KR102101236B1 - Novel SIRT 1 activator and medical use thereof - Google Patents

Abstract

The present invention relates to a SIRT 1 activator and a medical use thereof, and in the present invention, a novel SIRT 1 activator compound based on a benzo [d] oxazole skeleton, a crystalline form thereof, a hydrate or a salt thereof was prepared. The effect of improving obesity, insulin resistance and dyslipidemia by the compound, the effect of improving fatty liver, cell aging protection, oxidative stress protection, collagen synthesis and wrinkle improvement were confirmed.
Therefore, the novel SIRT 1 activator compound having the above-described effect is for preventing metabolic diseases including obesity, diabetes, dyslipidemia, liver disease including alcoholic or non-alcoholic fatty liver, hepatitis, or the like. It can be usefully used as a pharmaceutical composition for treatment, a cosmetic composition for preventing or improving wrinkles, and a health food composition for improving cell aging.

Description

New SIRT 1 activator and its medical use {Novel SIRT 1 activator and medical use thereof}

The present invention relates to a novel SIRT 1 (silent mating type information regulation 2 homolog; sirtuin 1) activator compound, a crystalline form thereof, a hydrate or salt thereof, and a composition containing the same as an active ingredient.

SIRT 1 is a nicotinamide adenine dinucleotide (NAD) -dependent histone deacetylase that is distributed in the cell nucleus or cytoplasm, and is primarily a lysine of histone H3 (Lys9 or Lys14) or histone H4 of various transcription factors in the nucleus (Lys9 or Lys14). Lys16) deacetylation. In addition to histones, SIRT 1 in mammals affects the signal transduction system through deacetylation of transcription factors. As transcription factors that interact with SIRT 1, p53, forkhead transcription factor (FOXO), and peroxisome proliferation factor-active receptor Gamma coactivator 1-alpha (peroxisome proliferator-activated receptor γ coactivator 1-α; PGC1-α) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) It is known to be related to aging, cell circulation regulation, apoptosis, metabolism, and inflammation.

 Resveratrol, a phytoalexin, is a type of polyphenol and is found in many plants, including grapes, peanuts, mulberries, raspberries, and berries such as raspberries. Resveratrol is known to have anti-cancer and potent antioxidant properties, as well as anti-viral, neuroprotective, anti-inflammatory, anti-aging and prolonging effects. Shows. In addition, resveratrol is a potent SIRT 1 activator and is known to enhance the survival rate of cells stressed by UV, as well as enhance SIRT 1 dependent cytoplasmic processes such as axonal protection, fat metabolism and NF-κB dependent transcriptional inhibition. have.

Recently, research to discover SIRT 1 activators stronger than resveratrol has attracted attention, and a compound called SRT1720 based on the skeleton of imdazo [2,1-b] thiazole is resveratrol. It has been reported to be a stronger SIRT 1 activator. In addition, recently, PPARβ / δ is a transcription factor that regulates the expression of SIRT 1, and several effects have been reported that the PPARβ / δ activator increases the expression of SIRT 1 to improve metabolic disease and cell aging.

Accordingly, the present invention synthesizes various compounds based on the benzo [d] oxazole skeleton similar to the skeleton of imidazo [2,1-b] thiazole, which is the structure of SRT1720, and the compound By searching for SIRT 1 activity and PPARβ / δ activity against them, various effects in metabolic diseases (obesity, diabetes, dyslipidemia, etc.), fatty liver, inflammation, and cell aging are to be confirmed.

U.S. Patent No. 5118707 (1992.06.02)

It is an object of the present invention to provide a novel SIRT 1 activator compound, its crystalline form, its hydrate or salt thereof.

Another object of the present invention is a pharmaceutical composition for preventing or treating metabolic disease, a pharmaceutical composition for preventing or treating liver disease, a cosmetic composition for preventing or improving wrinkles, or containing the compound, a crystalline form thereof, a hydrate or a salt thereof as an active ingredient. It is to provide a health food composition for improving cell aging.

In order to achieve the above object, the present invention provides a novel SIRT 1 activator compound, its crystalline form, its hydrate or salt thereof.

In addition, the present invention, a pharmaceutical composition for preventing or treating metabolic disease, pharmaceutical composition for preventing or treating liver disease, cosmetic composition for preventing or improving wrinkles, or cell aging, containing the compound, its crystalline form, its hydrate or salt thereof as an active ingredient Provide a health food composition for improvement.

In the present invention, a novel SIRT 1 activator compound based on a benzo [d] oxazole skeleton, a crystalline form thereof, a hydrate or a salt thereof was prepared, and the effect of improving obesity, insulin resistance and dyslipidemia by the compound, fatty liver Improvement effects, cell aging protection, oxidative stress protection, collagen synthesis and wrinkle improvement effects were confirmed.

Therefore, the novel SIRT 1 activator compound having the above-described effect is for preventing metabolic diseases including obesity, diabetes, dyslipidemia, liver disease including alcoholic or non-alcoholic fatty liver, hepatitis, or the like. It may be useful as a pharmaceutical composition for treatment, a cosmetic composition for preventing or improving wrinkles, or a health food composition for improving cell aging.

1A) to 1F) are results of confirming SIRT 1 activity of a candidate SIRT 1 activator compound (benzo [d] oxazole skeleton), and FIG. 1G) is a compound among candidate SIRT 1 activator compounds by performing a docking simulation. This is the result of confirming SIRT 1 binding force of 70c.
2 is an analysis of the effect of improving metabolic disease by compound 70c in a db / db mouse obesity animal model lacking the appetite-regulating hormone leptin receptor, A) dietary intake, B) body weight, and C) resistance , D) fasting blood sugar and E) serum insulin changes.
Figure 3 analyzes the effect of improving fatty liver by compound 70c in the db / db mouse obese animal model, A) triglyceride, B) lipid synthesis related gene, C) lipid oxidation related gene and D) vesicle stress related marker (p -IRE).
4 is a result confirming the effect of improving cell aging by compound 70c on skin fibroblasts with β-galactosidase staining.
5A) is a result of confirming the binding ability of SIRT 1 and PPARβ / δ of compound 69c among candidate SIRT 1 activator compounds (benzo [d] oxazole skeleton) by performing a docking simulation, and B) PPARβ / δ by compound 69c Expression, C) SIRT 1 expression and D) Cell aging marker (p53).
6A) is a result confirming the effect of improving cell aging by compound 69c on skin fibroblasts with β-galactosidase staining, and FIG. 6B) is a result confirming the effect of inhibiting reactive oxygen species by compound 69c.
7 is a result of confirming A) increased collagen synthesis and B) decreased matrix metalloproteinase (MMP) expression by compound 69c in skin fibroblast photoaging.

The inventors of the present invention synthesized a novel SIRT 1 compound based on the benzo [d] oxazole skeleton, a crystalline form thereof, a hydrate or a salt form thereof, and improved the obesity, insulin resistance and dyslipidemia of the compound , Fatty liver improvement effect, cell aging protection, oxidative stress protection, collagen synthesis and wrinkle improvement effect was confirmed, and the present invention was completed.

The present invention provides a compound represented by Formula 1 below, a crystalline form thereof, a hydrate thereof or a salt thereof:

[Formula 1]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of, wherein R 'is selected from the group consisting of NH, NCH ₃ , N-cyclohexyl and oxo.

Preferably, the compound represented by Chemical Formula 1, its crystalline form, its hydrate or its salt is a SIRT 1 (silent mating type information regulation 2 homolog; sirtuin 1) or peroxisome proliferator-activated receptor ; PPAR) can be activated.

The crystalline form means that at least 50% by weight, preferably at least 70%, 80% or 90% by weight of the compound is a crystalline form.

The hydrate means that the compounds or their salts are composed of water equivalently or non-equivalently.

The salt may be prepared by itself in the process of synthesis, separation or purification of the compound, or may be specially prepared. Examples of the salt prepared in this way are selected from the group consisting of sodium salt, potassium salt, calcium salt, lithium salt, magnesium salt, cesium salt, aluminum salt, ammonium salt, triethylaminium salt and pyridinium salt. It can be one or more basic salts, hydrochloric acid, bromic acid, sulfuric acid, sulfurous acid, phosphoric acid, citric acid, acetic acid, maleic acid, fumaric acid, gluconic acid, methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, oxalic acid, malonic acid, glutamic acid It may be one or more acidic salts selected from the group consisting of ric acid, acetic acid, trifluoroacetic acid, glycolic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, citric acid and aspartic acid , But is not limited to this.

Preferably, the compound may be a compound represented by Formula 1-1:

[Formula 1-1]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of

Preferably, the compound represented by 1-1 is N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56a), 2-methyl- N- (2- (4- (piperazin-1- ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [2-methyl- N - (2- (4- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride] (56b), 3-methyl- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3- Methyl- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56c), 4-methyl- N- (2- (4- (pipe Razin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Methyl- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol- 2-yl) phenyl) benzamide hydrochloride] (56d), 2-fluoro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Fluoro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56e), 3-fluoro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Fluoro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56f), 4-fluoro- N- (2- (4- (piperazin-1 -ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [4-Fluoro- N - (2- (4- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl ) phenyl) benzamide hydrochloride] (56g), 2-bromo- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ 2-Bromo- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56h), 3-bromo- N- (2- (4 -(Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Bromo- N- ( 2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56i), 4-bromo- N- (2- (4- (piperazin-1- ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [4-Bromo- N - (2- (4- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride] (56j), 2-chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2- Chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56k), 3-chloro- N- (2- (4- (pipe Razin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol- 2-yl) phenyl) benzamide hydrochloride] (56l), 4-chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydro Chloride [4-Chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56m), 3 -Nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56n), 4-nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] Oxazol-2-yl) phenyl) benzamide hydrochloride [4-Nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] ( 56o), 3,4,5-trimethoxy- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3, 4,5-Trimethoxy- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56p), 2,4-dichloro- N- (2 -(4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2,4-Dichloro- N- (2- (4- (piperazin-1- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56q), 3,4-dichloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] Oxazol-2-yl) phenyl) benzamide hydrochloride [3,4-Dichloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56r), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride [ N- (2- (4- (Piperazin- 1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) nicotinamide hydrochloride] (56s), N - (2- (4- ( piperazin-1-ylmethyl) benzo [d] oxazol-2-yl ) Phenyl) isonicotinamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) isonicotinamide hydrochloride] (56t), N- (2- (4 -(Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride] (56u), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2 -Naphthamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phen yl) -2-naphthamide hydrochloride] (56v), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydro Chloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride] (56w), N- (2- (4- (pipe 1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide hydrochloride [N advantage - (2- (4- (Piperazin- 1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide hydrochloride] (56x), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)- [1,1'-Biphenyl] -4-carboxamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1 '-biphenyl] -4-carboxamide hydrochloride] (56y), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydro Chloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (56z), N- ( 2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride] (56A) and phenyl (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) carbamate hydrochloride [ Phenyl (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) carbamate hydrochloride] (56B), but is not limited thereto.

Preferably, the compound may be a compound represented by Formula 1-2 below:

[Formula 1-2]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of

Preferably, the compound represented by Chemical Formula 1-2 is N- (2- (5- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide [ N- ( 2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (64a), 3,4,5-trimethoxy- N- (2- (5- (pipe 1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide [3,4,5-Trimethoxy- N - (2- (5- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide] (64b), N- (2- (5- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide [ N- (2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (64c) and N- (2- (5- (piperazin-1- Ilmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide 2,2,2-trifluoroacetate [ N- (2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide 2,2,2-trifluoroacetate] (64d), but is not limited thereto.

Preferably, the compound may be a compound represented by Chemical Formula 1-3:

[Formula 1-3]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of

Preferably, the compound represented by Chemical Formula 1-3 is N- (2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benz Amide [ N- (2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (69a), 3,4,5-trimethoxy- N- (2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide [3,4,5-Trimethoxy- N- (2 -(5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (69b), N- (2- (5-((4-methylpiperazin- 1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide [ N- (2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol -2-yl) phenyl) -2-naphthamide] (69c) and N- (2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl ) -2-naphthamide hydrochloride [ N- (2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] (69cc) , N - (2- (5 - ((4- methylpiperazin-l-yl) methyl) benzo [d] oxazol-2-yl) phenyl) quinolyl A [- - (((4- Methylpiperazin-1-yl) methyl) benzo [d] oxazol-2-yl) phenyl 2- (5) quinoxaline-2-carboxamide N] (69d) utilizing 2-carboxamide It may be selected from the group consisting of, but is not limited to.

Preferably, the compound may be a compound represented by Formula 1-4:

[Formula 1-4]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of

Preferably, the compound represented by Chemical Formula 1-4 is N- (2- (5-((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl ) Benzamide [ N- (2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (70a), N- (2- (5- ((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -3,4,5-trimethoxybenzamide [ N- (2- (5- ((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -3,4,5-trimethoxybenzamide] (70b), N- (2- (5-((4-cyclo Hexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide [ N- (2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (70c) and N- (2- (5-((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxa Zol-2-yl) phenyl) quinoxaline-2-carboxamide [ N- (2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline -2-carboxamide] (70d). But, it specifies a not limited thereto.

Preferably, the compound may be a compound represented by Formula 1-5:

[Formula 1-5]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of

Preferably, the compound represented by Chemical Formula 1-5 is N- (2- (5-((4-oxopiperidin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide [ N- (2- (5-((4-Oxopiperidin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (70e), It is not limited to this.

Preferably, the compound may be a compound represented by Formula 1-6:

[Formula 1-6]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of

Preferably, the compound represented by Chemical Formula 1-6 is N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77a), 2-methyl- N- (2- (6- (piperazin-1 -ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [2-methyl- N - (2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl ) phenyl) benzamide hydrochloride] (77b), 3-methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3 -Methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77c), 4-methyl- N- (2- (6- ( Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride ] (77d), 2-fluoro - N - (2- (6- (piperazin-1-yl Butyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [2-Fluoro- N - (2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl ) benzamide hydrochloride] (77e), 3-fluoro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3- Fluoro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77f), 4-fluoro- N- (2- (6- ( Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Fluoro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (77g), 2-bromo- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benz Amide hydrochloride [2-Bromo- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77h), 3-bromo- N- ( 2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3 -Bromo- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77i), 4-bromo- N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Bromo- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77j), 2-chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benz Amide hydrochloride [2-Chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77k), 3-chloro- N- (2 -(6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77l), 4-chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl ) Phenyl) benzamide hydrochloride [4-Chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochlori de] (77m), 3-nitro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Nitro- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77n), 4-nitro- N- (2- (6- (piperazin-1 -ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [4-Nitro- N - (2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl ) phenyl) benzamide hydrochloride] (77o), 3,4,5-trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) Benzamide hydrochloride [3,4,5-Trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77p), 3,4 , 5-Trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide 2,2,2-trifluoroacetate [ 3,4,5-trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide 2,2,2-trifluoroacetate] (77pp), 2, 4-dichloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2,4-Dichloro- N- (2- (6- (piperazin- 1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77q), 3,4-dichloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] Oxazol-2-yl) phenyl) benzamide hydrochloride [3,4-Dichloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77r), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride [ N- (2- (6- (piperazin- 1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) nicotinamide hydrochloride] (77s), N - (2- (6- ( piperazin-1-ylmethyl) benzo [d] oxazol-2-yl ) Phenyl) isonicotinamide hydrochloride [ N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) isonicotinamide hydrochloride] (77t), N- (2- (6 - (1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) - 1-naphtha amide hydrochloric La De [N - (2- (6- ( Piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride] (77u), N - (2- (6- ( piperazin- -1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2- yl) phenyl) -2-naphthamide hydrochloride] (77v), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carbox Mid hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride] (77w), N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamido dihydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide dihydrochloride] (77x), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) Phenyl) quinoxaline-2-carboxamide 2,2,2-trifluoroacetate [ N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quino xaline-2-carboxamide 2,2,2-trifluoroacetate] (77xx), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1 , 1'-Biphenyl] -4-carboxamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1'- biphenyl] -4-carboxamide hydrochloride] (77y), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (77z), N- (2- (6- (piperazin-1-ylmethyl ) Benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride] ( 77A) and 4-methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzenesulfonamide [4-Methyl- N- (2- (6- (piperazin-1-ylmethyl ) benzo [d] oxazol-2-yl) phenyl) benzenesulfonamide] ( it can be selected from the group consisting of 77BBB) Or, to express that not limited to this.

Preferably, the compound may be a compound represented by Formula 1-7:

[Formula 1-7]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of

Preferably, the compound represented by Chemical Formula 1-7 is N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86a), 2-fluoro- N- (2- (7- (piperazin- 1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Fluoro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2- yl) phenyl) benzamide hydrochloride] (86b), 4-fluoro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Fluoro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86c), 2-bromo- N- (2- ( 7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Bromo- N- (2- (7- (piperazin-1-ylmethyl) benzo] d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86d), 3-bromo- N- (2- (7- (piperazine) -1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Bromo- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2 -yl) phenyl) benzamide hydrochloride] (86e), 4-bromo- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydro Chloride [4-Bromo- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86f), 2-chloro- N- (2- ( 7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo] d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86g), 3-chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl ) Benzamide hydrochloride [3-Chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86h), 4-chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86i), 3-nitro- N- (2- (7 -(Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Nitro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86j), 4-nitro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) Benzamide hydrochloride [4-Nitro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86k), 3,4,5-tri Methoxy- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3,4,5-Trimethoxy- N- (2 -(7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86l), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] Oxazol-2-yl) phenyl) -1-naphthamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hy drochloride] (86m), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride [ N- (2- ( 7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] (86n), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline- 2-carboxamide hydrochloride] (86o), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1'-biphenyl]- 4-carboxamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1'-biphenyl] -4-carboxamide hydrochloride] (86p) and N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (86q) It may, but is not limited to.

In addition, the present invention provides a pharmaceutical composition for preventing or treating metabolic diseases containing the compound according to the present invention, its crystalline form, its hydrate or salt thereof as an active ingredient.

Preferably, the metabolic disease may be selected from the group consisting of obesity, diabetes, hyperinsulinemia, hyperuricemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, metabolic syndrome and endothelial dysfunction. It is stated that it does not work.

In addition, the present invention provides a pharmaceutical composition for preventing or treating liver disease containing the compound according to the present invention, its crystalline form, its hydrate or salt thereof as an active ingredient.

Preferably, the liver disease may be selected from the group consisting of alcoholic fatty liver, non-alcoholic fatty liver and hepatitis, but is not limited thereto.

When the composition of the present invention is a pharmaceutical composition, it may be formulated as a cream, gel, patch, spray, ointment, warning agent, lotion agent, linen agent, pasta agent, and cataplasma. On the other hand, the pharmaceutical composition may include a pharmaceutically acceptable carrier in addition to the active ingredient, such a pharmaceutically acceptable carrier is commonly used in pharmaceutical preparations, lactose, dextrose, sucrose, sorbitol, Mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, Talc, magnesium stearate, mineral oil, and the like, but is not limited thereto. In addition, the pharmaceutical composition may further include a lubricant, wetting agent, sweetener, flavoring agent, emulsifying agent, suspending agent, preservative, etc. as additives.

The method of administration of the pharmaceutical composition is determined according to the severity of symptoms, and a topical administration method is usually preferred. In addition, the dosage of the active ingredient in the pharmaceutical composition may vary depending on the administration route, the degree of disease, the patient's age, gender, weight, etc., and may be administered once to several times a day.

In addition, the present invention provides a cosmetic composition for preventing or improving wrinkles containing the compound according to the present invention, its crystalline form, its hydrate or its salt as an active ingredient.

When the composition of the present invention is a cosmetic composition, the cosmetic composition may include a conventional adjuvant such as a stabilizer, a solubilizing agent, vitamins, pigments and fragrances, and a carrier in addition to the active ingredient. In addition, the cosmetic composition may further include a skin absorption accelerator to enhance its effect.

The formulation of the cosmetic composition may be prepared in any formulation conventionally prepared in the art, for example, the cosmetic composition is a lotion, emulsion, skin, toner, lotion, essence, sunscreen, cream, makeup base, foundation , Powder, lipstick, pack, gel, shampoo, rinse, spray, ointment, patch, aerosol, body cleanser, makeup remover and detergent, etc., but may be formulated, but is not limited thereto.

When the formulation is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. .

When the formulation is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane / butane Or propellants such as dimethyl ether.

When the formulation is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 -Fatty acid esters of butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or sorbitan.

When the formulation is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, ethoxylated isostearyl alcohol, suspensions such as polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose , Aluminum metahydroxide, bentonite, agar or trakant, and the like.

In addition, the present invention provides a health food composition for improving cell aging containing a compound according to the present invention, a crystalline form thereof, a hydrate or a salt thereof as an active ingredient.

The health food composition may be provided in the form of a powder, granule, tablet, capsule, syrup, or beverage, and the health food composition is used together with other foods or food additives other than the active ingredient, and is suitably used according to a conventional method. You can. The mixing amount of the active ingredient may be appropriately determined according to its purpose of use, for example, prophylactic, health or therapeutic treatment.

The effective dose of the active ingredient contained in the health food composition may be used in accordance with the effective dose of the pharmaceutical composition, but in the case of long-term intake for health and hygiene purposes or for health control purposes, the effective dose may be less than or equal to the above range. It can be, it is clear that the active ingredient can be used in an amount above the range because there is no problem in terms of safety.

There are no particular restrictions on the type of the health food, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, drinks, tea, Drinks, alcoholic beverages, and vitamin complexes.

Hereinafter, the present invention will be described in more detail through examples. These examples are only intended to illustrate the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .

Example  One : Benzoxazole ( benzoxazole ) Compound Synthesis

1-1. Compound 50 to 56 synthesis

Compounds 50 to 56 were synthesized as shown in Scheme 1 below.

[Scheme 1]

One) ( E ) -3- methyl -2- (2- Nitrobenzylideneamino )phenol[( E ) -3-Methyl-2- (2-nitrobenzylideneamino) phenol] (50)

DMF ( N , N- dimethylformamide) containing 2-amino-3-methylphenol (2-amino-3-methylphenol, 5.0 g, 40.60 mmol) and 2-nitrobenzaldehyde (5.52 g, 36.53 mmol) , 30 mL) After heating the solution at 80 ° C. for 6 hours, the DMF was removed by concentration under reduced pressure and the remaining small amount of DMF was freeze-dried. The obtained residue was recrystallized with diethyl ether and filtered to obtain compound 50, and the process of recrystallizing the filtrate again with diethyl ether was repeated several times to collect the obtained filtration solid, followed by hexane: ethyl acetate (5: 1). Silica gel column chromatography was performed using the developing solvent to further obtain compound 50 (7.0 g, 67%).

2) 4- methyl -2- (2-nitrophenyl) benzo [ d ] Oxazole [4-Methyl-2- (2-nitrophenyl) benzo [ d ] oxazole] (51)

Add DDQ (2,3-dichloro-5,6-dicyano- p- benzoquinone, 6.3 g, 27.68 mmol) into a methylene chloride (80 mL) solution containing compound 50 (7.0 g, 27.32 mmol) and at room temperature 1 Stir for 50 minutes. The reaction mixture was filtered, the filtrate was diluted with methylene chloride, washed with sodium bicarbonate, and the organic layer was dried over anhydrous MgSO ₄ and filtered, and then the filtrate was concentrated under reduced pressure to obtain compound 51 (6.63 g, 95.5%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.14 (d, 1 H, J = 7.5 Hz), 7.91 (d, 1 H, J = 8.0 Hz), 7.74 (t, 1 H, J = 8.0 Hz), 7.68 (t, 1 H, J = 8.0 Hz), 7.39 (d, 1 H, J = 8.5 Hz), 7.29 (t, 1 H, J = 8.0 Hz), 7.18 (d, 1 H, J = 7.5 Hz) ), 2.66 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.4, 151.1, 149.3, 141.1, 132.7, 131.9, 131.8, 131.5, 125.9, 125.6, 124.5, 122.2, 108.4, 16.7.

3) 4- ( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] Oxazole [4-( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] oxazole] (52)

Slowly add NBS ( N- bromosuccinimide, 4.64 g, 26.07 mmol) and benzoyl peroxide (316 mg, 1.30 mmol) sequentially with a solution of chloroform (330 mL) containing compound 51 (6.63 g, 26.08 mmol) and for 36 hours It was stirred at reflux. After cooling, the mixture was added with methylene chloride and water as a reaction mixture, and then the organic layer was dried over anhydrous MgSO ₄ and filtered, and the filtrate was concentrated under reduced pressure to obtain compound 52 (8.60 g, 99%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.17 (dd, 1 H, J = 7.6, 1.6 Hz), 7.93 (dd, 1 H, J = 8.0, 1.6 Hz), 7.76 (td, 1 H, J = 8.0, 1.6 Hz), 7.71 (td, 1 H, J = 8.0, 1.6 Hz), 7.52 (dd, 1 H, J = 8.0, 1.2 Hz), 7.45 (dd, 1 H, J = 7.6, 1.2 Hz) , 7.38 (t, 1 H, J = 8.0 Hz), 4.91 (s, 2 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.4, 151.3, 149.3, 140.4, 132.8, 132.3, 132.0, 130.6, 126.3, 126.0, 124.6, 121.8, 111.3, 27.5.

4) Turt - Butyl  4-((2- (2-nitrophenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-nitrophenyl) benzo [ d ] oxazol -4-yl) methyl) piperazine-1-carboxylate] (53)

Triethylamine (11.2 mL, 80.36 mmol) was added into anhydrous tetrahydrofuran (80 mL) solution containing compound 52 (8.90 g, 26.72 mmol), followed by tert-butyl piperazine-1-carboxylate ( tert- Anhydrous THF (15 mL) solution containing butyl piperazine-1-carboxylate, 1-Boc-piperazine) 4.97 g, 26.68 mmol) was slowly added and stirred at room temperature for 15 hours. The reaction mixture was filtered and the filtrate was extracted with ethyl acetate and water. The organic layer was dried over anhydrous MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure, and the residue obtained was purified by silica gel column chromatography (developing solvent: methylene chloride → methylene chloride: methanol = 50: 1) to obtain compound 53 ( 8.25 g, 70.4%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.13 (dd, 1 H, J = 7.6, 1.6 Hz), 7.89 (dd, 1 H, J = 8.0, 1.2 Hz), 7.74 (td, 1 H, J = 7.6, 1.2 Hz), 7.68 (td, 1 H, J = 7.6, 1.6 Hz), 7.48 (dd, 1 H, J = 7.6, 1.6 Hz), 7.42 (dd, 1 H, J = 7.6, 1.6 Hz) , 7.37 (t, 1 H, J = 7.6 Hz), 4.00 (s, 2 H), 3.45 (brt, 4 H, J = 4.8 Hz), 2.51 (brt, 4 H, J = 4.8 Hz), 1.45 ( s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.7, 155.0, 154.9, 151.0, 141.3, 132.6, 132.1, 131.7, 126.0, 125.6, 124.4, 121.8, 109.8, 79.8, 57.1, 53.0, 43.2, 28.6.

5) Turt - Butyl  4-((2- (2-aminophenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1- Carboxylate [ tert- Butyl 4-((2- (2-aminophenyl) benzo [ d ] oxazol -4-yl) methyl) piperazine-1-carboxylate] (54)

Pd / C (10 wt% Degussa type E101, 130 mg) was added into a methylene chloride (15 mL) solution containing compound 53 (637 mg, 1.45 mmol) and the air in the reaction vessel was replaced with hydrogen, and then at room temperature. Stir for 2 hours. After filtering the reaction mixture, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (developing solvent: methylene chloride → methylene chloride: methanol = 10: 1) to obtain compound 54 (520 mg, 87.6%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 7.99 (d, 1 H, J = 8.0 Hz), 7.41 (d, 1 H, J = 8.0 Hz), 7.32 (d, 1 H, J = 7.2 Hz), 7.24 (t, 1 H, J = 8.0 Hz), 7.21 (td, 1 H, J = 7.6, 1.2 Hz), 6.75 (d, 1 H, J = 8.0 Hz), 6.72 (t, 1 H, J = 8.0 Hz), 6.24 (brs, 2 H), 4.00 (s, 2 H), 3.46 (brs, 4 H), 2.54 (brs, 4 H), 1.42 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.1, 154.9, 149.1, 148.2, 141.6, 132.6, 128.8, 128.3, 125.4, 124.6, 116.9, 116.5, 109.3, 108.6, 79.8, 57.2, 52.9, 43.1, 28.7.

6) Compound 55 (a to z, and A and B) synthesis

Pyridine (0.1 mL, 1.24 mmol) was slowly added into a solution of methylene chloride (4 mL) containing compound 54 (100 mg, 0.24 mmol) and appropriate acyl chloride (0.41 mmol) or phenyl chloroformate (0.41 mmol) and room temperature. Stir in. After the reaction mixture was extracted from methylene chloride and sodium bicarbonate, the organic layer was dried over anhydrous MgSO ₄ , filtered, and the residue obtained by concentrating the filtrate under reduced pressure was silica gel column chromatography (methylene chloride: methanol = 70: 1 to Purification with 90: 1) gave compound 55 .

Turt - Butyl  4-((2- (2-benzamidophenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1- Car Succinate [ tert -Butyl 4-((2- (2-benzamidophenyl) benzo [ d ] oxazol -4-yl) methyl) piperazine-1-carboxylate] (55a)

Reaction time, 3 hours; After extraction and purification by silica gel column chromatography, it was used for the next reaction.

Turt - Butyl  4-((2- (2- (2-methylbenzamido) phenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (2- methylbenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55b)

Reaction time, 5 hours; Yield, 53%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.44 (s, 1 H), 9.01 (d, 1 H, J = 8.5 Hz), 8.27 (dd, 1 H, J = 8.5, 1.5 Hz), 7.73 (d , 1 H, J = 7.5 Hz), 7.60 (td, 1 H, J = 8.0, 1.5 Hz), 7.50 (m, 1 H), 7.43 (td, 1 H, J = 7.5, 1.5 Hz), 7.37- 7.31 (m, 4 H), 7.25 (td, 1 H, J = 7.5, 1.0 Hz), 3.65 (s, 2 H), 3.30 (brs, 4 H), 2.59 (s, 3 H), 2.14 (brs , 4 H), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 169.0, 162.0, 154.9, 149.1, 140.4, 139.6, 137.4, 137.1, 133.2, 131.7, 130.7, 129.4, 128.5, 127.6, 126.3, 125.9, 125.7, 123.4, 120.6, 113.2 , 109.6, 79.8, 57.0, 52.6, 43.4, 28.7, 20.4.

Turt - Butyl  4-((2- (2- (3-methylbenzamido) phenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (3-methylbenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55c)

Reaction time, 6 hours; Yield, 80%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.55 (s, 1 H), 8.99 (dd, 1 H, J = 8.0, 1.0 Hz), 8.27 (dd, 1 H, J = 8.0, 1.5 Hz), 7.99 (d, 1 H, J = 8.0 Hz), 7.93 (s, 1 H), 7.59 (td, 1 H, J = 8.0, 1.5 Hz), 7.52 (d, 1 H, J = 8.5 Hz), 7.46 ( t, 1 H, J = 7.5 Hz), 7.44 (d, 1 H, J = 8.0 Hz), 7.42 (d, 1 H, J = 8.0 Hz), 7.37 (t, 1 H, J = 8.0 Hz), 7.25 (td, 1 H, J = 7.5, 1.0 Hz), 3.97 (s, 2 H), 3.36 (brs, 4 H), 2.49 (s, 3 H), 2.35 (s, 4 H), 1.43 (s , 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 167.1, 162.1, 154.9, 149.2, 140.4, 139.6, 139.0, 136.0, 133.1, 133.0, 129.7, 129.2, 128.7, 128.7, 125.7, 125.4, 124.6, 123.4, 120.9, 113.5 , 109.4, 79.8, 57.0, 52.9, 43.4, 28.6, 21.8.

Turt - Butyl  4-((2- (2- (4-methylbenzamido) phenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (4-methylbenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55d)

Reaction time, 6 hours; Yield, 86%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.56 (s, 1 H), 9.00 (dd, 1 H, J = 8.5, 1.0 Hz), 8.27 (dd, 1 H, J = 8.5, 1.5 Hz), 8.09 (d, 2 H, J = 8.5 Hz), 7.59 (td, 1 H, J = 8.0, 1.5 Hz), 7.51 (dd, 1 H, J = 8.0, 1.0 Hz), 7.47 (d, 1 H, J = 7.5 Hz), 7.38 (t, 1 H, J = 8.0 Hz), 7.37 (d, 2 H, J = 8.0 Hz), 7.24 (td, 1 H, J = 8.0, 1.0 Hz), 4.00 (s, 2 H), 3.39 (brs, 4 H), 2.47 (s, 3 H), 2.41 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.8, 162.1, 154.9, 149.2, 142.7, 140.4, 139.6, 133.2, 129.8, 129.7, 128.7, 128.1, 125.8, 125.3, 123.3, 120.8, 113.4, 109.4, 79.9, 57.1 , 53.1, 43.4, 28.6, 21.9.

Turt - Butyl  4-((2- (2- (2-fluorobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2-fluorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55e)

Reaction time, 5 hours; Yield, 83%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.53 (s, 1 H), 8.94 (d, 1 H, J = 8.0 Hz), 8.26 (d, 1 H, J = 8.0 Hz), 7.99 (td, 1 H, J = 7.5, 1.5 Hz), 7.61-7.53 (m, 2 H), 7.49 (d, 1 H, J = 7.5 Hz), 7.40 (d, 1 H, J = 7.5 Hz), 7.35 (t, 1 H, J = 8.0 Hz), 7.33 (t, 1 H, J = 7.5 Hz), 7.28-7.23 (m, 2 H), 3.84 (s, 2 H), 3.35 (brs, 4 H), 2.30 ( brs, 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.3, 161.7, 160.0 (d, J = 250.4 Hz), 154.9, 149.2, 140.5, 138.9, 133.5 (d, J = 8.4 Hz), 133.0, 131.5, 129.7, 128.6 , 125.7, 125.5, 125.0 (d, J = 3.8 Hz), 124.5 (d, J = 12.9 Hz), 123.8, 121.5, 116.7 (d, J = 22.0 Hz), 113.9, 109.4, 79.8, 56.9, 52.9, 43.6 , 28.7.

Turt - Butyl  4-((2- (2- (3-fluorobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-fluorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55f)

Reaction time, 7 hours; Yield, 87%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.62 (s, 1 H), 8.99 (d, 1 H, J = 8.5 Hz), 8.27 (dd, 1 H, J = 7.5, 1.5 Hz), 8.00 (d , 1 H, J = 7.5 Hz), 7.88 (dt, 1 H, J = 9.5, 1.5 Hz), 7.59 (td, 1 H, J = 7.5, 1.5 Hz), 7.55 (td, 1 H, J = 8.0 , 5.5 Hz), 7.51 (d, 1 H, J = 8.0 Hz), 7.50 (d, 1 H, J = 7.5 Hz), 7.39 (t, 1 H, J = 7.5 Hz), 7.32 (td, 1 H , J = 8.0, 2.5 Hz), 7.26 (t, 1 H, J = 8.0 Hz), 3.99 (s, 2 H), 3.40 (brs, 4 H), 2.41 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.2, 163.0 (d, J = 245.8 Hz), 162.0, 155.0, 149.2, 140.1, 139.2, 138.0 (d, J = 6.0 Hz), 133.2, 130.7 (d, J = 7.6 Hz), 130.1, 128.7, 125.9, 125.1, 123.9, 123.7, 120.8, 119.3 (d, J = 21.2 Hz), 115.2 (d, J = 22.8 Hz), 113.6, 109.3, 79.9, 57.0, 53.1, 43.2 , 28.6.

Turt - Butyl  4-((2- (2- (4-fluorobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-fluorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55g)

Reaction time, 7 hours; Yield, 90%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.58 (s, 1 H), 8.97 (d, 1 H, J = 8.5 Hz), 8.28 (dd, 1 H, J = 8.0, 1.5 Hz), 8.22 (dd , 2 H, J = 8.5, 5.5 Hz), 7.59 (td, 1 H, J = 7.5, 1.5 Hz), 7.52 (d, 1 H, J = 8.0 Hz), 7.48 (d, 1 H, J = 7.5 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 7.26 (t, 1 H, J = 7.5 Hz), 7.24 (t, 2 H, J = 8.5 Hz), 3.98 (s, 2 H), 3.41 (t, 4 H, J = 5.0 Hz), 2.41 (t, 4 H, J = 5.0 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3 (d, J = 251.9 Hz), 165.5, 162.1, 154.9, 149.2, 140.3, 139.4, 133.2, 132.1, 130.5 (d, J = 9.1 Hz), 129.7, 128.7 , 125.9, 125.3, 123.5, 120.8, 116.1 (d, J = 22.0 Hz), 113.5, 109.5, 79.9, 57.2, 53.2, 43.2, 28.6.

Turt - Butyl  4-((2- (2- (2-bromobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2- bromobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55h)

Reaction time, 8 hours; Yield, 94%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.55 (s, 1 H), 9.00 (d, 1 H, J = 8.4 Hz), 8.27 (d, 1 H, J = 8.0 Hz), 7.73-7.68 (m , 2 H), 7.61 (t, 1 H, J = 8.0 Hz), 7.51-7.45 (m, 2 H), 7.38 (t, 1 H, J = 8.0 Hz), 7.35-7.31 (m, 2 H) , 7.28 (t, 1 H, J = 7.6 Hz), 3.59 (s, 2 H), 3.30 (brs, 4 H), 2.11 (brs, 4 H), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.8, 161.8, 154.9, 149.1, 140.4, 139.4, 139.0, 134.0, 133.3, 131.8, 129.4, 128.5, 127.9, 126.1, 125.8, 123.8, 120.7, 120.0, 113.4, 109.6 , 79.9, 57.1, 52.8, 43.3, 28.7.

Turt - Butyl  4-((2- (2- (3-bromobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-bromobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55i)

Reaction time, 2 hours; Yield, 66.2%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.61 (s, 1 H), 8.95 (d, 1 H, J = 8.5 Hz), 8.28 (dd, 1 H, J = 8.0, 1.5 Hz), 8.24 (s , 1 H), 8.11 (d, 1 H, J = 7.5 Hz), 7.74 (d, 1 H, J = 7.5 Hz), 7.59 (td, 1 H, J = 8.0, 1.5 Hz), 7.52 (d, 1 H, J = 8.0 Hz), 7.47 (d, 1 H, J = 7.5 Hz), 7.45 (t, 1 H, J = 8.0 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 7.27 ( td, 1 H, J = 8.0, 1.5 Hz), 3.97 (s, 2 H), 3.36 (brs, 4 H), 2.36 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3, 162.0, 154.9, 149.2, 140.2, 139.2, 138.1, 135.2, 133.2, 131.4, 130.5, 130.0, 128.7, 126.4, 125.9, 125.4, 123.7, 123.4, 120.9, 113.6 , 109.4, 79.9, 57.1, 53.1, 43.3, 28.7.

Turt - Butyl  4-((2- (2- (4-bromobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-bromobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55j)

Reaction time, 5 hours; Yield, 87%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.64 (s, 1 H), 8.94 (d, 1 H, J = 8.4 Hz), 8.27 (dd, 1 H, J = 8.0, 1.6 Hz), 8.03 (d , 2 H, J = 8.4 Hz), 7.70 (d, 2 H, J = 8.4 Hz), 7.59 (td, 1 H, J = 8.0, 1.6 Hz), 7.51 (d, 1 H, J = 8.0 Hz) , 7.47 (d, 1 H, J = 7.6 Hz), 7.38 (t, 1 H, J = 8.0 Hz), 7.26 (td, 1 H, J = 8.0, 1.2 Hz), 3.93 (s, 2 H), 3.40 (t, 4 H, J = 4.8 Hz), 2.38 (t, 4 H, J = 4.8 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.8, 162.1, 154.9, 149.2, 140.2, 139.3, 134.9, 133.2, 132.3, 129.7, 128.7, 126.9, 125.9, 125.4, 123.7, 120.8, 113.5, 109.5, 79.9, 57.2 , 53.2, 43.6, 28.7.

Turt - Butyl  4-((2- (2- (2-chlorobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2- chlorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55k)

Reaction time, 6 hours; Yield, 78%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.56 (s, 1 H), 9.00 (d, 1 H, J = 8.5 Hz), 8.26 (d, 1 H, J = 8.0 Hz), 7.73 (dd, 1 H, J = 7.5, 1.5 Hz), 7.61 (td, 1 H, J = 8.0, 1.5 Hz), 7.54 (d, 1 H, J = 8.0 Hz), 7.51-7.46 (m, 2 H), 7.43 ( t, 1 H, J = 8.0 Hz), 7.34 (d, 1 H, J = 7.5 Hz), 7.34 (d, 1 H, J = 7.5 Hz), 7.27 (t, 1 H, J = 8.0 Hz), 3.62 (s, 2 H), 3.31 (brs, 4 H), 2.14 (brs, 4 H), 1.47 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.9, 161.9, 154.9, 149.1, 140.4, 139.1, 137.3, 133.3, 131.7, 131.5, 130.8, 129.6, 128.5, 127.4, 126.0, 125.8, 123.8, 120.8, 113.4, 109.6 , 79.9, 57.0, 52.8, 43.9, 28.7.

Turt - Butyl  4-((2- (2- (3-chlorobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-chlorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55l)

Reaction time, 3 hours; Yield, 73%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.61 (s, 1 H), 8.95 (d, 1 H, J = 8.8 Hz), 8.27 (d, 1 H, J = 7.6 Hz), 8.08 (d, 1 H, J = 1.2 Hz), 8.06 (d, 1 H, J = 8.0 Hz), 7.61-7.57 (m, 2 H), 7.53-7.49 (m, 2 H), 7.47 (d, 1 H, J = 7.6 Hz), 7.38 (t, 1 H, J = 8.0 Hz), 7.26 (t, 1 H, J = 7.6 Hz), 3.96 (s, 2 H), 3.36 (brs, 4 H), 2.36 (brs, 4 H), 1.43 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3, 162.0, 155.0, 149.2, 140.2, 139.2, 137.8, 135.2, 133.2, 132.2, 130.3, 130.0, 128.7, 128.4, 126.1, 125.9, 125.4, 123.7, 120.9, 113.6 , 109.4, 79.9, 57.1, 53.1, 43.3, 28.6.

Turt - Butyl  4-((2- (2- (4-chlorobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-chlorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55m)

Reaction time, 3 hours; Yield, 96%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.62 (s, 1 H), 8.94 (dd, 1 H, J = 8.4, 0.8 Hz), 8.26 (dd, 1 H, J = 7.6, 1.6 Hz), 8.11 (d, 2 H, J = 8.4 Hz), 7.58 (t, 1 H, J = 8.0, 1.6 Hz), 7.53 (d, 2 H, J = 8.8 Hz), 7.52 (dd, 1 H, J = 8.0 , 1.2 Hz), 7.47 (d, 1 H, J = 8.0 Hz), 7.38 (t, 1 H, J = 8.0 Hz), 7.25 (td, 1 H, J = 7.6, 1.2 Hz), 3.95 (s, 2 H), 3.39 (t, 4 H, J = 4.8 Hz), 2.38 (t, 4 H, J = 4.8 Hz), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.4, 161.9, 154.7, 148.9, 140.0, 139.1, 138.2, 134.2, 133.0, 129.3, 129.1, 128.5, 125.7, 125.2, 123.4, 120.6, 113.3, 109.3, 79.7, 56.9 , 52.9, 43.2, 28.4.

Turt - Butyl  4-((2- (2- (3-nitrobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-nitrobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55n)

Reaction time, 5 hours; Yield, 76%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.79 (s, 1 H), 8.96-8.94 (m, 2 H), 8.51 (dt, 1 H, J = 7.6, 1.2 Hz), 8.48 (ddd, 1 H , J = 7.6, 2.4, 1.2 Hz), 8.29 (dd, 1 H, J = 8.0, 1.6 Hz), 7.78 (t, 1 H, J = 8.0 Hz), 7.61 (td, 1 H, J = 8.0, 1.6 Hz), 7.52 (dd, 1 H, J = 8.0, 1.2 Hz), 7.48 (d, 1 H, J = 7.6 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 7.29 (td, 1 H, J = 7.6, 1.2 Hz), 3.85 (s, 2 H), 3.35 (t, 4 H, J = 4.8 Hz), 2.27 (t, 4 H, J = 4.8 Hz), 1.43 (s, 9 H ); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.2, 162.0, 154.9, 149.1, 148.8, 140.0, 138.8, 137.8, 133.7, 133.3, 130.2, 129.9, 128.8, 126.7, 126.1, 125.3, 124.1, 123.3, 120.9, 113.8 , 109.4, 79.9, 57.0, 53.1, 43.5, 28.6.

Turt - Butyl  4-((2- (2- (4-nitrobenzamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-nitrobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55o)

Reaction time, 3.5 hours; Yield, 77%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.83 (s, 1 H), 8.98 (d, 1 H, J = 8.5 Hz), 8.42 (d, 2 H, J = 8.5 Hz), 8.36 (d, 2 H, J = 8.5 Hz), 8.30 (d, 1 H, J = 7.5 Hz), 7.62 (t, 1 H, J = 8.0 Hz), 7.54 (d, 1 H, J = 7.5 Hz), 7.51 (d , 1 H, J = 7.5 Hz), 7.41 (t, 1 H, J = 8.0 Hz), 7.30 (t, 1 H, J = 8.0 Hz), 3.96 (s, 2 H), 3.40 (brs, 4 H ), 2.39 (brs, 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.4, 162.0, 155.0, 150.0, 149.2, 141.4, 140.0, 138.8, 133.4, 129.8, 129.3, 128.8, 126.1, 125.4, 124.2, 120.8, 113.7, 109.6, 80.0, 57.3 , 53.0, 43.4, 28.6.

Turt - Butyl  4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] Oxazole -4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55p)

Reaction time, 5 hours; Yield, 88%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.53 (s, 1 H), 8.85 (d, 1 H, J = 8.8 Hz), 8.27 (dd, 1 H, J = 8.0, 1.2 Hz), 7.60 (td , 1 H, J = 8.0, 1.6 Hz), 7.52 (dd, 1 H, J = 7.6, 1.2 Hz), 7.40 (d, 1 H, J = 7.6 Hz), 7.36 (t, 1 H, J = 7.6 Hz), 7.29 (s, 2 H), 7.26 (t, 1 H, J = 7.6 Hz), 3.95 (s, 3 H), 3.93 (s, 6 H), 3.83 (s, 2 H), 3.27 ( t, 4 H, J = 4.8 Hz), 2.23 (t, 4 H, J = 4.8 Hz), 1.41 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 167.1, 162.1, 154.9, 153.6, 149.2, 142.0, 140.4, 139.5, 133.1, 132.0, 129.7, 128.6, 125.8, 125.6, 123.5, 120.9, 113.6, 109.5, 106.3, 79.8 , 61.3, 57.0, 52.7, 43.5, 28.6.

Turt - Butyl  4-((2- (2- (2,4-dichlorobenzamido) phenyl) benzo [ d ] Oxazole -4-day) Me Tyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2,4-dichlorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55q)

Reaction time, 3 hours; Yield, 89%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.63 (s, 1 H), 8.95 (d, 1 H, J = 8.4 Hz), 8.26 (dd, 1 H, J = 8.4, 1.6 Hz), 7.68 (d , 1 H, J = 8.4 Hz), 7.60 (td, 1 H, J = 8.0, 1.6 Hz), 7.55 (d, 1 H, J = 1.6 Hz), 7.50 (dd, 1 H, J = 6.8, 2.4 Hz), 7.41 (dd, 1 H, J = 8.0, 2.0 Hz), 7.37 (d, 1 H, J = 7.2 Hz), 7.35 (t, 1 H, J = 7.6 Hz), 7.28 (td, 1 H , J = 7.6, 1.2 Hz), 3.58 (s, 2 H), 3.33 (t, 4 H, J = 4.8 Hz), 2.15 (t, 4 H, J = 4.8 Hz), 1.48 (s, 9 H) ; ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.9, 161.8, 154.9, 149.1, 140.3, 138.9, 137.1, 135.7, 133.3, 132.6, 130.7, 130.6, 129.6, 128.5, 127.8, 126.0, 125.9, 124.0, 120.7, 113.4 , 109.6, 79.9, 57.2, 53.0, 43.3, 28.7.

Turt - Butyl  4-((2- (2- (3,4-dichlorobenzamido) phenyl) benzo [ d ] Oxazole -4-day) Me Tyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3,4-dichlorobenzamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55r)

Reaction time, 5 hours; Yield, 90%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.63 (s, 1 H), 8.92 (d, 1 H, J = 8.4 Hz), 8.28 (dd, 1 H, J = 8.0, 1.6 Hz), 8.19 (d , 1 H, J = 2.0 Hz), 8.01 (dd, 1 H, J = 8.4, 2.0 Hz), 7.64 (d, 1 H, J = 8.4 Hz), 7.60 (td, 1 H, J = 8.0, 1.6 Hz), 7.53 (d, 1 H, J = 8.0 Hz), 7.48 (d, 1 H, J = 7.6 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 7.28 (td, 1 H, J = 8.0, 1.2 Hz), 3.94 (s, 2 H), 3.38 (t, 4 H, J = 4.8 Hz), 2.35 (t, 4 H, J = 4.8 Hz), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.5, 162.0, 154.9, 149.2, 140.2, 139.0, 136.7, 136.0, 133.5, 133.2, 131.1, 130.2, 130.0, 128.7, 127.2, 126.0, 125.5, 123.9, 120.9, 113.7 , 109.5, 79.9, 57.1, 53.1, 43.3, 28.6.

Turt - Butyl  4-((2- (2- (nicotinamido) phenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (nicotinamido) phenyl) benzo [ d ] oxazol -4-yl) methyl) piperazine-1-carboxylate] (55s)

Reaction time, 4 hours; Yield, 94%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.79 (s, 1 H), 9.47 (s, 1 H), 8.97 (d, 1 H, J = 8.4 Hz), 8.84 (d, 1 H, J = 4.4 Hz), 8.44 (d, 1 H, J = 8.0 Hz), 8.27 (d, 1 H, J = 8.0 Hz), 7.58 (t, 1 H, J = 8.0 Hz), 7.53-7.45 (m, 3 H ), 7.38 (t, 1 H, J = 8.0 Hz), 7.26 (t, 1 H, J = 8.0 Hz), 3.99 (s, 2 H), 3.38 (brs, 4 H), 2.42 (brs, 4 H) ), 1.43 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.6, 162.0, 155.0, 152.9, 149.2, 149.1, 140.1, 139.0, 135.9, 133.2, 131.4, 130.0, 128.7, 125.9, 125.6, 123.9, 120.8, 113.6, 109.5, 79.8 , 57.3, 53.1, 43.5, 28.7.

Turt - Butyl  4-((2- (2- (isonicotinamido) phenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (isonicotinamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55t)

Reaction time, 20 hours; Yield, 91%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.77 (s, 1 H), 8.98 (d, 1 H, J = 8.5 Hz), 8.89 (d, 2 H, J = 6.0 Hz), 8.28 (dd, 1 H, J = 8.5, 1.5 Hz), 8.03 (d, 2 H, J = 6.5 Hz), 7.59 (td, 1 H, J = 8.0, 1.5 Hz), 7.52 (d, 1 H, J = 8.5 Hz) , 7.52 (d, 1 H, J = 8.5 Hz), 7.40 (t, 1 H, J = 8.0 Hz), 7.28 (td, 1 H, J = 8.0, 1.0 Hz), 3.98 (s, 2 H), 3.42 (t, 4 H, J = 4.5 Hz), 2.43 (brs, 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.2, 161.7, 154.7, 150.8, 148.9, 142.5, 139.8, 138.5, 133.0, 128.5, 125.8, 125.0, 123.9, 121.5, 120.6, 113.5, 109.2, 79.7, 57.1, 53.0 , 43.7, 28.4.

Tert - butyl 4-((2- (2- (1 - naphthaamido ) phenyl) benzo [ d ] oxazol- 4 -yl ) methyl ) piperazine- 1-carboxylate [ tert -Butyl 4-(( 2- (2- (1-naphthamido) phenyl) benzo [ d ] oxazol -4-yl) methyl) piperazine-1-carboxylate] (55u)

Reaction time, 6 hours; Yield, 83%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.74 (s, 1 H), 9.14 (d, 1 H, J = 8.5 Hz), 8.52 (m, 1 H), 8.28 (d, 1 H, J = 8.5 Hz), 8.05 (d, 1 H, J = 8.5 Hz), 7.98 (d, 1 H, J = 7.0 Hz), 7.95 (m, 1 H), 7.66-7.60 (m, 2 H), 7.57-7.55 (m, 2 H), 7.47 (d, 1 H, J = 7.5 Hz), 7.32-7.26 (m, 3 H), 3.37 (s, 2 H), 3.14 (brs, 4 H), 1.98 (brs, 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 168.2, 161.7, 154.6, 148.9, 140.0, 139.4, 135.3, 133.9, 133.0, 131.2, 130.3, 128.5, 128.3, 127.3, 126.7, 125.8, 125.6, 125.5, 125.4, 124.9 , 123.3, 120.5, 113.1, 109.2, 79.5, 56.4, 52.2, 42.8, 28.4.

Turt - Butyl  4-((2- (2- (2-naphthaamido) phenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (2-naphthamido) phenyl) benzo [ d ] oxazol -4-yl) methyl) piperazine-1-carboxylate] (55v)

Reaction time, 19 hours; Yield, 55%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.76 (s, 1 H), 9.03 (d, 1 H, J = 8.0 Hz), 8.63 (s, 1 H), 8.30 (dd, 1 H, J = 8.0 , 1.5 Hz), 8.21 (dd, 1 H, J = 8.0, 1.5 Hz), 8.03 (d, 1 H, J = 7.5 Hz), 8.02 (d, 1 H, J = 9.0 Hz), 7.95 (d, 1 H, J = 8.0 Hz), 7.64-7.58 (m, 3 H), 7.52 (d, 1 H, J = 8.0 Hz), 7.43 (d, 1 H, J = 7.5 Hz), 7.37 (t, 1 H, J = 8.0 Hz), 7.27 (td, 1 H, J = 8.0, 1.0 Hz), 3.85 (s, 2 H), 3.23 (brs, 4 H), 2.10 (brs, 4 H), 1.43 (s , 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 167.1, 162.1, 154.8, 149.2, 140.4, 139.6, 135.2, 133.5, 133.2, 133.0, 129.9, 129.5, 129.0, 128.8, 128.7, 128.2, 128.2, 127.2, 125.8, 125.4 , 124.3, 123.5, 120.9, 113.6, 109.4, 79.8, 57.0, 52.8, 43.3, 28.7.

Turt - Butyl  4-((2- (2- (quinoline-2-carboxamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate ([ tert -Butyl 4-((2- (2- ( quinoline -2-carboxamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55w)

Reaction time, 5.5 hours; Yield, 82%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 13.04 (s, 1 H), 8.92 (dd, 1 H, J = 8.4, 0.8 Hz), 8.39 (s, 2 H), 8.32 (d, 1 H, J = 8.4 Hz), 8.30 (dd, 1 H, J = 8.4, 1.6 Hz), 7.95 (dd, 1 H, J = 8.4, 1.2 Hz), 7.82 (td, 1 H, J = 7.6, 1.6 Hz), 7.68 (td, 1 H, J = 7.6, 1.2 Hz), 7.61 (td, 1 H, J = 8.0, 1.6 Hz), 7.52 (dd, 1 H, J = 7.6, 1.2 Hz), 7.40 (dd, 1 H, J = 7.6, 1.2 Hz), 7.36 (t, 1 H, J = 7.6 Hz), 7.29 (td, 1 H, J = 7.6, 1.2 Hz), 3.98 (s, 2 H), 3.20 (brs, 4 H), 2.06 (t, 4 H, J = 4.8 Hz), 1.40 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.7, 161.7, 154.8, 151.6, 149.4, 146.9, 141.3, 138.6, 137.9, 132.7, 130.8, 130.4, 130.0, 129.7, 129.0, 128.4, 128.2, 125.5, 125.2, 124.0 , 122.0, 119.9, 115.3, 109.3, 79.7, 56.8, 52.5, 43.4, 28.6.

Turt - Butyl  4-((2- (2- (quinoxaline-2-carboxamido) phenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (quinoxaline-2-carboxamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55x)

Reaction time, 3.5 hours; Yield, 60%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 13.04 (s, 1 H), 9.79 (s, 1 H), 8.97 (d, 1 H, J = 8.8 Hz), 8.40 (dd, 1 H, J = 7.6 , 1.2 Hz), 8.31 (d, 1 H, J = 7.6 Hz), 8.26 (dd, 1 H, J = 8.4, 1.2 Hz), 7.93 (td, 1 H, J = 7.6, 1.6 Hz), 7.90 ( td, 1 H, J = 7.6, 1.6 Hz), 7.62 (t, 1 H, J = 8.0 Hz), 7.53 (d, 1 H, J = 7.6 Hz), 7.43 (d, 1 H, J = 7.6 Hz ), 7.38 (t, 1 H, J = 7.6 Hz), 7.32 (t, 1 H, J = 7.6 Hz), 4.10 (s, 2 H), 3.28 (brs, 4 H), 2.24 (brs, 4 H) ), 1.39 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.4, 161.6, 154.8, 149.4, 145.4, 145.0, 144.1, 141.1, 140.7, 138.2, 132.8, 132.1, 131.1, 130.6, 130.0, 129.7, 129.1, 125.7, 125.3, 124.4 , 121.9, 115.1, 109.4, 79.8, 56.8, 52.5, 43.3, 28.6.

Turt - Butyl  4-((2- (2-([1,1'-biphenyl] -4- Ilka Copy Mido ) Phenyl) Benzo [ d ] Oxazole -4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2-([1,1'-biphenyl] -4-ylcarboxamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55y)

Reaction time, 5 hours; Yield, 60%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.69 (s, 1 H), 9.02 (d, 1 H, J = 8.8 Hz), 8.29 (dd, 1 H, J = 7.6, 1.2 Hz), 8.27 (d , 2 H, J = 8.0 Hz), 7.79 (d, 2 H, J = 8.8 Hz), 7.67 (d, 2 H, J = 7.2 Hz), 7.60 (td, 1 H, J = 7.2, 1.2 Hz) , 7.53-7.49 (m, 3 H), 7.46-7.42 (m, 2 H), 7.38 (t, 1 H, J = 8.0 Hz), 7.25 (t, 1 H, J = 7.6 Hz), 4.02 (s , 2 H), 3.34 (brs, 4 H), 2.38 (brs, 4 H), 1.40 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.5, 162.1, 154.9, 149.2, 145.0, 140.4, 140.1, 139.6, 134.5, 133.2, 129.8, 129.3, 128.7, 128.6, 128.4, 127.7, 127.4, 125.8, 125.4, 123.4 , 120.8, 113.5, 109.5, 79.8, 57.3, 53.1, 43.3, 28.6.

Turt - Butyl  4-((2- (2- (cyclohexanecarboxamido) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (cyclohexanecarboxamido) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55z)

Reaction time, 4 hours; Yield, 87%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 11.87 (s, 1 H), 8.86 (d, 1 H, J = 8.5 Hz), 8.22 (dd, 1 H, J = 8.0, 1.5 Hz), 7.57-7.50 (m, 2 H), 7.48 (brd, 1 H, J = 7.0 Hz), 7.39 (t, 1 H, J = 7.5 Hz), 7.18 (td, 1 H, J = 8.0, 1.0 Hz), 4.01 ( s, 2 H), 3.48 (brs, 4 H), 2.51 (brs, 4 H), 2.49 (m, 1 H), 2.15 (m, 2 H), 1.92 (m, 2 H), 1.77 (m, 1 H), 1.68 (m, 2 H), 1.44 (s, 9 H), 1.43-1.30 (m, 3 H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 175.4, 161.9, 154.7, 148.9, 140.3, 139.4, 132.9, 129.4, 128.3, 125.5, 125.2, 122.7, 120.4, 112.7, 109.2, 79.7, 57.1, 53.1, 47.6, 43.1 , 29.8, 28.4, 26.0, 25.8.

( E )- Turt - Butyl  4-((2- (2-cinnamamidophenyl) benzo [ d ] Oxazole -4-day) methyl ) Piperazine-1-carboxylate [( E )- tert -Butyl 4-((2- (2-cinnamamidophenyl) benzo [ d ] oxazol -4-yl) methyl) piperazine-1-carboxylate] (55A)

Reaction time, 15 hours; Yield, 72%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.38 (s, 1 H), 8.95 (d, 1 H, J = 8.0 Hz), 8.24 (d, 1 H, J = 8.0 Hz), 7.82 (d, 1 H, J = 15.5 Hz), 7.61 (d, 2 H, J = 7.0 Hz), 7.56 (t, 1 H, J = 8.0 Hz), 7.53 (d, 1 H, J = 8.0 Hz), 7.48-7.38 (m, 5 H), 7.22 (t, 1 H, J = 8.0 Hz), 6.77 (d, 1 H, J = 15.5 Hz), 4.02 (s, 2 H), 3.43 (brs, 4 H), 2.50 (brs, 4 H), 1.40 (s, 9 H); ¹³ C NMR (125 MHz, CDCl ₃ ) δ 164.6, 161.9, 154.6, 148.9, 141.9, 140.1, 139.4, 134.8, 132.9, 130.1, 129.0, 128.2, 127.9, 125.6, 125.4, 123.0, 122.5, 120.5, 112.7, 109.3 , 79.6, 57.4, 53.3, 43.3, 28.4.

Turt - Butyl  4-((2- (2-((phenoxycarbonyl) amino) phenyl) benzo [ d ] Oxazol-4-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2-((phenoxycarbonyl) amino) phenyl) benzo [ d ] oxazol-4-yl) methyl) piperazine-1-carboxylate] (55B)

Reaction time, 10 hours; Yield, 83%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.07 (s, 1 H), 8.56 (d, 1 H, J = 8.5 Hz), 8.25 (dd, 1 H, J = 8.0, 1.5 Hz), 7.57-7.53 (m, 2 H), 7.43 (t, 2 H, J = 8.0 Hz), 7.40-7.36 (m, 2 H), 7.28-7.24 (m, 3 H), 7.21 (t, 1 H, J = 7.5 Hz), 4.04 (s, 2 H), 3.41 (brs, 4 H), 2.56 (brs, 4 H), 1.41 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 161.9, 154.6, 152.0, 150.7, 149.1, 140.5, 138.9, 132.9, 129.5, 128.3, 126.1, 125.7, 125.4, 122.5, 121.7, 118.9, 112.7, 109.6, 79.5, 57.4 , 52.7, 43.3, 28.4.

7) Synthesis of Compound 56 (a to z, and A and B)

To the compound 55 (1.0 eq), a volume corresponding to 8N-HCl (42.0 eq) and 1,4-dioxane and 8N-HCl (42.0 eq) were added in turn and stirred at room temperature. The solvent was concentrated under reduced pressure, and then recrystallized using a small amount of methanol and ether to give compound 56 (a to z, and A and B) in the form of HCl salt.

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56a)

White solid; Reaction time, 15 hours; Yield, 91%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 11.99 (s, 1 H), 9.53 (brs, 2 H), 8.69 (d, 1 H, J = 8.8 Hz), 8.26 (d, 1 H, J = 8.0 Hz), 8.10 (d, 2 H, J = 8.0 Hz), 7.91 (d, 1 H, J = 8.4 Hz), 7.77-7.68 (m, 5 H), 7.56 (t, 1 H, J = 8.0 Hz), 7.37 (t, 1 H, J = 7.6 Hz), 4.56 (s, 2 H), 3.32 (brs, 4 H), 3.18 (brs, 4 H).

2- methyl - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [2-Methyl- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56b)

White solid; Reaction time, 15 hours; Yield, 82%; ¹ H NMR (500 MHz, DMSO- d ₆ + 3 drops of CD ₃ OD) δ 8.68 (d, 1 H, J = 8.5 Hz), 8.25 (d, 1 H, J = 8.0 Hz), 7.87 (d, 1 H, J = 8.0 Hz), 7.80 (m, 1 H), 7.68 (t, 1 H, J = 8.0 Hz), 7.63 (brd, 1 H, J = 7.0 Hz), 7.54-7.48 (m, 3 H), 7.39-7.33 (m, 2 H), 4.34 (s, 2 H), 3.25 (brs, 4 H), 3.01 (brs, 4 H), 2.46 (s, 3 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of CD ₃ OD) δ 168.3, 162.7, 149.6, 141.3, 139.0, 137.1, 136.9, 133.8, 131.9, 131.5, 129.5, 128.6, 127.7, 126.9, 126.6, 124.5, 121.2, 114.3, 112.8, 54.7, 48.2, 41.6, 20.1.

3- methyl - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Methyl- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56c)

Ivory solid; Reaction time, 17 hours; Yield, 92%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.87 (s, 1 H), 9.57 (brs, 2 H), 8.64 (d, 1 H, J = 8.5 Hz), 8.24 (d, 1 H, J = 8.0 Hz), 7.93-7.89 (m, 2 H), 7.81 (s, 1 H), 7.77 (d, 1 H, J = 7.5 Hz), 7.69 (t, 1 H, J = 7.5 Hz), 7.66 (t, 1 H, J = 8.0 Hz), 7.56 (t, 1 H, J = 8.0 Hz), 7.50 (d, 1 H, J = 7.5 Hz), 7.37 (t, 1 H, J = 8.0 Hz) , 4.53 (s, 2 H), 3.29 (brs, 4 H), 3.16 (brs, 4 H), 2.44 (s, 3 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 166.5, 162.7, 149.5, 141.5, 139.3, 139.1, 135.6, 133.9, 133.8, 129.8, 129.7, 129.0, 128.7, 126.8, 124.8, 124.7, 121.9, 114.7, 112.9 , 54.4, 48.2, 41.6, 21.8.

4- methyl - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Methyl- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56d)

Ivory solid; Reaction time, 15 hours; Yield, 90%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.20 (brs, 1 H), 9.37 (brs, 2 H), 8.75 (d, 1 H, J = 8.4 Hz), 8.24 (d, 1 H, J = 8.0 Hz), 8.00 (d, 2 H, J = 8.0 Hz), 7.81 (brd, 1 H, J = 8.0 Hz), 7.67 (t, 1 H, J = 7.6 Hz), 7.53-7.48 (m, 4 H), 7.34 (t, 1 H, J = 7.6 Hz), 4.27 (brs, 2 H), 3.19 (brs, 4 H), 2.86 (brs, 4 H), 2.46 (s, 3 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 166.1, 162.1, 149.2, 143.5, 140.4, 139.1, 138.9, 133.8, 132.5, 130.3, 129.3, 128.1, 126.8, 126.5, 124.5, 120.9, 113.8, 111.2, 55.8 , 49.2, 42.7, 21.8.

2- Fluoro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [2- Fluoro - N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (56e)

White solid; Reaction time, 16 hours; Yield, 91%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 11.93 (s, 1 H), 9.60 (brs, 2 H), 8.67 (d, 1 H, J = 8.0 Hz), 8.25 (d, 1 H, J = 7.6 Hz), 7.98 (t, 1 H, J = 7.6 Hz), 7.91 (d, 1 H, J = 8.0 Hz), 7.77-7.64 (m, 4 H), 7.56 (t, 1 H, J = 8.0 Hz), 7.49 (t, 1 H, J = 7.6 Hz), 7.39 (t, 1 H, J = 7.6 Hz), 4.50 (brs, 2 H), 3.35 (brs, 4 H), 3.23 (brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 162.9, 162.4, 160.0 (d, J = 248.0 Hz), 149.6, 141.6, 138.6, 134.8 (d, J = 9.1 Hz), 133.9, 131.4, 129.7, 128.8 , 126.8, 126.0, 125.0, 123.8 (d, J = 12.9 Hz), 122.2, 117.7 (d, J = 22.7 Hz), 114.8, 112.8, 54.2, 48.2, 41.6.

3- Fluoro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [3- Fluoro - N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (56f)

White solid; Reaction time, 17 hours; Yield, 88%; ¹ H NMR (400 MHz, DMSO- d ₆ + CD ₃ OD) δ 8.64 (d, 1 H, J = 8.0 Hz), 8.26 (d, 1 H, J = 7.6 Hz), 7.98 (d, 1 H, J = 7.6 Hz), 7.91 (d, 1 H, J = 7.6 Hz), 7.85-7.75 (m, 3 H), 7.70 (t, 1 H, J = 7.2 Hz), 7.59-7.51 (m, 2 H ), 7.39 (t, 1 H, J = 7.6 Hz), 4.58 (s, 2 H), 3.34 (brs, 4 H), 3.21 (brs, 4 H).

4- Fluoro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [4- Fluoro - N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (56g)

White solid; Reaction time, 15 hours; Yield, 96%; ¹ H NMR (500 MHz, DMSO- d ₆ + 2 drops of D ₂ O) δ 8.45 (d, 1 H, J = 8.5 Hz), 8.19 (dd, 1 H, J = 8.0, 1.5 Hz), 8.05 ( dd, 2 H, J = 8.5, 5.5 Hz), 7.78 (dd, 1 H, J = 8.0, 1.5 Hz), 7.61 (td, 1 H, J = 8.0, 1.5 Hz), 7.53 (dd, 1 H, J = 7.5, 1.5 Hz), 7.50 (t, 1 H, J = 8.0 Hz), 7.42 (t, 2 H, J = 8.5 Hz), 7.33 (td, 1 H, J = 7.5, 1.0 Hz), 4.36 (s, 2 H), 3.18 (t, 4 H, J = 4.8 Hz), 3.04 (s, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 165.6, 165.2 (d, J = 250.3 Hz), 162.6, 149.5, 141.1, 138.3, 133.9, 131.7, 130.8 (d, J = 8.4 Hz), 129.8, 127.9 , 126.2, 125.2, 122.1, 116.8 (d, J = 22.8), 115.1, 112.4, 55.4, 48.7, 41.7.

2- Bromo - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [2-Bromo- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56h)

White solid; Reaction time, 20 hours; Yield, 90%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.71 (s, 1 H), 9.65 (brs, 2 H), 8.56 (brd, 1 H, J = 7.5 Hz), 8.23 (d, 1 H, J = 8.0 Hz), 7.91 (d, 1 H, J = 8.5 Hz), 7.84 (d, 1 H, J = 7.5 Hz), 7.83 (d, 1 H, J = 7.5 Hz), 7.72 (t, 1 H , J = 7.5 Hz), 7.71 (d, 1 H, J = 7.5 Hz), 7.70 (t, 1 H, J = 7.5 Hz), 7.53 (t, 1 H, J = 7.5 Hz), 7.53 (t, 1 H, J = 7.5 Hz), 7.41 (t, 1 H, J = 7.5 Hz), 4.31 (brs, 2 H), 3.32 (brs, 4 H), 3.10 (brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 166.4, 162.5, 149.7, 141.4, 138.9, 138.4, 134.2, 134.0, 133.0, 129.8, 129.8, 129.1, 126.7, 125.2, 122.0, 119.6, 115.3, 113.0, 54.3 , 48.2, 41.6.

3- Bromo - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Bromo- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56i)

White solid; Reaction time, 21 hours; Yield, 88%; ¹ H NMR (400 MHz, DMSO- d ₆ ), δ 11.84 (s, 1 H), 9.47 (brs, 2 H), 8.58 (d, 1 H, J = 8.0 Hz), 8.25 (d, 1 H, J = 8.0 Hz), 8.14-8.12 (m, 2 H), 7.91-7.87 (m, 2 H), 7.77-7.68 (m, 3 H), 7.56 (t, 1 H, J = 7.6 Hz), 7.40 (t, 1 H, J = 7.6 Hz), 4.55 (brs, 2 H), 3.31 (brs, 4 H), 3.16 (brs, 4 H).

4- Bromo - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Bromo- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56j)

White solid; Reaction time, 26 hours; Yield, 90%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.92 (s, 1 H), 8.96 (brs, 2 H), 8.50 (brd, 1 H, J = 7.5 Hz), 8.22 (d, 1 H, J = 8.0 Hz), 7.95 (d, 2 H, J = 7.5 Hz), 7.83 (d, 2 H, J = 7.5 Hz), 7.79 (d, 1 H, J = 8.0 Hz), 7.65 (d, 1 H , J = 7.5 Hz), 7.56-7.49 (m, 2 H), 7.36 (t, 1 H, J = 7.5 Hz), 4.31 (s, 2 H), 3.16 (s, 4 H), 2.97 (s, 4 H).

2- Chloro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [2-Chloro- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56k)

White solid; Reaction time, 15 hours; Yield, 91%; ¹ H NMR (500 MHz, DMSO- d ₆ + 2 drops of D ₂ O) δ 8.47 (d, 1 H, J = 8.0 Hz), 8.21 (d, 1 H, J = 7.5 Hz), 7.82 (d, 1 H, J = 8.0 Hz), 7.77 (d, 1 H, J = 7.5 Hz), 7.67 (t, 1 H, J = 8.0 Hz), 7.64 (d, 1 H, J = 7.5 Hz), 7.61- 7.56 (m, 2 H), 7.53 (d, 1 H, J = 7.5 Hz), 7.49 (t, 1 H, J = 8.0 Hz), 7.38 (t, 1 H, J = 8.0 Hz), 4.20 (s , 2 H), 3.20 (brs, 4 H), 2.96 (brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 165.7, 162.5, 149.6, 141.0, 138.0, 136.5, 134.0, 133.0, 131.0, 130.6, 129.9, 129.8, 128.5, 128.3, 126.9, 125.5, 122.0, 115.2, 112.8 , 55.1, 48.4, 41.4.

3- Chloro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Chloro- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56l)

White solid; Reaction time, 17 hours; Yield, 91%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.84 (s, 1 H), 9.62 (brs, 2 H), 8.58 (d, 1 H, J = 8.0 Hz), 8.24 (d, 1 H, J = 8.0 Hz), 8.09 (d, 1 H, J = 7.5 Hz), 7.99 (s, 1 H), 7.90 (d, 1 H, J = 7.5 Hz), 7.83-7.77 (m, 2 H), 7.75 (d, 1 H, J = 8.0 Hz), 7.70 (t, 1 H, J = 8.0 Hz), 7.56 (td, 1 H, J = 8.0, 1.5 Hz), 7.39 (td, 1 H, J = 7.5 , 1.5 Hz), 4.56 (s, 2 H), 3.33 (brs, 4H), 3.22 (brs, 4 H).

4- Chloro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Chloro- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56m)

White solid; Reaction time, 21 hours; Yield, 93%; ¹ H NMR (500 MHz, DMSO- d ₆ + 2 drops of D ₂ O) δ 8.36 (d, 1 H, J = 7.5 Hz), 8.15 (d, 1 H, J = 8.0 Hz), 7.94 (d, 2 H, J = 7.5 Hz), 7.71 (d, 1 H, J = 7.5 Hz), 7.65-7.55 (m, 3 H), 7.47 (m, 2 H), 7.31 (t, 1 H, J = 7.5 Hz), 4.27 (s, 2 H), 3.14 (brs, 4 H), 2.96 (brs, 4 H); ¹³ C NMR (125 MHz, DMSO- d ₆ ) δ 164.7, 162.4, 149.4, 141.3, 138.4, 137.3, 134.3, 133.6, 132.7, 131.7, 129.5, 128.5, 128.0, 126.4, 124.8, 122.1, 115.2, 112.6, 54.3 , 48.1, 41.4.

3-Nitro- N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Nitro- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56n)

White solid; Reaction time, 15 hours; Yield, 91%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.44 (s, 1 H), 9.64 (brs, 2 H), 8.77 (s, 1 H), 8.70 (d, 1 H, J = 8.5 Hz), 8.57-8.55 (m, 2 H), 8.27 (d, 1 H, J = 8.0 Hz), 8.00 (t, 1 H, J = 8.0 Hz), 7.71-7.68 (m, 2 H), 7.47-7.42 ( m, 2 H), 7.40 (t, 1 H, J = 7.5 Hz), 3.75 (s, 2 H), 2.63 (brs, 4 H), 2.22 (brs, 4 H).

4-Nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol- 2 -yl ) phenyl) benzamide hydrochloride [4-Nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56o)

Ivory solid; Reaction time, 21 hours; Yield, 93%; ¹ H NMR (400 MHz, DMSO- d ₆ + 2 drops of D ₂ O) δ 8.23 (d, 2 H, J = 7.6 Hz), 8.12 (d, 1 H, J = 7.6 Hz), 8.00 (d, 1 H, J = 7.6 Hz), 7.95 (d, 2 H, J = 7.6 Hz), 7.56 (t, 1 H, J = 7.6 Hz), 7.38-7.42 (m, 3 H), 7.19 (t, 1 H, J = 7.6 Hz), 4.21 (s, 2 H), 3.16 (brs, 4 H), 3.01 (brs, 4 H).

3,4,5- Trimethoxy - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [3,4,5- Trimethoxy - N -(2- (4- ( piperazin -One- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56p)

White solid; Reaction time, 21 hours; Yield, 85%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 11.39 (brs, 1 H), 9.50 (brs, 2 H), 8.33 (d, 1 H, J = 7.2 Hz), 8.23 (d, 1 H, J = 7.6 Hz), 7.86 (d, 1 H, J = 7.6 Hz), 7.73-7.67 (m, 2 H), 7.52 (t, 1 H, J = 7.6 Hz), 7.40 (t, 1 H, J = 7.6 Hz), 7.31 (s, 2 H), 4.50 (brs, 2 H), 3.83 (s, 6 H), 3.78 (s, 3 H), 3.61 (brs, 4 H), 3.27 (brs, 4 H) ); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 166.0, 163.0, 153.6, 149.9, 141.9, 138.7, 133.6, 131.0, 130.2, 129.0, 128.7, 126.5, 125.2, 123.6, 117.2, 112.8, 106.7, 61.0, 57.3 , 54.5, 48.2, 41.5.

2,4- Dichloro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [2,4- Dichloro - N -(2- (4- ( piperazin -One- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56q)

White solid; Reaction time, 15 hours; Yield, 90%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.64 (s, 1 H), 9.64 (brs, 2 H), 8.45 (brd, 1 H, J = 8.0 Hz), 8.22 (d, 1 H, J = 8.0 Hz), 7.92-7.87 (m, 3 H), 7.77 (d, 1 H, J = 8.5 Hz), 7.73-7.69 (m, 2 H), 7.53 (t, 1 H, J = 8.0 Hz) , 7.42 (t, 1 H, J = 8.0 Hz), 4.39 (brs, 2 H), 3.35 (brs, 4 H), 3.19 (brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.7, 162.4, 149.8, 141.6, 138.1, 136.4, 135.6, 133.8, 132.1, 131.3, 130.6, 130.1, 128.8, 128.6, 126.7, 125.5, 122.7, 116.2, 112.8 , 54.5, 48.3, 41.6.

3,4- Dichloro - N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [3,4- Dichloro - N -(2- (4- ( piperazin -One- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56r)

White solid; Reaction time, 15 hours; Yield, 91%; ¹ H NMR (400 MHz, DMSO- d ₆ + 2 drops of D ₂ O) δ 8.42 (d, 1 H, J = 8.0 Hz), 8.20 (d, 1 H, J = 7.6 Hz), 8.12 (d, 1 H, J = 1.6 Hz), 7.97 (dd, 1 H, J = 8.4, 2.0 Hz), 7.88 (d, 1 H, J = 8.4 Hz), 7.80 (d, 1 H, J = 7.6 Hz), 7.64 (t, 1 H, J = 8.0 Hz), 7.57 (d, 1 H, J = 7.6 Hz), 7.51 (t, 1 H, J = 8.0 Hz), 7.37 (t, 1 H, J = 8.0 Hz) ), 4.39 (s, 2 H), 3.20 (brt, 4 H, J = 4.8 Hz), 3.04 (brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.2, 162.5, 149.6, 141.2, 137.9, 136.0, 135.5, 133.8, 132.7, 132.0, 130.1, 129.9, 128.1, 128.0, 126.9, 125.5, 122.9, 122.5, 115.8 , 115.4, 55.3, 48.6, 41.6.

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) nicotinamide hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride] (56s)

Ivory solid; Reaction time, 15 hours; Yield, 94%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.03 (s, 1 H), 9.81 (brs, 2 H), 9.46 (s, 1 H), 8.96 (d, 1 H, J = 5.5 Hz), 8.69 (d, 1 H, J = 8.5 Hz), 8.57 (d, 1 H, J = 8.5 Hz), 8.28 (d, 1 H, J = 8.5 Hz), 7.97 (t, 1 H, J = 5.5 Hz) ), 7.94 (d, 1 H, J = 8.0 Hz), 7.81 (d, 1 H, J = 8.0 Hz), 7.73 (t, 1 H, J = 8.0 Hz), 7.57 (td, 1 H, J = 8.0, 1.5 Hz), 7.43 (t, 1 H, J = 8.0 Hz), 4.66 (s, 2 H), 3.41 (s, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.0, 162.6, 151.2, 149.7, 146.9, 141.5, 138.9, 138.0, 134.0, 132.0, 130.0, 129.0, 127.0, 126.0, 125.7, 122.5, 120.5, 115.7, 113.4 , 54.9, 48.5, 40.7.

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Isoninicotinamide  Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) isonicotinamide hydrochloride] (56t)

Yellow solid; Reaction time, 15 hours; Yield, 91%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.00 (s, 1 H), 9.85 (brs, 2 H), 9.15 (d, 2 H, J = 6.0 Hz), 8.49 (d, 1 H, J = 8.5 Hz), 8.32 (d, 2 H, J = 6.0 Hz), 8.29 (d, 1 H, J = 8.0 Hz), 7.94 (d, 1 H, J = 7.5 Hz), 7.82 (d, 1 H , J = 8.0 Hz), 7.74 (t, 1 H, J = 8.0 Hz), 7.57 (t, 1 H, J = 8.0 Hz), 7.47 (t, 1 H, J = 7.5 Hz), 4.62 (s, 2 H), 3.39 (s, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 163.9, 162.6, 149.8, 147.6, 146.4, 141.5, 137.2, 133.9, 130.3, 128.7, 127.0, 126.4, 124.0, 123.4, 120.7, 116.8, 113.3, 55.0, 48.3 , 40.9.

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) -1- Naphthaamide  Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride] (56u)

White solid; Reaction time, 19 hours; Yield, 81%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.99 (s, 1 H), 9.49 (brs, 2 H), 8.72 (brd, 1 H, J = 7.5 Hz), 8.37 (d, 1 H, J = 8.5 Hz), 8.26 (d, 1 H, J = 7.5 Hz), 8.21 (d, 1 H, J = 8.0 Hz), 8.15 (d, 1 H, J = 7.5 Hz), 8.07 (d, 1 H , J = 7.5 Hz), 7.89-7.85 (m, 2 H), 7.75 (t, 1 H, J = 8.0 Hz), 7.68-7.58 (m, 3 H), 7.51 (t, 1 H, J = 8.0 Hz), 7.42 (t, 1 H, J = 8.0 Hz), 4.18 (s, 2 H), 3.19 (s, 4 H), 3.01 (s, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 167.6, 162.4, 149.3, 141.1, 138.8, 134.5, 133.8, 132.1, 130.1, 129.6, 129.1, 128.4, 127.7, 127.1, 126.4, 126.3, 125.9, 125.7, 124.6 , 121.7, 114.9, 112.5, 54.1, 47.9, 41.6.

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) -2- Naphthaamide  Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] (56v)

Ivory solid; Reaction time, 6 hours; Yield, 71%; ¹ H NMR (400 MHz, DMSO- d ₆ + 2 drops of D ₂ O), δ 8.12-8.10 (m, 2 H), 7.85-7.80 (m, 3 H), 7.77 (d, 1 H, J = 7.6 Hz), 7.63 (d, 1 H, J = 8.4 Hz), 7.56 (t, 1 H, J = 7.6 Hz), 7.50 (t, 1 H, J = 7.6 Hz), 7.45 (d, 1 H, J = 8.4 Hz), 7.29-7.25 (m, 2 H), 7.21 (d, 1 H, J = 7.6 Hz), 6.99 (t, 1 H, J = 8.0 Hz), 3.94 (s, 2 H), 2.88 (brs, 4 H), 2.48 (brs, 4 H).

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoline-2- Carboxamide  Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride] (56w)

Yellow solid; Reaction time, 12 hours; Yield, 57%; ¹ H NMR (400 MHz, D ₂ O) δ 7.81 (d, 1 H, J = 8.4 Hz), 7.78 (d, 1 H, J = 8.4 Hz), 7.58 (d, 1 H, J = 7.6 Hz) , 7.50 (d, 1 H, J = 7.6 Hz), 7.38 (d, 1 H, J = 8.0 Hz), 7.32-7.24 (m, 3 H), 7.15 (d, 1 H, J = 7.6 Hz), 7.01-6.93 (m, 3 H), 6.80 (t, 1 H, J = 7.6 Hz), 4.11 (s, 2 H), 3.04 (brs, 4 H), 2.77 (brs, 4 H).

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoxaline-2- Carboxamide Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) quinoxaline-2-carboxamide hydrochloride] (56x)

Yellow solid; Reaction time, 12 hours; Yield, 65%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.86 (s, 1 H), 9.67 (s, 1 H), 9.05 (brs, 2 H), 8.90 (d, 1 H, J = 8.4 Hz), 8.36 (d, 1 H, J = 7.6 Hz), 8.32 (d, 1 H, J = 7.6 Hz), 8.26 (d, 1 H, J = 7.6 Hz), 8.09-8.04 (m, 2 H), 7.93 (d, 1 H, J = 8.0 Hz), 7.77-7.73 (m, 2 H), 7.59 (t, 1 H, J = 8.0 Hz), 7.43 (t, 1 H, J = 8.0 Hz), 4.66 ( brs, 2 H), 3.31 (brs, 4 H), 3.11 (brs, 4 H).

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl)-(1,1'- Biphenyl ] -4-carboxamide Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl)-[1,1'-biphenyl] -4-carboxamide hydrochloride] (56y)

White solid; Reaction time, 15 hours; Yield, 89%; ¹ H NMR (400 MHz, DMSO- d ₆ : D ₂ O = 5: 3) δ 8.16 (d, 1 H, J = 8.8 Hz), 7.87 (d, 1 H, J = 8.4 Hz), 7.77 (d , 2 H, J = 8.0 Hz), 7.62 (d, 2 H, J = 8.0 Hz), 7.56 (d, 2 H, J = 8.0 Hz), 7.51 (dd, 1 H, J = 7.2, 1.6 Hz) , 7.46-7.31 (m, 6 H), 7.08 (t, 1 H, J = 7.6 Hz), 4.08 (s, 2 H), 3.04 (brs, 4 H), 2.86 (brs, 4 H).

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Cyclohexanecarboxamide Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (56z)

Pale ocher solid; Reaction time, 18 hours; Yield, 90%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.09 (s, 1 H), 9.95 (brs, 2 H), 8.49 (d, 1 H, J = 7.5 Hz), 8.18 (dd, 1 H, J = 8.0, 1.5 Hz), 7.93 (d, 1 H, J = 8.0 Hz), 7.81 (d, 1 H, J = 7.5 Hz), 7.61 (td, 1 H, J = 8.5, 1.5 Hz), 7.57 ( t, 1 H, J = 8.0 Hz), 7.29 (td, 1 H, J = 7.5, 1.0 Hz), 4.69 (s, 2 H), 3.48 (s, 8 H), 2.63 (m, 1 H), 2.04-2.00 (m, 2 H), 1.79-1.74 (m, 2 H), 1.64 (m, 1 H), 1.50-1.38 (m, 4 H), 1.21 (m, 1 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 175.3, 162.8, 149.6, 142.0, 139.2, 133.8, 129.7, 129.3, 126.7, 124.2, 121.8, 120.3, 114.4, 113.3, 54.3, 48.2, 46.0, 41.6, 29.9 , 26.1, 25.7.

N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Shinnamamide  Hydrochloride [ N -(2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride] (56A)

White solid; Reaction time, 15 hours; Yield, 80%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.38 (s, 1 H), 9.67 (brs, 2 H), 8.63 (d, 1 H, J = 8.0 Hz), 8.23 (d, 1 H, J = 8.5 Hz), 7.93 (d, 1 H, J = 8.0 Hz), 7.78 (d, 2 H, J = 8.0 Hz), 7.73 (brd, 1 H, J = 7.5 Hz), 7.68 (d, 1 H , J = 15.0 Hz), 7.66 (t, 1 H, J = 8.0 Hz), 7.56 (t, 1 H, J = 8.0 Hz), 7.49 (t, 2 H, J = 7.5 Hz), 7.43 (t, 1 H, J = 7.5 Hz), 7.34 (t, 1 H, J = 7.5 Hz), 7.25 (d, 1 H, J = 15.0 Hz), 4.78 (s, 2 H), 3.42 (brs, 8 H) ; ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.9, 162.3, 149.7, 142.0, 139.1, 135.3, 133.7, 130.7, 129.8, 128.9, 126.7, 124.6, 123.5, 122.2, 114.5, 113.0, 54.4, 48.2, 41.6 .

Phenyl (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Carbamate Hydrochloride [Phenyl (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) carbamate hydrochloride] (56B)

White solid; Reaction time, 15 hours; Yield, 89%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.25 (s, 1 H), 9.68 (brs, 2 H), 8.24 (d, 1 H, J = 7.5 Hz), 8.23 (d, 1 H, J = 7.5 Hz), 7.97 (d, 1 H, J = 8.0 Hz), 7.74 (brd, 1 H, J = 7.5 Hz), 7.68 (t, 1 H, J = 8.0 Hz), 7.58 (t, 1 H , J = 8.0 Hz), 7.43 (t, 2 H, J = 7.5 Hz), 7.35 (t, 1 H, J = 8.0 Hz), 7.33 (d, 2 H, J = 8.0 Hz), 7.28 (t, 1 H, J = 7.5 Hz), 4.67 (s, 2 H), 3.38 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 162.5, 152.3, 151.1, 149.7, 141.7, 138.6, 134.0, 130.2, 129.9, 129.5, 126.8, 126.5, 124.4, 122.7, 120.8, 114.6, 113.2, 54.6, 48.2 , 41.5.

1-2. Synthesis of compounds 57 to 70

As shown in Scheme 2, compounds 57 to 70 were synthesized.

[Scheme 2]

8) 3-Amino-4- Hydroxybenzoic acid [3-Amino-4- hydroxybenzoic  acid] (57)

Concentrated hydrochloric acid (12N-HCl, 1.5 mL) was added with tin (II) chloride (207 mg, 1.09 mmol) adjusted to 0 ° C., followed by 4-hydroxy-3-nitrobenzoic acid (4- Hydroxy-3-nitrobenzoic acid, 100 mg, 0.55 mmol) was added and stirred under reflux for 1 hour, then water was added and 2N-NaOH was added to adjust the pH to 1. The resulting solid was filtered, washed with water, and the filtrate was concentrated under reduced pressure, methanol was added, and then filtered again. The residue obtained by concentrating the filtrate under reduced pressure was purified by silica gel column chromatography (methylene chloride: methanol = 5: 1) to give compound 57 (82 mg, 98%) as a brown solid.

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.30 (brs, 1 H), 9.42 (brs, 3 H), 7.79 (s, 1 H), 7.60 (d, 1 H, J = 8.0 Hz), 7.07 (d, 1 H, J = 8.0 Hz).

9) ( E )-4- Hydroxy -3- (2- Nitrobenzylideneamino ) Benzoic acid [( E )-4- Hydroxy -3- (2-nitrobenzylideneamino) benzoic acid] (58)

A DMF ( N , N- dimethylformamide, 12 mL) solution containing compound 57 (1.25 g, 8.16 mmol) and 2-nitrobenzaldehyde (1-24 g, 8.21 mmol) was stirred at 80 ° C. for 3 hours. . DMF was removed under reduced pressure and water was added, then the resulting solid was filtered and washed with water to give compound 58 (1.33 g, 57%) as a solid.

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.58 (brs, 1 H), 10.09 (s, 1 H), 9.00 (s, 1 H), 8.38 (d, 1 H, J = 7.5 Hz), 8.10 (d, 1 H, J = 8.0 Hz), 7.87 (t, 1 H, J = 7.5 Hz), 7.76 (t, 1 H, J = 8.0 Hz), 7.73 (d, 1 H, J = 7.5 Hz) ), 7.72 (s, 1 H), 6.98 (d, 1 H, J = 8.5 Hz); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 167.7, 157.6, 156.0, 150.0, 138.3, 134.3, 132.5, 131.0, 130.5, 130.3, 125.1, 122.8, 121.9, 116.9.

10) 2- (2-nitrophenyl) benzo [ d ] Oxazole -5- Carboxylic acid [2- (2-Nitrophenyl) benzo [ d ] oxazole-5-carboxylic acid] (59)

DDQ (2,3-dichloro-5,6-dicyano- p- benzoquinone, 888 mg, 3.91 mmol) was added in small portions at room temperature into a DMF (10 mL) solution containing compound 58 (1.0 g, 3.49 mmol). . After the reaction mixture was stirred at room temperature overnight, DMF was distilled off under reduced pressure, water was added to filter the resulting solid, and washed with water to obtain compound 59 (551 mg, 55.5%) as a solid.

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 8.34 (d, 1 H, J = 1.5 Hz), 8.21 (dd, 1 H, J = 7.5, 1.5 Hz), 8.15 (dd, 1 H, J = 8.0, 1.5 Hz), 8.09 (dd, 1 H, J = 8.5, 2.0 Hz), 7.95 (td, 1 H, J = 8.0, 1.5 Hz), 7.93-7.89 (m, 2 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 167.4, 160.5, 153.7, 149.3, 141.7, 134.1, 132.2, 128.9, 128.4, 125.3, 122.2, 120.3, 112.0.

11) (2- (2-nitrophenyl) benzo [ d ] Oxazole -5-yl) methanol [(2- (2-Nitrophenyl) benzo [ d ] oxazol-5-yl) methanol] (60)

N , N -diisopropylethylamine ( N , N- diisopropylethylamine, 0.06 mL, 0.34 mmol) and ethyl chloroformate into anhydrous tetrahydrofuran (1 mL) solution containing compound 59 (100 mg, 0.35 mmol) ethyl chloroformate, 0.034 mL, 0.36 mmol) was added at 0 ° C, stirred for 1 hour, NaBH ₄ (13.3 mg, 0.35 mmol) was slowly added at 0 ° C, ethanol (0.5 mL) was added, and stirred for 12 hours. Did. After THF and ethanol were distilled off under reduced pressure, water and methylene chloride were added and extracted, the organic layer was dried over anhydrous MgSO ₄ and filtered, and the residue obtained by distilling the filtrate under reduced pressure was silica gel column chromatography (hexane: ethyl acetate) = 1: 1) to give compound 60 (56.6 mg, 59.5%).

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 8.18 (dd, 1 H, J = 8.0, 1.5 Hz), 8.10 (dd, 1 H, J = 8.0, 1.5 Hz), 7.91 (td, 1 H, J = 7.5, 1.5 Hz), 7.87 (td, 1 H, J = 7.5, 1.5 Hz), 7.75 (d, 1 H, J = 1.5 Hz), 7.73 (d, 1 H, J = 8.5 Hz), 7.43 (dd, 1 H, J = 8.5, 1.5 Hz), 5.34 (t, 1 H, J = 5.5 Hz), 4.62 (d, 2 H, J = 5.5 Hz); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 159.1, 150.0, 149.4, 141.6, 140.9, 133.9, 133.6, 131.8, 125.7, 125.1, 120.6, 118.5, 111.3, 63.4.

12) Turt - Butyl  4-((2- (2-nitrophenyl) benzo [ d ] Oxazole -5 days) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-nitrophenyl) benzo [ d ] oxazol -5-yl) methyl) piperazine-1-carboxylate] (61)

To a solution of methylene chloride (10 mL) containing compound 60 (196.4 mg, 0.73 mmol) was added triethylamine (0.15 mL, 1.08 mmol) and methanesulfonyl chloride (methanesulfonyl chloride, 0.06 mL, 0.77 mmol) at room temperature. After stirring for 15 minutes, after adding methylene chloride and saturated brine, the separated organic layer was dried over anhydrous Na ₂ SO ₄ and filtered, and the filtrate obtained was concentrated under reduced pressure to obtain a residue. To the residue in anhydrous THF (2 mL) was added tert-butyl piperazine-1-carboxylate (tert -butyl piperazine-1-carboxylate , 1-Boc-piperazine) containing anhydrous THF solution (2N solution, 2.0 mL, 4.0 mmol) was added, followed by stirring at room temperature for 6 hours. THF was distilled off under reduced pressure, methylene chloride and water were added, and then the organic layer was dried over anhydrous Na ₂ SO ₄ , filtered, and the resulting filtrate was concentrated under reduced pressure to yield the residue obtained by silica gel column chromatography (hexane: ethyl acetate). = 2: 1) to give compound 61 (318.8 mg, 100%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.13 (d, 1 H, J = 8.0 Hz), 7.88 (dd, 1 H, J = 7.5, 1.0 Hz), 7.76 (s, 1 H), 7.74 (t , 1 H, J = 8.0 Hz), 7.68 (td, 1 H, J = 8.0, 1.0 Hz), 7.51 (d, 1 H, J = 8.5 Hz), 7.40 (d, 1 H, J = 8.5 Hz) , 3.64 (s, 2 H), 3.45 (brs, 4 H), 2.43 (brs, 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.3, 155.0, 150.5, 149.4, 141.9, 135.2, 132.6, 132.1, 131.6, 127.4, 124.4, 121.7, 121.2, 110.8, 79.8, 63.0, 53.0, 44.0, 28.6.

13) Turt - Butyl  4-((2- (2-aminophenyl) benzo [ d ] Oxazole -5 days) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-aminophenyl) benzo [ d ] oxazol -5-yl) methyl) piperazine-1-carboxylate] (62)

compound 10 wt.% Pd / C (palladium on carbon, 60 mg) was added into a methanol (4 mL) solution containing 61 (297.6 mg, 0.68 mmol) and the air in the reaction vessel was replaced with hydrogen gas, and then 1.5 hours at room temperature. Stir for a while. Celite was used as a filter filler and the reaction mixture was filtered and washed with acetone and methanol. The residue obtained by concentrating the filtrate under reduced pressure was purified by silica gel column chromatography (methylene chloride: methanol = 40: 1) to obtain compound 62 (127.5 mg, 46%).

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 7.89 (d, 1 H, J = 8.0 Hz), 7.66 (d, 1 H, J = 7.5 Hz), 7.66 (s, 1 H), 7.31 (d , 1 H, J = 8.5 Hz), 7.25 (t, 1 H, J = 8.0 Hz), 7.09 (s, 2 H), 6.88 (d, 1 H, J = 8.5 Hz), 6.66 (t, 1 H , J = 8.0 Hz), 3.59 (s, 2 H), 2.33 (brs, 8 H), 1.37 (s, 9 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 163.7, 154.4, 149.5, 148.4, 142.0, 135.3, 133.3, 128.7, 126.6, 119.8, 116.7, 116.1, 110.7, 107.0, 79.4, 62.4, 52.9, 43.9, 28.7 .

14) Compound 63 (a to d) synthesis

Pyridine (5 equivalents) and appropriate acyl chloride (2 equivalents) were added into a methylene chloride solution containing compound 62 (1 equivalent) at room temperature and stirred for 30 minutes to 2 hours, followed by addition of methylene chloride and water After washing with sodium bicarbonate water, the organic layer was dried over anhydrous MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure to obtain the residue obtained by silica gel column chromatography (methylene chloride: methanol = 10: 1 to 30: 1). Purification gave compound 63 (a-d) (81.0-99.4%).

Turt - Butyl  4-((2- (2-benzamidophenyl) benzo [ d ] Oxazole -5 days) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-benzamidophenyl) benzo [ d ] oxazol -5-yl) methyl) piperazine-1-carboxylate] (63a)

Yield, 85%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.76 (s, 1 H), 9.06 (d, 1 H, J = 8.5 Hz), 8.27 (m, 3 H), 7.72 (brs, 1 H), 7.63- 7.58 (m, 5 H), 7.44 (brd, 1 H, J = 8.0 Hz), 7.25 (t, 1 H, J = 8.5 Hz), 3.69 (s, 2 H), 3.49 (brs, 4 H), 2.48 (brs, 4 H), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 162.7, 155.4, 148.7, 141.2, 139.7, 135.5, 135.3, 133.3, 132.2, 129.0, 128.6, 128.0, 123.3, 120.8, 120.0, 113.4, 110.6, 79.8, 63.0 , 53.0, 43.8, 28.6.

Turt - Butyl  4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] Oxazole -5-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] oxazol-5-yl) methyl) piperazine-1-carboxylate] (63b)

Yield, 99.4%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.56 (s, 1 H), 9.04 (d, 1 H, J = 8.5 Hz), 8.28 (dd, 1 H, J = 8.5, 1.5 Hz), 7.65 (s , 1 H), 7.60 (td, 1 H, J = 8.5, 1.5 Hz), 7.59 (d, 1 H, J = 8.5 Hz), 7.46 (s, 2 H), 7.41 (brd, 1 H, J = 8.5 Hz), 7.25 (t, 1 H, J = 8.5 Hz), 4.03 (s, 6 H), 3.97 (s, 3 H), 3.64 (s, 2 H), 3.46 (brs, 4 H), 2.44 (brs, 4 H), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.2, 162.8, 155.4, 153.5, 148.7, 141.7, 141.3, 139.7, 135.7, 133.3, 130.9, 128.7, 127.1, 123.3, 120.6, 119.6, 113.4, 110.5, 105.6, 79.8 , 63.0, 61.2, 56.7, 53.0, 44.0, 28.6.

Turt - Butyl  4-((2- (2- (2-naphthaamido) phenyl) benzo [ d ] Oxazole -5 days) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (2-naphthamido) phenyl) benzo [ d ] oxazol -5-yl) methyl) piperazine-1-carboxylate] (63c)

Yield, 95.3%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.97 (s, 1 H), 9.11 (d, 1 H, J = 8.5 Hz), 8.82 (s, 1 H), 8.32 (d, 1 H, J = 9.0 Hz), 8.29 (d, 1 H, J = 8.5 Hz), 8.09 (d, 1 H, J = 9.5 Hz), 8.06 (d, 1 H, J = 9.0 Hz), 7.97 (d, 1 H, J = 8.0 Hz), 7.79 (s, 1 H), 7.65-7.61 (m, 3 H), 7.59 (d, 1 H, J = 8.5 Hz), 7.42 (brd, 1 H, J = 8.5 Hz), 7.26 (t, 1 H, J = 8.0 Hz), 3.69 (s, 2 H), 3.49 (m, 4 H), 2.48 (m, 4 H), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 162.9, 155.0, 148.9, 141.3, 139.8, 135.3, 133.3, 133.0, 132.7, 129.4, 128.8, 128.8, 128.6, 128.2, 128.1, 127.0, 124.5, 123.3, 120.7 , 119.8, 113.4, 110.7, 79.8, 62.9, 53.0, 43.3, 28.6.

Turt - Butyl  4-((2- (2- (quinoxaline-2-carboxamido) phenyl) benzo [ d ] Oxazole -5 days) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (quinoxaline-2-carboxamido) phenyl) benzo [ d ] oxazol-5-yl) methyl) piperazine-1-carboxylate] (63d)

Yield, 81%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.77 (s, 1 H), 9.09 (d, 1 H, J = 8.4 Hz), 8.42 (m, 1 H), 8.28-8.22 (m, 2 H), 7.96-7.90 (m, 3 H), 7.60 (t, 1 H, J = 8.4 Hz), 7.57 (d, 1 H, J = 8.0 Hz), 7.39 (d, 1 H, J = 8.0 Hz), 7.28 (t, 1 H, J = 7.6 Hz), 3.72 (s, 2 H), 3.49 (m, 4 H), 2.48 (m, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.2, 162.4, 155.0, 149.1, 144.8, 144.5, 144.1, 141.8, 140.8, 138.6, 133.0, 132.0, 131.1, 130.1, 129.9, 128.8, 126.9, 124.0, 121.1, 120.0 , 114.5, 110.6, 80.0, 63.0, 53.0, 44.2, 28.6.

15) Compound 64 (a to d) synthesis

Trifluoroaetic acid (13 equivalents) was added into a methylene chloride solution containing compound 63 (1.0 equivalents) and stirred for 15 hours to 2 days. In the separation and purification method, in the case of compounds 64a and 64b , after neutralizing with sodium bicarbonate or 1N NaOH, methylene chloride and sodium bicarbonate are added, the separated organic layer is dried over anhydrous MgSO ₄ , filtered, and the filtrate is concentrated under reduced pressure. The obtained residue was obtained by purification by silica gel column chromatography (methylene chloride: methanol = 5: 1), and in the case of compound 64d , the volatile solvent was distilled off under reduced pressure, and the resulting solid was filtered and washed with water to obtain. In the case of compound 64c , after adding and neutralizing methylene chloride and sodium bicarbonate water, the organic layer was dried over anhydrous MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure to obtain a mixed solvent (hexane: methylene chloride = 3: 1). It was obtained by recrystallization.

N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide [ N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (64a)

Yield, 53%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.76 (s, 1 H), 9.06 (d, 1 H, J = 8.5 Hz), 8.27 (m, 3 H), 7.67 (s, 1 H), 7.64- 7.59 (m, 4 H), 7.58 (d, 1 H, J = 8.0 Hz), 7.39 (d, 1 H, J = 8.0 Hz), 7.25 (t, 1 H, J = 7.5 Hz), 3.69 (s , 2 H), 3.02 (t, 4 H, J = 5.0 Hz), 2.58 (brs, 4 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.8, 163.0, 148.8, 141.0, 138.9, 134.9, 134.2, 132.9, 132.3, 128.9, 128.5, 127.7, 127.1, 123.5, 120.5, 119.9, 113.4, 110.6, 62.6, 53.6 , 43.9.

3,4,5- Trimethoxy - N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide [3,4,5-Trimethoxy- N -(2- (5- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (64b)

Yield, 73%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.55 (s, 1 H), 9.03 (d, 1 H, J = 8.5 Hz), 8.26 (d, 1 H, J = 8.0 Hz), 7.63 (s, 1 H), 7.58 (t, 1 H, J = 8.0 Hz), 7.55 (d, 1 H, J = 8.5 Hz), 7.46 (s, 2 H), 7.37 (d, 1 H, J = 8.5 Hz), 7.24 (t, 1 H, J = 8.0 Hz), 4.03 (s, 6 H), 3.97 (s, 3 H), 3.61 (s, 2 H), 2.98 (t, 4 H, J = 4.5 Hz), 2.53 (brs, 4 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.1, 162.9, 153.5, 148.8, 141.7, 141.3, 139.6, 135.2, 133.3, 130.9, 128.7, 127.0, 123.3, 120.6, 119.6, 113.3, 110.7, 105.7, 63.1, 61.3 , 56.7, 52.0, 44.9.

N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) -2- Naphthaamide [ N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (64c)

Yield, 31.4%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.99 (s, 1 H), 9.11 (d, 1 H, J = 9.0 Hz), 8.83 (s, 1 H), 8.32 (d, 1 H, J = 8.5 Hz), 8.29 (d, 1 H, J = 8.5 Hz), 8.09 (m, 1 H), 8.05 (d, 1 H, J = 9.0 Hz), 7.97 (m, 1 H), 7.77 (s, 1 H), 7.65-7.63 (m, 2 H), 7.62 (t, 1 H, J = 7.5 Hz), 7.58 (d, 1 H, J = 8.5 Hz), 7.40 (d, 1 H, J = 8.5 Hz ), 7.26 (t, 1 H, J = 7.5 Hz), 3.67 (s, 2 H), 3.00 (brt, 4 H, J = 5.0 Hz), 2.57 (brs, 4 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 163.0, 148.7, 141.2, 139.7, 135.6, 135.3, 133.2, 133.0, 132.7, 129.4, 128.8, 128.6, 128.2, 128.1, 127.0, 124.5, 123.3, 120.7, 119.7 , 113.4, 110.6, 63.3, 53.7, 45.8.

N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoxaline-2- Kaboksami Episode 2,2,2- Trifluoroacetate [ N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) quinoxaline-2-carboxamide 2,2,2- trifluoroacetate ] (64d)

Yield, 55.1%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 13.65 (s, 1 H), 9.63 (s, 1 H), 8.99 (d, 1 H, J = 8.5 Hz), 8.73 (brs, 2 H), 8.39 (d, 1 H, J = 8.0 Hz), 8.28-8.25 (m, 2 H), 8.14 (t, 1 H, J = 7.5 Hz), 8.08 (t, 1 H, J = 7.5 Hz), 7.93 (s, 1 H), 7.83 (d, 1 H, J = 8.5 Hz), 7.71 (t, 1 H, J = 8.0 Hz), 7.47 (d, 1 H, J = 8.5 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 3.80 (s, 2 H), 3.11 (brm, 4 H), 2.68 (brm, 4 H).

16) Compound 65 and 66 synthesis

Triethylamine (Et ₃ N, 1.64 eq.) And methanesulfonyl chloride (sulhfonyl chloride, 1.18 eq.) At room temperature into a solution of methylene chloride (1.0 eq.) Containing compound 60 (5 mL per 100 mg weight of compound 60 ). After adding and stirring for 15 minutes, after adding methylene chloride and saturated brine, the organic layer was dried over anhydrous Na ₂ SO ₄ and filtered, and the filtrate obtained was concentrated under reduced pressure to obtain a residue. Anhydrous THF (1 mL per 100 mg weight of Compound 60 ) was added to the residue and anhydrous containing 1-methylpiperazine (5-45 equivalents) or 1-cyclohexylpiperazine (5-45 equivalents) THF solution was added and then stirred at room temperature for 1 hour. After distilling off the THF under reduced pressure, adding methylene chloride and water, drying the organic layer over anhydrous Na ₂ SO ₄ and filtering, the resulting filtrate was concentrated under reduced pressure to give the residue obtained by silica gel column chromatography (methylene chloride: methanol). = 30: 1) to give compound 65 (95.5%) and 66 (74.3%), respectively.

5-((4- Methylpiperazine -1 day) methyl )-2- (2-nitrophenyl) benzo [ d ] Oxazole [5-((4-Methylpiperazin-1-yl) methyl) -2- (2-nitrophenyl) benzo [ d ] oxazole] (65)

¹ H NMR (400 MHz, DMSO- d ₆ ) δ 8.12 (d, 1 H, J = 8.0 Hz), 8.06 (d, 1 H, J = 8.0 Hz), 7.85 (t, 1 H, J = 8.0 Hz ), 7.82 (t, 1 H, J = 8.0 Hz), 7.66 (s, 1 H), 7.65 (d, 1 H, J = 8.0 Hz), 7.34 (d, 1 H, J = 8.4 Hz), 3.50 (s, 2 H), 2.27 (brs, 8 H), 2.07 (s, 3 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 159.0, 150.1, 149.3, 141.7, 136.4, 133.7, 133.5, 131.7, 127.7, 125.0, 120.7, 120.5, 111.2, 62.3, 55.3, 53.0, 46.2.

5-((4- Cyclohexylpiperazine -1 day) methyl )-2- (2-nitrophenyl) benzo [ d ] Oxazole [5-((4-Cyclohexylpiperazin-1-yl) methyl) -2- (2-nitrophenyl) benzo [ d ] oxazole] (66)

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 8.18 (dd, 1 H, J = 7.5, 1.5 Hz), 8.10 (dd, 1 H, J = 7.5, 1.5 Hz), 7.91 (td, 1 H, J = 7.5, 1.5 Hz), 7.87 (td, 1 H, J = 8.0, 1.5 Hz), 7.72 (d, 1 H, J = 8.5 Hz), 7.71 (s, 1 H), 7.40 (dd, 1 H , J = 8.5, 1.5 Hz), 3.55 (s, 2 H), 2.48 (brs, 4 H), 2.36 (brs, 4 H), 2.15 (m, 1 H), 1.70 (m, 4 H), 1.53 (m, 1 H), 1.14 (m, 4 H), 1.26 (m, 1 H).

17) Synthesis of Compounds 67 and 68

10 wt.% Pd / C (palladium on carbon, 20 mg per 100 mg of starting material) into a methanol (compound 65 or 66 1 mL per 20 mg) solution containing compound 65 (1.0 eq) or 66 (1.0 eq) Was added and the air in the reaction vessel was replaced with hydrogen gas, and then stirred at room temperature for 2-3 hours. The reaction mixture was filtered using celite as a filter filler and washed with acetone. The filtrate was concentrated under reduced pressure to obtain compounds 67 (96.7%) and 68 (100%), respectively.

2- (5- ((4-methylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) aniline [2- (5- ( (4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) aniline] (67)

¹ H NMR (400 MHz, DMSO- d ₆ ) δ 7.86 (d, 1 H, J = 8.4 Hz), 7.61 (d, 1 H, J = 8.4 Hz), 7.60 (s, 1 H), 7.26 (d , 1 H, J = 8.4 Hz), 7.23 (t, 1 H, J = 7.6 Hz), 7.09 (s, 2 H), 6.86 (d, 1 H, J = 8.4 Hz), 6.63 (t, 1 H , J = 7.6 Hz), 3.51 (s, 2 H), 2.32 (brs, 8 H), 2.11 (s, 3 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 163.6, 149.5, 148.3, 141.9, 135.7, 133.2, 128.6, 126.4, 119.6, 116.7, 116.0, 110.5, 107.0, 62.5, 55.3, 53.0, 46.3.

2- (5- ((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) aniline [2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) aniline] (68)

¹ H NMR (500 MHz, DMSO- d ₆ ) δ 7.88 (d, 1 H, J = 8.0 Hz), 7.64 (d, 1 H, J = 8.5 Hz), 7.62 (s, 1 H), 7.28 (d , 1 H, J = 8.5 Hz), 7.24 (t, 1 H, J = 7.5 Hz), 7.09 (s, 2 H), 6.88 (d, 1 H, J = 8.0 Hz), 6.65 (t, 1 H , J = 7.5 Hz), 3.53 (s, 2 H), 2.46 (brs, 4 H), 2.36 (brs, 4 H), 2.15 (m, 1 H), 1.70 (m, 4 H), 1.52 (m , 1 H), 1.13 (m, 4 H), 1.03 (m, 1 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 163.6, 149.4, 148.3, 141.9, 135.7, 133.2, 128.6, 126.5, 119.7, 116.7, 116.1, 110.5, 107.0, 63.2, 62.6, 53.7, 49.0, 29.0, 26.5 , 25.9.

18) Synthesis of Compounds 69 and 70

Pyridine (5.0 equivalents) and appropriate acyl chloride (2.0 equivalents) were added to a methylene chloride solution containing compound 67 (1.0 equivalents) or 68 (1.0 equivalents) at room temperature, stirred for 30 minutes to overnight, and then methylene chloride After adding and washing with water and sodium bicarbonate, the organic layer was dried over anhydrous MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure to obtain the residue obtained by silica gel column chromatography (methylene chloride: methanol = 40: 1 to 12). Purified with: 1) to obtain compound 69 (a to d) (34.6 to 58.2%) and compound 70 (a to d) (50.2 to 96%) in the free acid state, respectively.

69 cc (HCl salt of compound 69c ): into a compound 69c (1.0 eq.), Was added 1,4-dioxane and 8N-HCl (42.0 eq.) In volumes corresponding to 8N-HCl (42.0 eq.), Respectively, The reaction mixture was stirred at room temperature for 4 hours. The solvent was distilled off under reduced pressure to obtain 69 cc of the compound in the form of HCl salt.

N -(2- (5- ((4-methylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide [ N -(2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (69a)

Yield, 34.6%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.03 (d, 1 H, J = 8.4 Hz), 8.25-8.24 (m, 3 H), 7.67 (s, 1 H), 7.61-7.57 (m, 4 H ), 7.54 (d, 1 H, J = 8.8 Hz), 7.38 (d, 1 H, J = 8.8 Hz), 7.22 (t, 1 H, J = 7.6 Hz), 3.63 (s, 2 H), 2.53 (brs, 8 H), 2.31 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 162.7, 148.7, 141.2, 139.6, 135.7, 135.5, 133.1, 132.1, 128.9, 128.6, 128.1, 127.2, 123.3, 120.7, 120.0, 113.4, 110.4, 63.0, 55.2 , 53.1, 46.1.

3,4,5- Trimethoxy - N -(2- (5- ((4-methylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide [3,4,5-Trimethoxy- N -(2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (69b)

Yield, 48.4%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.59 (s, 1 H), 9.05 (d, 1 H, J = 8.5 Hz), 8.28 (dd, 1 H, J = 8.5, 1.5 Hz), 7.66 (d , 1 H, J = 1.5 Hz), 7.59 (td, 1 H, J = 8.5, 1.5 Hz), 7.56 (d, 1 H, J = 8.5 Hz), 7.47 (s, 2 H), 7.37 (dd, 1 H, J = 8.5, 1.5 Hz), 7.25 (td, 1 H, J = 8.0, 1.5 Hz), 4.04 (s, 6 H), 3.98 (s, 3 H), 3.62 (s, 2 H), 2.51 (brs, 8 H), 2.30 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.1, 162.8, 153.5, 148.7, 141.7, 141.3, 139.6, 136.0, 133.2, 130.9, 128.7, 127.1, 123.3, 120.6, 119.5, 113.4, 110.5, 105.6, 63.0, 61.2 , 56.7, 55.3, 53.2, 46.2.

N -(2- (5- ((4-methylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) -2- Naphthaamide [ N -(2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (69c) and N -(2- (5- ((4-methylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) -2-naphthamide Hydrochloride [ N -(2- (5- ( (4- Methylpiperazin -1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] (69cc)

Compound 69c : yield, 58.2%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.97 (s, 1 H), 9.10 (d, 1 H, J = 8.5 Hz), 8.81 (s, 1 H), 8.31 (d, 1 H, J = 8.0 Hz), 8.27 (d, 1 H, J = 8.0 Hz), 8.09 (m, 1 H), 8.05 (d, 1 H, J = 9.0 Hz), 7.96 (m, 1 H), 7.76 (s, 1 H), 7.64 (m, 2 H), 7.61 (t, 1 H, J = 8.5 Hz), 7.57 (d, 1 H, J = 8.5 Hz), 7.40 (d, 1 H, J = 8.0 Hz), 7.26 (t, 1 H, J = 8.0 Hz), 3.69 (s, 2 H), 2.65 (brs, 8 H), 2.41 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 162.8, 148.8, 141.2, 139.7, 135.5, 135.3, 133.2, 133.0, 132.7, 129.4, 128.8, 128.8, 128.6, 128.1, 128.1, 127.1 (x2), 124.5, 123.3, 120.7, 119.8, 113.4, 110.6, 62.7, 55.0, 52.5, 45.6.

Compound 69cc : ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.53 (s, 1 H), 8.87 (d, 1 H, J = 8.0 Hz), 8.73 (s, 1 H), 8.30-8.27 (m , 5 H), 8.04 (m, 1 H), 7.92 (d, 1 H, J = 8.5 Hz), 7.74-7.70 (m, 4 H), 7.38 (td, 1 H, J = 8.0, 1.0 Hz) , 4.50 (s, 2 H), 3.46 (brs, 8 H), 2.82 (s, 3 H).

N -(2- (5- ((4-methylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoxaline-2-carboxamide [ N -(2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide] (69d)

Yield, 51.5%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.78 (s, 1 H), 9.10 (d, 1 H, J = 8.4 Hz), 8.44 (dd, 1 H, J = 8.0, 1.2 Hz), 8.28 (dd , 1 H, J = 8.0, 1.2 Hz), 8.25 (dd, 1 H, J = 8.4, 1.6 Hz), 7.99 (td, 1 H, J = 8.4, 1.6 Hz), 7.97 (td, 1 H, J = 8.0, 1.6 Hz), 7.91 (d, 1 H, J = 1.2 Hz), 7.61 (td, 1 H, J = 8.4, 1.2 Hz), 7.57 (d, 1 H, J = 8.0 Hz), 7.39 ( dd, 1 H, J = 8.4, 1.2 Hz), 7.29 (td, 1 H, J = 8.0, 1.2 Hz), 3.71 (s, 2 H), 2.61 (brs, 8 H), 2.35 (s, 3 H ).

N -(2- (5- ((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide [ N -(2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (70a)

Yield, 52.6%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.79 (s, 1 H), 9.06 (d, 1 H, J = 8.5 Hz), 8.27 (m, 3 H), 7.68 (s, 1 H), 7.63- 7.58 (m, 4 H), 7.56 (d, 1 H, J = 8.5 Hz), 7.39 (d, 1 H, J = 8.0 Hz), 7.25 (t, 1 H, J = 8.0 Hz), 3.66 (s , 2 H), 2.69 (brs, 4 H), 2.62 (brs, 4 H), 2.34 (m, 1 H), 1.95 (brm, 2 H), 1.80 (brm, 2 H), 1.63 (m, 1 H), 1.24 (m, 4 H), 1.12 (m, 1 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 162.7, 148.7, 141.2, 139.7, 135.5, 133.2, 132.1, 129.0, 128.5, 128.0, 127.3, 123.3, 120.7, 120.1, 113.5, 110.4, 64.0, 63.0, 53.2 , 49.0, 28.9, 26.3, 26.0.

N -(2- (5- ((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) -3,4,5-trimethoxybenzamide [ N -(2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -3,4,5-trimethoxybenzamide] (70b)

Yield, 61.4%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.58 (s, 1 H), 9.04 (d, 1 H, J = 9.0 Hz), 8.28 (d, 1 H, J = 8.0 Hz), 7.65 (s, 1 H), 7.59 (t, 1 H, J = 8.5 Hz), 7.56 (d, 1 H, J = 8.5 Hz), 7.47 (s, 2 H), 7.36 (d, 1 H, J = 8.5 Hz), 7.25 (t, 1 H, J = 8.0 Hz), 4.03 (s, 6 H), 3.98 (s, 3 H), 3.63 (s, 2 H), 2.66 (brs, 4 H), 2.56 (brs, 4 H), 2.32 (m, 1 H), 1.93 (brm, 2 H), 1.79 (brm, 2 H), 1.63 (brm, 1 H), 1.25 (brm, 4 H), 1.11 (m, 1 H) ; ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.1, 162.8, 153.5, 148.7, 141.7, 141.3, 139.6, 135.7, 133.2, 130.9, 128.7, 127.1, 123.3, 120.6, 119.6, 113.4, 110.5, 105.6, 64.2, 62.8 , 61.2, 56.7, 52.9, 49.0, 28.6, 26.2, 25.9.

N -(2- (5- ((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) -2-naphthamide [ N -(2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (70c)

Yield, 96.0%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.98 (s, 1 H), 9.11 (d, 1 H, J = 8.5 Hz), 8.82 (s, 1 H), 8.32 (d, 1 H, J = 9.0 Hz), 8.28 (d, 1 H, J = 8.0 Hz), 8.09 (m, 1 H), 8.06 (d, 1 H, J = 9.0 Hz), 7.97 (m, 1 H), 7.75 (s, 1 H), 7.65-7.63 (m, 2 H), 7.62 (t, 1 H, J = 9.0 Hz), 7.57 (d, 1 H, J = 8.0 Hz), 7.39 (d, 1 H, J = 8.0 Hz ), 7.26 (t, 1 H, J = 8.0 Hz), 3.70 (s, 2 H), 2.72 (brs, 8 H), 2.30 (brm, 1 H), 2.02 (m, 2 H), 1.83 (brm , 2 H), 1.65 (brm, 1 H), 1.25 (brm, 4 H), 1.13 (m, 1 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.5, 163.0, 148.9, 141.4, 139.8, 135.3, 134.8, 133.4, 133.1, 132.7, 129.4, 129.0, 128.8, 128.6, 128.2, 128.1, 127.2, 127.0, 124.3, 123.3 , 120.8, 119.9, 113.3, 110.8, 64.0, 62.9, 52.7, 48.7, 29.9, 26.7, 25.3.

N -(2- (5- ((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoxaline-2-carboxamide [ N -(2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide] (70d)

Yield, 50.2% ;; ¹ H NMR (500 MHz, CDCl ₃ ) δ 13.81 (s, 1 H), 9.79 (s, 1 H), 9.11 (d, 1 H, J = 9.0 Hz), 8.44 (d, 1 H, J = 7.5 Hz), 8.28 (dd, 1 H, J = 8.0, 1.5 Hz), 8.26 (d, 1 H, J = 8.0 Hz), 8.01 (td, 1 H, J = 8.0, 1.0 Hz), 7.95 (td, 1 H, J = 8.5, 1.5 Hz), 7.88 (s, 1 H), 7.62 (td, 1 H, J = 8.0, 1.5 Hz), 7.58 (d, 1 H, J = 8.0 Hz), 7.40 (dd , 1 H, J = 8.5, 1.0 Hz), 7.30 (t, 1 H, J = 8.0 Hz), 3.73 (s, 2 H), 2.73 (brs, 8 H), 2.44 (brm, 1 H), 1.99 (m, 2 H), 1.82 (brm, 2 H), 1.64 (brm, 1 H), 1.26 (m, 4 H), 1.11 (m, 1 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.2, 162.3, 149.0, 144.8, 144.5, 144.1, 141.7, 140.8, 138.6, 135.3, 132.9, 132.0, 131.3, 130.1, 129.9, 128.8, 127.0, 124.0, 121.1, 120.2 , 114.6, 110.6, 64.3, 62.9, 52.7, 49.1, 28.6, 26.1, 25.9.

1-3. Compound 70e synthesis

Compound 70e was synthesized as in Scheme 3 below.

[Scheme 3]

( E )-4- methyl -2-((2- Nitrobenzylidene ) Amino) phenol [( E ) -4-Methyl-2-((2-nitrobenzylidene) amino) phenol] (70-1)

DMF ( N , N- dimethylformamide) containing 2-amino-4-methylphenol (2-amino-4-methylphenol, 5.0 g, 40.60 mmol) and 2-nitrobenzaldehyde (5-828 g, 38.57 mmol) , 30 mL) The solution was heated and stirred at 80 ° C. for 90 minutes, and then the DMF was concentrated under reduced pressure to remove the remaining small amount of DMF by freeze drying. Isopropyl alcohol / diethyl ether (1: 1) and a small amount of water were added to the residue to make a solid, filtered and washed with water to obtain compound 70-1 (7.135 g, 68.6%) as a solid.

¹ H NMR (500 MHz, CDCl ₃ ) δ 9.14 (s, 1 H), 8.26 (d, 1 H, J = 8.0 Hz), 8.06 (d, 1 H, J = 8.5 Hz), 7.74 (t, 1 H, J = 7.5 Hz), 7.63 (td, 1 H, J = 7.0, 1.0 Hz), 7.15 (s, 1 H), 7.06 (dd, 1 H, J = 8.0, 1.5 Hz), 6.97 (s, 1 H), 6.92 (d, 1 H, J = 8.0 Hz), 2.32 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 151.7, 150.8, 149.5, 134.4, 133.6, 131.5, 131.1, 130.8, 129.9, 129.7, 124.9, 116.9, 115.3, 21.0.

5- methyl -2- (2-nitrophenyl) benzo [ d ] Oxazole [5-Methyl-2- (2-nitrophenyl) benzo [ d ] oxazole] (70-2)

Add DDQ (2,3-dichloro-5,6-dicyano- p- benzoquinone, 6.32 g, 27.84 mmol) into a methylene chloride (130 mL) solution containing compound 70-1 (7.135 g, 27.84 mmol) and add to room temperature The mixture was stirred for 12 hours. The reaction mixture was filtered, the filtrate was diluted with methylene chloride, washed with sodium bicarbonate, and the organic layer was dried over anhydrous MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure to give compound 70-2 (6.53 g, 92.2%). Got.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.09 (d, 1 H, J = 7.6 Hz), 7.85 (d, 1 H, J = 8.0 Hz), 7.70 (t, 1 H, J = 7.6 Hz), 7.64 (t, 1 H, J = 7.6 Hz), 7.56 (s, 1 H), 7.41 (d, 1 H, J = 8.4 Hz), 7.18 (d, 1 H, J = 8.4 Hz), 2.46 (s , 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.0, 149.5, 149.3, 141.9, 135.1, 132.5, 131.9, 131.5, 127.4, 124.4, 121.4, 120.7, 110.5, 21.7.

5- ( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] Oxazole [5- ( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] oxazole] (70-3)

NBS ( N- bromosuccinimide, 4.34 g, 24.38 mmol) and benzoyl peroxide (311 mg, 1.28 mmol) were slowly added sequentially into a chloroform (60 mL) solution containing compound 70-2 (6.53 g, 25.68 mmol) and 24 It was stirred at reflux for an hour. After cooling, the mixture was added with methylene chloride and water as a reaction mixture, and then the organic layer was dried over anhydrous MgSO ₄ and filtered. The filtrate was concentrated under reduced pressure, diethyl ether was added to form a solid, and filtered, and diethyl ether Washed with to give compound 70-3 (6.38 g, 74.6%) as a solid.

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.12 (dd, 1 H, J = 8.0, 1.5 Hz), 7.91 (dd, 1 H, J = 8.0, 1.0 Hz), 7.84 (d, 1 H, J = 1.5 Hz), 7.75 (td, 1 H, J = 7.5, 1.5 Hz), 7.70 (td, 1 H, J = 7.5, 1.5 Hz), 7.54 (d, 1 H, J = 8.5 Hz), 7.45 (dd , 1 H, J = 8.5, 1.5 Hz), 4.64 (s, 2 H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 159.8, 150.8, 149.2, 141.8, 135.0, 132.4, 132.0, 131.4, 127.3, 124.3, 121.3, 121.2, 111.3, 33.3.

1-((2- (2-nitrophenyl) benzo [ d ] Oxazole -5 days) methyl ) Piperidine-4-one [1-((2- (2-Nitrophenyl) benzo [ d ] oxazol-5-yl) methyl) piperidin-4-one] (70-4)

Anhydrous acetonitrile containing 4-piperidone monohydrate hydrochloride (207 mg, 1.35 mmol) into anhydrous acetonitrile (8 mL) solution containing compound 70-3 (500 mg, 1.50 mmol) (3 mL) and K ₂ CO ₃ (467 mg, 3.38 mmol) were added slowly at room temperature, followed by stirring at reflux for 5 hours. After cooling to room temperature, the residue obtained by filtration and concentration of the filtrate under reduced pressure was purified by silica gel column chromatography (methylene chloride: methanol = 40: 1) to obtain compound 70-4 (428 mg, 81.2%).

¹ H NMR (500 MHz, CDCl ₃ ) δ 8.13 (d, 1 H, J = 8.0 Hz), 7.89 (d, 1 H, J = 8.0 Hz), 7.80 (s, 1 H), 7.74 (t, 1 H, J = 7.5 Hz), 7.69 (t, 1 H, J = 7.5 Hz), 7.53 (d, 1 H, J = 8.0 Hz), 7.43 (d, 1 H, J = 8.0 Hz), 3.74 (s , 2 H), 2.78 (t, 4 H, J = 6.0 Hz), 2.46 (t, 4 H, J = 6.0 Hz); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 209.5, 159.4, 150.6, 149.4, 142.0, 135.7, 132.6, 132.2, 131.6, 127.1, 124.4, 121.6, 120.9, 110.9, 62.0, 53.1, 41.6.

1-((2- (2-aminophenyl) benzo [ d ] Oxazole -5 days) methyl ) Piperidine-4-one [1-((2- (2-Aminophenyl) benzo [ d ] oxazol-5-yl) methyl) piperidin-4-one] (70-5)

10 wt.% Pd / C (palladium on carbon, 40 mg) was added into a methylene chloride (8.0 mL) solution containing compound 70-4 (400 mg, 1.14 mmol), and the air in the reaction vessel was replaced with hydrogen gas. Stir at room temperature for 8 hours. Celite was used as a filter filler and the reaction mixture was filtered and washed thoroughly with methylene chloride. The filtrate was concentrated under reduced pressure to give compound 70-5 (326 mg, 89.1%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (d, 1 H, J = 8.0 Hz), 7.70 (s, 1 H), 7.51 (d, 1 H, J = 8.0 Hz), 7.32 (d, 1 H, J = 8.0 Hz), 7.27 (t, 1 H, J = 7.6 Hz), 6.80 (d, 1 H, J = 8.0 Hz), 6.79 (t, 1 H, J = 7.6 Hz), 6.20 (s , 2 H), 3.73 (s, 2 H), 2.78 (t, 4 H, J = 6.0 Hz), 2.47 (t, 4 H, J = 6.0 Hz); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 209.7, 163.8, 148.8, 148.1, 142.3, 134.8, 132.7, 128.9, 125.8, 119.7, 117.0, 116.5, 110.1, 108.8, 62.1, 53.1, 41.6.

N- (2- (5- ((4-Oxopiperidin-1-yl) methyl) benzo [ d ] oxazol- 2 -yl ) phenyl) -2- naphthaamide [ N- (2- (5 -((4-Oxopiperidin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (70e)

Pyridine (0.1 mL, 1.29 mmol) and 2-naphthoyl chloride (95 mg, 0.48 mmol) into an anhydrous methylene chloride solution (3.0 mL) containing compound 70-5 (120 mg, 0.37 mmol). After adding at room temperature and stirring for 12 hours, methylene chloride was added, and after washing with water and sodium bicarbonate, respectively, the organic layer was dried over anhydrous MgSO ₄ , filtered, and the residue obtained by concentrating the filtrate under reduced pressure was a silica gel column. Purification by chromatography (methylene chloride: methanol = 40: 1) gave compound 70e (160 mg, 90%).

¹ H NMR (400 MHz, CDCl ₃ ) δ 12.96 (s, 1 H), 9.10 (dd, 1 H, J = 8.0, 0.8 Hz), 8.80 (d, 1 H, J = 0.8 Hz), 8.30 (dd , 1 H, J = 8.4, 1.6 Hz), 8.28 (dd, 1 H, J = 8.0, 1.6 Hz), 8.07 (d, 1 H, J = 8.0 Hz), 8.03 (d, 1 H, J = 8.4 Hz), 7.95 (d, 1 H, J = 8.0 Hz), 7.78 (d, 1 H, J = 1.6 Hz), 7.65-7.56 (m, 4 H), 7.44 (dd, 1 H, J = 8.0, 1.6 Hz), 7.26 (td, 1 H, J = 7.6, 1.2 Hz), 3.78 (s, 2 H), 2.83 (t, 4 H, J = 6.0 Hz), 2.50 (t, 4 H, J = 6.0 Hz).

1-4. Synthesis of Compounds 71 to 77

Compounds 71 to 77 were synthesized as in Scheme 4 below.

[Reaction Scheme 4]

19) ( E ) -5- methyl -2- (2- Nitrobenzylideneamino )phenol[( E ) -5-Methyl-2- (2-nitrobenzylideneamino) phenol] (71)

Anhydrous DMF ( N , N- dimethylformamide, in 2-amino-5-methylphenol (20.0 g, 162.4 mmol) and 2-nitrobenzaldehyde, 23.3 g, 154 mmol) 110 mL) was added, stirred at 80 ° C. for 1 hour and 20 minutes, then cooled at room temperature, followed by addition of a mixed solvent of isopropyl alcohol / diethyl ether (1: 1, 200 mL) and water (150 mL). After stirring, the resulting solid was filtered and washed with water to give compound 71 (38.2 g, 92%) as a dark yellow solid.

¹ H NMR (400 MHz, CDCl ₃ ) δ 9.09 (s, 1 H), 8.21 (d, 1 H, J = 8.0 Hz), 8.00 (d, 1 H, J = 8.0 Hz), 7.69 (t, 1 H, J = 7.2 Hz), 7.57 (t, 1 H, J = 7.2 Hz), 7.22 (d, 1 H, J = 8.0 Hz), 7.12 (s, 1 H), 6.81 (s, 1 H), 6.70 (d, 1 H, J = 8.0 Hz), 2.31 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 152.9, 150.6, 149.5, 141.2, 133.6, 132.4, 131.3, 130.9, 129.6, 124.9, 121.4, 116.2, 116.1, 21.8.

20) 6- methyl -2- (2-nitrophenyl) benzo [ d ] Oxazole [6-Methyl-2- (2-nitrophenyl) benzo [ d ] oxazole] (72)

DDQ (2,3-dichloro-5,6-dicyano- p- benzoquinone, 33.79 g, 0.149 mmol) was added in small portions into anhydrous methylene chloride solution (720 mL) containing compound 71 (38.2 g, 0.15 mol). . After stirring at room temperature for 3 hours and 30 minutes, after diluting with methylene chloride, water and sodium bicarbonate were added and the separated organic layer was dried over anhydrous MgSO ₄ , filtered and the filtrate was concentrated under reduced pressure to give compound 72 (34.8 g , 92%) as a yellow solid.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.09 (dd, 1 H, J = 7.6, 1.2 Hz), 7.83 (dd, 1 H, J = 7.6, 1.2 Hz), 7.69 (td, 1 H, J = 7.6, 1.2 Hz), 7.64-7.60 (m, 2 H), 7.33 (s, 1 H), 7.16 (d, 1 H, J = 8.0 Hz), 2.46 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 158.4, 151.5, 149.3, 139.5, 136.9, 132.5, 131.8, 131.5, 126.5, 124.3, 121.7, 120.2, 111.2, 22.1.

21) 6- ( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] Oxazole [6- ( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] oxazole] (73)

NBS ( N- bromosuccinimide, 11.2 g, 62.9 mmol) and benzoyl peroxide (0.76 g, 3.1 mmol) were slowly added into an anhydrous chloroform (70 mL) solution containing compound 72 (16.0 g, 0.06 mol), followed by 25 hours. While stirring at reflux. After adding methylene chloride and water, the organic layer was dried over anhydrous MgSO ₄ and filtered to concentrate the filtrate under reduced pressure, and the residue obtained was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to obtain compound 73 ( 11.1 g, 53%) as a beige solid.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.12 (dd, 1 H, J = 7.6, 1.6 Hz), 7.89 (dd, 1 H, J = 8.0, 1.6 Hz), 7.76 (d, 1 H, J = 8.4 Hz), 7.74 (td, 1 H, J = 8.0, 1.6 Hz), 7.69 (td, 1 H, J = 7.6, 1.6 Hz), 7.61 (d, 1 H, J = 1.6 Hz), 7.43 (dd , 1 H, J = 8.4, 1.6 Hz), 4.63 (s, 2 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 160.0, 151.2, 149.3, 141.9, 136.4, 132.7, 132.3, 131.6, 126.5, 124.5, 121.4, 121.1, 111.8, 33.5.

22) Turt - Butyl  4-((2- (2-nitrophenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-nitrophenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (74)

Tert -butyl piperazine-1-carboxylate ( tert -butyl) into an anhydrous THF (70 mL) solution containing compound 73 (11.1 g, 30 mmol) and anhydrous triethylamine (Et ₃ N, 13.0 mL, 93.3 mmol). Anhydrous THF (40 mL) solution containing piperazine-1-carboxylate, 1-Boc-piperazine, 5.6 g, 30.0 mmol) was slowly added. After stirring at room temperature for 33 hours, methylene chloride and water were added, and the organic layer was dried over anhydrous MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure to obtain a residue obtained by silica gel column chromatography (methylene chloride: methanol = 50: Purification with 1) gave compound 74 (11.1 g, 53%) as a beige solid.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.08 (dd, 1 H, J = 7.2, 1.2 Hz), 7.83 (dd, 1 H, J = 8.0, 1.2 Hz), 7.69 (td, 1 H, J = 7.2, 1.6 Hz), 7.60 (d, 1 H, J = 7.6 Hz), 7.63 (td, 1 H, J = 8.0, 1.6 Hz), 7.53 (s, 1 H), 7.31 (d, 1 H, J = 8.4 Hz), 3.59 (s, 2 H), 3.40 (brt, 4 H, J = 4.4 Hz), 2.37 (brs, 4 H), 1.41 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.1, 155.0, 151.5, 149.3, 141.0, 137.0, 132.6, 132.0, 131.5, 126.2, 124.4, 121.7, 120.3, 111.4, 79.8, 63.1, 53.1, 43.3, 28.6.

23) Turt - Butyl  4-((2- (2-aminophenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-aminophenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (75)

10 wt.% Pd / C (palladium on carbon, 300 mg) was added into a solution of compound 74 (3.0 g, 6.84 mmol) in methylene chloride (50 mL), and the air in the reaction vessel was replaced with hydrogen gas, followed by 4 hours at room temperature. Stir for a while. The reaction mixture was filtered using celite as a filter filler, and the filtrate was concentrated under reduced pressure to obtain compound 75 (2.749 g, 98.4%) as a beige solid.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, 1 H, J = 8.4 Hz), 7.62 (d, 1 H, J = 8.0 Hz), 7.56 (s, 1 H), 7.29-7.24 (m , 2 H), 6.80-6.76 (m, 2 H), 6.17 (s, 2 H), 3.65 (s, 2 H), 3.45 (brt, 4 H, J = 4.8 Hz), 2.44 (brs, 4 H ), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.5, 155.0, 149.7, 148.0, 141.4, 135.2, 132.6, 128.8, 125.6, 119.0, 117.0, 116.4, 110.9, 108.9, 79.9, 63.2, 53.1, 43.8, 28.7.

24) Compound 76 (a to z, and A and B) synthesis

Add appropriate acyl chloride (1.2 to 1.5 equivalents) or p -toluenesulfonyl chloride (1.3 equivalents) and anhydrous pyridine (5 equivalents) into an anhydrous methylene chloride (5 mL) solution containing compound 75 (100 mg, 0.24 mmol) Then, it was stirred at room temperature. Methylene chloride and sodium bicarbonate water were added to the reaction mixture, and the organic layer was dried over anhydrous MgSO ₄ , filtered, and the residue obtained by concentrating the filtrate under reduced pressure was subjected to silica gel column chromatography (methylene chloride: methanol = 40: 1-80: 1). ), Or recrystallized by adding acetone to the obtained material after column chromatography to obtain compound 76 (a to z, and A and B) as a solid.

Turt - Butyl  4-((2- (2-benzamidophenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-benzamidophenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (76a)

White solid; Reaction time, 7 hours; Yield, 39.8%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.79 (s, 1 H), 9.05 (d, 1 H, J = 8.4 Hz), 8.26-8.23 (m, 3 H), 7.67 (d, 1 H, J = 8.0 Hz), 7.65 (brs, 1 H), 7.61-7.55 (m, 4 H), 7.37 (d, 1 H, J = 8.0 Hz), 7.24 (t, 1 H, J = 8.0 Hz), 3.68 (s, 2 H), 3.47 (brs, 4 H), 2.46 (brs, 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 162.6, 155.0, 149.7, 140.3, 139.6, 135.5, 133.2, 132.2, 128.9, 128.5, 128.1, 126.3, 123.3, 120.7, 119.1, 113.4, 111.4, 80.0, 63.1 , 53.1, 43.6, 28.7.

Turt - Butyl  4-((2- (2- (2-methylbenzamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (2-methylbenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76b)

White solid; Reaction time, 5 hours; Yield, 59.8%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.37 (s, 1 H), 9.04 (d, 1 H, J = 8.5 Hz), 8.25 (d, 1 H, J = 8.0 Hz), 7.82 (d, 1 H, J = 7.5 Hz), 7.61-7.61 (s, 1 H), 7.59 (t, 1 H, J = 8.0 Hz), 7.51 (d, 1 H, J = 8.5 Hz), 7.43 (t, 1 H , J = 8.0 Hz), 7.37-7.29 (m, 3 H), 7.25 (t, 1 H, J = 8.0 Hz), 3.64 (s, 2 H), 3.44 (brt, 4 H, J = 4.5 Hz) , 2.63 (s, 3 H), 2.42 (brt, 4 H, J = 4.5 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 168.9, 162.3, 155.0, 149.7, 140.3, 139.6, 137.8, 136.8, 136.7, 133.0, 131.8, 130.7, 128.5, 127.9, 126.0, 123.3, 120.6, 119.2, 113.4, 111.1 , 79.9, 63.2, 53.1, 43.8, 28.7, 20.7.

Turt - Butyl  4-((2- (2- (3-methylbenzamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (3-methylbenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76c)

White solid; Reaction time, 5 hours; Yield, 62.4%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.77 (s, 1 H), 9.06 (dd, 1 H, J = 8.8, 1.2 Hz), 8.25 (dd, 1 H, J = 8.0, 1.6 Hz), 8.10 (s, 1 H), 8.06 (d, 1 H, J = 7.6 Hz), 7.67 (d, 1 H, J = 8.0 Hz), 7.64 (d, 1 H, J = 1.2 Hz), 7.58 (td, 1 H, J = 8.0, 1.6 Hz), 7.47 (t, 1 H, J = 7.6 Hz), 7.42 (brd, 1 H, J = 7.6 Hz), 7.37 (dd, 1 H, J = 8.0, 1.6 Hz ), 7.23 (t, 1 H, J = 7.6 Hz), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.54 (s, 3 H), 2.43 (brt, 4 H) , J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.6, 162.6, 155.0, 149.7, 140.3, 139.7, 138.6, 136.9, 135.4, 133.2, 132.9, 128.8, 128.7, 128.5, 126.2, 125.3, 123.2, 120.7, 119.0, 113.4 , 111.3, 79.9, 63.2, 53.1, 43.4, 28.7, 21.8.

Turt - Butyl  4-((2- (2- (4-methylbenzamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (4- methylbenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76d)

White solid; Reaction time, 5 hours; Yield, 60.5%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.74 (s, 1 H), 9.05 (dd, 1 H, J = 8.0, 1.2 Hz), 8.25 (dd, 1 H, J = 8.0, 2.0 Hz), 8.16 (d, 2 H, J = 8.4 Hz), 7.68 (d, 1 H, J = 8.4 Hz), 7.63 (s, 1 H), 7.58 (td, 1 H, J = 8.0, 1.6 Hz), 7.38 ( d, 2 H, J = 8.0 Hz), 7.36 (dd, 1 H, J = 8.0, 1.2 Hz), 7.23 (td, 1 H, J = 8.0, 1.2 Hz), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.47 (s, 3 H), 2.45 (brt, 4 H, J = 4.4 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.4, 162.6, 155.0, 149.7, 142.7, 140.3, 139.8, 136.9, 133.1, 132.7, 129.6, 128.5, 128.1, 126.1, 123.1, 120.7, 119.1, 113.4, 111.2, 79.9 , 63.2, 53.1, 43.6, 28.7, 21.8.

Turt - Butyl  4-((2- (2- (2-fluorobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2- fluorobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76e)

White solid; Reaction time, 2.5 hours; Yield, 77.0%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.62 (brs, 1 H), 8.99 (d, 1 H, J = 8.4 Hz), 8.22 (d, 1 H, J = 8.0 Hz), 8.07 (td, 1 H, J = 7.6, 1.2 Hz), 7.61-7.51 (m, 4 H), 7.33-7.22 (m, 4 H), 3.63 (s, 2 H), 3.44 (brt, 4 H, J = 4.4 Hz) , 2.42 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.2 (d, J = 2.3 Hz), 162.0, 160.5 (d, J = 251.9 Hz), 155.0, 149.8, 140.4, 139.1, 136.7, 133.6 (d, J = 9.1 Hz), 132.8, 131.7 (d, J = 2.3 Hz), 128.5, 126.1, 124.8 (d, J = 3.8 Hz), 123.8 (d, J = 12.1 Hz), 123.7, 121.5, 119.4, 116.7 (d, J = 22.8 Hz), 114.0, 111.1, 79.9, 63.2, 53.1, 43.5, 28.7.

Turt - Butyl  4-((2- (2- (3-fluorobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3- fluorobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76f)

White solid; Reaction time, 4 hours; Yield, 73.5%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.85 (s, 1 H), 9.02 (d, 1 H, J = 9.0 Hz), 8.26 (d, 1 H, J = 7.5 Hz), 8.05 (d, 1 H, J = 8.0 Hz), 8.02 (d, 1 H, J = 10.0 Hz), 7.70 (d, 1 H, J = 8.0 Hz), 7.64 (s, 1 H), 7.59 (t, 1 H, J = 8.5 Hz), 7.55 (td, 1 H, J = 8.0, 5.5 Hz), 7.38 (d, 1 H, J = 8.5 Hz), 7.31 (td, 1 H, J = 8.5, 2.5 Hz), 7.26 ( t, 1 H, J = 7.5 Hz), 3.67 (s, 2 H), 3.46 (brt, 4 H, J = 4.5 Hz), 2.44 (brt, 4 H, J = 4.5 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.9 (d, J = 2.3 Hz), 163.7 (d, J = 245.8 Hz), 162.5, 155.0, 149.7, 140.1, 139.3, 137.7 (d, J = 6.8 Hz) , 137.1, 133.2, 130.5 (d, J = 7.6 Hz), 128.5, 126.3, 123.8 (d, J = 3.1 Hz), 123.6, 120.7, 119.1 (d, J = 21.3 Hz), 119.1, 115.2 (d, J = 22.8 Hz), 113.5, 111.2, 79.9, 63.2, 53.1, 43.4, 28.7.

Turt - Butyl  4-((2- (2- (4-fluorobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4- fluorobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76g)

White solid; Reaction time, 4 hours; Yield, 80.1%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.76 (s, 1 H), 9.01 (d, 1 H, J = 8.5 Hz), 8.29-8.24 (m, 3 H), 7.66 (d, 1 H, J = 8.5 Hz), 7.64 (s, 1 H), 7.59 (td, 1 H, J = 8.5, 1.5 Hz), 7.38 (d, 1 H, J = 8.5 Hz), 7.27-7.24 (m, 3 H) , 3.67 (s, 2 H), 3.46 (brt, 4 H, J = 4.5 Hz), 2.44 (brt, 4 H, J = 4.5 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3 (d, J = 251.1 Hz), 165.3, 162.5, 155.0, 149.7, 140.2, 139.5, 137.0, 133.2, 131.7, 130.4 (d, J = 9.1 Hz), 128.6 , 126.2, 123.4, 120.6, 119.0, 116.0 (d, J = 21.3 Hz), 113.4, 111.3, 79.9, 63.2, 53.1, 43.9, 28.7.

Turt - Butyl  4-((2- (2- (2-bromobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2-bromobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76h)

White solid; Reaction time, 2.5 hours; Yield, 40.7%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.43 (s, 1 H), 9.00 (d, 1 H, J = 8.4 Hz), 8.24 (d, 1 H, J = 8.0 Hz), 7.75-7.71 (m , 2 H), 7.61-7.57 (m, 2 H), 7.49-7.44 (m, 2 H), 7.38 (t, 1 H, J = 7.6 Hz), 7.30-7.25 (m, 2 H), 3.63 ( s, 2 H), 3.43 (brt, 4 H, J = 4.4 Hz), 2.41 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.8, 162.1, 155.0, 149.7, 140.2, 139.0, 138.6, 136.8, 134.2, 133.1, 131.7, 129.6, 128.5, 127.7, 126.1, 123.8, 120.9, 120.4, 119.3, 113.6 , 111.2, 79.9, 63.1, 53.1, 43.5, 28.7.

Turt - Butyl  4-((2- (2- (3-bromobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-bromobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76i)

White solid; Reaction time, 1.5 hours; Yield, 72.4%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.85 (s, 1 H), 8.99 (d, 1 H, J = 8.4 Hz), 8.49 (s, 1 H), 8.22 (d, 1 H, J = 8.0 Hz), 8.16 (d, 1 H, J = 8.0 Hz), 7.80 (d, 1 H, J = 8.0 Hz), 7.71 (dd, 1 H, J = 8.0, 1.2 Hz), 7.61 (s, 1 H ), 7.56 (td, 1 H, J = 8.4, 1.2 Hz), 7.44 (t, 1 H, J = 8.0 Hz), 7.37 (d, 1 H, J = 8.0 Hz), 7.23 (t, 1 H, J = 7.6 Hz), 3.65 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.43 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.5, 162.4, 155.0, 149.7, 140.1, 139.3, 137.3, 137.0, 135.0, 133.2, 130.8, 130.6, 128.5, 127.2, 126.3, 123.6, 123.0, 120.6, 119.3, 113.5 , 111.2, 79.9, 63.2, 53.1, 43.8, 28.7.

Turt - Butyl  4-((2- (2- (4-bromobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4- bromobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76j)

White solid; Reaction time, 3 hours; Yield, 57.7%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.80 (s, 1 H), 9.00 (dd, 1 H, J = 8.4, 1.6 Hz), 8.25 (dd, 1 H, J = 7.6, 2.0 Hz), 8.12 (d, 2 H, J = 8.8 Hz), 7.71 (d, 2 H, J = 8.8 Hz), 7.66 (d, 1 H, J = 8.4 Hz), 7.64 (s, 1 H), 7.58 (td, 1 H, J = 8.0, 2.0 Hz), 7.37 (dd, 1 H, J = 8.0, 1.6 Hz), 7.25 (td, 1 H, J = 7.6, 1.2 Hz), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.8 Hz), 2.43 (brt, 4 H, J = 4.8 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.4, 162.5, 155.0, 149.7, 140.1, 139.4, 137.1, 134.4, 133.2, 132.2, 129.7, 128.6, 127.0, 126.2, 123.5, 120.7, 119.0, 113.5, 111.3, 79.9 , 63.2, 53.1, 43.9, 28.7.

Turt - Butyl  4-((2- (2- (2-chlorobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2- chlorobenzamido) phenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (76k)

White solid; Reaction time, 2.5 hours; Yield, 25.0%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.47 (s, 1 H), 9.01 (d, 1 H, J = 8.8 Hz), 8.24 (dd, 1 H, J = 8.0, 1.2 Hz), 7.79 (dd , 1 H, J = 7.2, 2.0 Hz), 7.61-7.57 (m, 2 H), 7.53 (dd, 1 H, J = 7.6, 1.6 Hz), 7.49 (d, 1 H, J = 8.4 Hz), 7.46 (td, 1 H, J = 7.6, 2.0 Hz), 7.42 (td, 1 H, J = 7.6, 1.6 Hz), 7.30-7.24 (m, 2 H), 3.63 (s, 2 H), 3.44 ( brt, 4 H, J = 4.4 Hz), 2.41 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.0, 162.1, 155.0, 149.7, 140.2, 139.1, 136.8, 136.5, 133.1, 132.0, 131.7, 130.9, 129.8, 128.5, 127.1, 126.1, 123.8, 120.9, 119.3, 113.6 , 111.2, 79.9, 63.2, 53.1, 44.0, 28.7.

Turt - Butyl  4-((2- (2- (3-chlorobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3- chlorobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76l)

White solid; Reaction time, 5 hours; Yield, 29.9%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.89 (s, 1 H), 9.00 (dd, 1 H, J = 8.8, 0.8 Hz), 8.35 (t, 1 H, J = 2.0 Hz), 8.24 (dd , 1 H, J = 8.0, 1.6 Hz), 8.13 (dt, 1 H, J = 7.6, 1.6 Hz), 7.76 (d, 1 H, J = 8.0 Hz), 7.64 (s, 1 H), 7.60- 7.55 (m, 2 H), 7.51 (t, 1 H, J = 7.6 Hz), 7.38 (dd, 1 H, J = 8.0, 1.6 Hz), 7.25 (td, 1 H, J = 7.6, 1.2 Hz) , 3.67 (s, 2 H), 3.46 (brt, 4 H, J = 4.4 Hz), 2.44 (brt, 4 H, J = 4.4 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.7, 162.4, 155.0, 149.7, 140.1, 139.3, 137.1, 137.0, 135.0, 133.2, 132.1, 130.3, 128.5, 128.0, 126.7, 126.4, 123.6, 120.6, 119.2, 113.5 , 111.3, 79.9, 63.2, 53.1, 43.8, 28.7.

Turt - Butyl  4-((2- (2- (4-chlorobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4- chlorobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76m)

White solid; Reaction time, 5 hours; Yield, 36.1%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.80 (s, 1 H), 9.01 (d, 1 H, J = 8.0 Hz), 8.25 (dd, 1 H, J = 8.0, 2.0 Hz), 8.20 (d , 2 H, J = 8.0 Hz), 7.66 (d, 1 H, J = 8.0 Hz), 7.64 (s, 1 H), 7.59 (t, 1 H, J = 8.0 Hz), 7.55 (d, 2 H , J = 8.4 Hz), 7.37 (dd, 1 H, J = 8.4, 1.2 Hz), 7.26 (td, 1 H, J = 8.0, 1.2 Hz), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.44 (brt, 4 H, J = 4.4 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3, 162.5, 155.0, 149.7, 140.1, 139.4, 138.5, 137.1, 133.9, 133.2, 129.5, 129.2, 128.6, 126.2, 123.5, 120.7, 119.0, 113.5, 111.3, 79.9 , 63.2, 53.1, 43.3, 28.7.

Turt - Butyl  4-((2- (2- (3-nitrobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-nitrobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76n)

solid; Reaction time, 6 hours; Yield, 82%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 13.12 (s, 1 H), 9.33 (t, 1 H, J = 2.0 Hz), 9.04 (dd, 1 H, J = 8.5, 1.0 Hz), 8.62 (dt , 1 H, J = 7.5, 1.0 Hz), 8.48 (ddd, 1 H, J = 8.0, 2.0, 1.0 Hz), 8.29 (dd, 1 H, J = 8.5, 1.0 Hz), 7.95 (d, 1 H) , J = 8.5 Hz), 7.78 (t, 1 H, J = 8.0 Hz), 7.65 (d, 1 H, J = 1.0 Hz), 7.61 (td, 1 H, J = 7.5, 2.0 Hz), 7.41 ( dd, 1 H, J = 8.5, 1.0 Hz), 7.30 (td, 1 H, J = 7.5, 1.0 Hz), 3.68 (s, 2 H), 3.46 (t, 4 H, J = 4.5 Hz), 2.45 (brt, 4 H, J = 4.5 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.1, 162.1, 154.8, 149.5, 148.3, 138.7, 137.0, 136.4, 134.8, 133.0, 130.0, 128.4, 126.5, 126.4, 123.8, 121.9, 120.4, 119.5, 113.5, 110.8 , 79.6, 62.9, 52.9, 43.4, 28.4.

Turt - Butyl  4-((2- (2- (4-nitrobenzamido) phenyl) benzo [ d ] Oxazole-6-yl) -methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4- nitrobenzamido) phenyl) benzo [ d ] oxazol-6-yl) -methyl) piperazine-1-carboxylate] (76o)

Yellow solid; Reaction time, 1.5 hours; Yield, 75.6%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.91 (s, 1 H), 8.93 (d, 1 H, J = 8.4 Hz), 8.36 (s, 4 H), 8.21 (d, 1 H, J = 8.0 Hz), 7.63-7.61 (m, 2 H), 7.55 (t, 1 H, J = 8.4 Hz), 7.36 (d, 1 H, J = 8.0 Hz), 7.25 (t, 1 H, J = 7.6 Hz ), 3.65 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.43 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.9, 162.3, 155.0, 150.0, 149.6, 140.8, 139.9, 138.9, 137.3, 133.2, 129.1, 128.6, 126.4, 124.1, 124.0, 120.6, 119.0, 113.6, 111.3, 79.9 , 63.1, 53.1, 43.8, 28.7.

Turt - Butyl  4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] Oxazole -6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76p)

White solid; Reaction time, 5 hours; Yield, 75.5%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.54 (s, 1 H), 9.03 (d, 1 H, J = 8.4 Hz), 8.26 (dd, 1 H, J = 8.4, 1.2 Hz), 7.64 (s , 1 H), 7.58 (td, 1 H, J = 8.0, 2.0 Hz), 7.57 (d, 1 H, J = 8.0 Hz), 7.45 (s, 2 H), 7.34 (dd, 1 H, J = 8.0, 1.6 Hz), 7.24 (td, 1 H, J = 7.6, 1.6 Hz), 4.01 (s, 6 H), 3.96 (s, 3 H), 3.65 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.43 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.2, 162.6, 155.0, 153.5, 149.7, 141.6, 140.3, 139.6, 137.0, 133.2, 130.9, 128.7, 126.2, 123.3, 120.6, 118.8, 113.4, 111.3, 105.6, 79.9 , 63.1, 61.3, 56.7, 53.1, 43.4, 28.7.

Turt - Butyl  4-((2- (2- (2,4-dichlorobenzamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (2,4-dichlorobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76q)

White solid; Reaction time, 5 hours; Yield, 13.7%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.49 (s, 1 H), 8.97 (d, 1 H, J = 8.4 Hz), 8.24 (dd, 1 H, J = 7.6, 1.6 Hz), 7.74 (d , 1 H, J = 8.4 Hz), 7.63 (brs, 1 H), 7.59 (td, 1 H, J = 8.0, 1.6 Hz), 7.55 (d, 1 H, J = 2.0 Hz), 7.52 (d, 1 H, J = 8.4 Hz), 7.41 (dd, 1 H, J = 8.0, 2.0 Hz), 7.31 (d, 1 H, J = 8.0 Hz), 7.27 (td, 1 H, J = 8.0, 1.2 Hz ), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.44 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.9, 162.1, 155.0, 149.7, 140.2, 138.8, 137.2, 136.9, 134.9, 133.1, 133.0, 130.8, 130.8, 128.5, 127.6, 126.2, 124.0, 120.9, 119.3, 113.6 , 111.3, 80.0, 63.1, 53.1, 43.2, 28.6.

Turt - Butyl  4-((2- (2- (3,4-dichlorobenzamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (3,4- dichlorobenzamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76r)

White solid; Reaction time, 7 hours; Yield, 83.4%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.88 (s, 1 H), 8.97 (dd, 1 H, J = 8.5, 1.0 Hz), 8.45 (d, 1 H, J = 2.5 Hz), 8.24 (dd , 1 H, J = 8.0, 1.5 Hz), 8.07 (dd, 1 H, J = 8.5, 2.5 Hz), 7.75 (d, 1 H, J = 8.0 Hz), 7.64 (d, 1 H, J = 8.5 Hz), 7.64 (s, 1 H), 7.58 (td, 1 H, J = 8.0, 1.5 Hz), 7.39 (dd, 1 H, J = 8.0, 1.5 Hz), 7.26 (td, 1 H, J = 7.5, 1.0 Hz), 3.67 (s, 2 H), 3.46 (brt, 4 H, J = 4.5 Hz), 2.44 (brt, 4 H, J = 4.5 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.8, 162.4, 155.0, 149.7, 140.0, 139.1, 137.2, 136.6, 135.1, 133.3, 133.2, 131.1, 129.8, 128.5, 127.7, 126.4, 123.7, 120.5, 119.1, 113.5 , 111.2, 79.9, 63.2, 53.1, 43.4, 28.7.

Turt - Butyl  4-((2- (2- (nicotinamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (nicotinamido) phenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (76s)

solid; Reaction time, 12 hours; Yield, 60%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.94 (s, 1 H), 9.52 (m, 1 H), 9.02 (d, 1 H, J = 9.0 Hz), 8.84 (dd, 1 H, J = 5.0 , 1.5 Hz), 8.52 (dt, 1 H, J = 8.0, 2.0 Hz), 8.23 (dd, 1 H, J = 8.5, 2.0 Hz), 7.74 (d, 1 H, J = 8.5 Hz), 7.65 ( s, 1 H), 7.61 (td, 1 H, J = 8.0, 1.5 Hz), 7.53 (dd, 1 H, J = 8.0, 5.0 Hz), 7.37 (d, 1 H, J = 8.5 Hz), 7.28 (t, 1 H, J = 8.5 Hz), 3.67 (s, 2 H), 3.46 (brt, 4 H, J = 4.5 Hz), 2.44 (brt, 4 H, J = 4.5 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.5, 162.4, 155.0, 152.8, 149.7, 149.2, 140.0, 139.1, 137.1, 136.0, 133.2, 131.1, 128.6, 126.3, 123.9, 120.8, 119.3, 113.6, 111.2, 79.9 , 63.2, 53.1, 43.4, 28.7.

Turt - Butyl  4-((2- (2- (isonicotinamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (isonicotinamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76t)

solid; Reaction time, 8 hours; Yield, 79%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.96 (s, 1 H), 8.99 (dd, 1 H, J = 8.4, 0.8 Hz), 8.89 (dd, 2 H, J = 4.4, 2.0 Hz), 8.26 (dd, 1 H, J = 7.6, 1.2 Hz), 8.07 (dd, 2 H, J = 4.8, 2.0 Hz), 7.67 (d, 1 H, J = 8.4 Hz), 7.64 (d, 1 H, J = 0.8 Hz), 7.59 (td, 1 H, J = 8.0, 1.6 Hz), 7.39 (dd, 1 H, J = 8.0, 1.2 Hz), 7.28 (td, 1 H, J = 7.6, 1.2 Hz), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz), 2.43 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.3, 162.4, 155.0, 151.0, 149.7, 142.5, 140.0, 138.8, 137.2, 133.2, 128.6, 126.4, 124.0, 121.7, 120.8, 119.0, 113.7, 111.3, 79.9, 63.1 , 53.1, 43.4, 28.7.

Turt - Butyl  4-((2- (2- (1-naphthaamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (1-naphthamido) phenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (76u)

White solid; Reaction time, 6 hours; Yield, 59.0%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.65 (s, 1 H), 9.15 (d, 1 H, J = 8.4 Hz), 8.65 (d, 1 H, J = 8.0 Hz), 8.26 (dd, 1 H, J = 8.0, 1.6 Hz), 8.05 (d, 1 H, J = 7.2 Hz), 8.04 (d, 1 H, J = 7.2 Hz), 7.94 (m, 1 H), 7.65-7.55 (m, 5 H), 7.37 (d, 1 H, J = 8.0 Hz), 7.30-7.24 (m, 2 H), 3.62 (s, 2 H), 3.43 (brt, 4 H, J = 4.4 Hz), 2.40 ( brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 168.5, 162.2, 155.0, 149.7, 140.2, 139.6, 136.8, 134.8, 134.2, 133.1, 131.7, 130.8, 128.6, 128.5, 127.5, 126.7, 126.4, 126.1, 126.0, 125.0 , 123.5, 120.7, 119.2, 113.5, 111.1, 79.9, 63.1, 53.1, 43.2, 28.7.

Turt - Butyl  4-((2- (2- (2-naphthaamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (2-naphthamido) phenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (76v)

White solid; Reaction time, 1.5 hours; Yield, 84.6%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.90 (s, 1 H), 9.07 (d, 1 H, J = 8.0 Hz), 8.75 (s, 1 H), 8.27 (d, 1 H, J = 7.6 Hz), 8.20 (d, 1 H, J = 7.2 Hz), 8.03-7.90 (m, 3 H), 7.67 (d, 1 H, J = 8.0 Hz), 7.60-7.54 (m, 4 H), 7.36 (d, 1 H, J = 8.0 Hz), 7.21 (t, 1 H, J = 7.6 Hz), 3.63 (s, 2 H), 3.46 (brt, 4 H, J = 4.4 Hz), 2.44 (brt, 4 H, J = 4.4 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.3, 162.5, 155.0, 149.7, 140.3, 139.7, 136.8, 135.2, 133.1, 133.0, 132.6, 129.4, 128.7, 128.7, 128.5, 128.1, 128.1, 127.0, 126.2, 124.6 , 123.3, 120.6, 119.0, 113.3, 111.3, 79.9, 63.1, 53.1, 43.4, 28.7.

Turt - Butyl  4-((2- (2- (quinoline-2-carboxamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (quinoline-2-carboxamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76w)

White solid; Reaction time, 2.5 hours; Yield, 44.4%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 13.83 (s, 1 H), 9.15 (d, 1 H, J = 8.0 Hz), 8.43 (d, 1 H, J = 8.4 Hz), 8.42 (d, 1 H, J = 8.4 Hz), 8.38 (d, 1 H, J = 8.4 Hz), 8.27 (d, 1 H, J = 8.0 Hz), 7.95-7.87 (m, 3 H), 7.69 (t, 1 H , J = 7.6 Hz), 7.65 (s, 1 H), 7.60 (t, 1 H, J = 8.4 Hz), 7.42 (d, 1 H, J = 8.0 Hz), 7.27 (t, 1 H, J = 7.6 Hz), 3.68 (s, 2 H), 3.46 (brt, 4 H, J = 4.4 Hz), 2.45 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.5, 162.2, 155.0, 150.9, 150.1, 147.0, 141.1, 139.0, 137.8, 136.6, 132.8, 130.4, 130.2, 129.7, 128.9, 128.4, 128.1, 126.1, 123.6, 121.0 , 119.5, 119.5, 114.6, 111.2, 79.9, 63.3, 53.1, 43.8, 28.7.

Turt - Butyl  4-((2- (2- (quinoxaline-2-carboxamido) phenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (quinoxaline-2-carboxamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76x)

Yellow solid; Reaction time, 5 hours; Yield, 72.4%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 13.78 (s, 1 H), 9.77 (s, 1 H), 9.10 (d, 1 H, J = 8.8 Hz), 8.38 (dd, 1 H, J = 8.4 , 1.6 Hz), 8.26 (dd, 1 H, J = 8.0, 1.2 Hz), 8.24 (dd, 1 H, J = 8.0, 1.6 Hz), 7.96 (td, 1 H, J = 7.2, 1.6 Hz), 7.92 (td, 1 H, J = 7.2, 1.2 Hz), 7.84 (d, 1 H, J = 8.4 Hz), 7.64 (s, 1 H), 7.60 (td, 1 H, J = 8.0, 1.6 Hz) , 7.42 (dd, 1 H, J = 8.0, 1.2 Hz), 7.28 (td, 1 H, J = 8.0, 1.2 Hz), 3.68 (s, 2 H), 3.46 (s, 4 H), 2.45 (s , 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.2, 162.1, 155.0, 150.0, 144.8, 144.5, 144.1, 140.9, 140.8, 138.6, 136.7, 132.9, 132.0, 131.2, 130.1, 129.9, 128.8, 126.2, 124.0, 121.0 , 119.3, 114.6, 111.3, 79.9, 63.2, 53.1, 43.8, 28.7.

Turt - Butyl  4-((2- (2-([1,1'-biphenyl] -4- Ilka Copy Mido ) Phenyl) Benzo [ d ] Oxazole -6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2-([1,1'-biphenyl] -4-ylcarboxamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76y)

solid; Reaction time, 12 hours; Yield, 60%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.86 (s, 1 H), 9.06 (d, 1 H, J = 8.0 Hz), 8.34 (d, 2 H, J = 8.4 Hz), 8.27 (dd, 1 H, J = 8.0, 1.6 Hz), 7.81 (d, 2 H, J = 8.4 Hz), 7.70 (d, 2 H, J = 7.6 Hz), 7.69 (d, 1 H, J = 8.0 Hz), 7.64 (s, 1 H), 7.60 (td, 1 H, J = 8.0, 1.2 Hz), 7.51 (t, 2 H, J = 7.6 Hz), 7.42 (tt, 1 H, J = 7.6, 0.8 Hz), 7.37 (dd, 1 H, J = 8.0, 0.8 Hz), 7.26 (td, 1 H, J = 7.6, 0.8 Hz), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.4 Hz) , 2.44 (brt, 4 H, J = 4.4 Hz), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.1, 162.5, 155.0, 149.7, 144.9, 140.3, 140.3, 139.7, 136.9, 134.1, 133.2, 129.2, 128.6, 128.5, 128.3, 127.6, 127.5, 126.2, 123.3, 120.7 , 119.1, 113.4, 111.3, 79.9, 63.2, 53.1, 43.5, 28.7.

Turt - Butyl  4-((2- (2- (cyclohexanecarboxamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (cyclohexanecarboxamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76z)

White solid; Reaction time, 2 hours; Yield, 55.9%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 11.89 (s, 1 H), 8.84 (d, 1 H, J = 8.8 Hz), 8.19 (dd, 1 H, J = 8.0, 1.6 Hz), 7.66 (d , 1 H, J = 8.0 Hz), 7.61 (s, 1 H), 7.51 (td, 1 H, J = 8.0, 1.6 Hz), 7.35 (dd, 1 H, J = 8.0, 1.2 Hz), 7.18 ( td, 1 H, J = 7.6, 1.2 Hz), 3.66 (s, 2 H), 3.45 (brt, 4 H, J = 4.8 Hz), 2.51-2.46 (m, 1 H), 2.43 (brt, 4 H) , J = 4.8 Hz), 2.16-2.11 (m, 2 H), 1.91-1.87 (m, 2 H), 1.77-1.63 (m, 3 H), 1.45 (s, 9 H), 1.45-1.29 (m , 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 176.0, 162.4, 155.0, 149.7, 140.4, 139.6, 136.8, 133.0, 128.4, 126.1, 122.9, 120.7, 119.2, 113.1, 111.2, 79.9, 63.2, 53.1, 47.7, 44.0 , 30.0, 28.7, 26.2, 26.1.

( E )- Turt - Butyl  4-((2- (2-cinnamamidophenyl) benzo [ d ] Oxazole -6-day) methyl ) Piperazine-1-carboxylate [( E )- tert -Butyl 4-((2- (2-cinnamamidophenyl) benzo [ d ] oxazol -6-yl) methyl) piperazine-1-carboxylate] (76A)

White solid; Reaction time, 5 hours; Yield, 51.2%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.21 (s, 1 H), 8.97 (d, 1 H, J = 9.0 Hz), 8.23 (dd, 1 H, J = 8.5, 1.5 Hz), 7.84 (d , 1 H, J = 15.5 Hz), 7.74 (d, 1 H, J = 8.0 Hz), 7.65-7.63 (m, 3 H), 7.55 (td, 1 H, J = 8.0, 1.0 Hz), 7.46- 7.41 (m, 3 H), 7.38 (d, 1 H, J = 9.0 Hz), 7.22 (t, 1 H, J = 7.5 Hz), 6.76 (d, 1 H, J = 15.5 Hz), 3.66 (s , 2 H), 3.46 (brt, 4 H, J = 4.5 Hz), 2.44 (brt, 4 H, J = 4.5 Hz), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.1, 162.4, 155.0, 149.7, 142.1, 140.3, 139.5, 136.9, 135.1, 133.0, 130.2, 129.2, 128.5, 128.3, 126.1, 123.2, 122.7, 120.8, 119.3, 113.1 , 111.2, 79.9, 63.2, 53.1, 43.9, 28.7.

Turt - Butyl  4-((2- (2- (4-methylphenylsulfonamido) phenyl) benzo [ d ] Oxazole-6-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-methylphenylsulfonamido) phenyl) benzo [ d ] oxazol-6-yl) methyl) piperazine-1-carboxylate] (76B)

solid; Reaction time, 12 hours; Yield, 76%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 11.74 (s, 1 H), 8.08 (dd, 1 H, J = 8.0, 1.6 Hz), 7.77-7.75 (m, 4 H), 7.60 (brs, 1 H ), 7.40 (td, 1 H, J = 7.2, 1.6 Hz), 7.37 (dd, 1 H, J = 8.0, 1.2 Hz), 7.14 (d, 2 H, J = 8.0 Hz), 7.13 (td, 1 H, J = 7.6, 1.2 Hz), 3.67 (s, 2 H), 3.46 (brs, 4 H), 2.44 (brs, 4 H), 2.29 (s, 3 H), 1.46 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 161.8, 155.0, 149.7, 144.0, 140.1, 138.3, 136.8, 132.8, 129.8, 128.7, 127.5, 126.4, 123.4, 119.7, 119.0, 113.8, 111.1, 80.0, 63.1, 53.1 , 44.0, 28.7, 21.7.

25) Synthesis of Compound 77 (a to z, and A and B)

Compound in the form of HCl salt: 1,4-dioxane and 8N-HCl (42.0 equivalents) in a volume corresponding to 8N-HCl (42.0 equivalents) were added sequentially into compound 76 (1.0 equivalent), followed by reaction mixture. Was stirred at room temperature. The solvent was removed by distillation under reduced pressure, and the resulting residue was filtered by adding diethyl ether in the presence of a small amount of methanol or in the absence of methanol to obtain the above compound.

Compounds in the form of trifluoroacetic acid (TFA) salts ( 77pp and 77xx ): methylene chloride solution containing TFA (30 equivalents) was added to the compounds 76p and 76x, reacted at room temperature, and concentrated under reduced pressure to obtain a residue. In the case of compound 77pp , the obtained residue was purified by short silica gel column chromatography (methylene chloride: methanol = 10: 1) to obtain a TFA salt form. In the case of compound 77xx , methylene chloride was added to the obtained residue and the solid was filtered. To obtain the TFA salt form.

Sulfonamide compound ( 77BBB ) in free acid form: After adding methylene chloride solution containing TFA (15 eq.) To compound 76B and reacting at room temperature, methylene chloride and sodium bicarbonate are added, and the organic layer is anhydrous MgSO ₄ After drying with filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (methylene chloride: methanol = 5: 1) to obtain compound 77BBB as a free acid solid.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77a)

White solid; Reaction time, 9 hours; Yield, 87.9%; ¹ H NMR (400 MHz, D ₂ O) δ 7.46 (d, 1 H, J = 8.0 Hz), 7.27 (t, 1 H, J = 7.2 Hz), 7.11 (d, 2 H, J = 7.6 Hz) , 7.01 (t, 2 H, J = 7.2 Hz), 6.97 (s, 1 H), 6.94 (d, 1 H, J = 7.6 Hz), 6.85 (t, 1 H, J = 7.6 Hz), 6.81 ( d, 1 H, J = 8.4 Hz), 6.56 (d, 1 H, J = 8.0 Hz), 6.54 (t, 1 H, J = 7.6 Hz), 3.98 (s, 2 H), 3.41 (brs, 4 H), 3.29 (brs, 4 H); ¹³ C NMR (100 MHz, D ₂ O) δ 166.1, 162.1, 148.1, 140.6, 136.9, 132.9, 132.7, 132.6, 128.8, 128.2, 127.8, 126.9, 125.9, 123.8, 119.4, 119.0, 113.2, 111.6, 60.5, 48.1, 41.1.

2- methyl - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [2-Methyl- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77b)

White solid; Reaction time, 8 hours; Yield, 55.3%; ¹ H NMR (500 MHz, D ₂ O) δ 7.60 (d, 1 H, J = 8.5 Hz), 7.32-7.29 (m, 2 H), 7.18 (d, 1 H, J = 8.0 Hz), 7.17 ( s, 1 H), 7.08 (t, 1 H, J = 8.0 Hz), 7.03-6.96 (m, 3 H), 6.83-6.79 (m, 2 H), 4.08 (s, 2 H), 3.39 (brs , 4 H), 3.28 (brs, 4 H), 2.18 (s, 3 H); ¹³ C NMR (100 MHz, D ₂ O) δ 169.5, 162.3, 148.5, 140.9, 137.3, 136.6, 134.2, 132.9, 131.9, 131.5, 128.5, 127.8, 127.2, 126.2, 126.0, 124.5, 120.1, 119.6, 113.3, 113.2, 60.6, 48.1, 41.1, 19.7.

3- methyl - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Methyl- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77c)

White solid; Reaction time, 9 hours; Yield, 96.5%; ¹ H NMR (400 MHz, D ₂ O) δ 7.32 (d, 1 H, J = 8.0 Hz), 6.89-6.84 (m, 2 H), 6.78-6.75 (m, 3 H), 6.73 (d, 1 H, J = 8.4 Hz), 6.68 (t, 1 H, J = 7.6 Hz), 6.52 (s, 1 H), 6.42 (d, 1 H, J = 8.0 Hz), 6.38 (t, 1 H, J = 7.2 Hz), 3.93 (s, 2 H), 3.40 (brs, 4 H, J = 4.4 Hz), 3.26 (brs, 4 H, J = 4.4 Hz), 1.69 (s, 3 H); ¹³ C NMR (100 MHz, D ₂ O) δ 165.6, 161.9, 148.0, 140.5, 138.2, 136.9, 133.1, 132.8, 132.2, 128.5, 128.0, 127.8, 126.5, 125.8, 124.4, 123.5, 119.1, 118.6, 113.2, 111.2, 60.4, 48.1, 41.0, 20.6.

4- methyl - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Methyl- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77d)

White solid; Reaction time, 7 hours; Yield, 98.3%; ¹ H NMR (500 MHz, D ₂ O + 6 drops of DMSO- d ₆ ) δ 7.88 (d, 1 H, J = 8.5 Hz), 7.47 (dd, 1 H, J = 8.0, 1.0 Hz), 7.34 ( d, 2 H, J = 8.0 Hz), 7.32 (s, 1 H), 7.19 (td, 1 H, J = 8.0, 1.5 Hz), 7.10 (dd, 1 H, J = 8.5, 1.0 Hz), 6.99 (d, 1 H, J = 8.0 Hz), 6.97 (d, 2 H, J = 8.5 Hz), 6.90 (t, 1 H, J = 8.0 Hz), 4.18 (s, 2 H), 3.47 (brs, 4 H), 3.38 (brs, 4 H), 2.24 (s, 3 H); ¹³ C NMR (125 MHz, D ₂ O + 6 drops of DMSO- d ₆ ) δ 164.9, 161.0, 147.1, 142.3, 139.4, 135.9, 131.6, 128.6, 127.9, 127.0, 126.4, 125.6, 125.2, 122.4, 118.1, 117.9, 111.8, 110.9, 59.2, 46.7, 39.7, 19.4.

2- Fluoro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [2- Fluoro - N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (77e)

White solid; Reaction time, 8 hours; Yield, 98.3%; ¹ H NMR (500 MHz, D ₂ O + 6 drops of DMSO- d ₆ ) δ 7.70 (d, 1 H, J = 8.5 Hz), 7.43 (m, 1 H), 7.32 (td, 1 H, J = 8.0, 2.0 Hz), 7.26 (dd, 1 H, J = 8.0, 1.5 Hz), 7.22 (s, 1 H), 7.07 (td, 1 H, J = 8.5, 1.5 Hz), 7.03 (t, 1 H , J = 8.0 Hz), 6.99 (dd, 1 H, J = 8.5, 1.0 Hz), 6.96 (dd, 1 H, J = 12.0, 8.5 Hz), 6.85 (d, 1 H, J = 8.0 Hz), 6.79 (t, 1 H, J = 7.5 Hz), 4.15 (s, 2 H), 3.45 (s, 4 H), 3.36 (s, 4 H); ¹³ C NMR (100 MHz, D ₂ O + 6 drops of DMSO- d ₆ ) δ 163.3, 162.0, 159.9 (d, J = 251.9 Hz), 148.5, 141.0, 136.7, 134.7 (d, J = 8.3 Hz), 132.9, 129.9, 128.4, 127.9, 125.9, 124.9 (d, J = 3.8 Hz), 124.4, 121.2 (d, J = 10.6 Hz), 120.2, 119.6, 117.0 (d, J = 22.8 Hz), 113.4, 112.6, 60.5, 48.1, 41.0.

3- Fluoro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [3- Fluoro - N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (77f)

Pink solid; Reaction time, 8 hours; Yield, 98.6%; ¹ H NMR (500 MHz, D ₂ O) δ 7.33 (d, 1 H, J = 8.0 Hz), 7.07 (s, 1 H), 6.97 (d, 1 H, J = 7.0 Hz), 6.92-6.82 ( m, 4 H), 6.75 (t, 1 H, J = 7.0 Hz), 6.59 (d, 1 H, J = 9.5 Hz), 6.53 (t, 1 H, J = 7.0 Hz), 6.48 (d, 1 H, J = 8.0 Hz), 4.09 (s, 2 H), 3.46 (brs, 4 H), 3.32 (brs, 4 H); ¹³ C NMR (150 MHz, D ₂ O + 3 drops of DMSO- d ₆ ) δ 163.7, 162.0, 161.9 (d, J = 243.9 Hz), 148.0, 140.2, 136.7, 134.4 (d, J = 7.5 Hz), 132.9, 130.4 (d, J = 7.7 Hz), 127.9, 127.8, 126.4, 123.7, 122.6, 119.2 (d, J = 20.3 Hz), 119.0, 118.7, 113.3 (d, J = 24.0 Hz), 113.1, 111.3, 60.4, 48.0, 41.0.

4- Fluoro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [4- Fluoro - N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (77 g)

White solid; Reaction time, 7 hours; Yield, 99.8%; ¹ H NMR (500 MHz, D ₂ O + 4 drops of DMSO- d ₆ ) δ 7.79 (d, 1 H, J = 8.5 Hz), 7.50 (d, 1 H, J = 7.5 Hz), 7.48 (dd, 2 H, J = 8.5, 5.5 Hz), 7.31 (s, 1 H), 7.14-7.08 (m, 3 H), 6.91-6.86 (m, 3 H), 4.15 (s, 2 H), 3.42 (brs , 4 H), 3.31 (brs, 4 H); ¹³ C NMR (150 MHz, D ₂ O + 4 drops of DMSO- d ₆ ) δ 164.0, 163.5 (d, J = 250.2 Hz), 161.0, 147.1, 139.3, 135.6, 131.6, 128.1 (d, J = 8.9 Hz ), 127.7, 127.0, 126.4, 125.7, 122.7, 118.4, 118.0, 114.2 (d, J = 22.7 Hz), 111.8, 111.3, 59.3, 46.8, 39.8.

2- Bromo - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Benzamide hydrochloride [2-Bromo- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77h)

White solid; Reaction time, 8 hours; Yield, 88.3%; ¹ H NMR (400 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.43 (d, 1 H, J = 7.6 Hz), 8.17 (dd, 1 H, J = 7.6, 1.6 Hz), 7.94 ( s, 1 H), 7.74 (dd, 1 H, J = 8.0, 1.2 Hz), 7.70 (d, 1 H, J = 7.2 Hz), 7.66 (t, 1 H, J = 8.4 Hz), 7.62 (d , 1 H, J = 8.4 Hz), 7.55 (td, 1 H, J = 7.6, 1.2 Hz), 7.50 (dd, 1 H, J = 8.0, 1.6 Hz), 7.47 (td, 1 H, J = 7.6 , 1.6 Hz), 7.37 (td, 1 H, J = 8.0, 1.2 Hz), 4.42 (s, 2 H), 3.33 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 166.6, 163.1, 149.6, 141.8, 138.3, 138.0, 134.2, 134.0, 133.0, 129.8, 129.7, 129.0, 128.9, 127.8, 125.5, 122.0, 120.3, 119.4, 115.2, 114.5, 59.9, 48.1, 40.9.

3- Bromo - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Bromo- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77i)

White solid; Reaction time, 5.5 hours; Yield, 99.4%; ¹ H NMR (500 MHz, D ₂ O) δ 7.32 (d, 1 H, J = 8.0 Hz), 7.10 (d, 1 H, J = 7.5 Hz), 7.03 (s, 1 H), 6.94 (d, 1 H, J = 7.5 Hz), 6.91 (d, 1 H, J = 7.0 Hz), 6.88 (s, 1 H), 6.82-6.78 (m, 2 H), 6.70 (d, 1 H, J = 8.0 Hz), 6.67 (t, 1 H, J = 7.5 Hz), 6.45 (t, 1 H, J = 7.5 Hz), 4.06 (s, 2 H), 3.46 (brs, 4 H), 3.31 (brs, 4 H); ¹³ C NMR (100 MHz, D ₂ O) δ 163.3, 161.9, 148.0, 140.3, 136.7, 134.9, 133.8, 132.9, 130.4, 128.5, 127.9, 126.2, 123.7, 122.0, 119.5, 118.6, 113.2, 111.1, 60.6, 48.2, 41.1.

4- Bromo - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Bromo- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77j)

White solid; Reaction time, 7 hours; Yield, 99.0%; ¹ H NMR (400 MHz, CD ₃ OD, + 4 drops of D ₂ O) δ 8.55 (d, 1 H, J = 8.4 Hz), 8.04 (d, 1 H, J = 7.6 Hz), 7.87 (d, 2 H, J = 8.4 Hz), 7.80 (s, 1 H), 7.67 (d, 2 H, J = 8.8 Hz), 7.62 (d, 1 H, J = 8.4 Hz), 7.53 (d, 1 H, J = 7.6 Hz), 7.52 (t, 1 H, J = 8.0 Hz), 7.23 (t, 1 H, J = 7.6 Hz), 4.34 (s, 2 H), 3.51 (brs, 4 H), 3.37 ( brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 4 drops of CD ₃ OD + 4 drops of D ₂ O) δ 163.8, 161.5, 147.8, 139.7, 137.1, 136.9, 131.8, 131.7, 130.6, 127.6, 127.1, 126.5 , 125.6, 122.5, 118.7, 118.1, 111.7, 111.5, 59.5, 47.3, 40.4.

2- Chloro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [2-Chloro- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77k)

White solid; Reaction time, 8 hours; Yield, 95.4%; ¹ H NMR (500 MHz, D ₂ O) δ 7.58 (d, 1 H, J = 8.5 Hz), 7.44-7.39 (m, 2 H), 7.35 (d, 1 H, J = 8.0 Hz), 7.22 ( s, 1 H), 7.18-7.10 (m, 3 H), 7.00 (d, 1 H, J = 8.5 Hz), 6.87 (t, 1 H, J = 7.5 Hz), 6.84 (d, 1 H, J = 7.5 Hz), 4.09 (s, 2 H), 3.41 (brs, 4 H), 3.28 (brs, 4 H); ¹³ C NMR (100 MHz, D ₂ O) δ 166.6, 162.2, 148.6, 140.7, 136.2, 133.4, 133.0, 132.8, 131.3, 131.2, 128.8, 128.6, 127.9, 127.4, 126.5, 124.9, 120.4, 119.6, 113.5, 113.4, 60.6, 48.1, 41.1.

3- Chloro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Chloro- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77l)

White solid; Reaction time, 8 hours; Yield, 96.5%; ¹ H NMR (400 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.49 (d, 1 H, J = 8.4 Hz), 7.98 (d, 1 H, J = 8.0 Hz), 7.93 (s, 1 H), 7.92 (s, 1 H), 7.84 (d, 1 H, J = 7.6 Hz), 7.64-7.61 (m, 2 H), 7.57-7.53 (m, 2 H), 7.49 (t, 1 H, J = 8.0 Hz), 7.20 (t, 1 H, J = 8.0 Hz), 4.51 (s, 2 H), 3.42 (s, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 163.8, 163.2, 149.1, 141.5, 138.6, 136.3, 134.3, 134.1, 132.7, 131.7, 129.3, 127.5, 126.8, 126.3, 126.1, 124.6, 120.5, 119.7, 114.8, 113.2, 59.5, 48.0, 40.7.

4- Chloro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Chloro- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77m)

White solid; Reaction time, 8 hours; Yield, 99.3%; ¹ H NMR (400 MHz, DMSO- d ₆ + 4 drops of D ₂ O) δ 8.70 (d, 1 H, J = 8.4 Hz), 8.22 (d, 1 H, J = 8.0 Hz), 8.10 (d, 2 H, J = 8.8 Hz), 7.93 (d, 1 H, J = 8.0 Hz), 7.91 (s, 1 H), 7.73 (d, 2 H, J = 8.8 Hz), 7.65 (t, 1 H, J = 7.6 Hz), 7.53 (d, 1 H, J = 8.4 Hz), 7.35 (t, 1 H, J = 7.6 Hz), 4.18 (s, 2 H), 3.25 (brs, 4 H), 3.05 ( brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 4 drops of D ₂ O) δ 164.9, 162.9, 149.4, 141.1, 138.9, 138.8, 138.0, 134.0, 133.6, 129.9, 129.9, 129.4, 128.4, 124.8, 121.0, 120.3, 114.1, 113.5, 60.5, 48.7, 42.0.

3-Nitro- N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Nitro- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77n)

Beige solid; Reaction time, 6 hours; Yield, 92%; ¹ H NMR (400 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.61 (s, 1 H), 8.41 (d, 1 H, J = 8.4 Hz), 8.30 (d, 1 H, J = 8.0 Hz), 8.17 (d, 1 H, J = 8.0 Hz), 7.88 (d, 1 H, J = 7.6 Hz), 7.79 (s, 1 H), 7.72 (t, 1 H, J = 8.0 Hz) , 7.60 (d, 1 H, J = 8.0 Hz), 7.41-7.44 (m, 2 H), 7.15 (t, 1 H, J = 7.6 Hz), 4.35 (s, 2 H), 3.37 (brs, 4 H), 3.31 (brs, 4 H); ¹³ C NMR (150 MHz, DMSO- d ₆ ) δ 163.2, 162.3, 149.1, 148.5, 140.9, 138.6, 135.9, 134.6, 133.9, 131.5, 128.9, 127.4, 126.0, 124.6, 122.1, 121.5, 120.7, 113.9, 113.4 , 60.1, 48.2, 41.2.

4-Nitro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol- 2 -yl ) phenyl) benzamide hydrochloride [4-Nitro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77o)

Yellow solid; Reaction time, 9 hours; Yield, 99.5%; ¹ H NMR (500 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.32 (d, 1 H, J = 8.0 Hz), 8.26 (d, 2 H, J = 8.0 Hz), 8.10-8.05 ( m, 3 H), 7.72 (s, 1 H), 7.68 (d, 1 H, J = 8.0 Hz), 7.53 (t, 1 H, J = 8.0 Hz), 7.41 (d, 1 H, J = 8.5 Hz), 7.29 (t, 1 H, J = 8.0 Hz), 4.29 (s, 2 H), 3.35 (brs, 4 H), 3.29 (brs, 4 H).

3,4,5- Trimethoxy - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [3,4,5- Trimethoxy - N -(2- (6- ( piperazin -1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77p) and 3,4,5- Site Remethoxy- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] Oxazol-2-yl) phenyl) benzamide 2,2,2-trifluoroacetate [3,4,5-trimethoxy- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide 2,2,2- trifluoroacetate ] ( 77pp )

HCl salt ( 77p ): white solid; Reaction time, 8 hours; Yield, 81.0%; ¹ H NMR (400 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.21 (brd, 1 H, J = 8.4 Hz), 7.74 (brd, 1 H, J = 8.0 Hz), 7.51 (s, 1 H), 7.24-7.11 (m, 3 H), 6.96 (t, 1 H, J = 8.4 Hz), 6.83 (s, 2 H), 3.99 (s, 2 H), 3.63 (s, 9 H) , 3.23 (brs, 4 H), 3.03 (brs, 4 H); ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.08 (s, 1 H), 9.55 (brs, 2 H), 8.80 (d, 1 H, J = 8.0 Hz), 8.28 (d, 1 H, J = 8.5 Hz), 8.18 (brs, 1 H), 7.79 (d, 1 H, J = 8.5 Hz), 7.71-7.67 (m, 2 H), 7.37-7.34 (m, 3 H), 4.49 (brs, 2 H), 3.91 (s, 6 H), 3.78 (s, 3 H), 3.38 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 165.6, 163.3, 153.7, 149.4, 141.8, 141.6, 139.4, 134.1, 130.6, 129.6, 129.2, 124.5, 121.0, 119.9, 114.7, 114.0, 105.7, 60.9, 59.3 , 56.8, 48.2, 41.0

TFA salt ( 77pp ): white solid; Reaction time, 15 hours; Yield, 82.7%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.15 (s, 1 H), 8.90 (brs, 2 H), 8.82 (d, 1 H, J = 8.5 Hz), 8.25 (d, 1 H, J = 8.0 Hz), 7.88 (s, 1 H), 7.72 (d, 1 H, J = 8.5 Hz), 7.68 (t, 1 H, J = 8.0 Hz), 7.47 (d, 1 H, J = 8.0 Hz ), 7.37 (s, 2 H), 7.35 (t, 1 H, J = 8.0 Hz), 3.94 (brs, 2 H), 3.91 (s, 6 H), 3.78 (s, 3 H), 3.18 (brs , 4 H), 2.81 (brs, 4 H).

2,4- Dichloro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [2,4- Dichloro - N -(2- (6- ( piperazin -One- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77q)

White solid; Reaction time, 8 hours; Yield, 92.1%; ¹ H NMR (400 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.39 (d, 1 H, J = 8.0 Hz), 8.20 (d, 1 H, J = 8.0 Hz), 7.96 (s, 1 H), 7.80 (d, 1 H, J = 8.0 Hz), 7.76 (d, 1 H, J = 2.0 Hz), 7.73 (d, 1 H, J = 8.0 Hz), 7.68 (td, 1 H, J = 8.0, 1.6 Hz), 7.62 (dd, 1 H, J = 8.4, 2.0 Hz), 7.52 (dd, 1 H, J = 8.4, 1.2 Hz), 7.41 (td, 1 H, J = 8.0, 1.2 Hz), 4.40 (s, 2 H), 3.32 (brs, 4 H), 3.29 (brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 164.8, 163.1, 149.6, 141.8, 137.7, 136.7, 135.0, 134.0, 132.1, 131.2, 130.6, 129.9, 128.9, 128.6, 128.4, 125.8, 122.5, 120.4, 115.9, 114.4, 59.9, 48.2, 41.1.

3,4- Dichloro - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [3,4- Dichloro - N -(2- (6- ( piperazin -One- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77r)

White solid; Reaction time, 7 hours; Yield, 99.2%; ¹ H NMR (400 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.50 (d, 1 H, J = 8.4 Hz), 8.09 (d, 1 H, J = 1.2 Hz), 8.04 (d, 1 H, J = 8.0 Hz), 7.91 (s, 1 H), 7.86 (dd, 1 H, J = 8.8, 1.2 Hz), 7.78 (d, 1 H, J = 8.4 Hz), 7.69 (d, 1 H, J = 7.6 Hz), 7.54-7.50 (m, 2 H), 7.24 (t, 1 H, J = 7.6 Hz), 4.33 (s, 2 H), 3.35 (brs, 4 H), 3.23 (brs , 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 163.2, 162.9, 149.2, 141.1, 138.5, 135.9, 134.9, 134.0, 132.5, 132.1, 129.7, 129.2, 129.1, 128.7, 128.2, 124.9, 120.6, 119.8, 113.8, 60.2, 48.5, 41.8.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) nicotinamide hydrochloride [ N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride] (77s)

White solid; Reaction time, 8 hours; Yield, 98%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.34 (s, 1 H), 9.84 (brs, 2 H), 9.33 (s, 1 H), 8.96 (d, 1 H, J = 4.8 Hz), 8.67-8.64 (m, 2 H), 8.28 (d, 1 H, J = 8.0 Hz), 8.24 (s, 1 H), 8.02 (d, 1 H, J = 8.0 Hz), 7.92 (dd, 1 H , J = 8.0, 5.2 Hz), 7.76 (d, 1 H, J = 8.0 Hz), 7.71 (t, 1 H, J = 8.0 Hz), 7.40 (t, 1 H, J = 7.6 Hz), 4.59 ( s, 2 H), 3.47 (brs, 8 H); ¹³ C NMR (125 MHz, DMSO- d ₆ ) δ 163.3, 163.0, 151.0, 149.2, 147.1, 141.6, 138.4, 137.9, 133.8, 131.3, 129.4, 129.3, 127.7, 125.6, 125.0, 121.6, 120.2, 114.8, 114.7 , 58.6, 47.7, 41.5.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Isoninicotinamide  Hydrochloride [ N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) isonicotinamide hydrochloride] (77t)

Yellow solid; Reaction time, 10 hours; Yield, 93%; ¹ H NMR (400 MHz, DMSO- d ₆ + 2 drops of D ₂ O) δ 8.99 (dd, 2 H, J = 5.2 Hz), 8.53 (d, 1 H, J = 8.4 Hz), 8.19-8.18 ( m, 3 H), 8.02 (s, 1 H), 7.94 (d, 1 H, J = 8.4 Hz), 7.66-7.60 (m, 2 H), 7.37 (t, 1 H, J = 8.0 Hz), 4.55 (s, 2 H), 3.43 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 163.1, 163.0, 149.3, 148.1, 145.3, 141.8, 137.8, 134.1, 129.6, 129.4, 127.3, 125.8, 123.5, 121.7, 120.7, 114.8, 59.5, 48.0, 40.6.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) -1- Naphthaamide  Hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride] (77u)

White solid; Reaction time, 6 hours; Yield, 98.9%; ¹ H NMR (400 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 8.55 (d, 1 H, J = 8.0 Hz), 8.29 (d, 1 H, J = 8.0 Hz), 8.15 (d, 1 H, J = 8.0 Hz), 8.11 (d, 1 H, J = 8.0 Hz), 8.00 (d, 1 H, J = 8.0 Hz), 7.94 (d, 1 H, J = 7.2 Hz), 7.81 ( s, 1 H), 7.68-7.60 (m, 2 H), 7.59-7.51 (m, 2 H), 7.46 (d, 1 H, J = 8.8 Hz), 7.40 (d, 1 H, J = 8.4 Hz ), 7.35 (t, 1 H, J = 7.6 Hz), 4.24 (s, 2 H), 3.26 (brs, 4 H), 3.17 (brs, 4 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of D ₂ O) δ 168.2, 163.1, 149.5, 141.5, 138.4, 134.0, 134.0, 133.9, 132.2, 130.1, 129.6, 129.2, 129.0, 128.6, 128.1, 127.4, 126.6, 125.8, 125.5, 125.3, 121.9, 120.0, 115.1, 114.0, 60.3, 48.3, 41.4.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) -2- Naphthaamide  Hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] (77v)

White solid; Reaction time, 5 hours; Yield, 97.2%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.54 (s, 1 H), 9.35 (brs, 2 H), 8.82 (d, 1 H, J = 8.0 Hz), 8.70 (s, 1 H), 8.23 (d, 1 H, J = 7.6 Hz), 8.16 (s, 1 H), 8.16-8.11 (m, 2 H), 8.05-8.01 (m, 2 H), 7.88 (d, 1 H, J = 8.4 Hz), 7.70-7.63 (m, 4 H), 7.34 (t, 1 H, J = 8.0 Hz), 4.35 (s, 2 H), 3.36 (brs, 4 H), 3.21 (brs, 4 H) ; ¹³ C NMR (125 MHz, D ₂ O) δ 164.7, 161.6, 147.5, 140.1, 136.7, 133.9, 132.5, 131.0, 128.8, 128.2, 127.9, 127.7, 127.6, 127.3, 127.1, 126.7, 126.4, 125.5, 123.1, 122.2, 118.5, 118.4, 112.7, 111.0, 60.2, 47.8, 40.8.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoline-2- Carboxamide  Hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride] (77w)

White solid; Reaction time, 7 hours; Yield, 98.0%; ¹ H NMR (500 MHz, D ₂ O) δ 7.73 (d, 1 H, J = 8.0 Hz), 7.69 (d, 1 H, J = 8.5 Hz), 7.44 (d, 1 H, J = 7.5 Hz) , 7.27 (td, 1 H, J = 7.5, 1.5 Hz), 7.21-7.16 (m, 2 H), 7.13 (d, 1 H, J = 8.0 Hz), 7.12 (d, 1 H, J = 8.0 Hz ), 6.94 (s, 1 H), 6.86-6.83 (m, 2 H), 6.81 (dd, 1 H, J = 8.0, 1.5 Hz), 6.64 (td, 1 H, J = 8.0, 1.0 Hz), 3.94 (s, 2 H), 3.43 (brs, 4 H), 3.26 (brs, 4 H).

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoxaline-2- Kaboksami Degree Dihydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) quinoxaline-2-carboxamide dihydrochloride ] (77x) and N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoxaline-2-carboxamide 2,2,2- Trifluoroacetate Tate [ N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide 2,2,2- trifluoroacetate ] ( 77xx )

HCl salt ( 77x ): yellow solid; Reaction time, 10 hours; Yield, 46%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 13.50 (s, 1 H), 12.39 (brs, 1 H), 9.64 (brs, 2 H), 9.57 (s, 1 H), 8.96 (d, 1 H, J = 8.5 Hz), 8.35 (d, 1 H, J = 8.0 Hz), 8.26-8.18 (m, 3 H), 8.11 (t, 1 H, J = 8.0 Hz), 8.06-8.01 (m, 2 H), 7.78 (brd, 1 H, J = 8.0 Hz), 7.69 (t, 1 H, J = 8.0 Hz), 7.36 (t, 1 H, J = 8.0 Hz), 4.57 (s, 2 H) , 3.47 (brs, 4 H), 3.31 (brs, 4 H); ¹³ C NMR (125 MHz, DMSO- d ₆ ) δ 162.8, 162.6, 149.3, 144.3, 144.2, 143.7, 141.9, 140.0, 138.4, 133.8, 132.9, 132.4, 130.1, 129.7, 129.4, 120.7, 120.0, 114.5, 113.8 , 58.9, 47.9, 40.8.

TFA salt ( 77xx ): yellow solid; Reaction time, 2 hours; Yield, 90%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 13.53 (s, 1 H), 9.57 (s, 1 H), 9.04 (brs, 2 H), 8.95 (d, 1 H, J = 8.8 Hz), 8.33 (d, 1 H, J = 8.0 Hz), 8.22 (d, 1 H, J = 8.0 Hz), 8.22 (d, 1 H, J = 8.0 Hz), 8.09 (t, 1 H, J = 8.0 Hz) ), 8.04 (t, 1 H, J = 7.6 Hz), 7.99 (d, 1 H, J = 8.4 Hz), 7.93 (s, 1 H), 7.67 (t, 1 H, J = 8.0 Hz), 7.58 (d, 1 H, J = 8.0 Hz), 7.36 (t, 1 H, J = 8.0 Hz), 4.23 (s, 2 H), 3.28 (brs, 4 H), 3.08 (brs, 4 H); ¹³ C NMR (125 MHz, DMSO- d ₆ ) δ 162.7, 162.2, 158.9 (q, J = 18.2 Hz), 149.4, 144.2, 144.2, 143.7, 141.2, 141.2, 140.0, 138.3, 133.6, 132.9, 132.3, 129.9 , 129.7, 129.1, 128.1, 124.5, 120.6, 119.8, 116.6 (q, J = 236.8 Hz), 113.9, 113.1, 60.3, 48.8, 42.1.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl)-(1,1'- Biphenyl ] -4-carboxamide Hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl)-[1,1'-biphenyl] -4-carboxamide hydrochloride] (77y)

White solid; Reaction time, 8 hours; Yield, 98%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.53 (s, 1 H), 9.65 (brs, 2 H), 8.87 (d, 1 H, J = 8.0 Hz), 8.27 (d, 1 H, J = 8.0 Hz), 8.24 (d, 2 H, J = 8.4 Hz), 8.09 (brs, 1 H), 8.09 (d, 1 H, J = 8.0 Hz), 8.01 (d, 2 H, J = 8.0 Hz ), 7.81 (d, 2 H, J = 8.0 Hz), 7.76 (brd, 1 H, J = 8.0 Hz), 7.69 (t, 1 H, J = 8.0 Hz), 7.53 (t, 2 H, J = 8.0 Hz), 7.44 (t, 1 H, J = 8.0 Hz), 7.35 (t, 1 H, J = 8.0 Hz), 4.55 (brs, 2 H), 3.38 (brs, 8 H); ¹³ C NMR (125 MHz, DMSO- d ₆ ) δ 165.1, 163.1, 149.1, 144.2, 141.4, 139.4, 139.3, 133.9, 133.5, 129.6, 129.2, 128.8, 128.5, 127.8, 127.5, 125.9, 124.2, 120.6, 120.2 , 114.6, 113.4, 58.9, 47.9, 41.0.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Cyclohexanecarboxamide Hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (77z)

White solid; Reaction time, 6 hours; Yield, 77.8%; ¹ H NMR (500 MHz, D ₂ O) δ 7.60 (d, 1 H, J = 8.5 Hz), 7.56 (d, 1 H, J = 7.5 Hz), 7.38 (s, 1 H), 7.24 (d, 1 H, J = 8.0 Hz), 7.19 (t, 1 H, J = 8.0 Hz), 7.18 (d, 1 H, J = 8.0 Hz), 7.00 (t, 1 H, J = 7.5 Hz), 4.26 ( s, 2 H), 3.47 (brs, 4 H), 3.41 (brs, 4 H), 2.00 (m, 1 H), 1.72-1.56 (m, 5 H), 1.20-1.02 (m, 5 H); ¹³ C NMR (125 MHz, D ₂ O) δ 177.9, 162.6, 148.8, 141.1, 136.5, 132.8, 128.8, 127.8, 126.3, 124.5, 121.2, 119.6, 114.4, 113.3, 60.6, 48.0, 46.3, 41.0, 29.2, 25.3, 25.2.

N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Shinnamamide  Hydrochloride [ N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride] (77A)

Yellow solid; Reaction time, 7 hours; Yield, 92.2%; ¹ H NMR (500 MHz, D ₂ O) δ 7.54 (d, 1 H, J = 8.5 Hz), 7.30 (d, 1 H, J = 8.0 Hz), 7.25 (t, 1 H, J = 7.5 Hz) , 7.18 (s, 1 H), 7.14 (t, 2 H, J = 7.5 Hz), 7.01 (dd, 1 H, J = 8.0, 1.5 Hz), 6.96-6.94 (m, 3 H), 6.88 (td , 1 H, J = 8.0, 1.5 Hz), 6.69 (d, 1 H, J = 16.5 Hz), 6.64 (t, 1 H, J = 8.0 Hz), 5.58 (d, 1 H, J = 16.0 Hz) , 3.98 (s, 2 H), 3.43 (brs, 4 H), 3.31 (brs, 4 H); ¹³ C NMR (150 MHz, D ₂ O + DMSO- d ₆ ) δ 165.6, 162.6, 148.7, 141.2, 141.2, 137.3, 133.6, 133.1, 130.7, 129.2, 128.5, 128.0, 127.9, 126.4, 124.0, 120.8, 119.7 , 113.5, 112.3, 60.5, 48.0, 41.0.

4- methyl - N -(2- (6- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Benzenesulfonamide [4-Methyl- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzenesulfonamide] (77BBB)

Yellow solid; Reaction time, 12 hours; Yield, 75%; ¹ H NMR (500 MHz, DMSO- d ₆ + 2 drops of D ₂ O) δ 8.02 (d, 1 H, J = 8.0 Hz), 7.83 (d, 1 H, J = 8.5 Hz), 7.70 (s, 1 H), 7.68 (d, 2 H, J = 8.0 Hz), 7.57 (d, 1 H, J = 8.0 Hz), 7.49 (td, 1 H, J = 8.0, 1.5 Hz), 7.40 (d, 1 H, J = 8.0 Hz), 7.14 (d, 2 H, J = 8.0 Hz), 7.20 (t, 1 H, J = 8.0 Hz), 3.62 (s, 2 H), 2.81 (t, 4 H, J = 4.5 Hz), 2.40 (brs, 4 H), 2.25 (s, 3 H).

1-5. Synthesis of Compounds 78-86

Compounds 78 to 86 were synthesized as in Scheme 5 below.

[Scheme 5]

26) 2- methyl -6-Nitrophenol [2-Methyl-6- nitrophenol ] (78)

After cooling the mixed solution of acetic acid (30 mL) and nitric acid (14 mL) to -15 ° C, a solution of acetic acid (20 mL) of o -cresol (10.0 g) was slowly added (the temperature of the reaction mixture was -10. It was added over 1 hour while not rising above ℃.). After stirring at room temperature for 1 hour, the reaction mixture was poured into ice water, and then left standing for 30 minutes. The resulting solid was obtained by filtration, dissolved in diethyl ether, washed with saturated aqueous sodium bicarbonate and water, and then the organic layer was dried over Na ₂ SO ₄ , and the filtrate obtained by filtration under reduced pressure was concentrated under reduced pressure to recrystallize the obtained residue in ethanol. Compound 78 (6.0 g) was obtained.

Light yellow solid; Yield, 42%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.90 (s, 1 H), 7.94 (d, 1 H, J = 8.0 Hz), 7.44 (d, 1 H, J = 8.0 Hz), 6.86 (t, 1 H, J = 8.0 Hz), 2.32 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 153.9, 138.4, 133.7, 129.7, 122.8, 119.5, 16.1.

27) 2-Amino-6- Methylphenol [2-Amino-6- methylphenol ] (79)

An aqueous solution (50 mL) containing Na ₂ S ₂ O ₄ (40.93 g, 235 mmol) was slowly added into a solution of methanol (50 mL) containing compound 78 (6.0 g, 39 mmol), and then the reaction mixture was 2 It was stirred at reflux for an hour. After cooling at room temperature, the resulting solid was filtered off, the filtrate was concentrated under reduced pressure, EtOAc and water were added, the EtOAc layer was dried over Na ₂ SO ₄ , and the filtrate obtained by filtration under reduced pressure was concentrated under reduced pressure to yield compound 79 . Got.

Orange solid; Yield, 77%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 6.71 (t, 1 H, J = 7.5 Hz), 6.65 (d, 1 H, J = 7.5 Hz), 6.63 (d, 1 H, J = 7.5 Hz), 4.16 (brs, 3 H), 2.22 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 143.3, 134.4, 124.5, 122.1, 121.1, 115.7, 16.1.

28) ( E )-2- methyl -6-((2- Nitrobenzylidene ) Amino) phenol [( E ) -2-Methyl-6-((2-nitrobenzylidene) amino) phenol] (80)

Anhydrous DMF ( N , N- dimethylformamide) solution containing compound 79 (3.7 g, 30 mmol) and 2-nitrobenzaldehyde (3.6 g, 30 mmol) was stirred at 80 ° C. for 90 minutes, Cool to room temperature, add butanol / diethyl ether (20 mL / 20 mL) and water and stir for 5 minutes. The resulting solid was filtered and washed with water to give compound 80 (5.617 g).

Yellow solid; Yield, 91%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 9.13 (s, 1 H), 8.24 (d, 1 H, J = 8.0 Hz), 8.04 (d, 1 H, J = 8.4 Hz), 7.73 (t, 1 H, J = 7.6 Hz), 7.62 (t, 1 H, J = 8.0 Hz), 7.29 (s, 1 H), 7.19 (d, 1 H, J = 8.0 Hz), 7.11 (d, 1 H, J = 7.6 Hz), 6.83 (t, 1 H, J = 7.6 Hz), 2.30 (s, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 151.9, 151.4, 149.5, 134.4, 133.6, 131.5, 131.5, 130.8, 129.7, 125.1, 124.9, 119.8, 114.0, 15.9.

29) 7- methyl -2- (2-nitrophenyl) benzo [ d ] Oxazole [7-Methyl-2- (2-nitrophenyl) benzo [ d ] oxazole] (81)

A small amount of DDQ (2,3-dichloro-5,6-dicyano- p- benzoquinone, 4.98 g, 21 mmol) at 0 ° C. into a solution of anhydrous methylene chloride (100 mL) containing compound 80 (5.617 g, 21 mmol) Each was added. After the reaction mixture was stirred at room temperature for 3 hours, methylene chloride and sodium bicarbonate were added to the filtrate obtained by passing through the celite filtration layer, the organic layer was dried over MgSO ₄ , and the filtrate obtained by filtration under reduced pressure was concentrated under reduced pressure to yield compound 81. (4.90 g, 88%).

Yellow solid; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 8.21 (dd, 1 H, J = 7.5, 1.5 Hz), 8.10 (dd, 1 H, J = 8.0, 1.0 Hz), 7.91 (td, 1 H, J = 7.5, 1.5 Hz), 7.87 (td, 1 H, J = 7.5, 1.5 Hz), 7.64 (d, 1 H, J = 8.0 Hz), 7.33 (t, 1 H, J = 7.5 Hz), 7.29 (d, 1 H, J = 7.5 Hz), 3.32 (s, 3 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 158.5, 150.1, 149.4, 141.2, 133.8, 133.6, 131.7, 127.7, 125.9, 125.0, 121.9, 120.5, 118.3, 15.4.

30) 7- ( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] Oxazole [7- ( Bromomethyl )-2- (2-nitrophenyl) benzo [ d ] oxazole] (82)

NBS ( N- bromosuccinimide, 4.67 g, 19.28 mmol) and benzoyl peroxide (170 mg, 0.96 mmol) were slowly added into an anhydrous chloroform (450 mL) solution containing compound 81 (4.90 g, 19.27 mmol), followed by 25 hours. While stirring at reflux. After adding methylene chloride and water, the organic layer was dried over anhydrous MgSO ₄ , filtered, and the resulting filtrate was concentrated under reduced pressure to recrystallize the obtained residue with a methylene chloride: hexane (5: 1) mixed solvent to give compound 82 (4.78 g, 74%) as a white solid.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.14 (d, 1 H, J = 8.0 Hz), 7.91 (d, 1 H, J = 8.0 Hz), 7.76-7.68 (m, 3 H), 7.41 (d , 1 H, J = 8.0 Hz), 7.35 (t, 1 H, J = 8.0 Hz), 4.72 (s, 2 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 173.4, 159.2, 149.2, 142.1, 132.7, 132.3, 131.7, 127.0, 125.5, 124.5, 121.9, 121.4, 121.3, 28.9.

31) Turt - Butyl  4-((2- (2-nitrophenyl) benzo [ d ] Oxazole -7 days) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-nitrophenyl) benzo [ d ] oxazol -7-yl) methyl) piperazine-1-carboxylate] (83)

Butyl piperazine-1-carboxylate (tert -butyl piperazine-1-carboxylate , 1-Boc-piperazine, 5.5 g, 29.53 - Compound 82 (3.28 g, 9.85 mmol) in anhydrous THF (50 mL) solution containing tert into mmol) and anhydrous triethylamine (Et ₃ N, 1.3 mL, 9.34 mmol) were added slowly. After stirring at room temperature for 12 hours, methylene chloride and water were added, and the organic layer was dried over anhydrous MgSO ₄ , filtered, and the filtrate was concentrated under reduced pressure to obtain a residue obtained by silica gel column chromatography (methylene chloride → methylene chloride: methanol). = 30: 1) to give compound 83 .

Beige solid; Yield, 74%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.16 (d, 1 H, J = 8.0 Hz), 7.88 (d, 1 H, J = 8.0 Hz), 7.76-7.71 (m, 2 H), 7.69 (t , 1 H, J = 8.0 Hz), 7.37 (d, 1 H, J = 8.0 Hz), 7.35 (t, 1 H, J = 8.0 Hz), 3.81 (s, 2 H), 3.44 (brt, 4 H , J = 4.4 Hz), 2.45 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.0, 155.0, 150.5, 149.5, 141.6, 132.5, 132.1, 131.6, 127.3, 125.1, 124.4, 121.8, 121.6, 119.8, 79.8, 56.9, 52.9, 44.4, 28.6.

32) Turt - Butyl  4-((2- (2-aminophenyl) benzo [ d ] Oxazole -7 days) methyl ) Piperazine-1- Carboxylate [ tert -Butyl 4-((2- (2-aminophenyl) benzo [ d ] oxazol -7-yl) methyl) piperazine-1-carboxylate] (84)

10 wt.% Pd / C (palladium on carbon, 250 mg) was added into a methylene chloride (50 mL) solution containing compound 83 (2.57 g, 5.86 mmol), and the air in the reaction vessel was replaced with hydrogen gas, and then at room temperature. Stir for 6 hours. The reaction mixture was filtered using celite as the filter filler, and the filtrate was concentrated under reduced pressure to obtain compound 84 (1.9 g, 79%) as a beige solid.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (dd, 1 H, J = 8.0, 1.6 Hz), 7.62 (dd, 1 H, J = 8.0, 2.0 Hz), 7.32-7.26 (m, 3 H) , 6.81-6.77 (m, 2 H), 6.19 (s, 2 H), 3.92 (s, 2 H), 3.45 (brs, 4 H), 2.51 (brs, 4 H), 1.44 (s, 9 H) ; ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.2, 155.0, 148.5, 148.1, 141.9, 132.6, 128.9, 126.0, 124.5, 120.7, 118.5, 117.0, 116.5, 108.8, 79.9, 56.9, 53.0, 44.2, 28.7.

33) Synthesis of Compound 85

Appropriate acyl chloride (1.3 eq) and anhydrous pyridine (5.0 eq) were added into an anhydrous methylene chloride (3 mL) solution containing compound 84 (65 mg, 0.16 mmol), followed by stirring at room temperature for 3 to 5 hours. Methylene chloride and sodium bicarbonate water were added to the reaction mixture, and the organic layer was dried over anhydrous MgSO ₄ , filtered, and the residue obtained by concentrating the filtrate under reduced pressure was subjected to silica gel column chromatography (methylene chloride: methanol = 40: 1 to 70: 1). ) To give compound 85 .

Turt - Butyl  4-((2- (2-benzamidophenyl) benzo [ d ] Oxazole -7 days) methyl ) Piperazine-1- Car Succinate [ tert -Butyl 4-((2- (2-benzamidophenyl) benzo [ d ] oxazol -7-yl) methyl) piperazine-1-carboxylate] (85a)

Yield, 91%; ¹ H-NMR (400 MHz, CDCl ₃ ) δ 12.79 (s, 1 H), 9.05 (d, 1 H, J = 8.8 Hz), 8.26-8.24 (m, 3 H), 7.64 (dd, 1 H, J = 7.2, 1.2 Hz), 7.60-7.56 (m, 4 H), 7.40 (d, 1 H, J = 7.6 Hz), 7.36 (t, 1 H, J = 7.6 Hz), 7.25 (t, 1 H , J = 7.6 Hz), 3.91 (s, 2 H), 3.46 (brs, 4 H), 2.51 (brs, 4 H), 1.44 (s, 9 H); ¹³ C-NMR (100MHz, CDCl ₃ ) δ 166.4, 162.3, 155.0, 148.5, 140.9, 139.7, 135.4, 133.2, 132.2, 128.9, 128.6, 128.1, 126.9, 125.2, 123.3, 121.6, 120.7, 118.4, 113.4, 79.9 , 56.8, 53.1, 43.3, 28.6.

Turt - Butyl  4-((2- (2- (2-fluorobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2-fluorobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85b)

Yield, 27%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.62 (s, 1 H), 9.00 (d, 1 H, J = 8.4 Hz), 8.24 (dd, 1 H, J = 8.0, 1.2 Hz), 8.08 (td , 1 H, J = 8.0, 1.6 Hz), 7.62-7.52 (m, 3 H), 7.39-7.23 (m, 5 H), 3.96 (s, 2 H), 3.48 (brs, 4 H), 2.56 ( brs, 4 H), 1.44 (s, 9 H).

Turt - Butyl  4-((2- (2- (4-fluorobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-fluorobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85c)

Yield, 86%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.70 (s, 1 H), 8.97 (d, 1 H, J = 8.4 Hz), 8.24-8.20 (m, 3 H), 7.59 (d, 1 H, J = 7.2 Hz), 7.54 (t, 1 H, J = 7.6 Hz), 7.39-7.33 (m, 2 H), 7.25-7.20 (m, 3 H), 3.89 (s, 2 H), 3.46 (brs, 4 H), 2.50 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3 (d, J = 251.1 Hz), 165.1, 162.2, 155.0, 148.5, 140.8, 139.5, 133.2, 131.6 (d, J = 3.0 Hz), 130.4 (d, J = 9.1 Hz), 128.5, 127.0, 125.2, 123.3, 121.6, 120.6, 118.3, 115.9 (d, J = 21.2 Hz), 113.3, 79.9, 56.8, 53.1, 43.4, 28.6.

Turt - Butyl  4-((2- (2- (2-bromobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2-bromobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85d)

Yield, 93%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.40 (s, 1 H), 9.00 (d, 1 H, J = 8.4 Hz), 8.25 (dd, 1 H, J = 8.0, 1.6 Hz), 7.76-7.71 (m, 2 H), 7.60 (m, 1 H), 7.49-7.45 (m, 2 H), 7.40-7.36 (m, 2 H), 7.33-7.24 (m, 2 H), 4.00 (s, 2 H), 3.50 (brs, 4 H), 2.59 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.8, 161.9, 154.9, 148.6, 140.9, 139.1, 138.6, 134.2, 133.2, 131.8, 129.6, 128.6, 127.7, 127.4, 125.2, 123.8, 120.9, 120.4, 120.2, 119.1 , 113.5, 80.1, 56.4, 52.7, 43.4, 28.6.

Turt - Butyl  4-((2- (2- (3-bromobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-bromobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85e)

Yield, 74%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.81 (s, 1 H), 8.98 (d, 1 H, J = 8.8 Hz), 8.46 (t, 1 H, J = 1.2 Hz), 8.21 (dd, 1 H, J = 8.0, 1.2 Hz), 8.15 (d, 1 H, J = 7.6 Hz), 7.77 (dd, 1 H, J = 7.2, 1.6 Hz), 7.70 (d, 1 H, J = 8.0, 1.2 Hz), 7.55 (td, 1 H, J = 8.0, 1.6 Hz), 7.44-7.34 (m, 3 H), 7.23 (t, 1 H, J = 8.4 Hz), 3.91 (s, 2 H), 3.47 (brs, 4 H), 2.52 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.5, 162.1, 154.9, 148.5, 140.8, 139.3, 137.2, 135.0, 133.3, 130.8, 130.6, 128.5, 127.2, 127.1, 125.3, 123.5, 123.0, 121.3, 120.6, 118.7 , 113.4, 79.9, 56.7, 53.0, 43.4, 28.6.

Turt - Butyl  4-((2- (2- (4-bromobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-bromobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85f)

Yield, 92%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.78 (s, 1 H), 8.99 (d, 1 H, J = 8.4 Hz), 8.24 (dd, 1 H, J = 8.0, 1.2 Hz), 8.11 (d , 2 H, J = 8.8 Hz), 7.70 (d, 2 H, J = 8.8 Hz), 7.63 (dd, 1 H, J = 7.2, 1.6 Hz), 7.58 (td, 1 H, J = 8.0, 1.2 Hz), 7.41-7.35 (m, 2 H), 7.26 (td, 1 H, J = 7.6, 1.2 Hz), 3.91 (s, 2 H), 3.46 (brs, 4 H), 2.51 (brs, 4 H) ), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3, 162.2, 155.0, 148.5, 140.8, 139.4, 134.3, 133.3, 132.1, 129.6, 128.6, 127.0, 125.2, 123.5, 121.6, 120.6, 118.4, 113.4, 79.9, 56.8 , 53.1, 43.9, 28.6.

Turt - Butyl  4-((2- (2- (2-chlorobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (2- chlorobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85g)

Yield, 78%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.47 (s, 1 H), 9.02 (d, 1 H, J = 8.8 Hz), 8.25 (d, 1 H, J = 8.4 Hz), 7.79 (dd, 1 H, J = 7.2, 1.6 Hz), 7.60 (t, 1 H, J = 8.0 Hz), 7.53 (d, 1 H, J = 7.6 Hz), 7.48-7.40 (m, 3 H), 7.37 (d, 1 H, J = 7.2 Hz), 7.33-7.26 (m, 2 H), 3.91 (s, 2 H), 3.46 (s, 4 H), 2.51 (s, 4 H), 1.44 (s, 9 H) ; ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.9, 161.9, 155.0, 148.5, 140.8, 139.1, 136.5, 133.2, 132.0, 131.7, 131.0, 129.8, 128.5, 127.2, 126.9, 125.1, 123.7, 121.3, 120.9, 118.7 , 113.6, 79.9, 56.8, 53.0, 43.8, 28.6.

Turt - Butyl  4-((2- (2- (3-chlorobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-chlorobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85h)

Yield, 92%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.83 (s, 1 H), 8.97 (d, 1 H, J = 8.4 Hz), 8.31 (t, 1 H, J = 1.6 Hz), 8.21 (dd, 1 H, J = 8.0, 1.2 Hz), 8.10 (dd, 1 H, J = 8.0, 1.2 Hz), 7.71 (dd, 1 H, J = 6.8, 2.0 Hz), 7.57-7.53 (m, 2 H), 7.48 (t, 1 H, J = 8.0 Hz), 7.39-7.34 (m, 2 H), 7.23 (t, 1 H, J = 7.6 Hz), 3.89 (s, 2 H), 3.46 (brs, 4 H ), 2.51 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.6, 162.1, 155.0, 148.5, 140.7, 139.3, 137.0, 135.0, 133.2, 132.1, 130.3, 128.5, 128.0, 127.0, 126.6, 125.3, 123.5, 121.5, 120.6, 118.5 , 113.4, 79.9, 56.8, 53.1, 44.3, 28.7.

Turt - Butyl  4-((2- (2- (4-chlorobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-chlorobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85i)

Yield, 37%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.80 (s, 1 H), 9.01 (d, 1 H, J = 8.4 Hz), 8.26 (d, 1 H, J = 8.0 Hz), 8.19 (d, 2 H, J = 8.8 Hz), 7.64 (d, 1 H, J = 7.2 Hz), 7.59 (t, 1 H, J = 7.6 Hz), 7.55 (d, 2 H, J = 8.4 Hz), 7.42-7.36 (m, 2 H), 7.26 (t, 1 H, J = 7.6 Hz), 3.92 (s, 2 H), 3.46 (brs, 4 H), 2.52 (brs, 4 H), 1.44 (s, 9 H ); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 165.3, 162.2, 155.0, 148.5, 140.8, 139.5, 138.5, 133.9, 133.3, 129.5, 129.2, 128.6, 127.0, 125.2, 123.5, 121.6, 120.7, 118.4, 113.4, 79.9 , 56.8, 53.1, 43.9, 28.6.

Turt - Butyl  4-((2- (2- (3-nitrobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3-nitrobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85j)

Yield, 82%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 13.07 (s, 1 H), 9.27 (t, 1 H, J = 1.6 Hz), 9.01 (d, 1 H, J = 8.4 Hz), 8.59 (d, 1 H, J = 8.0 Hz), 8.46 (d, 1 H, J = 8.0 Hz), 8.26 (dd, 1 H, J = 8.0, 1.2 Hz), 7.91 (m, 1 H), 7.76 (t, 1 H , J = 8.0 Hz), 7.59 (td, 1 H, J = 8.0, 1.6 Hz), 7.41-7.40 (m, 2 H), 7.28 (t, 1 H, J = 8.0 Hz), 3.91 (s, 2 H), 3.46 (brs, 4 H), 2.52 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 163.3, 162.0, 155.0, 148.4, 140.7, 139.0, 136.5, 135.0, 133.3, 130.2, 128.6, 127.2, 126.8, 125.5, 123.9, 122.1, 121.4, 120.6, 119.1, 113.6 , 79.9, 56.8, 53.1, 44.2, 28.6.

Turt - Butyl  4-((2- (2- (4-nitrobenzamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (4-nitrobenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85k)

Yield, 61%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.96 (s, 1 H), 8.97 (d, 1 H, J = 7.6 Hz), 8.40 (d, 2 H, J = 8.8 Hz), 8.38 (d, 2 H, J = 8.8 Hz), 8.26 (dd, 1 H, J = 8.0, 1.6 Hz), 7.63 (dd, 1 H, J = 7.6, 1.6 Hz), 7.59 (td, 1 H, J = 8.0, 1.6 Hz), 7.43-7.37 (m, 2 H), 7.29 (td, 1 H, J = 7.6, 1.2 Hz), 3.91 (s, 2 H), 3.46 (brt, 4 H, J = 4.8 Hz), 2.51 (brs, 4 H), 1.44 (s, 9 H).

Turt - Butyl  4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] Oxazole -7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (3,4,5-trimethoxybenzamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85l)

Yield, 84%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.55 (s, 1 H), 9.05 (d, 1 H, J = 8.4 Hz), 8.28 (d, 1 H, J = 8.0 Hz), 7.60 (t, 1 H, J = 8.0 Hz), 7.57 (d, 1 H, J = 8.0 Hz), 7.45 (s, 2 H), 7.40 (d, 1 H, J = 7.6 Hz), 7.36 (t, 1 H, J = 7.6 Hz), 7.26 (t, 1 H, J = 7.6 Hz), 4.01 (s, 6 H), 3.96 (s, 3 H), 3.93 (s, 2 H), 3.46 (brs, 4 H), 2.51 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.2, 162.4, 154.9, 153.5, 148.5, 141.6, 141.0, 139.7, 133.3, 130.9, 128.7, 127.0, 125.2, 123.3, 121.7, 120.6, 118.1, 113.3, 105.6, 79.9 , 61.3, 56.8, 56.7, 53.1, 44.3, 28.6.

Turt - Butyl  4-((2- (2- (1-naphthaamido) phenyl) benzo [ d ] Oxazole -7 days) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (1-naphthamido) phenyl) benzo [ d ] oxazol -7-yl) methyl) piperazine-1-carboxylate] (85m)

Yield, 90%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 12.62 (s, 1 H), 9.14 (d, 1 H, J = 8.5 Hz), 8.65 (dd, 1 H, J = 7.5, 1.5 Hz), 8.25 (d , 1 H, J = 8.0 Hz), 8.05 (d, 1 H, J = 7.0 Hz), 8.02 (d, 1 H, J = 8.5 Hz), 7.92 (dd, 1 H, J = 7.0, 2.0 Hz) , 7.63-7.53 (m, 4 H), 7.34-7.32 (m, 2 H), 7.28-7.23 (m, 2 H), 3.87 (s, 2 H), 3.44 (brs, 4 H), 2.48 (brs , 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 168.5, 162.0, 155.0, 148.5, 140.8, 139.7, 134.8, 134.2, 133.2, 131.7, 130.8, 128.6, 127.5, 126.9, 126.7, 126.4, 126.1, 125.0, 125.0, 123.5 , 121.4, 120.8, 118.6, 113.5, 79.9, 56.8, 53.1, 44.4, 28.7.

Turt - Butyl  4-((2- (2- (2-naphthaamido) phenyl) benzo [ d ] Oxazole -7 days) methyl ) Piperazine-1-carboxylate [ tert -Butyl 4-((2- (2- (2-naphthamido) phenyl) benzo [ d ] oxazol -7-yl) methyl) piperazine-1-carboxylate] (85n)

Yield, 92%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 12.94 (s, 1 H), 9.09 (d, 1 H, J = 8.8 Hz), 8.77 (s, 1 H), 8.28 (dd, 1 H, J = 8.8 , 1.2 Hz), 8.24 (d, 1 H, J = 8.0 Hz), 8.03 (m, 1 H), 7.99 (d, 1 H, J = 8.8 Hz), 7.91 (m, 1 H), 7.68 (dd , 1 H, J = 6.0, 2.8 Hz), 7.61-7.57 (m, 3 H), 7.40-7.36 (m, 2 H), 7.24 (t, 1 H, J = 8.0 Hz), 3.90 (s, 2 H), 3.47 (brs, 4 H), 2.52 (brs, 4 H), 1.45 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 166.3, 162.3, 155.0, 148.5, 140.9, 139.8, 135.3, 133.3, 133.0, 132.6 129.4, 128.7, 128.7, 128.6, 128.2, 128.1, 127.1, 126.9, 125.2, 124.6, 123.3, 121.6, 120.7, 118.4, 113.3, 79.9, 56.8, 53.1, 43.7, 28.7.

Turt - Butyl  4-((2- (2- (quinoline-2-carboxamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (quinoline-2-carboxamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85o)

Yield, 78%; ¹ H NMR (400 MHz, CDCl ₃ ) δ 13.81 (s, 1 H), 9.15 (d, 1 H, J = 8.4 Hz), 8.42 (d, 1 H, J = 8.0 Hz), 8.41 (d, 1 H, J = 8.4 Hz), 8.36 (d, 1 H, J = 8.4 Hz), 8.27 (dd, 1 H, J = 7.6, 1.6 Hz), 7.93-7.86 (m, 3 H), 7.67 (td, 1 H, J = 7.6, 1.2 Hz), 7.61 (td, 1 H, J = 7.6, 1.6 Hz), 7.45-7.40 (m, 2 H), 7.28 (td, 1 H, J = 8.0, 1.2 Hz) , 3.94 (s, 2 H), 3.46 (brs, 4 H), 2.52 (brs, 4 H), 1.44 (s, 9 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 164.5, 161.9, 155.0, 150.8, 148.9, 147.0, 141.8, 139.0, 137.8, 132.9, 130.5, 130.2, 129.7, 128.9, 128.4, 128.1, 126.7, 125.1, 123.5, 121.4 , 121.0, 119.5, 118.8, 114.6, 79.9, 56.9, 53.1, 43.6, 28.7.

Turt - Butyl  4-((2- (2-([1,1'-biphenyl] -4- Ilka Copy Mido ) Phenyl) Benzo [ d ] Oxazole -7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2-([1,1'-biphenyl] -4-ylcarboxamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85p)

Yield, 57%; ¹ H-NMR (400 MHz, CDCl ₃ ) δ 12.85 (s, 1 H), 9.07 (d, 1 H, J = 8.4 Hz), 8.33 (d, 2 H, J = 8.0 Hz), 8.26 (d, 1 H, J = 7.6 Hz), 7.80 (d, 2 H, J = 8.0 Hz), 7.70-7.67 (m, 3 H), 7.60 (t, 1 H, J = 8.0 Hz), 7.50 (t, 2 H , J = 7.6 Hz), 7.43-7.35 (m, 3 H), 7.26 (t, 1 H, J = 8.0 Hz), 3.92 (s, 2 H), 3.45 (brs, 4 H), 2.52 (brs, 4 H), 1.45 (s, 9 H); ¹³ C-NMR (100 MHz, CDCl ₃ ) δ 166.1, 162.3, 155.0, 148.6, 144.9, 140.9, 140.3, 139.7, 134.1, 133.3, 129.2, 128.6, 128.6, 128.3, 127.6, 127.5, 127.0, 125.2, 123.3, 121.6, 120.7, 118.4, 113.4, 79.9, 56.8, 53.1, 43.6, 28.7.

Turt - Butyl  4-((2- (2- (cyclohexanecarboxamido) phenyl) benzo [ d ] Oxazole-7-yl) methyl) piperazin-1-carboxylate [ tert -Butyl 4-((2- (2- (cyclohexanecarboxamido) phenyl) benzo [ d ] oxazol-7-yl) methyl) piperazine-1-carboxylate] (85q)

Yield, 90%; ¹ H NMR (500 MHz, CDCl ₃ ) δ 11.88 (s, 1 H), 8.84 (dd, 1 H, J = 8.5, 1.0 Hz), 8.19 (dd, 1 H, J = 8.0, 1.5 Hz), 7.63 (dd, 1 H, J = 7.0, 2.0 Hz), 7.51 (td, 1 H, J = 7.5, 1.5 Hz), 7.38 (dd, 1 H, J = 8.0, 2.0 Hz), 7.37 (t, 1 H , J = 7.5 Hz), 7.18 (td, 1 H, J = 7.5, 1.0 Hz), 3.90 (s, 2 H), 3.45 (brs, 4 H), 2.50 (brs, 4 H), 2.47 (tt, 1 H, J = 12.0, 3.5 Hz), 2.13 (m, 2 H), 1.88 (dt, 2 H, J = 8.0, 3.5 Hz), 1.75 (m, 1 H), 1.68 (m, 2 H), 1.44 (s, 9 H), 1.45-1.30 (m, 3 H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 176.0, 162.2, 155.0, 148.6, 141.0, 139.7, 133.1, 128.5, 126.9, 125.1, 122.9, 121.4, 120.7, 118.6, 113.0, 79.9, 56.8, 53.0, 47.7, 43.8 , 30.0, 28.6, 26.2, 26.1.

34) Synthesis of Compound 86

1,4-dioxane and 8N-HCl (42.0 eq.) In a volume corresponding to 8N-HCl (42.0 eq.) Were added to compound 85 (1.0 eq.) In turn, and the reaction mixture was added at room temperature for 5 to 9 hours. Stir for a while. The solvent was removed by distillation under reduced pressure, and the resulting residue was filtered by adding diethyl ether in the presence of a small amount of methanol to obtain Compound 86 in the form of an HCl salt.

N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [ N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86a)

Yield, 82%; ¹ H-NMR (400 MHz, DMSO- d ₆ ) δ 12.44 (s, 1 H), 9.71 (brs, 2 H), 8.84 (d, 1 H, J = 8.0 Hz), 8.48 (d, 1 H, J = 8.4 Hz), 8.16-8.14 (m, 2 H), 8.00 (d, 1 H, J = 7.6 Hz), 7.76 (d, 1 H, J = 6.8 Hz), 7.71-7.67 (m, 4 H ), 7.55 (t, 1 H, J = 8.0 Hz), 7.35 (t, 1 H, J = 8.0 Hz), 4.73 (s, 2 H), 3.45 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 165.7, 162.5, 149.2, 141.1, 139.3, 134.9, 134.1, 133.1, 129.9, 129.9, 128.0, 126.2, 124.2, 120.8, 114.0, 53.1, 48.4, 41.5.

2- Fluoro - N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide Hydrochloride [2- Fluoro - N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (86b)

Yield, 69%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.24 (s, 1 H), 9.42 (brs, 2 H), 8.77 (d, 1 H, J = 8.4 Hz,), 8.45 (d, 1 H, J = 8.4 Hz), 7.98 (td, 1 H, J = 7.6, 1.6 Hz), 7.81 (d, 1 H, J = 8.4 Hz), 7.73-7.69 (m, 3 H), 7.53-7.43 (m, 3 H), 7.39 (t, 1 H, J = 8.0 Hz), 4.65 (brs, 2 H), 3.42 (brs, 8 H).

4- Fluoro - N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Fluoro- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86c)

Yield, 51%; ¹ H-NMR (500 MHz, DMSO- d ₆ ) δ 12.41 (s, 1 H), 9.47 (brs, 2 H), 8.81 (d, 1 H, J = 8.5 Hz), 8.47 (d, 1 H, J = 8.0 Hz), 8.22 (dd, 2 H, J = 8.0, 5.5 Hz), 8.05 (d, 1 H, J = 8.0 Hz), 7.72-7.69 (m, 2 H), 7.57-7.53 (m, 3 H), 7.37 (t, 1 H, J = 8.0 Hz), 4.65 (brs, 2 H), 3.40 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ + 3 drops of CD ₃ OD) δ 165.2 (d, J = 249.1 Hz), 164.7, 162.4, 148.9, 140.9, 138.7, 133.9, 131.1, 130.6 (d, J = 8.8 Hz), 129.7, 129.6, 126.3, 124.5, 121.4, 120.6, 116.7 (d, J = 22.2 Hz), 113.6, 54.3, 48.5, 41.5.

2- Bromo - N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [2-Bromo- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86d)

Yield, 79%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 11.84 (s, 1 H), 9.68 (brs, 2 H), 8.66 (d, 1 H, J = 7.5 Hz), 8.47 (d, 1 H, J = 8.5 Hz), 7.80 (d, 1 H, J = 7.5 Hz), 7.80 (d, 1 H, J = 7.5 Hz), 7.74-7.71 (m, 3 H), 7.61 (t, 1 H, J = 7.5 Hz), 7.51 (t, 1 H, J = 7.5 Hz), 7.48 (t, 1 H, J = 7.5 Hz), 7.40 (t, 1 H, J = 8.0 Hz), 4.74 (brs, 2 H) , 3.45 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 166.4, 162.2, 149.3, 141.1, 138.6, 138.5, 134.2, 133.9, 132.9, 130.2, 129.8, 128.9, 126.1, 124.9, 121.5, 119.7, 119.7, 114.8, 53.5 , 48.2, 41.5.

3- Bromo - N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Bromo- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86e)

Yield, 84%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.43 (s, 1 H), 9.55 (brs, 2 H), 8.78 (d, 1 H, J = 8.0 Hz), 8.47 (d, 1 H, J = 8.4 Hz), 8.34 (t, 1 H, J = 1.6 Hz), 8.11 (d, 1 H, J = 7.6 Hz), 7.96 (d, 1 H, J = 8.4 Hz), 7.90 (d, 1 H , J = 8.0 Hz), 7.75 (d, 1 H, J = 8.0 Hz), 7.69 (t, 1 H, J = 8.0 Hz), 7.65 (t, 1 H, J = 8.4 Hz), 7.57 (t, 1 H, J = 7.6 Hz), 7.37 (t, 1 H, J = 8.0 Hz), 4.69 (brs, 2 H), 3.45 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.1, 162.5, 149.2, 141.0, 139.0, 137.1, 135.7, 134.1, 132.2, 130.6, 130.0, 127.4, 126.3, 124.5, 122.9, 120.8, 113.9, 53.5, 48.4 , 41.5.

4- Bromo - N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Bromo- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86f)

Yield, 85%; ¹ H-NMR (500 MHz, DMSO- d ₆ ) δ 12.47 (s, 1 H), 9.64 (brs, 2 H), 8.81 (d, 1 H, J = 8.0 Hz), 8.50 (d, 1 H, J = 8.0 Hz), 8.11-8.07 (m, 3 H), 7.93 (d, 2 H, J = 8.0 Hz), 7.79 (d, 1 H, J = 7.5 Hz), 7.70 (td, 1 H, J = 7.5, 1.5 Hz), 7.55 (t, 1 H, J = 8.0 Hz), 7.38 (t, 1 H, J = 7.5 Hz), 4.70 (brs, 2 H), 3.54 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.7, 162.5, 149.3, 141.0, 139.1, 134.1, 132.9, 130.5, 130.0, 130.0, 127.0, 126.1, 124.4, 122.0, 120.7, 113.8, 113.5, 53.4, 51.0 , 41.8.

2- Chloro - N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [2-Chloro- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86g)

Yield, 68%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 11.91 (s, 1 H), 9.55 (brs, 2 H), 8.66 (d, 1 H, J = 7.6 Hz), 8.45 (d, 1 H, J = 7.6 Hz), 7.84 (d, 1 H, J = 7.2 Hz), 7.73-7.68 (m, 3 H), 7.66-7.55 (m, 3 H), 7.47 (t, 1 H, J = 8.0 Hz) , 7.40 (t, 1 H, J = 8.0 Hz), 4.67 (brs, 2 H), 3.44 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.6, 162.5, 149.3, 141.0, 139.1, 137.9, 134.0, 133.7, 130.5, 130.0, 130.0, 129.9, 129.9, 126.1, 124.4, 122.0, 120.8, 113.9, 113.6 , 51.0, 48.3, 41.5.

3- Chloro - N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Chloro- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86h)

Yield, 84%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.45 (s, 1 H), 9.42 (brs, 2 H), 8.79 (d, 1 H, J = 8.4 Hz), 8.46 (d, 1 H, J = 8.4 Hz), 8.20 (t, 1 H, J = 1.6 Hz), 8.09 (dt, 1 H, J = 7.6, 1.6 Hz), 7.93 (d, 1 H, J = 7.6 Hz), 7.78 (dt, 1 H, J = 8.4, 1.6 Hz), 7.75-7.69 (m, 3 H), 7.57 (t, 1 H, J = 8.0 Hz), 7.38 (td, 1 H, J = 7.6, 1.6 Hz), 4.66 (brs, 2 H), 3.41 (brs, 8 H).

4- Chloro - N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Chloro- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86i)

Yield, 75%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.45 (s, 1 H), 9.65 (brs, 2 H), 8.80 (d, 1 H, J = 7.6 Hz), 8.48 (d, 1 H, J = 7.6 Hz), 8.15 (d, 2 H, J = 8.8 Hz), 8.09 (d, 1 H, J = 7.2 Hz), 7.78 (d, 2 H, J = 8.8 Hz), 7.76 (d, 1 H , J = 8.0 Hz), 7.69 (t, 1 H, J = 8.0 Hz), 7.55 (t, 1 H, J = 8.0 Hz), 7.36 (t, 1 H, J = 8.0 Hz), 4.74 (s, 2 H), 3.52 (brs, 8 H).

3-Nitro- N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [3-Nitro- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86j)

Yield, 74%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.62 (s, 1 H), 9.38 (brs, 2 H), 9.01 (s, 1 H), 8.81 (d, 1 H, J = 8.0 Hz), 8.54-8.50 (m, 3 H), 8.03 (d, 1 H, J = 8.0 Hz), 7.97 (t, 1 H, J = 8.0 Hz), 7.78 (d, 1 H, J = 7.5 Hz), 7.70 (t, 1 H, J = 8.0 Hz), 7.58 (t, 1 H, J = 8.0 Hz), 7.39 (t, 1 H, J = 8.0 Hz), 4.70 (brs, 2 H), 3.38 (brs, 8 H).

4-nitro- N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) benzamide hydrochloride [4-Nitro- N -(2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86k)

Yield, 89%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.55 (s, 1 H), 9.52 (brs, 2 H), 8.78 (d, 1 H, J = 8.5 Hz), 8.56 (d, 2 H, J = 8.5 Hz), 8.48 (d, 1 H, J = 7.5 Hz), 8.37 (d, 2 H, J = 9.0 Hz), 8.14 (d, 1 H, J = 7.5 Hz), 7.74-7.70 (m, 2 H), 7.55 (t, 1 H, J = 8.0 Hz), 7.40 (t, 1 H, J = 8.0 Hz), 4.66 (s, 2 H), 3.42 (brs, 8 H).

3,4,5 -trimethoxy - N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol- 2 -yl ) phenyl) benzamide hydrochloride [3,4 , 5- Trimethoxy - N- (2- (7- ( piperazin -1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86l)

Yield, 91%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 12.13 (s, 1 H), 9.57 (brs, 2 H), 8.84 (d, 1 H, J = 8.0 Hz), 8.49 (d, 1 H, J = 8.0 Hz), 7.82 (d, 1 H, J = 8.0 Hz), 7.73 (d, 1 H, J = 7.5 Hz), 7.70 (td, 1 H, J = 8.0, 1.5 Hz), 7.53 (t, 1 H, J = 7.5 Hz), 7.37 (s, 2 H), 7.36 (t, 1 H, J = 8.0 Hz), 4.69 (brs, 2 H), 3.92 (s, 6 H), 3.78 (s, 3 H), 3.42 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 165.6, 162.5, 153.7, 149.2, 141.6, 141.2, 139.3, 134.0, 130.5, 130.2, 126.3, 124.2, 121.0, 120.7, 113.8, 105.6, 60.9, 56.8, 53.4 , 48.3, 41.5.

N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) -1- Naphthaamide  Hydrochloride [ N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride] (86m)

Yield, 71%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.13 (s, 1 H), 9.51 (brs, 2 H), 8.82 (d, 1 H, J = 8.4 Hz), 8.48-8.44 (m, 2 H ), 8.19 (d, 1 H, J = 8.0 Hz), 8.11-8.06 (m, 2 H), 7.76 (d, 1 H, J = 7.6 Hz), 7.72 (d, 1 H, J = 8.0 Hz) , 7.68 (brd, 1 H, J = 7.2 Hz), 7.64-7.58 (m, 3 H), 7.46 (t, 1 H, J = 8.0 Hz), 7.41 (t, 1 H, J = 7.6 Hz), 4.64 (brs, 2 H), 3.44 (brs, 8 H).

N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) -2- Naphthaamide  Hydrochloride [ N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] (86n)

Yield, 99%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.59 (s, 1 H), 9.60 (brs, 2 H), 8.88 (d, 1 H, J = 8.0 Hz), 8.74 (s, 1 H), 8.48 (d, 1 H, J = 8.0 Hz), 8.19-8.15 (m, 3 H), 8.04 (d, 1 H, J = 8.0 Hz), 7.97 (d, 1 H, J = 7.6 Hz), 7.76 -7.66 (m, 4 H), 7.57 (t, 1 H, J = 8.0 Hz), 7.36 (t, 1 H, J = 7.6 Hz), 4.69 (brs, 2 H), 3.44 (brs, 8 H) .

N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) quinoline-2- Carboxamide  Hydrochloride [ N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride] (86o)

Yield, 93%; ¹ H NMR (500 MHz, DMSO- d ₆ ) δ 13.62 (s, 1 H), 9.84 (brs, 2 H), 9.02 (d, 1 H, J = 9.0 Hz), 8.64 (d, 1 H, J = 9.0 Hz), 8.51 (d, 1 H, J = 8.0 Hz), 8.33 (d, 1 H, J = 8.5 Hz), 8.29 (d, 1 H, J = 8.5 Hz), 8.13 (d, 1 H , J = 8.5 Hz), 8.07 (d, 1 H, J = 7.5 Hz), 8.02 (t, 1 H, J = 7.5 Hz), 7.81 (d, 1 H, J = 8.0 Hz), 7.79 (t, 1 H, J = 8.0 Hz), 7.70 (t, 1 H, J = 7.5 Hz), 7.62 (t, 1 H, J = 8.0 Hz), 7.36 (t, 1 H, J = 8.0 Hz), 4.81 ( s, 2 H), 3.49 (brs, 8 H); ¹³ C NMR (100 MHz, DMSO- d ₆ ) δ 164.1, 162.1, 150.2, 149.5, 146.6, 141.7, 139.2, 138.8, 133.9, 131.9, 130.2, 129.8, 129.8, 129.4, 129.0, 126.3, 124.3, 121.6, 120.7 , 119.5, 114.1, 114.1, 113.7, 53.4, 48.1, 41.5.

N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl)-(1,1'- Biphenyl ] -4-carboxamide Hydrochloride [ N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl)-[1,1'-biphenyl] -4-carboxamide hydrochloride] (86p)

Yield, 84%; ¹ H NMR (400 MHz, DMSO- d ₆ ) δ 12.55 (s, 1 H), 9.62 (brs, 2 H), 8.88 (d, 1 H, J = 8.8 Hz), 8.50 (d, 1 H, J = 8.0 Hz), 8.25 (d, 2 H, J = 8.8 Hz), 8.12 (d, 1 H, J = 7.6 Hz), 8.02 (d, 2 H, J = 8.4 Hz), 7.81 (d, 2 H , J = 7.6 Hz), 7.76 (d, 1 H, J = 7.2 Hz), 7.70 (t, 1 H, J = 7.6 Hz), 7.56 (t, 1 H, J = 8.0 Hz), 7.53 (t, 2 H, J = 8.0 Hz), 7.44 (t, 1 H, J = 7.2 Hz), 7.36 (t, 1 H, J = 7.6 Hz), 4.72 (brs, 2 H), 3.48 (brs, 8 H) .

N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] Oxazole -2-yl) phenyl) Cyclohexanecarboxami De Hydrochloride [ N -(2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (86q)

Yield, 99%; ¹ H NMR (400 MHz, 3 drops of CD ₃ OD + DMSO- d ₆ ) δ 8.46 (d, 1 H, J = 8.0 Hz), 8.30 (d, 1 H, J = 7.6 Hz), 7.82 (d, 1 H, J = 7.6 Hz), 7.61 (d, 1 H, J = 7.2 Hz), 7.54 (t, 1 H, J = 7.2 Hz), 7.50 (t, 1 H, J = 8.0 Hz), 7.25 ( t, 1 H, J = 7.6 Hz), 4.68 (s, 2 H), 3.49 (brs, 4 H), 3.39 (brs, 4 H), 2.34 (m, 1 H), 1.91 (m, 2 H) , 1.71 (m, 2 H), 1.61 (m, 1 H), 1.43 (m, 2 H), 1.29 (m, 2 H), 1.16 (m, 1 H).

Example  2 : Benzo [ d ] Oxazole  Of derivatives synthesized based on the skeleton SIRT  1 active navigation and SIRT  1 Excavator (Compound 70c) excavation

2-1. Compound 70c SIRT  1 Active check

SIRT 1 activity was measured using a SIRT 1 fluorometric drug discovery kit (AK-555, Biomol) for a candidate SIRT 1 activator compound synthesized based on a benzo [d] oxazole skeleton. Briefly, the substrate for analysis was 0.2 U / L as a mixture of Fluor de Lys-SIRT 1 substrate developer, which means amino acid 379382 of human p53 (Arg-His-Lys-Lys AC) and human SIRT 1 and auxiliary substrate NAD ⁺ are incubated. Fluor de Lys-Sirt1 In the 25 μM and NAD ⁺ 25 μM environment, the initial deacetylation degree of SIRT 1 for 100 μM candidate was measured using 100 μM resveratrol as a positive control. After the reaction was stopped using Fluor de Lys ^TM Developer II / 2 mM nicotinamide, fluorescence (Excitation: 360 nm, Emission: 460 nm) was measured.

As a result, referring to FIGS. 1A to 1F, it was confirmed that compound 70c exhibits a higher SIRT 1 activity effect than resveratrol, which is known as a strong SIRT 1 activator. Compounds with a value of 0 had too high a fluorescence value of their own, and it was impossible to measure with a SIRT 1 fluorometric kit (AK-555, Biomol) measured by fluorescence.

In addition, docking simulation was performed using the AutoDock4 and DOCK6 programs to confirm the binding force of SIRT 1 to compound 70c.

As a result, referring to Figure 1G, it was confirmed that the compound 70c has a higher binding force to SIRT 1 than resveratrol and SRT1720, which are known as strong SIRT 1 activators.

2-2. Confirmation of improvement of insulin resistance of compound 70c

The metabolic disease control ability of compound 70c was analyzed using a db / db mouse lacking the appetite-regulating hormone leptin receptor as an obese animal model. Compound 70c was administered orally to db / db mice (9 weeks old) at a concentration of 5 mg / kg daily for 4 weeks.

As a result, referring to FIGS. 2A and 2B, it was confirmed that the dietary intake and body weight were significantly increased in the db / m mice that are homozygous compared to the db / m mice that are heterozygous that do not exhibit the obesity phenotype. It means that the animal model was well derived. When the compound 70c was orally administered to the db / db mouse, it was confirmed that there was no difference in dietary intake and body weight when compared with the db / db mouse group.

Glucose tolerance test was performed 3 weeks after oral administration of compound 70c. The mice were kept on an empty stomach for at least 12 hours, and glucose (2 g / kg) was intraperitoneally injected, and then blood glucose collected from the tail of the mouse was used to measure sugar in the blood every hour with a glucometer (ACCU-CHECK). .

As a result, referring to FIG. 2C, the db / db mouse group showed sugar resistance in which high levels of blood glucose were maintained due to poor insulin signaling, whereas this sugar resistance was recovered in the group administered orally with compound 70c. It was confirmed that the blood sugar level decreased. In addition, referring to Figure 2D, when compared with the db / db mouse group, it was confirmed that the fasting blood glucose decrease in the compound 70c oral administration group.

Next, the insulin concentration in the blood was measured using an enzyme-linked immunosorbent assay (ELISA). Mouse insulin ELISA (TMB) kit (AKRIN-011T, SHIBAYAGI, Japan) was used, and serum isolated from animal blood was added to a 96 well plate coated with insulin primary antibody and reacted. , The secondary antibody and the substrate were added and reacted to measure the changed color with an absorbance meter.

As a result, referring to Figure 2E, when compared with the db / db mouse group, it was confirmed that the serum insulin concentration in the compound 70c oral administration group was decreased.

2-3. Confirmation of improvement of fatty liver of compound 70c

Since obesity and insulin resistance are typical diseases directly related to the development of non-alcoholic fatty liver, the effect of improving the fatty liver of compound 70c was analyzed. Compound 70c was administered orally to db / db mice (9 weeks old) at a concentration of 5 mg / kg daily for 4 weeks. First, fat accumulation in the liver, the most representative phenotype, was measured. Briefly, the liver was quantified to about 50 mg, crushed in cold phosphate buffered saline (PBS) or 0.9% sodium chloride (NaCl), and then crushed, followed by a 2: 1 volume ratio of chloroform and methanol (MeOH). The mixed solvent was treated and reacted for 2 hours. Thereafter, the sample was filtered using a paper filter, and the filtered liquid was removed in a dry-oven at 60 ° C. Then, the amount of triglyceride was measured by absorbance using a triglyceride measurement kit (Stanbio laboratory, TX USA).

As a result, referring to FIG. 3A, it was confirmed that triglyceride was accumulated in the liver of the obese animal model db / db mouse group, which means that non-alcoholic fatty liver is induced. On the other hand, it was confirmed that triglyceride decreased in the group orally administered with compound 70c, which means that the non-alcoholic fatty liver is alleviated.

In order to confirm the mechanism corresponding to this, mRNA expression of genes related to fat synthesis and degradation was analyzed. Briefly, about 25 mg of liver was quantified, RNA was isolated using RiboEx Total RNA (GeneAll Biotechnology), and then synthesized by cDNA using HyperscriptTM One-Step RT-PCR Master mix (GeneAll Biotechnology). The synthesized cDNA was subjected to a real-time polymerase chain reaction (quatative real-time PCR) capable of targeting a desired gene as a primer and quantifying in real time.

As a result, referring to Figure 3B, it was confirmed that the expression of fat synthesis-related genes (FASN, ACC, SREBP-1a, SREBP-1c and SREBP-2) increased in the db / db mouse group, whereas Compound 70c was observed. In the oral administration group, it was confirmed that the genes related to fat synthesis were significantly reduced. In comparison, with reference to FIG. 3C, the expression of the lipolysis-related genes (CPT1 and ACOX1) was not significantly different in the two groups. Through the above results, it is thought that the decrease in the expression of the genes related to fat synthesis by the compound 70c contributed to the improvement of non-alcoholic fatty liver by reducing triglycerides.

Although the cause of non-alcoholic liver disease (NAFLD) is unclear, recent studies report that ER stress may be related to the development of fatty liver and progression to non-alcoholic liver disease. have. Thus, in order to analyze the effect of compound 70c on endoplasmic reticulum stress, vesicular stress-related markers (p-IRE) were identified by Western blot. Briefly, about 50 mg of liver was quantified, and the protein was extracted by homogenizing and lysis. After quantifying the extracted protein and loading the same amount on the polyacrylamide gel, the protein was separated according to molecular weight through SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Proteins separated according to molecular weight were transferred to a membrane by applying an electric field, and desired proteins were detected using specific antibodies. After reacting the primary antibody specifically binding to the protein to be detected for 12 hours or more, react the secondary antibody specifically binding to the primary antibody for 1 hour, and HRP (horse radish peroxidase) present in the secondary antibody ), The expression of the protein can be analyzed by treating the developer containing the substrate.

As a result, referring to FIG. 3D, it was confirmed that the protein expression of the vesicle stress-related marker (p-IRE) increased in the db / db mouse group, which is an obese animal model, was significantly reduced in the group treated with orally compound 70c. α-tubulin (α-tubulin) is a housekeeping gene, and it can be confirmed that the protein was quantitatively loaded. Through this, it is believed that compound 70c reduced vesicle stress induced by obesity, which contributed to the relief of fatty liver.

2-4. Cell aging of compound 70c Protection  Confirm

Β-galactosidase (β), which induces cell aging of the fibroblast, the main cell of the skin epithelial layer, using UVB, which is known as the most important environmental factor in skin aging, and is used as the most common marker for cell aging. -galactosidase) staining to analyze the cellular aging protective capacity of compound 70c.

As a result, referring to FIG. 4, it was confirmed that cells stained with β-galactosidase were increased by UVB at 12 mJ / cm ² , and in the group pretreated with compound 70c at a concentration of 1 μM for 24 hours, β -It was confirmed that the galactosidase staining decreased. This means that compound 70c has a protective effect in cell aging.

Example  3: Benzo [ d ] Oxazole  SIRT 1 of derivative compound 69c synthesized based on skeleton and PPARβ / δ active search

3-1. Compound 69c SIRT  1 and PPARβ / δ activity check

To confirm the binding force of SIRT 1 and PPARβ / δ for compound 69c, docking simulation was performed using AutoDock4 and DOCK6 programs.

As a result, referring to Figure 5A, it was confirmed that the compound 69c has a higher binding force to SIRT 1 than resveratrol, which is known as a strong SIRT 1 activator. In addition, as a result of measuring the binding force with PPARβ / δ, which is reported to control the transcription of SIRT 1, it was confirmed that compound 69c has a higher binding force with PPARβ / δ than GW501516 known as PPARβ / δ agonist.

Next, in order to analyze the effect of PPARβ / δ activity of compound 69c, a luciferase assay (PPAR response element (PPRE) -luciferase assay) was performed on fibroblasts, the main cells of the skin epithelial layer. Cells are treated with plasmids that bind the PPARβ / δ binding site region, that is, the PPRE region upstream of the luciferase gene, with lipofectamine in the cells, and then transfection. ). Through this process, DNA is surrounded by lipofectamine, making it easy to pass through the cell membrane. In addition, by overexpressing PPARβ / δ in addition to the endogenous PPAR subtype, it can be confirmed which PPAR subtype effect is among the PPAR subtypes. After 18 to 24 hours of transduction, after the candidate compound was treated and at least 5 hours later, the substrate of the luciferase assay system was added to measure fluorescence. The luciferase expression level can be analyzed through the fluorescence value, and the activity level of PPARβ / δ can be analyzed through the results.

As a result, referring to FIG. 5B, it was confirmed that compound 69c has a higher PPARβ / δ activity than GW501516. In addition, it was confirmed by Western blot results that the intracellular nucleus metastasis of PPARβ / δ increased after 1 hour and 30 minutes after treating the compound 69c with the cells, which means that PPARβ / δ was activated and moved into the nucleus.

To confirm whether compound 69c increases the expression of SIRT 1 through activation of PPARβ / δ, real-time polymerase chain reaction (real-time PCR) and western blot were performed.

As a result, referring to FIG. 5C, it was confirmed that mRNA and protein expression levels of SIRT 1 were increased by compound 69c.

In addition, SIRT 1 is known to exert its function through deacetylation of various substrate proteins. Referring to FIG. 5D, it was confirmed that acetylation of p53, which is a marker of cellular aging and a target protein of SIRT 1, was increased by UVB, and that compound 69c inhibited acetylation of p53 increased by UVB.

Therefore, when synthesizing the above results, it was confirmed that compound 69c increases the expression of SIRT 1 through PPARβ / δ activation, leading to deacetylation of p53, a marker of cellular aging.

3-2. Cell aging and oxidative stress of compound 69c Protection  Confirm

Β-galactosidase (β), which induces cell aging of the fibroblast, the main cell of the skin epithelial layer, using UVB, which is known as the most important environmental factor in skin aging, and is used as the most common marker for cell aging. -galactosidase) staining to analyze the cellular aging protective capacity of compound 69c.

As a result, referring to FIG. 6A, it was confirmed that cells stained with β-galactosidase were increased by UVB at 10 mJ / cm ² , and β- in the group pretreated with compound 69c at a concentration of 10 μM for 24 hours. It was confirmed that the galactosidase staining decreased. This means that compound 69c has a protective effect in cell aging.

In addition, as a result of analyzing a reactive oxygen species (ROS), which is a kind of oxidative stress, with a fluorescent dye of DCF-DA (2 ', 7'-dichlorofluorescin diacetate), referring to Figure 6B, it is induced by UVB It was confirmed that the activated oxygen species were inhibited by compound 69c.

Therefore, when synthesizing the above results, it was confirmed that Compound 69c increases SIRT 1 expression through PPARβ / δ activation, thereby inhibiting cellular aging and oxidative stress.

3-3. Skin cells For photoaging  Collagen synthesis / resolution of compound 69c

Wrinkles are bones formed on the surface of the skin due to the loss of collagen and elastic fibers in the dermis of the skin. The main mechanism associated with the formation of wrinkles on the skin is oxidative stress from harmful environments such as air pollution, UV exposure, stress or disease. As it is continuously exposed to, the increased radicals in the body destroy collagen, elastin, and hyaluronic acids, which are the connective tissues of the dermis, causing the skin to settle.

In order to improve the wrinkles of the skin, ascorbic acid, α-tocopherol, retinol and its derivatives, super oxide dismutase (SOD), etc. have been formulated in cosmetics or medicines to improve skin wrinkles. It has been used to prevent other skin diseases, but the above materials are not only expensive, but also have poor chemical stability, which makes it difficult to expect a practical effect.

In order to solve these problems, in the pharmaceutical, food, and cosmetic fields, many studies are being conducted to develop substances that are safer and have a high effect on skin wrinkle improvement. In particular, as studies on the effectiveness of wrinkle improvement through SIRT 1 have been recently reported, SIRT 1 is regarded as a target protein for wrinkle improvement.

First, the effect of compound 69c on pro-collagen expression by cell photoaging was analyzed. A collagen reduction model by UVB was constructed using skin fibroblasts and experiments were conducted. Skin fibroblasts were pretreated with 10 μM of compound 69c 1 hour ago, and irradiated with 8 mJ / cm ² of UVB. After 6 hours, the cells were lysed and expression of pro-collagen was confirmed through Western blot.

As a result, referring to FIG. 7A, it was confirmed that the expression of pro-collagen decreased by UVB was increased by compound 69c.

Next, according to a study on the formation of skin wrinkles due to photoaging, the activity of matrix metalloproteinase (MMPs), which acts to break down the elastic collagen and other connective tissue components of the dermis, is known to increase as the amount of UV irradiation increases. , It has been reported that the reason collagen decreases during light damage is a phenomenon in which collagen synthesis is inhibited due to increased activity of MMP1 / 13.

Based on this, in order to confirm the effect of compound 69c on the expression level of intracellular MMPs, 10 μM of compound 69c was pretreated on skin fibroblasts 1 hour before, and 8 mJ / cm ² of UVB was irradiated. After 6 hours, the cells were lysed and the expression levels of MMP1 and MMP13 were confirmed by Western blot.

As a result, referring to FIG. 7B, it was confirmed that the expression of MMP1 and MMP13 increased by UVB was decreased by compound 69c.

Therefore, when synthesizing the above results, it was confirmed that Compound 69c is effective in improving wrinkles caused by photoaging by increasing the synthesis of pro-collagen and reducing the expression of MMPs (MMP1 / 13).

The specific parts of the present invention have been described in detail above, and it is obvious that for those skilled in the art, these specific techniques are only preferred embodiments, and the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

The scope of the present invention is indicated by the following claims, and all modifications or variations derived from the meaning and scope of the claims and their equivalent concepts should be interpreted to be included in the scope of the present invention.

Claims (22)

A compound represented by Formula 1, a hydrate or a salt thereof:
[Formula 1]

R is (C1-C4) alkyl, (C1-C4) alkoxy, halogen, nitro or phenyl, one or more substituted or unsubstituted benzamide, nicotinamide, isonicotinamide, isonicotinamide, naphthamide, Quinoline-2-carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea And phenyl carbamate.
R 'is one selected from the group consisting of NH, NCH ₃ , N-cyclohexyl and oxo. The compound according to claim 1, wherein the compound is a compound represented by the following Chemical Formula 1-1, a hydrate or a salt thereof:
[Formula 1-1]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of The compound according to claim 2, wherein the compound represented by 1-1 is N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56a), 2-methyl- N- (2- (4- (piperazin- 1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Methyl- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2- yl) phenyl) benzamide hydrochloride] (56b), 3-methyl- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ 3-Methyl- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56c), 4-methyl- N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Methyl- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56d), 2-fluoro - N - (2- (4- (piperazin-1-ylmethyl) ben [D] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [2-Fluoro- N - (2- (4- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride ] (56e), 3-fluoro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Fluoro- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56f), 4-fluoro- N- (2- (4- (piperazin- 1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Fluoro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2- yl) phenyl) benzamide hydrochloride] (56g), 2-bromo- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Bromo- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56h), 3-bromo- N- (2- ( 4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Bromo- N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56i), 4-bromo- N- (2- (4- (piperazin- 1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Bromo- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2- yl) phenyl) benzamide hydrochloride] (56j), 2-chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ 2-Chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56k), 3-chloro- N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56l), 4-chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benz Amide hydrochloride [4-Chloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56m) , 3-Nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Nitro- N- (2- ( 4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56n), 4-nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Nitro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride ] (56o), 3,4,5-trimethoxy- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ 3,4,5-Trimethoxy- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56p), 2,4-dichloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2,4-Dichloro- N- (2- (4- (piperazin- 1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56q), 3,4-dichloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3,4-Dichloro- N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (56r), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride [ N- (2- (4- ( Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride] (56s), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazole-2 -Yl) phenyl) isonicotinamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) isonicotinamide hydrochloride] (56t), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride] (56u), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) p henyl) -2-naphthamide hydrochloride] (56v), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydro Chloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride] (56w), N- (2- (4- (pipe 1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide hydrochloride [N advantage - (2- (4- (Piperazin- 1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide hydrochloride] (56x), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)- [1,1'-Biphenyl] -4-carboxamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1 '-biphenyl] -4-carboxamide hydrochloride] (56y), N- (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydro Chloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (56z), N -(2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride [ N- (2- (4- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride] (56A) and phenyl (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) carbamate hydro Chloride [Phenyl (2- (4- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) carbamate hydrochloride] (56B), a hydrate or salt thereof . According to claim 1, wherein the compound is a compound, a hydrate or a salt thereof, characterized in that the compound represented by Formula 1-2:
[Formula 1-2]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of The compound according to claim 4, wherein the compound represented by Chemical Formula 1-2 is N- (2- (5- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide [ N -(2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (64a), 3,4,5-trimethoxy- N- (2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide [3,4,5-Trimethoxy- N- (2- (5- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (64b), N- (2- (5- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphtha Amide [ N- (2- (5- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (64c) and N- (2- (5- (piperazin- 1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide 2,2,2-trifluoroacetate [ N- (2- (5- (Piperazin-1- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide 2,2,2-trifluoroacetate] (64d), a hydrate or a salt thereof. The compound, a hydrate or a salt thereof according to claim 1, wherein the compound is a compound represented by the following Chemical Formula 1-3:
[Formula 1-3]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of 7. The compound of claim 6, wherein the compound represented by Chemical Formula 1-3 is N- (2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl ) Benzamide [ N- (2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (69a), 3,4,5-trime Methoxy- N- (2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide [3,4,5-Trimethoxy- N- (2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (69b), N- (2- (5-((4-methylpipet 1-yl) methyl) benzo [d] oxazol-2-yl) phenyl) -2-naphthamide amide [N - (2- (5 - ((4-Methylpiperazin-1-yl) methyl) benzo [d ] oxazol-2-yl) phenyl) -2-naphthamide] (69c) and N- (2- (5-((4-methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl ) Phenyl) -2-naphthamide hydrochloride [ N- (2- (5-((4-Methylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] ( 69cc), N - (2- ( 5 - ((4- methylpiperazin-l-yl) methyl) benzo [d] oxazol-2-yl) phenyl) Rust utilizing 2-carboxamide [N - (2- (5 - ((4-Methylpiperazin-1-yl) methyl) benzo [d] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide] (69d) A compound, a hydrate or a salt thereof, characterized in that it is selected from the group consisting of. According to claim 1, wherein the compound is a compound, a hydrate or a salt thereof, characterized in that the compound represented by the following formula 1-4:
[Formula 1-4]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of The method of claim 8, wherein the compound represented by Formula 1-4 is N- (2- (5-((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl ) Phenyl) benzamide [ N- (2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide] (70a), N- (2- ( 5-((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -3,4,5-trimethoxybenzamide [ N- (2- ( 5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -3,4,5-trimethoxybenzamide] (70b), N- (2- (5-((4 -Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide [ N- (2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (70c) and N- (2- (5-((4-cyclohexylpiperazin-1-yl) methyl) benzo [ d ] Oxazol-2-yl) phenyl) quinoxaline-2-carboxamide [ N- (2- (5-((4-Cyclohexylpiperazin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl ) quinoxaline-2-carboxamide] (70d) Compound, a hydrate thereof or a salt thereof, characterized by. According to claim 1, wherein the compound is a compound, a hydrate or a salt thereof, characterized in that the compound represented by Formula 1-5:
[Formula 1-5]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of The compound according to claim 10, wherein the compound represented by Chemical Formula 1-5 is N- (2- (5-((4-oxopiperidin-1-yl) methyl) benzo [ d ] oxazol-2-yl) Phenyl) -2-naphthamide [ N- (2- (5-((4-Oxopiperidin-1-yl) methyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide] (70e) Characterized compounds, hydrates or salts thereof. According to claim 1, wherein the compound is a compound, a hydrate or a salt thereof, characterized in that the compound represented by the following formula 1-6:
[Formula 1-6]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of The compound according to claim 12, wherein the compound represented by Chemical Formula 1-6 is N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride. [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77a), 2-methyl- N- (2- (6- (piperazine -1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2 -yl) phenyl) benzamide hydrochloride] (77b), 3-methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77c), 4-methyl- N- (2- (6 -(Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl ) benzamide hydrochloride] (77d), 2-fluoro - N - (2- (6- (piperazin-1 Methyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [2-Fluoro- N - (2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl ) benzamide hydrochloride] (77e), 3-fluoro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3- Fluoro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77f), 4-fluoro- N- (2- (6- ( Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Fluoro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol -2-yl) phenyl) benzamide hydrochloride] (77g), 2-bromo- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benz Amide hydrochloride [2-Bromo- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77h), 3-bromo- N- ( 2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloric Lai [3-Bromo- N - (2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride] (77i), 4- bromo - N - (2- ( 6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [4-Bromo- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77j), 2-chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl ) Benzamide hydrochloride [2-Chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77k), 3-chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Chloro- N- (2- (6- (piperazin-1- ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77l), 4-chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazole-2 -Yl) phenyl) benzamide hydrochloride [4-Chloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydroch loride] (77m), 3-nitro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Nitro- N -(2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77n), 4-nitro- N- (2- (6- (piperazin-1 -ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride was prepared from [4-Nitro- N - (2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl ) phenyl) benzamide hydrochloride] (77o), 3,4,5-trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) Benzamide hydrochloride [3,4,5-Trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77p), 3,4 , 5-Trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide 2,2,2-trifluoroacetate [ 3,4,5-trimethoxy- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide 2,2,2-trifluoroacetate] (77pp), 2, 4-dichloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2,4-Dichloro- N- (2- (6- ( piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77q), 3,4-dichloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3,4-Dichloro- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (77r), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride [ N- (2- (6- ( piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) nicotinamide hydrochloride] (77s), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazole-2 -Yl) phenyl) isonicotinamide hydrochloride [ N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) isonicotinamide hydrochloride] (77t), N- (2- (6- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) - 1-naphtha amide hydrochloric Id [N - (2- (6- ( Piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride] (77u), N - (2- (6- ( piperazin- -1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2- yl) phenyl) -2-naphthamide hydrochloride] (77v), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carbox Mid hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride] (77w), N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamido dihydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoxaline-2-carboxamide dihydrochloride] (77x), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) Phenyl) quinoxaline-2-carboxamide 2,2,2-trifluoroacetate [ N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) q uinoxaline-2-carboxamide 2,2,2-trifluoroacetate] (77xx), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1 , 1'-Biphenyl] -4-carboxamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1'- biphenyl] -4-carboxamide hydrochloride] (77y), N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (77z), N- (2- (6- (piperazin-1-ylmethyl ) Benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride [ N- (2- (6- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cinnamamide hydrochloride] ( 77A) and 4-methyl- N- (2- (6- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzenesulfonamide [4-Methyl- N- (2- (6- (piperazin-1-ylmethyl ) benzo [d] oxazol-2-yl) phenyl) is selected from the group consisting of benzenesulfonamide] (77BBB) Compound according to claim, its hydrate or a salt thereof. According to claim 1, wherein the compound is a compound, a hydrate or a salt thereof, characterized in that the compound represented by the following formula 1-7:
[Formula 1-7]

Wherein R is (C1 ~ C4) alkyl, (C1 ~ C4) alkoxy, halogen, nitro or phenyl with one or more substituents unsubstituted or substituted benzamide, nicotinamide, isonicotinamide, naphthamide, quinoline-2- Carboxamide, benzenesulfonamide, quinoxaline-2-carboxamide, cyclohexane-carboxamide, cinnamic amide, adamantane-1-carboxamide, phenylurea, naphthylurea, benzylurea and phenylcarbamate One selected from the group consisting of 15. The method of claim 14, wherein the compound represented by Formula 1-7 is N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86a), 2-fluoro- N- (2- (7- (pipe Razin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Fluoro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol- 2-yl) phenyl) benzamide hydrochloride] (86b), 4-fluoro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide Hydrochloride [4-Fluoro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86c), 2-bromo- N- (2 -(7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Bromo- N- (2- (7- (piperazin-1-ylmethyl) benzo [d] oxazol-2- yl) phenyl) benzamide hydrochloride] (86d), 3- bromo - N - (2- (7- (l -1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Bromo- N - (2- (7- (piperazin-1-ylmethyl) benzo [d] oxazol- 2-yl) phenyl) benzamide hydrochloride] (86e), 4-bromo- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide Hydrochloride [4-Bromo- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86f), 2-chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [2-Chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86g), 3-chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) Phenyl) benzamide hydrochloride [3-Chloro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86h), 4-chloro- N - (2- (7- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloric La De [4-Chloro- N - (2- (7- (piperazin-1-ylmethyl) benzo [d] oxazol-2-yl) phenyl) benzamide hydrochloride] (86i), 3- nitro - N - (2- ( 7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3-Nitro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86j), 4-nitro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl ) Benzamide hydrochloride [4-Nitro- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86k), 3,4,5- Trimethoxy- N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride [3,4,5-Trimethoxy- N- ( 2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) benzamide hydrochloride] (86l), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -1-naphthamid e hydrochloride] (86m), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) -2-naphthamide hydrochloride] (86n), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline-2-carboxamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) quinoline -2-carboxamide hydrochloride] (86o), N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1'-biphenyl] -4-carboxamide hydrochloride [ N- (2- (7- (Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl)-[1,1'-biphenyl] -4-carboxamide hydrochloride ] (86p) and N- (2- (7- (piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride [ N- (2- (7 -(Piperazin-1-ylmethyl) benzo [ d ] oxazol-2-yl) phenyl) cyclohexanecarboxamide hydrochloride] (86q) Characterized in that the compound, a hydrate or salt thereof. 16. The method according to any one of claims 1 to 15, wherein the compound, a hydrate or a salt thereof is a SIRT 1 (silent mating type information regulation 2 homolog; sirtuin 1) or a peroxisome proliferator-active receptor (peroxisome proliferator-) A compound characterized by activating activated receptor (PPAR), a hydrate or salt thereof. A pharmaceutical composition for preventing or treating metabolic disease, comprising the compound according to any one of claims 1 to 15, a hydrate or a salt thereof as an active ingredient. 18. The method of claim 17, wherein the metabolic disease is characterized by being selected from the group consisting of obesity, diabetes, hyperinsulinemia, hyperuricemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, metabolic syndrome and endothelial dysfunction. Pharmaceutical composition for preventing or treating metabolic disease. A pharmaceutical composition for preventing or treating liver disease, comprising the compound according to any one of claims 1 to 15, a hydrate or a salt thereof as an active ingredient. The pharmaceutical composition for preventing or treating liver disease according to claim 19, wherein the liver disease is selected from the group consisting of alcoholic fatty liver, non-alcoholic fatty liver and fatty hepatitis. A cosmetic composition for preventing or improving wrinkles containing the compound according to any one of claims 1 to 15, a hydrate or a salt thereof as an active ingredient. delete

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