Novel compound and organic light-emitting device comprising same

Abstract

The present disclosure relates to a novel compound and an organic light emitting device comprising the same.

Description

Technical Field

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of Korean Patent Application No. 10-2022-0129527 filed on October 11, 2022, in the Korean Intellectual Property Office, and Korean Patent Application No. 10-2023-0135250 filed on October 11, 2023, in the Korean Intellectual Property Office, the disclosures of which are incorporated herein by reference in their entirety.

[0003] The present disclosure relates to novel compounds and organic light-emitting devices comprising the same. Background Art

[0004] Generally, the organic light emitting phenomenon refers to the phenomenon of converting electrical energy into light energy by using organic materials. Organic light emitting devices using the organic light emitting phenomenon have characteristics such as wide viewing angle, excellent contrast, fast response time, excellent brightness, driving voltage and response speed, and therefore many studies have been conducted.

[0005] An organic light-emitting device generally has a structure including an anode, a cathode, and an organic material layer between the anode and the cathode. The organic material layer often has a multilayer structure including different materials to improve the efficiency and stability of the organic light-emitting device. For example, the organic material layer may be formed of a hole injection layer, a hole transport layer, a light-emitting layer, an electron transport layer, an electron injection layer, etc. In the structure of the organic light-emitting device, if a voltage is applied between two electrodes, holes are injected from the anode into the organic material layer, and electrons are injected from the cathode into the organic material layer, and when the injected holes and electrons meet each other, excitons are formed, and when the excitons fall back to the ground state, light is emitted.

[0006] There is a continuing need to develop new materials for organic materials used in organic light emitting devices as described above.

[0007] [Prior art literature]

[0008] Patent Document 1: Korean Unexamined Patent Publication No. 10-2000-0051826 Summary of the invention

[0009] Technical issues

[0010] An object of the present disclosure is to provide a new organic light-emitting material and an organic light-emitting device comprising the same.

[0011] Technical Solution

[0012] Provided herein is a compound represented by the following Chemical Formula 1:

[0013] [Chemical formula 1]

[0014]

[0015] Wherein, in Chemical Formula 1,

[0016] D is deuterium,

[0017] a to c are each independently an integer from 0 to 6,

[0018] R 1 To R 3 are each independently hydrogen; deuterium; or -L a -R a , the condition is R 1 To R 3 At least one of them is -L a -R a ,

[0019] L a is a single bond; or substituted or unsubstituted C 6-30 Arylene,

[0020] R a is substituted or unsubstituted C 6-30 Aryl; substituted or unsubstituted C containing at least one heteroatom of O and S 2-30 Heteroaryl; substituted or unsubstituted C 3-12 Aliphatic ring and C 6-30 A fused ring of an aromatic group; or a substituted or unsubstituted C 6-30 Arylsilyl,

[0021] The condition is that R is not included 1 To R 3 All of them are unsubstituted phenyl groups.

[0022] Also provided herein is an organic light-emitting device comprising: a first electrode; a second electrode disposed opposite to the first electrode; and one or more organic material layers disposed between the first electrode and the second electrode, wherein at least one of the organic material layers comprises the compound represented by Chemical Formula 1.

[0023] Beneficial Effects

[0024] The compound represented by Chemical Formula 1 can be used as a material of an organic material layer in an organic light-emitting device, and can improve efficiency, achieve low driving voltage and / or improve life characteristics in the organic light-emitting device. In particular, the compound represented by Chemical Formula 1 can be used as a hole transport auxiliary material. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 An example of an organic light emitting device including a substrate 1 , an anode 2 , an organic material layer 3 , and a cathode 4 is shown.

[0026] Figure 2 An example of an organic light-emitting device including a substrate 1, an anode 2, a hole injection layer 5, a hole transport layer 6, a hole transport auxiliary layer 7, a light-emitting layer 8, a hole blocking layer 9, an electron transport layer 10, an electron injection layer 11 and a cathode 4 is shown.

[0027] Figure 3 An example of an organic light-emitting device including a substrate 1, an anode 2, a hole injection layer 5, a hole transport layer 6, a hole transport auxiliary layer 7, a light-emitting layer 8, a hole blocking layer 9, an electron injection and transport layer 12 and a cathode 4 is shown. DETAILED DESCRIPTION

[0028] Hereinafter, embodiments of the present disclosure will be described to help understand the disclosed subject matter.

[0029] The present disclosure provides a compound represented by Chemical Formula 1.

[0030] In this disclosure, the symbol It refers to the bond to another substituent.

[0031] In the present disclosure, the term "substituted or unsubstituted" means unsubstituted or substituted with one or more substituents selected from the following: deuterium; halogen group; nitrile group; nitro group; hydroxyl group; carbonyl group; ester group; imide group; amino group; phosphine oxide group; alkoxy group; aryloxy group; alkylthio group; arylthio group; alkylsulfonyl group; arylsulfonyl group; silyl group; boron group; alkyl group; cycloalkyl group; alkenyl group; aryl group; aralkyl group; aralkenyl group; alkylaryl group; alkylamino group; aralkylamino group; heteroarylamino group; arylamino group; arylphosphino group; and heterocyclic group containing at least one of N, O and S atoms, or unsubstituted or substituted with substituents in which two or more substituents are connected among the substituents exemplified above. For example, "substituents in which two or more substituents are connected" can be biphenyl. That is, the biphenyl group can be an aryl group, or it can be interpreted as a substituent formed by connecting two phenyl groups.

[0032] In one example, the term "substituted or unsubstituted" can be understood to mean "unsubstituted or selected from deuterium, halogen, cyano, C 1-10 Alkyl, C 1-10 Alkoxy and C 6-20 In addition, the term "substituted with one or more substituents" as used herein may be understood to mean "substituted with one to the maximum number of replaceable hydrogens".

[0033] In the present disclosure, the carbon number of the carbonyl group is not particularly limited, but is preferably 1 to 40. Specifically, it may be a group having the following structure, but is not limited thereto.

[0034]

[0035] In the present disclosure, the ester group may have a structure in which the oxygen of the ester group may be substituted by a linear, branched or cyclic alkyl group having 1 to 25 carbon atoms, or an aryl group having 6 to 25 carbon atoms. Specifically, the ester group may be a group having the following structural formula, but is not limited thereto.

[0036]

[0037] In the present disclosure, the carbon number of the imide group is not particularly limited, but is preferably 1 to 25. Specifically, the imide group may be a group having the following structural formula, but is not limited thereto.

[0038]

[0039] In the present disclosure, specific examples of the silyl group include trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, vinyldimethylsilyl, propyldimethylsilyl, triphenylsilyl, diphenylsilyl, phenylsilyl and the like, but are not limited thereto.

[0040] In the present disclosure, the boryl group specifically includes a trimethylboryl group, a triethylboryl group, a tert-butyldimethylboryl group, a triphenylboryl group, and a phenylboryl group, but is not limited thereto.

[0041] In the present disclosure, examples of halogen groups include fluorine, chlorine, bromine, or iodine.

[0042] In the present disclosure, the alkyl group may be linear or branched, and its carbon number is not particularly limited, but is preferably 1 to 40. According to one embodiment, the carbon number of the alkyl group is 1 to 20. According to another embodiment, the carbon number of the alkyl group is 1 to 10. According to another embodiment, the carbon number of the alkyl group is 1 to 6. Specific examples of the alkyl group include methyl, ethyl, propyl, n-propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl, cyclopentylmethyl, cyclohexylmethyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethyl-propyl, 1,1-dimethyl-propyl, isohexyl, 2-methylpentyl, 4-methylhexyl, 5-methylhexyl and the like, but are not limited thereto.

[0043] In the present disclosure, the alkenyl group may be linear or branched, and the carbon number thereof is not particularly limited, but is preferably 2 to 40. According to one embodiment, the carbon number of the alkenyl group is 2 to 20. According to another embodiment, the carbon number of the alkenyl group is 2 to 10. According to yet another embodiment, the carbon number of the alkenyl group is 2 to 6. Specific examples thereof include vinyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 3-methyl-1-butenyl, 1,3-butadienyl, allyl, 1-phenylvinyl-1-yl, 2-phenylvinyl-1-yl, 2,2-diphenylvinyl-1-yl, 2-phenyl-2-(naphthyl-1-yl)vinyl-1-yl, 2,2-bis(diphenyl-1-yl)vinyl-1-yl, stilbene, styryl, etc., but are not limited thereto.

[0044] In the present disclosure, the cycloalkyl group is not particularly limited, but its carbon number is preferably 3 to 60. According to another embodiment, the carbon number of the cycloalkyl group is 3 to 30. According to another embodiment, the carbon number of the cycloalkyl group is 3 to 20. According to another embodiment, the carbon number of the cycloalkyl group is 3 to 6. Specific examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, 3-methylcyclopentyl, 2,3-dimethylcyclopentyl, cyclohexyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 2,3-dimethylcyclohexyl, 3,4,5-trimethylcyclohexyl, 4-tert-butylcyclohexyl, cycloheptyl, cyclooctyl and the like, but are not limited thereto.

[0045] In the present disclosure, the aryl group is not particularly limited, but its carbon number is preferably 6 to 60, and it may be a monocyclic aryl group or a polycyclic aryl group. According to one embodiment, the carbon number of the aryl group is 6 to 30. According to one embodiment, the carbon number of the aryl group is 6 to 20. As a monocyclic aryl group, the aryl group may be phenyl, biphenyl, terphenyl, etc., but is not limited thereto. Polycyclic aryl groups include naphthyl, anthracenyl, phenanthrenyl, pyrenyl, peryl, fluorenyl, etc., but are not limited thereto.

[0046] In the present disclosure, the fluorenyl group may be substituted, and two substituents may be connected to each other to form a spirocyclic structure. In the case where the fluorenyl group is substituted, etc. However, the structure is not limited thereto.

[0047] In the present disclosure, the heterocyclic group is a heterocyclic group containing one or more of O, N, Si and S as a heteroatom, and the carbon number thereof is not particularly limited, but is preferably 2 to 60. Examples of the heterocyclic group include thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, Azolyl, oxadiazolyl, triazolyl, pyridyl, bipyridyl, pyrimidyl, triazinyl, acridinyl, pyridazinyl, pyrazinyl, quinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, pyrazinopyrazinyl, isoquinolyl, indolyl, carbazolyl, benzo oxazolyl, benzimidazolyl, benzothiazolyl, benzocarbazolyl, benzothiophenyl, dibenzothiophenyl, benzofuranyl, phenanthroline, isothiophene oxazolyl, thiadiazolyl, phenothiazinyl, dibenzofuranyl and the like, but are not limited thereto.

[0048] In the present disclosure, the aryl in aralkyl, aralkenyl, alkylaryl and arylamine is the same as the example of aryl as defined above. In the present disclosure, the alkyl in aralkyl, alkylaryl and alkylamine is the same as the example of alkyl as defined above. In the present disclosure, the heteroaryl in heteroarylamine can apply the description of heterocyclic group as defined above. In the present disclosure, the alkenyl in aralkenyl is the same as the example of alkenyl as defined above. In the present disclosure, the description of aryl as defined above can be applied, except that arylene is a divalent group. In the present disclosure, the description of heterocyclic group as defined above can be applied, except that heteroarylene is a divalent group. In the present disclosure, the description of aryl or cycloalkyl as defined above can be applied, except that hydrocarbon ring is not a monovalent group but is formed by combining two substituents. In the present disclosure, the description of heterocyclic group as defined above can be applied, except that heterocyclic group is not a monovalent group but is formed by combining two substituents.

[0049] In the present disclosure, the term "deuterated or deuterium-substituted" means that at least one of the replaceable hydrogens in a compound, a divalent linking group, or a monovalent substituent is replaced with deuterium.

[0050] In addition, the term "unsubstituted or substituted with deuterium" or "substituted with deuterium or unsubstituted" means "unsubstituted or substituted with a single to maximum number of replaceable hydrogens by deuterium". In one example, considering that the maximum number of hydrogens that can be replaced by deuterium in the phenanthryl structure is 9, the term "unsubstituted or substituted with deuterium phenanthryl" can be understood to mean "phenanthryl that is unsubstituted or substituted with 1 to 9 deuterium atoms".

[0051] In addition, "deuterated structure" means a compound, a divalent linking group or a monovalent substituent including all structures in which at least one hydrogen is replaced by deuterium. As an example, the deuterated structure of phenyl can be understood to refer to the following monovalent substituents in which at least one replaceable hydrogen in phenyl is replaced by deuterium.

[0052]

[0053] In addition, the "deuterium substitution rate" or "deuteration degree" of a compound means the ratio of the number of substituted deuterium atoms to the total number of hydrogen atoms that can be present in the compound (the sum of the number of hydrogen atoms that can be replaced by deuterium in the compound and the number of substituted deuterium atoms) calculated as a percentage. Therefore, when the "deuterium substitution rate" or "deuteration degree" of a compound is "K%", it means that K% of the hydrogen atoms that can be replaced by deuterium in the compound are replaced by deuterium.

[0054] At this time, the "deuterium substitution rate" or "deuteration degree" can be measured by using MALDI-TOF MS (Matrix-Assisted Laser Desorption / Ionization Time-of-Flight Mass Spectrometer), nuclear magnetic resonance spectroscopy ( 1 HNMR), TLC / MS (Thin-Layer Chromatography / Mass Spectrometry), GC / MS (Gas Chromatography / Mass Spectrometry), etc. More specifically, when MALDI-TOF MS is used, the "deuterium substitution rate" or "deuteration degree" can be obtained by determining the number of deuterium substituted in the compound through MALDI-TOF MS analysis, and then calculating the ratio of the number of deuterium substituted to the total number of hydrogen atoms that can be present in the compound as a percentage.

[0055] The compound of Chemical Formula 1 is an amine to which three dibenzofurans are bonded, wherein at least one of the three dibenzofurans is bonded to the amine via carbon 1, and at least one of the three dibenzofurans has a residue consisting of -L a -R a Represents a substituent.

[0056] When such a structure is satisfied, the compound of Chemical Formula 1 may be used in an organic material layer, particularly a light-emitting layer, of an organic light-emitting device, and thus exhibit low voltage, high efficiency and / or long life characteristics.

[0057] In the compound of Chemical Formula 1, at least one hydrogen in three dibenzofurans may be replaced by deuterium. a -R a At least one hydrogen in the represented substituent may be replaced by deuterium.

[0058] Preferably, L a is a single bond; phenylene; biphenyldiyl; or naphthalenediyl.

[0059] In one embodiment, R a C 6-30 Aryl; C containing at least one heteroatom of O and S 2-30 Heteroaryl; C 3-12 Aliphatic ring and C 6-30 A fused ring of an aromatic group; or C 6-30 Arylsilyl.

[0060] C 6-30 Aryl, C containing at least one heteroatom of O and S 2-30 Heteroaryl, C 3-12 Aliphatic ring and C 6-30 Aromatic fused ring, or C 6-30 The arylsilyl group may be unsubstituted or substituted with at least one deuterium and / or at least one C 1-10 Alkyl substitution.

[0061] Preferably, R a It can be phenyl; biphenyl; terphenyl; naphthyl; (phenyl) naphthyl; phenanthryl; fluoranthenyl; benzo[a]phenanthryl; benzo[c]phenanthryl; dibenzofuran; dibenzothiophene; triphenylsilyl; 2,3-dihydro-1H-indenyl; 1,2,3,4-tetrahydronaphthyl; or 6,7,8,9-tetrahydro-5H-benzo[7]annulene, wherein R a It may be unsubstituted or substituted with at least one substituent selected from the group consisting of deuterium, methyl, ethyl, propyl, isopropyl and tert-butyl.

[0062] Preferably, R aIt can be phenyl; biphenyl; terphenyl; naphthyl; (phenyl) naphthyl; phenanthryl; benzo[a]phenanthryl; benzo[c]phenanthryl; triphenylene; 1,1,3,3-tetramethyl-2,3-dihydro-1H-indenyl; 1,2,3,4-tetrahydronaphthyl; 1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthyl; or 6,7,8,9-tetrahydro-5H-benzo[7]annulene.

[0063] The compound represented by Chemical Formula 1 may not include deuterium, or may include at least one deuterium.

[0064] When the compound represented by Chemical Formula 1 contains deuterium, the deuterium substitution rate of the compound may be 1% to 100%. Specifically, the deuterium substitution rate of the compound may be 4% or more, 10% or more, 15% or more, 20% or more, 25% or more, 30% or more, 35% or more, or 40% or more, and 100% or less, 97% or less, 95% or less, 90% or less, or 89% or less.

[0065] In one example, the compound may contain no deuterium, or may contain 1 to 50 deuteriums. More specifically, the compound may contain no deuterium, or may contain 1 or more, 3 or more, 5 or more, 8 or more, or 10 or more, and 45 or less, 40 or less, 38 or less, 35 or less, or 33 or less deuteriums.

[0066] Representative examples of the compound represented by Chemical Formula 1 are as follows:

[0067]

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090]

[0091]

[0092]

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099]

[0100]

[0101]

[0102]

[0103]

[0104]

[0105]

[0106]

[0107]

[0108]

[0109]

[0110]

[0111]

[0112]

[0113]

[0114]

[0115] wherein Dn means the deuterium (D) substitution number of each compound described in the square brackets, which is different for each compound, n is an integer of 0 or more, and the maximum value of n is the total number of hydrogens contained in each compound in the square brackets.

[0116] For example, due to The total number of hydrogens in is 25, so Where n is an integer from 0 to 25, To include wherein 1 to 25 hydrogen atoms are replaced by deuterium; and

[0117] Furthermore, according to the present disclosure, a method for preparing the compound represented by Chemical Formula 1 is provided.

[0118] [Reaction Scheme 1]

[0119]

[0120] In Reaction Scheme 1, the remaining substituents except X' are the same as defined in Chemical Formula 1, and X' is a halogen. Preferably, X' is chlorine or bromine.

[0121] Reaction Scheme 1 is an amine substitution reaction, which is preferably carried out in the presence of a palladium catalyst and a base, and the reactive group used for the amine substitution reaction can be varied as known in the art.

[0122] The method for preparing the compound represented by Chemical Formula 1 may be further presented in the preparation examples described below.

[0123] In addition, according to the present disclosure, there is provided an organic light-emitting device including a compound represented by Chemical Formula 1. In one example, the present disclosure provides an organic light-emitting device including: a first electrode; a second electrode disposed opposite to the first electrode; and one or more organic material layers disposed between the first electrode and the second electrode, wherein at least one of the organic material layers includes the compound represented by Chemical Formula 1.

[0124] The organic material layer of the organic light-emitting device of the present disclosure may have a single-layer structure, or it may have a multilayer structure in which two or more organic material layers are stacked. For example, the organic light-emitting device of the present disclosure may have a structure including a hole injection layer, a hole transport layer, a hole transport auxiliary layer, a light-emitting layer, an electron transport layer, an electron injection layer, etc. as an organic material layer. However, the structure of the organic light-emitting device is not limited thereto, and it may include a smaller number of organic layers.

[0125] In addition, the organic material layer may include a hole injection layer, a hole transport layer, or a hole transport auxiliary layer, wherein the hole injection layer, the hole transport layer, or the hole transport auxiliary layer includes the compound represented by Chemical Formula 1.

[0126] In addition, the organic light-emitting device according to the present disclosure may be a normal type organic light-emitting device in which an anode, one or more organic material layers, and a cathode are sequentially stacked on a substrate. In addition, the organic light-emitting device according to the present disclosure may be an inverted type organic light-emitting device in which a cathode, one or more organic material layers, and an anode are sequentially stacked on a substrate. For example, Figures 1 to 3 The structure of an organic light emitting device according to one embodiment of the present disclosure is shown.

[0127] Figure 1 An example of an organic light emitting device including a substrate 1, an anode 2, an organic material layer 3, and a cathode 4 is shown. In such a structure, the compound represented by Chemical Formula 1 may be contained in the organic material layer.

[0128] Figure 2 An example of an organic light-emitting device including a substrate 1, an anode 2, a hole injection layer 5, a hole transport layer 6, a hole transport auxiliary layer 7, a light-emitting layer 8, a hole blocking layer 9, an electron transport layer 10, an electron injection layer 11, and a cathode 4 is shown. In such a structure, for example, the compound represented by Chemical Formula 1 may be contained in the hole transport auxiliary layer.

[0129] Figure 3An example of an organic light-emitting device including a substrate 1, an anode 2, a hole injection layer 5, a hole transport layer 6, a hole transport auxiliary layer 7, a light-emitting layer 8, a hole blocking layer 9, an electron injection and transport layer 12, and a cathode 4 is shown. In such a structure, for example, the compound represented by Chemical Formula 1 may be contained in the hole transport auxiliary layer.

[0130] The organic light emitting device according to the present disclosure can be manufactured by materials and methods known in the art, except that at least one of the organic material layers contains the compound represented by Chemical Formula 1. In addition, when the organic light emitting device includes a plurality of organic material layers, the organic material layers may be formed of the same material or different materials.

[0131] For example, an organic light-emitting device according to the present disclosure can be manufactured by sequentially stacking a first electrode, an organic material layer, and a second electrode on a substrate. In this case, the organic light-emitting device can be manufactured by depositing a metal, a conductive metal oxide, or an alloy thereof on a substrate using a PVD (physical vapor deposition) method such as a sputtering method or an electron beam evaporation method to form an anode, forming an organic material layer including a hole injection layer, a hole transport layer, a hole transport auxiliary layer, a light-emitting layer, a hole blocking layer, an electron injection and transport layer, etc. on the anode, and then depositing a material that can be used as a cathode on the organic material layer. In addition to such a method, an organic light-emitting device can also be manufactured by sequentially depositing a cathode material, an organic material layer, and an anode material on a substrate.

[0132] In addition, when manufacturing an organic light-emitting device, the compound represented by Chemical Formula 1 can be formed into an organic layer by a solution coating method and a vacuum deposition method. The solution coating method means spin coating, dip coating, blade coating, inkjet printing, screen printing, spraying, roller coating, etc., but is not limited thereto.

[0133] In addition to such a method, an organic light emitting device can also be manufactured by sequentially depositing a cathode material, an organic material layer, and an anode material on a substrate (International Publication WO2003 / 012890). However, the manufacturing method is not limited thereto.

[0134] In one example, the first electrode is an anode and the second electrode is a cathode, or alternatively, the first electrode is a cathode and the second electrode is an anode.

[0135] As the anode material, it is generally preferred to use a material having a large work function so that holes can be smoothly injected into the organic material layer. Specific examples of the anode material include metals such as vanadium, chromium, copper, zinc and gold, or alloys thereof; metal oxides such as zinc oxide, indium oxide, indium tin oxide (ITO) and indium zinc oxide (IZO); combinations of metals and oxides such as ZnO:Al or SnO 2:Sb; conductive polymers such as poly(3-methylthiophene), poly[3,4-(ethylene-1,2-dioxy)thiophene] (PEDOT), polypyrrole and polyaniline; and the like, but not limited thereto.

[0136] As the cathode material, it is generally preferred to use a material having a small work function so that electrons can be easily injected into the organic material layer. Specific examples of the cathode material include metals such as magnesium, calcium, sodium, potassium, titanium, indium, yttrium, lithium, gadolinium, aluminum, silver, tin and lead, or alloys thereof; multilayer structure materials such as LiF / Al or LiO 2 / Al; and so on, but not limited to.

[0137] The hole injection layer is a layer for injecting holes from the electrode, and the hole injection material is preferably such a compound: it has the ability to transport holes, so it has the effect of injecting holes in the anode and has an excellent hole injection effect on the light-emitting layer or the light-emitting material, preventing the excitons generated in the light-emitting layer from moving to the hole injection layer or the electron injection material, and the ability to form a thin film is still excellent. Preferably, the HOMO (highest occupied molecular orbital) of the hole injection material is between the work function of the anode material and the HOMO of the surrounding organic material layer. Specific examples of hole injection materials include metal porphyrins, oligothiophenes, organic materials based on arylamines, organic materials based on hexanitrile hexaazatriphenylene, organic materials based on quinacridone, organic materials based on perylene, anthraquinone, polyaniline and polythiophene conductive polymers, but are not limited to this.

[0138] The hole transport layer is a layer that receives holes from the hole injection layer and transports the holes to the light-emitting layer. The hole transport material is suitably a material having a large hole mobility, which can receive holes from the anode or the hole injection layer and transfer the holes to the light-emitting layer. Specific examples thereof include organic materials based on arylamine, conductive polymers, block copolymers in which conjugated parts and non-conjugated parts exist simultaneously, etc., but are not limited thereto.

[0139] The hole transport auxiliary layer is a layer located between the hole transport layer and the light-emitting layer to adjust the transfer speed or injection speed of the hole, and is not particularly limited as long as it is a material with a low hole injection barrier and a high hole mobility, and any material known in the art can be used without limitation. In one embodiment, the compound represented by Chemical Formula 1 can be used as a hole transport auxiliary layer material, and in this case, it can smoothly transfer holes to the light-emitting layer and improve the stability of the excitons formed in the light-emitting layer, which is preferred.

[0140] An electron blocking layer may be inserted between the hole transport auxiliary layer and the light emitting layer. The electron blocking layer is used to inhibit the electrons injected in the cathode from transferring to the anode side without recombination in the light emitting layer, thereby improving the efficiency of the organic light emitting device. The electron blocking layer is preferably a material having a smaller electron affinity than the electron transport layer.

[0141] The luminescent material is preferably a material that can receive holes and electrons transmitted from the hole transport layer and the electron transport layer, respectively, and combine the holes and electrons to emit light in the visible light region, and has good quantum efficiency for fluorescence or phosphorescence. Specific examples of luminescent materials include 8-hydroxy-quinoline aluminum complexes (Alq 3 ); carbazole-based compounds; diphenylethylene-based compounds; BAlq; 10-hydroxybenzoquinoline-metal compounds; benzoquinoline-based azole-, benzothiazole-, and benzimidazole-based compounds; poly(p-phenylenevinylene) (PPV)-based polymers; spiro compounds; polyfluorenes; rubrene; and the like, but are not limited thereto.

[0142] The light-emitting layer may include a host material and a dopant material. The host material includes a fused aromatic ring derivative, a heterocyclic compound, and the like. Specific examples of the fused aromatic ring derivative include anthracene derivatives, pyrene derivatives, naphthalene derivatives, pentacene derivatives, phenanthrene compounds, fluoranthene compounds, and the like. Examples of heterocyclic compounds include carbazole derivatives, dibenzofuran derivatives, ladder-type furan compounds, pyrimidine derivatives, and the like, but are not limited thereto. In particular, in the present disclosure, the compound represented by Chemical Formula 1 may be used as a host material of the light-emitting layer, and in this case, low voltage, high efficiency, and / or long life characteristics of an organic light-emitting device may be obtained.

[0143] Examples of dopant materials include aromatic amine derivatives, styrylamine compounds, boron complexes, fluoranthene compounds, metal complexes, etc. Specifically, the aromatic amine derivative is a substituted or unsubstituted fused aromatic ring derivative having an arylamino group, and examples thereof include pyrene, anthracene, , diindenopyrene, etc. The styrylamine compound is a compound in which at least one arylvinyl group is substituted in a substituted or unsubstituted arylamine, wherein one or two or more substituents selected from aryl, silyl, alkyl, cycloalkyl and arylamino are substituted or unsubstituted. Specific examples thereof include styrylamine, styryldiamine, styryltriamine, styryltetramine, etc., but are not limited thereto. In addition, the metal complex includes iridium complex, platinum complex, etc., but are not limited thereto.

[0144] The electron transport layer is a layer that can receive electrons from the electron injection layer and transport the electrons to the light-emitting layer. The electron transport material is suitably a material that can well receive electron injection from the cathode and transfer the electrons to the light-emitting layer and has a large electron mobility. Specific examples of the electron transport material include: Al complexes of 8-hydroxyquinoline, Alq 3 The electron transport layer may be used together with any desired cathode material as used according to conventional techniques. In particular, suitable examples of cathode materials are typical materials with low work functions, followed by an aluminum layer or a silver layer. Specific examples thereof include cesium, barium, calcium, ytterbium and samarium, in each case followed by an aluminum layer or a silver layer.

[0145] The electron injection layer is a layer that injects electrons from the electrode, and is preferably a compound that has the ability to transport electrons, has an effect of injecting electrons from the cathode and has an excellent effect of injecting electrons into the light-emitting layer or the light-emitting material, prevents the excitons generated by the light-emitting layer from moving to the hole injection layer, and is also excellent in the ability to form a thin film. Specific examples of the electron injection layer include fluorenone, anthraquinone dimethane, diphenoquinone, thiopyran dioxide, Azoles, Oxadiazole, triazole, imidazole, perylenetetracarboxylic acid, fluorenyl methane, anthrone, etc., and derivatives thereof; metal complex compounds; nitrogen-containing 5-membered ring derivatives; etc., but not limited thereto.

[0146] Examples of metal complex compounds include 8-hydroxyquinoline lithium, bis(8-hydroxyquinoline) zinc, bis(8-hydroxyquinoline) copper, bis(8-hydroxyquinoline) manganese, tris(8-hydroxyquinoline) aluminum, tris(2-methyl-8-hydroxyquinoline) aluminum, tris(8-hydroxyquinoline) gallium, bis(10-hydroxybenzo[h]quinoline) beryllium, bis(10-hydroxybenzo[h]quinoline) zinc, bis(2-methyl-8-quinoline) gallium chloride, bis(2-methyl-8-quinoline)(o-cresol) gallium, bis(2-methyl-8-quinoline)(1-naphthol) aluminum, bis(2-methyl-8-quinoline)(2-naphthol) gallium, and the like, but are not limited thereto.

[0147] The organic light emitting device according to the present disclosure may include an electron injection and transport layer that simultaneously functions as an electron transport layer and an electron injection layer instead of the electron transport layer and the electron injection layer.

[0148] The organic light emitting device according to the present disclosure may be a bottom emission type device, a top emission type device, or a double-sided emission type device, and in particular, it may be a bottom emission type light emitting device requiring relatively high light emission efficiency.

[0149] Furthermore, the compound represented by Chemical Formula 1 may be included in an organic solar cell or an organic transistor in addition to an organic light emitting device.

[0150] The preparation of the compound represented by Chemical Formula 1 and an organic light-emitting device including the same will be described in detail in the following examples. However, these examples are given for illustrative purposes only and are not intended to limit the scope of the present disclosure.

[0151] [Synthesis example]

[0152] Synthesis example 1

[0153]

[0154] Amine 1 (15 g, 42.9 mmol), sub1 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.7 g of compound 1. (Yield: 62%, MS: [M+H]+=592)

[0155] Synthesis example 2

[0156]

[0157] Amine 2 (15 g, 42.9 mmol), sub2 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.2 g of compound 2. (Yield: 52%, MS: [M+H] + = 592)

[0158] Synthesis example 3

[0159]

[0160] Amine 3 (15 g, 42.9 mmol), sub3 (14.8 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.6 g of compound 3. (Yield: 53%, MS: [M+H] + = 642)

[0161] Synthesis example 4

[0162]

[0163] Amine 4 (15 g, 42.9 mmol), sub4 (19.4 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 19.1 g of compound 4. (Yield: 60%, MS: [M+H] + = 744)

[0164] Synthesis example 5

[0165]

[0166] Amine 5 (15 g, 28.3 mmol), sub5 (6 g, 29.7 mmol) and sodium tert-butoxide (4.1 g, 42.5 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 11.2 g of compound 5. (yield: 57%, MS: [M+H] + = 696)

[0167] Synthesis example 6

[0168]

[0169] Amine 3 (15 g, 42.9 mmol), sub6 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 17.5 g of compound 6. (Yield: 69%, MS: [M+H]+=592)

[0170] Synthesis Example 7

[0171]

[0172] Amine 6 (15 g, 42.9 mmol), sub7 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.5 g of compound 7. (Yield: 61%, MS: [M+H] + = 592)

[0173] Synthesis example 8

[0174]

[0175] Amine 3 (15 g, 42.9 mmol), sub8 (17.1 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 20.2 g of compound 8. (Yield: 68%, MS: [M+H] + = 692)

[0176] Synthesis example 9

[0177]

[0178] Amine 4 (15 g, 42.9 mmol), sub9 (16.9 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.2 g of compound 9. (Yield: 55%, MS: [M+H] + = 688)

[0179] Synthesis example 10

[0180]

[0181] Amine 1 (15 g, 42.9 mmol), sub10 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.7 g of compound 10. (yield: 58%, MS: [M+H] + = 592)

[0182] Synthesis Example 11

[0183]

[0184] Amine 1 (15 g, 42.9 mmol), sub11 (14.8 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 19 g of compound 11. (Yield: 69%, MS: [M+H] + = 642)

[0185] Synthesis example 12

[0186]

[0187] Amine 6 (15 g, 42.9 mmol), sub12 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15 g of compound 12. (Yield: 59%, MS: [M+H] + = 592)

[0188] Synthesis example 13

[0189]

[0190] Amine 1 (15 g, 42.9 mmol), sub13 (19.4 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 19.5 g of compound 13. (Yield: 61%, MS: [M+H]+=744)

[0191] Synthesis example 14

[0192]

[0193] Amine 1 (15 g, 42.9 mmol), sub14 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.5 g of compound 14. (Yield: 53%, MS: [M+H]+=592)

[0194] Synthesis Example 15

[0195]

[0196] Amine 1 (15 g, 42.9 mmol), sub15 (17.1 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.8 g of compound 15. (Yield: 50%, MS: [M+H] + = 692)

[0197] Synthesis example 16

[0198]

[0199] Amine 6 (15 g, 42.9 mmol), sub16 (19.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 21 g of compound 16. (yield: 66%, MS: [M+H] + = 742)

[0200] Synthesis Example 17

[0201]

[0202] Amine 1 (15 g, 42.9 mmol), sub17 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.9 g of compound 17. (Yield: 51%, MS: [M+H]+=592)

[0203] Synthesis Example 18

[0204]

[0205] Amine 1 (15 g, 42.9 mmol), sub18 (19.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 19.7 g of compound 18. (Yield: 62%, MS: [M+H]+=742)

[0206] Synthesis example 19

[0207]

[0208] Amine 1 (15 g, 42.9 mmol), sub19 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.2 g of compound 19. (Yield: 52%, MS: [M+H]+=592)

[0209] Synthesis example 20

[0210]

[0211] Amine 6 (15 g, 42.9 mmol), sub20 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.5 g of compound 20. (yield: 57%, MS: [M+H] + = 592)

[0212] Synthesis Example 21

[0213]

[0214] Amine 6 (15 g, 42.9 mmol), sub21 (15.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 18.4 g of compound 21. (Yield: 65%, MS: [M+H] + = 660)

[0215] Synthesis example 22

[0216]

[0217] Amine 1 (15 g, 42.9 mmol), sub22 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.2 g of compound 22. (Yield: 52%, MS: [M+H] + = 592)

[0218] Synthesis example 23

[0219]

[0220] Amine 4 (15 g, 42.9 mmol), sub23 (18.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.4 g of compound 23. (Yield: 50%, MS: [M+H] + = 718)

[0221] Synthesis example 24

[0222]

[0223] Amine 4 (15 g, 42.9 mmol), sub24 (18.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 18.8 g of compound 24. (yield: 61%, MS: [M+H] + = 718)

[0224] Synthesis example 25

[0225]

[0226] Amine 7 (15 g, 35.3 mmol), sub2 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.1 g of compound 25. (yield: 64%, MS: [M+H] + = 668)

[0227] Synthesis Example 26

[0228]

[0229] Amine 8 (15 g, 29.9 mmol), sub5 (6.4 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 11.2 g of compound 26. (yield: 56%, MS: [M+H] + = 668)

[0230] Synthesis Example 27

[0231]

[0232] Amine 9 (15 g, 35.3 mmol), sub25 (13.1 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.5 g of compound 27. (Yield: 59%, MS: [M+H]+=744)

[0233] Synthesis example 28

[0234]

[0235] Amine 10 (15 g, 35.3 mmol), sub26 (15 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14 g of compound 28. (yield: 50%, MS: [M+H] + = 794)

[0236] Synthesis Example 29

[0237]

[0238] Amine 11 (15 g, 31.1 mmol), sub27 (11 g, 32.7 mmol) and sodium tert-butoxide (4.5 g, 46.7 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.3 g of compound 29. (Yield: 59%, MS: [M+H]+=780)

[0239] Synthesis example 30

[0240]

[0241] Amine 12 (15 g, 35.3 mmol), sub6 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.5 g of compound 30. (yield: 66%, MS: [M+H] + = 668)

[0242] Synthesis Example 31

[0243]

[0244] Amine 13 (15 g, 35.3 mmol), sub6 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.2 g of compound 31. (Yield: 52%, MS: [M+H] + = 668)

[0245] Synthesis example 32

[0246]

[0247] Amine 14 (15 g, 29.9 mmol), sub28 (10.3 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.3 g of compound 32. (Yield: 52%, MS: [M+H]+=794)

[0248] Synthesis example 33

[0249]

[0250] Amine 15 (15 g, 35.3 mmol), sub29 (14 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.7 g of compound 33. (Yield: 58%, MS: [M+H]+=768)

[0251] Synthesis example 34

[0252]

[0253] Amine 16 (15 g, 35.3 mmol), sub30 (13.1 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.4 g of compound 34. (Yield: 51%, MS: [M+H] + = 744)

[0254] Synthesis Example 35

[0255]

[0256] Amine 17 (15 g, 35.3 mmol), sub31 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.9 g of compound 35. (Yield: 55%, MS: [M+H] + = 688)

[0257] Synthesis Example 36

[0258]

[0259] Amine 18 (15 g, 35.3 mmol), sub32 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.9 g of compound 36. (yield: 55%, MS: [M+H] + = 688)

[0260] Synthesis Example 37

[0261]

[0262] Amine 19 (15 g, 3.5 mmol), sub33 (1.2 g, 3.7 mmol) and sodium tert-butoxide (0.5 g, 5.3 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0 g, 0 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 1.8 g of compound 37. (yield: 69%, MS: [M+H] + = 722)

[0263] Synthesis example 38

[0264]

[0265] Amine 20 (15 g, 29.9 mmol), sub5 (6.4 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.4 g of compound 38. (yield: 67%, MS: [M+H] + = 688)

[0266] Synthesis Example 39

[0267]

[0268] Amine 21 (15 g, 35.3 mmol), sub34 (12.2 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.7 g of compound 39. (Yield: 66%, MS: [M+H] + = 718)

[0269] Synthesis Example 40

[0270]

[0271] Amine 22 (15 g, 35.3 mmol), sub35 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.6 g of compound 40. (yield: 62%, MS: [M+H] + = 668)

[0272] Synthesis Example 41

[0273]

[0274] Amine 23 (15 g, 35.3 mmol), sub36 (14 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.9 g of compound 41. (yield: 55%, MS: [M+H] + = 768)

[0275] Synthesis Example 42

[0276]

[0277] Amine 24 (15 g, 35.3 mmol), sub37 (13.1 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16 g of compound 42. (yield: 61%, MS: [M+H] + = 744)

[0278] Synthesis Example 43

[0279]

[0280] Amine 25 (15 g, 35.3 mmol), sub38 (12.4 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.3 g of compound 43. (Yield: 52%, MS: [M+H]+=724)

[0281] Synthesis Example 44

[0282]

[0283] Amine 26 (15 g, 27.2 mmol), sub39 (8 g, 28.6 mmol) and sodium tert-butoxide (3.9 g, 40.8 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.5 g of compound 44. (Yield: 67%, MS: [M+H] + = 794)

[0284] Synthesis Example 45

[0285]

[0286] Amine 27 (15 g, 29.9 mmol), sub40 (10.3 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.6 g of compound 45. (yield: 70%, MS: [M+H] + = 794)

[0287] Synthesis Example 46

[0288]

[0289] Amine 28 (15 g, 24.9 mmol), sub2 (7.3 g, 26.2 mmol) and sodium tert-butoxide (3.6 g, 37.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.2 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.8 g of compound 46. (yield: 61%, MS: [M+H] + = 844)

[0290] Synthesis Example 47

[0291]

[0292] Amine 28 (15 g, 24.9 mmol), sub41 (7.3 g, 26.2 mmol) and sodium tert-butoxide (3.6 g, 37.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.2 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 11.1 g of compound 47. (yield: 53%, MS: [M+H] + = 844)

[0293] Synthesis Example 48

[0294]

[0295] Amine 29 (15 g, 26 mmol), sub42 (9 g, 27.3 mmol) and sodium tert-butoxide (3.7 g, 38.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.2 g of compound 48. (yield: 54%, MS: [M+H] + = 870)

[0296] Synthesis Example 49

[0297]

[0298] Amine 30 (15 g, 24.9 mmol), sub28 (8.6 g, 26.2 mmol) and sodium tert-butoxide (3.6 g, 37.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.2 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.6 g of compound 49. (yield: 61%, MS: [M+H] + = 894)

[0299] Synthesis Example 50

[0300]

[0301] Amine 31 (15 g, 29.9 mmol), sub43 (11.1 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.2 g of compound 50. (yield: 54%, MS: [M+H] + = 820)

[0302] Synthesis Example 51

[0303]

[0304] Amine 32 (15 g, 29.9 mmol), sub44 (11.1 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.4 g of compound 51. (yield: 67%, MS: [M+H] + = 820)

[0305] Synthesis example 52

[0306]

[0307] Amine 33 (15 g, 24.9 mmol), sub12 (7.3 g, 26.2 mmol) and sodium tert-butoxide (3.6 g, 37.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.2 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12 g of compound 52. (Yield: 57%, MS: [M+H]+=844)

[0308] Synthesis example 53

[0309]

[0310] Amine 34 (15 g, 29.9 mmol), sub45 (11.9 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.6 g of compound 53. (Yield: 50%, MS: [M+H] + = 844)

[0311] Synthesis example 54

[0312]

[0313] Amine 35 (15 g, 24.4 mmol), sub35 (7.2 g, 25.7 mmol) and sodium tert-butoxide (3.5 g, 36.7 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.2 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.6 g of compound 54. (Yield: 65%, MS: [M+H] + = 856)

[0314] Synthesis example 55

[0315]

[0316] Amine 36 (15 g, 29.9 mmol), sub46 (10.5 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.6 g of compound 55. (yield: 61%, MS: [M+H] + = 800)

[0317] Synthesis Example 56

[0318]

[0319] Amine 37 (15 g, 42.9 mmol), sub47 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.2 g of compound 56_P1. (yield: 52%, MS: [M+H] + = 592)

[0320] Compound 56_P1 (10g, 16.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (8.5g, 422.9mmol) is added to trifluoromethanesulfonic anhydride (23.9g, 84.6mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.4g compound 56. (Yield: 63%, MS: [M+H]+=603).

[0321] Synthesis Example 57

[0322]

[0323] Amine 37 (15 g, 42.9 mmol), sub48 (19.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 21.3 g of compound 57_P1. (yield: 67%, MS: [M+H] + = 742)

[0324] Compound 57_P1 (10g, 13.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.8g, 337.3mmol) is added to trifluoromethanesulfonic anhydride (19g, 67.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7g compound 57. (Yield: 69%, MS: [M+H]+=755)

[0325] Synthesis Example 58

[0326]

[0327] Amine 1 (15 g, 42.9 mmol), sub49 (21.7 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 17.7 g of compound 58_P1. (yield: 52%, MS: [M+H] + = 794)

[0328] Compound 58_P1 (10g, 12.6mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.3g, 315.2mmol) is added to trifluoromethanesulfonic anhydride (17.8g, 63mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.6g compound 58. (Yield: 55%, MS: [M+H]+=809)

[0329] Synthesis Example 59

[0330]

[0331] Amine 1 (15 g, 42.9 mmol), sub50 (15 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium (0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.9 g of compound 59_P1. (yield: 61%, MS: [M+H] + = 646)

[0332] Compound 59_P1 (10g, 15.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7.8g, 387.5mmol) is added to trifluoromethanesulfonic anhydride (21.9g, 77.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.1g compound 59. (Yield: 50%, MS: [M+H]+=659)

[0333] Synthesis Example 60

[0334]

[0335] Amine 4 (15 g, 42.9 mmol), sub51 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15 g of compound 60_P1. (yield: 59%, MS: [M+H] + = 592)

[0336] Compound 60_P1 (10g, 16.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (8.5g, 422.9mmol) is added to trifluoromethanesulfonic anhydride (23.9g, 84.6mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.7g compound 60. (Yield: 66%, MS: [M+H]+=602)

[0337] Synthesis Example 61

[0338]

[0339] Amine 37 (15 g, 42.9 mmol), sub52 (19.4 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium (0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 22 g of compound 61_P1. (yield: 69%, MS: [M+H] + = 744)

[0340] Compound 61_P1 (10g, 13.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.7g, 336.4mmol) is added to trifluoromethanesulfonic anhydride (19g, 67.3mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7.1g compound 61. (Yield: 70%, MS: [M+H]+=757)

[0341] Synthesis example 62

[0342]

[0343] Amine 3 (15 g, 42.9 mmol), sub53 (15 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15 g of compound 62_P1. (yield: 54%, MS: [M+H] + = 646)

[0344] Compound 62_P1 (10g, 15.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7.8g, 387.5mmol) is added to trifluoromethanesulfonic anhydride (21.9g, 77.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.4g compound 62. (Yield: 63%, MS: [M+H]+=657)

[0345] Synthesis example 63

[0346]

[0347] Amine 4 (15 g, 42.9 mmol), sub54 (19.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 17.8 g of compound 63_P1. (yield: 56%, MS: [M+H] + = 742)

[0348] Compound 63_P1 (10g, 13.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.8g, 337.3mmol) is added to trifluoromethanesulfonic anhydride (19g, 67.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.9g compound 63. (Yield: 68%, MS: [M+H]+=756)

[0349] Synthesis example 64

[0350]

[0351] Amine 2 (15 g, 42.9 mmol), sub35 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.5 g of compound 64_P1. (yield: 65%, MS: [M+H] + = 592)

[0352] Compound 64_P1 (10g, 16.9mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (8.5g, 422.9mmol) was added to trifluoromethanesulfonic anhydride (23.9g, 84.6mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture was cooled to room temperature, and the organic layer and the aqueous layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.4g compound 64. (Yield: 63%, MS: [M+H]+=604)

[0353] Synthesis Example 65

[0354]

[0355] Amine 1 (15 g, 42.9 mmol), sub55 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.5 g of compound 65_P1. (Yield: 57%, MS: [M+H] + = 592)

[0356] Compound 65_P1 (10g, 16.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (8.5g, 422.9mmol) is added to trifluoromethanesulfonic anhydride (23.9g, 84.6mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6g compound 65. (Yield: 59%, MS: [M+H]+=603)

[0357] Synthesis example 66

[0358]

[0359] Amine 3 (15 g, 42.9 mmol), sub56 (15.1 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.8 g of compound 66_P1. (yield: 57%, MS: [M+H] + = 648)

[0360] Compound 66_P1 (10g, 15.4mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7.7g, 386.2mmol) is added to trifluoromethanesulfonic anhydride (21.8g, 77.2mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.5g of compound 66. (Yield: 54%, MS: [M+H]+=661)

[0361] Synthesis Example 67

[0362]

[0363] Amine 1 (15 g, 42.9 mmol), sub57 (14.8 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.4 g of compound 67_P1. (Yield: 56%, MS: [M+H] + = 642)

[0364] Compound 67_P1 (10g, 15.6mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7.8g, 389.9mmol) is added to trifluoromethanesulfonic anhydride (22g, 78mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.4g compound 67. (Yield: 63%, MS: [M+H]+=654)

[0365] Synthesis example 68

[0366]

[0367] Amine 38 (15 g, 35.3 mmol), sub2 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.2 g of compound 68_P1. (yield: 69%, MS: [M+H] + = 668)

[0368] Compound 68_P1 (10g, 15mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7.5g, 374.7mmol) is added to trifluoromethanesulfonic anhydride (21.1g, 74.9mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6g compound 68. (Yield: 59%, MS: [M+H]+=680)

[0369] Synthesis Example 69

[0370]

[0371] Amine 39 (15 g, 35.3 mmol), sub58 (15.9 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 18.2 g of compound 69_P1. (yield: 63%, MS: [M+H] + = 818)

[0372] Compound 69_P1 (10g, 12.2mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.1g, 305.9mmol) is added to trifluoromethanesulfonic anhydride (17.3g, 61.2mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.7g compound 69. (Yield: 56%, MS: [M+H]+=832)

[0373] Synthesis Example 70

[0374]

[0375] Amine 40 (15 g, 35.3 mmol), sub28 (12.2 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.4 g of compound 70_P1. (Yield: 57%, MS: [M+H] + = 718)

[0376] Compound 70_P1 (10g, 13.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7g, 348.6mmol) is added to trifluoromethanesulfonic anhydride (19.7g, 69.7mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.4g compound 70. (Yield: 63%, MS: [M+H]+=731)

[0377] Synthesis Example 71

[0378]

[0379] Amine 41 (15 g, 35.3 mmol), sub28 (12.2 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.6 g of compound 71_P1. (yield: 50%, MS: [M+H] + = 718)

[0380] Compound 71_P1 (10g, 13.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7g, 348.6mmol) is added to trifluoromethanesulfonic anhydride (19.7g, 69.7mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.7g compound 71. (Yield: 66%, MS: [M+H]+=732)

[0381] Synthesis Example 72

[0382]

[0383] Amine 42 (15 g, 35.3 mmol), sub59 (13.9 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.1 g of compound 72_P1. (yield: 60%, MS: [M+H] + = 764)

[0384] Compound 72_P1 (10g, 13.1mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.6g, 327.5mmol) is added to trifluoromethanesulfonic anhydride (18.5g, 65.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.2g compound 72. (Yield: 51%, MS: [M+H]+=781)

[0385] Synthesis Example 73

[0386]

[0387] Amine 43 (15 g, 29.9 mmol), sub5 (6.4 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 10.4 g of compound 73_P1. (yield: 52%, MS: [M+H] + = 668)

[0388] Compound 73_P1 (10g, 15mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7.5g, 374.7mmol) is added to trifluoromethanesulfonic anhydride (21.1g, 74.9mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6g compound 73. (Yield: 59%, MS: [M+H]+=681)

[0389] Synthesis Example 74

[0390]

[0391] Amine 44 (15 g, 33.1 mmol), sub60 (10.7 g, 34.7 mmol) and sodium tert-butoxide (4.8 g, 49.6 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.7 g of compound 74_P1. (yield: 53%, MS: [M+H] + = 724)

[0392] Compound 74_P1 (10g, 13.8mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.9g, 345.6mmol) is added to trifluoromethanesulfonic anhydride (19.5g, 69.1mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.4g compound 74. (Yield: 63%, MS: [M+H]+=740)

[0393] Synthesis Example 75

[0394]

[0395] Amine 45 (15 g, 35.3 mmol), sub3 (12.2 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.2 g of compound 75_P1. (yield: 56%, MS: [M+H] + = 718)

[0396] Compound 75_P1 (10g, 13.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7g, 348.6mmol) is added to trifluoromethanesulfonic anhydride (19.7g, 69.7mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.6g compound 75. (Yield: 65%, MS: [M+H]+=732)

[0397] Synthesis Example 76

[0398]

[0399] Amine 46 (15 g, 35.3 mmol), sub35 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.7 g of compound 76_P1. (yield: 54%, MS: [M+H] + = 668)

[0400] Compound 76_P1 (10g, 15mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (7.5g, 374.7mmol) is added to trifluoromethanesulfonic anhydride (21.1g, 74.9mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.6g compound 76. (Yield: 65%, MS: [M+H]+=680)

[0401] Synthesis Example 77

[0402]

[0403] Amine 47 (15 g, 31.3 mmol), sub61 (10.9 g, 32.8 mmol) and sodium tert-butoxide (4.5 g, 46.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.3 g of compound 77_P1. (Yield: 63%, MS: [M+H] + = 776)

[0404] Compound 77_P1 (10g, 12.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.5g, 322.5mmol) is added to trifluoromethanesulfonic anhydride (18.2g, 64.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7g compound 77. (Yield: 69%, MS: [M+H]+=792)

[0405] Synthesis Example 78

[0406]

[0407] Amine 48 (15 g, 35.3 mmol), sub62 (15.9 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.4 g of compound 78_P1. (yield: 57%, MS: [M+H] + = 818)

[0408] Compound 78_P1 (10g, 12.2mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.1g, 305.9mmol) is added to trifluoromethanesulfonic anhydride (17.3g, 61.2mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.3g compound 78. (Yield: 52%, MS: [M+H]+=833)

[0409] Synthesis Example 79

[0410]

[0411] Amine 49 (15 g, 29.9 mmol), sub63 (10.3 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.8 g of compound 79_P1. (Yield: 58%, MS: [M+H] + = 794)

[0412] Compound 79_P1 (10g, 12.6mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.3g, 315.2mmol) is added to trifluoromethanesulfonic anhydride (17.8g, 63mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.3g compound 79. (Yield: 52%, MS: [M+H]+=810)

[0413] Synthesis example 80

[0414]

[0415] Amine 50 (15 g, 29.9 mmol), sub28 (10.3 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.2 g of compound 80_P1. (yield: 64%, MS: [M+H] + = 794)

[0416] Compound 80_P1 (10g, 12.6mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (6.3g, 315.2mmol) was added to trifluoromethanesulfonic anhydride (17.8g, 63mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture was cooled to room temperature, and the organic layer and the aqueous layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 5.8g of compound 80. (Yield: 57%, MS: [M+H]+=809)

[0417] Synthesis example 81

[0418]

[0419] Amine 51 (15 g, 24.9 mmol), sub63 (8.6 g, 26.2 mmol) and sodium tert-butoxide (3.6 g, 37.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.2 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.7 g of compound 81_P1. (yield: 66%, MS: [M+H] + = 894)

[0420] Compound 81_P1 (10g, 11.2mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (5.6g, 279.9mmol) was added to trifluoromethanesulfonic anhydride (15.8g, 56mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture was cooled to room temperature, and the organic layer and the aqueous layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.2g compound 81. (Yield: 61%, MS: [M+H]+=912)

[0421] Synthesis example 82

[0422]

[0423] Amine 52 (15 g, 29.9 mmol), sub64 (11.9 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.6 g of compound 82_P1. (Yield: 58%, MS: [M+H] + = 844)

[0424] Compound 82_P1 (10g, 11.9mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (5.9g, 296.5mmol) was added to trifluoromethanesulfonic anhydride (16.7g, 59.3mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture was cooled to room temperature, and the organic layer and the water layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.9g compound 82. (Yield: 68%, MS: [M+H]+=861)

[0425] Synthesis example 83

[0426]

[0427] Amine 53 (15 g, 29.9 mmol), sub65 (10.9 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 18 g of compound 83_P1. (yield: 70%, MS: [M+H] + = 862)

[0428] Compound 83_P1 (10g, 11.6mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (5.8g, 290.3mmol) is added to trifluoromethanesulfonic anhydride (16.4g, 58.1mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.5g compound 83. (Yield: 64%, MS: [M+H]+=881)

[0429] Synthesis example 84

[0430]

[0431] Amine 1 (15 g, 42.9 mmol), sub66 (16 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16 g of compound 84_P1. (Yield: 56%, MS: [M+H] + = 668)

[0432] Compound 84_P1 (10g, 15mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.8g, 539.6mmol) was added to trifluoromethanesulfonic anhydride (38.1g, 134.9mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture was cooled to room temperature, and the organic layer and the aqueous layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 7.2g compound 84. (Yield: 70%, MS: [M+H]+=691)

[0433] Synthesis example 85

[0434]

[0435] Amine 1 (15 g, 42.9 mmol), sub67 (17.5 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.6 g of compound 85_P1. (Yield: 55%, MS: [M+H]+=702)

[0436] Compound 85_P1 (10g, 14.3mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.3g, 513.3mmol) was added to trifluoromethanesulfonic anhydride (36.2g, 128.3mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 4 hours, the reaction mixture was cooled to room temperature, and the organic layer and the aqueous layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 7.1g compound 85. (Yield: 68%, MS: [M+H]+=730)

[0437] Synthesis example 86

[0438]

[0439] Amine 37 (15 g, 42.9 mmol), sub6 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 17.5 g of compound 86_P1. (yield: 69%, MS: [M+H] + = 592)

[0440] Compound 86_P1 (10g, 16.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (12.2g, 609mmol) is added to trifluoromethanesulfonic anhydride (43g, 152.2mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.5g compound 86. (Yield: 53%, MS: [M+H]+=612)

[0441] Synthesis example 87

[0442]

[0443] Amine 4 (15 g, 42.9 mmol), sub68 (18.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.6 g of compound 87_P1. (Yield: 54%, MS: [M+H] + = 718)

[0444] Compound 87_P1 (10g, 13.9mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.1g, 501.9mmol) was added to trifluoromethanesulfonic anhydride (35.4g, 125.5mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture was cooled to room temperature, and the organic layer and the aqueous layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.8g compound 87. (Yield: 66%, MS: [M+H]+=745)

[0445] Synthesis example 88

[0446]

[0447] Amine 4 (15 g, 42.9 mmol), sub69 (19.3 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 22.3 g of compound 88_P1. (Yield: 70%, MS: [M+H] + = 742)

[0448] Compound 88_P1 (10g, 13.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.7g, 485.7mmol) is added to trifluoromethanesulfonic anhydride (34.3g, 121.4mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7g compound 88. (Yield: 68%, MS: [M+H]+=768)

[0449] Synthesis example 89

[0450]

[0451] Amine 37 (15 g, 42.9 mmol), sub70 (21.7 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 21.8 g of compound 89_P1. (yield: 64%, MS: [M+H] + = 794)

[0452] Compound 89_P1 (10g, 12.6mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.1g, 453.8mmol) is added to trifluoromethanesulfonic anhydride (32g, 113.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.9g compound 89. (Yield: 57%, MS: [M+H]+=825)

[0453] Synthesis Example 90

[0454]

[0455] Amine 4 (15 g, 42.9 mmol), sub71 (20.5 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 19.1 g of compound 90_P1. (Yield: 58%, MS: [M+H] + = 768)

[0456] Compound 90_P1 (10g, 13mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.4g, 469.2mmol) is added to trifluoromethanesulfonic anhydride (33.1g, 117.3mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.8g compound 90. (Yield: 56%, MS: [M+H]+=798)

[0457] Synthesis Example 91

[0458]

[0459] Amine 37 (15 g, 42.9 mmol), sub72 (15 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 19.4 g of compound 91_P1. (yield: 70%, MS: [M+H] + = 646)

[0460] Compound 91_P1 (10g, 15.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (11.2g, 557.9mmol) is added to trifluoromethanesulfonic anhydride (39.4g, 139.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.5g of compound 91. (Yield: 53%, MS: [M+H]+=670)

[0461] Synthesis Example 92

[0462]

[0463] Amine 2 (15 g, 42.9 mmol), sub73 (18.5 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 18.9 g of compound 92_P1. (Yield: 61%, MS: [M+H] + = 724)

[0464] Compound 92_P1 (10g, 13.8mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10g, 497.7mmol) is added to trifluoromethanesulfonic anhydride (35.1g, 124.4mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.3g compound 92. (Yield: 51%, MS: [M+H]+=750)

[0465] Synthesis Example 93

[0466]

[0467] Amine 2 (15 g, 42.9 mmol), sub74 (16 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 21.1 g of compound 93_P1. (yield: 66%, MS: [M+H] + = 744)

[0468] Compound 93_P1 (10g, 13.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.7g, 484.4mmol) is added to trifluoromethanesulfonic anhydride (34.2g, 121.1mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.5g compound 93. (Yield: 63%, MS: [M+H]+=772)

[0469] Synthesis Example 94

[0470]

[0471] Amine 4 (15 g, 42.9 mmol), sub41 (12.6 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.7 g of compound 94_P1. (Yield: 54%, MS: [M+H] + = 592)

[0472] Compound 94_P1 (10g, 16.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (12.2g, 609mmol) is added to trifluoromethanesulfonic anhydride (43g, 152.2mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7g compound 94. (Yield: 67%, MS: [M+H]+=615)

[0473] Synthesis Example 95

[0474]

[0475] Amine 4 (15 g, 42.9 mmol), sub75 (21 g, 45.1 mmol) and sodium tert-butoxide (6.2 g, 64.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 21.4 g of compound 95_P1. (yield: 64%, MS: [M+H] + = 778)

[0476] Compound 95_P1 (10g, 12.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.3g, 463.1mmol) is added to trifluoromethanesulfonic anhydride (32.7g, 115.8mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.3g compound 95. (Yield: 51%, MS: [M+H]+=807)

[0477] Synthesis Example 96

[0478]

[0479] Amine 54 (15 g, 35.3 mmol), sub76 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.9 g of compound 96_P1. (Yield: 55%, MS: [M+H] + = 668)

[0480] Compound 96_P1 (10g, 15mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.8g, 539.6mmol) is added to trifluoromethanesulfonic anhydride (38.1g, 134.9mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the aqueous layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.3g compound 96. (Yield: 51%, MS: [M+H]+=694)

[0481] Synthesis Example 97

[0482]

[0483] Amine 9 (15 g, 35.3 mmol), sub3 (12.2 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 17.7 g of compound 97_P1. (yield: 70%, MS: [M+H] + = 718)

[0484] Compound 97_P1 (10g, 13.9mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.1g, 501.9mmol) is added to trifluoromethanesulfonic anhydride (35.4g, 125.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7g compound 97. (Yield: 67%, MS: [M+H]+=745)

[0485] Synthesis example 98

[0486]

[0487] Amine 55 (15 g, 35.3 mmol), sub7 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.9 g of compound 98_P1. (Yield: 59%, MS: [M+H] + = 668)

[0488] Compound 98_P1 (10g, 15mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.8g, 539.6mmol) is added to trifluoromethanesulfonic anhydride (38.1g, 134.9mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 6.7g compound 98. (Yield: 65%, MS: [M+H]+=693)

[0489] Synthesis Example 99

[0490]

[0491] Amine 56 (15 g, 35.3 mmol), sub77 (13.1 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.1 g of compound 99_P1. (yield: 54%, MS: [M+H] + = 744)

[0492] Compound 99_P1 (10g, 13.5mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.7g, 484.4mmol) is added to trifluoromethanesulfonic anhydride (34.2g, 121.1mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.7g compound 99. (Yield: 55%, MS: [M+H]+=772)

[0493] Synthesis example 100

[0494]

[0495] Amine 57 (15 g, 35.3 mmol), sub78 (12.2 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 13.7 g of compound 100_P1. (Yield: 54%, MS: [M+H] + = 718)

[0496] Compound 100_P1 (10g, 13.9mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.1g, 501.9mmol) was added to trifluoromethanesulfonic anhydride (35.4g, 125.5mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture was cooled to room temperature, and the organic layer and the water layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.7g compound 100. (Yield: 65%, MS: [M+H]+=745)

[0497] Synthesis Example 101

[0498]

[0499] Amine 58 (15 g, 35.3 mmol), sub79 (10.3 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 12.5 g of compound 101_P1. (yield: 53%, MS: [M+H] + = 668)

[0500] Compound 101_P1 (10g, 15mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (10.8g, 539.6mmol) was added to trifluoromethanesulfonic anhydride (38.1g, 134.9mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture was cooled to room temperature, and the organic layer and the water layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.1g compound 101. (Yield: 59%, MS: [M+H]+=693)

[0501] Synthesis Example 102

[0502]

[0503] Amine 59 (15 g, 24.9 mmol), sub5 (5.3 g, 26.2 mmol) and sodium tert-butoxide (3.6 g, 37.4 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.2 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 11.3 g of compound 102_P1. (yield: 59%, MS: [M+H] + = 768)

[0504] Compound 102_P1 (10g, 13mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.4g, 469.2mmol) is added to trifluoromethanesulfonic anhydride (33.1g, 117.3mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.7g compound 102. (Yield: 55%, MS: [M+H]+=798)

[0505] Synthesis example 103

[0506]

[0507] Amine 60 (15 g, 35.3 mmol), sub80 (14 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.6 g of compound 103_P1. (yield: 54%, MS: [M+H] + = 768)

[0508] Compound 103_P1 (10g, 13mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.4g, 469.2mmol) is added to trifluoromethanesulfonic anhydride (33.1g, 117.3mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.4g compound 103. (Yield: 52%, MS: [M+H]+=796)

[0509] Synthesis example 104

[0510]

[0511] Amine 61 (15 g, 35.3 mmol), sub81 (16 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 19.1 g of compound 104_P1. (Yield: 66%, MS: [M+H] + = 820)

[0512] Compound 104_P1 (10g, 12.2mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (8.8g, 439.4mmol) is added to trifluoromethanesulfonic anhydride (31g, 109.9mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7.3g compound 104. (Yield: 70%, MS: [M+H]+=852)

[0513] Synthesis example 105

[0514]

[0515] Amine 62 (15 g, 31.3 mmol), sub82 (10.9 g, 32.8 mmol) and sodium tert-butoxide (4.5 g, 46.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 14.3 g of compound 105_P1. (Yield: 59%, MS: [M+H] + = 776)

[0516] Compound 105_P1 (10g, 12.9mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.3g, 464.3mmol) was added to trifluoromethanesulfonic anhydride (32.8g, 116.1mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture was cooled to room temperature, and the organic layer and the water layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.4g compound 105. (Yield: 62%, MS: [M+H]+=798)

[0517] Synthesis example 106

[0518]

[0519] Amine 63 (15 g, 29.9 mmol), sub42 (10.3 g, 31.4 mmol) and sodium tert-butoxide (4.3 g, 44.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.4 g of compound 106_P1. (yield: 65%, MS: [M+H] + = 794)

[0520] Compound 106_P1 (10g, 12.6mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.1g, 453.8mmol) is added to trifluoromethanesulfonic anhydride (32g, 113.5mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 5.6g compound 106. (Yield: 54%, MS: [M+H]+=824)

[0521] Synthesis Example 107

[0522]

[0523] Amine 64 (15 g, 27.2 mmol), sub83 (9.4 g, 28.6 mmol) and sodium tert-butoxide (3.9 g, 40.8 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.1 g, 0.3 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 15.4 g of compound 107_P1. (yield: 67%, MS: [M+H] + = 844)

[0524] Compound 107_P1 (10g, 11.9mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (8.6g, 426.9mmol) was added to trifluoromethanesulfonic anhydride (30.1g, 106.7mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture was cooled to room temperature, and the organic layer and the water layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.3g compound 107. (Yield: 61%, MS: [M+H]+=877)

[0525] Synthesis example 108

[0526]

[0527] Amine 65 (15 g, 35.3 mmol), sub65 (12.8 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 17.6 g of compound 108_P1. (yield: 68%, MS: [M+H] + = 736)

[0528] Compound 108_P1 (10g, 13.6mmol) is added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (9.8g, 489.6mmol) is added to trifluoromethanesulfonic anhydride (34.5g, 122.4mmol) at 0°C, and the mixture is stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide is added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture is stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture is cooled to room temperature, and the organic layer and the water layer are separated. Then, the organic layer is neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer is separated, anhydrous magnesium sulfate is added thereto, stirred, then filtered, and the filtrate is distilled under reduced pressure. The concentrated compound is purified by silica gel column chromatography to prepare 7g compound 108. (Yield: 68%, MS: [M+H]+=758)

[0529] Synthesis Example 109

[0530]

[0531] Amine 66 (15 g, 35.3 mmol), sub84 (11.9 g, 37 mmol) and sodium tert-butoxide (5.1 g, 52.9 mmol) were added to 300 ml of xylene under a nitrogen atmosphere, and the mixture was stirred and refluxed. Then, bis(tri-tert-butylphosphine)palladium(0) (0.2 g, 0.4 mmol) was added thereto. The reaction was complete after 5 hours, the reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Then, the compound was completely dissolved in chloroform again, washed twice with water, and then the organic layer was separated, treated with anhydrous magnesium sulfate, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 16.6 g of compound 109_P1. (Yield: 57%, MS: [M+H] + = 828)

[0532] Compound 109_P1 (10g, 12.1mmol) was added to 200ml 1,2,4-trichlorobenzene and stirred at room temperature. In another container, deuterium oxide (8.7g, 435.1mmol) was added to trifluoromethanesulfonic anhydride (30.7g, 108.8mmol) at 0°C, and the mixture was stirred for 5 hours to prepare a solution. Then, a mixed solution of trifluoromethanesulfonic anhydride and deuterium oxide was added dropwise to the mixed solution of prepared 1,2,4-trichlorobenzene, and the mixture was stirred while being heated to 140°C and then maintaining the temperature. After reacting for 10 hours, the reaction mixture was cooled to room temperature, and the organic layer and the water layer were separated. Then, the organic layer was neutralized with potassium carbonate aqueous solution. After washing twice with water, the organic layer was separated, anhydrous magnesium sulfate was added thereto, stirred, then filtered, and the filtrate was distilled under reduced pressure. The concentrated compound was purified by silica gel column chromatography to prepare 6.1g compound 109. (Yield: 59%, MS: [M+H]+=855)

[0533] [Example]

[0534] Example 1-1

[0535] It is coated with a thickness of The glass substrate of ITO (indium tin oxide) as film is put into the distilled water dissolved with detergent therein, and carries out ultrasonic cleaning.Use the product manufactured by Fischer Co. as detergent, and as distilled water, use the distilled water filtered twice by the filter manufactured by Millipore Co..After ITO was cleaned for 30 minutes, use distilled water to repeat ultrasonic cleaning twice for 10 minutes.After finishing with distilled water cleaning, use isopropyl alcohol, acetone and methanol solvent to carry out ultrasonic cleaning to substrate, dry, then transfer to plasma cleaner.In addition, use oxygen plasma to clean substrate for 5 minutes, then transfer in vacuum deposition device.

[0536] On the thus prepared ITO transparent electrode, the following compound HI-1 was applied as The hole injection layer was formed into a layer with a thickness of 1.5 wt % by weight, but the following compound A-1 was p-doped at a concentration of 1.5 wt %. The following compound HT-1 was vacuum deposited on the hole injection layer to form a layer with a thickness of Then, the compound 1 prepared in Synthesis Example 1 was thermally vacuum deposited onto Then, the compound represented by the following chemical formula BH-1 and BD-1 was vacuum deposited onto the substrate at a weight ratio of 25:1. Next, a compound represented by the following chemical formula HB-1 was vacuum deposited onto Next, a compound represented by the following chemical formula ET-1 and a compound represented by LiQ were thermally vacuum deposited onto the substrate at a weight ratio of 1:1. The thickness of the electron injection and transport layer is used as the electron injection and transport layer. Lithium fluoride (LiF) and aluminum are sequentially deposited on the electron injection and transport layer to a thickness of respectively and To form a cathode, thereby completing the manufacture of an organic light-emitting device.

[0537]

[0538] During the above process, the deposition rate of the organic material is maintained at to The deposition rates of magnesium and silver were kept at and The vacuum during deposition was maintained at 2 × 10 -7 Up to 5×10 -6 Support, thereby manufacturing an organic light-emitting device.

[0539] Examples 1-2 to 1-109

[0540] Organic light-emitting devices of Examples 1-2 to 1-109 were manufactured in the same manner as in Example 1-1, except that the compounds listed in the following Table 1 were used instead of Compound 1.

[0541] Comparative Examples 1-1 to 1-8

[0542] Organic light-emitting devices of Comparative Examples 1-1 to 1-8 were manufactured in the same manner as in Example 1-1, except that the compounds listed in the following Table 1 were used instead of Compound 1.

[0543] Compounds C-1 to C-8 used in Comparative Examples 1-1 to 1-8 are as follows.

[0544]

[0545] Experimental example

[0546] By applying 15 mA / cm to the organic light emitting devices manufactured in Examples 1-1 to 1-109 and Comparative Examples 1-1 to 1-8, 2 The voltage and efficiency were measured with a current of 100 nits, and the results are shown in the following Table 1. The lifespan T95 means the time required for the luminance to decrease to 95% of the initial luminance (1000 nits).

[0547] [Table 1]

[0548]

[0549]

[0550]

[0551]

[0552]

[0553] Referring to Table 1, it is determined that the driving voltage of the organic light-emitting devices of Examples 1-1 to 1-109 in which the compound represented by Chemical Formula 1 is used as the hole transport auxiliary layer material of the blue light-emitting layer is lower than that of Comparative Examples 1-1 to 1-8, and the efficiency and lifespan are significantly improved. In particular, it is determined that when the deuterium-substituted compound represented by Chemical Formula 1 is used, the lifespan characteristics of the organic light-emitting device are further improved. It is believed that the device of the embodiment exhibits excellent characteristics in terms of driving voltage, efficiency and lifespan because the compound represented by Chemical Formula 1 contributes to the stability of the excitons formed in the light-emitting layer.

[0554] [reference numerals]

[0555] 1: Substrate 2: Anode

[0556] 3: Organic material layer 4: Cathode

[0557] 5: Hole injection layer 6: Hole transport layer

[0558] 7: Hole transport auxiliary layer 8: Light-emitting layer

[0559] 9: Hole blocking layer 10: Electron transport layer

[0560] 11: Electron injection layer 12: Electron injection and transport layer

Claims

1. A compound represented by the following chemical formula 1: [Chemical formula 1] in, In Chemical Formula 1, D is deuterium, a to c are each independently an integer from 0 to 6, R1 to R3 are each independently hydrogen; deuterium; or -L a -R a , provided that at least one of R1 to R3 is -L a -R a , L a is a single bond; or substituted or unsubstituted C 6-30 Arylene, R a is substituted or unsubstituted C 6-30 Aryl; substituted or unsubstituted C containing at least one heteroatom of O and S 2-30 Heteroaryl; substituted or unsubstituted C 3-12 Aliphatic ring and C 6-30 A fused ring of an aromatic group; or a substituted or unsubstituted C 6-30 Arylsilyl, Provided that the case where all of R1 to R3 are unsubstituted phenyl groups is not included.

2. The compound according to claim 1, wherein: R a At least one deuterium and / or at least one C 1-10 Alkyl substitution.

3. The compound according to claim 1, wherein: L a is a single bond; phenylene; biphenyldiyl; or naphthalenediyl.

4. The compound according to claim 1, wherein: R a is phenyl; biphenyl; terphenyl; naphthyl; (phenyl) naphthyl; phenanthryl; fluoranthenyl; benzo[a]phenanthryl; benzo[c]phenanthryl; dibenzofuran; dibenzothiophene; triphenylsilyl; 2,3-dihydro-1H-indenyl; 1,2,3,4-tetrahydronaphthyl; or 6,7,8,9-tetrahydro-5H-benzo[7]annulene, Wherein R a unsubstituted or substituted with at least one substituent selected from the group consisting of deuterium, methyl, ethyl, propyl, isopropyl and tert-butyl.

5. The compound according to claim 1, wherein: The compound represented by Chemical Formula 1 is any one selected from the following: wherein Dn means the deuterium (D) substitution number of each compound described in the square brackets, which is different for each compound, n is an integer of 0 or more, and the maximum value of n is the total number of hydrogens contained in each compound in the square brackets.

6. An organic light-emitting device, comprising: a first electrode; a second electrode disposed opposite to the first electrode; and one or more organic material layers provided between the first electrode and the second electrode, wherein at least one of the organic material layers comprises the compound according to any one of claims 1 to 5.

7. The organic light emitting device according to claim 6, wherein: The organic material layer containing the compound is a hole transport auxiliary layer.

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