+1) 1 H NMR (500 MHz, CD3OD) δδ8.07 (s, 1H), 8.00 (d, 1H), 7.57 (d, 1H), 7.45 (t, 1H), 7.00 (m, 5H), 6.81 (d, 1H), 6.09 (s, 2H), 5.17 (s, 2H), 3.94 (s, 3H)

[0344] Step B: Preparation of 3-((3-(benzo[d][1,3]dioxol-5-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((3-(benzo[d][1,3]dioxol-5-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (58 mg, 0.132 mmol) obtained in step A, the title compound (55 mg, 99% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 423 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ7.97 (d, 1H), 7.86 (m, 1H), 7.61 (m, 1H), 7.53 (m, 1H), 7.24 (d, 1H), 7.18 (s, 1H), 7.15 (d, 1H), 7.09 (m, 1H), 7.03 (d, 1H), 6.96 (d, 1H), 6.14 (s, 2H), 5.22 (s, 2H)

[0345] Example 10: Production of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0346] Step A: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and (4-(dimethylamino)phenyl)boronic acid (104 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (78 mg, 57% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 436 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 7.99 (d, 1H), 7.58 (d, 1H), 7.44 (t, 1H), 7.35 (d, 2H), 7.00 (d, 2H), 6.85 (d, 2H), 6.79 (d, 1H), 5.17 (s, 2H), 3.94 (s, 3H), 3.04 (s, 6H)

[0347] Step B: Production of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(dimethylamino)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (78 mg, 0.178 mmol) obtained in step A, the title compound (69 mg, 92% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 422 (M+1) 1H NMR (500 MHz, DMSO-D6) δ7.96 (s, 1H), 7.87 (d, 1H), 7.61 (d, 1H), 7.49 (m, 1H), 7.33 (d, 2H), 7.23 (d, 1H), 7.12 (d, 1H), 6.87 (m, 3H), 5.20 (s, 2H), 2.96 (s, 6H)

[0348] Example 11: Preparation of 3-((5-chloro-3-(4-isobutylamidophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0349] Step A: Preparation of 3-((5-chloro-3-(4-isobutylamidophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.316 mmol) and (4-isobutylamidophenyl)boronic acid (131 mg, 0.631 mmol) obtained in the above-mentioned Production Example 1, the title compound (78 mg, 52% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 478 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.00 (d, 1H), 7.73 (d, 2H), 7.57 (d, 1H), 7.48 (m, 4H), 7.04 (d, 2H), 6.83 (d, 1H), 5.18 (s, 2H), 3.94 (s, 3H), 2.56 (m, 1H), 1.30 (d, 6H)

[0350] Step B: Preparation of 3-((5-chloro-3-(4-isobutylamidophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-isobutylamidophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (78 mg, 0.163 mmol) obtained in step A, the title compound (51 mg, 67% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 464 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ10.08 (s, 1H), 7.97 (s, 1H), 7.87 (d, 1H), 7.82 (d, 2H), 7.62 (d, 1H), 7.50 (d, 3H), 7.26 (d, 1H), 7.15 (d, 1H), 7.02 (d, 1H), 5.21 (s, 2H), 2.63 (td, 1H), 1.14 (d, 6H)

[0351] Example 12: Preparation of 3-((3-(4-(tert-butyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0352] Step A: Preparation of 3-((3-(4-(tert-butyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester (60 mg, 0.189 mmol) and (4-(tert-butyl)phenyl)boronic acid (68 mg, 0.379 mmol) obtained in the above-mentioned Production Example 1, the title compound (78 mg, 92% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 449 (M+1) 1H NMR (400 MHz, CD3OD) δ8.04 (s, 1H), 7.96 (d, 1H), 7.54 (dd, 3H), 7.43 (m, 2H), 7.41 (m, 1H), 7.07 (s, 1H), 6.99 (d, 1H), 6.79 (d, 1H), 5.15 (s, 2H), 3.90 (s, 3H), 1.36 (s, 9H)

[0353] Step B: Preparation of 3-((3-(4-(tert-butyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((3-(4-(tert-butyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (78 mg, 0.174 mmol) obtained in step A, the title compound (66 mg, 87% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 435 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ7.92 (s, 1H), 7.82 (d, 1H), 7.57 (m, 3H), 7.45 (m, 3H), 7.22 (d, 1H), 7.12 (dd, 1H), 6.98 (d, 1H), 5.17 (s, 2H), 1.31 (s, 9H)

[0354] Example 13: Preparation of 3-((5-chloro-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0355] Step A: Preparation of 3-((5-chloro-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (150 mg, 0.474 mmol) and (4-hydroxyphenyl)boronic acid (131 mg, 0.947 mmol) obtained in the above-mentioned Production Example 1, the title compound (131 mg, 68% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 409 (M+1) 1 H NMR (400 MHz, CD3OD) δ8.05 (s, 1H), 7.97 (d, 1H), 7.55 (d, 1H), 7.43 (t, 1H), 7.25 (d, 1H), 7.23 (d, 1H), 7.01 (d, 1H), 6.94 (d, 1H), 6.85 (d, 2H), 6.81 (d, 1H), 6.68 (s, 1H), 5.16 (s, 2H), 3.91 (s, 3H)

[0356] Step B: Production of 3-((5-chloro-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.122 mmol) obtained in step A, the title compound (40 mg, 84% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 395 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ9.81 (s, 1H), 7.92 (s, 1H), 7.82 (m, 1H), 7.57 (d, 1H), 7.44 (t, 1H), 7.30 (td, 2H), 7.19 (d, 1H), 7.09 (dd, 1H), 6.89 (td, 2H), 6.86 (d, 1H), 5.15 (s, 2H)

[0357] Example 14: Production of 3-((5-chloro-3-(4-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0358] Step A: Preparation of 3-((5-chloro-3-(4-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-isopropoxyphenyl)boronic acid (56.8 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (50 mg, 70% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 451 (M+1) 1 H NMR (400 MHz, CD3OD) δ8.03 (s, 1H), 7.96 (dd, 1H), 7.55 (d, 1H), 7.39 (m, 3H), 7.03 (s, 1H), 7.00 (m, 3H), 6.78 (d, 1H), 5.14 (s, 2H), 4.59 (m, 1H), 3.90 (s, 3H), 1.37 (d, 6H)

[0359] Step B: Production of 3-((5-chloro-3-(4-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.111 mmol) obtained in step A, the title compound (40 mg, 83% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 437 (M+1) 1H NMR (500 MHz, DMSO-D6) δ13.08 (s, 1H), 7.97 (s, 1H), 7.87 (d, 1H), 7.63 (d, 1H), 7.50 (d, 3H), 7.47 (d, 2H), 7.27 (d, 1H), 7.16 (d, 1H), 7.01 (s, 1H), 5.22 (s, 2H), 3.00 (m, 1H), 1.27 (d, 6H)

[0360] Example 15: Preparation of 3-((3-([1,1'-biphenyl]-4-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0361] Step A: Preparation of 3-((3-([1,1'-biphenyl]-4-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and [1,1'-biphenyl]-4-ylboronic acid (62.5 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (52 mg, 70% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 469 (M+1) 1 H NMR (400 MHz, CD3OD) δ8.06 (s, 1H), 7.99 (d, 1H), 7.75 (d, 2H), 7.63 (m, 4H), 7.58 (d, 1H), 7.47 (t, 2H), 7.43 (d, 1H), 7.38 (d, 1H), 7.13 (d, 1H), 7.02 (d, 1H), 6.81 (d, 1H), 5.17 (s, 2H), 3.91 (s, 3H)

[0362] Step B: Preparation of 3-((3-([1,1'-biphenyl]-4-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((3-([1,1'-biphenyl]-4-yl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (52 mg, 0.110 mmol) obtained in step A, the title compound (42 mg, 84% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 455 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ13.08 (s, 1H), 8.00 (s, 1H), 7.89 (m, 3H), 7.76 (d, 2H), 7.70 (d, 2H), 7.65 (d, 1H), 7.51 (m, 3H), 7.42 (t, 1H), 7.29 (d, 1H), 7.18 (d, 1H), 7.12 (s, 1H), 5.24 (s, 2H)

[0363] Example 16: Preparation of 3-((3-(4-butylphenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0364] Step A: Preparation of 3-((3-(4-butylphenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-butylphenyl)boronic acid (56.2 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (55 mg, 77% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 449 (M+1) 1H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.00 (d, 1H), 7.58 (d, 1H), 7.45 (m, 3H), 7.37 (d, 2H), 7.08 (s, 1H), 7.03 (d, 1H), 6.82 (d, 1H), 5.18 (s, 2H), 3.94 (s, 3H), 2.71(t, 2H), 1.67 (m, 2H), 1.43 (m, 2H), 0.98 (t, 3H)

[0365] Step B: Production of 3-((3-(4-butylphenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 3-((3-(4-butylphenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (54.6 mg, 0.122 mmol) obtained in step A, the title compound (46 mg, 87% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 435 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ13.07 (s, 1H), 7.98 (s, 1H), 7.87 (d, 1H), 7.63 (d, 1H), 7.49 (t, 3H), 7.41 (d, 2H), 7.27 (d, 1H), 7.16 (d, 1H), 7.00 (s, 1H), 5.22 (s, 2H), 2.67 (t, 2H), 1.62 (m, 2H), 1.36 (td, 2H), 0.93 (t, 3H)

[0366] Example 17: Manufacture of 3-((5-chloro-3-(4-isopropylphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0367] Step A: Preparation of 3-((5-chloro-3-(4-isopropylphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-isopropylphenyl)boronic acid (51.8 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (55 mg, 80% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 435 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.00 (d, 1H), 7.59 (d, 1H), 7.46 (m, 3H), 7.42 (m, 2H), 7.09 (s, 1H), 7.03 (d, 1H), 6.82 (d, 1H), 5.18 (s, 2H), 3.94 (s, 3H), 3.01 (m, 1H), 1.33 (d, 6H)

[0368] Step B: Production of 3-((5-chloro-3-(4-isopropylphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-isopropylphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (55 mg, 0.126 mmol) obtained in step A, the title compound (49 mg, 92% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 421 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ13.08 (s, 1H), 7.97 (s, 1H), 7.87 (d, 1H), 7.63 (d, 1H), 7.50 (d, 3H), 7.47 (d, 2H), 7.27 (d, 1H), 7.16 (d, 1H), 7.01 (s, 1H), 5.22 (s, 2H), 3.00 (m, 1H), 1.27 (d, 6H)

[0369] Example 18: Preparation of 3-((5-chloro-3-(4-(2-hydroxypropan-2-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0370] Step A: Preparation of 3-((5-chloro-3-(4-(2-hydroxypropan-2-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-(2-hydroxypropan-2-yl)phenyl)boronic acid (56.8 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (52 mg, 73% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 451 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.08 (s, 1H), 8.00 (d, 1H), 7.70 (d, 2H), 7.59 (d, 1H), 7.53 (d, 2H), 7.45 (t, 1H), 7.10 (s, 1H), 7.06 (d, 1H), 6.83 (d, 1H), 5.18 (s, 2H), 3.93 (s, 3H), 1.66 (s, 6H)

[0371] Step B: Preparation of 3-((5-chloro-3-(4-(2-hydroxypropan-2-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(2-hydroxypropan-2-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (52 mg, 0.115 mmol) obtained in step A, the title compound (27 mg, 54% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 437 (M+1) 1H NMR (500 MHz, DMSO-D6) δ7.95 (s, 1H), 7.85 (d, 1H), 7.68 (d, 2H), 7.57 (d, 1H), 7.51 (d, 2H), 7.46 (t, 1H), 7.26 (d, 1H), 7.16 (d, 1H), 7.01 (s, 1H), 5.20 (s, 2H), 1.49 (s, 6H)

[0372] Example 19: Preparation of 3-((5-chloro-3-(4-(methylsulfonamide)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0373] Step A: Preparation of 3-((5-chloro-3-(4-(methylsulfonamide)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-(methylsulfonamide)phenyl)boronic acid (67.9 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (25 mg, 32% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 486 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ9.98 (s, 1H), 7.96 (s, 1H), 7.84 (d, 1H), 7.61 (d, 1H), 7.51 (m, 2H), 7.47 (d, 1H), 7.34 (d, 2H), 7.21 (d, 1H), 7.12 (d, 1H), 6.99 (s, 1H), 5.17 (s, 2H), 3.8 (s, 3H), 3.04 (s, 3H)

[0374] Step B: Preparation of 3-((5-chloro-3-(4-(methylsulfonamide)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(methylsulfonamide)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (24 mg, 0.049 mmol) obtained in step A, the title compound (8 mg, 33% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 472 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ7.94 (s, 1H), 7.84 (d, 1H), 7.59 (m, 2H), 7.50 (d, 1H), 7.41 (m, 3H), 7.25 (d, 1H), 7.17 (d, 1H), 7.05 (s, 1H), 5.19 (s, 2H), 3.09 (s, 3H)

[0375] Example 20: Production of 3-((5-chloro-3-(4-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0376] Step A: Preparation of 3-((5-chloro-3-(4-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-ethoxyphenyl)boronic acid (52.4 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (49 mg, 71% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 437 (M+1) 1H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.00 (d, 1H), 7.58 (d, 1H), 7.43 (d, 3H), 7.07 (d, 2H), 7.01 (m, 2H), 6.81 (d, 1H), 5.17 (s, 2H), 4.12 (q, 2H), 3.94 (s, 3H), 1.48 (t, 3H)

[0377] Step B: Production of 3-((5-chloro-3-(4-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (49 mg, 0.112 mmol) obtained in step A, the title compound (41 mg, 86% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 423 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ13.08 (s, 1H), 7.98 (s, 1H), 7.87 (d, 1H), 7.62 (d, 1H), 7.49 (dd, 3H), 7.25 (d, 1H), 7.13 (m, 3H), 6.93 (s, 1H), 5.21 (s, 2H), 4.11 (q, 2H), 1.38 (t, 3H)

[0378] Example 21: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0379] Step A: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester (50 mg, 0.158 mmol) and (4-(dimethylcarbamoyl)phenyl)boronic acid (60.9 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (52 mg, 71% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 464 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.08 (s, 1H), 8.01 (d, 1H), 7.64 (m, 4H), 7.59 (d, 1H), 7.46 (t, 1H), 7.14 (s, 1H), 7.07 (d, 1H), 6.86 (d, 1H), 5.19 (s, 2H), 3.94 (s, 3H), 3.18 (s, 3H), 3.08 (s, 4H)

[0380] Step B: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (51 mg, 0.110 mmol) obtained in step A, the title compound (41 mg, 83% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 450 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ13.08 (s, 1H), 7.99 (s, 1H), 7.87 (d, 1H), 7.64 (m, 5H), 7.50 (t, 1H), 7.29 (d, 1H), 7.19 (d, 1H), 7.16 (s, 1H), 5.23 (s, 2H), 3.01 (d, 6H)

[0381] Example 22: Preparation of 3-((5-chloro-3-(4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0382] Step A: Preparation of 3-((5-chloro-3-(4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-(methylcarbamoyl)phenyl)boronic acid (56.5 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (55 mg, 77% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 450 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.01 (d, 1H), 7.98 (d, 2H), 7.68 (d, 2H), 7.58 (d, 1H), 7.46 (t, 1H), 7.15 (s, 1H), 7.08 (d, 1H), 6.86 (d, 1H), 6.23 (d, 1H), 5.19 (s, 2H), 3.94 (s, 3H), 3.08 (d, 3H)

[0383] Step B: Production of 3-((5-chloro-3-(4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (55 mg, 0.122 mmol) obtained in step A, the title compound (46 mg, 85% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 436 (M+1) 1H NMR (500 MHz, DMSO-D6) δ13.07 (s, 1H), 8.59 (s, 1H), 8.03 (d, 2H), 7.99 (s, 1H), 7.87 (d, 1H), 7.72 (d, 2H), 7.64 (d, 1H), 7.50 (t, 1H), 7.29 (d, 1H), 7.19 (d, 1H), 7.14 (s, 1H), 5.23 (s, 2H), 2.83 (d, 3H)

[0384] Example 23: Preparation of 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)carbamoyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0385] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)carbamoyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and (4-((2,2,2-trifluoroethyl)carbamoyl)phenyl)boronic acid (78 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (75 mg, 92% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 518 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.09 (s, 1H), 8.03 (m, 3H), 7.73 (m, 2H), 7.59 (d, 1H), 7.48 (t, 1H), 7.16 (s, 1H), 7.09 (d, 1H), 6.88 (t, 1H), 6.55 (s, 1H), 5.20 (s, 2H), 4.19 (m, 2H), 3.92 (s, 3H)

[0386] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)carbamoyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)carbamoyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (55 mg, 0.106 mmol) obtained in step A, the title compound (44 mg, 81% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 504 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ9.27 (t, 1H), 8.10 (d, 2H), 7.96 (s, 1H), 7.85 (d, 1H), 7.75 (d, 2H), 7.55 (d, 1H), 7.43 (t, 1H), 7.27 (d, 1H), 7.18 (m, 2H), 5.21 (s, 2H), 4.14 (m, 2H)

[0387] Example 24: Preparation of 3-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0388] Step A: Preparation of 3-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.99 g, 2.85 mmol) and 3-(bromomethyl)benzoate methyl ester (0.65 g, 2.85 mmol) obtained in the above-mentioned Production Example 11 were dissolved in 15 mL of AN, and then K2CO3 (0.78 g, 5.68 mmol) was added and the mixture was stirred at 70°C for 16 hours. After the reaction was completed, the solid was filtered and the filtrate was purified by MPLC to obtain the title compound (0.90 g, 64% yield). 1H-NMR (400 MHz, DMSO-d6) δ8.01 (d, 1H), 7.89 (dd, 1H), 7.65 (dd, 1H), 7.53 (t, 1H), 7.39 (d, 2H), 7.22 (dd, 1H), 7.10 (d, 1H), 7.05 (d, 2H), 5.21 (s, 2H), 3.85 (s, 3H), 3.77 (m, 4H), 3.19 (m, 4H)

[0389] Step B: Preparation of 3-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid To the 3-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.90 g, 1.8 mmol) obtained in step A, 30 mL of EtOH, 10 mL of THF, and 5.4 mL of 1N NaOH aqueous solution were added, and the mixture was stirred at room temperature for 16 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure and the pH was adjusted to 3 using 1N hydrochloric acid aqueous solution. The precipitated solid was filtered and dried to obtain the title compound (0.84 g, 96% yield). MS [M+H] = 482 (M+1) 1 H-NMR (400 MHz, DMSO-d6) δ7.94 (d, 1H), 7.84 (dd, 1H), 7.55 (dd, 1H), 7.40 (t, 1H), 7.37 (d, 2H), 7.24 (dd, 1H), 7.08 (d, 1H), 7.05 (d, 2H), 5.18 (s, 2H), 3.77 (m, 4H), 3.19 (m, 4H)

[0390] Example 25: Production of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0391] Step A: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(4-(dimethylamino)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one (3.25 g, 10.6 mmol) and 3-(bromomethyl)benzoate methyl ester (2.43 g, 10.6 mmol) obtained in the above-mentioned Production Example 8, the title compound (3.93 g, 81% yield) was obtained by the same method as in step A of Example 24. 1 H-NMR (400 MHz, DMSO-d6) δ8.00 (d, 1H), 7.89 (dd, 1H), 7.63 (dd, 1H), 7.52 (t, 1H), 7.33 (d, 2H), 7.24 (dd, 1H), 7.10 (d, 1H), 6.80 (d, 2H), 5.21 (s, 2H), 3.85 (s, 3H), 2.97 (s, 6H)

[0392] Step B: Production of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(dimethylamino)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (3.62 g, 7.98 mmol) obtained in step A, the title compound (2.26 g, 64% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 440 (M+1) 1 H-NMR (400 MHz, DMSO-d6) δ7.97 (d, 1H), 7.86 (dd, 1H), 7.50 (dd, 1H), 7.48 (t, 1H), 7.31 (d, 2H), 7.22 (dd, 1H), 7.20 (d, 1H), 6.80 (d, 2H), 5.20 (s, 2H), 2.97 (s, 6H)

[0393] Example 26: Manufacture of 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)sulfonamide)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A, B, C, and D.

[0394] Step A: Preparation of 3-((5-chloro-3-(4-nitrophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.157 g, 0.496 mmol) and (4-nitrophenyl)boronic acid (0.165 g, 0.991 mmol) obtained in the above-mentioned Production Example 1, the title compound (0.22 g, 99% yield) was obtained by the same method as in step A of Example 2. 1 H-NMR (400 MHz, CDCl3) δ8.43 (d, 2H), 8.05 (d, 1H), 8.00 (dd, 1H), 7.84 (d, 2H), 7.56 (dd, 1H), 7.46 (t, 1H), 7.20 (d, 1H), 7.10 (dd, 1H), 6.87 (d, 1H), 5.17 (s, 2H), 3.92 (s, 3H)

[0395] Step B: Preparation of 3-((3-(4-aminophenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-3-(4-nitrophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.22 g, 0.50 mmol) obtained in step A, the title compound (0.19 g, 95% yield) was obtained by the same method as in step B of production example 7. 1H-NMR (400 MHz, CDCl3) δ8.05 (d, 1H), 7.97 (dd, 1H), 7.55 (dd, 1H), 7.42 (t, 1H), 7.26 (d, 2H), 7.00 (2H), 6.81 (d, 2H), 6.77 (d, 1H), 5.15 (s, 2H), 3.92 (s, 3H), 3.85 (brs, 2H)

[0396] Step C: Preparation of 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)sulfonamide)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 3-((3-(4-aminophenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.086 g, 0.21 mmol) obtained in step B above was dissolved in 2 mL of DCM, cooled to 0°C, and 2,2,2-trifluoroethane-1-sulfonyl chloride (0.046 g, 0.25 mmol) and DIPEA (0.037 mL, 0.21 mmol) were added in sequence, and the mixture was stirred for 1 hour. After the reaction was completed, water and DCM were added, and the organic layer was separated. The organic layer was dried and purified by MPLC to obtain the title compound (0.01 g, 9% yield). 1 H-NMR (400 MHz, CDCl3) δ8.16 (d, 1H), 8.00 (dd, 1H), 7.57 (3H), 7.44 (3H), 7.07 (2H), 7.00 (dd, 1H), 5.17 (s, 2H), 3.92 (s, 3H), 3.86 (q, 2H)

[0397] Step D: Production of 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)sulfonamide)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(4-((2,2,2-trifluoroethyl)sulfonamide)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.01 g, 0.018 mmol) obtained in step C, the title compound (0.007 g, 77% yield) was obtained by the same method as in step B of Example 24. 1H-NMR (400 MHz, CDCl3) δ8.17 (d, 1H), 8.03 (dd, 1H), 7.61 (2H), 7.45 (3H), 7.08 (2H), 6.85 (dd, 1H), 5.18 (s, 2H), 4.13 (q, 3H)

[0398] Example 27: Preparation of 3-((5-chloro-3-(4-(cyclobutylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0399] Step A: Preparation of 3-((5-chloro-3-(4-(cyclobutylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 3-((5-chloro-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.122 mmol) obtained in step A of Example 13 was mixed with 2 mL of DMF, then (bromomethyl)cyclobutane (36.5 mg, 0.245 mmol) and K2CO3 (33.8 mg, 0.245 mmol) were added, and the mixture was stirred at 80°C for 16 hours. The solid was filtered, and the filtrate was purified by MPLC to obtain the title compound (41 mg, 70% yield). MS [M+H] = 477 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.00 (d, 1H), 7.58 (d, 1H), 7.44 (m, 3H), 7.08 (d, 2H), 7.02 (m, 2H), 6.81 (d, 1H), 5.18 (s, 2H), 4.01 (d, 2H), 3.94 (s, 3H), 2.84 (m, 1H), 2.21 (m, 2H), 1.99 (m, 4H)

[0400] Step B: Preparation of 3-((5-chloro-3-(4-(cyclobutylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(cyclobutylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (41 mg, 0.086 mmol) obtained in step A, the title compound (35 mg, 88% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 463 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ13.02 (s, 1H), 7.98 (s, 1H), 7.87 (d, 1H), 7.63 (d, 1H), 7.47 (m, 3H), 7.25 (d, 1H), 7.12 (m, 3H), 6.93 (d, 1H), 5.21 (s, 2H), 4.03 (d, 2H), 2.76 (m, 1H), 2.13 (m, 2H), 1.92 (m, 4H)

[0401] Example 28: Preparation of 3-((5-chloro-2-oxo-3-(4-(2-oxopiperidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0402] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(2-oxopiperidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 1-(4-((5-chloro-2-nitrophenyl)amino)phenyl)piperidine-2-one (0.12 g, 0.35 mmol) obtained in the above-mentioned Production Example 16, the title compound (0.055 g, 32% yield) was obtained by the same method as in step B of Production Example 8 and step A of Example 24. 1H-NMR (400 MHz, CDCl3) δ8.05 (d, 1H), 7.98 (dd, 1H), 7.58 (d, 2H), 7.55 (dd, 1H), 7.47 (d, 2H), 7.42 (dd, 1H), 7.16 (d, 1H), 7.03 (dd, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 3.92 (s, 2H), 3.73 (m, 2H), 2.611 (m, 2H), 1.99 (m, 4H)

[0403] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-(2-oxopiperidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(4-(2-oxopiperidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.055 g, 0.11 mmol) obtained in step A, the title compound (0.020 g, 37% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 476 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.09 (d, 1H), 8.02 (dd, 1H), 7.59 (3H), 7.47 (d, 2H), 7.45 (t, 1H), 7.16 (d, 1H), 7.03 (dd, 1H), 6.82 (d, 1H), 5.16 (s, 2H), 3.71 (m, 2H), 2.63 (m, 2H), 1.99 (m, 4H)

[0404] Example 29: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A, B, and C.

[0405] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester 3-((5-chloro-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (70 mg, 0.171 mmol) obtained in step A of Example 13 was mixed with 3 mL of toluene, then TEA (26.0 mg, 0.257 mmol) and trifluoromethanesulfonic anhydride (72.5 mg, 0.257 mmol) were added at 0°C and the mixture was stirred at room temperature for 2 hours. After the reaction was completed, water was added and the organic layer was separated and dried over Na2SO4. The solid was filtered, and the filtrate was distilled under reduced pressure and purified by MPLC to obtain the title compound (82 mg, 89% yield). MS [M+H] = 541 (M+1)

[0406] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 3-((5-chloro-2-oxo-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (80 mg, 0.148 mmol) obtained in step A above was mixed with 3 mL of toluene, then pyrrolidine (12.6 mg, 0.177 mmol), Cs2CO3 (72.3 mg, 0.222 mmol), Xantphos (17.1 mg, 0.030 mmol), and Pd2(dba)3 (27.1 mg, 0.030 mmol) were added, and the mixture was stirred at 95°C for 16 hours. After the reaction was completed, the solid was filtered, and the filtrate was purified by MPLC to obtain the title compound (39 mg, 57% yield). MS [M+H] = 462 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 7.99 (d, 1H), 7.58 (d, 1H), 7.45 (t, 1H), 7.32 (d, 2H), 6.98 (s, 2H), 6.78 (d, 1H), 6.68 (d, 2H), 5.17 (s, 2H), 3.94 (s, 3H), 3.36 (m, 4H), 2.07 (m, 4H)

[0407] Step C: Production of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (38 mg, 0.082 mmol) obtained in step B, the title compound (12 mg, 33% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 448 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ7.96 (s, 1H), 7.87 (d, 1H), 7.62 (d, 1H), 7.50 (d, 1H), 7.30 (d, 2H), 7.23 (d, 1H), 7.12 (d, 1H), 6.84 (s, 1H), 6.68 (d, 2H), 5.20 (s, 2H), 3.30 (m, 4H), 2.00 (m, 4H)

[0408] Example 30: Preparation of 3-((5-chloro-3-(4-(cyclobutylmethoxy)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A, B, and C.

[0409] Step A: Preparation of 3-((5-chloro-3-(3-fluoro-4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (99 mg, 0.311 mmol) and (3-fluoro-4-hydroxyphenyl)boronic acid (97 mg, 0.622 mmol) obtained in the above-mentioned Production Example 1, the title compound (77 mg, 58% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 427 (M+1) 1H NMR (500 MHz, CD3OD) δ8.08 (s, 1H), 8.01 (d, 1H), 7.58 (d, 1H), 7.47 (t, 1H), 7.28 (d, 4H), 7.19 (d, 1H), 7.12 (t, 1H), 7.06 (d, 1H), 7.03 (s, 1H), 6.85 (d, 1H), 6.11 (s, 1H), 5.19 (s, 2H), 3.94 (d, 3H)

[0410] Step B: Preparation of 3-((5-chloro-3-(4-(cyclobutylmethoxy)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate To the 3-((5-chloro-3-(3-fluoro-4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (40 mg, 0.094 mmol) obtained in step A, 2 mL of DMF was added, followed by the addition of (bromomethyl)cyclobutane (27.9 mg, 0.187 mmol) and K2CO3 (25.9 mg, 0.187 mmol), and the mixture was stirred at 80°C for 16 hours. The solid was filtered, and the filtrate was purified by MPLC to obtain the title compound (39 mg, 83% yield). MS [M+H] = 495 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.03 (s, 1H), 7.97 (d, 1H), 7.55 (d, 1H), 7.41 (t, 1H), 7.30 (m, 1H), 7.24 (m, 1H), 7.21 (d, 1H), 7.09 (t, 1H), 7.01 (m, 2H), 6.79 (d, 1H), 5.13 (s, 2H), 4.05 (d, 2H), 3.90 (s, 3H), 2.84 (m, 1H), 2.17 (m, 2H), 1.93 (m, 4H)

[0411] Step C: Preparation of 3-((5-chloro-3-(4-(cyclobutylmethoxy)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(cyclobutylmethoxy)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (41 mg, 0.083 mmol) obtained in step B, the title compound (32 mg, 80% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 481 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ13.05 (s, 1H), 7.99 (s, 1H), 7.87 (d, 1H), 7.62 (d, 1H), 7.53 (d, 1H), 7.49 (t, 1H), 7.36 (m, 2H), 7.25 (d, 1H), 7.16 (d, 1H), 7.03 (s, 1H), 5.20 (s, 2H), 4.12 (d, 2H), 2.78 (m, 1H), 2.10 (m, 2H), 1.90 (m, 4H)

[0412] Example 31: Manufacture of 3-(1-(5-chloro-2-oxo-3-(4-propylphenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)chloropropyl)methyl benzoate (52 mg, 0.152 mmol) obtained in Production Example 3 and (4-propylphenyl)boronic acid, the title compound (32 mg, 47% yield) was obtained by the same method as in Steps A and B of Example 1. 1 H NMR (400 MHz, MeOD) δ 7.82 (m, 2H), 7.35 (m, 6H), 7.23 (m, 1H), 7.12 (m, 1H), 6.96 (m, 1H), 2.67 (m, 2H), 1.70 (m, 6H), 0.97 (t, 3H)

[0413] Example 32: Preparation of 3-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-4-fluorobenzoic acid [ka] Using 6-chloro-1-phenyl-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.123 mmol) obtained in Production Example 5 and methyl 3-(bromomethyl)-4-fluorobenzoate, the title compound (25 mg, 51% yield) was obtained by the same method as in step A of Production Example 21 and the same method as in step B of Example 1. 1 H NMR (400 MHz, MeOD) δ 7.99 (m, 2H), 7.54 (m, 5H), 7.21 (t, 1H), 7.10 (m, 2H), 7.00 (m, 1H), 5.25 (s, 2H).

[0414] Example 33: Preparation of 3-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 6-chloro-1-phenyl-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.123 mmol) obtained in Production Example 5 and methyl 3-(aminomethyl)-2-fluorobenzoate, the title compound (21 mg, 43% yield) was obtained by the same method as in step A of Production Example 21 and the same method as in step B of Example 1. 1 H NMR (400 MHz, MeOD) δ 7.84 (t, 1H), 7.56 (m, 2H), 7.50 (m, 4 H), 7.21 (t, 1H), 7.12 (m, 2H), 7.00 (m, 1H), 5.25 (s, 2H).

[0415] Example 34: Preparation of 3-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-5-fluorobenzoic acid [ka] Using 6-chloro-1-phenyl-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.123 mmol) obtained in Production Example 5 and methyl 3-(bromomethyl)-5-fluorobenzoate, the title compound (13 mg, 27% yield) was obtained by the same method as in step A of Production Example 21 and the same method as in step B of Example 1. 1 H NMR (400 MHz, MeOD) δ 7.83 (t, 1H), 7.56 (m, 6H), 7.32 (m, 1H), 7.11 (m, 2H), 7.04 (m, 1H), 5.21 (s, 2H).

[0416] Example 35: Preparation of 5-((5-chloro-2-oxo-3-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 6-chloro-1-phenyl-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.123 mmol) obtained in Production Example 5 and methyl 5-(bromomethyl)-2-fluorobenzoate, the title compound (31 mg, 64% yield) was obtained by the same method as in step A of Production Example 21 and the same method as in step B of Example 1. 1 H NMR (400 MHz, MeOD) δ 7.93 (t, 1H), 7.54 (m, 6H), 7.17 (m, 1 H), 7.11 (m, 2H), 7.00 (m, 1H), 5.17 (s, 2H)

[0417] Example 36: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A, B, and C.

[0418] Step A: Preparation of methyl 3-((5-chloro-3-(3-fluoro-4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester (50 mg, 0.158 mmol) and (3-fluoro-4-(methylcarbamoyl)phenyl)boronic acid (62.2 mg, 0.316 mmol) obtained in the above-mentioned Production Example 1, the title compound (55 mg, 75% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 468 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.18 (t, 1H), 8.07 (s, 1H), 8.02 (d, 1H), 7.58 (d, 1H), 7.51 (m, 2H), 7.47 (d, 1H), 7.23 (s, 1H), 7.11 (d, 1H), 6.88 (d, 1H), 5.18 (s, 2H), 4.00 (s, 3H), 3.94 (s, 3H)

[0419] Step B: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate To the 3-((5-chloro-3-(3-fluoro-4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (55 mg, 0.118 mmol) obtained in step A, 2 mL of THF was added, and then NaOH (7.05 mg, 0.294 mmol) was added and the mixture was stirred at 0°C for 30 minutes. Then, iodomethane (25.0 mg, 0.176 mmol) was added and the mixture was stirred at room temperature for 16 hours. After the reaction was completed, water was added to separate the organic layer, which was dried over Na2SO4. The solid was removed, and the filtrate was distilled under reduced pressure and separated by MPLC to obtain the title compound (29 mg, 51% yield). MS [M+H] = 482 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.01 (d, 1H), 7.62 (t, 1H), 7.58 (d, 1H), 7.48 (m, 2H), 7.43 (d, 1H), 7.18 (s, 1H), 7.09 (d, 1H), 6.86 (d, 1H), 5.18 (s, 2H), 3.94 (s, 3H), 3.19 (s, 3H), 3.04 (s, 3H)

[0420] Step C: Production of 3-((5-chloro-3-(4-(dimethylcarbamoyl)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(dimethylcarbamoyl)-3-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (29 mg, 0.060 mmol) obtained in step B, the title compound (18 mg, 64% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 468 (M+1) 1H NMR (500 MHz, DMSO-D6) δ7.99 (s, 1H), 7.87 (d, 1H), 7.63 (m, 3H), 7.56 (d, 1H), 7.50 (t, 1H), 7.27 (m, 2H), 7.20 (d, 1H), 5.22 (s, 2H), 3.04 (s, 3H), 2.93 (s, 3H)

[0421] Example 37: Manufacture of 3-((6-chloro-3-(4-(dimethylamino)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] Using 5-chloro-1-(4-(dimethylamino)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.050 g, 0.16 mmol) and 3-(bromomethyl)benzoate methyl ester (0.037 g, 0.16 mmol) obtained in the above-mentioned Production Example 27, the title compound (0.020 g, 28% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 440 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.05 (2H), 7.60 (dd, 1H), 7.48 (t, 1H), 7.32 (d, 2H), 6.85 (dd, 1H), 6.78 (d, 2H), 6.71 (d, 1H), 5.15 (s, 2H), 3.01 (s, 6H)

[0422] Example 38: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (50 mg, 0.149 mmol) obtained in step C of the above-mentioned Production Example 2, and (4-(dimethylcarbamoyl)phenyl)boronic acid, the title compound (43 mg, 62% yield) was obtained by the same method as in steps A and B of the above-mentioned Example 1. 1 H NMR (500 MHz, MeOD) δ 8.27(m, 1H), 7.89 (m, 1H), 7.72 (m, 3H), 7.57 (m, 1H), 7.22 (m, 4H), 5.30 (s, 2H), 3.10 (d, 6H)

[0423] Example 39: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (50 mg, 0.149 mmol) obtained in step C of the above-mentioned Production Example 2, and (4-(dimethylamino)phenyl)boronic acid, the title compound (39 mg, 60% yield) was obtained by the same method as in steps A and B of the above-mentioned Example 1. 1 H NMR (500 MHz, MeOD) δ 7.90 (t, 1H), 7.55 (t, 1H), 7.26 (m, 3H), 7.13 (m, 2H), 6.93 (m, 3H), 5.28 (s, 2H), 3.04 (s, 6H)

[0424] Example 40: Preparation of 3-((5-chloro-3-(4-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (50 mg, 0.149 mmol) obtained in step C of the above-mentioned Production Example 2, and (4-isopropoxyphenyl)boronic acid, the title compound (35 mg, 52% yield) was obtained by the same method as in steps A and B of the above-mentioned Example 1. 1 H NMR (500 MHz, MeOD) δ 7.90 (t, 1H), 7.56 (t, 1H), 7.42 (d, 2H), 7.25 (t, 1H), 7.12 (m, 4H), 6.97 (s, 1H), 5.28 (s, 2H), 4.71 (m, 1H), 1.38 (d, 6H).

[0425] Example 41: Preparation of 3-((5-chloro-3-(4-(methylsulfonamide)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (50 mg, 0.149 mmol) obtained in step C of the above-mentioned Production Example 2, and 4-(methylsulfonamide)phenyl)boronic acid, the title compound (31 mg, 43% yield) was obtained by the same method as in steps A and B of the above-mentioned Example 1. 1 H NMR (500 MHz, MeOD) δ 7.90 (t, 1H), 7.53 (m, 5H), 7.25 (t, 1H), 7.15 (m, 2H), 7.05 (s, 1H), 5.28 (s, 2H), 3.07 (s, 3H)

[0426] Example 42: Preparation of 3-((5-chloro-3-(4-(cyclopropylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0427] Step A: Preparation of 3-((5-chloro-3-(4-(cyclopropylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-3-(4-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (70 mg, 0.171 mmol) and (bromomethyl)cyclopropane (46.2 mg, 0.342 mmol) obtained in step A of Example 13, the title compound (47 mg, 59% yield) was obtained by the same method as in step A of Example 27. MS [M+H] = 463 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.00 (d, 1H), 7.56 (d, 1H), 7.42 (m, 3H), 7.08 (d, 2H), 7.01 (m, 2H), 6.81 (d, 1H), 5.17 (s, 2H), 3.94 (s, 3H), 3.88 (d, 2H), 1.33 (m, 1H), 0.70 (m, 2H), 0.41 (m, 2H)

[0428] Step B: Preparation of 3-((5-chloro-3-(4-(cyclopropylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(cyclopropylmethoxy)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (41 mg, 0.089 mmol) obtained in step A, the title compound (39 mg, 98% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 449 (M+1) 1H NMR (400 MHz, DMSO-D6) δ7.98 (s, 1H), 7.81 (d, 1H), 7.58 (d, 1H), 7.42 (m, 3H), 7.20 (d, 1H), 7.08 (m, 3H), 6.87 (s, 1H), 5.15 (s, 2H), 3.85 (d, 2H), 1.22 (m, 1H), 0.55 (m, 2H), 0.31 (m, 2H)

[0429] Example 43: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0430] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(4-(piperidine-1-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (100.0 mg, 0.28 mmol) obtained in the above-mentioned Production Example 22 and methyl 3-(bromomethyl)benzoate, the title compound (62.1 mg, 44% yield) was obtained by the same method as in step A of Production Example 1. MS [M+H] = 504 (M+1) 1 H NMR (500 MHz, CDCl3) δ8.05 (s, 1H), 7.99 (d, 1H), 7.62 (m, 5H), 7.45 (m, 1H), 7.11 (s, 1H), 7.05 (d, 1H), 6.84 (d, 1H), 5.16 (s, 2H), 3.92 (s, 3H), 3.74 (m, 2H), 3.48 (m, 2H), 1.71 (m, 4H), 1.56 (m, 2H)

[0431] Step B: Production of 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the methyl 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (62.0 mg, 0.12 mmol) obtained in step A, the title compound (54.4 mg, 90% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 490 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.10 (s, 1H), 8.04 (d, 1H), 7.61 (m, 5H), 7.48 (t, 1H), 7.11 (s, 1H), 7.06 (d, 1H), 6.85 (s, 1H) 5.18 (s, 2H), 3.75 (m, 2H), 3.42 (m, 2H), 1.71 (m, 4H), 1.56 (m, 2H)

[0432] Example 44: Preparation of 3-((5-chloro-3-(4-(morpholine-4-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0433] Step A: Preparation of 3-((5-chloro-3-(4-(morpholine-4-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(4-(morpholine-4-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (100.0 mg, 0.28 mmol) obtained in the above-mentioned Production Example 23 and methyl 3-(bromomethyl)benzoate, the title compound (96.9 mg, 69% yield) was obtained by the same method as in step A of Production Example 1. MS [M+H] = 506 (M+1) 1H NMR (500 MHz, CDCl3) δ8.05 (s, 1H), 7.99 (d, 1H), 7.65 (m, 4H), 7.57 (d, 1H), 7.45 (m, 1H), 7.11 (s, 1H), 7.06 (d, 1H), 6.84 (d, 1H), 5.16 (s, 2H), 3.91 (s, 3H), 3.80-3.45 (m, 8H)

[0434] Step B: Preparation of 3-((5-chloro-3-(4-(morpholine-4-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(morpholine-4-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (96.0 mg, 0.19 mmol) obtained in step A, the title compound (78.4 mg, 84% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 492 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.10 (1, 1H), 8.05 (d, 1H), 7.65 (m, 5H), 7.48 (m, 1H), 7.12 (s, 1H), 7.07 (d, 1H), 6.86 (d, 1H), 5.18 (s, 2H), 3.80-3.49 (m, 8H)

[0435] Example 45: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0436] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(4-(pyrrolidine-1-carbonyl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (55.0 mg, 0.16 mmol) obtained in the above-mentioned Production Example 24 and methyl 3-(bromomethyl)benzoate, the title compound (68.0 mg, 86% yield) was obtained by the same method as in step A of Production Example 1. MS [M+H] = 490 (M+1) 1 H NMR (500 MHz, CDCl3) δ8.05 (s, 1H), 7.99 (d, 1H), 7.73 (d, 2H), 7.62 (d, 2H), 7.57 (t, 1H), 7.11 (s, 1H), 7.05 (d, 1H), 6.83 (d, 1H), 5.16 (d, 2H), 3.92 (s, 3H), 3.70 (t, 2H), 3.52 (t, 2H), 2.00 (m, 2H), 1.93 (m, 2H)

[0437] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (68.0 mg, 0.14 mmol) obtained in step A, the title compound (63.6 mg, 96% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 476 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.10 (s, 2H), 8.04 (d, 1H), 7.74 (d, 2H), 7.63 (m, 3H), 7.47 (m, 1H), 7.11 (s, 1H), 7.06 (d, 1H), 6.85 (d, 1H), 5.18 (s, 2H), 3.71 (t, 2H), 3.52 (t, 2H), 2.01 (m, 2H), 1.93 (m, 2H)

[0438] Example 46: Preparation of 4-(3-(3-carboxybenzyl)-6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)-3-fluorobenzoic acid [ka] The title compound was obtained through the following steps A and B.

[0439] Step A: Preparation of 3-((5-chloro-3-(2-fluoro-4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester (150 mg, 0.474 mmol) and (2-fluoro-4-(methylcarbamoyl)phenyl)boronic acid (187 mg, 0.947 mmol) obtained in the above-mentioned Production Example 1, the title compound (25 mg, 11% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 468 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.19 (d, 2H), 7.91 (t, 1H), 7.64 (d, 3H), 7.20 (t, 1H), 7.13 (m, 2H), 7.03 (d, 1H), 5.22 (s, 2H), 3.97 (s, 3H), 1.64 (s, 3H)

[0440] Step B: Preparation of 4-(3-(3-carboxybenzyl)-6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)-3-fluorobenzoic acid Using the 3-((5-chloro-3-(2-fluoro-4-(methylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (12 mg, 0.025 mmol) obtained in step A, the title compound (10 mg, 91% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 441 (M+1) 1H NMR (500 MHz, DMSO-D6) δ7.98 (m, 3H), 7.86 (m, 2H), 7.63 (d, 1H), 7.50 (t, 1H), 7.30 (d, 1H), 7.20 (d, 1H), 7.03 (s, 1H), 5.24 (s, 2H)

[0441] Example 47: Preparation of 3-((5-chloro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0442] Step A: Preparation of 3-((5-chloro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-3-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.092 mmol) and morpholine (8.05 mg, 0.092 mmol) obtained in step A of Example 29, the title compound (17 mg, 38% yield) was obtained by the same method as in step B of Example 29. MS [M+H] = 478 (M+1) 1 H NMR (500 MHz, CD3OD) δ8.07 (s, 1H), 8.00 (d, 1H), 7.65 (m, 1H), 7.59 (d, 1H), 7.51 (1H), 7.46 (m, 2H), 7.06 (d, 2H), 7.01 (s, 1H), 6.80 (d, 1H), 5.17 (s, 2H), 3.94 (s, 3H), 3.92 (m, 4H), 3.25 (m, 4H)

[0443] Step B: Preparation of 3-((5-chloro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 3-((5-chloro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (16 mg, 0.033 mmol) obtained in step A, the title compound (5 mg, 32% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 464 (M+1) 1 H NMR (500 MHz, DMSO-D6) 7.95 (s, 1H), 7.85 (d, 1H), 7.58 (d, 1H), 7.46 (t, 1H), 7.40 (d, 2H), 7.23 (d, 1H), 7.12 (m, 3H), 6.91 (s, 1H), 5.19 (s, 2H), 3.78 (m, 4H), 3.20 (m, 4H)

[0444] Example 48: Preparation of 5-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.086 mmol) obtained in step D of the above-mentioned Production Example 11, the title compound (21 mg, 70% yield) was obtained by the same method as in step C of the above-mentioned Production Example 7 and the same method as in step B of the above-mentioned Example 1. 1 H NMR (500 MHz, MeOD) δ 7.95 (m, 1H), 7.59 (m, 1H), 7.39 (m, 2H), 7.19 (m, 2H), 7.12 (m, 2H), 7.00 (m, 1H), 5.19 (s, 2H), 3.88 (m, 4H), 3.26 (m, 4H)

[0445] Example 49: Preparation of 3-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-5-fluorobenzoic acid [ka] Using 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.086 mmol) obtained in step D of the above-mentioned Production Example 11 and methyl 3-(bromomethyl)-5-fluorobenzoate, the title compound (17 mg, 55% yield) was obtained by the same method as in step C of the above-mentioned Production Example 7 and step B of the above-mentioned Example 1. 1 H NMR (500 MHz, CDCl3) δ 7.85 (s, 1H), 7.63 (d, 1H), 7.37 (d, 3H), 7.17 (t, 1H), 7.10 (d, 1H), 6.96 (d, 1H), 5.22 (s, 2H), 3.85 (m, 4H), 3.23 (m, 4H).

[0446] Example 50: Preparation of 3-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-4-fluorobenzoic acid [ka] Using 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.086 mmol) obtained in step D of the above-mentioned Production Example 11 and methyl 3-(bromomethyl)-4-fluorobenzoate, the title compound (26 mg, 72% yield) was obtained by the same method as in step C of the above-mentioned Production Example 7 and step B of the above-mentioned Example 1. 1H NMR (500 MHz, CDCl3) δ 8.01 (m, 2H), 7.36 (d, 2H), 7.26 (t, 1H), 7.18 (t, 1H), 7.10 (d, 2H), 6.96 (d, 1H), 5.26 (s, 2H), 3.85 (m, 4H), 3.24 (m, 4H)

[0447] Example 51: Preparation of 3-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.086 mmol) obtained in step D of the above-mentioned Production Example 11 and methyl 3-(bromomethyl)-2-fluorobenzoate, the title compound (25 mg, 67% yield) was obtained by the same method as in step C of the above-mentioned Production Example 7 and step B of the above-mentioned Example 1. 1 H NMR (500 MHz, MeOD) δ 7.83 (m, 1H), 7.50 (m, 1H), 7.36 (d, 3H), 7.19 (m, 2H), 7.07 (d, 1H), 6.98 (d, 1H), 5.25 (s, 2H), 3.86 (m, 4H), 3.24 (m, 4H)

[0448] Example 52: Preparation of 6-((5-chloro-4-fluoro-3-(4-morpholinophenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)picolinic acid [ka] Using 6-chloro-7-fluoro-1-(4-morpholinophenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (30 mg, 0.086 mmol) obtained in step D of the above-mentioned Production Example 11 and methyl 6-(bromomethyl)picolinate, the title compound (17 mg, 74% yield) was obtained by the same method as in step C of the above-mentioned Production Example 7 and step B of the above-mentioned Example 1. 1 H NMR (500 MHz, MeOD) δ 8.07 (m, 1H), 7.96 (m, 1H), 7.52 (m, 1H), 7.41 (m, 2H), 7.17 (m, 1H), 7.12 (m, 2H), 7.05 (m, 1H), 5.35 (s, 2H), 3.89 (m, 4H), 3.26 (m, 4H)

[0449] Example 53: Preparation of 3-((5-chloro-4-fluoro-3-(4-(3-hydroxyazetidine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] Using 1-(4-(6-chloro-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)phenyl)azetidine-3-yl acetate (0.04 g, 0.10 mmol) and 3-(bromomethyl)methyl benzoate (0.024 g, 0.10 mmol) obtained in the above-mentioned Production Example 14, the title compound (0.022 g, 44% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 468 (M+1) 1H-NMR (500 MHz, MeOH-d4) δ8.01 (m, 1H), 7.96 (m, 1H), 7.57 (m, 1H), 7.45 (t, 1H), 7.29 (d, 2H), 7.13 (m, 1H), 6.92 (m, 1H), 6.60 (d, 2H), 5.21 (s, 2H), 4.70 (m, 1H), 4.20 (m, 2H), 3.68 (m, 2H)

[0450] Example 54: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0451] Step A: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.075 g, 0.22 mmol) and (4-(dimethylcarbamoyl)phenyl)boronic acid (0.086 g, 0.44 mmol) obtained in the above-mentioned Production Example 15, the title compound (0.095 g, 88% yield) was obtained by the same method as in step A of Example 2. 1 H-NMR (500 MHz, MeOH-d4) δ8.02 (m, 1H), 7.97 (m, 1H), 7.62 (m, 1H), 7.48 (m, 1H), 7.30 (d, 2H), 7.06 (m, 1H), 6.99 (m, 1H), 6.82 (d, 2H), 5.30 (s, 2H), 3.89 (s, 3H), 3.07 (s, 6H)

[0452] Step B: Preparation of 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.095 g, 0.20 mmol) obtained in step A, the title compound (0.020 g, 21% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 468 (M+1) 1 H-NMR (400 MHz, MeOH-d4) δ 8.02 (m, 1H), 7.95 (dd, 1H), 7.68 (m, 4H), 7.58 (dd, 1H), 7.45 (t, 1H), 7.06 (dd, 1H), 6.98 (d, 1H), 5.30 (s, 2H), 3.14 (s, 3H), 3.07 (s, 3H)

[0453] Example 55: Preparation of 3-((5-chloro-3-(4-(methylthio)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] The title compound was obtained through the following steps A and B.

[0454] Step A: Preparation of 3-((5-chloro-3-(4-(methylthio)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (50 mg, 0.15 mmol) and (4-(methylthio)phenyl)boronic acid (38 mg, 0.22 mmol) obtained in the above-mentioned Production Example 2, the title compound (58 mg, 85% yield) was obtained by the same method as in step A of Example 2.

[0455] Step B: Preparation of 3-((5-chloro-3-(4-(methylthio)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid Using 3-((5-chloro-3-(4-(methylthio)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (58 mg, 0.12 mmol) obtained in step A, the title compound (39 mg, 70% yield) was obtained by the same method as in step B of Example 2. 1 H NMR (500 MHz, DMSO-D6) δ 7.76 (t, 1H), 7.48 (m, 3H), 7.41 (d, 2H), 7.17 (m, 2H), 7.14 (d, 1H), 6.98 (s, 1H), 5.17 (s, 2H), 2.50 (s, 3H)

[0456] Example 56: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] The title compound was obtained through the following steps A, B, C, and D.

[0457] Step A: Preparation of 3-((3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (200 mg, 0.60 mmol) and (4-(tert-butoxycarbonylphenyl)boronic acid (265 mg, 1.20 mmol) obtained in the above-mentioned Production Example 2, the title compound (120 mg, 40% yield) was obtained by the same method as in step A of Example 2. 1 H-NMR (500 MHz, CDCl3) δ8.17 (d, 2H), 7.89 (t, 1H), 7.61 (d, 3H), 7.18 (t, 1H), 7.11 (d, 2H), 7.00 (d, 1H), 5.20 (s, 2H), 3.94 (s, 3H), 1.62 (s, 9H)

[0458] Step B: Preparation of 4-(6-chloro-3-(2-fluoro-3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid The 3-((3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (120 mg, 0.23 mmol) obtained in step A above was dissolved in 1 mL of DCM and 1 mL of TFA, and the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction mixture was concentrated under reduced pressure and purified by MPLC to obtain the title compound (105 mg, 98% yield).

[0459] Step C: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester To the 4-(6-chloro-3-(2-fluoro-3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (50 mg, 0.11 mmol) obtained in step B, 2 mL of DMF, pyrrolidine (7.8 mg, 0.11 mmol), HATU (63 mg, 0.16 mmol), and TEA (30 μL, 0.22 mmol) were added, and the mixture was stirred at room temperature for 16 hours. After adding water and RINKAN to the reaction mixture, the organic layer was separated and dried over anhydrous Na2SO4. The mixture was purified by MPLC to obtain the title compound (57 mg, 99% yield). 1 H-NMR (500 MHz, CDCl3) δ7.89 (t, 1H), 7.71 (d, 2H), 7.60 (m, 3H), 7.18 (t, 1H), 7.11 (m, 2H), 7.00 (d, 1H), 5.20 (s, 2H), 3.94 (s, 3H), 3.68 (t, 2H), 3.49 (t, 2H), 1.99 (m, 2H), 1.92 (m, 2H)

[0460] Step D: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid Using 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (57 mg, 0.11 mmol) obtained in step C, the title compound (35 mg, 62% yield) was obtained by the same method as in step B of Example 2. 1 H NMR (400 MHz, DMSO-D6) δ7.78 (t, 1H), 7.68 (d, 2H), 7.62 (d, 2H), 7.52 (t, 1H), 7.20 (m, 3H), 7.11 (s, 1H), 5.20 (s, 2H), 3.45 (m, 4H), 1.82 (m, 4H)

[0461] Example 57: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] The title compound was obtained through the following steps A and B.

[0462] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester Using 4-(6-chloro-3-(2-fluoro-3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (50 mg, 0.11 mmol) and piperidine (14 mg, 0.16 mmol) obtained in step B of Example 56, the title compound (61 mg, 99% yield) was obtained by the same method as in step C of Example 56. 1H-NMR (500 MHz, CDCl3) δ7.89 (t, 1H), 7.62 (t, 1H), 7.57 (m, 4H), 7.18 (t, 1H), 7.01 (m, 2H), 6.74 (m, 1H), 5.20 (s, 2H), 3.94 (s, 3H), 3.74 (br, 2H), 3.41 (br, 2H), 1.70 (br, 4H), 1.55 (br, 2H)

[0463] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid Using 3-((5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (60 mg, 0.11 mmol) obtained in step A, the title compound (46 mg, 78% yield) was obtained by the same method as in step B of Example 2. 1 H-NMR (400 MHz, CDCl3) δ7.95 (t, 1H), 7.66 (t, 1H), 7.58 (m, 4H), 7.19 (t, 1H), 7.10 (m, 2H), 7.01 (d, 1H), 5.20 (s, 2H), 3.75 (br, 2H), 3.40 (br, 2H), 1.70 (br, 2H), 1.55 (br, 2H)

[0464] Example 58: Preparation of 3-((3-(4-(azetidine-1-carbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0465] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (43.6 mg, 0.10 mmol) and azetidine (6.27 mg, 0.11 mmol) obtained in the above-mentioned Production Example 25 were dissolved in DMF and cooled to 0°C. HATU (45.5 mg, 0.12 mmol) and DIPEA (52.3 μL, 0.30 mmol) were added, and the mixture was stirred while increasing the temperature to room temperature. After the reaction was completed, the DMF was removed by vacuum distillation, further diluted with ethyl acetate, and the organic layer was extracted with ethyl acetate and saturated aqueous solution of NH4Cl, and dried over Na2SO4. The solid was filtered, and the filtrate was purified by vacuum distillation and then by MPLC to obtain the title compound (43.0 mg, 90% yield). MS [M+H] = 476 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.99 (d, 1H), 7.83 (d, 2H), 7.63 (d, 2H), 7.56 (d, 1H), 7.45 (t, 1H), 7.12 (s, 1H), 7.06 (d, 1H), 6.84 (d, 1H), 5.16 (s, 2H), 4.37 (m, 2H), 4.27 (m, 2H), 3.91 (s, 3H), 2.40 (m, 2H)

[0466] Step B: Preparation of 3-((3-(4-(azetidine-1-carbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid The 3-((5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (43.0 mg, 0.090 mmol) obtained in step A above was used to obtain the title compound (38.2 mg, 92% yield) in the same manner as in step B of Example 1 above. MS [M+H] = 462 (M+1) 1H NMR (500 MHz, CDCl3) δ 8.09 (s, 1H), 8.04 (d, 1H), 7.84 (d, 2H), 7.64 (m, 3H), 7.48 (t, 1H), 7.13 (s, 1H), 7.07 (d, 1H), 6.85 (d, 1H), 5.18 (s, 2H), 4.37 (m, 2H), 4.28 (m, 2H), 2.40 (m, 2H)

[0467] Example 59: Preparation of 3-((5-chloro-3-(4-(3-methoxypyrrolidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0468] Step A: Preparation of 3-((5-chloro-3-(4-(3-methoxypyrrolidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (43.6 mg, 0.10 mmol) and 3-methoxypyrrolidine (11.10 mg, 0.11 mmol) obtained in the above-mentioned Production Example 25, the title compound (51.2 mg, 99% yield) was obtained by the same method as in step A of Example 58. MS [M+H] = 520 (M+1) 1 H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 8.01 (d, 1H), 7.75 (m, 2H), 7.63 (d, 2H), 7.57 (d, 1H), 7.45 (m, 1H), 7.11 (s, 1H), 7.05 (d, 1H), 6.84 (d, 1H), 5.16 (s, 2H), 4.07 (s, 1H), 3.91 (s, 3H), 3.79 (m, 2H), 3.69 (m, 1H), 3.59 (m, 1H), 3.39 (s, 3H), 2.13 (m, 2H)

[0469] Step B: Preparation of 3-((5-chloro-3-(4-(3-methoxypyrrolidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the methyl 3-((5-chloro-3-(4-(3-methoxypyrrolidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (43.0 mg, 0.090 mmol) obtained in step A, the title compound (38.2 mg, 92% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 506 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.10 (s, 1H), 8.05 (d, 1H), 7.76 (m, 2H), 7.63 (m, 3H), 7.48 (t, 1H), 7.12 (s, 1H), 7.06 (d, 1H), 6.85 (d, 1H) 5.18 (s, 2H), 4.07 (s, 1H), 3.83 (m, 2H), 3.70 (m, 1H), 3.57 (m, 1H), 3.39 (s, 3H), 2.13 (m, 2H)

[0470] Example 60: Preparation of 3-((5-chloro-3-(4-(4-methylpiperazine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0471] Step A: Preparation of 3-((5-chloro-3-(4-(4-methylpiperazine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate The 4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (43.6 mg, 0.10 mmol) and 1-methylpiperazine (11.00 mg, 0.110 mmol) obtained in the above-mentioned Production Example 25 were purified in the same manner as in step A of Example 58 to obtain the title compound (43.3 mg, 83% yield). MS [M+H] = 520 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.99 (d, 1H), 7.63 (m, 4H), 7.57 (d, 1H), 7.45 (t, 1H), 7.11 (s, 1H), 7.06 (d, 1H), 6.84 (d, 1H), 5.16 (s, 2H), 3.91 (s, 3H), 3.84 (m, 2H), 3.53 (m, 2H), 2.53 (m, 2H), 2.41 (m, 2H), 2.35 (s, 3H)

[0472] Step B: Preparation of 3-((5-chloro-3-(4-(4-methylpiperazine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(4-methylpiperazine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (43.3 mg, 0.083 mmol) obtained in step A, the title compound (17.0 mg, 92% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 505 (M+1) 1 H NMR (400 MHz, DMSO-d6) δ 7.97 (s, 1H), 7.87 (d, 1H), 7.70-7.60 (m, 6H), 7.51 (t, 1H), 7.30 (d, 1H), 7.20 (m, 2H), 5.22 (s, 2H), 3.56 (m, 2H), 3.49 (m, 2H), 2.53 (m, 2H), 2.41 (m, 2H), 2.35 (s, 3H)

[0473] Example 61: Preparation of 3-((5-chloro-3-(4-(4-hydroxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0474] Step A: Preparation of 3-((5-chloro-3-(4-(4-hydroxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate 4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (43.6 mg, 0.10 mmol) obtained in the above-mentioned Production Example 25 was dissolved in DCM, cooled to 0°C, and SOCl2 (59.49 mg, 0.50 mmol) and a catalytic amount of DMF were added. The mixture was stirred for 3 hours while increasing the temperature to room temperature. After that, the excess solvent and reactants were removed by reducing the pressure, and the condensed reactants were further dissolved in DCM. The reactants were cooled to 0°C, and 4-hydroxypiperidine (11.13 mg, 0.110 mmol) and TEA (20.24 mg, 0.20 mmol) were added. The mixture was then stirred while increasing the temperature to room temperature. After the reaction was completed, the organic layer was extracted with DCM and saturated aqueous NaCl solution and dried over Na2SO4. The solid was filtered, and the filtrate was purified by vacuum distillation and then MPLC to obtain the title compound (43.1 mg, 91% yield). MS [M+H] = 520 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.99 (m, 1H), 7.63 (m, 4H), 7.57 (m, 1H), 7.45 (t, 1H), 7.11 (s, 1H), 7.05 (d, 1H), 6.84 (d, 1H), 5.16 (s, 2H), 4.21 (m, 1H), 4.02 (m, 1H), 3.92 (s, 3H), 3.77 (m, 1H), 3.44 (m, 2H), 2.02 (m, 2H), 1.65 (m, 2H)

[0475] Step B: Preparation of 3-((5-chloro-3-(4-(4-hydroxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(4-hydroxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (43.1 mg, 0.083 mmol) obtained in step A, the title compound (25.4 mg, 61% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 506 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.09 (s, 1H), 8.04 (d, 1H), 7.62 (m, 5H), 7.48 (d, 1H), 7.12 (s, 1H), 7.07 (d, 1H), 6.85 (d, 1H), 5.18 (s, 2H), 4.22 (m, 1H), 4.02 (m, 1H), 3.75 (m, 1H), 3.45 (m, 2H), 2.00 (m, 2H), 1.66 (m, 2H)

[0476] Example 62: Preparation of 3-((5-chloro-3-(4-(4-methoxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0477] Step A: Preparation of 3-((5-chloro-3-(4-(4-methoxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 4-(6-chloro-3-(3-(methoxycarbonyl)benzyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (43.6 mg, 0.10 mmol) and 4-methoxypiperidine (12.64 mg, 0.110 mmol) obtained in the above-mentioned Production Example 25, the title compound (46.0 mg, 86% yield) was obtained by the same method as in step A of Example 58. MS [M+H] = 535 (M+1)

[0478] Step B: Preparation of 3-((5-chloro-3-(4-(4-methoxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(4-methoxypiperidine-1-carbonyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (43.0 mg, 0.090 mmol) obtained in step A, the title compound (29.5 mg, 66% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 520 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.10 (s, 1H), 8.04 (d, 1H), 7.63 (m, 5H), 7.48 (t, 1H), 7.12 (s, 1H), 7.07 (d, 1H), 6.85 (d, 1H), 5.18 (d, 2H), 4.04 (m, 1H), 3.68 (m, 1H), 3.58 (m, 1H), 3.51 (m, 1H), 3.38 (s, 3H), 3.31 (m, 1H), 1.96-1.60 (m, 4H)

[0479] Example 63: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] The title compound was obtained through the following steps A, B, C, and D.

[0480] Step A: Preparation of 3-(1-(3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (200 mg, 0.58 mmol) and (4-(tert-butoxycarbonylphenyl)boronic acid (194 mg, 0.88 mmol) obtained in the above-mentioned Production Example 3, the title compound (181 mg, 60% yield) was obtained by the same method as in step A of Example 2. 1H-NMR (500 MHz, CDCl3) δ8.16 (d, 2H), 7.90 (d, 1H), 7.88 (s, 1H), 7.62 (d, 2H), 7.50 (d, 1H), 7.36 (t, 1H), 7.12 (m, 3H), 3.90 (s, 3H), 1.73 (m, 2H), 1.68 (m, 2H), 1.62 (s, 9H)

[0481] Step B: Preparation of 4-(6-chloro-3-(1-(3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid Using the 3-(1-(3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (181 mg, 0.35 mmol) obtained in step A, the title compound (161 mg, 99% yield) was obtained by the same method as in step B of Example 56.

[0482] Step C: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using the 4-(6-chloro-3-(1-(3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (50 mg, 0.11 mmol) and pyrrolidine (9.2 mg, 0.13 mmol) obtained in step B, the title compound (54 mg, 98% yield) was obtained by the same method as in step C of Example 56. 1 H-NMR (500 MHz, CDCl3) δ7.90 (d, 1H), 7.88 (s, 1H), 7.71 (d, 2H), 7.60 (d, 2H), 7.50 (d, 1H), 7.36 (t, 1H), 7.15 (d, 1H), 7.10 (d, 2H), 3.90 (s, 3H), 3.68 (t, 2H), 3.49 (t, 2H), 1.98 (m, 2H), 1.93 (m, 2H), 1.73 (m, 2H), 1.68 (m, 2H)

[0483] Step D: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid Using 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (54 mg, 0.10 mmol) obtained in step C, the title compound (20 mg, 38% yield) was obtained by the same method as in step B of Example 2. 1 H NMR (500 MHz, DMSO-D6) δ7.81 (d, 1H), 7.73 (d, 3H), 7.66 (d, 2H), 7.46 (m, 2H), 7.28 (d, 1H), 7.20 (d, 1H), 7.16 (s, 1H), 3.51 (m, 2H), 3.47 (m, 2H), 1.87 (m, 2H), 1.84 (m, 2H), 1.69 (m, 4H)

[0484] Example 64: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0485] Step A: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using 4-(6-chloro-3-(1-(3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (53 mg, 0.10 mmol) and piperidine (11 mg, 0.13 mmol) obtained in step B of Example 63, the title compound (53 mg, 92% yield) was obtained by the same method as in step C of Example 56. 1H-NMR (500 MHz, CDCl3) δ7.92 (m, 2H), 7.60 (m, 4H), 7.53 (d, 1H), 7.38 (t, 1H), 7.17 (d, 1H), 7.13 (d, 2H), 3.92 (s, 3H), 3.76 (br, 2H), 3.43 (br, 2H), 1.71 (m, 6H), 1.58 (m, 4H)

[0486] Step B: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid Using the 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (53 mg, 0.10 mmol) obtained in step A, the title compound (31 mg, 60% yield) was obtained by the same method as in step B of Example 2. 1 H NMR (500 MHz, DMSO-D6) δ13.04 (s, 1H), 7.81 (d, 1H), 7.72 (s, 1H), 7.66 (d, 2H), 7.58 (d, 2H), 7.46 (m, 2H), 7.28 (d, 1H), 7.19 (m, 2H), 3.62 (br, 2H), 3.32 (br, 2H), 1.64 (m, 6H), 1.54 (m, 4H)

[0487] Example 65: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-5-fluorobenzoic acid [ka] The title compound was obtained through the following steps A and B.

[0488] Step A: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-5-fluorobenzoate methyl ester Using 5-chloro-1,2-difluoro-3-nitrobenzene (0.641 g, 3.31 mmol) and methyl 3-(aminomethyl)-5-fluorobenzoate (0.607 g, 3.31 mmol) obtained in Production Example 6, the title compound (15 mg) was obtained sequentially by the same method as in Step A and Step B of Production Example 8 and Step A of Example 2. 1 H-NMR (400 MHz, CDCl3) δ7.88 (d, 1H), 7.64 (dd, 1H), 7.30 (dd, 1H), 7.27 (d, 2H), 6.82 (4H), 5.23 (s, 2H), 3.93 (s, 3H), 3.00 (s, 6H)

[0489] Step B: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-5-fluorobenzoic acid Using 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-5-fluorobenzoate methyl ester (15 mg, 0.032 mmol) obtained in step A, the title compound (7 mg, 48% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 458 (M+1) 1 H-NMR (400 MHz, CDCl3) δ7.95 (d, 1H), 7.68 (dd, 1H), 7.36 (dd, 1H), 7.27 (d, 2H), 6.83 (4H), 5.26 (s, 2H), 3.01 (s, 6H)

[0490] Example 66: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0491] Step A: Preparation of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.080 g, 0.24 mmol) and (4-(dimethylamino)phenyl)boronic acid (0.079 g, 0.48 mmol) obtained in the above-mentioned Production Example 15, the title compound (0.09 g, 83% yield) was obtained by the same method as in step A of Example 2. 1 H-NMR (500 MHz, CDCl3) δ8.08 (d, 1H), 7.97 (dd, 1H), 7.61 (dd, 1H), 7.41 (t, 1H), 7.28 (d, 2H), 6.80 (4H), 5.25 (s, 2H), 3.91 (s, 3H), 3.01 (s, 6H)

[0492] Step B: Production of 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(dimethylamino)phenyl)-7-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.09 g, 0.20 mmol) obtained in step A, the title compound (0.075 g, 86% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 440 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.14 (d, 1H), 8.01 (dd, 1H), 7.66 (dd, 1H), 7.44 (t, 1H), 7.30 (d, 2H), 6.84 (4H), 5.27 (s, 2H), 3.02 (s, 6H)

[0493] Example 67: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoic acid [ka] The title compound was obtained through the following steps A, B, C, and D.

[0494] Step A: Preparation of 3-(1-(3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester (200 mg, 0.55 mmol) and (4-(tert-butoxycarbonylphenyl)boronic acid (194 mg, 0.88 mmol) obtained in the above-mentioned Production Example 4, the title compound (198 mg, 67% yield) was obtained by the same method as in step A of Example 2. 1 H-NMR (400 MHz, CDCl3) δ8.12 (m, 3H), 7.85 (m, 2H), 7.53 (d, 3H), 7.18 (t, 2H), 7.05 (d, 1H), 3.90 (s, 3H), 1.68 (m, 2H), 1.63 (m, 2H), 1.58 (s, 9H)

[0495] Step B: Preparation of 4-(6-chloro-3-(1-(2-fluoro-3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid Using 3-(1-(3-(4-(tert-butoxycarbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester (198 mg, 0.37 mmol) obtained in step A, the title compound (156 mg, 88% yield) was obtained by the same method as in step B of Example 56. 1 H-NMR (500 MHz, CDCl3) δ8.25 (d, 2H), 8.15 (t, 1H), 7.86 (t, 1H), 7.63 (d, 2H), 7.57 (d, 1H), 7.20 (m, 2H), 7.10 (s, 1H), 3.91 (s, 3H), 1.66(m, 2H), 1.64 (m 2H)

[0496] Step C: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester Using 4-(6-chloro-3-(1-(2-fluoro-3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (50 mg, 0.10 mmol) and pyrrolidine (8.9 mg, 0.12 mmol) obtained in step B, the title compound (50 mg, 89% yield) was obtained by the same method as in step C of Example 56. 1 H-NMR (500 MHz, CDCl3) δ8.15 (t, 1H), 7.85 (t, 1H), 7.67 (d, 2H), 7.53 (m, 3H), 7.19 (m, 2H), 7.04 (s, 1H), 3.90 (s, 3H), 3.66 (t, 2H), 3.46 (t, 2H), 1.98 (m, 2H0, 1.91 (m, 2H), 1.68 (m, 2H), 1.64 (m, 2H)

[0497] Step D: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoic acid Using 3-(1-(5-chloro-2-oxo-3-(4-(pyrrolidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester (50 mg, 0.09 mmol) obtained in step C, the title compound (42 mg, 87% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 520 (M+1) 1 H-NMR (400 MHz, DMSO-d6) δ7.92 (t, 1H), 7.73 (t, 1H), 7.65 (dt, 2H), 7.55 (d, 2H), 7.46 (dd, 1H), 7.23 (m, 2H), 7.03 (d, 1H), 3.45 (t, 2H), 3.40 (t, 2H), 1.83 (m, 4H), 1.60 (d, 4H)

[0498] Example 68: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoic acid [ka] The title compound was obtained through the following steps A and B.

[0499] Step A: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester Using 4-(6-chloro-3-(1-(2-fluoro-3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (50 mg, 0.10 mmol) and piperidine (8.9 mg, 0.10 mmol) obtained in step B of Example 67, the title compound (53 mg, 92% yield) was obtained by the same method as in step C of Example 56. MS [M+H] = 549 (M+1) 1 H-NMR (500 MHz, CDCl3) δ8.14 (t, 1H), 7.85 (t, 1H), 7.52 (m, 5H), 7.18 (m, 2H), 7.03 (s, 1H), 3.90 (s, 3H), 3.72 (m, 2H), 3.38 (m, 2H), 1.69 (m, 6H), 1.63 (m, 2H), 1.56 (m, 2H)

[0500] Step B: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoic acid Using 3-(1-(5-chloro-2-oxo-3-(4-(piperidine-1-carbonyl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester (53 mg, 0.096 mmol) obtained in step A, the title compound (48 mg, 87% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 534 (M+1) 1H-NMR (500 MHz, CDCl3) δ8.22 (t, 1H), 7.95 (t, 1H), 7.57 (d, 3H), 7.54 (d, 2H), 7.23 (t, 1H), 7.18 (d, 1H), 7.05 (s, 1H), 3.76 (m, 2H), 3.41 (m, 2H), 1.72 (m, 6H), 1.65 (m, 2H), 1.55 (m, 2H)

[0501] Example 69: Preparation of 3-(1-(5-chloro-3-(4-(dimethylamino)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (40 mg, 0.117 mmol) and (4-(dimethylamino)phenyl)boronic acid obtained in the above-mentioned Production Example 3, the title compound (20 mg, 38% yield) was obtained by the same method as in steps A and B of Example 1. 1 H NMR (500 MHz, CDCl3) δ 7.96 (d, 1H), 7.92 (s, 1H), 7.56 (d, 1H), 7.41 (t, 1H), 7.35 (d, 2H), 7.09 (dd, 2H), 7.03 (s, 1H), 7.85 (m, 2H), 3.04 (s, 6H), 1.74 (m, 4H)

[0502] Example 70: Preparation of 3-(1-(5-chloro-3-(4-(dimethylamino)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoic acid [ka] Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester (40 mg, 0.111 mmol) and (4-(dimethylamino)phenyl)boronic acid obtained in the above-mentioned Production Example 4, the title compound (10 mg, 19% yield) was obtained by the same method as in steps A and B of Example 1. 1 H NMR (500 MHz, CDCl3) δ 8.26 (t, 1H), 7.95 (t, 1H), 7.53 (d, 1H), 7.24 (m, 3H), 7.14 (d, 1H), 6.95 (s, 1H), 6.81 (d, 2H), 3.01 (s, 6H), 1.69 (m, 4H)

[0503] Example 71: Preparation of 3-(1-(5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (40 mg, 0.117 mmol) and (4-(dimethylcarbamoyl)phenyl)boronic acid obtained in the above-mentioned Production Example 3, the title compound (20 mg, 36% yield) was obtained by the same method as in steps A and B of Example 1. 1 H NMR (500 MHz, CDCl3) δ 7.97 (d, 1H), 7.94 (s, 1H), 7.63 (m, 4H), 7.55 (d, 1H), 7.41 (t, 1H), 7.15 (m, 3H), 3.13 (d, 6H), 1.74 (m, 4H).

[0504] Example 72: Preparation of 3-(1-(5-chloro-3-(4-(dimethylcarbamoyl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoic acid [ka] Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester (40 mg, 0.111 mmol) and (4-(dimethylcarbamoyl)phenyl)boronic acid obtained in the above-mentioned Production Example 4, the title compound (25 mg, 46% yield) was obtained by the same method as in steps A and B of Example 1. 1 H NMR (500 MHz, CDCl3) δ 8.22 (t, 1H), 7.95 (t, 1H), 7.58 (m, 5H), 7.23 (t, 1H), 7.19 (d, 1H), 7.05 (s, 1H), 3.11 (d, 6H), 1.69 (m, 4H)

[0505] Example 73: Preparation of 3-((5-chloro-2-oxo-3-(pyridine-3-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0506] Step A: Preparation of 3-((5-chloro-2-oxo-3-(pyridine-3-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (50 mg, 0.158 mmol) and pyridine-3-ylboronic acid (19.4 mg, 0.158 mmol) obtained in the above-mentioned Production Example 1, the title compound (11 mg, 18% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 394 (M+1) 1 H NMR (400 MHz, CD3OD) δ8.89 (s, 1H), 8.70 (s, 1H), 8.04 (s, 1H), 7.98 (dt, 1H), 7.94 (d, 1H), 7.56 (d, 2H), 7.42 (t, 1H), 7.09 (d, 1H), 7.04 (dd, 1H), 6.82 (d, 1H), 5.19 (s, 2H), 3.90 (s, 3H)

[0507] Step B: Production of 3-((5-chloro-2-oxo-3-(pyridine-3-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-2-oxo-3-(pyridine-3-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (11 mg, 0.028 mmol) obtained in step A, the title compound (10 mg, 94% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 380 (M+1) 1 H NMR (500 MHz, DMSO-D6) δ8.80 (d, 1H), 8.63 (dd, 1H), 8.05 (dq, 1H), 7.95 (s, 1H), 7.82 (d, 1H), 7.60 (dd, 2H), 7.44 (t, 1H), 7.25 (d, 1H), 7.15 (dd, 1H), 7.10 (d, 1H), 5.18 (s, 2H)

[0508] Example 74: Preparation of 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0509] Step A: Preparation of 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using methyl 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate (120 mg, 0.379 mmol) and (6-fluoropyridine-3-yl)boronic acid (107 mg, 0.758 mmol) obtained in the above-mentioned Production Example 1, the title compound (64 mg, 41% yield) was obtained by the same method as in step A of Example 2. MS [M+H] = 412 (M+1) 1 H NMR (400 MHz, CD3OD) δ8.45 (s, 1H), 8.03 (m, 2H), 7.98 (d, 1H), 7.53 (d, 1H), 7.42 (t, 1H), 7.15 (dd, 1H), 7.07 (d, 1H), 7.04 (d, 1H), 6.84 (d, 1H), 5.15 (s, 2H), 3.90 (s, 3H)

[0510] Step B: Preparation of 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (64 mg, 0.155 mmol) obtained in step A, the title compound (58 mg, 94% yield) was obtained by the same method as in step B of Example 2. MS [M+H] = 398 (M+1) 1 H NMR (400 MHz, DMSO-D6) δ8.49 (d, 1H), 8.25 (ddd, 1H), 7.96 (s, 1H), 7.83 (m, 1H), 7.59 (d, 1H), 7.44 (t, 1H), 7.40 (dd, 1H), 7.23 (m, 1H), 7.14 (m, 2H), 5.18 (s, 2H)

[0511] Example 75: Preparation of 3-((5-chloro-3-(6-ethoxypyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid (25 mg, 0.063 mmol) obtained in Example 74 was mixed with 2 mL of DMF, then NaOH (2.41 mg, 0.101 mmol) was added at 0°C and the mixture was stirred for 30 minutes. EtOH (4.34 mg, 0.094 mmol) was then added and the mixture was stirred at room temperature for 16 hours. After the reaction was completed, water was added to separate the organic layer, which was dried over Na2SO4. The solid was removed, and the filtrate was distilled under reduced pressure and separated by MPLC to obtain the title compound (17 mg, 63% yield). MS [M+H] = 424 (M+1) 1 H NMR (400 MHz, CD3OD) δ8.33 (d, 1H), 7.94 (s, 1H), 7.89 (dd, 1H), 7.82 (d, 1H), 7.57 (d, 1H), 7.44 (t, 1H), 7.21 (d, 1H), 7.12 (dd, 1H), 6.98 (d, 1H), 6.96 (d, 1H), 5.16 (s, 2H), 4.34 (q, 2H), 1.32 (t, 3H)

[0512] Example 76: Preparation of 3-((5-chloro-2-oxo-3-(6-propoxypyridine-3-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] Using 6-chloro-1-(6-propoxypyridine-3-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.20 g, 0.66 mmol) and 3-(bromomethyl)methyl benzoate (0.17 g, 0.72 mmol) obtained in the above-mentioned Production Example 7, the title compound (0.10 g, 35% yield) was obtained by the same method as in steps A and B of Example 24. MS [MH] = 436 (M-1) 1 H-NMR (400 MHz, CDCl3) δ8.32 (d, 1H), 8.10 (d, 1H), 8.03 (dd, 1H), 7.74 (dd, 1H), 7.60 (m, 1H), 7.46 (t, 1H), 7.03 (dd, 1H), 7.00 (d, 1H), 6.91 (d, 1H), 6.83 (d, 1H), 5.17 (s, 2H), 4.32 (t, 2H), 1.83 (m, 2H), 1.05 (t, 3H)

[0513] Example 77: Production of 3-((5-chloro-3-(6-(3-hydroxyazetidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0514] Step A: Preparation of 3-((5-chloro-3-(6-(3-hydroxyazetidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.065 g, 0.16 mmol) obtained in step A of Example 74 and azetidine-3-ol hydrochloride (0.052 g, 0.47 mmol), the title compound (0.020 g, 27% yield) was obtained by the same method as in step A of Example 24. 1 H-NMR (400 MHz, CDCl3) δ8.28 (m, 1H), 8.05 (m, 1H), 7.97 (m, 1H), 7.59 (m, 2H), 7.43 (m, 1H), 7.02 (m, 1H), 6.96 (m, 1H), 6.80 (m, 1H), 6.45 (m, 1H), 5.15 (s, 2H), 4.85 (m, 1H), 4.38 (m, 2H), 3.97 (m, 2H), 3.92 (s, 3H)

[0515] Step B: Preparation of 3-((5-chloro-3-(6-(3-hydroxyazetidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(6-(3-hydroxyazetidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.02 g, 0.043 mmol) obtained in step A, the title compound (0.01 g, 52% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 451 (M+1) 1 H-NMR (400 MHz, MeOH-d4) δ8.18 (d, 1H), 7.03 (d, 1H), 7.96 (dd, 1H), 7.69 (dd, 1H), 7,61 (dd, 1H), 7.47 (t, 1H), 7.10 (2H), 6.95 (d, 1H), 6.61 (d, 1H), 5.22 (s, 2H), 4.70 (m, 1H), 4.35 (m, 2H), 3.91 (m, 2H)

[0516] Example 78: Preparation of 3-((5-chloro-3-(6-morpholinopyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0517] Step A: Preparation of 3-((5-chloro-3-(6-morpholinopyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.12 g, 0.29 mmol) obtained in step A of Example 74 and morpholine (0.051 g, 0.58 mmol), the title compound (0.063 g, 45% yield) was obtained by the same method as in step A of Example 24. 1H-NMR (400 MHz, CDCl3) δ 8.33 (dd, 1H), 8.05 (d, 1H), 7.98 (dd, 1H), 7.65 (dd, 1H), 7.56 (dd, 1H), 7.43 (t, 1H), 7.00 (2H), 6.78 (2H), 5.15 (s, 2H), 3.92 (s, 3H), 3.85 (m, 4H), 3.59 (m, 4H)

[0518] Step B: Preparation of 3-((5-chloro-3-(6-morpholinopyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(6-morpholinopyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.06 g, 0.12 mmol) obtained in step A, the title compound (0.052 g, 89%) was obtained by the same method as in step B of Example 24. MS [M+H] = 465 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.34 (d, 1H), 8.09 (d, 1H), 8.03 (dd, 1H), 7.65 (dd, 1H), 7.60 (dd, 1H), 7.49 (t, 1H), 7.03 (dd, 1H), 7.01 (d, 1H), 6.80 (2H), 5.17 (s, 2H), 3.86 (m, 4H), 3.50 (m, 4H)

[0519] Example 79: Preparation of 3-((5-chloro-3-(6-(dimethylamino)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0520] Step A: Preparation of 3-((5-chloro-3-(6-(dimethylamino)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.07 g, 0.17 mmol) obtained in step A of Example 74 and dimethylamine hydrochloride (0.042 g, 0.51 mmol), the title compound (0.022 g, 30% yield) was obtained by the same method as in step A of Example 24. 1 H-NMR (400 MHz, CDCl3) δ 8.28 (dd, 1H), 8.06 (m, 1H), 8.00 (dd, 1H), 7.55 (2H), 7.43 (t, 1H), 6.98 (2H), 6.78 (d, 1H), 6.64 (dd, 1H), 5.15 (s, 2H), 3.92 (s, 3H), 3.15 (s, 6H)

[0521] Step B: Preparation of 3-((5-chloro-3-(6-(dimethylamino)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(6-(dimethylamino)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.022 g, 0.05 mmol) obtained in step A, the title compound (0.018 g, 85%) was obtained by the same method as in step B of Example 24. MS [M+H] = 423 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.35 (d, 1H), 8.07 (d, 1H), 8.02 (dd, 1H), 7.70 (m, 1H), 7.59 (dd, 1H), 7.45 (t, 1H), 7.03 (dd, 1H), 7.00 (d, 1H), 6.83 (d, 1H), 6.74 (m, 1H), 5.16 (s, 2H), 3.25 (s, 6H)

[0522] Example 80: Preparation of 3-((5-chloro-3-(6-(3,3-difluoropyrrolinidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] Using 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.07 g, 0.17 mmol) and 3,3-difluoropyrrolidine hydrochloride (0.066 g, 0.51 mmol) obtained in step A of Example 74, the title compound (0.005 g, 23% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 485 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.34 (d, 1H), 8.09 (d, 1H), 8.03 (dd, 1H), 7.65 (dd, 1H), 7.60 (dd, 1H), 7.46 (t, 1H), 7.02 (dd, 1H), 6.97 (d, 1H), 6.81 (d, 1H), 6.53 (d, 1H), 5.17 (s, 2H), 3.92 (t, 2H), 3.76 (t, 2H), 2.54 (m, 2H)

[0523] Example 81: Preparation of 3-((5-chloro-3-(6-(4-methylpiperazine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0524] Step A: Preparation of 3-((5-chloro-3-(6-(4-methylpiperazine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester Using 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.07 g, 0.17 mmol) and 1-methylpiperazine (0.051 g, 0.051 mmol) obtained in step A of Example 74, the title compound (0.033 g, 40% yield) was obtained by the same method as in step A of Example 24. 1 H-NMR (400 MHz, CDCl3) δ8.31 (d, 1H), 8.05 (d, 1H), 7.97 (dd, 1H), 7.63 (dd, 1H), 7.56 (dd, 1H), 7.42 (t, 1H), 7.00 (2H), 6.78 (2H), 5.15 (s, 2H), 3.92 (s, 3H), 3.66 (m, 4H), 2.55 (m, 4H), 2.37 (s, 3H)

[0525] Step B: Preparation of 3-((5-chloro-3-(6-(4-methylpiperazine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(6-(4-methylpiperazine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.033 g, 0.067 mmol) obtained in step A, the title compound (0.028 g, 85%) was obtained by the same method as in step B of Example 24. MS [M+H] = 478 (M+1) 1 H-NMR (400 MHz, DMSO-d6) δ8.26 (d, 1H), 7.96 (d, 1H), 7.84 (dd, 1H), 7.71 (dd, 1H), 7.60 (dd, 1H), 7.50 (t, 1H), 7.20 (d, 1H), 7.13 (d, 1H), 7.01 (d, 1H), 6.93 (d, 1H), 5.18 (s, 2H), 3.60 (m, 4H), 2.52 (m, 4H), 2.31 (s, 3H)

[0526] Example 82: Preparation of 3-((5-chloro-3-(6-(4,4-difluoropiperidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0527] Step A: Preparation of 3-((5-chloro-3-(6-(4,4-difluoropiperidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester Using 3-((5-chloro-3-(6-fluoropyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.07 g, 0.17 mmol) and 4,4-difluoropiperidine hydrochloride (0.070 g, 0.51 mmol) obtained in step A of Example 74, the title compound (0.032 g, 37% yield) was obtained by the same method as in step A of Example 24. 1 H-NMR (400 MHz, CDCl3) δ8.32 (d, 1H), 8.05 (d, 1H), 7.98 (dd, 1H), 7.65 (dd, 1H), 7.55 (dd, 1H), 7.43 (t, 1H), 7.02 (2H), 6.85 (d, 1H), 6.80 (d, 1H), 5.15 (s, 2H), 3.92 (s, 3H), 3.82 (m, 4H), 2.05 (m, 4H)

[0528] Step B: Preparation of 3-((5-chloro-3-(6-(4,4-difluoropiperidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(6-(4,4-difluoropiperidine-1-yl)pyridine-3-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.032 g, 0.17 mmol) obtained in step A, the title compound (10 mg, 32% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 499 (M+1) 1H-NMR (400 MHz, CDCl3) δ8.33 (d, 1H), 8.10 (d, 1H), 8.04 (dd, 1H), 7.66 (dd, 1H), 7.63 (dd, 1H), 7.46 (t, 1H), 7.03 (dd, 1H), 7.00 (d, 1H), 6.85 (d, 1H), 6.82 (d, 1H), 5.18 (s, 2H), 3.82 (m, 4H), 2.05 (m, 4H)

[0529] Example 83: Preparation of 3-((5-chloro-3-(2-morpholinopyrimidine-5-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] Using 6-chloro-1-(2-morpholinopyrimidine-5-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.045 g, 0.136 mmol) and 3-(bromomethyl)methyl benzoate (0.031 g, 0.136 mmol) obtained in the above-mentioned Production Example 26, the title compound (0.040 g, 63% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 466 (M+1) 1 H-NMR (400 MHz, MeOH-d4) δ8.52 (s, 2H), 8.03 (d, 1H), 7.95 (dd, 1H), 7.60 (dd, 1H), 7.47 (t, 1H), 7.11 (m, 2H), 7.01 (d, 1H), 5.22 (s, 2H), 3.88 (m, 4H), 3.77 (m, 4H)

[0530] Example 84: Preparation of 3-((5-chloro-2-oxo-3-(1-propyl-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0531] Step A: Preparation of 3-((5-chloro-2-oxo-3-(1-propyl-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(1-propyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.015 g, 0.054 mmol) and 3-(bromomethyl)benzoate methyl ester (0.013 g, 0.054 mmol) obtained in the above-mentioned Production Example 12, the title compound (0.011 g, 46% yield) was obtained by the same method as in step A of Production Example 21. 1 H-NMR (500 MHz, CDCl3) δ8.00 (2H), 7.82 (s, 1H), 7.78 (s, 1H), 7.53 (m, 1H), 7.40 (m, 1H), 7.11 (s, 1H), 7.02 (d, 1H), 6.79 (d, 1H), 5.14 (s, 2H), 4.16 (t, 2H), 3.91 (s, 3H), 1.97 (m, 2H), 0.99 (t, 3H)

[0532] Step B: Preparation of 3-((5-chloro-2-oxo-3-(1-propyl-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 3-((5-chloro-2-oxo-3-(1-propyl-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (8.5 mg, 0.02 mmol) obtained in step A, the title compound (5 mg, 61% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 411 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.00 (m, 1H), 7.97 (m, 1H), 7.75 (s, 1H), 7.75 (s, 1H), 7.48 (m, 1H), 7.40 (m, 1H), 7.08 (m, 1H), 7.00 (m, 1H), 6.78 (m, 1H), 5.11 (s, 2H), 4.12 (t, 2H), 1.94 (m, 2H), 0.96 (t, 3H)

[0533] Example 85: Preparation of 3-((5-cyclopropyl-2-oxo-3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] Using 6-cyclopropyl-1-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.075 g, 0.23 mmol) and 3-(bromomethyl)methyl benzoate (0.064 g, 0.28 mmol) obtained in the above-mentioned Production Example 17, the title compound (0.020 g, 20% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 459 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.10 (m, 1H), 8.01 (m, 1H), 7.91 (s, 1H), 7.83 (s, 1H), 7.58 (m, 1H), 7.43 (t, 1H), 6.88 (m, 1H), 6.80 (m, 2H), 5.15 (s, 2H), 4.42 (m, 1H), 4.15 (m, 2H), 3.57 (m, 2H), 2.17 (m, 4H), 1.90 (m, 1H), 0.92 (m, 2H), 0.63 (m, 2H)

[0534] Example 86: Production of 3-((5-chloro-2-oxo-3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0535] Step A: Preparation of 3-((5-chloro-2-oxo-3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.11 g, 0.34 mmol) and 3-(bromomethyl)methyl benzoate (0.10 g, 0.45 mmol) obtained in the above-mentioned Production Example 9, the title compound (0.090 g, 56% yield) was obtained by the same method as in step A of Example 24. 1 H-NMR (400 MHz, CDCl3) δ8.03 (m, 1H), 7.98 (dd, 1H), 7.87 (s, 1H), 7.80 (s, 1H), 7.53 (dd, 1H), 7.42 (t, 1H), 7.11 (d, 1H), 7.03 (dd, 1H), 6.80 (d, 1H), 5.14 (s, 2H), 4.40 (m, 1H), 4.14 (m, 2H), 3.91 (s, 3H), 3.60 (m, 2H), 2.15 (m, 4H)

[0536] Step B: Production of 3-((5-chloro-2-oxo-3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 3-((5-chloro-2-oxo-3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.09 g, 0.19 mmol) obtained in step A, the title compound (0.035 g, 40% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 453 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.19 (d, 1H), 8.03 (dd, 1H), 7.89 (s, 1H), 7.81 (s, 1H), 7.58 (m, 1H), 7.48 (t, 1H), 7.12 (d, 1H), 7.06 (dd, 1H), 6.82 (d, 1H), 5.17 (s, 2H), 4.41 (m, 1H), 4.14 (m, 2H), 3.58 (m, 2H), 2.17 (m, 4H)

[0537] Example 87: Preparation of 3-((5-chloro-2-oxo-3-(1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A, B, and C.

[0538] Step A: Preparation of N-(5-chloro-2-nitrophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-amine N-(5-chloro-2-nitrophenyl)-1H-pyrazole-4-amine (0.16 g, 0.67 mmol) obtained in the above-mentioned Production Example 10 was dissolved in 3 mL of DMF, cooled to 0°C, and NaH (0.021 g, 0.87 mmol) was added, followed by stirring for 20 minutes. 4-methylbenzenesulfonic acid 2,2,2-trifluoroethyl ester (0.20 g, 0.80 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. After the reaction was completed, an aqueous ammonium chloride solution was added, followed by extraction with siRNA. The organic layer was separated and purified by MPLC to obtain the title compound (0.069 g, 32% yield). 1 H-NMR (400 MHz, CDCl3) δ9.19 (brs, 1H), 8.16 (d, 1H), 7.63 (s, 1H), 7.60 (s, 1H), 6.75 (d, 1H), 6.73 (dd, 1H), 4.74 (q, 2H)

[0539] Step B: Preparation of 6-chloro-1-(1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Using the N-(5-chloro-2-nitrophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-amine (0.065 g, 0.20 mmol) obtained in step A, the title compound (0.024 g, 37% yield) was obtained by the same method as in step B of production example 7 and step C of production example 3. 1H-NMR (400 MHz, CDCl3) δ8.19 (brs, 1H), 7.97 (s, 1H), 7.90 (s, 1H), 7.12 (2H), 7.00 (d, 1H), 4.78 (q, 2H)

[0540] Step C: Preparation of 3-((5-chloro-2-oxo-3-(1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 6-chloro-1-(1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.024 g, 0.076 mmol) and 3-(bromomethyl)methyl benzoate (0.017 g, 0.076 mmol) obtained in step B, the title compound (0.010 g, 29% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 451 (M+1) 1 H-NMR (400 MHz, CDCl3) δ8.17-8.02 (3H), 7.92 (s, 1H), 7.58 (m, 1H), 7.47 (m, 1H), 7.15 (d, 1H), 7.06 (dd, 1H), 6.83 (d, 1H), 5.15 (s, 2H), 4.80 (q, 2H)

[0541] Example 88: Production of 3-((5-chloro-4-fluoro-2-oxo-3-(1-propyl-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] Using 6-chloro-7-fluoro-1-(1-propyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.083 g, 0.28 mmol) and 3-(bromomethyl)benzoate methyl ester (0.065 g, 0.28 mmol) obtained in the above-mentioned Production Example 13, the title compound (0.097 g, 80% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 430 (M+1) 1 H-NMR (400 MHz, MeOH-d4) δ8.03 (m, 1H), 8.01 (m, 1H), 7.95 (dd, 1H), 7.74 (d, 1H), 7.57 (m, 1H), 7.47 (t, 1H), 7.16 (dd, 1H), 6.94 (d, 1H), 5.21 (s, 2H), 4.18 (t, 2H), 1.92 (m, 2H), 0.95 (t, 3H)

[0542] Example 89: Preparation of 3-((5-chloro-3-(1-isopropyl-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0543] Step A: Preparation of 3-((5-chloro-3-(1-isopropyl-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(1-isopropyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (15.6 mg, 0.054 mmol) and methyl 3-(bromomethyl)benzoate obtained in the above-mentioned Production Example 18, the title compound (15.4 mg, 67% yield) was obtained by the same method as in step A of Production Example 1. MS [M+H] = 425 (M+1)

[0544] Step B: Preparation of 3-((5-chloro-3-(1-isopropyl-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the methyl 3-((5-chloro-3-(1-isopropyl-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (15.4 mg, 0.035 mmol) obtained in step A, the title compound (9.9 mg, 68% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 411 (M+1) 1 H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 8.04 (d, 1H), 7.87 (s, 1H), 7.80 (s, 1H), 7.59 (d, 1H), 7.46 (t, 1H), 7.12 (m, 1H), 7.04 (m, 1H), 6.83 (d, 1H), 5.16 (s, 1H), 4.63 (m, 1H), 1.59 (d, 6H)

[0545] Example 90: Preparation of 3-((5-chloro-3-(1-cyclopropylmethyl-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0546] Step A: Preparation of 3-((5-chloro-3-(1-(cyclopropylmethyl)-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester Using 6-chloro-1-(1-(cyclopropylmethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (55.3 mg, 0.19 mmol) and methyl 3-(bromomethyl)benzoate obtained in the above-mentioned Production Example 19, the title compound (52.1 mg, 63% yield) was obtained by the same method as in step A of Production Example 1. MS [M+H] = 437 (M+1)

[0547] Step B: Preparation of 3-((5-chloro-3-(1-(cyclopropylmethyl)-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(1-(cyclopropylmethyl)-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (52.1 mg, 0.12 mmol) obtained in step A, the title compound (25.6 mg, 52% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 423 (M+1) 1H NMR (500 MHz, CDCl3) δ 8.07 (s, 1H), 8.03 (d, 1H), 7.95 (s, 1H), 7.78 (s, 1H), 7.59 (d, 1H), 7.47 (m, 1H), 7.13 (s, 1H), 7.04 (d, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 4.07 (d, 2H), 1.36 (m, 1H), 0.88 (m, 2H), 0.45 (m, 2H)

[0548] Example 91: Preparation of 3-((5-chloro-3-(1-cyclobutylmethyl-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0549] Step A: Preparation of 3-((5-chloro-3-(1-(cyclobutylmethyl)-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester Using 6-chloro-1-(1-(cyclobutylmethyl)-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (10.6 mg, 0.033 mmol) and methyl 3-(bromomethyl)benzoate obtained in the above-mentioned Production Example 20, the title compound (10.1 mg, 68% yield) was obtained by the same method as in step A of Production Example 1. MS [M+H] = 451 (M+1) 1 H NMR (500 MHz, CDCl3) δ8.02 (s, 1H), 7.97 (d, 2H), 7.79 (m, 2H), 7.54 (m, 1H), 7.43 (m, 1H), 7.11 (s, 1H), 7.02 (d, 1h), 6.79 (d, 1H), 5.14 (s, 2H), 4.21 (d, 2H), 3.91 (s, 3H), 2.91 (m, 1H), 2.16 (m, 2H), 1.97 (m, 4H)

[0550] Step B: Preparation of 3-((5-chloro-3-(1-(cyclobutylmethyl)-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(1-(cyclobutylmethyl)-1H-pyrazole-4-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (10.1 mg, 0.022 mmol) obtained in step A, the title compound (7.6 mg, 79% yield) was obtained by the same method as in step B of Example 1. MS [M+H] = 437 (M+1) 1 H NMR (500 MHz, CDCl3) δ 8.08 (s, 1H), 8.04 (d, 1H), 7.80 (d, 2H), 7.58 (d, 2H), 7.46 (t, 1H), 7.12 (s, 1H), 7.04 (d, 1H), 6.82 (d, 1H), 5.16 (s, 2H), 4.22 (d, 2H), 2.92 (m, 1H), 2.14 (m, 2H), 1.96 (m, 4H)

[0551] Example 92: Preparation of 3-((5-chloro-4-fluoro-2-oxo-3-(1-propyl-1H-pyrazole-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] Using 6-chloro-1-(1-propyl-1H-pyrazole-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.056 g, 0.19 mmol) and methyl 3-(bromomethyl)-2-fluorobenzoate (0.047 g, 0.190 mmol) obtained in the above-mentioned Production Example 12, the title compound (0.052 g, 61% yield) was obtained by the same method as in steps A and B of Example 24. MS [M+H] = 447 (M+1) 1H-NMR (500 MHz, DMSO-d6) δ13.5 (brs, 1H), 8.13 (m, 1H), 7.69 (s, 1H), 7.65 (m, 1H), 7.28 (m, 1H), 7.25 (m, 1H), 7.16 (m, 1H), 7.07 (m, 1H), 5.17 (s, 2H), 4.11 (t, 2H), 1.82 (m, 2H), 0.84 (t, 3H)

[0552] Example 93: Preparation of 3-(1-(3-(4-(7-oxa-2-azaspiro[3.5]nonane-2-carbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0553] Step A: Preparation of 3-(1-(3-(4-(7-oxa-2-azaspiro[3.5]nonane-2-carbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using 4-(6-chloro-3-(1-(3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (100 mg, 0.22 mmol) and 7-oxa-2-azaspiro[3.5]nonane (32 mg, 0.26 mmol) obtained in step B of Example 63, the title compound (63 mg, 51% yield) was obtained by the same method as in step C of Example 56. 1 H NMR (400 MHz, CDCl3) δ7.91 (m, 1H), 7.89 (m, 1H), 7.83 (d, 2H), 7.62 (d, 2H), 76.49 (m, 1H), 7.37 (t, 1H), 7.13 (3H), 4.13 (s, 2H), 4.03 (s, 2H), 3.91 (s, 3H), 3.65 (m, 4H), 1.84 (m, 4H), 1.70 (m, 4H)

[0554] Step B: Preparation of 3-(1-(3-(4-(7-oxa-2-azapiro[3.5]nonane-2-carbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid Using the 3-(1-(3-(4-(7-oxa-2-azaspiro[3.5]nonanyl-2-carbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (63 mg, 0.11 mmol) obtained in step A, the title compound (43 mg, 70% yield) was obtained by the same method as in step B of Example 2. 1 H NMR (400 MHz, DMSO-d6) δ7.87 (d, 2H), 7.85 (m, 1H), 7.68 (3H), 7.45 (2H), 7.28 (d, 1H), 7.21 (m, 1H), 7.15 (m, 1H), 4.14 (s, 2H), 3.83 (s, 2H), 3.53 (4H), 1.70 (8H)

[0555] Example 94: Preparation of 3-((5-chloro-3-(4-(4,4-difluoropiperidine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0556] Step A: Preparation of 3-((5-chloro-3-(4-(4,4-difluoropiperidine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester Using 6-chloro-1-(4-(4,4-difluoropiperidine-1-yl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (0.25 g, 0.68 mmol) and 3-(bromomethyl)methyl benzoate (0.16 g, 0.68 mmol) obtained in Preparation Example 28, the title compound (0.35 g, 99% yield) was obtained by the same method as in step A of Example 24. 1H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.97 (dd, 1H), 7.56 (dd, 1H), 7.43 (d, 1H), 7.40 (d, 2H), 7.07 (d, 2H), 7.00 (d, 2H), 6.78 (d, 1H), 5.15 (s, 2H), 3.92 (s, 3H), 3.44 (m, 4H), 2.12 (m, 4H)

[0557] Step B: Preparation of 3-((5-chloro-3-(4-(4,4-difluoropiperidine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(4,4-difluoropiperidine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.35 g, 0.68 mmol) obtained in step A, the title compound (0.34 g, 99% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 498 (M+1) 1 H-NMR (400 MHz, DMSO-d6) δ 7.96 (d, 1H), 7.85 (dd, 1H), 7.60 (dd, 1H), 7.47 (t, 1H), 7.39 (d, 2H), 7.23 (d, 1H), 7.18 (d, 2H), 7.13 (dd, 1H), 6.92 (d, 1H), 5.19 (s, 2H), 3.45 (m, 4H), 2.08 (m, 4H)

[0558] Example 95: Preparation of 3-((5-chloro-3-(4-(4-(cyclopropanecarbonyl)piperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0559] Step A: Preparation of 3-((5-chloro-3-(4-(4-(cyclopropanecarbonyl)piperazin-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester Using the hydrochloride salt (0.10 g, 0.19 mmol) of 3-((5-chloro-2-oxo-3-(4-(piperazin-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate obtained in Preparation Example 29 and cyclopropane carbonyl chloride (0.022 g, 0.21 mmol), the title compound (0.083 g, 78% yield) was obtained by the same method as in step C of Example 26. 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.97 (dd, 1H), 7.56 (dd, 1H), 7.42 (3H), 7.06 (d, 2H), 7.00 (2H), 6.79 (d, 1H), 5.15 (s, 2H), 3.92 (s, 3H), 3.88 (m, 4H), 3.28 (m, 4H), 1.80 (m, 1H), 1.04 (m, 2H), 0.81 (m, 2H)

[0560] Step B: Preparation of 3-((5-chloro-3-(4-(4-(cyclopropanecarbonyl)piperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(4-(cyclopropanecarbonyl)piperazin-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.083 g, 0.15 mmol) obtained in step A, the title compound (0.065 g, 80% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 531 (M+1) 1 H-NMR (400 MHz, CDCl3) δ 8.10 (d, 1H), 8.01 (dd, 1H), 7.59 (dd, 1H), 7.45 (3H), 7.12 (d, 2H), 7.02 (2H), 6.82 (d, 1H), 5.18 (s, 2H), 3.91 (m, 4H), 3.31 (m, 4H), 1.80 (m, 1H), 1.06 (m, 2H), 0.84 (m, 2H)

[0561] Example 96: Preparation of 3-((5-chloro-3-(4-(4-(isopropoxycarbonyl)piperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0562] Step A: Preparation of 3-((5-chloro-3-(4-(4-(isopropoxycarbonyl)piperazin-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester Triphosgene (0.058 g, 0.19 mmol) was mixed with 3 mL of DCM and DIPEA (0.068 mL, 0.39 mmol), and then cooled to 0°C. 2-propanol (0.030 mL, 0.39 mmol) was slowly added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and then 5 mL of DCM, 3-((5-chloro-2-oxo-3-(4-(piperazin-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl methyl benzoate hydrochloride (0.10 g, 0.19 mmol) obtained in Preparation Example 29, and DIPEA (0.068 mL, 0.39 mmol) were added, and the mixture was stirred at room temperature for 1 hour. After adding water to the reaction mixture, the organic layer was separated and the title compound (0.044 g, 40% yield) was obtained by MPLC. 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.97 (dd, 1H), 7.55 (dd, 1H), 7.42 (3H), 7.05 (d, 2H), 7.00 (2H), 6.79 (d, 1H), 5.15 (s, 2H), 4.97 (m, 1H), 3.92 (s, 3H), 3.66 (m, 4H), 3.23 (m, 4H), 1.27 (d, 6H)

[0563] Step B: Preparation of 3-((5-chloro-3-(4-(4-(isopropoxycarbonyl)piperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the methyl ester (0.044 g, 0.075 mmol) of 3-((5-chloro-3-(4-(4-(isopropoxycarbonyl)piperazin-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid obtained in step A, the title compound (0.032 g, 83% yield) was obtained by the same method as in step B of Example 24. MS [MH] = 547 (M-1) 1 H-NMR (400 MHz, CDCl3) δ 8.11 (d, 1H), 8.03 (dd, 1H), 7.60 (dd, 1H), 7.45 (t, 1H), 7.41 (d, 2H), 7.06 (d, 2H), 7.01 (2H), 6.81 (d, 1H), 5.18 (s, 2H), 4.98 (m, 1H), 3.66 (m, 4H), 3.22 (m, 4H), 1.28 (d, 6H)

[0564] Example 97: Preparation of 3-((5-chloro-3-(4-(4-methylpiperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0565] Step A: Preparation of 3-((5-chloro-3-(4-(4-methylpiperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester To the hydrochloride salt (0.15 g, 0.29 mmol) of 3-((5-chloro-2-oxo-3-(4-(piperazine-1-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate obtained in Preparation Example 29, 6 mL of dichloroethane, paraformaldehyde (0.044 g, 1.46 mmol), and acetic acid (0.033 mL, 0.58 mmol) were added, and the mixture was stirred at room temperature for 2 hours. Sodium triacetoxyburohydride (0.155 g, 0.73 mmol) was then added, and the mixture was stirred at room temperature for 16 hours. After adding saturated aqueous solution of sodium bicarbonate to the reaction mixture, the organic layer was separated and dried over anhydrous Na2SO4 to obtain the title compound (0.075 g, 52% yield). 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.97 (dd, 1H), 7.55 (dd, 1H), 7.42 (t, 1H), 7.38 (d, 2H), 7.05 (d, 2H), 7.00 (2H), 6.78 (d, 1H), 5.15 (s, 2H), 3.91 (s, 3H), 3.32 (4H), 2.65 (4H), 2.40 (s, 3H)

[0566] Step B: Preparation of 3-((5-chloro-3-(4-(4-methylpiperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(4-methylpiperazine-1-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (0.075 g, 0.15 mmol) obtained in step A, the title compound (0.044 g, 60% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 477 (M+1) 1H-NMR (400 MHz, DMSO-d6) δ 7.96 (d, 1H), 7.86 (dd, 1H), 7.61 (dd, 1H), 7.49 (t, 1H), 7.37 (d, 2H), 7.23 (d, 1H), 7.12 (3H), 6.91 (d, 1H), 5.20 (s, 2H), 3.25 (m, 4H), 2.55 (m, 4H), 2.29 (s, 3H)

[0567] Example 98: Manufacture of 3-(1-(5-chloro-3-(4-cyclohexylphenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (50 mg, 0.145 mmol) and (4-cyclohexylphenyl)boronic acid (59 mg, 0.29 mmol) obtained in Production Example 3, the title compound (20 mg, 28% yield) was obtained by the same method as in Step A and Step B of Example 1. 1 H-NMR (400 MHz, CDCl3) δ7.97 (d, 1H), 7.94 (s, 1H), 7.57 (d, 1H), 7.41 (m, 5H), 7.13 (m, 3H), 2.60 (m, 1H), 1.92 (m, 4H), 1.75 (m, 6H), 1.45 (m, 4H).

[0568] Example 99: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0569] Step A: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (78 mg, 0.23 mmol) and (4-(tetrahydro-2H-pyran-4-yl)phenyl)boronic acid (60 mg, 0.29 mmol) obtained in Production Example 3, the title compound (58 mg, 50% yield) was obtained by the same method as in Step A of Example 1. 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.98 (dd, 1H), 7.56 (dd, 1H), 7.48 (d, 2H), 7.40 (3H), 7.01 (d, 1H), 7.03 (dd, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 4.11 (m, 2H), 3.82 (s, 3H), 3.58 (m, 2H), 2.85 (m, 1H), 1.83 (m, 4H)

[0570] Step B: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)benzoic acid Using the 3-(1-(5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)methyl benzoate (58 mg, 0.115 mmol) obtained in step A, the title compound (46 mg, 82% yield) was obtained by the same method as in step B of Example 1. 1 H-NMR (400 MHz, CDCl3) δ 7.94 (dd, 1H), 7.91 (d, 1H), 7.54 (dd, 1H), 7.47 (d, 2H), 7.40 (3H), 7.13 (d, 1H), 7.08 (2H), 4.10 (m, 2H), 3.56 (m, 2H), 2.83 (m, 1H), 1.85 (4H), 1.74 (m, 2H), 1.68 (m, 2H)

[0571] Example 100: Preparation of 3-((5-chloro-3-(4-(1-(cyclopropanecarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0572] Step A: Preparation of 3-((5-chloro-3-(4-(1-(cyclopropancarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester To the 3-((5-chloro-2-oxo-3-(4-(piperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate hydrochloride (0.10 g, 0.19 mmol) obtained in Preparation Example 30, 2 mL of DCM, cyclopropane carbonyl chloride (19 μL, 0.22 mmol), and DIPEA (85 μL, 0.49 mmol) were added, and the mixture was stirred at room temperature for 1 hour. After adding water to the reaction mixture and separating the organic layer, the mixture was purified by MPLC to obtain the title compound (0.095 g, 89% yield). 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.98 (dd, 1H), 7.56 (dd, 1H), 7.48 (d, 2H), 7.43 (t, 1H), 7.39 (d, 2H), 7.07 (d, 1H), 7.02 (dd, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 4.82 (m, 1H), 4.40 (m, 1H), 3.91 (s, 3H), 3.24 (m, 1H), 2.87 (m, 1H), 2.70 (m, 1H), 1.98 (m, 2H), 1.81 (m, 1H), 1.71 (m, 2H), 1.02 (m, 2H), 0.79 (m, 2H)

[0573] Step B: Preparation of 3-((5-chloro-3-(4-(1-(cyclopropanecarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(1-(cyclopropanecarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (95 mg, 0.17 mmol) obtained in step A, the title compound (74 mg, 80% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 530 (M+1) 1 H-NMR (400 MHz, CDCl3) δ 8.11 (d, 1H), 8.03 (dd, 1H), 7.60 (dd, 1H), 7.46 (3H), 7.39 (d, 2H), 7.08 (d, 1H), 7.04 (dd, 1H), 6.83 (d, 1H), 5.18 (s, 2H), 4.80 (m, 1H), 4.40 (m, 1H), 3.20 (m, 1H), 2.87 (m, 1H), 2.70 (m, 1H), 1.96 (m, 2H), 1.81 (m, 1H), 1.70 (m, 2H), 1.04 (m, 2H), 0.80 (m, 2H)

[0574] Example 101: Preparation of 3-((5-chloro-3-(4-(1-(cyclobutancarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0575] Step A: Preparation of 3-((5-chloro-3-(4-(1-(cyclobutancarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate methyl ester To the 3-((5-chloro-2-oxo-3-(4-(piperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate hydrochloride (100 mg, 0.19 mmol) obtained in Preparation Example 30, 2 mL of DCM, cyclobutanecarboxylic acid (21 mg, 0.22 mmol), HATU (82 mg, 0.22 mmol), and DIPEA (85 μL, 0.49 mmol) were added, and the mixture was stirred at room temperature for 3 hours. After concentrating the reaction mixture under reduced pressure, it was purified by MPLC to obtain the title compound (90 mg, 83% yield). 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.98 (dd, 1H), 7.56 (dd, 1H), 7.48 (d, 2H), 7.45 (t, 1H), 7.36 (d, 2H), 7.07 (d, 1H), 7.02 (dd, 1H), 6.80 (d, 1H), 5.16 (s, 2H), 4.81 (m, 1H), 3.92 (s, 3H), 3.87 (m, 1H), 3.30 (m, 1H), 3.08 (m, 1H), 2.82 (m, 1H), 2.66 (m, 1H), 2.38 (m, 2H), 2.20 (m, 1H), 1.94 (m, 4H), 1.60 (m, 3H)

[0576] Step B: Preparation of 3-((5-chloro-3-(4-(1-(cyclobutancarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(1-(cyclobutanecarbonyl)piperidine-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (90 mg, 0.16 mmol) obtained in step A, the title compound (88 mg, 99% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 544 (M+1) 1H-NMR (400 MHz, CDCl3) δ 8.10 (d, 1H), 8.03 (dd, 1H), 7.60 (dd, 1H), 7.46 (3H), 7.36 (d, 2H), 7.07 (d, 1H), 7.03 (dd, 1H), 6.82 (d, 1H), 5.18 (s, 2H), 4.80 (m, 1H), 3.85 (m, 1H), 3.32 (m, 1H), 3.08 (m, 1H), 2.82 (m, 1H), 2.67 (m, 1H), 2.40 (m, 2H), 2.17 (m, 2H), 1.92 (4H), 1.62 (m, 2H)

[0577] Example 102: Preparation of 3-((5-chloro-2-oxo-3-(4-(1-propionylpiperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0578] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(1-propionylpiperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate To the 3-((5-chloro-2-oxo-3-(4-(piperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate hydrochloride (100 mg, 0.19 mmol) obtained in Preparation Example 30, 2 mL of DCM, propionyl chloride (20 mg, 0.22 mmol), and DIPEA (85 µl, 0.49 mmol) were added, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, the organic layer was separated, and the mixture was purified by MPLC to obtain the title compound (82 mg, 79% yield). 1H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.98 (dd, 1H), 7.56 (dd, 1H), 7.48 (d, 2H), 7.43 (t, 1H), 7.37 (d, 2H), 7.07 (d, 1H), 7.02 (dd, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 4.85 (m, 1H), 4.04 (m, 1H), 3.90 (s, 3H), 3.16 (m, 1H), 2.85 (m, 1H), 2.66 (m, 1H), 2.42 (q, 2H), 1.95 (m, 2H), 1.66 (m, 2H), 1.32 (t, 3H)

[0579] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-(1-propionylpiperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 3-((5-chloro-2-oxo-3-(4-(1-propionylpiperidine-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (80 mg, 0.15 mmol) obtained in step A, the title compound (75 mg, 96% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 518 (M+1) 1 H-NMR (400 MHz, CDCl3) δ 8.10 (d, 1H), 8.03 (dd, 1H), 7.61 (dd, 1H), 7.48 (3H), 7.37 (d, 2H), 7.07 (d, 1H), 7.03 (dd, 1H), 6.82 (d, 1H), 5.18 (s, 2H), 4.87 (m, 1H), 4.02 (m, 1H), 3.17 (m, 1H), 2.83 (m, 1H), 2.68 (m, 1H), 2.42 (q, 2H), 1.96 (m, 2H), 1.67 (m, 2H), 1.18 (t, 3H)

[0580] Example 103: Preparation of 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0581] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (100 mg, 0.32 mmol) and (4-(tetrahydro-2H-pyran-4-yl)phenyl)boronic acid (130 mg, 0.63 mmol) obtained in Production Example 1, the title compound (114 mg, 75% yield) was obtained by the same method as in step A of Example 1. 1 H-NMR (400 MHz, CDCl3) δ 8.05 (d, 1H), 7.98 (dd, 1H), 7.56 (dd, 1H), 7.48 (d, 2H), 7.40 (3H), 7.01 (d, 1H), 7.03 (dd, 1H), 6.81 (d, 1H), 5.16 (s, 2H), 4.11 (m, 2H), 3.82 (s, 3H), 3.58 (m, 2H), 2.85 (m, 1H), 1.83 (m, 4H)

[0582] Step B: Production of 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (114 mg, 0.29 mmol) obtained in step A, the title compound (100 mg, 91% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 463 (M+1) 1H-NMR (400 MHz, CDCl3) δ 8.11 (d, 1H), 8.03 (dd, 1H), 7.62 (dd, 1H), 7.48 (3H), 7.41 (d, 2H), 7.08 (d, 1H), 7.03 (dd, 1H), 6.83 (d, 1H), 5.18 (s, 2H), 4.12 (m, 2H), 3.57 (m, 2H), 2.85 (m, 1H), 1.83 (4H)

[0583] Example 104: Preparation of 3-((5-chloro-3-(4-(3,6-dihydro-2H-pyran-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0584] Step A: Preparation of 3-((5-chloro-3-(4-(3,6-dihydro-2H-pyran-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(4-(3,6-dihydro-2H-pyran-4-yl)phenyl)-1,3-dihydro-2H-benzo[d]imidazole-2-one (60 mg, 0.184 mmol) and 3-(bromomethyl)benzoate methyl ester (42 mg, 0.184 mmol) obtained in Preparation Example 31, the title compound (60 mg, 69% yield) was obtained by the same method as in step C of Preparation Example 7. 1 H-NMR (500 MHz, CDCl3) δ8.09 (s, 1H), 8.00 (d, 1H), 7.54 (m, 4H), 7.45 (m, 2H), 7.11 (s, 1H), 7.05 (d, 1H), 6.83 (d, 1H), 6.28 (s, 1H), 5.18 (s, 2H), 4.38 (m, 2H), 3.99 (m, 2H), 2.59 (m, 2H)

[0585] Step B: Preparation of 3-((5-chloro-3-(4-(3,6-dihydro-2H-pyran-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(3,6-dihydro-2H-pyran-4-yl)phenyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (60 mg, 0.126 mmol) obtained in step A, the title compound (11 mg, 19% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 461 (M+1) 1 H-NMR (400 MHz, DMSO-d6) δ7.98 (s, 1H), 7.87 (d, 1H), 7.66 (d, 2H), 7.62 (d, 1H), 7.59 (d, 2H), 7.50 (m, 1H), 7.27 (d, 1H), 7.17 (d, 1H), 7.06 (s, 1H), 6.38 (s, 1H), 5.22 (s, 2H), 4.27 (m, 2H), 3.86 (t, 2H), 2.50 (m, 2H)

[0586] Example 105: Preparation of 3-((5-chloro-3-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A and B.

[0587] Step A: Preparation of 3-((5-chloro-3-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 6-chloro-1-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-7-fluoro-1,3-dihydro-2H-benzo[d]imidazole-2-one (50 mg, 0.136 mmol) and 3-(bromomethyl)methyl benzoate (31 mg, 0.136 mmol) obtained in Preparation Example 32, the title compound (70 mg, 99% yield) was obtained by the same method as in step C of Preparation Example 7. 1H-NMR (400 MHz, CDCl3) δ8.03 (d, 1H), 7.98 (dd, 1H), 7.57 (dd, 1H), 7.36 (t, 1H), 7.34 (d, 2H), 7.02 (dd, 1H), 6.64 (3H), 5.14 (s, 2H), 3.92 (s, 3H), 3.73 (t, 2H), 3.58 (t, 2H), 2.52 (m, 2H)

[0588] Step B: Preparation of 3-((5-chloro-3-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using the 3-((5-chloro-3-(4-(3,3-difluoropyrrolidine-1-yl)phenyl)-4-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (70 mg, 0.136 mmol) obtained in step A, the title compound (35 mg, 51% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 502 (M+1) 1 H-NMR (400 MHz, CDCl3+MeOH-d4) δ8.06 (d, 1H), 8.00 (dd, 1H), 7.58 (dd, 1H), 7.45 (t, 1H), 7.35 (d, 2H), 7.03 (m, 1H), 6.64 (3H), 5.16 (s, 2H), 3.73 (t, 2H), 3.59 (t, 2H), 2.53 (m, 2H)

[0589] Example 106: Preparation of 3-(1-(5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoic acid [ka] Using 3-(1-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)-2-fluorobenzoate methyl ester (59 mg, 0.16 mmol) and (4-(tetrahydro-2H-pyran-4-yl)phenyl)boronic acid (67 mg, 0.32 mmol) obtained in Production Example 4, the title compound (20 mg, 24% yield) was obtained by the same method as in step A of Example 1 and step B of Example 24. 1 H-NMR (400 MHz, CDCl3) δ8.10 (t, 1H), 7.81 (t, 1H), 7.47 (d, 1H), 7.35 (dd, 4H), 7.09 (t, 1H), 7.04 (d, 1H), 6.97 (s, 1H), 4.10 (d, 2H), 3.53 (t, 2H), 2.79 (m, 1H), 1.79 (m, 4H), 1.59 (m, 4H)

[0590] Example 107: Preparation of 3-(1-(3-(4-(7-oxa-2-azaspiro[3.5]nonane-2-carbonyl)phenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)cyclopropyl)2-fluorobenzoic acid [ka] Using 4-(6-chloro-3-(1-(2-fluoro-3-(methoxycarbonyl)phenyl)cyclopropyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)benzoic acid (50 mg, 0.10 mmol) and 7-oxa-2-azaspiro[3.5]nonane (16 mg, 0.13 mmol) obtained in step B of Example 67, the title compound (16 mg, 28% yield) was obtained by the same method as in step C of Example 56 and step B of Example 24. MS [M+H] = 576 (M+1) 1H-NMR (400 MHz, DMSO-d6) δ7.93 (m, 1H), 7.83 (d, 2H), 7.75 (m, 1H), 7.61 (dd, 2H), 7.50 (m, 1H), 7.27 (m, 2H), 7.06 (d, 1H), 4.12 (s, 2H), 3.82 (s, 2H), 3.50 (m, 4H), 1.82 (m, 4H), 1.64 (m, 4H)

[0591] Example 108: Preparation of 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid [ka] The title compound was obtained through the following steps A and B.

[0592] Step A: Preparation of 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (0.050 g, 0.149 mmol) and (4-(tetrahydro-2H-pyran-4-yl)phenyl)boronic acid (0.092 g, 0.448 mmol) obtained in Production Example 2, the title compound (0.028 g, 38% yield) was obtained by the same method as in Step A of Example 1. 1 H-NMR (400 MHz, CDCl3) δ7.89 (m, 1H), 7.62 (m, 1H), 7.45 (d, 2H), 7.40 (d, 2H), 7.17 (t, 1H), 7.07 (m, 1H), 6.97 (d, 1H), 6.72 (d, 1H), 5.20 (s, 2H), 4.10 (m, 2H), 3.95 (s, 3H), 3.55 (m, 2H), 2.85 (m, 1H), 1.84 (m, 4H)

[0593] Step B: Preparation of 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoic acid Using 3-((5-chloro-2-oxo-3-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)-2-fluorobenzoate methyl ester (0.028 g, 0.057 mmol) obtained in step A, the title compound (0.027 g, 99% yield) was obtained by the same method as in step B of Example 24. MS [MH] = 479 (M-1) 1 H-NMR (400 MHz, DMSO-d6) δ7.80 (td, 1H), 7.50 (5H), 7.25 (t, 1H), 7.22 (d, 1H), 7.16 (dd, 1H), 7.01 (d, 1H), 5.22 (s, 2H), 3.98 (m, 2H), 3.48 (m, 2H), 2.88 (m, 1H), 1.75 (m, 4H)

[0594] Example 109: Preparation of 3-((5-chloro-2-oxo-3-(2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid [ka] The title compound was obtained through the following steps A, B, and C.

[0595] Step A: Preparation of 3-((3-(4-bromophenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate Using 3-((5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (170 mg, 0.537 mmol) and (4-bromophenyl)boronic acid (216 mg, 1.07 mmol) obtained in Preparation Example 1, the title compound (193 mg, 76% yield) was obtained by the same method as in step A of Preparation Example 25. MS [M+H] = 472 (M+1) 1H-NMR (400 MHz, CDCl3) δ8.03 (s, 1H), 7.97 (d, 1H), 7.68 (d, 2H), 7.53 (d, 1H), 7.43 (m, 3H), 7.05 (m, 2H), 6.80 (d, 1H), 5.14 (s, 2H), 3.90 (s, 3H)

[0596] Step B: Preparation of 3-((5-chloro-2-oxo-3-(2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoate To the 3-((3-(4-bromophenyl)-5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl benzoate (60 mg, 0.127 mmol) obtained in step A, 2-(cyclohexa-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (29.1 mg, 0.14 mmol), Cs2CO3 (124 mg, 0.382 mmol), and 2.5 mL of 1,4-dioxane were added, and the mixture was then filled with nitrogen gas. PdCl2(dppf)-CH2Cl2 (9.31 mg, 0.013 mmol) was added to the mixture, and the mixture was stirred at 80°C for 16 hours. After the reaction was completed, the solid was filtered using Celite, and the filtrate was purified by MPLC to obtain the title compound (28 mg, 46.5% yield). 1 H-NMR (400 MHz, CDCl3) δ8.04 (s, 1H), 7.96 (d, 1H), 7.53 (m, 3H), 7.43 (m, 3H), 7.06 (s, 1H), 7.00 (d, 1H), 6.79 (d, 1H), 6.18 (s, 1H), 5.14 (s, 2H), 3.90 (s, 3H), 2.43 (m, 2H), 2.23 (m, 2H), 1.80 (m, 2H), 1.68 (m, 2H)

[0597] Step C: Preparation of 3-((5-chloro-2-oxo-3-(2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)benzoic acid Using 3-((5-chloro-2-oxo-3-(2',3',4',5'-tetrahydro-[1,1'-biphenyl]-4-yl)-2,3-dihydro-1H-benzo[d]imidazole-1-yl)methyl)methyl benzoate (28 mg, 0.059 mmol) obtained in step B, the title compound (25 mg, 91.5% yield) was obtained by the same method as in step B of Example 24. MS [M+H] = 459 (M+1) 1 H-NMR (500 MHz, DMSO-d6) δ7.99 (s, 1H), 7.87 (d, 1H), 7.61 (m, 3H), 7.51 (m, 3H), 7.27 (d, 1H), 7.18 (d, 1H), 7.03...

Claims

1. A compound having the chemical structure of the following chemical formula 1, or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 (In the above chemical formula 1, Q １ and Q ２ Each is independently selected from the group consisting of carbon and nitrogen. X １ and X ２ Each is independently one selected from the group consisting of hydrogen; halogen; substituted or unsubstituted alkyl; substituted or unsubstituted cycloalkyl; and substituted or unsubstituted alkoxy; A is an aryl or heteroaryl; X ３ , X ４ , and X ５ Each is independently one selected from the group consisting of hydrogen; halogen; hydroxyl; oxo; carboxyl; substituted or unsubstituted alkoxy; substituted or unsubstituted thio; substituted or unsubstituted amino; substituted or unsubstituted carbamoyl; substituted or unsubstituted sulfonyl; substituted or unsubstituted alkyl; substituted or unsubstituted cycloalkyl; substituted or unsubstituted tricycloalkyl; substituted or unsubstituted heterocycloalkyl; substituted or unsubstituted oxoheterocycloalkyl; substituted or unsubstituted heterobicycloalkyl; substituted or unsubstituted cycloalkenyl; substituted or unsubstituted heterocycloalkenyl; substituted or unsubstituted oxazabicycloalkyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; substituted or unsubstituted heterocycloalkylcarbonyl; and substituted or unsubstituted heterobicycloalkylcarbonyl; Said X ３ , X ４ , and X ５ are each independently substituted with at least one selected from the group consisting of halogen; hydroxy; alkoxy; alkoxycarbonyl; sulfonyl; alkylsulfonyl; haloalkylsulfonyl; oxo; alkyl; haloalkyl; hydroxyalkyl; cycloalkyl; halocycloalkyl; heterocycloalkyl; alkyloxoheterocycloalkyl; aryl; heteroaryl; haloalkylheteroaryl; acetyl; alkylcarbonyl; haloalkylcarbonyl; cycloalkylcarbonyl; halocycloalkylcarbonyl; heterocycloalkylcarbonyl; haloheterocycloalkylcarbonyl; hydroxyheterocycloalkylcarbonyl; alkylheterocycloalkylcarbonyl; alkylamino; cycloalkylamino; cycloalkylalkylamino; and alkylaminocarbonyl; n is an integer between 0 and 3. R １ and R ２ Each of these is independently one selected from the group consisting of hydrogen; substituted or unsubstituted alkyl groups; and substituted or unsubstituted cycloalkyl groups, or the R １ and R ２ These are linked together to form substituted or unsubstituted hydrocarbon rings. B is an aryl or heteroaryl; X ６ and X ７ Each is independently one selected from the group consisting of hydrogen; halogen; hydroxyl; oxo; substituted or unsubstituted alkoxy; substituted or unsubstituted amino; substituted or unsubstituted alkyl; and substituted or unsubstituted cycloalkyl; The aforementioned X １ , X ２ , X ６ , X ７ , R １ , and R ２ The substituted functional groups are halogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, cycloalkyl, heterocycloalkyl, -OR ３ ,-(CO)-R ３ , - (CO) - OR ３ Substituted with at least one selected from the group consisting of alkylamino and oxo, and the R ３ (It is hydrogen or alkyl.)

2. The aforementioned Q １ and Q ２ This is either both being carbon, or only one being nitrogen. The aforementioned X １ and X ２ Each of these is independently selected from the group consisting of hydrogen; halogen; halogen-substituted or unsubstituted alkyl; halogen-substituted or unsubstituted cycloalkyl; and halogen-substituted or unsubstituted alkoxy; n is an integer between 0 and 1. R １ and R ２ Each of these is independently hydrogen; or a substituted or unsubstituted alkyl group; or the R １ and R ２ These are linked together to form one selected from the group consisting of substituted or unsubstituted cycloalkyls; substituted or unsubstituted heterocycloalkyls; substituted or unsubstituted aryls; and substituted or unsubstituted heterocycloaryls. B is phenyl; or a heteroaryl comprising at least one selected from the group consisting of N and O; X ６ and X ７ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein each is independently selected from the group consisting of hydrogen; halogen; hydroxyl; oxo; and substituted or unsubstituted alkyl.

3. The aforementioned X １ and X ２ Each is independently selected from the group consisting of hydrogen; halogen; halogen-substituted or unsubstituted alkyl; unsubstituted cycloalkyl; and halogen-substituted alkoxy; The aforementioned R １ and R ２ Each of these is independently hydrogen; or a substituted or unsubstituted C1-C6 alkyl group; or the R １ and R ２ These are linked together to form substituted or unsubstituted cycloalkyl groups. The aforementioned B is one selected from the group consisting of phenyl; pyridine; oxazole; and isoxazole. The aforementioned X ６ and X ７ The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein each is independently hydrogen or a halogen.

4. The aforementioned X １ and X ２ Each of these is independently selected from the group consisting of hydrogen; halogen; halogen-substituted or unsubstituted C1-C3 alkyl; unsubstituted C3-C6 cycloalkyl; and halogen-substituted C1-C3 alkoxy; The aforementioned R １ and R ２ Each is independently hydrogen; or methyl; or the R １ and R ２ The compound according to claim 3 or a pharmaceutically acceptable salt thereof, wherein the atoms are linked to each other to form a cycloalkyl group having 3 to 6 carbon atoms.

5. The above A is one selected from the group consisting of phenyl; benzodioxolyl; pyridinyl; pyrimidinyl; pyrazolyl; dihydroindenyl; isoindolinyl; benzothiazolyl; dihydroisobenzofuranyl; and dihydrobenzooxazinyl. The aforementioned X ３ , X ４ , and X ５ These are, independently, hydrogen; halogen; hydroxy; oxo; carboxy; substituted or unsubstituted alkoxy; alkylthio; substituted or unsubstituted amino; substituted or unsubstituted carbamoyl; substituted or unsubstituted sulfonyl; substituted or unsubstituted alkyl; substituted or unsubstituted cycloalkyl; substituted or unsubstituted tricycloalkyl; substituted or unsubstituted morpholino; substituted or unsubstituted pyrrolidinyl; substituted or unsubstituted azetidinyl yl); substituted or unsubstituted piperazinyl; substituted or unsubstituted piperidinyl; substituted or unsubstituted oxazepanyl; substituted or unsubstituted oxetanyl; substituted or unsubstituted tetrahydrofuranyl; substituted or unsubstituted tetrahydropyranyl; substituted or unsubstituted oxopiperidinyl; substituted or unsubstituted These include unsubstituted oxoxazolidinyl; substituted or unsubstituted oxoxazaspiroalkanyl; substituted or unsubstituted azaspiroalkanyl; substituted or unsubstituted oxazaspiroalkanyl; substituted or unsubstituted diazaspiroalkanyl; substituted or unsubstituted cycloalkenyl; and substituted or unsubstituted dihydropyra dihydrofuranyl; substituted or unsubstituted dihydrofuranyl; substituted or unsubstituted oxazabicycloalkyl; substituted or unsubstituted phenyl; substituted or unsubstituted oxadiazolyl; substituted or unsubstituted pyrazolyl; substituted or unsubstituted pyrrolidinecarbonyl; substituted or unsubstituted piperazinecarbonyl;The compound according to claim 4, or a pharmaceutically acceptable salt thereof, selected from the group consisting of substituted or unsubstituted piperidine carbonyl; substituted or unsubstituted morpholine carbonyl; substituted or unsubstituted azetidine carbonyl; and substituted or unsubstituted oxazaspiroalkane carbonyl;

6. The above A is phenyl; benzo[d][1,3]dioxolyl; pyridine-2-yl; pyridine-3-yl; pyrimidine-5-yl; 1H-pyrazole-4-yl; 2,3-dihydro-1H-inden-5-yl; isoindoline It is one selected from the group consisting of -5-yl (isoindolin-5-yl); benzo[d]thiazol-2-yl (benz[d]thiazol-2-yl); 1,3-dihydroisobenzofuran-5-yl (1,3-dihydroisobenzofuran-5-yl); and 3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl (3,4-dihydro-2H-benz[b][1,4]oxazin-7-yl), The aforementioned X ３ , X ４ , and X ５ These are, independently, hydrogen; halogen; hydroxy; oxo; carboxy; methoxy; ethoxy; propoxy; isopropoxy; cyclobutyl methoxy; cyclopropyl methoxy; methylthio; dimethylamino (ylamino); isobutyrylamide; methylsulfonamide; (2,2,2-trifluoroethyl)sulfonamide; methylcarbamoyl; dimethylcarbamoyl; (2,2,2-trifluoroethyl)sulfonamide; (2,2,2-trifluoroethyl)sulfonamide; (2,2,2-trifluoroethyl)carbamoyl; methylsulfonyl; morpholinosulfonyl; piperidin-1-ylsulfonyl; pyrrolidine-1-ylsulfonyl; N,N-di Methylsulfamoyl (N,N-dimethylsulfamoyl); N-cyclopropylsulfamoyl (N-cyclopropylsulfamoyl); N-(cyclobutylmethyl)sulfamoyl (N-(cyclobutylmethyl)sulfamoyl); methyl (methyl); propyl (propyl); isopropyl (isopropyl); tert-butyl (tert-butyl); Butyl; 2-hydroxypropan-2-yl; trifluoromethyl; 2,2,2-trifluoroethyl; 2-hydroxy-2-methylpropyl; 2-fluoro-2-methylpropyl;1-hydroxy-2-methylpropan-2-yl; 1-fluoro-2-methylpropan-2-yl; (2-oxopyrrolidine-1-yl)methyl((2-oxopyrrolidine-1-yl)methyl); ((3-(trifluoromethyl)-1H-pyrazole-4-yl)methyl(((3-(trifluoromethyl)-1H-pyrazole-4-yl)methyl); (4-(trifluoro (methyl)-1H-imidazole-1-yl)methyl((4-(trifluoromethyl)-1H-imidazol-1-yl)methyl); (3-methyl-2-oxo-imidazolin-1-yl)methyl((3-methyl-2-oxo-imidazolin-1-yl)methyl); oxetan-3-ylmethyl(oxetan-3-ylmethyl); 2-(dimethylamino)-2-oxoethyl(2-(dimethylamino)-2-oxoethyl); 2-oxo-2-(pyrrolidine-1-yl)ethyl( 2-oxo-2-(pyrrolidin-1-yl)ethyl); morpholinomethyl; 2-morpholino-2-oxoethyl; 2-(4,4-difluoropiperidine-1-yl)-2-oxoethyl; 2-(3-hydroxyazetidine-1-yl)-2-oxoethyl; 2-(2-methylmorpholino)-2-oxoethyl; 2-(3-methylmorpholino)-2-oxoethyl; cyclopropylmethyl; cyclobutylmethyl; cyclopropyl; 1-(hydroxymethyl)cyclopropyl;1-(hydroxymethyl)cyclobutyl (1-(hydroxymethyl)cyclobutyl); 1-hydroxycyclobutyl (1-hydroxycyclobutyl); cyclohexyl (cyclohexyl); (3r,5r,7r)-adamantan-1-yl ((3r,5r,7r)-adamantan-1-yl); morpholino (morpholino); 3-methyloxetan-3-yl (3-methyloxetan-3-yl); 3-hydroxyoxetan-3-yl (3-hydroxyoxetan- 3-yl); tetrahydro-2H-pyran-4-yl; tetrahydrofuran-3-yl; 2-oxo-piperidine-1-yl; pyrrolidine-1-yl; 3-hydroxyazetidine-1-yl; 3,3-difluoroazetidine-1-yl ); 3,3-difluoropyrrolidine-1-yl; 4-methylpiperazin-1-yl; 4,4-difluoropiperidine-1-yl; 4-(cyclopropanecarbonyl)piperazin-1-yl; 4-(cyclobutanecarbonyl)piperazin-1-yl 4-(isopropoxycarbonyl)piperazin-1-yl); 4-(4,4-difluorocyclohexane-1-carbonyl)piperazin-1-yl; 1-(oxetan-3-yl)piperidine-4-yl;1-(cyclopropanecarbonyl)piperidine-4-yl; 1-(cyclobutanecarbonyl)piperidine-4-yl; 1-(cyclobutanecarbonyl)piperidine-4-yl; 1-propionylpiperidine-4-yl; 4-propionylpiperazin-1-yl; 3,6-dihydro-2H-pyran-4-yl (3,6 2-dihydrofuran-3-yl; 2-azaspiro[3.3]heptan-2-yl; 7-oxa-2-azaspiro[3.5]nonan-2-yl; 2-oxa-6-azaspiro[3.3]heptan-6-yl; 2-oxa-5-azaspiro Clo[2.2.1]heptan-5-yl; 8-oxa-3-azabicyclo[3.2.1]octan-3-yl; 1,4-oxazepan-4-yl; 7-acetyl-2,7-diazaspiro[3.5]nonan-2-yl; 7-(tert-butoxycarbonyl) )-2,7-diazaspiro[3.5]nonan-2-yl(7-(tert-butoxycarbonyl)-2,7-diazaspiro[3.5]nonan-2-yl); 4,4-dimethyl-2-oxo-oxazolidine-3-yl(4,4-dimethyl-2-oxo-oxazolidine-3-yl); 5-oxo-6-oxa-4-azaspiro[2.4]heptan-4-yl(5-oxo-6-oxa-4-azaspiro[2.4]heptan-4-yl); cyclohexen-1-yl(cyclohexen-1-yl);4-methyl-cyclohexen-1-yl; 4',4'-dimethyl-cyclohexen-1-yl; phenyl; chlorophenyl; 5-cyclopropyl-1,3,4-oxadiazole-2-yl; 5-cyclopentyl-1,3,4-oxadiazole-2-yl ,3,4-oxadiazol-2-yl);5-cyclohexyl-1,3,4-oxadiazol-2-yl;5-cycloheptyl-1,3,4-oxadiazol-2-yl;5-(tetrahydro-2H-pyran-4-yl)-1,3,4-oxadiazol-2-yl;5-(tetrahydro-2H-pyran-4-yl)-1,3,4-oxadiazol-2-yl);5- (4,4-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl (5-(4,4-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl); 1-propyl-1H-pyrazole-4-yl (1-propyl-1H-pyrazole-4-yl); piperidine-1-carbonyl (piperidine-1-carbonyl); morpholine-4-carbonyl (morpholine-4-carbonyl); 3-methylmorpholino-4-carbonyl (3-methylmorpholino- 4-carbonyl); pyrrolidine-1-carbonyl; azetidine-1-carbonyl; 3-hydroxyazetidine-1-carbonyl; 3,3-difluoroazetidine-1-carbonyl; 3-methoxypyrrolidine-1-carbonyl;3,3-difluoropyrrolidine-1-carbonyl; 4-methylpiperazine-1-carbonyl; 4-hydroxypiperidine-1-carbonyl; 4-methoxypiperidine-1-carbonyl; The compound according to claim 5 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of (-methoxypiperidine-1-carbonyl); 4,4-difluoropiperidine-1-carbonyl; 7-oxa-2-azaspiro[3.5]nonane-2-carbonyl; and 2-oxa-6-azaspiro[3.3]heptane-6-carbonyl.

7. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, wherein the compound having the chemical structure of chemical formula 1 is at least one selected from the group consisting of the compounds listed in Table 3 below. Table 1 Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8 Table 9 Table 10 Table 11 Table 12 Table 13 Table 14

8. A pharmaceutical composition comprising a compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition according to claim 8, for the prevention or treatment of autotaxin-mediated diseases.

10. The pharmaceutical composition according to claim 9, wherein the autotaxin-mediated disease is a disease induced by overexpression or overactivation of autotaxin.

11. The pharmaceutical composition according to claim 10, wherein the autotaxin-mediated disease is cancer or fibrosis.

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