KR20210052269A - Novel Compound for Crop Protection - Google Patents

Abstract

The present invention provides a compound represented by chemical formula I, and a pest control composition containing the same. The pest control composition according to the present invention containing the compound expresses an excellent mortality rate even under a relatively low concentration.

Description

New compound for crop protection agent {Novel Compound for Crop Protection}

The present invention relates to a novel compound for a crop protection agent.

Some insects survive while parasitic to animals and plants, and among these insects, insects that cause damage to crops, in particular, are referred to as so-called plant pests. Plant pests are causing great damage to crop cultivation by extorting nutrients from the roots, stems, or leaves of crops or by eating the crop itself.

On the other hand, various types of control agents are used to remove pests. Nevertheless, as resistance to control agents is expressed in pests, it is difficult to effectively eradicate various pests. Accordingly, it is considered to use a more highly toxic and high-concentration control agent, but this may cause serious contamination of the soil, and may cause secondary damage to humans or animals eating the crop due to the control agent remaining in the crop.

Therefore, there is a need for a new material that can be safer for humans and livestock while having excellent control effect against pests at a relatively low concentration.

An object of the present invention is to provide a novel insecticidal active compound and a control composition comprising the same.

The compounds according to the present invention can exhibit excellent mortality even under relatively low concentrations against pests, for example aphids.

In one embodiment, the invention provides a compound represented by formula (I):

[Formula I]

In the above formula,

X ¹ is oxygen or sulfur,

Ring A is a substituted or unsubstituted, aliphatic or aromatic 5-membered heterocycle group consisting of 2 carbon atoms and 3 hetero atoms, and A ¹ and A ² are each independently nitrogen, oxygen or sulfur,

R ¹ , R ² and R ³ are each independently selected from hydrogen or the following substituent group I,

n4 is an integer of 1 to 3, R ⁴ is the same as or different from each other when n4 is 2 or more, and each independently selected from hydrogen or the following substituent group I and / or fused to each other and substituted with carbon bonded thereto or Forming an unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 membered heterocycle group,

The substituent group I is a substituted or unsubstituted C _1-10 alkyl group, a substituted or unsubstituted C _2-10 alkenyl group, a substituted or unsubstituted C _3-20 carbocycle group, a substituted or unsubstituted C _3-20 Cycloalkyl group, substituted or unsubstituted C _6-30 aryl group, substituted or unsubstituted 3 to 30 membered heterocycle group, substituted or unsubstituted C _1-10 alkoxy group, substituted or unsubstituted C _2-10 alkenyloxy group , A substituted or unsubstituted C _3-10 cycloalkyloxy group, a substituted or unsubstituted C _6-30 aryloxy group, a substituted or unsubstituted 3 to 30 membered heterocycleoxy group, a substituted or unsubstituted C _1-10 alkylcarbonyl Group, substituted or unsubstituted C _2-10 alkenylcarbonyl group, substituted or unsubstituted C _3-10 cycloalkylcarbonyl group, substituted or unsubstituted C _6-30 arylcarbonyl group, substituted or unsubstituted 3 to 30 A membered heterocyclecarbonyl group, a substituted or unsubstituted C _1-10 alkylthio group, a substituted or unsubstituted C _2-10 alkenylthio group, a substituted or unsubstituted C _3-10 cycloalkylthio group, a substituted or unsubstituted C _6-30 arylthio group, substituted or unsubstituted 3 to 30 membered heterocyclethio group, aldehyde group, carboxyl group, halogen group, C _1-10 haloalkyl group, hydroxyl group, substituted or unsubstituted amino group, imine group , A cyano group, a nitro group, an amide group, a thiol group, a sulfone group and a phosphoric acid group,

Here, C _1-10 alkyl moiety is _{-O-, -S-, -SO-, -SO 2} -, -NR a - (R a is hydrogen or a substituted or unsubstituted C _1-10 alkyl), -N = , =N-, -POR ^a -and -PO ₄ R ^a -, and the heterocycle moiety includes at least one of sulfur, nitrogen, phosphorus and oxygen as a ring member.

In one embodiment, the present invention provides acceptable salts of the above compounds, enantiomers thereof, diastereomers thereof, solvates thereof, geometric isomers thereof or tautomers thereof.

In one embodiment, the present invention provides a control composition comprising as an active substance at least one of an acceptable salt thereof, an enantiomer thereof, a diastereomer thereof, a solvate thereof, a geometric isomer thereof and a tautomer thereof.

Such a control composition may include 0.01 to 3,000 ppm of the active substance, in detail 0.1 to 1,000 ppm, and more specifically 0.1 to 100 ppm. The control composition has a mortality of 30% or more, specifically 50, against pests, specifically, Bansi mok (Norinwood) pests, and more specifically, pests with aphids, even at relatively low concentrations as described above. % Or more, more specifically 70% or more, particularly 99% or more.

The compounds according to the invention are capable of effective killing action against pests, for example pests with aphids.

The control composition according to the present invention containing the compound exhibits excellent mortality even under a relatively low concentration.

Hereinafter, the intention, action, and effect of the present invention will be described in more detail through embodiments of the present invention and specific examples thereof. However, the following examples are presented as examples to aid the understanding of the present invention, and the scope of the invention is not limited or limited thereto.

Embodiments of the invention are described in more detail in the order of “compound” and “control composition” according to the invention.

Prior to this, terms or words used in the specification and claims should not be construed as being limited to their usual or dictionary meanings, and the inventors appropriately explain the concept of terms in order to explain their own invention in the best way. Based on the principle that it can be defined, it should be interpreted as a meaning and concept consistent with the technical idea of the present invention.

Therefore, the configuration of the embodiments described in the present specification is only one of the most preferred embodiments of the present invention, and does not represent all the technical spirit of the present invention, and various equivalents and modifications that can replace them at the time of application It should be understood that examples may exist.

In this specification, expressions in the singular include plural expressions unless the context clearly indicates otherwise.

In the present specification, when a certain part "includes" a certain component, it means that other components may be further included rather than excluding other components unless specifically stated to the contrary. Thus, for example, a composition comprising Compound A may contain other compounds in addition to A. However, the term “comprising” also encompasses “consisting essentially/essentially of” and “consisting of” in a more restrictive sense as a specific embodiment thereof, for example, “comprising compound A. The "composition" can also (essentially/essentially) consist of Compound A.

In connection with this, in the present specification, terms such as "having" or "having" are intended to designate that a feature, number, step, component, or combination thereof is present, but one or more other features or numbers. It is to be understood that the possibility of the presence or addition of, steps, components, or combinations thereof is not preliminarily excluded.

As used herein, enantiomer refers to two stereoisomers of a compound that are mirror images that are not superimposed with each other.

As used herein, diastereomers refer to stereoisomers that have two or more chiral centers and the molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting point, boiling point, spectral properties and reactivity. Mixtures of diastereomers can be separated under high resolution analytical procedures such as electrophoresis and chromatography.

In the present specification, geometric isomers refer to cis type in which atoms or groups of the same type are on the same side with a double bond as the center, trans type in which atoms or groups of the same type are on the opposite side with a double bond as the center, or in CIP priority. It means E-type or Z-type according to.

As used herein, tautomeric or tautomeric forms refer to structural isomers of different energies that are compatible through a low energy barrier. For example, proton tautomers (also known as proton tautomers) include interconversions through the transfer of protons, such as keto-enol and imine-enamine isomerization. Valence tautomers involve interconversion by retransfer of some bonding electrons.

As used herein, solvate refers to an aggregate or complex of one or more solvent molecules and a compound of the present invention. Examples of solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethylsulfoxide, ethyl acetate, acetic acid and ethanolamine. Hydrate refers to a complex in which the solvent molecule is water.

As used herein, the term "acceptable salt" refers to a salt of an active compound prepared with an acid or a base, which depends on the specific substituents based on the compounds described herein. When the compounds according to the invention contain relatively acidic functional groups, base addition salts can be obtained by contacting such compounds in a neutral state with a sufficient amount of the desired base in a solvent-free or suitable inert solvent.

Acceptable salts include, for example, alkali metal salts such as sodium or potassium salts; Alkaline earth metal salts such as calcium or magnesium salts; Ammonium salt; Aliphatic amino salts such as trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine or procaine salt; Aralkyl amine salts such as N,N-dibenzylethylenediamine salt; Heterocyclic aromatic amine salts such as pyridine salt, picolino salt, quinoline salt or isoquinoline salt; Quaternary ammonium salts such as tetramethylammonium salt, tetraethylammonium salt, benzyltrimethylammonium salt, benzyltriethylammonium salt, benzyltributylammonium salt, methyltrioctylammonium salt or tetrabutylammonium salt; And basic amino acid salts such as arginine salts or lysine salts. Acid salts include, for example, inorganic acid salts such as hydrochloride, sulfate salt, nitrate salt, phosphate salt, carbonate salt, hydrogen carbonate or perchlorate; Organic acid salts such as acetate, propionate, lactate, malate, fumarate, tartaric acid salt, malate, fumarate, citrate salt, ascorbate, formic acid; Sulfonates such as methanesulfonate, isothionate, benzenesulfonate or p-toluenesulfonate; And acidic amino acid salts such as aspartate or glutamate. Solvates of the compounds of the present invention include, but are not limited to, alcoholates and hydrates.

In the present specification, when an amount, concentration, or other value or parameter is given as a range, a preferred range or an enumeration of a preferred upper and lower preferred value, any pair of any upper range limits, regardless of whether the range is disclosed separately. Or it is to be understood as specifically disclosing the preferred values and any lower range limits or all ranges that may be formed with preferred values. When a range of numerical values is mentioned in the specification, unless otherwise stated, for example, unless there is a limiting term such as more than, less than, the range is intended to include the end value and all integers and fractions within the range. Is intended. It is intended that the scope of the invention is not limited to the specific values recited when defining the range.

In the present specification, the term "pest" broadly refers to an invertebrate that is directly or indirectly harmful to humans, and narrowly refers to an invertebrate that directly or indirectly damages at least one of animals and plants, and more specifically, direct to plants. It refers to an invertebrate that causes damage.

Examples of the pests intended in the present invention include, but are not limited to, Psoriasis (Lepidoptera) pests, Bansi (Lepidoptera) pests, Pseudomonas (Bermatophytes) Pests, Pseudomonas (Paris) Pests, Maxima (Felling) Pests, And locust tree pests, thrips order pests, mite order pests, cockroach order pests, tomato moth (Tuta absoluta), and nematodes.

Incidentally, the compound according to the present invention may be particularly effective in insecticidal activity against Bansi-mok (Norinwood) pests and/or nematodes, and among them, it may express particularly strong insecticidal activity on pests belonging to the Bansi-Organic Aphid family.

An example of a bansi-mok (Norin lumber) pest. Without limitation, Nezara antennata, Stenotus rubrovittatus, Graphosoma rubrolineatum, Trigonotylus coelestialium, etc., red weeds (Aeschynteles maculatus), wing Creontiades pallidifer), Dysdercus cingulatus, Chrysomphalus ficus, Aonidiella aurantii, Graptopsaltria nigrofuscata, Bliss cingulatus Blissusleucopterus), Iseria purchasi, Piezodorus hybneri, Lagynotomus elongatus, Thaia subrufa, Scotinophara lurida, Sitobion rae aphid , Stariodes iwasakii, Aspidiotus destructor, Taylorilygus pallidulus, Myzusmumecola, Pseudaulacaspis prunicola, Pea beard aphid (Acyrthosiphon pisum) Anacanthocoris striicornis, Ectometopterus micantulus, Eysarcoris lewisi, Molipteryx fulginosa, Horse cicada (Cicadella viridis) Rhopalosophum rufiabdominalis, Saissetia oleae, Trialeurodes vaporarioru m), Agriahana quercus, Lygus spp., Euceraphis punctipennis, Andaspis kashicola, Coccus pseudomagnoliarum, half-winged Cavelerius saccharivorus, Galeatus spinifrons, Chrysanthemum aphid (Macrosiphoniella sanborni), Aonidiella citrina, Halyomorpha mista, Halyomorpha mista, Stephanitis fasciicarina, Stephanitis fascicarina Trioza camphorae, Leptocorisa chinensis, Trioza quercicola, Uhlerites latius, Erythroneura comes, Paromius exigus (Paromius exiguus), Duplaspidiotus claviger, Nepotetics nigropictus, Halticiellus insularis, Perkinsiella saccharicida, Perkinsiella saccharicida (Perkinsiella saccharicida) Psylla malivorella, Anomomeura mori, Pseudococcus longispinis, Pseudaulacaspis pentagona, Pulvinaria kuwacola, Green. Apolygus lucorum, Togo hemipterus, Toxoptera aurantii, Saccharicoccus sacchari, Geoica luc ifuga), Numata muiri, Comstockaspis perniciosa, Unaspis citri, Aulacorthum solani, Eysarcoris ventralis, Bemicia argenti Bemisia argentifolii, Cicadella spectra, Aspidiotus hederae, Liorhyssus hyalinus, Calophya nigridorsalis, Whiteback ( Sogatella furcifera), Megoura crassicauda, Cabbage aphid (Brevicoryne brassicae), Soybean aphid (Aphis glycines), Leptocorisa oratorius (Leptocorisa oratorius), Two-pointed cicada (Nephotettix virescens) Uroeucon formosanum, Cytopeltis tennuis, Bemisia tabaci, Lecanium persicae, Parlatoria theae, Pseudaonidia paeoniae, O Empoasca onukii, Brown-winged stali, Dysaphis tulipae, Macrosiphum euphorbiae, Stephanitis pyrioides, Ceroplastes ceriferus Camellia camelliae, Apolygus spinolai, Nephotettix cincticeps, Glaucias subpunctatus, Orthotylus flavosparsus), Rhopalosiphum maidis, Peregrinus maidis, Eysarcoris parvus, Cimex lectularius, Psylla abieti, Psylla abieti, Nilaparvata lugens Psylla tobirae, Eurydema rugosum, Schizaphis piricola, Psylla pyricola, Parlatoreopsis pyri, Stephanitis nashi, wisteria Dysmicoccus wistariae, Lopoleucaspis japonica, Sappaphis piri, Lipaphis erysimi, Neotoxoptera formosana, Lopalo (Rhopalosophum nymphaeae), Edwardsianarosae, Pinnaspisaspidistrae, Psylla alni, Speusotettix subfusculus, Alnetoidia Alnetoidia alneti, Sogatella panicicola, Adelphocoris lineolatus, Dysdercus poecilus, Parlatoria ziziphi, oak Uhlerites debile, Laodelphax striatella, Eurydema pulchrum, Cletus trigonus, Clovia punctata, paulownia cicada (Empoasca) sp.), Fig. hesperidum, Pachybrachius luridus, Greenhouse dusty beetle (Planococcus kraunhiae), Stenotus binotatus, Arboridia apicalis, Macrosteles fascifrons, Dolycoris baccarum, Adelphocoris triannulatus, Viteus vitifolii, Acanthocoris sorcifrons, leptocoris sordiduta ), Macropes obnubilus, Cletus punctiger, Riptortus clavatus, Paratrioza cockerelli, Aphrophora costalis, Ligus Lygus disponsi, Lygus saundersi, Crisicoccus pini, Empoasca abietis, Crisicoccus matsumotoi, Aphis craccivora, Margaret Megacopta punctatissimum, Eysarcoris guttiger, Lepidosaphes beckii, Diaphorina citri, Toxoptoccus citriidus, Tangerine aphid (Planococcus citricidus) ), Dialeurodes citri, Aleurocanthus spiniferus, Pseudococcus citriculus, Zyginella citri, Fulbinaria chitri Pulvinaria citricola, Coccus discrepans, Pseudaonidia duplex, Pulvinaria aurantii, Lecanium corni, Nezara viridula, Stenodema calcaratum, Rhopalosiphum padi, Sitobion akebiae, Schizaphis graminum, Sorhoanus tritici, Prunus aphid Brachycaudus helichrysi), Carpocoris purpureipennis, peach aphid (Myzus persicae), peach aphid (Hyalopterus pruni), Aphis farinose yanagicola (Aphis farinose yanagicola), popula shield bug (Metasalis populi) Unaspis yanonensis, Mesohomotoma camphorae, Aphis spiraecola, Aphis pomi, Lepidosaphes ulmi, Psylla mali, apple Heterocordylus flavipes, Myzus malisuctus, Aphidonuguis mali, Orientus ishidai, Ovatus malicolens, and Eriosoma lanigerum , Ceroplastes rubens, and cotton aphids (Aphis gossypii).

Nematodes are root-knot nematodes (Meloidogyne spp.), cyst nematodes (Globodera spp.), seed nematodes (Anguina spp.), stem bulbous nematodes (Ditylenchus spp.), stem nematodes (Ditylenchusspp.), depending on their morphology, attack pattern, and host. , Root rotting nematodes (Pratylenchus spp.), leaf nematodes (Aphelenchoides spp.), citrus nematodes (Rotylenchulus spp.), etc., and examples of nematodes include Meloidogyne incognita, Meloido Meloidogyne incognita acrita, Meloidogyne javanica, Meloidogyne kikuyensis, Meloidogyne naasi, Meloidogyne paranaensis ), Meloidogyne thamesi, Meloidogyne acronea, Meloidogyne africana, Meloidogyne arenaria, Meloidogyne arenaria arenariathamesi), Meloidogyne artiella, Meloidogyne chitwoodi, Meloidogyne coffeicola, Meloidogyne ethiopica, Meloidogyne ethiopica, Meloidogyne ethiopica Gua (Meloidogyne exigua), Meloidogyne graminicola, Meloidogyne graminis, and Meloidogyne hapla, but are not limited thereto.

In the present specification, the term "pest control" means to kill insects belonging to the pest, or to prevent or hinder the occurrence, growth and reproduction of the pest.

In the present specification, the term "insecticide activity" paralyzes the nervous system of an insect to be controlled, inhibits the production of the epidermis of the insect, or inhibits the respiration of the insect, which is helpful in controlling the target insect. It means a property or ability.

In the present specification, the term "substitution" may mean that a hydrogen atom bonded to a compound or each of the substituents listed in the substituent group is replaced by an optional substituent and bonded. In this case, the position to be substituted is not limited as long as the compound or the position at which the hydrogen atom bonded to each of the substituents listed in the substituent group exists, that is, the position at which the hydrogen atom can be substituted with a substituent. If more than one is substituted, the two or more substituents may be the same or different from each other. Conversely, "unsubstituted" may mean that no hydrogen atom bonded to a carbon atom has been replaced with an optional substituent.

Any substituent applicable to the above "substituent" may be appropriately selected from the substituents listed in the substituent group as described herein, but the scope of the substituent that can be substituted is not limited to such a substituent group.

Substituents preferably applicable to the "substitution" are, in detail, a halogen group, a C _1-10 alkyl group, a C _2-10 alkenyl group, a C _2-10 alkynyl group, a C _{3-10 carbocycle} group, C _3-10 cycloalkyl group, C _6-30 aryl group, 3 to 30 membered heterocycle group, C _1-10 alkoxy group, C _2-10 alkenyloxy group, C _2-10 alkynyloxy group, C _{3 -10} cycloalkyloxy group, C _6-30 aryloxy group, 3 to 30 membered heterocycleoxy group, C _1-10 alkylcarbonyl group, C _1-10 alkenylcarbonyl group, C _1-10 alkylcarboxyl Group, C _1-10 alkenylcarboxyl group, C _1-10 cycloalkylcarbonyl group, C _6-30 arylcarbonyl group, 3 to 30 membered heterocyclecarbonyl group, C _1-10 alkylthio group, C _1-10 alkenylthio group, C _1-10 cycloalkylthio group, C _6-30 arylthio group, 3 to 30 membered heterocyclethio group, aldehyde group, carboxyl group, hydroxyl group, amino group, imine group, It may be selected from the group consisting of a cyano group, a nitro group, an amide group, a thiol group, a sulfone group and a phosphoric acid group.

If, in the formula described in the present specification, a substituent group is not separately described or mentioned, hydrogen may be considered to be bonded, and in some cases, a substituent may be absent depending on a ring member constituting a heterocycle.

In the present specification, the term "group" as described herein is combined with a preceding substituent, for example alkyl, to form the term "alkyl group", and alkyl may be bonded to any position of the compound or substituent, or It means that it is combined.

In the present specification, halogen may include Cl, F, Br and I.

_{In the present specification, alkyl is a straight chain having the number of carbon atoms indicated (i.e., C 1-10} means 1 to 10 carbons), by itself or as part of another substituent, unless otherwise stated It means a branched chain monovalent hydrocarbon.

Examples of alkyl include methyl, ethyl, propyl, n-propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n -Pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl , n-heptyl, 1-methylhexyl, 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, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethyl-propyl, 1,1-dimethyl-propyl, isohexyl, 2-methylpentyl, 4-methylhexyl, 5-methylhexyl, etc. , This is a non-limiting example, and the scope of the present invention is not limited thereto.

In the present specification, alkenyl may be linear or branched. Alkenyl is, for example, ethenyl, 1-propenyl, 2-propenyl or 1-methylethenyl, ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl or 2-methyl-2-propenyl, 1-pentenyl , 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-moiety Tenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1 -Dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1- Hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3 -Pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3 -Methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl- 3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3 ,3-dimethyl-1-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2- Ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl , 1-ethyl-2-methyl-1-propenyl, 1-ethyl-2-methyl-2-propenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 1-octenyl, 2-oxy Tenyl, 3-octenyl, 4-octenyl, 1-nonenyl, 2-no Neyl, 3-nonenyl, 4-nonenyl, 1-decenyl, 2-decenyl, 3-decenyl, 4-decenyl, 5-decenyl, and the like, but are not limited thereto.

In the present specification, alkynyl may be a straight chain or branched chain, for example, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propy Nyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3 -Methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5- Hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3- Methyl-1-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl -3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1- Ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl, 2,5-hexadiynyl, and the like, but are not limited thereto.

In the present specification, haloalkyl is synonymous with "halogenated alkyl" and "halogen substituted alkyl", wherein any hydrogen atom in the alkyl is substituted with any halogen, for example, a halogen atom selected from Cl, F, Br and I. May mean alkyl. For example, -CF ₃ , -CH ₂ Cl, -CH ₂ CF ₃ , -C(Cl ₂ )CF ₃ and the like are haloalkyl groups, but the scope of the present invention is not limited thereto.

In the present specification, alkoxy refers to a substituent in which oxygen is bonded to an alkyl group, which may be a straight chain, branched chain, or cyclic chain. Examples of the alkoxy group are specifically, methoxy, ethoxy, n-propoxy, isopropoxy, i-propyloxy, n-butoxy, isobutoxy, tert-butoxy, sec-butoxy, n-pentyloxy , Neopentyloxy, isopentyloxy, n-hexyloxy, 3,3-dimethylbutyloxy, 2-ethylbutyloxy, n-octyloxy, n-nonyloxy, n-decyloxy, benzyloxy, p- Methylbenzyloxy or monohalogenated and polyhalogenated variants thereof, and the like, but the scope of the present invention is not limited thereto.

In this specification, amino is intended to encompass monovalent primary amines, monovalent secondary amines, and monovalent tertiary amines. That is, the amino group refers to both a monovalent group in which two hydrogen atoms are bonded to a nitrogen atom and a monovalent group in which at least one hydrogen atom is substituted with another substituent. In the above, a group in which two hydrogen atoms are bonded to a nitrogen atom may be an unsubstituted amino group, and when at least one hydrogen atom is substituted with another substituent, it may be a substituted amino group. Meanwhile, in the amino group including two substituents, each of the substituents may be the same or different from each other.

In the present specification, "carbocycle" and "carbocyclic" mean a ring in which a ring member consists of carbon. Carbocycles may be aliphatic or aromatic, may be saturated or unsaturated, and may be monocyclic or polycyclic. The polycycle can be a fused, bridged, or spiro polycyclic ring. Monocyclic carbocycles may have 3 to 17 carbon atoms, in particular 3 to 14 carbon atoms, more specifically 3 to 10 carbon atoms, especially 3 to 7 carbon atoms.

In the present specification, cycloalkyl refers to a monovalent aliphatic carbocycle in which one hydrogen atom is omitted at any position among carbon atoms constituting the ring. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, 3-methylcyclopentyl, 2,3-dimethylcyclopentyl, cyclohexylene 3-methylcyclohexyl, 4-methylcyclohexyl, 2,3-dimethylcyclohexyl , 3,4,5-trimethylcyclohexyl, 4-tert-butylcyclohexyl, cycloheptyl, cyclooctyl, and the like, but are not limited thereto.

In the present specification, aryl refers to a ring comprising a polyunsaturated, typically aromatic hydrocarbon ring, wherein aryl may be a single ring or a polycyclic ring. In the case of a polycyclic ring, only an aromatic hydrocarbon ring is fused, and an aliphatic hydrocarbon ring is fused together with an aromatic hydrocarbon. Examples of such aryl include a phenyl group, a biphenyl group, a terphenyl group, a quarterphenyl group, and the like as a monocyclic aryl, and a naphthyl group, an anthracenyl group, a phenanthrenyl group, a pyrenyl group, a benzopyrenyl group, and the like as a polycyclic aryl. .

In the present specification, the heterocycle refers to an atom other than carbon, that is, a ring including 1 to 5 heteroatoms selected from O, N, P and S as ring members. At this time, the heterocycle may be aromatic, aliphatic, monocyclic or polycyclic, and non-limiting examples include thiophenyl group, furanyl group, pyrrolyl group, imidazolyl group, thiazolyl group, oxazolyl group, oxadiazolyl group, pyri Denyl group, bipyridinyl group, pyrimidinyl group, triazinyl group, triazolyl group, pyridazinyl group, pyrazinyl group, pyrido pyrimidyl group, pyrido pyrazinyl group, pyrazino pyrazinyl group, isoxazolyl group , A thiadiazolyl group, and the like, but the scope of the present invention is not limited thereto.

In the present specification, heteroaryl refers to an aromatic heterocycle, and may be a single ring or multiple rings. The multi-ring includes a form in which a plurality of aromatic rings are fused, as well as a form in which an aromatic ring and an aliphatic ring are fused. Examples of heteroaryl include pyridinyl group, pyrrolyl group, furanyl group, thiophenyl group, acridyl group, quinolinyl group, quinazolinyl group, quinoxalinyl group, phthalazinyl group, isoquinolinyl group, indolyl group, carbazolyl Group, benzoxazolyl group, benzimidazolyl group, benzothiazolyl group, benzocarbazolyl group, benzothiophene group, dibenzothiophene group, benzofuranyl group, phenanthroline group, phenothiazinyl group , A dibenzofuranyl group and a fluorenyl group, but the scope of the present invention is not limited thereto.

In the present specification, oxy is a substituent that may be represented by ^{"-OR oxy ", wherein R oxy} is, respectively, substituted or unsubstituted, C _1-10 alkyl, C _2-10 alkenyl, C _{3-10 carbocycle} , C _3-10 cycloalkyl, C _6-30 aryl, 3 to 30 membered heterocycle, C _1-10 may be haloalkyl, and the definitions of each of these are as described above.

In the present specification, carbonyl is a substituent that may be represented by ^{"-C(=O)R car ", wherein R car} is, respectively, substituted or unsubstituted, C _1-10 alkyl, C _2-10 alkenyl, substituted or unsubstituted C _3-10 carbocycle, C _3-10 cycloalkyl, C _6-30 aryl, may be a 3 to 30 membered heterocycle, C _1-10 haloalkyl, each of the definitions thereof are as described above .

In the present specification, thio is a substituent that may be represented by ^{"-SR thio ", wherein R thio} is, respectively, substituted or unsubstituted, C _1-10 alkyl, C _2-10 alkenyl, C _{3-10 carbocycle} , C _3-10 cycloalkyl, C _6-30 aryl, 3 to 30 membered heterocycle, C _1-10 may be haloalkyl, and the definitions of each of these are as described above.

In the present specification, imine or imino is a monovalent primary ketimine (-C(NH)R ^i-1 ), secondary ketimine (-C(NR ^i-2 )R ^i-1 ), primary aldimine (-C( NH)H), secondary aldimine (-C(NR ^i-1 ) H). At this time, R ^i-1 and R ^i-2 is Each independently, C _1-10 alkyl, C _2-10 alkenyl, C _3-10 carbocycle, C _3-10 cycloalkyl, C _6-30 aryl, 3-30 membered heterocycle, C _1-10 haloalkyl It may be alkyl, each of which may be substituted or unsubstituted, and each definition is as described above.

In the present specification, sulfone is a substituent that may be represented by _{"-S(=O) 2} R ^{s ", wherein R s} is, respectively, substituted or unsubstituted, C _1-10 alkyl, C _2-10 alkenyl, C _3-10 carbocycle, C _3-10 cycloalkyl, C _6-30 aryl, 3 to 30 membered heterocycle, C _1-10 haloalkyl, each of which has the same definition as previously described.

In the present specification, phosphoric acid is a substituent that may be represented by "-OP(=O)(OH) ₂ "or "-OP(=O)(OH)(OR ^{P )", wherein R P} is each substituted or unsubstituted, C _1-10 alkyl, C _2-10 alkenyl, C _3-10 carbocycle, C _3-10 cycloalkyl, C _6-30 aryl, 3-30 membered heterocycle, C _1-10 haloalkyl Alkyl, and each of these definitions is as described above.

compound

Compounds according to the invention are compounds represented by the following formula (I):

[Formula I]

In the above formula,

X ¹ is oxygen or sulfur,

Ring A is a substituted or unsubstituted, aliphatic or aromatic 5-membered heterocycle group consisting of 2 carbon atoms and 3 hetero atoms, and A ¹ and A ² are each independently nitrogen, oxygen or sulfur,

R ¹ , R ² and R ³ are each independently selected from hydrogen or the following substituent group I,

n4 is an integer of 1 to 3, R ⁴ is the same as or different from each other when n4 is 2 or more, and each independently selected from hydrogen or the following substituent group I and / or fused to each other and substituted with carbon bonded thereto or Forming an unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 membered heterocycle group,

The substituent group I is a substituted or unsubstituted C _1-10 alkyl group, a substituted or unsubstituted C _2-10 alkenyl group, a substituted or unsubstituted C _3-20 carbocycle group, a substituted or unsubstituted C _3-20 Cycloalkyl group, substituted or unsubstituted C _6-30 aryl group, substituted or unsubstituted 3 to 30 membered heterocycle group, substituted or unsubstituted C _1-10 alkoxy group, substituted or unsubstituted C _2-10 alkenyloxy group , A substituted or unsubstituted C _3-10 cycloalkyloxy group, a substituted or unsubstituted C _6-30 aryloxy group, a substituted or unsubstituted 3 to 30 membered heterocycleoxy group, a substituted or unsubstituted C _1-10 alkylcarbonyl Group, substituted or unsubstituted C _2-10 alkenylcarbonyl group, substituted or unsubstituted C _3-10 cycloalkylcarbonyl group, substituted or unsubstituted C _6-30 arylcarbonyl group, substituted or unsubstituted 3 to 30 A membered heterocyclecarbonyl group, a substituted or unsubstituted C _1-10 alkylthio group, a substituted or unsubstituted C _2-10 alkenylthio group, a substituted or unsubstituted C _3-10 cycloalkylthio group, a substituted or unsubstituted C _6-30 arylthio group, substituted or unsubstituted 3 to 30 membered heterocyclethio group, aldehyde group, carboxyl group, halogen group, C _1-10 haloalkyl group, hydroxyl group, substituted or unsubstituted amino group, imine group , A cyano group, a nitro group, an amide group, a thiol group, a sulfone group and a phosphoric acid group,

Here, C _1-10 alkyl moiety is _{-O-, -S-, -SO-, -SO 2} -, -NR a - (R a is hydrogen or a substituted or unsubstituted C _1-10 alkyl), -N = , =N-, -POR ^a -and -PO ₄ R ^a -, and the heterocycle moiety includes at least one of sulfur, nitrogen, phosphorus and oxygen as a ring member.

In one specific example, R ² and R ³ may each independently be a substituted or unsubstituted C _1-4 alkyl group.

In one specific example, X ¹ may be oxygen.

In one specific example, in ring A,

A ¹ is oxygen and A ² is nitrogen;

A ¹ is sulfur and A ² is nitrogen; or

A ¹ may be nitrogen and A ² may be oxygen.

In one specific example, R ⁴ is selected from the following substituent group I-1, which is a subgroup of the substituent group I, and/or ^{two of R 4} are fused to each other and are substituted or unsubstituted C _{3 together with the carbon bonded thereto. -8} carbocycle groups or substituted or unsubstituted 3 to 8 membered heterocycle groups.

The substituent group I-1 is a halogen group, a substituted or unsubstituted C _1-10 alkyl group, a C _1-10 haloalkyl group, a substituted or unsubstituted C _3-20 cycloalkyl group, a substituted or unsubstituted C _6-30 aryl Group, a substituted or unsubstituted 3 to 30 membered heterocycle group, a substituted or unsubstituted C _1-10 alkoxy group, a substituted or unsubstituted C _3-10 cycloalkylcarbonyl group, and a substituted or unsubstituted amino group.

Here, when the substituent of the substituent group I-1 is substituted, oxygen, a halogen group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _1-4 haloalkyl group, a C _1-10 alkylcarbonyl group, It _{may be a group substituted with one or more selected from the group consisting of a C 3-10} cycloalkyl group, a C _1-4 alkylthio group, a sulfonyl group and a sulfino group, and/or two of those selected from the group are fused to each other and A substituted or unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 membered heterocycle group may be formed together with the bonded carbon.

In one specific example, R ¹ may be a substituted or unsubstituted 3 to 30 membered heterocycle group.

In one specific example, the compound of Formula I may be represented by the following Formula I-1.

[Formula I-1]

In the above formula,

R ¹ , R ² , R ⁴ , n4, rings A, A ¹ and A ² are as defined in Formula I.

In one specific example, the compound of Formula I may be represented by any one of the following Formulas I-1-1 to I-1-5:

[Formula I-1-1]

[Formula I-1-2]

[Formula I-1-3]

[Formula I-1-4]

[Formula I-1-5]

In the above formula,

R ¹ is as defined in formula I,

R ² is a methyl group or an ethyl group,

R ⁴ is selected from hydrogen or said substituent group I,

R ^4a and R ^4b are independently selected from hydrogen or the substituent group I, and/or fused to each other and together with the carbon bonded thereto, a substituted or unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 Forming a membered heterocycle group, provided that R ^4a and R ^4b are not hydrogen at the same time,

R ^4c is selected from hydrogen or the above substituent group I.

In one specific example, the compound of Formula I may be represented by the following Formula Ia:

[Formula Ia]

In the above formula,

Ring B is a substituted or unsubstituted C _3-30 carbocycle group or a 3 to 30 membered heterocycle group containing at least one of substituted or unsubstituted sulfur, nitrogen, phosphorus and oxygen as a ring member,

Rings A, R ² , R ³ , R ⁴ , n4, X ¹ , A ¹ , A ² are as defined in Formula I.

In one specific example, the compound of Formula Ia may be represented by the following Formula Ia-1:

[Formula Ia-1]

In the above formula,

R ² , R ⁴ , R ⁵ , rings A, A ¹ and A ² , n4 and n5 are as defined in the formula (I), n5 is an integer of 0 to 4, when n5 is 2 or more, R ⁵ is different from or identical to each other, and R ⁵ is each independently selected from the substituent group I.

In one specific example, the compound of Formula I may be represented by any one of the following Formulas Ia-1-1 to Ia-1-5:

[Formula Ia-1-1]

[Formula Ia-1-2]

[Formula Ia-1-3]

[Formula Ia-1-4]

[Formula Ia-1-5]

In the above formula,

R ⁴ is selected from hydrogen or said substituent group I,

R ² is a methyl group or an ethyl group,

R ^4a and R ^4b are independently selected from hydrogen or the substituent group I, and/or fused to each other and together with the carbon bonded thereto, a substituted or unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 Forming a membered heterocycle group, provided that R ^4a and R ^4b are not hydrogen at the same time,

R ^4c is selected from hydrogen or the above substituent group I.

Hereinafter, a method of synthesizing the compounds represented by the formulas Ia-1-1, Ia-1-2, Ia-1-3, Ia-1-4 and Ia-1-5 will be described. However, these descriptions are intended to aid the understanding of those skilled in the art, and the method of synthesizing the compounds of the present invention is not limited thereto. In addition, the intermediate compound used in the following description may be prepared by a known method, and it is a matter of course that the case by such a method may be included in the scope of the present invention:

Synthesis Method 1: Synthesis of a compound represented by Formula Ia-1-1

1-methyl-1H-imidazole-5-carboxylic acid was added to acetonitrile at room temperature and dissolved. After adding dimethylformamide to the solution, cool it with ice water. To the cooled solution, oxalyl chloride is slowly added dropwise. After completion of the dropwise addition, the temperature was raised to room temperature and reacted at room temperature for 5 hours. After completion of the reaction, it was concentrated under reduced pressure, and the concentrated residual mulberry was crystallized with isopropyl ether. The resulting solid was filtered and dried to obtain the target compound (1).

3-bromopyridine, amine compound (a), and Cu powder are put in a sealed tube, the temperature is raised to about 100°C, and the mixture is stirred at 100°C overnight. After completion of the reaction, it was cooled to room temperature and extracted with ethyl acetate. The organic layer _{was dried over anhydrous MgSO 4} , filtered, and concentrated to obtain the target compound (2).

Compound (1) is dissolved in dichloromethane (DCM; methylene chloride; MC). Cool the solution using ice water. To the solution, a solution obtained by dissolving Compound (2) in DCM is slowly added dropwise. After the addition of N,N-diisopropylethylamine was completed, the temperature was raised to room temperature and reacted at room temperature for 30 minutes. 50 The mixture was heated to °C, reacted for 3 hours, and then cooled to room temperature. The reaction was quenched with water and extracted with DCM. The organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated, and purified by silica gel column chromatography to obtain the target compound (3).

Compound (3) is dissolved in tetrahydrofuran (THF), and toluene is added. After purging the N ₂ gas, it is cooled to -78 °C using acetone and dry ice. Slowly add n-BuLi dropwise to the cooled solution. After the dropwise addition was completed, the mixture was stirred at -78°C for 40 minutes. A solution in which p-toluenesulfonyl cyanide is dissolved in THF is slowly added dropwise. After the dropwise addition was completed, the mixture was stirred at -78°C for 1 hour. Then, the temperature was raised to room temperature, and the mixture was stirred for 4 hours. After quenching with methanol, it is concentrated under reduced pressure. Purified by silica gel column chromatography to obtain the target compound (4).

Compound (4) was dissolved in ethanol, and an _{aqueous NH 2} OH solution was slowly added dropwise, followed by stirring at room temperature for 1 hour. After completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (5).

Carboxylic acid compound (b), EDCI·HCl (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) and hydroxybenzotriazole (HOBt) were dissolved in DCM for 1 hour at room temperature. The reaction proceeds. A solution in which DCM was dissolved in compound (5) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, it was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (6).

After dissolving compound (6) in toluene, the reaction proceeds by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (7).

Synthesis Method 2: Synthesis of a compound represented by Formula Ia-1-2

After compound (4) was obtained in the same manner as in Synthesis Method 1 above, thiourea compound (c) was dissolved in dimethyl sulfoxide, potassium tert-butoxide was added and stirred at room temperature for 5 minutes, and compound (4) was added. Add. After stirring at room temperature for 3 hours, H ₂ O was added to terminate the reaction, extracted with ethyl acetate, and the combined organic layers were dried over _{anhydrous MgSO 4 and filtered.} The filtrate was concentrated under reduced pressure to obtain the target compound (5), which was used in the next reaction without further purification.

After compound (1) is dissolved in dimethyl sulfoxide, H ₂ O is added. Iodine and potassium hydroxide were added, followed by stirring at room temperature for 24 hours. After completion of the reaction, a saturated Na ₂ S ₂ O ₃ aqueous solution was added to terminate the reaction, followed by extraction with ethyl acetate. The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (6).

Synthesis Method 3: Synthesis of a compound represented by Formula Ia-1-3

After compound (3) was obtained in the same manner as in Synthesis Method 1 above, this compound (3) and paraformaldehyde were dissolved in methanol. The temperature was raised to 140° C. and reacted for 3 days. After completion of the reaction, the mixture was cooled to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (4).

Compound (4) was dissolved in THF, MnO ₂ was slowly added dropwise and stirred at room temperature overnight. After completion of the reaction, the mixture was filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (5).

After dissolving compound (5) and carbohydrazine-based compound (D) in ethanol, the reaction was carried out overnight at room temperature. After confirming the completion of the reaction, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (6).

After dissolving compound (6), I ₂ and K ₂ CO ₃ in 1,4-dioxane, the mixture was stirred at 80° C. overnight. After completion of the reaction, 5% NaS ₂ O ₃ aqueous solution was added and extracted with DCM. The organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated, and purified by silica gel column chromatography to obtain the target compound (7).

Synthesis Method 4: Synthesis of Compounds Represented by Formulas Ia-1-4 and Ia-1-5

After compound (5) (30 mg, 0.1041 mmol) was dissolved in acetic acid (0.3 mL), compound (8) (0.4683 mmol, 3.0 eq) was added, followed by stirring at room temperature for 5 days. After completion of the reaction, it _{was neutralized with saturated NaHCO 3} aqueous solution, and extracted with ethyl acetate (EtOAc) (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (9).

After dissolving compound (9) (0.1350 mmol) in THF (0.5 mL), NaH (8 mg, 0.2025 mmol, 1.5 eq) was added under cooling in an ice bath, followed by stirring for 30 minutes. R ^4c -Y (0.2025 mmol, 1.5 eq) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (10-1) and/or the title compound (10-2). In other words, when synthesizing according to Synthesis Method 4, compound (10-1) and compound (10-2) can be obtained at the same time, and in some cases, any of compound (10-1) and compound (10-2) Only one may be obtained.

In one specific example, the compound of formula I may be represented by any one selected from the following formula group:

In the above formula group, Me, Et, and Boc each mean a methyl group, an ethyl group, and a tert-butoxycarbonyl group.

Compounds of the formulas Ia-1-1-1 to Ia-1-1-52 may be named as follows:

Chemical formula designation Ia-1-1-1 N-ethyl-1-methyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-1-2 2-(5-(difluoromethyl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole- 5-carboxamide Ia-1-1-3 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-1H-imidazole- 5-carboxamide Ia-1-1-4 N-ethyl-1-methyl-2-(1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-1-5 2-(5-(tert-butyl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide Ia-1-1-6 N-ethyl-2-(5-isopropyl-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-1-7 N-ethyl-1-methyl-2-(5-propyl-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-1-8 N-ethyl-2-(5-ethyl-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-1-9 2-(5-Butyl-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-1-10 2-(5-(sec-butyl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide Ia-1-1-11 N-ethyl-1-methyl-2-(5-neopentyl-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-1-12 2-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-1-13 2-(5-cyclopentyl-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-1-14 2-(5-cyclohexyl-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-1-15 2-(5-(cyclohexylmethyl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide Ia-1-1-16 2-(5-(cyclopropylmethyl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide Ia-1-1-17 2-(5-((3r,5r,7r)-adamantan-1-yl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridine -3-yl)-1H-imidazole-5-carboxamide Ia-1-1-18 N-ethyl-1-methyl-2-(5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole -5-carboxamide Ia-1-1-19 2-(5-cyclobutyl-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-1-20 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(trichloromethyl)-1,2,4-oxadiazol-3-yl)-1H-imidazole-5 -Carboxamide Ia-1-1-21 N-ethyl-1-methyl-2-(5-phenyl-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-1-22 N-ethyl-1-methyl-2-(5-(oxazol-4-yl)-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-im Dazole-5-carboxamide Ia-1-1-23 N-ethyl-1-methyl-2-(5-(oxazol-5-yl)-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-im Dazole-5-carboxamide Ia-1-1-24 N-ethyl-1-methyl-2-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole -5-carboxamide Ia-1-1-25 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(tetrahydro-2H-pyran-4-yl)-1,2,4-oxadiazol-3-yl) -1H-imidazole-5-carboxamide Ia-1-1-26 N-ethyl-1-methyl-2-(5-(piperidin-1-yl)-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-27 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyrrolidin-1-yl)-1,2,4-oxadiazol-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-28 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyrimidin-5-yl)-1,2,4-oxadiazol-3-yl)-1H-im Dazole-5-carboxamide Ia-1-1-29 N-ethyl-1-methyl-2-(5-(pyridazin-4-yl)-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-im Dazole-5-carboxamide Ia-1-1-30 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyridin-3-yl)-1,2,4-oxadiazol-3-yl)-1H-imidazole -5-carboxamide Ia-1-1-31 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyridin-4-yl)-1,2,4-oxadiazol-3-yl)-1H-imidazole -5-carboxamide Ia-1-1-32 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(1-(pyridin-3-yl)cyclopropyl)-1,2,4-oxadiazol-3-yl )-1H-imidazole-5-carboxamide Ia-1-1-33 N-ethyl-2-(5-(isopropylamino)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide Ia-1-1-34 2-(5-(cyclohexylamino)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide Ia-1-1-35 N-ethyl-2-(5-(ethylamino)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5- Carboxamide Ia-1-1-36 2-(5-(dimethylamino)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5- Carboxamide Ia-1-1-37 N-ethyl-1-methyl-2-(5-morpholino-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-1-38 N-ethyl-2-(5-(N-isopropylacetamido)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-39 2-(5-(N-cyclohexylacetamido)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-40 N-ethyl-2-(5-(2-(ethylthio)pyridin-3-yl)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl )-1H-imidazole-5-carboxamide Ia-1-1-41 N-ethyl-2-(5-(N-isopropylpivalamido)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-42 Ethyl (3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1,2,4-oxadiazol-5-yl) (iso Profile) Carbamate Ia-1-1-43 N-ethyl-2-(5-(2-(ethylthio)phenyl)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-44 N-ethyl-2-(5-(2-(ethylsulfonyl)phenyl)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H -Imidazole-5-carboxamide Ia-1-1-45 2-(5-(4-(dimethylamino)phenyl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-46 2-(5-(2-ethoxyphenyl)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole -5-carboxamide Ia-1-1-47 tert-Butyl 3-(3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1,2,4-oxadiazole-5- Il) Pyrrolidine-1-carboxylate Ia-1-1-48 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyrrolidin-3-yl)-1,2,4-oxadiazol-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-49 tert-Butyl 4-(3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1,2,4-oxadiazole-5- Il) piperidine-1-carboxylate Ia-1-1-50 N-ethyl-1-methyl-2-(5-(piperidin-4-yl)-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-1-51 tert-Butyl 2-(3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1,2,4-oxadiazole-5- Il) Pyrrolidine-1-carboxylate Ia-1-1-52 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyrrolidin-2-yl)-1,2,4-oxadiazol-3-yl)-1H- Imidazole-5-carboxamide

In one specific example, the compound of formula I may be represented by any one selected from the following formula group:

In the above formula group, Et means an ethyl group.

Compounds of the formulas Ia-1-2-1 to Ia-1-2-3 may be named as follows:

Chemical formula designation Ia-1-2-1 N-ethyl-1-methyl-2-(5-(methylamino)-1,2,4-thiadiazol-3-yl)-N-(pyridin-3-yl)-1H-imidazole-5- Carboxamide Ia-1-2-2 N-ethyl-2-(5-(ethylamino)-1,2,4-thiadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5- Carboxamide Ia-1-2-3 2-(5-((2-bromophenyl)amino)-1,2,4-thiadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H -Imidazole-5-carboxamide

In one specific example, the compound of formula I may be represented by any one selected from the following formula group:

In the above formula group, Me and Et mean a methyl group and an ethyl group, respectively.

Compounds of the formulas Ia-1-3-1 to Ia-1-3-3 may be named as follows:

Chemical formula designation Ia-1-3-1 2-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-N,1-dimethyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-3-2 2-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Maid Ia-1-3-3 N-ethyl-1-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide

In one specific example, the compound of Formula I may be represented by any one selected from the following formula group:

In the above formula group, Me, Et, and Boc each mean a methyl group, an ethyl group, and a tert-butoxycarbonyl group, ^{and C represented in the ring constituent atoms is when R 4a} and R ^4b are fused together to form a spiro ring. It is a carbon shared with Ring A.

Compounds of the formulas Ia-1-4-1 to Ia-1-4-44 may be named as follows:

Chemical formula designation Ia-1-4-1 2-(5,5-dimethyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H -Imidazole-5-carboxamide Ia-1-4-2 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(4,5,5-trimethyl-4,5-dihydro-1,2,4-oxadiazol-3-yl) -1H-imidazole-5-carboxamide Ia-1-4-3 2-(4-(cyclopropanecarbonyl)-5,5-dimethyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N- (Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-4 2-(5,5-diethyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)- 1H-imidazole-5-carboxamide Ia-1-4-5 2-(5,5-diethyl-4-methyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-6 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(1-oxa-2,4-diazaspiro[4.4]non-2-en-3-yl)-1H-imidazole -5-carboxamide Ia-1-4-7 N-ethyl-1-methyl-2-(4-methyl-1-oxa-2,4-diazaspiro[4.4]non-2-en-3-yl)-N-(pyridin-3-yl)- 1H-imidazole-5-carboxamide Ia-1-4-8 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-1H-imidazole -5-carboxamide Ia-1-4-9 N-ethyl-1-methyl-2-(4-methyl-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-(pyridin-3-yl)- 1H-imidazole-5-carboxamide Ia-1-4-10 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(1,8-dioxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-1H -Imidazole-5-carboxamide Ia-1-4-11 N-ethyl-1-methyl-2-(4-methyl-1,8-dioxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-(pyridin-3- Sun)-1H-imidazole-5-carboxamide Ia-1-4-12 2-(4-(cyclopropanecarbonyl)-1,8-dioxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N- (Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-13 2-(4-Benzyl-1,8-dioxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N-(pyridin-3- Sun)-1H-imidazole-5-carboxamide Ia-1-4-14 N-ethyl-1-methyl-2-(8-methyl-1-oxa-2,4,8-triazaspiro[4.5]dec-2-en-3-yl)-N-(pyridin-3-yl )-1H-imidazole-5-carboxamide Ia-1-4-15 2-(4,8-dimethyl-1-oxa-2,4,8-triazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-16 2-(4,8-dimethyl-1-oxa-2,4,8-triazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-17 tert-Butyl 3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1-oxa-2,4,8-triazaspiro[4.5 ] Deck-2 -ene -8-carboxylate Ia-1-4-18 tert-Butyl 3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-4-methyl-1-oxa-2,4,8-tri Azaspiro[4.5] Deck-2 - N-8-carboxylate Ia-1-4-19 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(1-oxa-2,4,8-triazaspiro[4.5]dec-2-en-3-yl)-1H- Imidazole-5-carboxamide Ia-1-4-20 N-ethyl-1-methyl-2-(4-methyl-1-oxa-2,4,8-triazaspiro[4.5]dec-2-en-3-yl)-N-(pyridin-3-yl )-1H-imidazole-5-carboxamide Ia-1-4-21 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(1-oxa-8-thia-2,4-diazaspiro[4.5]dec-2-en-3-yl)- 1H-imidazole-5-carboxamide Ia-1-4-22 N-ethyl-1-methyl-2-(4-methyl-1-oxa-8-thia-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-23 2-(4-(cyclopropanecarbonyl)-1-oxa-8-thia-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N -(Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-24 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(8-(trifluoromethyl)-1-oxa-2,4-diazaspiro[4.5]dec-2-ene- 3-yl)-1H-imidazole-5-carboxamide Ia-1-4-25 N-ethyl-1-methyl-2-(4-methyl-8-(trifluoromethyl)-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N -(Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-26 2-(4-(cyclopropanecarbonyl)-8-(trifluoromethyl)-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-ethyl- 1-Methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-27 N-ethyl-1-methyl-2-(8-oxa-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-(pyridin-3-yl)- 1H-imidazole-5-carboxamide Ia-1-4-28 N-ethyl-1-methyl-2-(4-methyl-8-oxo-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-29 2-(1,9,12-trioxa-2,4-diazadisspiro[4.2.48.25]tetradec-2-en-3-yl)-N-ethyl-1-methyl-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-30 2-(8,8-Difluoro-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-31 2-(8-(tert-butyl)-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-4-32 2-(8-(tert-butyl)-4-methyl-1-oxa-2,4-diazaspiro[4.5]dec-2-en-3-yl)-N-ethyl-1-methyl-N- (Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-33 N-ethyl-2-(5-(2-fluorophenyl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3- Sun)-1H-imidazole-5-carboxamide Ia-1-4-34 N-ethyl-2-(5-(2-fluoropyridin-3-yl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl-N-( Pyridine-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-35 N-ethyl-2-(5-(2-fluoropyridin-3-yl)-4-methyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl -N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-36 N-ethyl-2-(5-(3-fluoropyridin-4-yl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl-N-( Pyridine-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-37 N-ethyl-1-methyl-2-(5-phenyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-im Dazole-5-carboxamide Ia-1-4-38 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyridin-3-yl)-4,5-dihydro-1,2,4-oxadiazole-3- Sun)-1H-imidazole-5-carboxamide Ia-1-4-39 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(5-(pyridin-4-yl)-4,5-dihydro-1,2,4-oxadiazole-3- Sun)-1H-imidazole-5-carboxamide Ia-1-4-40 2-(5-(2-ethoxypyridin-3-yl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-( Pyridine-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-41 2-(5-cyclopropyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H- Imidazole-5-carboxamide Ia-1-4-42 N-ethyl-2-(5-(2-(ethylthio)pyridin-3-yl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl-N -(Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-4-43 N-ethyl-1-methyl-2-(5-methyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-N-(pyridin-3-yl)-1H-im Dazole-5-carboxamide Ia-1-4-44 N-ethyl-2-(5-ethyl-4,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-im Dazole-5-carboxamide

In one specific example, the compound of Formula I may be represented by any one selected from the following formula group:

In the above formula group, Me, Et, and Boc each mean a methyl group, an ethyl group, and a tert-butoxycarbonyl group, ^{and C represented in the ring constituent atoms is when R 4a} and R ^4b are fused together to form a spiro ring. It is a carbon shared with Ring A.

The compounds of formulas la-1-5-1 to la-1-5-11 may be named as follows:

Chemical formula designation Ia-1-5-1 N-ethyl-1-methyl-N-(pyridin-3-yl)-2-(2,5,5-trimethyl-2,5-dihydro-1,2,4-oxadiazol-3-yl) -1H-imidazole-5-carboxamide Ia-1-5-2 N-ethyl-1-methyl-2-(2-methyl-1,8-dioxa-2,4-diazaspiro[4.5]dec-3-en-3-yl)-N-(pyridin-3- Sun)-1H-imidazole-5-carboxamide Ia-1-5-3 tert-Butyl 3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-2-methyl-1-oxa-2,4,8-tri Azaspiro[4.5] deck-3 -ene -8-carboxylate Ia-1-5-4 N-ethyl-1-methyl-2-(2-methyl-1-oxa-2,4,8-triazaspiro[4.5]dec-3-en-3-yl)-N-(pyridin-3-yl )-1H-imidazole-5-carboxamide Ia-1-5-5 N-ethyl-1-methyl-2-(2-methyl-1-oxa-8-thia-2,4-diazaspiro[4.5]dec-3-en-3-yl)-N-(pyridin-3 -Yl)-1H-imidazole-5-carboxamide Ia-1-5-6 N-ethyl-1-methyl-2-(2-methyl-8-(trifluoromethyl)-1-oxa-2,4-diazaspiro[4.5]dec-3-en-3-yl)-N -(Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-5-7 2-(8-(tert-butyl)-2-methyl-1-oxa-2,4-diazaspiro[4.5]dec-3-en-3-yl)-N-ethyl-1-methyl-N- (Pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-5-8 N-ethyl-2-(5-(2-fluorophenyl)-2-methyl-2,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl-N-( Pyridine-3-yl)-1H-imidazole-5-carboxamide Ia-1-5-9 N-ethyl-2-(5-(2-fluoropyridin-3-yl)-2-methyl-2,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl -N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-5-10 N-ethyl-2-(5-(3-fluoropyridin-4-yl)-2-methyl-2,5-dihydro-1,2,4-oxadiazol-3-yl)-1-methyl -N-(pyridin-3-yl)-1H-imidazole-5-carboxamide Ia-1-5-11 N-ethyl-1-methyl-2-(2-methyl-1-oxa-2,4-diazaspiro[4.4]non-3-en-3-yl)-N-(pyridin-3-yl)- 1H-imidazole-5-carboxamide

Control composition

The control composition according to the present invention may contain at least one of a compound according to the present invention, an acceptable salt thereof, an enantiomer thereof, a diastereomer thereof, a solvate thereof, a geometric isomer thereof, and a tautomer thereof as an effective substance. .

The control composition of the present invention has a remarkable control effect against pests that damage cultivated crops, field crops, fruit trees, vegetables, other crops and pollen, etc., according to the time when the occurrence of pests is predicted, before the occurrence or occurrence of pests. At the time of this confirmation, it is possible to expect a control effect by treating it with seedling facilities, pears, fields, fruit trees, vegetables, other crops, seeds such as pollen, cultivation carriers such as stalks, foliage or soil.

The useful plants to which the control composition of the present invention can be used are not particularly limited, and examples thereof include cereals (eg, rice, barley, wheat, rye, oats, corn, etc.), legumes (soybeans, red beans, silkworms, peas, etc.) , Shingen beans, peanuts, etc.), fruit trees and fruits (apples, citrus fruits, pears, grapes, peaches, plums, cherries, walnuts, chestnuts, almonds, bananas, etc.), leaves and vegetables (cabbage, tomatoes, spinach, broccoli, lettuce, Onions, green onions (chives, chives), bell peppers, eggplants, peppers, strawberries, peppers, okra, leek, etc.), root vegetables (carrots, potatoes, sweet potatoes, taro, radishes, turnips, lotus roots, burdock, garlic, salt bridges, etc.) ), crops for processing (cotton, hemp, beet, hops, sugar cane, sugar beet, olive, rubber, coffee, tobacco, tea, etc.), external products (pumpkin, cucumber, watermelon, melon, melon, etc.), grasses (new grass, Sorghum, thymesh, clover, alfalfa, etc.), grasses (Koryeo grass, ventgrass, etc.), appreciation crops (lavender, rosemary, thyme, parsley, pepper, ginger, etc.), pollen (chrysanthemum, rose, carnation, etc.) Orchids, tulips, lilies, etc.), garden trees (ginkgo, cherry, Japanese oak, etc.), forest trees (spruce, spruce, pine, Japanese birch, cedar, cypress, eucalyptus, etc.). have.

Examples of the "plant" include HPPD inhibitors such as isoxaflutole, ALS inhibitors such as imazetafil and thifensulpronmethyl, EPSP synthase inhibitors such as glyphosate, glutamine synthase inhibitors such as glufosinate, and cetoxy Plants to which tolerance to acetyl CoA carboxylase inhibitors such as Dim and other herbicides such as bromoxynil, dicamba, and 2,4-D are given resistance by classical breeding methods or genetic recombination techniques are also included.

In order to control various pests, the control composition of the present invention may be used in an amount effective for controlling pests or nematodes in an amount effective for controlling pests or nematodes as it is or in a form that is appropriately diluted with water or the like, for the plant where the occurrence of the pests and nematodes is predicted. , For example, pests and nematodes occurring in fruit trees, grains, vegetables, etc., in addition to spraying on the foliage, immersion of seeds with drugs, seed treatment such as seed powder, carupa treatment, full soil mixing, It can also be used after processing in soil, such as planting application, mixing of bottom soil, cell seedling treatment, planting blood treatment, main source treatment, top dressing, seedling box treatment, water surface application, etc., and absorbed from the roots. In addition, application to nutrient solution in nutrient solution (hydroponics) cultivation, smoking or use by injection of tree trunks is also possible.

The control composition of the present invention can be formulated and used in a shape convenient for use according to a conventional method on the formulation. That is, at least one of the compounds according to the invention, their acceptable salts, their enantiomers, their diastereomers, their solvates, their geometrical isomers and their tautomers, in an appropriate inert carrier or, if necessary, together with an adjuvant. Dissolve, separate, suspend, mix, impregnate, adsorb, or adhere by mixing in proportions and formulated into suitable formulations such as suspension, emulsion, liquid, wettable, granular wettable, granule, powder, tablet, pack, etc. have. Control using the control composition of the present invention may be achieved by, for example, pouring, spraying, atomizing, scattering or spreading.

The control composition of the present invention, in addition to the compound according to the present invention as an active substance, an acceptable salt thereof, an enantiomer thereof, a diastereomer thereof, a solvate thereof, a geometric isomer thereof, or a tautomer thereof, as necessary It may contain additive ingredients commonly used in biological control agents. As this additive component, carriers such as solid carriers and liquid carriers, surfactants, pigment dispersants, wetting agents, binders, tackifiers, thickeners, colorants, photoelectric agents, electrodeposition agents, antifreeze agents, anti-caking agents, disintegrating agents, and decomposition agents, etc. For example. In addition, if necessary, preservatives, plant pieces, and the like may be used in the additive component. These additive components may be used alone or in combination of two or more.

As a solid carrier, for example, natural minerals such as quartz, clay, kaolinite, pyrophyllite, sericite, talc, bentonite, acid clay, attapulgite, zeolite, diatomaceous earth, calcium carbonate, ammonium sulfate, sodium sulfate, potassium chloride, etc. Inorganic salts, synthetic silicic acid, synthetic silicate, starch, cellulose, organic solid carriers such as plant powders (e.g., sawdust, coconut husks, corn cobs, tobacco stalks, etc.), polyethylene, polypropylene, polyvinylidene chloride, etc. There are plastic carriers, urea, inorganic hollow bodies, plastic hollow bodies, fumed silica (white carbon), and the like. These may be used alone or in combination of two or more.

Examples of the liquid carrier include monohydric alcohols such as methanol, ethanol, propanol, isopropanol and butanol, and polyhydric alcohols such as ethylene glycol, diethylene glycol, propylene glycol, hexylene glycol, polyethylene glycol, polypropylene glycol, and glycerin. Alcohols such as these, polyhydric alcohol compounds such as propylene glycol ether, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, diisobutyl ketone, and cyclohexanone, ethyl ether, dioxane, ethylene glycol monoethyl ether , Ethers such as dipropyl ether, tetrahydrofuran, aliphatic hydrocarbons such as normal paraffin, naphthene, isoparaffin, kerosene and mineral oil, aromatic hydrocarbons such as benzene, toluene, xylene, solvent naphtha, and alkyl naphthalene, dichloro Halogenated hydrocarbons such as methane, chloroform, carbon tetrachloride, ethyl acetate, diisopropylphthalate, dibutylphthalate, dioctylphthalate, esters such as dimethyl adipic acid, lactones such as γ-butyrolactone, dimethylformamide, Amides such as diethylformamide, dimethylacetamide, N-alkylpyrrolidinone, nitriles such as acetonitrile, sulfur compounds such as dimethyl sulfoxide, vegetable oils such as soybean oil, rapeseed oil, cottonseed oil, castor oil, water Etc. These may be used alone or in combination of two or more.

As a surfactant used as a dispersing agent or a wetting agent, for example, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene resin acid ester, polyoxyethylene fatty acid diester , Polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene dialkyl phenyl ether, polyoxyethylene alkylphenyl ether formalin condensate, polyoxyethylene polyoxypropylene block copolymer, polystyrene Polyoxyethylene block polymer, alkylpolyoxyethylene polypropylene block copolymer ether, polyoxyethylene alkylamine, polyoxyethylene fatty acid amide, polyoxyethylene fatty acid bisphenyl ether, polyalkylenebenzylphenyl ether, polyoxyalkylene styrylphenyl Nonionic surfactants such as ether, acetylenediol, polyoxyalkylene-added acetylenediol, polyoxyethylene ether silicone, ester silicone, fluorine-based surfactant, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, alkyl sulfates, Polyoxyethylene alkyl ether sulfate, polyoxyethylene alkylphenyl ether sulfate, polyoxyethylene styrylphenyl ether sulfate, alkylbenzene sulfonate, alkylaryl sulfonate, lignin sulfonate, alkyl sulfosuccinate, naphthalene sulfonate, alkylnaphthalene sulfonic acid Salt, salt of formalin condensate of naphthalenesulfonic acid, salt of formalin condensation of alkylnaphthalenesulfonic acid, fatty acid salt, polycarboxylic acid salt, polyacrylate salt, N-methyl-fatty acid sarcosinate, resin acid salt, polyoxyethylene alkyl ether phosphate, Anionic surfactants such as polyoxyethylene alkylphenyl ether phosphate, laurylamine hydrochloride, stearylamine hydrochloride, oleylamine hydrochloride, stearylamine acetate, stearylaminopropylamine acetate, alkyltrimethylammonium chloride, alkyldimethyl Cationic surfactants such as alkylamine salts such as benzalkonium chloride, amphoteric surfactants such as amino acid type or betaine type. These surfactants may be used alone or in combination of two or more.

Examples of binders and tackifiers include carboxymethyl cellulose and salts thereof, dextrin, water-soluble starch, xanthan gum, guar gum, sucrose, polyvinylpyrrolidone, gum arabic, polyvinyl alcohol, polyvinyl acetate, and polyacrylic acid. Sodium, polyethylene glycol with an average molecular weight of 6000 to 20,000, polyethylene oxide with an average molecular weight of 100,000 to 5 million, phospholipids (e.g., ceparin, lecithin, etc.), cellulose powder, dextrin, processed starch, polyaminocarboxylic acid chelate compound, crosslinked poly Vinylpyrrolidone, copolymer of maleic acid and styrene, (meth)acrylic acid-based copolymer, polymer consisting of polyhydric alcohol and half ester of dicarboxylic anhydride, water-soluble salt of polystyrene sulfonic acid, paraffin, terpene, polyamide resin, poly Acrylic acid salt, polyoxyethylene, wax, polyvinyl alkyl ether, alkylphenol formalin condensate, synthetic resin emulsion, and the like.

As a thickener, for example, xanthan gum, guar gum, diutan gum, carboxymethylcellulose, polyvinylpyrrolidone, carboxyvinyl polymer, acrylic polymer, starch compound, water-soluble polymer such as polysaccharide, high purity bentonite, And inorganic fine powders such as fumed silica (white carbon).

Examples of the colorant include inorganic pigments such as iron oxide, titanium oxide, and Prussian blue, alizarin dyes, azo dyes, and organic dyes such as metal phthalocyanine dyes.

Examples of the antifreeze agent include polyhydric alcohols such as ethylene glycol, diethylene glycol, propylene glycol, and glycerin.

As auxiliary agents for preventing caking or promoting disintegration, for example, polysaccharides such as starch, alginic acid, mannose, galactose, polyvinylpyrrolidone, fumed silica (white carbon), ester gum, petroleum resin, sodium tripolyphosphate , Sodium hexamethaphosphate, metal stearate, cellulose powder, dextrin, copolymer of methacrylic acid ester, polyvinylpyrrolidone, polyaminocarboxylic acid chelate compound, sulfonated styrene/isobutylene/maleic anhydride copolymer, Starch/polyacrylonitrile graft copolymer, and the like.

Examples of the decomposition inhibitor include zeolite, quicklime, drying agents such as magnesium oxide, antioxidants such as phenol compounds, amine compounds, sulfur compounds, and phosphoric acid compounds, and ultraviolet absorbers such as salicylic acid compounds and benzophenone compounds.

Examples of the preservative include potassium sorbate and 1,2-benzothiazolin-3-one.

In addition, if necessary, other auxiliary agents such as functional electrodeposition agents, activity enhancing agents such as metabolic decomposition inhibitors such as piperonylbutoxide, freeze drying agents such as propylene glycol, antioxidants such as BHT, and ultraviolet absorbers may also be used.

The blending ratio of the active substance compound can be adjusted as needed, and may be appropriately selected and used in the range of ^{10 -6 to 90 parts by weight among 100 parts by weight of the control composition of the present invention. For example, powders, granules,} When it is used as an emulsion or a wettable agent, it can be used in an amount of 0.01 to 50 parts by weight (0.01 to 50% by weight based on the total weight of the control composition).

The amount of use of the control composition of the present invention varies depending on various factors, such as the purpose, target pests, the growth situation of crops, the occurrence tendency of pests, weather, environmental conditions, formulation, application method, application place, application time, etc. As a substance compound, it may be appropriately selected according to the purpose in the range of 0.00001 g to 10 kg, preferably 0.0001 g to 1 kg per 10 are.

The control composition of the present invention may be used in combination with other control compositions, acaricides, nematodes, fungicides, biological pesticides, etc. for the purpose of expanding the control target pests, timely control, or reducing the amount of medicine. In addition, it is also possible to mix and use herbicides, plant growth regulators, fertilizers, etc. depending on the use situation.

Another control composition, acaricide, nematocide, which may be combined with the control composition of the present invention, may be, for example, the following substances:

3,5-xylyl methylcarbamate (XMC), Bacillus thuringiensis aizawai, Bacillus thuringiensis israelensis, Bacillus thuringiensis japonensis japonensis), Bacillus thuringiensis kurstaki, Bacillus thuringiensis tenebrionis, Bacillus thuringiensis, a crystalline protein toxin produced by BPMC, Bt toxin-based insecticidal compounds, CPCBS (chlorfenson) , DCIP (dichlorodiisopropyl ether), DD (1,3-Dichloropropene), DDT, NAC, O-4-dimethylsulfamoylphenyl O,O-diethyl phosphorothioate (DSP), O-ethyl O- 4-nitrophenyl phenylphosphonothioate (EPN), tripropylisocyanurate (TPIC), acrinathrin, azadirachtin, azinphos-methyl ), acequinocyl, acetamiprid, acetoprole, acephate, abamectin, avermectin-B, amidoflumet, Amitraz, alanycarb, aldicarb, aldoxycarb, aldrin, alpha-endosulfan, alpha-cypermethrin, Albendazole, alletrin in), isazofos, isamidofos, isoamidofos, isoxathion, isopenphos, isoprocarb (MIPC), ivermectin (ivermectin), imicyafos, imidacloprid (imidac1oprid), imiprothrin, indoxacarb, esfenvalerate, ethiofencarb, ethion ), ethiprole, etoxazole, etopenprox, ethoprophos, etrimfos, emamectin, emamectin-benzoate , Endosulfan, enfenthrin, oxamyl, oxydemeton-methyl, oxydeprofos (ESP), oxibendazole, oxpendazole (oxfendazole), potassium oleate (Potassium oleate), sodium oleate (sodium oleate), cadusafos, cartap, carbary1, carbosulfan, carbofuran , Gamma-cyhalothrin, xylylcarb, quinalphos, kinoprene, chinomethionat, cloethocarb, cloethocarb, clothianidine (clothianidin), clofentezine, chromafenozide, chlorantraniliprole, chlorethoxyfos, chlordimeform, chlordimeform, ch lordane), chlorpyrifos, chlorpyrifos-methyl, chlorphenapyr, chlorfenson, ch1orfenvinphos, chlorfluazuron, chloro Benzylate, chlorobenzoate, kelsen (dicofol), salithion, cyanophos (CYAP), diafenthiuron, diamidafos, Cyantraniliprole, theta-cypermethrin, dienochlor, cyenopyrafen, dioxabenzofos, diofenolan, sigma -Sigma-cypermethrin, diclofenthion (ECP), cycloprothrin, dichlorvos (DDVP), disulfoton, dinotefuran, cyhal Cyhalothrin, cyphenothrin, cyfluthrin, diflubenzuron, cyflumetofen, diflovidazin, cyhexatin, cy Cypermethrin, dimethylvinphos, dimethoate, dimefluthrin, silafluofen, cyromazine, spinetoram, spinosad ), spirodiclofen, spirotetramat, spiromesifen, sulfluramide ( sulfluramid), sulprofos, sulfoxaflor, zeta-cypermethrin, diazinon, tau-fluvalinate, dazomet, thia Thiacloprid, thiamethoxam, thiodicarb, thiocyclam, thiosultap, thiosultap-sodium, thionazin, thio Thiometon, deet, dildrin, tetrachlorvinphos, tetradifon, tetramethylfluthrin, tetramethrin, tebupyrimphos ( tebupirimfos), tebufenozide, tebufenpyrad, tefluthrin, teflubenzuron, demeton-S-methyl, temefos temephos), deltamethrin, terbufos, tralopyril, tralomethrin, transfluthrin, triazamate, triazuron, Trichlamide, trichlorphon (DEP), triflumuron, tolfenpyrad, naled: BRP, nithiazine, nitenpyram, Novaluron, noviflumuron, hydroprene, vaniliprole, vamidothion, parathion, parathion-m ethyl), halfenprox, halofenozide, bistrifluron, bisultap, hydramethylnon, hydroxy propyl starch, vinapark Binapacryl, bifenazate, bifenthrin, pymetrozine, pyrachlorfos, pyrafluprole, pyridafenthion, Pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, pyrimicarb, pyrimidifen, pyrimi Phosmethyl (pirimiphos-methy1), pyrethrins (pyrethrins), fivpronil (fiproni1), fenazaquin (fenazaquin), fenamiphos (fenamiphos), phenisobromorate (bromopropylate), fenitrothione (fenitrothion: MEP), fenoxycarb, fenothiocarb, phenothrin, fenobucarb, fensulfothion, fenthion (MPP), phenthoate : PAP), fenvalerate, fenpyroximate, fenpropathrin, fenbendazole, fosthiazate, formetanate, butathio Butathiofos, buprofezin, furathiocarb, prallethrin, fluacrypyrim, fluazinam, fluazuron ), fluensulfone, flucycloxuron, flucythrinate, fluvalinate, flupyrazofos, flufenerim, flufenox Flufenoxuron, flufenzine, flufenoprox, fluproxyfen, flubrocythrinate, flubendiamide, flumethrin, flu Flurimfen, prothiofos, protrifenbute, flonicamid, propaphos, propargite (BPPS), propenofos, Profluthrin, propoxur (PHC), bromopropylate, beta-cyfluthrin, hexaflumuron, hexythiazox, hep Tenofos, permethrin, benclothiaz, bendiocarb, bensu1tap, benzoximate, benfuracarb, phoxim , Phosalone, Fosthiazate, Fosthietan, Phosphamidon, Phosphamidon, Phosphamidon, Phosmet (PMP), Polynactins , Formetanate, formothion, forate, machine oil, malathion, milbemycin, milbemycin-A, Milbemectin, mecarbam, mesulfenfos, methomyl, metaldehyde, metaflumizone, metamidophos, metamammonium -mmonium), meta-sodium, methiocarb, methidathion (DMTP), methylisothiocyanate, methylneodecanamide, methylparathion ), metoxadiazone, methoxychlor, methoxyfenozide, metofluthrin, metoprene, metolcarb, meperfluthrin (meperfluthrin), mevinphos, monocrotophos, monosultap, lambda-cyhalothrin, ryanodine, lufenuron, resmethrin (resmethrin), lepimectin, rotenone, lebamisol hydrochloride, fenbutatin oxide, morantel tartarate, methyl bromide, hydroxide tree Cyhexatin, calcium cyanamide, calcium polysulfide, sulfur, and sulfur nicotine-sulfate.

Fungicides that can be combined with the control composition of the present invention can be, for example, the following substances:

Aureofungin, azaconazole, azithiram, acipetacs, acibenzolar, acibenzolar-S-methyl, subfamily Cystrobin, anilazine, amisulbrom, ampropylfos, amethoctradin, allyl alcohol, aldimorph, amobam amobam), isotianil, isovaledione, isopyrazam, isoprothiolane, ipconazole, iprodione, iprovalicarb ), iprobenfos, imazalil, iminoctadine, iminoctadine-albesilate, iminoctadine-triacetate, imibenconazole ), uniconazole, uniconazole-P, echlomezole, edifenphos, etaconazole, ethaboxam, ethirimol ( ethirimol), etem, ethoxyquin, etridiazole, energy strike lobe (enestroburin), epoxyconazole, oxadixyl, oxycarboxin, oxy Copper quinolinolate, oxytetracycline, copper-oxinate, oxpoconazole, oxpoconazole-fumarate, oxytetracycline Oxolinic acid, octhilinone, ofurace, orysastrobin, meta-sodium, kasugamycin, carbamorph, Carpropamid, carbendazim, carboxin, carvone, quinazamid, quinacetol, quinoxyfen, quinomethio Quinomethionate, captafol, captan, kiralaxyl, quinconazole, quintozene, guazatine, cufraneb, cup Cuprobam, glyodin, grisofulvin, climbazole, cresol, kresoxim-methyl, chlozolinate, clotrimazole ( clotrimazole), clobenthiazone, chloraniformethan, chloranil, chlorquinox, chloropicrin, chlorfenazole, chlorodinitronaphthalene ), chlorothalonil, chloroneb, zarilamid, salicylanilide, cyazofamid, diethyl pyrocarbonate, diethofencarb ), cyclafuramid, diclocymet, diclozoline, diclobutrazol, diclofluanide (dic hlofluanid), cycloheximide, diclomezine, dicloran, dichlorophen, diclone, disulfiram, ditalimfos, Dithianon, diniconazole, diniconazole-M, zineb, dinocap, dinocton, dinosulfon, dinoter Dinoterbon, dinobuton, dinopenton, dipyrithione, diphenylamine, difenoconazole, cyflufenamid, diflumetorim (diflumetorim), cyproconazole, cyprodinil, cyprofuram, cypendazole, simeconazole, dimethirimol, dimethirimol, dimetomorph ( dimethomorph), cymoxanil, dimoxystrobin, methyl bromide, ziram, silthiofam, streptomycin, spiroxamine, sultro Sultropen, sedaxane, zoxamide, dazomet, thiadiazin, thiadinil, thiadifluor, thiabendazole , Thioxymid, thiochlorfenphim, thiophanate, thiophanate-methyl, thiiofen, thioquinox, kinomethionate ( chi nomethionat), thiofluzamide, thiram, decafentin, tecnazene, tecloftalam, tecoram, tetraconazole, debacarb (debacarb), dehydroacetic acid, tebuconazole, tebufloquin, dodicin, dodine, dodecylbenzenesulfonic acid bisethylenediamine copper complex (II) (DBEDC), dodemorph, drazoxolon, triadimenol, triadimefon, triazbutil, triazoxide, triamifos triamiphos), triarimol, trichlamide, tricyclazole, triticonazole, tridemorph, tributyltin oxide, triflumi Triflumizole, trifloxystrobin, triforine, tolylflualanide, tolclofos-methyl, natamycin, nabam, nitrotasal Isopropyl, nitrostyrene, nuarimol, copper nonylphenol sulfonate, halacrinate, validamycin, valifenalate , Harpin protein, bixafen, picoxystrobin, picobenzamide, bithionol, bitertanol ), hydroxyisoxazole, hydroisoxazole-potassium, binapacryl, biphenyl, piperalin, hymexazol, pyraoxystrobin ( pyraoxystrobin), pyracarbolid, pyraclostrobin, pyrazophos, pyrametostrobin, pyriofenone, pyridinitril, pyrife Pyrifenox, pyribencarb, pyrimethanil, pyroxychlor, pyroxyfur, pyroquilon, vinclozolin, famoxadon ( famoxadone), fenapanil, fenamidone, fenaminosulf, fenarimol, fenitropan, fenoxanil, ferimzone, perbam (ferbam), fentin, fenpiclonil, fenpyrazamine, fenbuconazole, fenfuram, fenpropidin, fenpropimorph ), fenhexamid, phthalide, butiobate, butylamine, bupirimate, fuberidazole, blasticidin-S (blasticidin -S), furametpyr, furalaxyl, fluacrypyrim, fluazinam, fluoxastrobin, fluotrimazole, fluopicol Fluopicolide, fluopyram, fluoroimide, furcarbanil, fluxapyroxad, fluquinconazole, furconazole, purcona Furconazole-cis, fludioxonil, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol , Furfural, furmecyclox, flumetover, flumorph, proquinazid, prochloraz, procymidone, pro Thiocarb, prothioconazole, propamocarb, propiconazole, propineb, furophanate, probenazole, Bromuconazole, hexachlorobutadiene, hexaconazole, hexylthiofos, betoxazin, benalaxyl, benalaxyl-M, Benodanil, benomyl, pefurazoate, benquinox, penconazole, benzamorf, pencycuron, benzohydroxamic acid acid), bentaluron, benthiazole, benthiavalicarb-isopropyl, penthiopyrad, penflu fen), boscalid, fosdiphen, fosetyl, fosetylAl, polyoxins, polyoxorim, polycarbamate, poly Folpet, formaldehyde, machine oil, maneb, mancozeb, mandipropamid, myclozolin, myclobutanil myclobutanil), mildiomycin, milneb, mecarbinzid, metasulfocarb, metazoxolon, metam, metam-sodium ), metalaxyl, metalaxyl-M, metiram, methyl isothiocyanate, methyldinocap, metconazole, metsulfo Box (metsulfovax), metfuroxam, metominostrobin, metrafenone, mepanipyrim, mefenoxam, mephyldinocap, mepro Mepronil, mebenil, methyl iodide (iodomethane), rabenzazole, benzalkonium chloride, basic copper chloride, basic copper sulfate, metallic silver Inorganic disinfectants such as (silver), sodium hypochlorote, cupric hydroxide, wettable sulfur, calcium polysulfide, carbonic acid Potassium hydrogen carbonate, sodium hydrogen carbonate, inorganic sulfur, copper sulfate anhydride, nickel dimethyldithiocarbamate, 8-hydroxyquinoline copper Copper compounds such as copper), zinc sulfate, and copper sulfate pentahydrate.

Herbicides that can be combined with the control composition of the present invention can be, for example, the following substances:

1-naphthylacetamide, 2,4-PA, 2,3,6-TBA, 2,4,5-T, 2,4,5-TB, 2,4-D, 2,4-DB, 2 ,4-DEB, 2,4-DEP, 3,4-DA, 3,4-DB, 3,4-DP, 4-CPA, 4-CPB, 4-CPP, MCP, MCPA, MCPA thioethyl, MCPB , Ioxynil, aclonifen, azafenidin, acifluorfen, aziprotryne, aziprotryne, azimsulfuron, asulam, aceto Chlor (acetochlor), atrazine, atraton, anisuron, anilofos, aviglycine, abscisic acid, amicarbazone, Amidosulfuron, amitrol, aminocyclopyrachlor, aminopyralid, amibuzin, amiprophos-methyl, ametridione , Ametryn, alachlor, allidochlor, alloxydim, alorac, isouron, isocarbamid, isoxachlor Tol (isoxachlortole), isoxapyrifop, isoxaflutole, isoxaben, isocil, isonoruron, isoproturon, isopropalin (isopropalin), isopolinate, isomethiozin, inabenfide, ipazine, ipfencarbazone, iprymidam, imazaquin (im) azaquin), imazapic, imazapyr, imazamethapyr, imazamethabenz, imazamethabenz-methyl, imazamox, Imazethapyr, imazosulfuron, indaziflam, indanofan, indolebutyric acid, uniconazole-P, eglinazine ), esprocarb, ethametsulfuron, ethametsulfuron-methyl, etalfluralin, ethiolate, ethychlozate ethyl , Ethidimuron, ethinofen, ethephon, ethoxysulfuron, ethoxyfen, etnipromid, ethofumesate, Etobenzanid, epronaz, erbon, endothal, oxadiazon, oxadiargyl, oxaziclomefone, oxaziclomefone, oxa Sulfuron, oxapyrazon, oxyfluorfen, oryzalin, orthosulfamuron, orbencarb, cafenstrole, campendichlor (cambendichlor), carbasulam, carfentrazone, carfentrazone-ethyl, carbutilate, carbetamide, carb oxazole), quizalofop, quizalofop-P, quizalofop-ethyl, xylachlor, quinoclamine, quinonamid ), quinclorac, quinmerac, cumyluron, cliodinate, glyphosate, glufosinate, glufosinate-P ( glufosinate-P), credazine, clethodim, cloxyfonac, clodinafop, clodinafop-propargyl, chlorotoluron, clo Pyralid, cloproxydim, cloprop, chlorbromuron, clofop, clomazone, clomethoxynil, clomethoxy Chlomethoxyfen, clomeprop, chlorazifop, chlorazine, cloransulam, chloranocryl, chloramben, chloransulam-methyl (cloransulam-methyl), chloridazon, chlorimuron, chlorimuron-ethyl, chlorsulfuron, chlorthal, chlorthiamid , Chlortoluron, chlornitrofen, chlorfenac, chlorfenprop, chlorbufam, chlorflurazole, chlorflurenol, chlor Pro Chlorprocarb, chlorpropham, chlormequat, chloreturon, chloroxynil, chloroxuron, chloropon, saflufenacyl ( saflufenacil), cyanazine, cyanatryn, di-allate, diuron, diethamquat, dicamba, cycluron, cyclo Cycloate, cycloxydim, diclosulam, cyclosulfamuron, dichlorprop, dichlorprop-P, diclobenil , Diclofop, diclofop-methyl, dichlormate, dichloralurea, diquat, cisanilide, disul , Ciduron, dithiopyr, dinitramine, cinidon-ethyl, dinosam, cinosulfuron, dinoseb, dino Dinoterb, dinofenate, dinoprop, cyhalofop-butyl, diphenamid, difenoxuron, difenopenten, Difenzoquat, cybutryne, cyprazine, cyprazole, diflufenican, diflufenzopyr, dipropetryn, cipro Cypromid, cyperquat, gibber ellin), simazine, dimexano, dimethachlor, dimidazon, dimethametryn, dimethenamid, simetryn ), simeton, dimepiperate, dimefuron, cinmethylin, swep, sulglycapin, sulcotrione, sulfa Sulfallate, sulfentrazone, sulfosulfuron, sulfometuron, sulfometuron-methyl, secbumeton, setoxydim, three Butylazine, terbacil, daimuron, dazomet, dalapon, thiazafluron, thiazopyr, thiencarbazone ), thiencarbazone-methyl, thiocarbazil, thiochlorim, thiobencarb, thidiazimin, thidiazuron, thipensulfurone (thifensulfuron), thifensulfuron-methyl, desmedipham, desmetryn, tetrafluron, tenylchlor, tebutam, tebuthiuron (tebuthiuron), tepraloxydim, tefuryltrione, tembotrione, delachlor, terbacil, terbucarb, terbuchlor terbuchlor), terbutyla Terbuthylazine, terbutryn, topramezone, tralkoxydim, triaziflam, triasulfuron, triafamone, trialal Tri-allate, trietazine, tricamba, triclopyr, tridiphane, tritac, tritosulfuron, triflusulfuron ), triflusulfuron-methyl, trifluralin, trifloxysulfuron, tripropindan, tribenuron-methyl, tribenuron , Trifop, trifopsime, trimeturon, naphthalam, naproanilide, napropamide, nicosulfuron, Nitralin, nitrofen, nitrofluorfen, nipyraclofen, neburon, norflurazon, noruron, barban , Paclobutrazol, paraquat, parafluron, haloxydine, haloxyfop, haloxyfop-P, haloxypopmethyl (haloxyfop-methyl), halosafen, halosulfuron, halosulfuron-methyl, picloram, picolinafen, bicyclopyrone, Bispyribac , Bispyribac-sodium, pydanon, pinoxaden, bifenox, piperophos, hymexazol, pyraclonil, pyra Sulfotol, pyrazoxyfen, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazolate, bilanafos, pyraflufenethyl ( pyraflufen-ethyl), pyrichlor, pyridafol, pyrithiobac, pyrithiobac-sodium, pyridate, pyriftalid, pyributy Pyributicarb, pyribenzoxim, pyrimisulfan, primisulfuron, pyriminobac-methyl, pyroxasulfone, pyroxsulam, Fenasulam, phenisopham, fenuron, fenoxasulfone, fenoxaprop, fenoxaprop-P, fenoxaprop- ethyl), phenothiol, fenoprop, phenobenzuron, fenthiaprop, penteracol, fentrazamide, phenm edipham), phenmedipham-ethyl, butachlor, butafenacil, butamifos, buthiuron, buthidazole, butyrate butylate), buturon, Butenachlor, butroxydim, butralin, plazasulfuron, flamprop, furyloxyfen, prinachlor, primoperon Methyl (primisulfuron-methyl), fluazifop, fluazifop-P, fluazifop-butyl, fluazolate, fluroxypyr, fluorine Thiuron, fluometuron, fluoroglycofen, flurochloridone, fluorodifen, fluoronitrofen, fluoromidine ), flucarbazone, flucarbazone-sodium, fluchloralin, flucetosulfuron, fluthiacet, fluthiacet-methyl , Flupyrsulfuron, flufenacet, flufenican, flufenpyr, flupropacil, flupropanate, flupoxam , Flumioxazin, flumiclorac, flumiclorac-pentyl, flumipropyn, flumezin, fluometuron, flumet Flumetsulam, fluridone, flurtamone, fluroxypyr, pretilachlor, proxan, proglinazine, procyazine (procyazine), prodiamine, prosulfalin, prosulfuron, prosulfocarb, propaquizafop, propachlor, propazine ), propanil, propyzamide, propisochlor, prohydrojasmon, propyrisulfuron, propham, profluazol , Profluralin, prohexadione-calcium, propoxycarbazone, propoxycarbazone-sodium, propoxydim, bromacil, Brompyrazon, prometryn, prometon, bromoxynil, bromofenoxim, bromobutide, bromobonil, flora Sulam, hexachloroacetone, hexazinone, pethoxamid, benazolin, penoxsulam, pebulate, beflubutamid ), benolate, perfluidone, bencarbazone, benzadox, benzipram, benzylaminopurine, benzthiazuron, benz Benzfendizone, bensulide, bensulfuron-methyl, benzoylprop, benzobicycl on), benzofenap, benzofluor, bentazone, pentanochlor, benthiocarb, pendimethalin, pentoxazone, benflu Benfluralin, benfuresate, fosamine, fomesafen, foramsulfuron, forchlorfenuron, maleic hydrazide, meco Mecoprop, mecoprop-P, medinoterb, mesosulfuron, mesosulfuron-methyl, mesotrione, mesoprazine ( mesoprazine), metoprotryne, metazachlor, metazole, metazosulfuron, metabenzthiazuron, metamitron, metamipop , Metham, metalpropalin, methiuron, methiozolin, methiobencarb, methyldymron, metoxuron, metosulam metosulam), metsulfuron, metsulfuron-methyl, metflurazon, metobromuron, metobenzuron, methometon, metola Chlor (metolachlor), metribuzin, mepiquat-chloride, mefenacet, mefluidide, monalide, monisouron (m onisouron), monuron, monochloroacetic acid, monolinuron, molinate, morfamquat, iodosulfuron, iodosulfuron methyl sodium (iodosulfuron-methyl-sodium), iodobonil, iodomethane, lactofen, linuron, rimsulfuron, lenacil, rhodetanil , Calcium peroxide, methyl bromide.

The biological pesticide that can be combined with the control composition of the present invention can be, for example, the following substances:

Virus preparations such as Nuclear polyhedrosis virus (NPV), Granulosis virus (GV), Cytoplasmic polyhedrosis virus (CPV), Entomopoxi virus (EPV), monacross Used as insecticides or nematodes such as Monacrosporium phymatophagum, Steinernema carpocapsae, Steinernema kushidai, Pasteuria penetrans, etc. Microbial pesticides, Trichoderma lignorum, Agrobacterium radiobactor, non-pathogenic Erwinia carotovora, Bacillus subtilis, etc. The same effect can be expected by mixing with microbial pesticides used as fungicides, biological pesticides used as herbicides such as Xanthomonas campestris, etc. In addition, as biological pesticides, for example, greenhouse powder Encarsia formosa, Aphidius colemani, Aphidoletes aphidimyza, Diglyphus isaea, Dacnusa sibirica, Phytoseiulus persimilis, Amblyseius persimilis cucumeris), natural enemies such as Orius sauteri, microbial pesticides such as Beauveria brongniartii, (Z)-10-tetradecenyl=acetato, (E,Z)-4, 10-tetradecadiniel=acetate, (Z)-8-dodecenyl=acetato, (Z)-11-tetradecenyl=acetato, (Z)-13-ico It is also possible to use in combination with pheromones such as sen-10-one and 14-methyl-1-octadecene.

On the other hand, hereinafter, in order to specifically describe the disclosure of the present invention as described above and the intended action and effect in the present invention, the present invention will be described in detail by way of examples. However, the embodiments may be modified in various other forms, and the scope of the present specification is not to be construed as being limited only to this embodiment. It is emphasized that the examples are provided to represent the present invention in more detail to those skilled in the art.

<Example 1>

Synthesis of compounds of formula Ia-1-1-1

Step 1: Add 1-methyl-1H-imidazole-5-carboxylic acid (38.81 g, 307.7 mmol) to acetonitrile (160 mL) at room temperature and dissolve. After adding dimethylformamide (0.5 mL) to the solution, cool it with ice water. To the cooled solution, oxalyl chloride (31.25 mL, 369.2 mmol, 1.2 equiv.) was slowly added dropwise. After completion of the dropwise addition, the temperature was raised to room temperature and reacted at room temperature for 5 hours. After completion of the reaction, it was concentrated under reduced pressure, and the concentrated residual mulberry was crystallized with isopropyl ether. The resulting solid was filtered and dried to obtain the target compound (62.47 g, quant., ivory solid).

Step 2: 3-bromopyridine (35.00 g, 221.5 mmol), ethylamine (66.0-72.0% H ₂ O solution, 93.4 mL, 1107.6 mmol, 5.0 equiv.), Cu powder (0.71 g, 11.1 mmol, 0.05 equiv .) was put in a sealed tube, the temperature was raised to 100° C., and stirred at 100° C. overnight. After completion of the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate. The organic layer _{was dried over anhydrous MgSO 4} , filtered, and concentrated to obtain the target compound (23.3 g, 86%, brown oil).

Step 3: Dissolve 1-methyl-1H-imidazole-5-carbonyl chloride·HCl salt (55.7 g, 307.7 mmol, 1.6 equiv.) in dichloromethane (DCM, 300 mL). Cool the solution using ice water. To the solution, a solution in which N-methylpyridin-3-amine (23.3 g, 191.3 mmol) was dissolved in DCM (100 mL) was slowly added dropwise. After the addition of N,N-diisopropylethylamine (133.0 mL, 765.2, 4.0 equiv.) was added dropwise, the temperature was raised to room temperature and reacted at room temperature for 30 minutes. 50 It was heated to °C, reacted for 3 hours, and then cooled to room temperature. The reaction was quenched with water and extracted with DCM. The organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated and purified by silica gel column chromatography to obtain the target compound (43.89 g, 99%, brown oil).

Step 4: Dissolve N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (10.0 g, 43.4 mmol) in tetrahydrofuran (THF, 100 mL) Then, toluene (150 mL) was added. After purging the N ₂ gas, it is cooled to -78 °C using acetone and dry ice. To the cooled solution, n-BuLi (2.5M in hexane solution, 17.7 mL, 44.2 mmol, 1.02 equiv.) was slowly added dropwise. After the dropwise addition was completed, the mixture was stirred at -78°C for 40 minutes. A solution in which p-toluenesulfonyl cyanide (9.44 g, 52.1 mmol, 1.2 equiv.) was dissolved in THF (50 mL) was slowly added dropwise. After the dropwise addition was completed, the mixture was stirred at -78°C for 1 hour. After that, the temperature was raised to room temperature and further stirred for 4 hours. After quenching with methanol, it is concentrated under reduced pressure. Purified by silica gel column chromatography to obtain the target compound (4.29 g, 39%, light brown oil).

Step 5: 2-cyano-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (4.29 g, 16.8 mmol) in ethanol (30 mL) After dissolving, an aqueous solution of NH ₂ OH ( _{50% in H 2} O, 2.06 mL, 33.6 mmol, 2.0 equiv.) was slowly added dropwise, followed by stirring at room temperature for 1 hour. After completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (3.87 g, 80%, pale yellow solid).

Step 6: Dissolve acetic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), hydroxybenzotriazole (HOBt, 58.0 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) After the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (83.2 mg, 80%, colorless oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-1 (63.9 mg, 66%, brown oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54 (d, 1H), 8.42 (s, 1H), 7.54 (d, 1H), 7.36 (q, 1H), 6.49 (s, 1H), 4.22 (s, 3H), 3.97 (q, 2H), 2.65 (s, 3H), 1.25 (t, 3H).

<Example 2>

Synthesis of compounds of formula Ia-1-1-2

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.173 mmol), 1,1 After adding ,5,5-tetrafluoropentane-2,4-dione (15 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-2 (27.2 mg, 45.0%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54 (d, 1H), 8.40 (s, 1H), 7.53 (d, 1H), 7.35 (q, 1H), 6.86 (t, 1H), 6.50 (s, 1H), 4.24 (s, 3H), 3.97 (q, 2H), 1.25 (t, 3H).

<Example 3>

Synthesis of compounds of formula Ia-1-1-3

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.173 mmol), 1,1 After adding ,1,5,5,5-hexafluoropentane-2,4-dione (15 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-2 (78.1 mg, 87.2%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.56 (d, 1H), 8.41 (s, 1H), 7.56 (d, 1H), 7.37 (q, 1H), 6.52 (s, 1H), 4.25 (s, 3H), 3.98 (q, 2H), 1.26 (t, 7H).

<Example 4>

Synthesis of compounds of formula Ia-1-1-4

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.173 mmol), p -toluene Sulphonic acid (0.82 mg, 0.004 mmol, 0.025 equiv.) and triethyl orthoformate (0.22 mL, 1.318 mmol, 7.6 equiv.) were added and reflux reaction was performed for 2.5 hours. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-4 (11.4 mg, 22%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.82 (s, 1H), 8.54 (d, 1H), 8.40 (s, 1H), 7.53 (d, 1H), 7.34 (q, 1H), 6.49 (s, 1H), 4.25 (s, 3H), 3.97 (q, 2H), 1.26 (t, 3H).

<Example 5>

Synthesis of compounds of formula Ia-1-1-5

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.173 mmol), 2,2 After adding ,6,6-tetramethylheptane-3,5-dione (15 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-5 (57.8 mg, 94.1%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.51 (d, 1H), 8.39 (s, 1H), 8.51 (d, 1H), 7.31 (q, 1H), 6.45 (s, 1H), 4.20 (s, 3H), 3.94 (q, 2H), 1.45 (s, 9H), 1.23 (t, 3H)

<Example 6>

Synthesis of compounds of formula Ia-1-1-6

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Isobutyric acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), hydroxybenzotriazole (HOBt, 58.0 mg, 0.380 mmol, 1.2 equiv.) was added to DCM (2 mL) After dissolving in, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (102.1mg, 90.4%, colorless liquid).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-6 (30.6 mg, 40.3%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52 (d, 1H), 8.40 (s, 1H), 7.50 (d, 1H), 7.31 (q, 1H), 6.46 (s, 1H), 4.22 (s, 3H), 3.96 (q, 2H), 3.31-3.26 (m, 1H), 1.45-1.43 (m, 6H), 1.25 (t, 3H)

<Example 7>

Synthesis of compounds of formula Ia-1-1-7

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Butyric acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), hydroxybenzotriazole (HOBt, 58.0 mg, 0.380 mmol, 1.2 equiv.) was added to DCM (2 mL). After dissolving, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (105.3 mg, 93.3%, colorless liquid).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-7 (52.6 mg, 69.2%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52 (d, 1H), 8.40 (s, 1H), 7.50 (d, 1H), 7.32 (q, 1H), 6.45 (s, 1H), 4.21 (s, 3H), 3.95 (q, 2H), 2.91 (t, 2H), 1.91-1.86 (m, 2H), 1.24 (t, 3H), 1.01 (t, 3H)

<Example 8>

Synthesis of compounds of formula Ia-1-1-8

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Dissolve propionic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) for 1 hour at room temperature. The reaction proceeded. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (107.4 mg, 99%, yellow liquid).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-8 (56.5 mg, 55.0%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.51-8.50 (m, 1H), 8.38 (d, 1H), 7.51-7.48 (m, 1H), 7.32-7.29 (m, 1H), 6.44 ( s, 1H), 4.20(s, 3H), 3.94(q, 2H), 2.94(q, 2H), 1.40(t, 3H), 1.23(t, 3H)

<Example 9>

Synthesis of compounds of formula Ia-1-1-9

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving valeric acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL), 1 at room temperature Time reaction proceeded. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (87.2 mg, 74.3%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-9 (30.5 mg, 27.3%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.51-8.50 (m, 1H), 8.38 (d, 1H), 7.50-7.48 (m, 1H), 7.32-7.29 (m, 1H), 6.44 ( s, 1H), 4.20 (s, 3H), 3.94 (q, 2H), 2.92 (t, 2H), 1.85-1.79 (m, 2H), 1.42-1.36 (m, 2H), 1.23 (t, 3H) , 0.91(t, 3H)

<Example 10>

Synthesis of compounds of formula Ia-1-1-10

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving 2-methylbutyric acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL), The reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (112.6 mg, 96%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-10 (63.8 mg, 57.2%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.50-8.498 (m, 1H), 8.37 (d, 1H), 7.49-7.47 (m, 1H), 7.30-7.27 (m, 1H), 6.43 ( s, 1H), 4.19 (s, 3H), 3.93 (q, 2H), 3.12-3.05 (m, 1H), 1.92-1.83 (m, 1H), 1.76-1.67 (m, 1H), 1.37 (d, 3H), 1.21 (t, 3H), 0.89 (t, 3H)

<Example 11>

Synthesis of compounds of formula Ia-1-1-11

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol), 3,3-dimethylbutyryl chloride (0.051 mL, 0.364 mmol, 1.05 equiv.) and TEA (0.053 mL, 0.382 mmol, 1.1 equiv.) were dissolved in DMF (1 mL) and refluxed overnight to proceed with the reaction. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-11 (17.2 mg, 13.5% yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.40 (d, 1H), 7.53-7.50 (m, 1H), 7.34-7.31 (m, 1H), 6.47 ( s, 1H), 4.23(s, 3H), 3.96(q, 2H), 2.85(s, 2H), 1.25(t, 3H), 1.06(s, 9H)

<Example 12>

Synthesis of compounds of formula Ia-1-1-12

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving cyclopropanecarboxylic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL), The reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (111.1 mg, 99.1%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-12 (68.1 mg, 63.9%, brown liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.56 (d, 1H), 8.44 (s, 1H), 7.55 (d, 1H), 7.37 (q, 1H), 6.49 (s, 1H), 4.23 (s, 3H), 3.99(q, 2H), 2.27(m, 1H), 1.27(m, 7H)

<Example 13>

Synthesis of compounds of formula Ia-1-1-13

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving cyclopentanecarboxylic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL), The reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (118.7 g, 98%, yellow liquid).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-13 (43.4 mg, 37.6%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.40 (d, 1H), 7.52-7.49 (m, 1H), 7.33-7.31 (m, 1H), 6.46 ( s, 1H), 4.21 (s, 3H), 3.95 (q, 2H), 3.41-3.35 (m, 1H), 2.15-2.12 (m, 2H), 2.01-1.997 (m, 2H), 1.84-1.79 ( m, 2H), 1.70-1.67 (m, 2H), 1.24 (t, 3H)

<Example 14>

Synthesis of compounds of formula Ia-1-1-14

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving cyclohexanecarboxylic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL), The reaction was carried out at room temperature for 1 hour. To N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution in which DCM (1 mL) was dissolved was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (121.7 g, 97%, pale yellow solid).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-14 (38.4 mg, 32.0%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.51 (m, 1H), 8.40 (d, 1H), 7.52-7.49 (m, 1H), 7.33-7.30 (m, 1H), 6.46 ( s, 1H), 4.21(s, 3H), 3.95(q, 2H), 3.02-2.97(m, 1H), 2.11-2.08(m, 2H), 1.84-1.80(m, 2H), 1.72-1.65( m, 2H), 1.45-1.34 (m, 2H), 1.33-1.21 (m, 5H)

<Example 15>

Synthesis of compounds of formula Ia-1-1-15

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving cyclohexaneacetic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) at room temperature, The reaction was carried out for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (121.1 g, 93.2%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-15 (24.5 mg, 19.7%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52 (d, 1H), 8.40 (s, 1H), 7.50 (d, 1H), 7.31 (q, 1H), 6.46 (s, 1H), 4.21 (s, 3H), 3.95 (q, 2H), 2.81 (d, 2H), 1.97-1.84 (m, 1H), 1.74-1.62 (m, 5H), 1.25-1.02 (m, 8H)

<Example 16>

Synthesis of compounds of formula Ia-1-1-16

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving cyclopropylacetic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) at room temperature, The reaction was carried out for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (107.3 g, 92%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-16 (44.8 mg, 40.4%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.40 (d, 1H), 7.52-7.50 (m, 1H), 7.33-7.31 (m, 1H), 6.46 ( s, 1H), 4.21(s, 3H), 3.95(q, 2H), 2.83(d, 2H), 1.25-1.17(m, 4H), 0.62-0.59(m, 2H), 0.31-0.28(m, 2H)

<Example 17>

Synthesis of compounds of formula Ia-1-1-17

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Add adamantane-2-carboxylic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), HOBt (58 mg, 0.380 mmol, 1.2 equiv.) to DCM (2 mL) After dissolving in, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (88.5mg, 62.4%, brown oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-17 (56.1 mg, 41.2%, brown liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54-8.52 (m, 1H), 8.41 (d, 1H), 7.52-7.50 (m, 1H), 7.34-7.27 (m, 1H), 6.46 ( s, 1H), 4.22(s, 3H), 3.96(q, 2H), 2.12-2.01(m, 8H), 1.81-1.71(m, 7H), 1.25(t, 3H)

<Example 18>

Synthesis of compounds of formula Ia-1-1-18

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: 3-oxocyclobutane-1-carboxylic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), hydroxybenzotriazole (HOBt, 58.0 mg, 0.380 mmol, 1.2 equiv .) was dissolved in DCM (2 mL) and the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (120 mg, 99%, colorless oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-18 (13.2 mg, 11.4%, light yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.39 (d, 1H), 7.53-7.51 (m, 1H), 7.34-7.32 (m, 1H), 6.47 ( s, 1H), 4.23 (s, 3H), 3.98-3.89 (m, 3H), 3.72-3.66 (m, 2H), 3.62-3.57 (m, 2H), 1.25 (t, 3H)

<Example 19>

Synthesis of compounds of formula Ia-1-1-19

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol), Cyclobutanecarbonyl chloride (0.042 mL, 0.364 mmol, 1.05 equiv.) and TEA (0.053 mL, 0.382 mmol, 1.1 equiv.) were dissolved in DMF (1 mL) and refluxed overnight to proceed with the reaction. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-19 (28.8 mg, 23.6% yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.40 (d, 1H), 7.52-7.50 (m, 1H), 7.33-7.31 (m, 1H), 6.46 ( s, 1H), 4.21(s, 3H), 3.95(q, 2H), 3.83-3.76(m, 1H), 2.57-2.41(m, 4H), 2.15-2.03(m, 2H), 1.24(t, 3H)

<Example 20>

Synthesis of compounds of formula Ia-1-1-20

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.173 mmol), trichloroacetic acid (0.032 mL, 0.173 mmol, 1.0 equiv.) was dissolved in toluene (1 mL) and refluxed for 2.5 hours to proceed with the reaction. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-20 (52.3 mg, 72.6%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.63-8.59 (m, 2H), 7.98-7.95 (m, 1H), 7.71-7.68 (m, 1H), 6.72 (s, 1H), 4.26 ( s, 3H), 4.04 (q, 2H), 1.28 (t, 3H)

<Example 21>

Synthesis of compounds of formula Ia-1-1-21

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Dissolve benzoic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), hydroxybenzotriazole (HOBt, 58.0 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) After the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (107.3 g, 78.8%, colorless oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-21 (10.0 mg, 10.5%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.55 (d, 1H), 8.44 (s, 1H), 8.24 (d, 2H), 7.58 (q, 4H), 7.35 (q, 1H), 6.52 (s, 1H), 4.29 (s, 3H), 3.99 (q, 2H), 1.27 (t, 3H)

<Example 22>

Synthesis of compounds of formula Ia-1-1-22

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Oxazole-4-carboxylic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) After dissolving, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (82.1 mg, 68%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-22 (10.0 mg, 8.7%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.58 (d, 1H), 8.55-8.54 (m, 1H), 8.43 (d, 1H), 8.08 (d, 1H), 7.54-7.51 (m, 1H), 7.35-7.33(m, 1H), 6.50(s, 1H), 4.29(s, 3H), 3.98(q, 2H), 1.27(t, 3H)

<Example 23>

Synthesis of compounds of formula Ia-1-1-23

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Oxazole-5-carboxylic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) After dissolving, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (86.9 g, 72%, brown oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-23 (29.5 mg, 25.6%, brown liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.56-8.54 (m, 1H), 8.42 (d, 1H), 8.17 (s, 1H), 8.06 (s, 1H), 7.55-7.53 (m, 1H), 7.36-7.28(m, 1H), 6.51(s, 1H), 4.28(s, 3H), 3.98(q, 2H), 1.26(t, 3H)

<Example 24>

Synthesis of compounds of formula Ia-1-1-24

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving 3-fluorobenzoic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL), The reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, and concentrated under reduced pressure to obtain an intermediate compound (110 mg), which was used in the next reaction without further purification.

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-24 (78.1 mg, 63.0%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.56-8.54 (m, 1H), 8.44 (d, 1H), 8.29-8.26 (m, 1H), 7.64-7.59 (m, 1H), 7.54- 7.52(m, 1H), 7.36-7.32(m, 2H), 7.31-7.28(m, 1H), 6.51(s, 1H), 4.30(s, 3H), 3.99(q, 2H), 1.27(t, 3H)

<Example 25>

Synthesis of compounds of formula Ia-1-1-25

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol), Tetrahydro-2H-pyran-4-carbonyl chloride (54.1 mg, 0.364 mmol, 1.05 equiv.), TEA (0.053 mL, 0.382 mmol, 1.1 equiv.) was dissolved in DMF (1 mL) and refluxed overnight to react. Proceeded. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-25 (19.4 mg, 14.6% yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.40 (d, 1H), 7.53-7.51 (m, 1H), 7.35-7.32 (m, 1H), 6.47 ( s, 1H), 4.22(s, 3H), 4.05-4.01(m, 2H), 3.96(q, 2H), 3.57-3.52(m, 2H), 3.28-3.24(m, 1H), 2.07-2.02( m, 4H), 1.26-1.24 (t, 3H)

<Example 26>

Synthesis of compounds of formula Ia-1-1-26

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol), Piperidine-1-carbonyl chloride (0.046 mL, 0.364 mmol, 1.05 equiv.) and TEA (0.053 mL, 0.382 mmol, 1.1 equiv.) were dissolved in DMF (1 mL) and refluxed overnight to proceed with the reaction. . After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-26 (25.3 mg, 18.2% brown liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.62-8.61 (m, 1H), 8.40 (d, 1H), 7.54-7.51 (m, 1H), 7.40-7.38 (m, 1H), 6.23 ( s, 1H), 4.07(s, 3H), 3.94(q, 2H), 3.17-3.15(m, 2H), 1.57-1.54(m, 4H), 1.26-1.23(m, 7H)

<Example 27>

Synthesis of compounds of formula Ia-1-1-27

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol), Pyrrolidine-1-carbonyl chloride (0.041 mL, 0.364 mmol, 1.05 equiv.) and TEA (0.053 mL, 0.382 mmol, 1.1 equiv.) were dissolved in DMF (1 mL) and refluxed overnight to proceed with the reaction. . After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-27 (58.2 mg, 43.5% yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.59-8.58 (m, 1H), 8.37 (d, 1H), 7.52-7.50 (m, 1H), 7.38-7.35 (m, 1H), 6.21 ( s, 1H), 4.04(s, 3H), 3.91(q, 2H), 3.35-3.33(m, 4H), 1.81-1.78(m, 4H), 1.22(t, 3H)

<Example 28>

Synthesis of compounds of formula Ia-1-1-28

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Pyrimidine-5-carboxylic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), HOBt (58 mg, 0.380 mmol, 1.2 equiv.) was added to DCM (2 mL) After dissolving, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (89.4 mg, 72%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-28 (15.1 mg, 12.7%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 9.52 (s, H), 9.43 (s, 1H), 8.55-8.54 (m, 1H), 8.41 (d, 1H), 7.56-7.53 (m, 1H), 7.36-7.34(m, 1H), 6.51(s, 1H), 4.29(s, 3H), 3.98(q, 2H), 1.26(t, 3H)

<Example 29>

Synthesis of compounds of formula Ia-1-1-29

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Pyridazine-4-carboxylic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), HOBt (58 mg, 0.380 mmol, 1.2 equiv.) was added to DCM (2 mL) After dissolving, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 1.1 mmol) A solution dissolved in DCM (2 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (86.9 g, 70%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-29 (5.6 mg, 4.7%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 9.94-9.93 (m, 1H), 9.53-9.52 (m, 1H), 8.57-8.56 (m, 1H), 8.41 (d, 1H), 8.22- 8.20(m, 1H), 7.57-7.55(m, 1H), 7.38-7.35(m, 1H), 6.53(s, 1H), 4.31(s, 3H), 4.00(q, 2H), 1.28(t, 3H)

<Example 30>

Synthesis of compounds of formula Ia-1-1-30

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: After dissolving nicotinic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) for 1 hour at room temperature The reaction proceeded. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (102.9 g, 83%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-30 (35.0 mg, 30%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 9.42 (d, 1H), 8.83-8.81 (m, 1H), 8.53-8.52 (m, 1H), 8.49-8.47 (m 1H), 8.41 (d , 1H), 7.54-7.47(m, 2H), 7.34-7.32(m, 1H), 6.50(s, 1H), 4.27(s, 3H), 3.96(q, 2H), 1.25(t, 3H)

<Example 31>

Synthesis of compounds of formula Ia-1-1-31

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Dissolve isonicotinic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) and then 1 at room temperature. Time reaction proceeded. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 1.1 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (101.61 g, 82%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-31 (38.1 mg, 32.2%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.86-8.85 (m, 2H), 8.53-8.52 (m, 2H), 8.40 (d, 2H), 8.05-8.03 (m, 2H), 7.54- 7.51(m, 1H), 7.34-7.32(m, 1H), 6.49(s, 1H), 4.27(s, 3H) 3.96(q, 2H), 1.25(t, 3H)

<Example 32>

Synthesis of compounds of formula Ia-1-1-32

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: 1-(pyridin-3-yl)cyclopropane-1-carboxylic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), HOBt (58 mg, 0.380 mmol, 1.2 equiv .) was dissolved in DCM (2 mL) and the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (116.1 g, 85%, yellow oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-32 (27.1 mg, 20.7%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.70 (d, 1H), 8.58-8.57 (m, 1H), 8.52-8.51 (m, 1H), 8.37 (d, 1H), 7.80-7.77 ( m, 1H), 7.50-7.48 (m, 1H), 7.32-7.29 (m, 2H), 6.43 (s, 1H), 4.15 (s, 3H), 3.94 (q, 2H), 1.96 (q, 2H) , 1.58(q, 2H), 1.23(t, 3H)

<Example 33>

Synthesis of compounds of formula Ia-1-1-33

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.347 mmol), diisopropyl After dissolving methanediimine (DIC, 0.11 mL, 0.728 mmol, 2.1 equiv.) in toluene (1 mL), the reaction was carried out under reflux for 4 hours. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-33 (82.3 mg, 66.8%, yellow oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.50-8.48 (m, 1H), 8.38 (d, 1H), 7.49-7.47 (m, 1H), 7.31-7.28 (m, 1H), 6.40 ( s, 1H), 5.93(d, 1H), 4.15(s, 3H), 4.03-3.98(m, 1H), 3.93(q, 2H), 1.23-1.20(m, 9H)

<Example 34>

Synthesis of compounds of formula Ia-1-1-34

*394 Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.347 mmol), dicyclohexyl After dissolving methanediimine (DCC, 150.29 mg. 0.728 mmol, 2.1 equiv.) in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-34 (84.8 mg, 61.8%, yellow oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.50-8.49 (m, 1H), 8.38 (d, 1H), 7.49-7.47 (m, 1H), 7.31-7.28 (m, 1H), 6.41 ( s, 1H), 5.82 (d, 1H), 4.15 (s, 3H), 3.93 (q, 2H), 2.02-1.99 (m, 2H), 1.71-1.67 (m, 2H), 1.36-1.09 (m, 9H)

<Example 35>

Synthesis of compounds of formula Ia-1-1-35

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (0.432 mmol), 1-ethyl After dissolving -3-(3dimethylaminopropyl)carboimide (EDCI, 0.2 mL) in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-35 (68.2 mg, 41.7%, white solid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.51-8.50 (m, 1H), 8.40 (d, 1H), 7.49-7.47 (m, 1H), 7.32-7.29 (m, 1H), 6.90 ( br s, 1H), 6.39 (s, 1H), 4.17 (s, 3H), 3.94 (q, 2H), 3.48-3.42 (m, 2H), 1.23 (t, 3H), 1.18 (t, 3H)

<Example 36>

Synthesis of compounds of formula Ia-1-1-36

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol), TBTU(2-(1H-benzotriazol-1-yl)1,1,3,3-tetramethylaminium tetrafluoroborate, 122.5 mg, 0.382 mmol. 1.1 equiv.), DIPEA (0.121 mL, 0.694 mmol) , 2.0 equiv.) was dissolved in DCM (1 mL) and the reaction was carried out at room temperature for 3.5 hours. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-36 (95.0 mg, 80.2%, white solid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.49-8.47 (m, 1H), 8.37 (d, 1H), 7.47-7.45 (m, 1H), 7.29-7.26 (m, 1H), 6.39 ( s, 1H), 4.14 (s, 3H), 3.92 (q, 2H), 3.15 (s, 6H), 1.20 (t, 3H)

<Example 37>

Synthesis of compounds of formula Ia-1-1-37

* Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol), After dissolving morpholine-4-carboxyl chloride (0.061 mL, 0.520 mmol, 1.5 equiv.) in pyridine (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-37 (3.0 mg, 2.3%, colorless oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.41 (d, 1H), 7.51-7.48 (m, 1H), 7.33-7.27 (m, 1H), 6.44 ( s, 1H), 4.19(s, 3H), 3.96(q, 2H), 3.79-3.77(m, 4H), 3.71-3.69(m, 4H), 1.25(t, 3H)

<Example 38>

Synthesis of compounds of formula Ia-1-1-38

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(5-(isopropylamino)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide (0.137 mmol), N,N-dimethyl-cyclohexylamine (0.05 mL, 0.343 mmol, 2.5 equiv.), dimethylaminopyridine (DMAP, 1.71 mg, 0.014 mmol, 0.1 equiv.), acetic anhydride ( 0.03 mL, 0.274 mmol, 2.0 equiv.) was dissolved in DMF (0.5 mL) and refluxed for time to proceed with the reaction. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-38 (46.4 mg, 85.2%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.39 (d, 1H), 7.56-7.54 (m, 1H), 7.37-7.34 (m, 1H), 6.49 ( s, 1H), 5.08-5.02 (m, 1H), 4.24 (s, 3H), 3.97 (q, 2H), 2.38 (s, 3H), 1.36 (s, 3H), 1.35 (s, 3H), 1.26 (t, 3H)

<Example 39>

*418 Synthesis of the compound of formula Ia-1-1-39

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

2-(5-(cyclohexylamino)-1,2,4-oxadiazol-3-yl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide (0.101 mmol), N,N-dimethyl-cyclohexylamine (0.04 mL, 0.253 mmol, 2.5 equiv.), DMAP (1.22 mg, 0.010 mmol, 0.1 equiv.), acetic anhydride (0.02 mL, 0.202 mmol, 2.0 equiv.) was dissolved in DMF (0.5 mL) and refluxed for time to proceed with the reaction. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-39 (38.4 mg, 86.8%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54-8.52 (m, 1H), 8.38 (d, 1H), 7.55-7.53 (m, 1H), 7.36-7.33 (m, 1H), 6.48 ( s, 1H), 4.61-4.56 (m, 1H), 4.22 (q, 2H), 3.96 (q, 2H), 2.29 (s, 3H), 1.78 (d, 4H), 1.71-1.61 (m, 3H) , 1.37-1.34(m, 2H), 1.25(t, 3H), 1.13-1.10(m, 1H)

<Example 40>

Synthesis of compounds of formula Ia-1-1-40

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Dissolve 2-(ethylthio)nicotinic acid (0.315 mmol), EDCI HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) After the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, and concentrated under reduced pressure to obtain an intermediate compound, which was used in the next reaction without further purification.

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-40 (98.8 mg, 72%, colorless oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.63-8.62 (m, 1H), 8.56-8.55 (m, 1H), 8.44-8.41 (m, 2H), 7.54-7.52 (m, 1H), 7.36-7.33(m, 1H), 7.17-7.14(m, 1H), 6.53(s, 1H), 4.33(s, 3H), 3.99(q, 2H), 3.29(q, 2H), 1.40(t, 3H), 1.27 (t, 3H)

<Example 41>

Synthesis of compounds of formula Ia-1-1-41

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(5-(isopropylamino)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Carboxamide (0.312 mmol), N,N-dimethyl-cyclohexylamine (0.12 mL, 0.781 mmol, 2.5 equiv.), DMAP (3.82 mg, 0.031 mmol, 0.1 equiv.), Pivaloyl chloride (Pivaloyl chloride) , 0.08 mL, 0.625 mmol, 2.0 equiv.) was dissolved in DMF (0.5 mL) and refluxed for time to proceed with the reaction. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-41 (82.5 mg, 60.1%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.51 (m, 1H), 8.37 (d, 1H), 7.55-7.53 (m, 1H), 7.34-7.32 (m, 1H), 6.46 ( s, 1H), 4.84-4.79 (m, 1H), 4.22 (s, 3H), 3.95 (q, 2H), 1.25-1.19 (m, 9H), 1.12 (s, 9H)

<Example 42>

Synthesis of compounds of formula Ia-1-1-42

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

N-ethyl-2-(5-(isopropylamino)-1,2,4-oxadiazol-3-yl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5 -Dissolve carboxamide (0.328 mmol), ethyl chloroformate (0.03 mL, 0.328 mmol, 1.0 equiv.), and DIPEA (0.06 mL, 0.328 mmol, 1.0 equiv.) in acetone (1.0 mL) and reflux for time. The reaction proceeded. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-41 (86.5 mg, 61.6%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.39 (d, 1H), 7.52-7.50 (m, 1H), 7.34-7.31 (m, 1H), 6.46 ( s, 1H), 4.84-4.79 (m, 1H), 4.30 (q, 2H), 4.21 (s, 3H), 3.95 (q, 2H), 1.39 (s, 3H), 1.38 (s, 3H), 1.31 (t, 3H), 1.24 (t, 3H)

<Example 43>

Synthesis of compounds of formula Ia-1-1-43

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: Dissolve 2-(ethylthio)benzoic acid (0.315 mmol), EDCI·HCl (72.85 mg, 0.380 mmol, 1.2 equiv.), and HOBt (58 mg, 0.380 mmol, 1.2 equiv.) in DCM (2 mL) After the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg, 0.347 mmol) A solution dissolved in DCM (1 mL) was slowly added, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (107.0 mg, 75.1%, pale yellow solid).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-43 (28.3 mg, 20.7%, colorless oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.44-8.43 (m, 1H), 8.17-8.15 (m, 1H), 7.54-7.50 (m, 2H), 7.44-7.43(m, 1H), 7.35-7.33(m, 1H), 7.29-7.28(m, 1H), 6.52(s, 1H), 4.32(s, 3H), 3.98(q, 2H), 3.03( q, 2H), 1.38 (t, 3H), 1.27 (t, 3H)

<Example 44>

Synthesis of compounds of formula Ia-1-1-44

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Ia-1-1-43 compound (0.046 mmol), m CPBA (19.86 mg, 0.115 mmol, 2.5 equiv.) was dissolved in DCM (1 mL), followed by a room temperature reaction overnight. After washing with water and layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to form a compound represented by Formula Ia-1-1-44 (16 mg, 74.5%, colorless oil) Was obtained.

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.23-8.21 (m, 1H), 8.14-8.13 (m, 2H), 7.92-7.90 (m, 1H), 7.84-7.82 (m, 2H), 7.30-7.27(m, 1H), 7.10-7.08(m, 1H), 6.82(s, 1H), 4.26(s, 3H), 3.95(q, 2H), 3.64(q, 2H), 1.35(t, 3H), 1.27 (t, 3H)

<Example 45>

Synthesis of compounds of formula Ia-1-1-45

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg) was added to 1,4 -After dissolving in dioxane (5 ml) and N-methyl-2-pyrrolidone (0.5 mL), cool with ice water. Pyridine (0.06 mL) and 4-(dimethylamino)benzoyl chloride (76.4 mg) were slowly added dropwise to the cooled solution. After dropwise addition, the temperature was raised to room temperature and stirred overnight. After completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain an intermediate (116.2 mg, 80.3%, white solid). After dissolving the intermediate in toluene (1 mL), the reaction was carried out overnight while refluxing. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-45 (8.9mg, 7.9%, white solid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.44 (d, 1H), 8.07 (s, 1H), 8.06 (s, 1H), 7.52-7.50 (m, 1H), 7.34-7.31(m, 1H), 6.74(s, 1H), 6.72(s, 1H), 6.49(s, 1H), 4.28(s, 3H), 3.98(q, 2H), 3.08(s , 6H), 1.26 (t, 3H)

<Example 46>

Synthesis of compounds of formula Ia-1-1-46

N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg) was added to 1,4 -After dissolving in dioxane (5 ml) and N-methyl-2-pyrrolidone (0.5 mL), cool with ice water. Pyridine (0.06 mL) and 2-ethoxybenzoyl chloride (0.06 mL) were slowly added dropwise to the cooled solution. After dropwise addition, the temperature was raised to room temperature and stirred overnight. After completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain an intermediate (339.6 mg, NMP mixture, colorless liquid). After dissolving the intermediate in toluene (1 mL), the reaction was carried out overnight while refluxing. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound (37.2mg, 25.6%, white solid) represented by Formula Ia-1-1-46.

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.56 (d, 1H), 8.50 (br s, 1H), 8.23 (d, 1H), 7.68 (br s, 1H), 7.54 (t, 1H) , 7.47(br s, 1H), 7.08-7.05(m, 1H), 6.61(s, 1H), 4.31(s, 3H), 4.2(q, 2H), 4.01(q, 2H), 1.53(t, 3H), 1.28 (t, 3H)

<Example 47>

Synthesis of compounds of formula Ia-1-1-47

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: 1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid (135.7 mg), EDCI HCl (145.1 mg, 0.757 mmol, 1.2 equiv.), HOBt (102.3 mg, 0.757 mmol, 1.2 equiv.) was dissolved in DCM (3 mL) and the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (200 mg, 0.694 mmol, 1.1 equiv.) in DCM (1 mL) was slowly added thereto, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (295.4 mg, 96.5%, colorless oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-47 (212.4 mg, 74.7%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.47 (d, 1H), 8.34 (s, 1H), 7.49-7.47 (m, 1H), 7.30-7.27 (m, 1H), 6.41 (s, 1H), 4.16(s, 3H), 3.90(q, 2H), 3.80-3.37(m, 6H), 2.35-2.31(m, 2H), 1.39(s, 9H), 1.19(t, 3H)

<Example 48>

Synthesis of compounds of formula Ia-1-1-48

Tert-butyl 3-(3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1,2,4 prepared according to Example 47 -Oxadiazol-5-yl)pyrrolidine-1-carboxylate (82.2 mg) and triethylamine (TEA, 1.5 mL) were dissolved in DCM (1.5 mL), followed by reaction at room temperature for 3 hours. After completion of the reaction, it _{was neutralized with NaHCO 3} aqueous solution, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-48 (44.7 mg, 69.2%, pale yellow oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.37 (d, 1H), 7.53-7.51 (m, 1H), 7.34-7.32 (m, 1H), 6.45 ( s, 1H), 4.19(s, 3H), 3.96(q, 2H), 3.86-3.82(m, 1H), 3.73-3.69(m, 1H), 3.46(t, 2H), 2.61-2.54(m, 1H), 2.40-2.33(m, 1H), 1.24(t, 3H)

<Example 49>

Synthesis of compounds of formula Ia-1-1-49

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (144.67 mg), EDCI HCl (145.1 mg, 0.757 mmol, 1.2 equiv.), HOBt (102.3 mg, 0.757 mmol, 1.2 equiv.) was dissolved in DCM (3 mL) and the reaction was carried out at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (200 mg, 0.694 mmol, 1.1 equiv.) in DCM (1 mL) was slowly added thereto, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (265.7 g, 84.3%, colorless oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-49 (214.8 mg, 70.7%, yellow oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.41 (d, 1H), 7.56-7.54 (m, 1H), 7.37-7.34 (m, 1H), 6.48 ( s, 1H), 4.21(s, 3H), 4.08(br s, 2H), 3.96(q, 2H), 3.19-3.13(m, 1H), 2.97-2.93(m, 2H), 2.01-2.07(m) , 2H), 1.91-1.83 (m, 2H), 1.44 (s, 9H), 1.24 (t, 3H)

<Example 50>

Synthesis of the compound of formula Ia-1-1-50

Tert-butyl 4-(3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1,2,4 prepared according to Example 49 -Oxadiazol-5-yl)piperidine-1-carboxylate (118.2 mg) and TEA (2.0 mL) were dissolved in DCM (2.0 mL), followed by reaction at room temperature for 3 hours. After completion of the reaction, it _{was neutralized with NaHCO 3} aqueous solution, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-50 (35.0 mg, 37.4%, yellow oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.37 (d, 1H), 7.53-7.52 (m, 1H), 7.34-7.32 (m, 1H), 6.45 ( s, 1H), 4.21(s, 3H), 3.95(q, 2H), 3.44-3.32(m, 3H), 3.11-3.06(m, 2H), 2.36-2.33(m, 2H), 2.26-2.19( m, 2H), 1.24 (t, 3H)

<Example 51>

Synthesis of compounds of formula Ia-1-1-51

Synthesis was performed in the same manner as in Example 1, except that steps 6 and 7 were changed as follows.

Step 6: (tert-butoxycarbonyl) proline (135.78 mg), EDCI HCl (145.1 mg, 0.757 mmol, 1.2 equiv.), HOBt (102.3 mg, 0.757 mmol, 1.2 equiv.) to DCM (3 mL) After dissolving in, the reaction was performed at room temperature for 1 hour. N-ethyl-2-(N'-hydroxycarbamidoyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (200 mg, 0.694 mmol, 1.1 equiv.) in DCM (1 mL) was slowly added thereto, and the reaction was carried out overnight at room temperature. After completion of the reaction, the mixture was washed with water and extracted by adding DCM. After layer separation, the organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (225.1 g, 73.5%, white oil).

Step 7: After dissolving the compound obtained in Step 6 in toluene (1 mL), the reaction was carried out by refluxing overnight. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-1-51 (191.6 mg, 65.0%, yellow oil).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.50 (br s, 1H), 8.38 (d, 1H), 7.54-7.47 (m, 1H), 7.34-7.31 (m, 1H), 6.44 (s , 1H), 5.16-5.04(m, 1H), 4.18(d, 3H), 3.93(q, 2H), 3.65-3.61(m, 1H), 3.53-3.39(m, 1H), 2.38-2.30(m) , 1H), 2.14-2.05(m, 2H), 1.97-1.92(m, 1H), 1.40(s, 4H), 1.26(s, 5H), 1.229(t, 3H)

<Example 52>

Synthesis of compounds of formula Ia-1-1-52

Tert-butyl 2-(3-(5-(ethyl(pyridin-3-yl)carbamoyl)-1-methyl-1H-imidazol-2-yl)-1,2,4 prepared according to Example 51 -Oxadiazol-5-yl)pyrrolidine-1-carboxylate (93.3 mg) and TEA (1.5 mL) were dissolved in DCM (1.5 mL), followed by reaction at room temperature for 3 hours. After completion of the reaction, it _{was neutralized with NaHCO 3} aqueous solution, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain 60.2 mg (82.1%, yellow oil) of a compound represented by Formula Ia-1-1-52.

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.39 (d, 1H), 7.50-7.48 (m, 1H), 7.33-7.31 (m, 1H), 6.49 ( s, 1H), 4.76-4.74 (m, 1H), 4.21 (s, 3H), 3.96 (q, 2H), 3.31-3.19 (m, 2H), 2.44-2.37 (m, 1H), 2.26-2.19 ( m, 1H), 2.05-1.96 (m, 2H), 1.24 (t, 3H)

<Example 53>

Synthesis of compound of formula Ia-1-2-1

1-methylthiourea (71 mg, 0.7835 mmol) was dissolved in dimethyl sulfoxide (DMSO, 0.5 mL), potassium tert-butoxide (88 mg, 0.7835 mmol) was added and stirred at room temperature for 5 minutes, Example 2-cyano-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide ( 100 mg, 0.3917 mmol) was added. The mixture was stirred at room temperature for 3 hours, and H ₂ O (5.0 mL) was added to terminate the reaction. Extracted with ethyl acetate (5.0 mL x2), and the combined organic layers were dried over _{anhydrous MgSO 4 and filtered.} The filtrate was concentrated under reduced pressure to obtain an intermediate compound (110 mg), which was used in the next reaction without further purification.

The intermediate compound (110 mg, 0.3184 mmol) thus obtained was dissolved in DMSO (0.5 mL), and H ₂ O (0.05 mL) was added. Iodine (178 mg, 0.7006 mmol) and potassium hydroxide (36 mg, 0.6368 mmol) were added, followed by stirring at room temperature for 24 hours. After completion of the reaction, saturated Na ₂ S ₂ O ₃ aqueous solution (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain a compound (30.5 mg, 28%, white solid) represented by Formula Ia-1-2-1.

¹ H-NMR (500 MHz): CDCl ³ (δ) 8.51-8.50 (m, 1H), 8.42 (d, 1H), 7.66 (s, 1H), 7.49-7.46 (m, 1H), 7.31-7.29 ( m, 1H), 6.39(s, 1H), 4.28(s, 3H), 3.96(q, 2H), 2.96(d, 3H), 1.25(t, 3H)

<Example 54>

Synthesis of compounds of formula Ia-1-2-2

1-ethylthiourea (41 mg, 0.3917 mmol) was dissolved in DMSO (0.3 mL), potassium tert-butoxide (44 mg, 0.3917 mmol) was added and stirred at room temperature for 10 minutes, step 1 of Example 1 , 2-cyano-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (50 mg, 0.1959 mmol) was added. The mixture was stirred at room temperature for 3 hours, and H ₂ O (0.5 mL) was added to terminate the reaction. Extracted with ethyl acetate (5.0 mL x2), and the combined organic layers were dried over _{anhydrous MgSO 4 and filtered.} The filtrate was concentrated under reduced pressure to obtain an intermediate compound, which was used in the next reaction without further purification.

The intermediate compound thus obtained was dissolved in DMSO (0.5 mL), and H ₂ O (0.05 mL) was added. Iodine (109 mg, 0.4310 mmol) and potassium hydroxide (22 mg, 0.3917 mmol) were added, followed by stirring at room temperature for 24 hours. After completion of the reaction, saturated Na ₂ S ₂ O ₃ aqueous solution (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-2-2 (19.5 mg, 28%, ivory solid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.50-8.49 (m, 1H), 8.40 (d, 1H), 7.48-7.46 (m, 1H), 7.40 (s, 1H), 7.30-7.27 ( m, 1H), 6.36(s, 1H), 4.25(s, 3H), 3.95(q, 2H), 3.30-3.24(m, 2H), 1.23(t, 3H), 1.17(t, 3H)

<Example 55>

Synthesis of compounds of formula Ia-1-2-3

After dissolving 1-(2-bromophenyl)thiourea (91 mg, 0.3917 mmol) in DMSO (0.3 mL), potassium tert-butoxide (44 mg, 0.3917 mmol) was added and stirred at room temperature for 10 minutes, 2-cyano-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa obtained by sequentially performing steps 1, 2, 3, and 4 of Example 1 Mide (50 mg, 0.1959 mmol) was added. The mixture was stirred at room temperature for 3 hours, and H ₂ O (0.5 mL) was added to terminate the reaction. Extracted with ethyl acetate (5.0 mL x2), and the combined organic layers were dried over _{anhydrous MgSO 4 and filtered.} The filtrate was concentrated under reduced pressure to obtain an intermediate compound, which was used in the next reaction without further purification.

The intermediate compound thus obtained was dissolved in DMSO (0.5 mL), and H ₂ O (0.05 mL) was added. Iodine (109 mg, 0.4310 mmol) and potassium hydroxide (22 mg, 0.3917 mmol) were added, followed by stirring at room temperature for 24 hours. After completion of the reaction, saturated Na ₂ S ₂ O ₃ aqueous solution (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain a compound (33.4 mg, 35%, ivory solid) represented by Formula Ia-1-2-3.

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.51-8.49 (m, 1H), 8.40 (d, 1H), 7.60-7.58 (m, 1H), 7.53-7.51 (m, 1H), 7.49- 7.46(m, 1H), 7.40-7.36(m, 1H), 7.31-7.28(m, 1H), 7.04-7.01(m, 1H), 6.33(s, 1H), 4.29(s, 3H), 3.95( q, 2H), 3.45 (s, 1H), 1.23 (t, 3H)

<Example 56>

Synthesis of compounds of formula Ia-1-3-1

1-Methyl-1H-imidazole-5-carbonyl chloride·HCl salt (2.01 g) is dissolved in DCM (20 mL). A solution in which N-methylpyridin-3-amine (1.0 g) and N,N-diisopropylethylamine (DIPEA, 6.44 mL) were dissolved in DCM (10 mL) was slowly added dropwise to the solution cooled with ice water. After the dropwise addition was completed, the temperature was raised to room temperature and reacted at room temperature for 30 minutes. The mixture was heated to 50° C., reacted for 2 hours, and then cooled to room temperature. After completion of the reaction, it was quenched with water and extracted with DCM. The organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated, and purified by silica gel column chromatography to obtain the target compound (816.4 mg, 40.8%, brown liquid).

N,1-dimethyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (816 mg) and paraformaldehyde (3.67 g) are dissolved in methanol (2 mL). The temperature was raised to 140° C. and reacted for 3 days. After completion of the reaction, the mixture was cooled to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (572 mg, 58.2%, brown liquid).

2-(hydroxymethyl)-N,1-dimethyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (480.0 mg) is dissolved in THF (50 mL). MnO ₂ (802.4 mg) was slowly added dropwise and stirred at room temperature overnight. After completion of the reaction, the mixture was filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (198.9 mg, 42.2%, yellow liquid).

2-formyl-N,1-dimethyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (100 mg) and cyclopropanecarbohydrazide (45.1 mg) in ethanol (1 mL) and the reaction was carried out overnight at room temperature. After confirming the completion of the reaction, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (99.3 mg, 74.3%, colorless oil).

(E)-2-((2-(cyclopropanecarbonyl)hydrazineylidene)methyl)-N,1-dimethyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide ( 40 mg), I ₂ (37.33 mg), K ₂ CO ₃ (50.82 mg) were dissolved in 1,4-dioxane (1 mL) and stirred at 80° C. overnight. After completion of the reaction, 5% NaS ₂ O ₃ aqueous solution was added and extracted with DCM. The organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated, and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-3-1 (31.0 mg, 78.1%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.42 (d, 1H), 7.53-7.51 (m 1H), 7.33-7.30 (m, 1H), 6.43 (s , 1H), 4.30(s, 3H), 3.49(s, 3H), 2.24-2.18(m, 1H), 1.23-1.15(m, 4H)

<Example 57>

Synthesis of compounds of formula Ia-1-3-2

N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (2.0 g) and paraformaldehyde (9.0 g) were dissolved in methanol (20 mL). The temperature was raised to 140° C. and reacted for 3 days. After completion of the reaction, the mixture was cooled to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (1.97 g, 43.6%, yellow liquid).

N-ethyl-2-(hydroxymethyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (400 mg) is dissolved in THF (10 mL). MnO ₂ (667.8 mg) was slowly added dropwise and stirred at room temperature overnight. After completion of the reaction, the mixture was filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (310.2 mg, 78.2%, white solid).

N-ethyl-2-formyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (150 mg) and cyclopropanecarbohydrazide (64.0 mg) in ethanol After dissolving in (1 mL), the reaction was carried out overnight at room temperature. After confirming the completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain a compound (104.8 mg, 53.0%, white form).

(E)-2-((2-(cyclopropanecarbonyl)hydrazineylidene)methyl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxa Mide (82.3 mg), I ₂ (73.64 mg), and K ₂ CO ₃ (100.25 mg) were dissolved in 1,4-dioxane (1 mL), followed by stirring at 80° C. overnight. After completion of the reaction, 5% NaS ₂ O ₃ aqueous solution was added and extracted with DCM. The organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated, and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-3-2 (66.7 mg, 81.5%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.53-8.51 (m, 1H), 8.38 (d, 1H), 7.51-7.48 (m 1H), 7.33-7.31 (m, 1H), 6.39 (s , 1H), 4.29(s, 3H), 3.94(q, 2H), 2.23-2.17(m, 1H), 1.23(t, 3H), 1.21-1.14(m, 4H)

<Example 58>

Synthesis of compounds of formula Ia-1-3-3

N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (2.0 g) and paraformaldehyde (9.0 g) were dissolved in methanol (20 mL). The temperature was raised to 140° C. and reacted for 3 days. After completion of the reaction, the mixture was cooled to room temperature, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (1.97 g, 43.6%, yellow liquid).

N-ethyl-2-(hydroxymethyl)-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (400 mg) is dissolved in THF (10 mL). MnO ₂ (667.8 mg) was slowly added dropwise and stirred at room temperature overnight. After completion of the reaction, the mixture was filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (310.2 mg, 78.2%, white solid).

N-ethyl-2-formyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (150 mg) and acetohydrazide (47.3 mg) in ethanol (1 mL) and the reaction was carried out overnight at room temperature. After confirming the completion of the reaction, the target compound was concentrated under reduced pressure and purified by silica gel column chromatography. (169.1 mg, 92.6%, colorless oil) was obtained.

(E)-2-((2-acetylhydrazineylidene)methyl)-N-ethyl-1-methyl-N-(pyridin-3-yl)-1H-imidazole-5-carboxamide (132.2 mg) , I ₂ (128.1 mg), K ₂ CO ₃ (174.4 mg) was dissolved in 1,4-dioxane (1 mL) and stirred at 80° C. overnight. After completion of the reaction, 5% NaS ₂ O ₃ aqueous solution was added and extracted with DCM. The organic layer _{was dried over anhydrous MgSO 4} , filtered, concentrated, and purified by silica gel column chromatography to obtain a compound represented by Formula Ia-1-3-3 (108.9 mg, 83.1%, yellow liquid).

¹ H-NMR (500 MHz): CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.39 (d, 1H), 7.52-7.50 (m 1H), 7.34-7.32 (m, 1H), 6.41 (s , 1H), 4.31(s, 3H), 3.95(q, 2H), 2.58(s, 3H), 1.24(t, 3H)

<Example 59>

Synthesis of compounds of formula Ia-1-4-1

Step 1: After dissolving 1-methyl-1H-imidazole-5-carboxylic acid (37.80 g, 300.0 mmol) in acetonitrile (400 mL) under ice bath cooling, oxalyl chloride (30.5 mL, 360.0 mmol) was added to 10 After adding dropwise for a minute, N,N-dimethylformamide (0.5 mL, mmol) was added dropwise. The reaction mixture was heated to room temperature and stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was dispersed in isopropyl ether (200 mL), followed by stirring for 15 minutes. The resulting solid was filtered, washed with isopropyl ether (100 mL), and dried to obtain the target compound (1) (53.92 g, 99%, ivory solid). 3-bromopyridine (40.0 g, 253.2 mmol), ethylamine (66.0-72.0% H ₂ O solution, 107 mL, 1265.8 mmol), and Cu powder (805 mg, 12.66 mmol) were sequentially added to the sealed tube, and then 100 It was stirred at °C for 3 days. After completion of the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate (100 mL x5). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, and concentrated to obtain the title compound (2) (29.61 g, 96%, light brown liquid). After dispersing compound (1) (52.65 g, 290.8 mmol) in dichloromethane (300 mL), a solution in which compound (2) (29.61 g, 242.3 mmol) was dissolved in dichloromethane (100 mL) under ice bath cooling was added dropwise for 10 minutes. Then, N,N-diisopropylethylamine (169 mL, 969.2 mmol) was added dropwise for 15 minutes. The reaction mixture was heated to room temperature, stirred at room temperature for 30 minutes, and then stirred under reflux for 2 hours. After completion of the reaction, the mixture was cooled to room temperature and H ₂ O (200 mL) was added to terminate the reaction. The mixture was extracted with dichloromethane (100 mL x4). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated and purified by silica gel column chromatography to obtain the title compound (3) (48.97 g, 88%, brown oil).

Step 2: Compound (3) (10.0 g, 43.4 mmol) obtained in step 1 was dissolved in tetrahydrofuran (THF) (100 mL), and toluene (150 mL) was added. It was cooled to -78 °C under _{N 2 conditions using acetone and dry ice.} While maintaining the reaction temperature below -70 °C, n-butyllithium (n-BuLi) (2.5M n-hexane solution, 17.7 mL, 44.2 mmol) was slowly added dropwise, followed by stirring at -78 °C for 40 minutes. A solution in which p-toluenesulfonyl cinide (9.44 g, 52.1 mmol) was dissolved in THF (50 mL) was slowly added dropwise. After the dropwise addition was completed, the mixture was stirred at -78°C for 1 hour, the temperature was raised to room temperature, and further stirred for 4 hours. Methanol was added to terminate the reaction and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the target compound (4) (4.29 g, 39%, brown liquid).

Step 3: Dissolve compound (4) (4.29 g, 16.8 mmol) in ethanol (30 mL _{) and slowly add NH 2} OH (50% H ₂ O solution, 2.06 mL, 33.6 mmol) dropwise, and then stir at room temperature for 1 hour. I did. After completion of the reaction, it was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (5) (3.87 g, 80%, pale yellow solid). After dissolving the prepared compound (5) (30 mg, 0.1041 mmol) in acetic acid (0.3 mL), acetone (0.012 mL, 0.1561 mmol, 1.5 eq) was added as compound (6), followed by stirring at room temperature for 5 days. . After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Ia-1-4-1) (11.5 mg, 34%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.53 (d, 1H), 8.39 (d, 1H), 7.50-7.47 (m, 1H), 7.34-7.32 (m, 1H), 6.29 (s, 1H), 5.64 (s, 1H), 4.12(s, 3H), 3.94(q, 2H), 1.51(s, 6H), 1.23(t, 3H)

<Example 60>

Synthesis of compounds of formula Ia-1-4-2

Compound (Ia-1-4-1) (50mg, 0.1523 mmol) was dissolved in THF (0.5 mL), NaH (9 mg, 0.2284 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.028 mL, 0.4569 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture containing a compound of formula Ia-1-4-2 and a compound of formula Ia-1-5-1. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-2) (19.6 mg, 38%, yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.38 (d, 1H), 7.51-7.49 (m, 1H), 7.35-7.32 (m, 1H), 6.36 (s, 1H) , 4.17(s, 3H), 3.96(q, 2H), 3.25(s, 3H), 1.55(s, 6H), 1.25(t, 3H)

<Example 61>

Synthesis of compounds of formula Ia-1-4-3

Compound (Ia-1-4-1) (30 mg, 0.0914 mmol) was dissolved in THF (0.3 mL), NaH (3 mg, 0.1370 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Cyclopropanecarbonyl chloride (0.025 mL, 0.2741 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-3) (24.3 mg, 67%, colorless liquid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.53 (m, 1H), 8.43 (d, 1H), 7.50-7.47 (m, 1H), 7.34-7.31 (m, 1H), 6.32 (s, 1H) , 3.99(s, 3H), 3.93(q, 2H), 2.17-2.12(m, 1H), 1.61(s, 6H), 1.22(t, 3H), 1.05-1.03(m, 2H), 0.94-0.92 (m, 2H)

<Example 62>

Synthesis of compounds of formula Ia-1-4-4

After dissolving compound (5) (50 mg, 0.0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 3-pentanone (0.037 mL, 0.3468 mmol, 2 equivalents) was added and stirred at room temperature for 6 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-4) (12.5 mg, 20%, colorless oil).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.39 (d, 1H), 7.51-7.49 (m, 1H), 7.34-7.32 (m, 1H), 6.29 (s, 1H) , 5.30(s, 1H), 4.11(s, 3H), 3.94(q, 2H), 1.77-1.68(m, 4H), 1.23(t, 3H), 0.94(t, 6H)

<Example 63>

Synthesis of compounds of formula Ia-1-4-5

Compound (Ia-1-4-4) (9.5 mg, 0.0267 mmol) was dissolved in THF (0.2 mL), NaH (2.1 mg, 0.05331 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.005 mL, 0.0800 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (3.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-5) (3,4 mg, 34%, yellow oil). .

¹ H-NMR: CDCl ₃ (δ) 8.55-8.53 (m, 1H), 8.39 (d, 1H), 7.53-7.51 (m, 1H), 7.35-7.33 (m, 1H), 6.36 (s, 1H) , 4.18(s, 3H), 3.96(q, 2H), 3.21(s, 3H), 1.84-1.72(m, 4H), 1.25(t, 3H), 0.95(t, 6H)

<Example 64>

Synthesis of compounds of formula Ia-1-4-6

After dissolving compound (5) (50 mg, 0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), cyclopentanone (0.031 mL, 0.3468 mmol, 2 equivalents) as compound (6) Was added and stirred at room temperature for 6 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Ia-1-4-6) (35.8 mg, 58%, yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.39 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.32 (m, 1H), 6.30 (s, 1H) , 5.32(s, 1H), 4.13(s, 3H), 3.95(q, 2H), 2.15-2.11(m, 2H), 1.79-1.73(m, 4H), 1.68-1.66(m, 2H), 1.24 (t, 3H)

<Example 65>

Synthesis of compounds of formula Ia-1-4-7

Compound (Ia-1-4-6) (10.9 mg, 0.0308 mmol) was dissolved in THF (0.5 mL), NaH (2.5 mg, 0.0.0615 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.006 mL, 0.0923 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture including a compound of Formula Ia-1-4-7 and a compound of Formula Ia-1-5-11. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-7) (4.1 mg, 36%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.38 (d, 1H), 7.51-7.49 (m, 1H), 7.34-7.32 (m, 1H), 6.36 (s, 1H) , 4.18(s, 3H), 3.95(q, 2H), 3.22(s, 3H), 1.98-1.96(m, 4H), 1.79-1.77(m, 4H), 1.24(t, 3H)

<Example 66 >

Synthesis of compounds of formula Ia-1-4-8

After dissolving compound (5) (50 mg, 0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), cyclohexanone (0.027 mL, 0.2601 mmol, 1.5 equivalents) as compound (6) Was added and stirred at room temperature for 2 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-8) (33 mg, 52%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.38 (d, 1H), 7.50-7.47 (m, 1H), 7.34-7.31 (m, 1H), 6.29 (s, 1H) , 5.47(s, 1H), 4.12(s, 3H), 3.94(q, 2H), 1.89-1.85(m, 2H), 1.75-1.64(m, 2H), 1.55-1.44(m, 3H), 1.40 -1.34(m, 1H), 1.23(t, 3H)

<Example 67 >

Synthesis of compounds of formula Ia-1-4-9

After dissolving the compound (Formula Ia-1-4-8) (12.5 mg, 0.0339 mmol) in THF (0.4 mL), NaH (2 mg, 0.0509 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.003 mL, 0.0509 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-9) (4.2 mg, 32%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.37 (d, 1H), 7.52-7.49 (m, 1H), 7.34-7.32 (m, 1H), 6.36 (s, 1H) , 4.18(s, 3H), 3.95(q, 2H), 3.24(s, 3H), 1.84-1.76(m, 4H), 1.71-1.65(m, 4H), 1.49-1.46(m, 2H), 1.24 (t, 3H)

<Example 68 >

Synthesis of compounds of formula Ia-1-4-10

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), tetrahydro-4H-pyran-4-one (_0. 014 mL, 0.1561 mmol, 1.5 eq) was added and stirred at room temperature for 4 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Ia-1-4-10) (21.9 mg, 57%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.36 (d, 1H), 7.50-7.47 (m, 1H), 7.34-7.31 (m, 1H), 6.27 (s, 1H) , 5.86(s, 1H), 4.11(s, 3H), 3.93(q, 2H), 3.79-3.77(m, 4H), 1.97-1.94(m, 2H), 1.83-1.77(m, 2H), 1.22 (t, 3H)

<Example 69 >

Synthesis of Compounds of Formula Ia-1-4-11

After dissolving the compound (Formula Ia-1-4-10) (50 mg, 0.1350 mmol) in THF (0.5 mL), NaH (8 mg, 0.2025 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.025 mL, 0.4050 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture containing a compound of formula Ia-1-4-11 and a compound of formula Ia-1-5-2. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-11) (25.6 mg, 49%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.36 (d, 1H), 7.53-7.51 (m, 1H), 7.35-7.33 (m, 1H), 6.38 (s, 1H) , 4.19(s, 3H), 3.96(q, 2H), 3.87-3.84(m, 4H), 3.29(s, 3H), 1.97-1.88(m, 4H), 1.25(t, 3H)

<Example 70 >

Synthesis of compounds of formula Ia-1-4-12

Compound (Ia-1-4-10) (18.8 mg, 0.0508 mmol) was dissolved in THF (0.3 mL), NaH (4.1 mg, 0.0.1015 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Cyclopropanecarbonyl chloride (0.014 mL, 0.1523 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-12) (17.4 mg, 78%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.56-8.55 (m, 1H), 8.44 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.32 (m, 1H), 6.33 (s, 1H) , 4.00(s, 3H), 3.95-3.84(m, 6H), 2.20-2.17(m, 1H), 2.83-1.93(m, 4H), 1.23(t, 3H), 1.06-1.04(m, 2H) , 0.96-0.94 (m, 2H)

<Example 71 >

Synthesis of Compounds of Formula Ia-1-4-13

Compound (Ia-1-4-10) (33.3 mg, 0.0899 mmol) was dissolved in THF (0.4 mL), NaH (7.2 mg, 0.1798 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Benzyl bromide (0.032 mL, 0.2697_ mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-13) (15.8 mg, 38%, colorless liquid).

¹ H-NMR: CDCl ₃ (δ) 8.56-8.55 (m, 1H), 8.40 (d, 1H), 7.56-7.53 (m, 1H), 7.37-7.35 (m, 1H), 7.27-7.26 (m, 3H), 7.01-6.99(m, 2H), 6.46(s, 1H), 4.75(s, 2H), 4.03(s, 3H), 3.98(q, 2H), 3.75(t, 4H), 1.69-1.59 (m, 4H), 1.27 (t, 3H)

<Example 72 >

Synthesis of compounds of formula Ia-1-4-14

After dissolving compound (5) (300 mg, 1.041 mmol) obtained in step 3 of Example 59 in acetic acid (2.0 mL), 1-methylpiperidin-4-one (_0. 26 mL, 2.081 mmol, 2.0 equivalent) was added and stirred at room temperature for 3 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (_10.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Ia-1-4-14) (114.1 mg, 29%, ivory solid).

¹ H-NMR: CDCl ₃ (δ) 8.46-8.45 (m, 1H), 8.31 (d, 1H), 7.44-7.42 (m, 1H), 7.28-7.25 (m, 1H), 6.21 (s, 1H) , 5.96(s, 1H), 4.04(s, 3H), 3.87(q, 2H), 2.45-2.41(m, 4H), 2.20(s, 3H), 1.93-1.89(m, 2H), 1.76-1.73 (m, 2H), 1.15 (t, 3H)

<Example 73 >

Synthesis of compounds of formula Ia-1-4-15

After dissolving the compound synthesized in Example 78 (Chemical Formula Ia-1-4-20) (20 mg, 0.0522 mmol) in THF (0.4 mL), K ₂ CO ₃ (22 mg, 0.1565 mmol) was added and 30 minutes Stirred. Iodomethane (0.010 mL, 0.1565 mmol) was added, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture including a compound of formula Ia-1-4-15 and a compound of formula Ia-1-4-16. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-15) (16 mg, 77%, white solid).

¹ H-NMR: CD ₃ OD (δ) 9.27 (s, 1H), 8.85 (d, 1H), 8.61-8.59 (m, 1H), 8.01-8.07 (m, 1H), 6.99 (s, 1H), 4.47(s, 3H), 4.21(s, 3H), 4.13(q, 2H), 3.75-3.62(m, 4H), 3.32(s, 3H), 2.40-2.35(m, 2H), 2.30-2.27( m, 2H), 1.30 (t, 3H)

<Example 74>

Synthesis of compounds of formula Ia-1-4-16

In the same manner as in Example 73, a mixture including the compound of Formula Ia-1-4-15 and the compound of Formula Ia-1-4-16 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-16) (4 mg, 19%, colorless liquid).

¹ H-NMR: CD ₃ OD (δ) 9.20 (s, 1H), 8.84 (d, 1H), 8.57-8.55 (m, 1H), 8.09-8.06 (m, 1H), 6.98 (s, 1H), 4.43(s, 3H), 4.19(s, 3H), 4.11(q, 2H), 3.67-3.63(m, 4H), 3.32(s, 3H), 2.41-2.35(m, 2H), 2.28-2.25( m, 2H), 1.28 (t, 3H)

<Example 75 >

Synthesis of compounds of formula Ia-1-4-17

After dissolving compound (5) (300 mg, 1.041 mmol) obtained in step 3 of Example 59 in acetic acid (2.0 mL), tert-butyl 4-oxopiperidine-1-carboxyl as compound (6) Rate (_415 mg, 2.081 mmol, 2.0 equivalent) was added and stirred at room temperature for 2 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (10.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-17) (109 mg, 22%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.34 (d, 1H), 7.47-7.45 (m, 1H), 7.32-7.29 (m, 1H), 6.23 (s, 1H) , 6.08(s, 1H), 4.08(s, 3H), 3.91(q, 2H), 3.78-3.72(m, 2H), 3.29-3.24(m, 2H), 1.91-1.88(m, 2H), 1.65 -1.60(m, 2H), 1.42(s, 9H), 1.20(t, 3H)

<Example 76 >

Synthesis of compounds of formula Ia-1-4-18

After dissolving the compound (Formula Ia-1-4-17) (200 mg, 0.4259 mmol) in THF (2.0 mL), NaH (25.5 mg, 0.6389 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.080 mL, 1.278 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (10.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture containing a compound of formula Ia-1-4-18 and a compound of formula Ia-1-5-3. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-18) (111 mg, 57%, yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.36 (d, 1H), 7.53-7.50 (m, 1H), 7.35-7.32 (m, 1H), 6.37 (s, 1H) , 4.17(s, 3H), 3.95(q, 2H), 3.62-3.55(m, 4H), 3.28(s, 3H), 1.87-1.80(m, 4H), 1.47(s, 9H), 1.24(t , 3H)

<Example 77 >

Synthesis of compounds of formula Ia-1-4-19

After dissolving the compound (Formula Ia-1-4-17) (30 mg, 0.0639 mmol) in dichloromethane (0.5 mL), trifluoroacetic acid (TFA) (0.5 mL) was slowly added dropwise, followed by stirring at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was concentrated under reduced pressure _{, neutralized with saturated NaHCO 3} aqueous solution, and extracted with dichloromethane (5.0 mL x4). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered and concentrated under reduced pressure to obtain the title compound (Chemical Formula Ia-1-4-19) (6.1 mg, 26%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.53 (m, 1H), 8.38 (d, 1H), 7.51-7.49 (m, 1H), 7.35-7.32 (m, 1H), 6.30 (s, 1H) , 5.38(s, 1H), 4.13(s, 3H), 3.95(q, 2H), 3.05-3.00(m, 2H), 2.92-2.89(m, 2H), 1.98-1.96(m, 2H), 1.78 -1.73(m, 2H), 1.24(t, 3H)

<Example 78 >

Synthesis of compounds of formula Ia-1-4-20

After dissolving the compound (Formula Ia-1-4-18) (104 mg, 0.2151 mmol) in dichloromethane (1.5 mL), trifluoroacetic acid (TFA) (1.5 mL) was slowly added dropwise, followed by stirring at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was concentrated under reduced pressure _{, neutralized with saturated NaHCO 3} aqueous solution, and extracted with dichloromethane (5.0 mL x4). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered and concentrated under reduced pressure to obtain the target compound (Chemical Formula Ia-1-4-19) (70 mg, 85%, yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.53 (m, 1H), 8.36 (d, 1H), 7.54-7.42 (m, 1H), 7.36-7.33 (m, 1H), 6.39 (s, 1H) , 4.18(s, 3H), 3.97(q, 2H), 3.39-3.36(m, 2H), 3.34(s, 3H), 3.32-3.30(m, 2H), 2.23-2.19(m, 2H), 2.11 -2.07(m, 2H), 1.26(t, 3H)

<Example 79 >

Synthesis of compounds of formula Ia-1-4-21

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), tetrahydro-4H-thiopyran-4-one as compound (6-1) (_18 mg, 0.1561 mmol, 1.5 equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (_5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-21) (29.6 mg, 67%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.36 (d, 1H), 7.50-7.47 (m, 1H), 7.34-7.31 (m, 1H), 6.28 (s, 1H) , 5.73(s, 1H), 4.10(s, 3H), 3.93(q, 2H), 2.97-2.91(m, 2H), 2.60-2.57(m, 2H), 2.25-2.21(m, 2H), 1.93 -1.87(m, 2H), 1.22(t, 3H)

<Example 80 >

Synthesis of Compounds of Formula Ia-1-4-22

After dissolving the compound (Formula Ia-1-4-21) (50 mg, 0.1294 mmol) in THF (0.5 mL), NaH (8 mg, 0.1941 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.019 mL, 0.3082 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture containing a compound of formula Ia-1-4-22 and a compound of formula Ia-1-5-5. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-22) (28.4 mg, 55%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.36 (d, 1H), 7.53-7.51 (m, 1H), 7.35-7.33 (m, 1H), 6.37 (s, 1H) , 4.18(s, 3H), 3.95(q, 2H), 3.28(s, 3H), 2.83-2.82(m, 4H), 2.17-2.11(m, 2H), 2.09-2.04(m, 2H), 1.25 (t, 3H)

<Example 81 >

Synthesis of compounds of formula Ia-1-4-23

After dissolving the compound (Formula Ia-1-4-21) (30 mg, 0.0776 mmol) in THF (0.5 mL), NaH (5 mg, 0.1164 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Cyclopropanecarbonyl chloride (0.021 mL, 0.2329 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-23) (20.0 mg, 57%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.43 (d, 1H), 7.50-7.47 (m, 1H), 7.33-7.31 (m, 1H), 6.32 (s, 1H) , 4.00(s, 3H), 3.93(q, 2H), 2.87-2.84(m, 4H), 2.25-2.11(m, 5H), 1.22(t, 3H), 1.06-1.04(m, 4H), 0.96 -0.94 (m, 2H)

<Example 82 >

Synthesis of Compounds of Formula Ia-1-4-24

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 4-(trifluoromethyl)cyclohexane-1- On (_0.021 mL, 0.1561 mmol, 1.5 eq) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (_5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-24) (17.7 mg, 39%, colorless liquid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.36 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.31 (m, 1H), 6.27 (s, 1H) , 5.69(s, 1H), 4.11(s, 3H), 3.94(q, 2H), 2.17-2.14(m, 2H), 2.03-1.98(m, 1H), 1.92-1.89(m, 2H), 1.82 -1.73(m, 2H), 1.50-1.44(m, 2H), 1.23(t, 3H)

<Example 83 >

Synthesis of Compounds of Formula Ia-1-4-25

After dissolving the compound (Formula Ia-1-4-24) (50 mg, 0.1146 mmol) in THF (0.5 mL), NaH (7 mg, 0.0.1718 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.021 mL, 0.3438 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture containing a compound of formula Ia-1-4-25 and a compound of formula Ia-1-5-6. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-25) (10.3 mg, 20%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.36 (d, 1H), 7.52-7.50 (m, 1H), 7.34-7.32 (m, 1H), 6.38-6.36 (m, 1H), 4.19(s, 1H), 4.16(s, 2H), 3.98-3.93(m, 2H), 3.27(1, 3H), 3.26(s, 2H), 2.17-2.07(m, 1H), 2.04 -1.92(m, 4H), 1.86-1.79(m, 2H), 1.76-1.70(m 2H), 1.24(t, 3H)

<Example 84 >

Synthesis of Compounds of Formula Ia-1-4-26

After dissolving the compound (Formula Ia-1-4-24) (30 mg, 0.0687 mmol) in THF (0.5 mL), NaH (4 mg, 0.1031 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Cyclopropanecarbonyl chloride (0.019 mL, 0.2062 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-26) (16 mg, 46%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.43 (d, 1H), 7.49-7.47 (m, 1H), 7.33-7.31 (m, 1H), 6.32 (s, 1H) , 3.99(s, 3H), 3.93(q, 2H), 2.21-2.18(m, 2H), 2.06-2.02(m, 4H), 1.95-1.88(m, 2H), 1.76-1.67(m, 2H) , 1.22(t, 3H), 1.07-1.04(m, 2H), 0.99-0.96(m, 2H)

<Example 85 >

Synthesis of compounds of formula Ia-1-4-27

After dissolving compound (5) (200 mg, 0.0.6937 mmol) obtained in step 3 of Example 59 in acetic acid (2.0 mL), cyclohexane-1,4-dione (389) as compound (6) mg, 3.468 mmol, 5.0 eq) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (10.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-27) (124 mg, 46%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.36 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.32 (m, 1H), 6.26 (s, 1H) , 6.06(s, 1H), 4.13(s, 3H), 3.94(q, 2H), 2.78-2.71(m, 2H), 2.38-2.30(m, 4H), 2.02-1.96(m, 2H), 1.23 (t, 3H)

<Example 86 >

Synthesis of compounds of formula Ia-1-4-28

Compound (Formula Ia-1-4-27) (50 mg, 0.1307 mmol) was dissolved in THF (0.3 mL), NaH (8 mg, 0.1961 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.016 mL, 0.2614 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-28) (5.0 mg, 10%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.36 (d, 1H), 7.54-7.52 (m, 1H), 7.36-7.34 (m, 1H), 6.39 (s, 1H) , 4.19(s, 3H), 3.97(q, 2H), 3.33(s, 3H), 2.65-2.54(m, 4H), 2.26-2.15(m, 4H), 1.25(t, 3H)

<Example 87 >

Synthesis of compounds of formula Ia-1-4-29

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 4,5-dioxaspiro[4,5]decane as compound (6) -8-one (33 mg, 0.2081 mmol, 2.0 equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-29) (39.7 mg, 89%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.37 (d, 1H), 7.49-7.46 (m, 1H), 7.33-7.30 (m, 1H), 6.28 (s, 1H) , 5.63(s, 1H), 4.10(s, 3H), 3.95-3.90(m, 6H), 2.06-2.02(m, 2H), 1.97-1.83(m, 4H), 1.71-1.67(m, 2H) , 1.21(t, 3H)

<Example 88 >

Synthesis of compounds of formula Ia-1-4-30

After dissolving compound (5) (50 mg, 0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 4,4-difluorocyclohexan-1-one as compound (6) (47 mg, 0.3468 mmol, 2.0 equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-30) (56.2 mg, 80%, pale pink solid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.37 (d, 1H), 7.49-7.47 (m, 1H), 7.34-7.31 (m, 1H), 6.26 (s, 1H) , 5.89(s, 1H), 4.10(s, 3H), 3.93(q, 2H), 2.22-2.01(m, 6H), 1.85-1.79(m, 2H), 1.22(t, 3H)

<Example 89 >

Synthesis of compounds of formula Ia-1-4-31

After dissolving compound (5) (50 mg, 0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 4-(tert-butyl)cyclohexan-1-one as compound (6) (54 mg, 0.3468 mmol, 2.0 equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-31) (71.2 mg, 97%, pale yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.38 (d, 1H), 7.50-7.47 (m, 1H), 7.33-7.30 (m, 1H), 6.29-6.28 (m, 1H), 5.64(s, 0.4H), 5.41(s, 0.6H), 4.12(s, 1.2H), 4.11(s, 1.8H), 3.96-3.91(m, 2H), 2.12-2.10(m, 1H), 2.03-1.99 (m, 1H), 1.84-1.82 (m, 1H), 1.72-1.63 (m, 2H), 1.45-1.43 (m, 2H), 1.24-1.21 (m, 3H), 1.08- 0.98(m, 2H), 0.86(s, 5.4H), 0.82(s, 3.6H)

<Example 90 >

Synthesis of Compounds of Formula Ia-1-4-32

After dissolving the compound (Formula Ia-1-4-31) (26 mg, 0.0612 mmol) in THF (0.5 mL), NaH (5 mg, 0.1225 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.011 mL, 0.1837 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture containing a compound of formula Ia-1-4-32 and a compound of formula Ia-1-5-7. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-32) (7.4 mg, 28%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.38 (d, 1H), 7.52-7.48 (m, 1H), 7.35-7.32 (m, 1H), 6.37-6.36 (m, 1H), 4.19(s, 1.2H), 4.16(s, 1.8H), 3.98-3.93(m, 2H), 3.24(s, 3H), 1.93-1.90(m, 2H), 1.80-1.72(m, 4H), 1.55-1.47 (m, 1H), 1.38-1.30 (m, 1H), 1.26-1.23 (m, 3H), 1.15-1.03 (m, 1H)

<Example 91 >

Synthesis of Compounds of Formula Ia-1-4-33

After dissolving compound (5) (50 mg, 0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 2-fluorobenzaldehyde (0.037 mL, 0.3468 mmol, 2.0) as compound (6) Equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-33) (57.9 mg, 85%, colorless liquid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.37 (d, 1H), 7.59-7.55 (m, 1H), 7.49-7.47 (m, 1H), 7.35-7.31 (m, 2H), 7.16(t, 1H), 7.05(t, 1H), 6.79(s, 1H), 6.27(s, 1H), 5.97(s, 1H), 4.14(s, 3H), 3.94(q, 2H) ), 1.23 (t, 3H)

<Example 92 >

Synthesis of Compounds of Formula Ia-1-4-34

After dissolving compound (5) (150 mg, 0.5203 mmol) obtained in step 3 of Example 59 in acetic acid (1.0 mL), 2-fluoronicotinaldehyde (130 mg, 1.041 mmol, 2.0 equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (10.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-34) (130 mg, 63%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.37 (d, 1H), 8.24-8.22 (m, 1H), 8.07-8.03 (m, 1H), 7.53-7.50 (m, 1H), 7.36-7.33(m, 1H), 7.26-7.24(m, 1H), 6.76(s, 1H), 6.31(s, 1H), 5.80(s, 1H), 4.16(s, 3H), 3.96 (q, 2H), 1.25 (t, 3H)

<Example 93 >

Synthesis of compounds of formula Ia-1-4-35

After dissolving the compound (Formula Ia-1-4-34) (50 mg, 0.1265 mmol) in THF (0.3 mL), NaH (8 mg, 0.1898 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.016 mL, 0.2529 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} and filtered to obtain a mixture containing a compound of formula Ia-1-4-35 and a compound of formula Ia-1-5-9. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-35) (3.9 mg, 8%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.38 (d, 1H), 8.24-8.23 (m, 1H), 7.95-7.91 (m, 1H), 7.53-7.51 (m, 1H), 7.36-7.34(m, 1H), 7.25-7.22(m, 1H), 6.96(s, 1H), 6.41(s, 1H), 4.20(s, 3H), 3.97(q, 2H), 3.39 (s, 3H), 1.25 (t, 3H)

<Example 94 >

Synthesis of Compounds of Formula Ia-1-4-36

After dissolving compound (5) (50 mg, 0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 3-fluoroisonicotinaldehyde (43 mg, 0.3468 mmol) as compound (6) , 2.0 equivalent) and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-36) (22.3 mg, 33%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.47-8.45 (m, 2H), 8.36 (d, 1H), 7.52-7.49 (m, 2H), 7.35-7.32 (m, 1H), 6.78(s, 1H), 6.40(s, 1H), 6.27(s, 1H), 4.14(s, 3H), 3.94(q, 2H), 1.23(t, 3H)

<Example 95 >

Synthesis of Compounds of Formula Ia-1-4-37

After dissolving compound (5) (60 mg, 0.2081 mmol) obtained in step 3 of Example 59 in acetic acid (0.5 mL), benzaldehyde (0.042 mL, 0.4162 mmol, 2.0 equivalents) was added as compound (6). And stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-37) (42.9 mg, 55%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.39 (d, 1H), 8.50 (d, 1H), 7.50-7.48 (m, 3H), 7.40-7.39 (m, 3H) , 7.34-7.32(m, 1H), 6.48(s, 1H), 6.28(s, 1H), 5.81(s, 1H), 4.16(s, 3H), 3.96-3.94(m, 2H), 1.24(t , 3H)

<Example 96 >

Synthesis of Compounds of Formula Ia-1-4-38

After dissolving compound (5) (60 mg, 0.2081 mmol) obtained in step 3 of Example 59 in acetic acid (0.5 mL), nicotinealdehyde (0.039 mL, 0.4162 mmol, 2.0 equivalents) was obtained as compound (6). It was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-38) (47 mg, 60%, ivory solid).

¹ H-NMR: CDCl ₃ (δ) 8.65-8.64 (m, 1H), 8.62-8.61 (m, 1H), 8.51-8.50 (m, 1H), 8.35 (d, 1H), 7.84-7.81 (m, 1H), 7.49-7.47(m, 1H), 7.33-7.30(m, 2H), 6.48(s, 1H), 6.38(s, 1H), 6.22(s, 1H), 4.13(s, 3H), 3.93 -3.91(m, 2H), 1.21(t, 3H)

<Example 97 >

Synthesis of compounds of formula Ia-1-4-39

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), isonicotinaldehyde (0.020 mL, 0.2081 mmol, 2.0 equivalents) as compound (6) Was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-39) (18.3 mg, 47%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.64-8.63 (m, 2H), 8.53-8.52 (m, 1H), 8.35 (d, 1H), 7.50-7.48 (m, 1H), 7.39-7.37 (m, 2H), 7.34-7.32(m, 1H), 6.50(s, 1H), 6.45(s, 1H), 6.23(s, 1H), 4.13(s, 3H), 3.96-3.91(m, 2H), 1.23 (t, 3H)

<Example 98 >

Synthesis of compounds of formula Ia-1-4-40

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), 2-ethoxynicotinaldehyde (47 mg, 0.3122 mmol, 3.0 equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-40) (36 mg, 82%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.36 (d, 1H), 8.11-8.09 (m, 1H), 7.80-7.78 (m, 1H), 7.48-7.46 (m, 1H), 7.32-7.30(m, 1H), 6.89-6.87(m, 1H), 6.66(s, 1H), 6.28(s, 1H), 5.87(s, 1H), 4.42-4.36(m, 2H) , 4.14(s, 3H), 3.93(q, 2H), 1.35(t, 3H), 1.22(t, 3H)

<Example 99 >

Synthesis of Compounds of Formula Ia-1-4-41

After dissolving compound (5) (50 mg, 0.1734 mmol) obtained in step 3 of Example 59 in acetic acid (0.4 mL), cyclopropanecarboxaldehyde (61 mg, 0.8671 mmol, 5.0) as compound (6). Equivalent) was added and stirred at room temperature for 5 days. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-41) (54 mg, 91%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.52-8.51 (m, 1H), 8.36 (d, 1H), 7.49-7.46 (m, 1H), 7.32-7.30 (m, 1H), 6.28 (s, 1H) , 5.82(s, 1H), 5.04-5.03(m, 1H), 4.09(s, 3H), 3.94-3.90(m, 2H), 1.21(t, 3H), 0.61-0.56(m, 1H), 0.53 -0.47(m, 1H), 0.45-0.40(m, 1H), 0.32-0.27(m, 1H)

<Example 100>

After dissolving the compound (Formula Ia-1-4-34) (25 mg, 0.0632 mmol) in N,N-dimethylformamide (0.3 mL), sodium ethanethiolate (16 mg, 0.1897 mmol, 3.0 eq) was added. And stirred at room temperature for 4 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x3). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-4-42) (2.6 mg, 9%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.43-8.41 (m, 1H), 8.38 (d, 1H), 7.82-7.80 (m, 1H), 7.51-7.49 (m, 1H), 7.35-7.32(m, 1H), 7.06-7.03(m, 1H), 6.71(s, 1H), 6.30(s, 1H), 5.83(s, 1H), 4.16(s, 3H), 3.95 (q, 2H), 3.26 (q, 2H), 1.37 (t, 3H), 1.24 (t, 3H)

<Example 101>

Synthesis of Compounds of Formula Ia-1-4-43

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), acetaldehyde (0.017 mL, 0.3123 mmol, 3.0 equivalents) was obtained as compound (6). It was added and stirred at room temperature for 1 day. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-43) (25.9 mg, 79%, colorless liquid).

¹ H-NMR: CDCl ₃ (δ) 8.53-8.52 (m, 1H), 8.37 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.32 (m, 1H), 6.29 (s, 1H) , 5.83(s, 1H), 5.72(q, 1H), 4.11(s, 3H), 3.93(q, 2H), 1.42(d, 3H), 1.21(t, 3H)

<Example 102>

Synthesis of Compounds of Formula Ia-1-4-44

After dissolving compound (5) (30 mg, 0.1041 mmol) obtained in step 3 of Example 59 in acetic acid (0.3 mL), propionaldehyde (0.022 mL, 0.3123 mmol, 3.0 equivalents) was obtained as compound (6). It was added and stirred at room temperature for 1 day. After completion of the reaction, it _{was neutralized with a saturated aqueous NaHCO 3} solution and extracted with EtOAc (5.0 mL x2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-4-44) (30.1 mg, 88%, yellow liquid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.39 (d, 1H), 7.52-7.49 (m, 2H), 7.36-7.34 (m, 1H), 6.32 (s, 1H) , 5.77(s, 1H), 5.59(t, 3H), 4.12(s, 3H), 3.96-3.92(m, 2H), 1.81-1.68(m, 2H), 1.23(t, 3H), 0.97(t , 3H)

<Example 103>

Synthesis of compounds of formula Ia-1-5-1

In the same manner as in Example 60, a mixture containing a compound of Formula Ia-1-4-2 and a compound of Formula Ia-1-5-1 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-5-1) (5.1 mg, 10%, yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.40 (d, 1H), 7.50-7.47 (m, 1H), 7.34-7.32 (m, 1H), 6.38 (s, 1H) , 4.08(s, 3H), 3.95(q, 2H), 2.95(s, 3H), 1.50(s, 6H), 1.24(t, 3H)

<Example 104>

Synthesis of compounds of formula Ia-1-5-2

In the same manner as in Example 69, a mixture including a compound of Formula Ia-1-4-11 and a compound of Formula Ia-1-5-2 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Ia-1-5-2) (5.3 mg, 10%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.39 (d, 1H), 7.51-7.49 (m, 1H), 7.35-7.32 (m, 1H), 6.38 (s, 1H) , 4.08(s, 3H), 3.99-3.93(m, 4H), 3.79-3.75(m, 2H), 2.97(s, 3H), 2.06-2.00(m, 2H), 1.83-1.80(m, 2H) , 1.24 (t, 3H)

<Example 105>

Synthesis of compounds of formula Ia-1-5-3

In the same manner as in Example 76, a mixture including a compound of Formula Ia-1-4-18 and a compound of Formula Ia-1-5-3 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Ia-1-5-3) (21 mg, 10%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.38 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.32 (m, 1H), 6.37 (s, 1H) , 4.21-4.06 (m, 5H), 3.95 (q, 2H), 3.12-3.08 (m, 2H), 2.94 (s, 3H), 1.84-1.83 (m, 4H), 1.46 (s, 9H), 1.23 (t, 3H)

<Example 106 >

Synthesis of compounds of formula Ia-1-5-4

After dissolving the compound of formula Ia-1-5-3 (15 mg, 0.0310 mmol) in dichloromethane (0.2 mL), trifluoroacetic acid (TFA) (0.2 mL) was slowly added dropwise, followed by stirring at room temperature for 30 minutes. After completion of the reaction, the reaction mixture was concentrated under reduced pressure _{, neutralized with saturated NaHCO 3} aqueous solution, and extracted with dichloromethane (5.0 mL x4). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered and concentrated under reduced pressure to obtain the title compound (Chemical Formula Ia-1-5-4) (8.1 mg, 68%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.39 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.33 (m, 1H), 6.38 (s, 1H) , 4.07(s, 3H), 3.95(q, 2H), 3.08-3.05(m, 2H), 3.02-2.99(m, 2H), 2.96(s, 3H), 1.89-1.86(m, 4H), 1.24 (t, 3H)

<Example 107>

Synthesis of compounds of formula Ia-1-5-5

In the same manner as in Example 80, a mixture including a compound of Formula Ia-1-4-22 and a compound of Formula Ia-1-5-5 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-5-5) (4.1 mg, 8%, yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.54 (m, 1H), 8.39 (d, 1H), 7.51-7.49 (m, 1H), 7.35-7.33 (m, 1H), 6.38 (s, 1H) , 4.07(s, 3H), 3.95(q, 2H), 3.14-3.08(m, 2H), 2.97(s, 3H), 2.59-2.56(m, 2H), 2.24-2.21(m, 2H), 2.05 -2.01(m, 2H), 1.24(t, 3H)

<Example 108>

Synthesis of compounds of formula Ia-1-5-6

In the same manner as in Example 83, a mixture containing a compound of Formula Ia-1-4-25 and a compound of Formula Ia-1-5-6 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-5-6) (7.8 mg, 15%, yellow solid).

¹ H-NMR: CDCl ₃ (δ) 8.55-8.53 (m, 1H), 8.39 (d, 1H), 7.51-7.48 (m, 1H), 7.35-7.33 (m, 1H), 6.38 (s, 1H) , 4.07(s, 3H), 3.95(q, 2H), 2.96(s, 3H), 2.06-1.95(m, 5H), 1.86-1.82(m, 2H), 1.73-1.70(m, 2H), 1.24 (t, 3H)

<Example 109>

Synthesis of compounds of formula Ia-1-5-7

In the same manner as in Example 90, a mixture including a compound of Formula Ia-1-4-32 and a compound of Formula Ia-1-5-7 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-5-7) (2.3 mg, 9%, ivory solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.40 (d, 1H), 7.50-7.48 (m, 1H), 7.34-7.32 (m, 1H), 6.38 (s, 1H) , 4.07(s, 3H), 3.95(q, 2H), 2.93(s, 3H), 1.99-1.96(m, 2H), 1.78-1.75(m, 2H), 1.69-1.63(m, 2H), 1.53 -1.47(m, 2H), 1.24(t, 3H), 1.02-0.97(m, 1H), 0.88(s, 9H), 0.89(s, 3.6H), 0.88(s, 5.4H)

<Example 110 >

Synthesis of compounds of formula Ia-1-5-8

After dissolving the compound of formula Ia-1-4-33 (16.2 mg, 0.0411 mmol) in THF (0.3 mL), NaH (3.3 mg, 0.0822 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.008 mL, 0.1232 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-5-8) (1.8 mg, 11%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.56-8.54 (m, 1H), 8.41 (d, 1H), 7.61-7.58 (m, 1H), 7.52-7.50 (m, 1H), 7.40-7.34 (m, 2H), 7.22-1.19(m, 1H), 7.12-7.08(m, 1H), 6.52(s, 1H), 6.41(s, 1H), 4.14(s, 3H), 3.97(q, 2H), 2.93 (s, 3H), 1.25 (t, 3H)

<Example 111>

Synthesis of compounds of formula Ia-1-5-9

In the same manner as in Example 93, a mixture including a compound of Formula Ia-1-4-35 and a compound of Formula Ia-1-5-9 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-5-9) (13.2 mg, 25%, orange solid).

¹ H-NMR: CDCl ₃ (δ) 8.56-8.55 (m, 1H), 8.40 (d, 1H), 8.27-8.26 (m, 1H), 8.07-8.04 (m, 1H), 7.54-7.51 (m, 1H), 7.37-7.34(m, 1H), 7.29-7.27(m, 1H), 6.46(s, 1H), 6.40(s, 1H), 4.13(s, 3H), 4.00-3.95(m, 2H) , 2.99(s, 3H), 1.26(t, 3H)

<Example 112 >

Synthesis of compounds of formula Ia-1-5-10

After dissolving the compound of formula Ia-1-4-36 (15.5 mg, 0.0392 mmol) in THF (0.2 mL), NaH (3 mg, 0.0588 mmol) was added under cooling in an ice bath, followed by stirring for 30 minutes. Iodomethane (0.005 mL, 0.0784 mmol) was added, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, H ₂ O (5.0 mL) was added to terminate the reaction, followed by extraction with ethyl acetate (5.0 mL x 2). The combined organic layers _{were dried over anhydrous MgSO 4} , filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the title compound (Chemical Formula Ia-1-5-10) (6.0 mg, 37%, colorless oil).

¹ H-NMR: CDCl ₃ (δ) 8.56-8.54 (m, 1H), 8.53 (d, 1H), 8.50 (d, 1H), 8.39 (d, 1H), 7.53-7.51 (m, 2H), 7.36 -7.34(m, 1H), 6.51(s, 1H), 6.40(s, 1H), 4.13(s, 3H), 3.98-3.95(m, 2H), 3.01(s, 3H), 1.25(t, 3H) )

<Example 113>

Synthesis of the compound of formula Ia-1-5-11

In the same manner as in Example 65, a mixture including the compound of Formula Ia-1-4-7 and the compound of Formula Ia-1-5-11 was obtained. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target compound (Chemical Formula Ia-1-5-11) (2.0 mg, 18%, white solid).

¹ H-NMR: CDCl ₃ (δ) 8.54-8.53 (m, 1H), 8.40 (d, 1H), 7.50-7.47 (m, 1H), 7.34-7.31 (m, 1H), 6.38 (s, 1H) , 4.07(s, 3H), 3.95(q, 2H), 2.97(s, 3H), 1.95-1.93(m, 4H), 1.81-1.78(m, 2H), 1.71-1.66(m, 2H), 1.24 (t, 3H)

<Experimental Example 1>

Insecticidal activity test against peach aphids 1

Peppers were planted in plastic pots with a diameter of 8 cm and a height of 8 cm, and peach aphids were propagated, and the number of peach aphids in each pot was investigated. Some of the compounds prepared in the examples were selected, and the compound was dispersed in water to dilute the chemical solution to a concentration of about 5 ppm to prepare a chemical solution.

The medicinal solution was sprayed with hand spray on the leaves of pepper planted in a pot, and after air drying, the pot was stored in a greenhouse.

On the fifth day after application of the drug, the number of peach aphids parasitic in each pepper was investigated, the mortality rate was calculated from the following equation, and the grade of each compound was investigated.

-Mortality rate = {(Number of first peach aphids-Number of peach aphids after inoculation of compound chemical solution) / Number of first peach aphids}*100

-Grade A: More than 90% to 100% mortality

-Grade B: More than 80% to less than 90% mortality

-Grade C: Less than 80% mortality

Investigation result, Ia-1-1-1, Ia-1-1-8, Ia-1-1-12, Ia-1-1-25, Ia-1-1-26 Ia-1-1-27 , Ia-1-1-36, Ia-1-1-43, Ia-1-3-2, Ia-1-3-3, Ia-1-4-2, Ia-1-4-22, Ia The compound of -1-4-36, Ia-1-4-41, Ia-1-4-43, Ia-1-4-44, Ia-1-5-2, Ia-1-5-6 is A Belonged to the class. From these results, it can be seen that the present invention provides a novel compound capable of effectively killing pests even at a relatively low concentration.

<Experimental Example 2>

Insecticidal activity test against peach aphid 2

Peppers were planted in plastic pots with a diameter of 8 cm and a height of 8 cm, and peach aphids were propagated, and the number of peach aphids in each pot was investigated. Some of the compounds prepared in the examples were selected, and the compound was dispersed in water and diluted to a concentration of about 25 ppm to prepare a chemical solution.

The chemical solution was sprayed on the leaves of pepper planted in a pot, and after air drying, the pot was stored in a greenhouse.

On the 5th day after application of the drug, the number of peach aphids parasitic in each pepper was investigated, the mortality rate was calculated from the following equation, and the grade of each compound was investigated.

-Mortality rate = {(Number of first peach aphids-Number of peach aphids after inoculation of compound chemical solution) / Number of first peach aphids}*100

-Grade A: More than 90% to 100% mortality

-Grade B: More than 80% to less than 90% mortality

-Grade C: Less than 80% mortality

As a result of the investigation, not only the compound belonging to the class A in Experimental Example 1, but also the formulas Ia-1-1-2, Ia-1-1-5, Ia-1-1-6, Ia-1-1-7, Ia- 1-1-16 Ia-1-1-21, Ia-1-1-22, Ia-1-1-23, Ia-1-1-24, Ia-1-1-30, Ia-1-1 -31, Ia-1-1-33, Ia-1-1-35, Ia-1-1-37, Ia-1-1-38, Ia-1-4-3, Ia-1-4-4 , Ia-1-4-10, Ia-1-4-12, Ia-1-4-25, Ia-1-4-33, Ia-1-4-34, Ia-1-5-1, Ia The compounds of -1-5-2, Ia-1-5-3, and Ia-1-5-9 further belonged to the class A. On the other hand, among the compounds whose effect was confirmed, most of the compounds other than those listed above belonged to the B grade.

When summarizing the above experimental results, it was clearly demonstrated that the present invention contributes to solving the conventional problem by providing a compound capable of expressing effective insecticidal activity even under a relatively low concentration.

Claims (20)

Compounds represented by the following formula (I):
[Formula I]

In the above formula,
X ¹ is oxygen or sulfur,
Ring A is a substituted or unsubstituted, aliphatic or aromatic 5-membered heterocycle group consisting of 2 carbon atoms and 3 hetero atoms, and A ¹ and A ² are each independently nitrogen, oxygen or sulfur,
R ¹ , R ² and R ³ are each independently selected from hydrogen or the following substituent group I,
n4 is an integer of 1 to 3, R ⁴ is the same as or different from each other when n4 is 2 or more, and each independently selected from hydrogen or the following substituent group I and / or fused to each other and substituted with carbon bonded thereto or Forming an unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 membered heterocycle group,
The substituent group I is a substituted or unsubstituted C _1-10 alkyl group, a substituted or unsubstituted C _2-10 alkenyl group, a substituted or unsubstituted C _3-20 carbocycle group, a substituted or unsubstituted C _3-20 Cycloalkyl group, substituted or unsubstituted C _6-30 aryl group, substituted or unsubstituted 3 to 30 membered heterocycle group, substituted or unsubstituted C _1-10 alkoxy group, substituted or unsubstituted C _2-10 alkenyloxy group , A substituted or unsubstituted C _3-10 cycloalkyloxy group, a substituted or unsubstituted C _6-30 aryloxy group, a substituted or unsubstituted 3 to 30 membered heterocycleoxy group, a substituted or unsubstituted C _1-10 alkylcarbonyl Group, substituted or unsubstituted C _2-10 alkenylcarbonyl group, substituted or unsubstituted C _3-10 cycloalkylcarbonyl group, substituted or unsubstituted C _6-30 arylcarbonyl group, substituted or unsubstituted 3 to 30 A membered heterocyclecarbonyl group, a substituted or unsubstituted C _1-10 alkylthio group, a substituted or unsubstituted C _2-10 alkenylthio group, a substituted or unsubstituted C _3-10 cycloalkylthio group, a substituted or unsubstituted C _6-30 arylthio group, substituted or unsubstituted 3 to 30 membered heterocyclethio group, aldehyde group, carboxyl group, halogen group, C _1-10 haloalkyl group, hydroxyl group, substituted or unsubstituted amino group, imine group , A cyano group, a nitro group, an amide group, a thiol group, a sulfonyl group, a sulfino group and a phosphoric acid group,
Here, C _1-10 alkyl moiety is _{-O-, -S-, -SO-, -SO 2} -, -NR a - (R a is hydrogen or a substituted or unsubstituted C _1-10 alkyl), -N = , =N-, -POR ^a -and -PO ₄ R ^a -, and the heterocycle moiety includes at least one of sulfur, nitrogen, phosphorus and oxygen as a ring member. The method of claim 1,
R ² and R ³ are each independently a substituted or unsubstituted C _1-4 alkyl group. The method of claim 1,
X ¹ is an oxygen compound. The method of claim 1,
In ring A,
A ¹ is oxygen and A ² is nitrogen;
A ¹ is sulfur and A ² is nitrogen; or
A ¹ is nitrogen and A ² is oxygen. The method of claim 1,
R ⁴ is selected from the following substituent group I-1, which is a subgroup of the above substituent group I, and/or ^{two of R 4} are fused to each other and together with the carbon bonded thereto, a substituted or unsubstituted C _3-8 carbocycle group Or a compound forming a substituted or unsubstituted 3 to 8 membered heterocycle group:
The substituent group I-1 is a halogen group, a substituted or unsubstituted C _1-10 alkyl group, a C _1-10 haloalkyl group, a substituted or unsubstituted C _3-20 cycloalkyl group, a substituted or unsubstituted C _6-30 aryl Group, a substituted or unsubstituted 3 to 30 membered heterocycle group, a substituted or unsubstituted C _1-10 alkoxy group, a substituted or unsubstituted C _3-10 cycloalkylcarbonyl group, and a substituted or unsubstituted amino group. The method of claim 1,
R ¹ is a substituted or unsubstituted 3 to 30 membered heterocycle group. The method of claim 1,
The compound of formula (I) is a compound represented by the following formula (I-1):
[Formula I-1]

In the above formula,
R ¹ , R ² , R ⁴ , n4, rings A, A ¹ and A ² are as defined in claim 1. The method of claim 1,
The compound of formula (I) is a compound represented by any one of the following formulas I-1-1 to I-1-5:
[Formula I-1-1]

[Formula I-1-2]

[Formula I-1-3]

[Formula I-1-4]

[Formula I-1-5]

In the above formula,
R ¹ is as defined in claim 1,
R ² is a methyl group or an ethyl group,
R ⁴ is selected from hydrogen or said substituent group I,
R ^4a and R ^4b are independently selected from hydrogen or the substituent group I, and/or fused to each other and together with the carbon bonded thereto, a substituted or unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 Forming a membered heterocycle group, provided that R ^4a and R ^4b are not hydrogen at the same time,
R ^4c is selected from hydrogen or the above substituent group I. The method of claim 1,
The compound of formula (I) is a compound represented by the following formula (Ia):
[Formula Ia]

In the above formula,
Ring B is a substituted or unsubstituted C _3-30 carbocycle group or a 3 to 30 membered heterocycle group containing at least one of substituted or unsubstituted sulfur, nitrogen, phosphorus and oxygen as a ring member,
Rings A, R ² , R ³ , R ⁴ , n4, X ¹ , A ¹ , A ² are as defined in claim 1. The method of claim 9,
The compound of formula (Ia) is a compound represented by the following formula (Ia-1):
[Formula Ia-1]

In the above formula,
R ² , R ⁴ , R ⁵ , rings A, A ¹ and A ² , n4 and n5 are as defined in claim 1, n5 is an integer of 0 to 4, when n5 is 2 or more, R ⁵ is different from or identical to each other, and R ⁵ is each independently selected from the substituent group I. The method of claim 1,
The compound of formula (I) is a compound represented by any one of the following formulas Ia-1-1 to Ia-1-5:
[Formula Ia-1-1]

[Formula Ia-1-2]

[Formula Ia-1-3]

[Formula Ia-1-4]

[Formula Ia-1-5]

In the above formula,
R ⁴ is selected from hydrogen or said substituent group I,
R ² is a methyl group or an ethyl group,
R ^4a and R ^4b are independently selected from hydrogen or the substituent group I, and/or fused to each other and together with the carbon bonded thereto, a substituted or unsubstituted C _3-8 carbocycle group or a substituted or unsubstituted 3 to 8 Forming a membered heterocycle group, provided that R ^4a and R ^4b are not hydrogen at the same time,
R ^4c is selected from hydrogen or the above substituent group I. The method of claim 1,
The compound of formula (I) is represented by any one selected from the following formula group:

In the above formula group, Me, Et, and Boc each mean a methyl group, an ethyl group, and a tert-butoxycarbonyl group. The method of claim 1,
The compound of formula (I) is represented by any one selected from the following formula group:

In the above formula group, Et means an ethyl group. The method of claim 1,
The compound of formula (I) is a compound represented by any one selected from the following formula group:

In the above formula group, Me and Et mean a methyl group and an ethyl group, respectively. The method of claim 1,
The compound of formula (I) is represented by any one selected from the following formula group:

In the above formula group, Me, Et, and Boc each mean a methyl group, an ethyl group, and a tert-butoxycarbonyl group, ^{and C represented in the ring constituent atoms is when R 4a} and R ^4b are fused together to form a spiro ring. It is a carbon shared with Ring A. The method of claim 1,
The compound of formula (I) is represented by any one selected from the following formula group:

In the above formula group, Me, Et, and Boc each mean a methyl group, an ethyl group, and a tert-butoxycarbonyl group, ^{and C represented in the ring constituent atoms is when R 4a} and R ^4b are fused together to form a spiro ring. It is a carbon shared with Ring A. Acceptable salts of the compounds according to claim 1, solvates thereof, enantiomers thereof, diastereomers thereof, geometric isomers thereof or tautomers thereof. A control composition comprising as an active substance at least one of the compound according to claim 1, an acceptable salt thereof, a solvate thereof, an enantiomer thereof, a diastereomer thereof, a geometric isomer thereof, and a tautomer thereof. The method of claim 18,
A control composition having a mortality of 30% or more for pests with aphids. The method of claim 18,
Control composition comprising the active substance in a concentration of 0.1 to 1,000 ppm.