JP3058945B2 - N- (3,3-disubstituted acryloyl) piperazine derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[Object of the invention]

[0002]

The present invention relates to a novel N- (3,3-disubstituted acryloyl) piperazine derivative having an excellent platelet activating factor (PAF) antagonism. PAF
Is an in vivo ether-type phospholipid having a strong physiological action (platelet aggregation activating action, leukocyte activating action, blood pressure lowering action, etc.), and acts as one of mediators of immune response. It is thought to be deeply involved in certain disease states. Therefore, a substance having a PAF antagonistic action is
It can be a therapeutic agent for various diseases in which F is considered to be involved, for example, endotoxin shock, anaphylactic shock, nephritis, myocardial infarction, angina, asthma, psoriasis, gastric ulcer and the like. It can also be used as a preventive agent for rejection during organ transplantation.

[0003]

2. Description of the Related Art Compounds having a bis (aryl) methylene group are disclosed in Japanese Patent Application Laid-Open Nos.
It is known that the compound described in JP-A-4-31766 is a compound having a piperazine skeleton, and the compound described in JP-A-64-77 has PAF antagonistic activity.

[0004]

SUMMARY OF THE INVENTION The present inventors have developed a PAF
As a result of years of intensive studies on the synthesis of derivatives having an antagonistic activity and their pharmacological activities, a novel N- (3,3-disubstituted acryloyl) piperazine derivative having a structure different from that of known compounds is excellent. The present inventors have found that the compound has a PAF antagonistic effect, has low toxicity, and that a stable and high blood concentration can be obtained by oral administration.

[0005]

Configuration of the Invention

[0006]

According to the present invention, there is provided a novel N- (3,3
-Disubstituted acryloyl) piperazine derivatives have the general formula

[0007]

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Wherein R ¹ and R ² are the same or different and each have a group having the formula —R ⁶ [wherein R ⁶ is an aryl group which may be substituted; A 1 to 5 substituents selected from the following group A) or an optionally substituted heteroaryl group (the substituents may be 1 to 5 substituents selected from the following group A) There is). ]
A group having the formula —CH = CH—R ⁶ (wherein R ⁶ has the same meaning as described above), or a group having the formula —C≡C—R ⁶ (wherein
R ⁶ has the same meaning as described above. ). R ³ represents a hydrogen atom, a lower alkyl group, a cyano group, or a group having the formula —R ⁶ (wherein R ⁶ has the same meaning as described above), or together with R ⁵ , And a general formula-(CH ₂ ) _p- (where p represents 1 to 3). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituent is 1 to 5 substituents selected from the following groups A and B), or an optionally substituted heteroaryl group (The substituent is 1 to 5 selected from the following group A)
Substituents. ). R ⁵ represents a hydrogen atom or a lower alkyl group, or together with R ³ ,
And a general formula-(CH ₂ ) _p- (where p represents 1 to 3). m represents 1 or 2. n represents 1 or 2. However, when R ⁴ represents a 3-pyridyl group, R ³ represents a hydrogen atom or a lower alkyl group, R ⁵ represents a hydrogen atom or a lower alkyl group, and m and n each represent ¹ , R ^{1 represents} And R ² are the same or different and have a group having the formula —R ^{6 ′ wherein} R ^{6 ′} is a substituted aryl group (wherein the substituents are 1 to 5 selected from Group A below) ) Or a heteroaryl group which may be substituted (the substituent is 1 to 5 substituents selected from Group A below). ] In groups (having the formula -CH = CH-R ^6,
R ⁶ has the same meaning as described above. Or a group having the formula —C≡C—R ⁶ (wherein R ⁶ has the same meaning as described above). }, And a prophylactic or therapeutic agent for a disease caused by PAF of the present invention is represented by the general formula:

[0009]

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Wherein R ¹ and R ² are the same or different and are each a group having the formula —R ⁶ [wherein R ⁶ is an aryl group which may be substituted; A 1 to 5 substituents selected from the following group A) or an optionally substituted heteroaryl group (the substituents may be 1 to 5 substituents selected from the following group A) There is). ]
A group having the formula —CH = CH—R ⁶ (wherein R ⁶ has the same meaning as described above), or a group having the formula —C≡C—R ⁶ (wherein
R ⁶ has the same meaning as described above. ). R ³ represents a hydrogen atom, a lower alkyl group, a cyano group, or a group having the formula —R ⁶ (wherein R ⁶ has the same meaning as described above), or together with R ⁵ , And a general formula-(CH ₂ ) _p- (where p represents 1 to 3). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituent is 1 to 5 substituents selected from the following groups A and B), or an optionally substituted heteroaryl group (The substituent is 1 to 5 selected from the following group A)
Substituents. ). R ⁵ represents a hydrogen atom or a lower alkyl group, or together with R ³ ,
And a general formula-(CH ₂ ) _p- (where p represents 1 to 3). m represents 1 or 2. n represents 1 or 2. ｝
Or a salt thereof. [Group A] a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a hydroxyl group, an alkylenedioxy group having 1 to 4 carbon atoms, an acyloxy group, a halogen atom, a cyano group and a nitro group. [Group B] a lower alkylsulfonyl group, a lower alkylsulfinyl group and a lower alkylthio group.

In the general formula (I), the term "aryl group" of the "optionally substituted aryl group" in the definition of R ⁶ means a group having 5 carbon atoms such as phenyl and naphthyl.
There may be mentioned up to 12 aromatic hydrocarbon groups, preferably a phenyl group.

The "heteroaryl group" of the "optionally substituted heteroaryl group" in the definition of R ⁴ and R ⁶
Is an optionally condensed 5- to 14-membered aromatic heterocyclic group containing 1 to 3 sulfur atoms, oxygen atoms and / or nitrogen atoms, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, Oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl,
Pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,
Indolyl, indazolyl, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, sinolinyl, pteridinyl, carbazolyl, carbolinyl, phenanthridinyl and acridinyl, preferably sulfur atom, oxygen atom or / and / or An optionally condensed 5- to 10-membered aromatic heterocyclic group containing 1 to 2 nitrogen atoms, more preferably a furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, quinolyl and isoquinolyl group is there.

[0013] The term "optionally substituted heteroaryl"
When the heteroaryl group includes a nitrogen atom, the substitution position of the "aryl group" may be on the nitrogen atom.

"Lower alkyl group" in the definition of R ³ and R ⁵ and "lower alkyl group" in the definition of group A include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl , T-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, a straight-chain or branched alkyl group having 1 to 6 carbon atoms such as 2,3-dimethylbutyl, Is a linear or branched alkyl group having 1 to 4 carbon atoms.

The "lower alkylene group" in the definition of A includes, for example, methylene, methylmethylene, ethylene, propylene, trimethylene, tetramethylene, 1-methyltrimethylene, 2-methyltrimethylene, 3-methyltrimethylene, pentamethylene. , Such as hexamethylene
There may be mentioned 6 to 6 alkylene groups, preferably methylene, ethylene, trimethylene or tetramethylene.

The term "halogeno lower alkyl group" in the definition of Group A means a group in which a halogen atom such as fluorine, chlorine, bromine or iodine is bonded to the above "lower alkyl group", for example, trifluoromethyl, Trichloromethyl,
Difluoromethyl, dichloromethyl, dibromomethyl,
Groups such as fluoromethyl, pentafluoroethyl, 2,2,2-trichloroethyl, 2,2,2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2,2-dibromoethyl Mention may be made of, preferably trifluoromethyl, trichloromethyl and pentafluoroethyl.

"Lower alkoxy group" in the definition of group A
Represents a group in which the above-mentioned "lower alkyl group" is bonded to an oxygen atom, for example, methoxy, ethoxy, n-propoxy,
Isopropoxy, n-butoxy, isobutoxy, s-butoxy, t-butoxy, n-pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, n-hexyloxy, 4-
Methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,
A linear or branched alkoxy group having 1 to 6 carbon atoms such as 3-dimethylbutoxy or 2,3-dimethylbutoxy, preferably a linear or branched alkoxy group having 1 to 4 carbon atoms; Group.

The term "alkylenedioxy group having 1 to 4 carbon atoms" in the definition of Group A means that the alkylene moiety is a straight-chain or branched-chain alkylene group, for example, methylenedioxy, ethylidenedioxy, It represents a group such as dimethylenedioxy, isopropylenedioxy, trimethylenedioxy, tetramethylenedioxy, and is preferably methylenedioxy.

The "acyloxy group" in the definition of Group A includes, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy,
Pentanoyloxy, pivaloyloxy, valeryloxy, isovaleryloxy, octanoyloxy, nonylcarbonyloxy, decylcarbonyloxy, 3-methylnonylcarbonyloxy, 8-methylnonylcarbonyloxy, 3-ethyloctylcarbonyloxy, 3,7- Dimethyloctylcarbonyloxy, undecylcarbonyloxy, dodecylcarbonyloxy, tridecylcarbonyloxy, tetradecylcarbonyloxy, pentadecylcarbonyloxy, hexadecylcarbonyloxy,
1-methylpentadecylcarbonyloxy, 14-methylpentadecylcarbonyloxy, 13,13-dimethyltetradecylcarbonyloxy, heptadecylcarbonyloxy, 15-methylhexadecylcarbonyloxy, octadecylcarbonyloxy, 1-methylheptadecylcarbonyloxy , Nonadecylcarbonyloxy, eicosylcarbonyloxy, alkylcarbonyloxy groups such as henicosylcarbonyloxy, chloroacetyloxy, dichloroacetyloxy, trichloroacetyloxy, halogenated alkylcarbonyloxy groups such as trifluoroacetyloxy, A lower alkoxyalkylcarbonyloxy group such as methoxyacetyloxy,
(E) aliphatic acyloxy groups such as unsaturated alkylcarbonyloxy groups such as 2-methyl-2-butenoyloxy; arylcarbonyloxy groups such as benzoyloxy, α-naphthoyloxy and β-naphthoyloxy Halogenated arylcarbonyloxy groups such as, 2-bromobenzoyloxy and 4-chlorobenzoyloxy; lower alkylated arylcarbonyloxy groups such as 2,4,6-trimethylbenzoyloxy and 4-toluoyloxy Groups, lower alkoxylated arylcarbonyloxy groups such as 4-anisoyloxy, nitrated arylcarbonyloxy groups such as 4-nitrobenzoyloxy and 2-nitrobenzoyloxy, 2- (methoxycarbonyl) benzoyl Lower alkoxycarbonylated arylcarbonyloxy group such as oxy, 4-phenylbenzoyloxy Aromatic acyloxy groups such as arylated arylcarbonyloxy groups such as xy; lower alkoxycarbonyloxy groups such as methoxycarbonyloxy, ethoxycarbonyloxy, t-butoxycarbonyloxy and isobutoxycarbonyloxy; An alkoxycarbonyloxy group such as a lower alkoxycarbonyloxy group substituted with a halogen or a tri-lower alkylsilyl group such as 2,2-trichloroethoxycarbonyloxy and 2-trimethylsilylethoxycarbonyloxy; vinyloxycarbonyloxy, allyloxycarbonyloxy Benzyloxycarbonyloxy, 4-methoxybenzyloxycarbonyloxy, 3,4-dimethoxybenzyloxycarbonyloxy, 2-nitrobenzyloxy An aralkyloxycarbonyloxy group in which the aryl ring may be substituted with one or two lower alkoxy or nitro groups such as carbonyloxy and 4-nitrobenzyloxycarbonyloxy; pivaloyloxymethyloxycarbonyloxy Acyloxy groups that are easily hydrolyzed in vivo for prodrug formation when administered to living organisms; lower alkanesulfonyloxy groups such as methanesulfonyloxy, ethanesulfonyloxy and 1-propanesulfonyloxy; trifluoromethanesulfonyl Oxy, fluorinated lower alkanesulfonyloxy groups such as pentafluoroethanesulfonyloxy and arylsulfonyloxy groups such as benzenesulfonyloxy and p-toluenesulfonyloxy. An acyloxy group, more preferably an alkyl carbonyloxy group.

The "halogen atom" in the definition of Group A represents fluorine, chlorine, bromine or iodine.

The term "lower alkylsulfonyl group" in the definition of Group B refers to a group in which the above "lower alkyl group" is bonded to a sulfonyl group. n-butanesulfonyl, isobutanesulfonyl, s-butanesulfonyl, t-butanesulfonyl, n-pentanesulfonyl, isopentanesulfonyl, 2-methylbutanesulfonyl, neopentanesulfonyl, n-hexanesulfonyl, 4-methylpentanesulfonyl, 3-methyl Pentanesulfonyl, 2-methylpentanesulfonyl, 3,3-
Dimethylbutanesulfonyl, 2,2-dimethylbutanesulfonyl, 1,1-dimethylbutanesulfonyl, 1,2-dimethylbutanesulfonyl, 1,3-dimethylbutanesulfonyl, 2,3-
It represents a linear or branched alkanesulfonyl group having 1 to 6 carbon atoms such as dimethylbutanesulfonyl, and preferably a linear or branched alkanesulfonyl group having 1 to 4 carbon atoms.

The term "lower alkylsulfinyl group" in the definition of Group B refers to a group in which the above "lower alkyl group" is bonded to a sulfinyl group, such as methanesulfinyl, ethanesulfinyl, n-propanesulfinyl, isopropanesulfinyl, n-butanesulfinyl, isobutanesulfinyl, s-butanesulfinyl, t-butanesulfinyl, n-pentanesulfinyl, isopentanesulfinyl, 2-methylbutanesulfinyl, neopentanesulfinyl, n-hexanesulfinyl, 4-methylpentanesulfinyl, 3-methyl Pentanesulfinyl, 2-methylpentanesulfinyl, 3,3-dimethylbutanesulfinyl, 2,2-dimethylbutanesulfinyl, 1,
A linear or branched alkane sulfinyl group having 1 to 6 carbon atoms such as 1-dimethylbutanesulfinyl, 1,2-dimethylbutanesulfinyl, 1,3-dimethylbutanesulfinyl, and 2,3-dimethylbutanesulfinyl; Preferably, it is a linear or branched alkanesulfinyl group having 1 to 4 carbon atoms.

The term "lower alkylthio group" in the definition of Group B refers to a group in which the above "lower alkyl group" is bonded to a sulfur atom, for example, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutyl Thio, s-butylthio, t-butylthio, n-pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, n-hexylthio, 4-methylpentylthio, 3-
Methylpentylthio, 2-methylpentylthio, 3,3-dimethylbutylthio, 2,2-dimethylbutylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 1 carbon such as 2,3-dimethylbutylthio
Represents from 6 to 6 linear or branched alkylthio groups,
Preferably, it is a linear or branched alkylthio group having 1 to 4 carbon atoms.

Some of the compounds (I) of the present invention can be converted into salts.
Preferably, inorganic salts such as hydrohalides such as hydrofluoride, hydrochloride, hydrobromide and hydroiodide, nitrates, perchlorates, sulfates and phosphates Lower alkyl sulfonates such as methanesulfonate, trifluoromethanesulfonate and ethanesulfonate, aryl sulfonates such as benzenesulfonate and p-toluenesulfonate, and fumarate , Succinate, citrate,
Organic acid salts such as tartrate, oxalate and maleate, and amino acid salts such as glutamate and aspartate can be mentioned.

When R ⁴ represents a “heteroaryl group” containing a nitrogen atom, the nitrogen atom is, for example,
The lower alkylation using a halogeno lower alkyl can give an onium salt, and the corresponding anion of such a salt is preferably a fluorine anion, a chlorine anion, a bromine anion or an iodine anion. Inorganic anions such as a halogen anion, a nitrate anion, a perchlorate anion, a sulfate anion and a phosphate anion.

The compound (I) of the present invention may have an asymmetric carbon in the molecule, and in this case, there are stereoisomers each having the (R) or (S) configuration. Further, since it has a double bond, there are geometric isomers of the (Z) -form or (E) -form, and each of them or a mixture thereof is included in the present invention.

In the compound (I), preferred examples of the compound include: (1) R ¹ and R ^{2 each} represent a group having the formula —R ⁶ (wherein R ⁶
Has the same significance as described above. (2) a compound wherein at least one of R ¹ and R ² is an aryl group substituted with a substituent selected from the group A (3) a compound wherein R ³ is a hydrogen atom or a lower alkyl group (4) A compound in which R ³ together with R ^{5 represents} a general formula — (CH ₂ ) _p — (wherein p represents 1 to 3). (5) R ⁴ represents 1 to 5 (6) R ⁴ is a heteroaryl group which may be substituted (the substituent may be one to three substituents selected from the following group A) . a group), compound (7) X is an oxygen atom the compound (8) or R ⁵ represents a hydrogen atom, or taken together with R ^3, the general formula - (CH _{2) p} - ( (Wherein p represents 1 to 3.) (9) a compound wherein m is 1 (10) a compound wherein n is 1 (11) R ¹ and R ² are a group represented by the formula -R ⁶ Having a group (wherein, R ⁶
Has the same significance as described above. ) Or R ¹ and R
² is an aryl group substituted with a substituent selected from Group A, R ³ is a hydrogen atom or a lower alkyl group, and R ⁴ is substituted with 1 to 5 lower alkoxy groups A phenyl group, X is an oxygen atom,
A compound in which R ⁵ is a hydrogen atom, m is 1, and n is 1 (12) R ¹ and R ² are a group having the formula —R ⁶ (wherein R ⁶
Has the same significance as described above. ) Or R ¹ and R
^At least one of ² is a substituent selected from Group A,
A substituted aryl group wherein R ³ together with R ⁵ are represented by the general formula — (CH ₂ ) _p — (wherein p represents 1-3)
Wherein R ⁴ is a phenyl group substituted with 1 to 5 lower alkoxy groups, X is an oxygen atom, and m is 1
Wherein n is 1 (13) R ¹ and R ² are a group having the formula -R ⁶ (wherein R ⁶
Has the same significance as described above. ) Or R ¹ and R
² is an aryl group substituted with a substituent selected from Group A, R ³ is a hydrogen atom or a lower alkyl group, and R ⁴ is an optionally substituted heteroaryl group (the The substituent is one to three substituents selected from the following group A.) wherein X is an oxygen atom;
A compound wherein R ⁵ is a hydrogen atom, m is 1 and n is 1; (14) R ¹ and R ^{2 each} represent a group having the formula —R ⁶ (wherein R ⁶
Has the same significance as described above. ) Or R ¹ and R
^At least one of ² is a substituent selected from Group A,
A substituted aryl group wherein R ³ together with R ⁵ are represented by the general formula — (CH ₂ ) _p — (wherein p represents 1-3)
Wherein R ⁴ is an optionally substituted heteroaryl group (the substituent is one to three substituents selected from Group A below), X is an oxygen atom, a compound wherein m is 1 and n is 1 (15) a compound wherein R ¹ is phenyl substituted with at least one lower alkyl group, halogeno lower alkyl group, lower alkoxy group, halogen atom or cyano group ( 16) R ² is a phenyl group, or at least one lower alkyl group, a halogeno-lower alkyl group, a lower alkoxy group, a cyano group or compound is a phenyl substituted with a halogen atom (17) R ² is at least 1 (18) compounds in which R ² is at least one lower alkyl group, halogeno lower alkyl group, halogeno lower alkyl group, lower alkoxy group or phenyl substituted with a halogen atom; Group, a cyano group or a halogen atom phenyl compounds wherein substituted with (19) in the case of a group having the R ² substituents, compounds substituted position is the meta position (20) R ³ is a compound which is a hydrogen atom (21) A compound in which R ³ together with R ^{5 represents} the general formula — (CH ₂ ) _p — (wherein p represents 1-2). (22) R ⁴ represents 1-3 (23) R ⁴ is a heteroaryl group which may be substituted (the substituent is one substituent selected from the following group A) And (24) a compound in which B is a carbonyl group.

Representative compounds of the present invention include, for example,
The compounds listed in Tables 1 to 4 and their geometric isomers can be mentioned, but the present invention is not limited to these compounds.

In the table, in Examples and Reference Examples, Bu
Is a butyl group, iBu is an isobutyl group, sBu is an s-butyl group, CN is a cyano group, Et is an ethyl group, Np is a naphthyl group, Ph is a phenyl group, Pr is a propyl group, Pyr Is
Pyridyl group and Quin represent a quinolyl group, and Thi represents a thienyl group.

Table 1

[0031]

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{Compound No. R ¹ R ² A} ──────────────────────────────── 1 Ph Ph C = O 2 4-CH ₃ OPh 4-CH ₃ OPh C = O 3 4-ClPh 4-ClPh C = O 4 2-Thi 2-Thi C = O 5 4-Pyr 4-Pyr C = O 62-Np 2-Np C = O 71-Np 1-Np C = O 8 3-Pyr 3-Pyr C = O 9 2-Pyr 2-Pyr C = O 10 2-Quin 2-Quin C = O 11 PhC ≡C- PhC≡C- C = O 12 PhCH = CH- PhCH = CH- C = O 13 3-Thi 3-Thi C = O 14 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh C = O 15 3,4,5-TriCH ₃ OPh 3,4,5- TriCH ₃ OPh C = O 16 Ph 4-CH ₃ OPh C = O 17 Ph 4-ClPh C = O 18 Ph 2-Thi C = O 19 Ph 4-Pyr C = O 20 Ph 2-Np C = O 21 Ph 1-Np C = O 22 Ph 3-Pyr C = O 23 Ph 2-Pyr C = O 24 Ph 2-Quin C = O 25 Ph PhC≡C- C = O 26 Ph PhCH = CH- C = O 27 Ph 3-Thi C = O 28 Ph 3,4-diCH ₃ OPh C = O 29 Ph 3,4,5-TriCH ₃ OPh C = O 30 4-CH ₃ OPh 4-ClPh C = O 31 4-CH ₃ OPh 2-Thi C = O 32 3-CH ₃ OPh 4-Pyr C = O 33 4-CH ₃ OPh 2-Np C = O 34 4-CH ₃ OPh 1-Np C = O 35 4-CH ₃ OPh 3- Pyr C = O 36 4-CH ₃ OPh 2-Pyr C = O 37 4-CH ₃ OPh 2-Quin C = O 38 4-CH ₃ OPh PhC≡C- C = O 39 4-CH ₃ OPh PhCH = CH -C = O 40 4-CH ₃ OPh 3-Thi C = O 41 4-CH ₃ OPh 3,4-diCH ₃ OPh C = O 42 4-CH ₃ OPh 3,4,5-TriCH ₃ OPh C = O 43 4-ClPh 2-Thi C = O 44 4-ClPh 4-Pyr C = O 45 4-ClPh 2-Np C = O 46 4-ClPh 1-Np C = O 47 2-ClPh 3-Pyr C = O 48 3-ClPh 2-Pyr C = O 49 4-ClPh 2-Quin C = O 50 4-ClPh PhC≡C- C = O 51 4-ClPh PhCH = CH- C = O 52 4-ClPh 3-Thi C = O 53 4-ClPh 3,4-diCH ₃ OPh C = O 54 4-ClPh 3,4,5-TriCH ₃ OPh C = O 55 2-Thi 4-Pyr C = O 56 2-Thi 2-Np C = O 57 2-Thi 1-Np C = O 58 2-Thi 3-Pyr C = O 59 2-Thi 2-Pyr C = O 60 2-Thi 2-Quin C = O 61 2-Thi PhC≡C- C = O 62 2-Thi PhCH = CH- C = O 63 2-Thi 3-Thi C = O 64 2-Thi 3,4-diCH ₃ OPh C = O 65 2-Thi 3,4,5-TriCH ₃ OPh C = O 66 4-Pyr 2-Np C = O 67 4-Pyr 1-Np C = O 68 4-Pyr 3-Pyr C = O 69 4-Pyr 2-Pyr C = O 70 4-Pyr 2-Quin C = O 71 4-Pyr PhC≡C- C = O 72 4-Pyr PhCH = CH- C = O 73 4-Pyr 3 -Thi C = O 74 4-Pyr 3,4-diCH ₃ OPh C = O 75 4-Pyr 3,4,5-TriCH ₃ OPh C = O 76 2-Np 1-Np C = O 77 2-Np 3 -Pyr C = O 78 2-Np 2-Pyr C = O 79 2-Np 2-Quin C = O 80 2-Np PhC≡C- C = O 81 2-Np PhCH = CH- C = O 82 2- Np 3-Thi C = O 83 2-Np 3,4-diCH ₃ OPh C = O 84 2-Np 3,4,5-TriCH ₃ OPh C = O 85 1-Np 3-Pyr C = O 86 1- Np 2-Pyr C = O 87 1-Np 2-Quin C = O 88 1-Np PhC≡C- C = O 89 1-Np PhCH = CH- C = O 90 1-Np 3-Thi C = O 91 1-Np 3,4-diCH ₃ OPh C = O 92 1-Np 3,4,5-TriCH ₃ OPh C = O 93 3-Pyr 2-Pyr C = O 94 3-Pyr 2-Quin C = O 95 3-Pyr PhC≡C- C = O 96 3-Pyr PhCH = CH- C = O 97 3-Pyr 3-Thi C = O 98 3-Pyr 3,4-diCH ₃ OPh C = O 99 3-Pyr 3 , 4,5-TriCH ₃ OPh C = O 100 2-Pyr 2-Quin C = O 101 3-Pyr PhC≡C- C = O 102 2-Pyr PhCH = CH- C = O 103 3-Pyr 3-Thi C = O 104 2-Quin PhC≡C- C = O 105 2-Quin PhCH = CH- C = O 106 2-Quin 3-Thi C = O 107 2-Quin 3,4-diCH ₃ OPh C = O 108 2-Quin 3,4,5-TriCH ₃ OPh C = O 109 PhC ≡C- PhCH = CH- C = O 110 PhC ≡C- 3-Thi C = O 111 PhC ≡C- 3,4-diCH ₃ OPh C = O 112 PhC ≡C- 3,4,5-TriCH ₃ OPh C = O 113 PhCH = CH-3-Thi C = O 114 PhCH = CH- 3,4-diCH ₃ OPh C = O 115 PhCH = CH- 3,4,5-TriCH ₃ OPh C = O 116 Ph Ph C = S 117 4-CH ₃ OPh 4-CH ₃ OPh C = S 118 4-ClPh 4-ClPh C = S 119 2-Thi 2-Thi C = S 120 4-F-Ph 4-F-Ph C = S 121 2-Np 2-Np C = S 122 1 -Np 1-Np C = S 123 3-Pyr 3-Pyr C = S 124 2-Pyr 2-Pyr C = S 125 2-Quin 2-Quin C = S 126 PhC ≡C- PhC≡C- C = S 127 PhCH = CH- PhCH = CH- C = S 128 3-Thi 3-Thi C = S 129 Ph 4-CH ₃ OPh C = S 130 Ph 4-ClPh C = S 131 Ph 2-Thi C = S 132 Ph 4-Pyr C = S 133 Ph 2-Np C = S 134 Ph 1-Np C = S 135 Ph 3-Pyr C = S 136 Ph 2-Pyr C = S 137 Ph 2-Quin C = S 138 Ph PhC≡ C- C = S 139 Ph PhCH = CH- C = S 140 Ph 3-Thi C = S 141 4-CH ₃ OP h 4-ClPh C = S 142 2-CH ₃ OPh 2-Thi C = S 143 3-CH ₃ OPh 4-Pyr C = S 144 4-CH ₃ OPh 2-Np C = S 145 4-CH ₃ OPh 1 -Np C = S 146 4-CH ₃ OPh 3-Pyr C = S 147 4-CH ₃ OPh 2-Pyr C = S 148 4-CH ₃ OPh 2-Quin C = S 149 4-CH ₃ OPh PhC≡C -C = S 150 4-CH ₃ OPh PhCH = CH- C = S 151 4-CH ₃ OPh 3-Thi C = S 152 4-ClPh 2-Thi C = S 153 4-ClPh 4-Pyr C = S 154 3-ClPh 2-Np C = S 155 3-ClPh 1-Np C = S 156 2-ClPh 3-Pyr C = S 157 3-ClPh 2-Pyr C = S 158 4-ClPh 2-Quin C = S 159 4-ClPh PhC≡C- C = S 160 4-ClPh PhCH = CH- C = S 161 4-ClPh 3-Thi C = S 162 2-Thi 4-Pyr C = S 163 2-Thi 2-Np C = S 164 2-Thi 1-Np C = S 165 2-Thi 3-Pyr C = S 166 2-Thi 2-Pyr C = S 167 2-Thi 2-Quin C = S 168 2-Thi PhC≡C- C = S 169 2-Thi PhCH = CH- C = S 170 2-Thi 3-Thi C = S 171 4-Pyr 2-Np C = S 172 4-Pyr 1-Np C = S 173 4-Pyr 3-Pyr C = S 174 4-Pyr 2-Pyr C = S 175 4-Pyr 2-Quin C = S 176 4-Pyr PhC≡C- C = S 177 4-Pyr PhCH = CH- C = S 178 4-Pyr 3-Thi C = S 179 2-Np 1-Np C = S 180 2-Np 3-Pyr C = S 181 2-Np 2-Pyr C = S 182 2-Np 2-Quin C = S 183 2-Np PhC≡C- C = S 184 2-Np PhCH = CH- C = S 185 2-Np 3-Thi C = S 186 1-Np 3-Pyr C = S 187 1-Np 2-Pyr C = S 188 1-Np 2-Quin C = S 189 1-Np PhC≡C- C = S 190 1-Np PhCH = CH- C = S 191 1-Np 3 -Thi C = S 192 3-Pyr 2-Pyr C = S 193 3-Pyr 2-Quin C = S 194 3-Pyr PhC≡C- C = S 195 3-Pyr PhCH = CH- C = S 196 3- Pyr 3-Thi C = S 197 2-Pyr 2-Quin C = S 198 3-Pyr PhC≡C- C = S 199 2-Pyr PhCH = CH- C = S 200 3-Pyr 3-Thi C = S 201 2-Quin PhC≡C- C = S 202 2-Quin PhCH = CH- C = S 203 2-Quin 3-Thi C = S 204 PhC ≡C- PhCH = CH- C = S 205 PhC ≡C- 3- Thi C = S 206 PhCH = CH- 3-Thi C = S 207 Ph Ph SO ₂ 208 4-CH ₃ OPh 4-CH ₃ OPh SO ₂ 209 4-ClPh 4-ClPh SO ₂ 210 2-Thi 2-Thi SO ₂ 211 4-Pyr 4-Pyr SO ₂ 212 2-Np 2-Np SO ₂ 213 1-Np 1-Np SO ₂ 214 3-Pyr 3-Pyr SO ₂ 215 2-Pyr 2-Pyr SO 216 2-Quin 2-Quin SO ₂ 217 PhC ≡C- PhC≡C-SO ₂ 218 PhCH = CH- PhCH = CH -SO ₂ 219 3-Thi 3-Thi SO ₂ 220 Ph 4-CH ₃ OPh SO ₂ 221 Ph 4-ClPh SO ₂ 222 Ph 2-Thi SO ₂ 223 Ph 4-Pyr SO ₂ 224 Ph 2-Np SO ₂ 225 Ph 1-Np SO ₂ 226 Ph 3-Pyr SO ₂ 227 Ph 2-Pyr SO ₂ 228 Ph 2-Quin SO ₂ 229 Ph PhC≡C-SO ₂ 230 Ph PhCH = CH-SO ₂ 231 Ph 3-Thi SO ₂ 232 4-CH ₃ OPh 4-ClPh SO ₂ 233 2-CH ₃ OPh 2-Thi SO ₂ 234 3-CH ₃ OPh 4-Pyr SO ₂ 235 4-CH ₃ OPh 2-Np SO ₂ 236 4-CH ₃ OPh 1-Np SO ₂ 237 4-CH ₃ OPh 3-Pyr SO 238 4-CH ₃ OPh 2-Pyr SO ₂ 239 4-CH ₃ OPh 2-Quin SO ₂ 240 4-CH ₃ OPh PhC≡C-SO ₂ 241 4-CH ₃ OPh PhCH = CH-SO ₂ 242 4-CH ₃ OPh 3-Thi SO ₂ 243 4-ClPh 2-Thi SO ₂ 244 4-ClPh 4-Pyr SO ₂ 245 4-ClPh 2-Np SO ₂ 246 4-ClPh 1-Np SO 247 2-ClPh 3-Pyr SO ₂ 248 3-ClPh 2-Pyr SO ₂ 249 4-ClPh 2-Quin SO ₂ 250 4-ClPh PhC≡C-SO ₂ 251 4-ClPh PhCH = CH-SO ₂ 252 4-ClPh 3-Thi SO ₂ 253 2-Thi 4-Pyr SO ₂ 254 2-Thi 2-Np SO ₂ 255 2-Thi 1-Np SO ₂ 256 2-Thi 3-Pyr SO 257 2-Thi 2-Pyr SO ₂ 258 2-Thi 2-Quin SO ₂ 259 2-Thi PhC≡C -SO ₂ 260 2-Thi PhCH = CH- SO ₂ 261 2-Thi 3-Thi SO ₂ 262 4-Pyr 2-Np SO ₂ 263 4-Pyr 1-Np SO ₂ 264 4-Pyr 3-Pyr SO ₂ 265 4-Pyr 2-Pyr SO ₂ 266 4-Pyr 2-Quin SO ₂ 267 4-Pyr PhC≡C-SO ₂ 268 4-Pyr PhCH = CH-SO 269 4-Pyr 3-Thi SO ₂ 270 2-Np 1 -Np SO ₂ 271 2-Np 3-Pyr SO ₂ 272 2-Np 2-Pyr SO ₂ 273 2-Np 2-Quin SO ₂ 274 2-Np PhC≡C-SO ₂ 275 2-Np PhCH = CH- SO ₂ 276 2-Np 3-Thi SO ₂ 277 1-Np 3-Pyr SO ₂ 278 1-Np 2-Pyr SO ₂ 279 1-Np 2-Quin SO ₂ 280 1-Np PhC≡C-SO ₂ 281 1- Np PhCH = CH- SO 282 1- Np 3-Thi SO 2 283 3-Pyr 2-Pyr SO 2 284 3-Pyr 2-Quin SO 2 28 _{3-Pyr PhC≡C- SO 2 286 3} -Pyr PhCH = CH- SO 2 287 3-Pyr 3-Thi SO 2 288 2-Pyr 2-Quin SO 2 289 3-Pyr PhC≡C- SO 2 290 2- Pyr PhCH = CH- SO ₂ 291 3-Pyr 3-Thi SO ₂ 292 2-Quin PhC≡C- SO ₂ 293 2-Quin PhCH = CH- SO ₂ 294 2-Quin 3-Thi SO ₂ 295 PhC ≡C- PhCH = CH-SO ₂ 296 PhC ≡C-3-Thi SO ₂ 297 PhCH = CH- 3-Thi SO ₂ 298 Ph Ph CH ₂ 299 4-CH ₃ OPh 4-CH ₃ OPh CH ₂ 300 4-ClPh 4- ClPh CH ₂ 301 2-Thi 2-Thi CH ₂ 302 4-Pyr 4-Pyr CH ₂ 303 2-Np 2-Np CH ₂ 304 1-Np 1-Np CH ₂ 305 3-Pyr 3-Pyr CH ₂ 306 2 -Pyr 2-Pyr CH ₂ 307 2-Quin 2-Quin CH ₂ 308 PhC ≡C- PhC≡C-CH ₂ 309 PhCH = CH- PhCH = CH-CH ₂ 310 3-Thi 3-Thi CH ₂ 311 3, 4-diCH ₃ OPh 3,4-diCH ₃ OPh CH ₂ 312 3,4,5-TriCH ₃ OPh 3,4,5-TriCH ₃ OPh CH ₂ 313 Ph 4-CH ₃ OPh CH ₂ 314 Ph 4-ClPh CH _{2 315 Ph 2-Thi CH 2} 316 Ph 4-Pyr CH 2 317 Ph 2-Np CH 2 318 Ph 1-Np CH 2 31 _{Ph 3-Pyr CH 2 320 Ph} 2-Pyr CH 2 321 Ph 2-Quin CH 2 322 Ph PhC≡C- CH 2 323 Ph PhCH = CH- CH 2 324 Ph 3-Thi CH 2 325 Ph 3,4-diCH ₃ OPh CH ₂ 326 Ph 3,4,5-TriCH ₃ OPh CH ₂ 327 4-CH ₃ OPh 4-ClPh CH ₂ 328 2-CH ₃ OPh 2-Thi CH ₂ 329 3-CH ₃ OPh 4-Pyr CH ₂ 330 4-CH ₃ OPh 2-Np CH ₂ 331 4-CH ₃ OPh 1-Np CH ₂ 332 4-CH ₃ OPh 3-Pyr CH ₂ 333 4-CH ₃ OPh 2-Pyr CH ₂ 334 4-CH ₃ OPh 2-Quin CH ₂ 335 4-CH ₃ OPh PhC≡C- CH ₂ 336 4-CH ₃ OPh PhCH = CH- CH ₂ 337 4-CH ₃ OPh 3-Thi CH ₂ 338 4-CH ₃ OPh 3,4- diCH ₃ OPh CH ₂ 339 4-CH ₃ OPh 3,4,5-TriCH ₃ OPh CH ₂ 340 4-ClPh 2-Thi CH ₂ 341 4-ClPh 4-Pyr CH ₂ 342 3-ClPh 2-Np CH ₂ 343 3-ClPh 1-Np CH ₂ 344 2-ClPh 3-Pyr CH ₂ 345 3-ClPh 2-Pyr CH ₂ 346 4-ClPh 2-Quin CH ₂ 347 4-ClPh PhC≡C-CH ₂ 348 4-ClPh PhCH = CH- CH ₂ 349 4-ClPh 3-Thi CH ₂ 350 4-ClPh 3,4-diCH ₃ OPh CH ₂ 351 4-ClPh 3,4,5- TriCH ₃ OPh CH ₂ 352 2-Thi 4-Pyr CH ₂ 353 2-Thi 2-Np CH ₂ 354 2-Thi 1-Np CH ₂ 355 2-Thi 3-Pyr CH ₂ 356 2-Thi 2-Pyr CH ₂ 357 2-Thi 2-Quin CH ₂ 358 2-Thi PhC≡C- CH ₂ 359 2-Thi PhCH = CH- CH ₂ 360 2-Thi 3-Thi CH ₂ 361 2-Thi 3,4-diCH ₃ OPh CH ₂ 362 2-Thi 3,4,5-TriCH ₃ OPh CH ₂ 363 4-Pyr 2-Np CH ₂ 364 4-Pyr 1-Np CH ₂ 365 4-Pyr 3-Pyr CH ₂ 366 4-Pyr 2-Pyr CH ₂ 367 4-Pyr 2-Quin CH ₂ 368 4-Pyr PhC≡C-CH ₂ 369 4-Pyr PhCH = CH-CH ₂ 370 4-Pyr 3-Thi CH ₂ 371 4-Pyr 3,4-diCH ₃ OPh CH ₂ 372 4-Pyr 3,4,5-TriCH ₃ OPh CH ₂ 373 2-Np 1-Np CH ₂ 374 2-Np 3-Pyr CH ₂ 375 2-Np 2-Pyr CH ₂ 376 2-Np 2 -Quin CH ₂ 377 2-Np PhC≡C- CH ₂ 378 2-Np PhCH = CH- CH ₂ 379 2-Np 3-Thi CH ₂ 380 2-Np 3,4-diCH ₃ OPh CH ₂ 381 2-Np 3,4,5-TriCH ₃ OPh CH ₂ 382 1-Np 3-Pyr CH ₂ 383 1-Np 2-Pyr CH ₂ 384 1-Np 2-Quin CH ₂ 385 1-Np PhC≡C- CH ₂ 386 1-Np PhCH = CH- CH ₂ 387 1-Np 3-Thi CH ₂ 388 1-Np 3,4-diCH ₃ OPh CH ₂ 389 1-Np 3,4,5-TriCH ₃ OPh CH ₂ 390 3-Pyr 2-Pyr CH ₂ 391 3-Pyr 2-Quin CH ₂ 392 3-Pyr PhC-C-CH ₂ 393 3-Pyr PhCH = CH- CH ₂ 394 3-Pyr 3-Thi CH ₂ 395 3-Pyr 3,4-diCH ₃ OPh CH ₂ 396 3-Pyr 3,4,5-TriCH ₃ OPh CH ₂ 397 2-Pyr 2-Quin CH ₂ 398 3-Pyr PhC≡C-CH ₂ 399 2-Pyr PhCH = CH -CH ₂ 400 3-Pyr 3-Thi CH ₂ 401 2-Quin PhC≡C- CH ₂ 402 2-Quin PhCH = CH- CH ₂ 403 2-Quin 3-Thi CH ₂ 404 2-Quin 3,4-diCH ₃ OPh CH ₂ 405 2-Quin 3,4,5-TriCH ₃ OPh CH ₂ 406 PhC ≡C- PhCH = CH- CH ₂ 407 PhC ≡C- 3-Thi CH ₂ 408 PhC ≡C- 3,4-diCH ₃ OPh CH ₂ 409 PhC ≡C- 3,4,5-TriCH ₃ OPh CH ₂ 410 PhCH = CH- 3-Thi CH ₂ 411 3-CH ₃ OPh 3-CH ₃ OPh C = O 412 3-CH ₃ OPh 4-CH ₃ OPh C = O 413 2-CH ₃ OPh 2-CH ₃ OPh C = O 414 2-CH ₃ OPh 3-CH ₃ OPh C = O 415 2-CH ₃ OPh 4-CH ₃ OPh C = O 416 2-ClPh 2-ClPh C = O 417 2-ClPh 3-ClPh C = O 418 2-ClPh 4-ClPh C = O 419 3-ClPh 3-ClPh C = O 420 3-ClPh 4-ClPh C = O 421 2-CH ₃ Ph 2-CH ₃ Ph C = O 422 2-CH ₃ Ph 3-CH ₃ Ph C = O 423 2-CH ₃ Ph 4-CH ₃ Ph C = O 424 3-CH ₃ Ph 3-CH ₃ Ph C = O 425 3-CH ₃ Ph 4-CH ₃ Ph C = O 426 3-CF ₃ Ph 3-CF ₃ Ph C = O 427 3-CF ₃ CH ₂ Ph 3-CF ₃ CH ₂ Ph C = O 428 2-PrOPh 2-PrOPh C = O 429 2-PrOPh 3-PrOPh C = O 430 2-PrOPh 4-PrOPh C = O 431 3-PrOPh 3-PrOPh C = O 432 3-PrOPh 4-PrOPh C = O 433 4-PrOPh 4-PrOPh C = O 434 3-s-BuOPh 3-s-BuOPh C = O 435 4-s-BuOPh 4-s-BuOPh C = O 436 3-i-BuOPh 3-i-BuOPh C = O 437 4-i-BuOPh 4-i-BuOPh C = O 438 2-EtPh 2-EtPh C = O 439 2-EtPh 3-EtPh C = O 440 2-EtPh 4-EtPh C = O 441 3- EtPh 3-EtPh C = O 442 3-EtPh 4-EtPh C = O 443 4-EtPh 4-EtPh C = O 444 2-PrPh 2-PrPh C = O 445 2-PrPh 3-PrPh C = O 446 2- PrPh 4-PrPh C = O 447 3-PrPh 3-PrPh C = O 448 3-PrPh 4-PrPh C = O 449 4-PrPh 4-PrPh C = O 450 3-i-BuPh 3-i-BuPh C = O 451 3-i-BuPh 4-i-BuPh C = O 452 2-ClPh Ph C = O 453 2- ClPh 3-CH ₃ OPh C = O 454 2-ClPh 4-CH ₃ OPh C = O 455 2-ClPh 3-PrOPh C = O 456 2-ClPh 4-PrOPh C = O 457 2-ClPh 3-BuOPh C = O 458 2-ClPh 4-BuOPh C = O 459 2-ClPh 3-CH ₃ Ph C = O 460 2-ClPh 4-CH ₃ Ph C = O 461 2-ClPh 3-CF ₃ Ph C = O 462 2- ClPh 3,4-diCH ₃ OPh C = O 463 2-ClPh 3-CH ₃ O-4-PrOPh C = O 464 2-ClPh 3,4-diPrOPh C = O 465 2-ClPh 3,4-diClPh C = O 466 3-ClPh Ph C = O 467 3-ClPh 3-CH ₃ OPh C = O 468 3-ClPh 4-CH ₃ OPh C = O 469 3-ClPh 4-EtOPh C = O 470 3-ClPh 4-PrOPh C = O 471 3-ClPh 3-i-BuOPh C = O 472 3-ClPh 4-i-BuOPh C = O 473 3-ClPh 2-CH ₃ Ph C = O 474 3-ClPh 3-CH ₃ Ph C = O 475 3-ClPh 4-CH ₃ Ph C = O 476 3-ClPh 3-CF ₃ Ph C = O 477 3-ClPh 3-EtPh C = O 478 3-ClPh 4-EtPh C = O 479 3-ClPh 3 -PrPh C = O 480 3-ClPh 4-PrPh C = O 481 3-ClPh 2,3-diCH ₃ OPh C = O 482 3-ClPh 3,4-diCH ₃ OPh C = O 483 3-ClPh 4-CH ₃ O-3-PrOPh C = O 484 3-ClPh 3,4-diPrOPh C = O 485 3- ClPh 2,3-diClPh C = O 486 3-ClPh 3,4-diClPh C = O 487 4-ClPh 3-CH ₃ OPh C = O 488 4-ClPh 4-CH ₃ OPh C = O 489 4-ClPh 3 -PrOPh C = O 490 4-ClPh 4-PrOPh C = O 491 4-ClPh 3-i-BuOPh C = O 492 4-ClPh 4-i-BuOPh C = O 493 4-ClPh 2,3-diClPh C = O 494 2,3-diClPh Ph C = O 495 2,3-diClPh 3-CH ₃ OPh C = O 496 2,3-diClPh 4-CH ₃ OPh C = O 497 2,3-diClPh 3-PrOPh C = O 498 2,3-diClPh 4-PrOPh C = O 499 2,3-diClPh 3-s-BuOPh C = O 500 2,3-diClPh 4-s-BuOPh C = O 501 2,3-diClPh 3,4 -diCH ₃ OPh C = O 502 2,3-diClPh 3-CH ₃ Ph C = O 503 2,3-diClPh 4-CH ₃ Ph C = O 504 2,3-diClPh 3-EtPh C = O 505 2, 3-diClPh 4-EtPh C = O 506 2,3-diClPh 3-PrPh C = O 507 2,3-diClPh 4-PrPh C = O 508 2,3-diClPh 3-i-BuOPh C = O 509 2, 3-diClPh 4-i-BuOPh C = O 510 3,4-diClPh Ph C = O 511 3,4-diClPh 2-CH ₃ OPh C = O 512 3,4-diClPh 3-CH ₃ OPh C = O 513 3,4-diClPh 4-CH ₃ OPh C = O 514 3,4-diClPh 3-PrOPh C = O 515 3,4-diClPh 4 -PrOPh C = O 516 3,4-diClPh 3-i-BuOPh C = O 517 3,4-diClPh 4-i-BuOPh C = O 518 3,4-diClPh 3-CH ₃ Ph C = O 519 3, 4-diClPh 4-CH ₃ Ph C = O 520 3,4-diClPh 3-PrPh C = O 521 3,4-diClPh 4-PrPh C = O 522 3,4-diClPh 3-i-BuPh C = O 523 3,4-diClPh 4-i-BuPh C = O 524 3-FPh 3-FPh C = O 525 4-FPh 4-FPh C = O 526 3-FPh Ph C = O 527 3-FPh 4-FPh C = O 528 3-FPh 3-CH ₃ OPh C = O 529 3-FPh 4-CH ₃ OPh C = O 530 3-FPh 3-PrOPh C = O 531 3-FPh 4-PrOPh C = O 532 3-FPh 3 -i-BuOPh C = O 533 3-FPh 4-i-BuOPh C = O 534 3-FPh 3-CH ₃ Ph C = O 535 3-FPh 4-CH ₃ Ph C = O 536 3-FPh 3,4 -diCH ₃ Ph C = O 537 3-FPh 3-CF ₃ Ph C = O 538 3-FPh 3-EtPh C = O 539 3-FPh 4-PrPh C = O 540 3-FPh 4-i-BuPh C = O 541 3-FPh 3,4-diCH ₃ OPh C = O 542 3-FPh 2-ClPh C = O 543 3-FPh 3-ClPh C = O 544 3-FPh 4-ClPh C = O 545 3-FPh 2,3-diClPh C = O 546 3-FPh 3,4-diClPh C = O 547 3-FPh 4-PrPh C = O 548 3-FPh 4-i -BuPh C = O 549 4-FPh Ph C = O 550 4-FPh 3,4-diClPh C = O 551 4-FPh 3,4-diCH ₃ OPh C = O 552 4-FPh 3,4,5-triCH ₃ OPh C = O 553 4-FPh 3-CH ₃ Ph C = O 554 4-FPh 4-CH ₃ Ph C = O 555 4-FPh 3,4-diCH ₃ Ph C = O 556 3-CF ₃ Ph Ph C = O 557 3-CF ₃ Ph 3-CH ₃ OPh C = O 558 3-CF ₃ Ph 4-CH ₃ OPh C = O 559 3-CF ₃ Ph 3-PrOPh C = O 560 3-CF ₃ Ph 4 -PrOPh C = O 561 3-CF ₃ Ph 3-i-BuOPh C = O 562 3-CF ₃ Ph 4-i-BuOPh C = O 563 3-CF ₃ Ph 3-CH ₃ Ph C = O 564 3- CF ₃ Ph 4-CH ₃ Ph C = O 565 3-CF ₃ Ph 2,3-diCH ₃ Ph C = O 566 3-CF ₃ Ph 3,4-diCH ₃ Ph C = O 567 3-CF ₃ Ph 3 -EtPh C = O 568 3-CF ₃ Ph 4-EtPh C = O 569 3-CF ₃ Ph 3-PrPh C = O 570 3-CF ₃ Ph 4-PrPh C = O 571 3-CF ₃ Ph 3-i -BuPh C = O 572 3-CF ₃ Ph 4-i-BuPh C = O 573 3-CF ₃ Ph 2,3-diCH ₃ OPh C = O 574 3-CF ₃ Ph 3,4-diCH ₃ OPh C = O 5 75 2-CH ₃ Ph Ph C = O 576 2-CH ₃ Ph 3,4-diCH ₃ Ph C = O 577 2-CH ₃ Ph 3,4-diCH ₃ OPh C = O 578 2-CH ₃ Ph 3- PrPh C = O 579 2-CH ₃ Ph 4-i-BuPh C = O 580 3-CH ₃ Ph Ph C = O 581 3-CH ₃ Ph 1-Np C = O 582 3-CH ₃ Ph 2-Np C = O 583 3-CH ₃ Ph 3,4-diCH ₃ Ph C = O 584 3-CH ₃ Ph 3-EtPh C = O 585 3-CH ₃ Ph 4-EtPh C = O 586 3-CH ₃ Ph 3- PrPh C = O 587 3-CH ₃ Ph 4-PrPh C = O 588 3-CH ₃ Ph 3-i-BuPh C = O 589 3-CH ₃ Ph 4-i-BuPh C = O 590 3-CH ₃ Ph 3,4-diCH ₃ OPh C = O 591 3-CH ₃ Ph 3-CH ₃ OPh C = O 592 3-CH ₃ Ph 4-CH ₃ OPh C = O 593 3-CH ₃ Ph 3-PrOPh C = O 594 3-CH ₃ Ph 4-PrOPh C = O 595 3-CH ₃ Ph 3-i-BuOPh C = O 596 3-CH ₃ Ph 4-i-BuOPh C = O 597 4-CH ₃ Ph Ph C = O 598 4-CH ₃ Ph 3,4-diCH ₃ OPh C = O 599 4-CH ₃ Ph 3-CH ₃ OPh C = O 600 4-CH ₃ Ph 4-CH ₃ OPh C = O 601 4-CH ₃ Ph 3,4-diPrOPh C = O 602 4-CH ₃ Ph 3-CH ₃ O-4-PrOPh C = O 603 3-CH ₃ O-4-PrOPh Ph C = O 604 3-CH ₃ O-4-PrOPh 2-Np C = O 605 3-CH ₃ O-4-PrOPh 1-Np C = O 606 3,4-diPrOPh Ph C = O 607 3-CH ₃ OPh Ph C = O 608 3-PrOPh Ph C = O 609 4-PrOPh Ph C = O 610 3-i-BuOPh Ph C = O 611 4-i-BuOPh Ph C = O 612 3-EtPh Ph C = O 613 3-EtPh 1-Np C = O 614 3-EtPh 2-Np C = O 615 3-PrPh Ph C = O 616 3-PrPh 1-Np C = O 617 3-PrPh 2-Np C = O 618 3-i-BuPh Ph C = O 619 3-i-BuPh 1-Np C = O 620 3-i-BuPh 2-Np C = O 621 3,4-diCH ₃ Ph Ph C = O 622 Ph 3-CH ₃ O-4-EtO-Ph C = O 623 Ph 3-CH ₃ O-4 -EtO-Ph C = S 624 Ph 3-CH ₃ O-4-EtO-Ph CH ₂ 625 Ph 3-CH ₃ O-4-PrO-Ph C = S 626 Ph 3-CH ₃ O-4-PrO- Ph CH ₂ 627 Ph 3-CH ₃ O-4-BuO-Ph C = O 628 Ph 3-CH ₃ O-4-C ₅ H ₁₁ O-Ph C = O 629 Ph 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 630 Ph 3-EtO-4-CH ₃ O-Ph C = O 631 Ph 3-PrO-4-CH ₃ O-Ph C = O 632 Ph 3-BuO-4-CH ₃ O-Ph C = O 633 Ph 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 634 Ph 3-C ₆ H ₁₃ O-4-CH ₃ O-Ph C = O 635 Ph 3 , 4-di-CH ₃ O-Ph C = S 636 Ph 3,4- di-CH ₃ O-Ph CH ₂ 637 Ph 3,4-di-EtO-Ph C = O 638 Ph 3,4-di-PrO-Ph C = S 639 Ph 3,4-di-PrO-Ph CH ₂ 640 Ph 3,4-di-BuOPh C = O 641 Ph 4-EtOPh C = O 642 Ph 4-BuOPh C = O 643 Ph 4-C 5 H 11 OPh C = O 644 Ph 4-C 6 H 13 OPh C = O 645 Ph 3-CH ₃ OPh C = O 646 Ph 3-EtOPh C = O 647 Ph 3-BuOPh C = O 648 Ph 3-BuPh C = O 649 Ph 4-BuPh C = O 650 Ph 3- C ₅ H ₁₁ OPh C = O 651 Ph 3-C ₆ H ₁₃ OPh C = O 652 Ph 3,4-diEtPh C = O 653 Ph 3,4-diPrPh C = O 654 Ph 3,4-diBuPh C = O 655 3-BuOPh 3-BuOPh C = O 656 4-ClPh 2,3-di-CH ₃ O-Ph C = O 657 2,3-diClPh 3-BuPh C = O 658 2,3-diClPh 4-BuPh C = O 659 3,4-diClPh 3-EtPh C = O 660 3,4-diClPh 4-EtPh C = O 661 3,4-diClPh 3-BuPh C = O 662 3,4-diClPh 4-BuPh C = O 666 3,4-diClPh 4-CH ₃ OPh C = S 664 3,4-diClPh 4-CH ₃ OPh CH ₂ 665 3,4-diClPh 4-PrOPh C = S 666 3,4-diClPh 3-PrOPh CH ₂ 667 3,4-diClPh 3-BuOPh C = O 668 3,4-diClPh 4-BuOPh C = O 6 69 3,4-diClPh 3,4-di-CH ₃ O-Ph C = O 670 3-CF ₃ Ph 3-EtOPh C = O 671 3-CF ₃ Ph 4-EtOPh C = O 672 3-CF ₃ Ph 3-BuOPh C = O 673 3-CF ₃ Ph 3-C ₅ H ₁₁ OPh C = O 674 3-CF ₃ Ph 3-C ₆ H ₁₃ OPh C = O 675 3-CF ₃ Ph 4-BuOPh C = O 676 3-CF ₃ Ph 4-C ₅ H ₁₁ OPh C = O 677 3-CF ₃ Ph 4-C ₆ H ₁₃ OPh C = O 678 3-CF ₃ Ph 4-BuPh C = O 679 3-CF ₃ Ph 3-EtO-4-CH ₃ O-Ph C = O 680 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph C = O 681 3-CF ₃ Ph 3-BuO-4-CH ₃ O- Ph C = O 682 3-CF ₃ Ph 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 683 3-CF ₃ Ph 3-C ₆ H ₁₃ O-4-CH ₃ O-Ph C = O 684 3-CF ₃ Ph 3-CH ₃ O-4-EtO-Ph C = O 685 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph C = O 686 3-CF ₃ Ph 3- CH ₃ O-4-PrO-Ph C = S 687 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph CH ₂ 688 3-CF ₃ Ph 3-CH ₃ O-4-BuO-Ph C = O 689 3-CF ₃ Ph 3-CH ₃ O-4-C ₅ H ₁₁ O-Ph C = O 690 3-CF ₃ Ph 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 691 3-CF ₃ Ph 3,4-di-CH ₃ O-Ph C = S 692 3-CF ₃ Ph 3,4-di-CH ₃ O-Ph CH ₂ 693 3-CF ₃ Ph 3,4-di- EtO -Ph C = O 694 3-CF ₃ Ph 3,4-di-PrO-Ph C = O 695 3-CF ₃ Ph 3,4-di-PrO-Ph C = S 696 3-CF ₃ Ph 3,4 -di-PrO-Ph CH ₂ 697 3-CF ₃ Ph 3,4-di-BuO-Ph C = O 698 3-CH ₃ Ph 3-CH ₃ Ph C = S 699 3-CH ₃ Ph 3-CH ₃ Ph CH ₂ 700 3-CH ₃ Ph 3-BuPh C = O 701 3-CH ₃ Ph 4-BuPh C = O 702 3-CH ₃ Ph 3-EtOPh C = O 703 3-CH ₃ Ph 4-EtOPh C = O 704 3-CH ₃ Ph 3-BuOPh C = O 705 3-CH ₃ Ph 3-C ₅ H ₁₁ OPh C = O 706 3-CH ₃ Ph 3-C ₆ H ₁₃ OPh C = O 707 3-CH ₃ Ph 4-BuOPh C = O 708 3-CH ₃ Ph 4-C ₅ H ₁₁ OPh C = O 709 3-CH ₃ Ph 4-C ₆ H ₁₃ OPh C = O 710 3-CH ₃ Ph 3-CH ₃ O -4-PrO-Ph C = O 711 3-CH ₃ Ph 3-CH ₃ O-4-PrO-Ph C = S 712 3-CH ₃ Ph 3-CH ₃ O-4-PrO-Ph CH ₂ 713 3 -CH ₃ Ph 3-CH ₃ O-4-EtO-Ph C = O 714 3-CH ₃ Ph 3-CH ₃ O-4-BuO-Ph C = O 715 3-CH ₃ Ph 3-CH ₃ O- 4-C ₅ H ₁₁ O-Ph C = O 716 3-CH ₃ Ph 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 717 3-CH ₃ Ph 3-EtO-4-CH ₃ O-Ph C = O 718 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph C = O 719 3-CH ₃ Ph 3-BuO-4-CH ₃ O-Ph C = O 720 3-CH ₃ Ph 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 721 3-CH ₃ Ph 3-C ₆ H ₁₃ O-4-CH ₃ O -Ph C = O 722 3-CH ₃ Ph 3,4-di-CH ₃ O-Ph C = S 723 3-CH ₃ Ph 3,4-di-CH ₃ O-Ph CH ₂ 724 3-CH ₃ Ph 3,4-di-EtO-Ph C = O 725 3-CH ₃ Ph 3,4-di-PrO-Ph C = O 726 3-CH ₃ Ph 3,4-di-BuO-Ph C = O 727 3 , 4-Methylenedioxy-Ph Ph C = O 728 3,4-methylenedioxy-Ph 3-ClPh C = O 729 3,4-methylenedioxy-Ph 3,4-diClPh C = O 730 3,4 -Methylenedioxy-Ph 3-CH ₃ Ph C = O 731 3,4-Methylenedioxy-Ph 3-CF ₃ Ph C = O 732 3-ClPh 3-EtOPh C = O 733 3-ClPh 4-EtOPh C = O 734 3-ClPh 3-BuOPh C = O 735 3-ClPh 3-C ₅ H ₁₁ OPh C = O 736 3-ClPh 3-C ₆ H ₁₃ OPh C = O 737 3-ClPh 4-BuOPh C = O 738 3-ClPh 4-C ₅ H ₁₁ OPh C = O 739 3-ClPh 4-C ₆ H ₁₃ OPh C = O 740 3-ClPh 3-CH ₃ O-4-PrO-Ph C = O 741 3-ClPh 3-CH ₃ O-4-PrO-Ph C = S 742 3-ClPh 3-CH ₃ O-4-PrO-Ph CH ₂ 743 3-ClPh 3-CH ₃ O-4-EtO-Ph C = O 74 4 3-ClPh 3-CH ₃ O-4-C ₅ H ₁₁ O-Ph C = O 745 3-ClPh 3-CH ₃ O-4-C ₆ H ₁₃ O-Ph C = O 746 3-ClPh 3- EtO-4-CH ₃ O-Ph C = O 747 3-ClPh 3-BuO-4-CH ₃ O-Ph C = O 748 3-ClPh 3-C ₅ H ₁₁ O-4-CH ₃ O-Ph C = O 749 3-ClPh 3-C ₆ H ₁₃ O-4-CH ₃ O-Ph C = O 750 3-ClPh 3,4-di-CH ₃ O-Ph C = S 751 3-ClPh 3,4- di-CH ₃ O-Ph CH ₂ 752 3-ClPh 3,4-di-EtO-Ph C = O 754 3-ClPh 3,4-di-PrO-Ph C = S 754 3-ClPh 3,4-di -PrO-Ph CH ₂ 755 3-ClPh 3,4-di-BuO-Ph C = O 756 3-ClPh 3-BuPh C = O 757 3-ClPh 4-BuPh C = O 758 1-Np 3-ClPh C = O 759 2-Np 3-ClPh C = O 760 1-Np 3,4-diClPh C = O 761 2-Np 3,4-diClPh C = O 762 1-Np 3-CF ₃ Ph C = O 763 2 -Np 3-CF ₃ Ph C = O 764 3-BrPh 3-BrPh C = O 765 3-BrPh 3-CH ₃ OPh C = O 766 3-BrPh 3-EtOPh C = O 767 3-BrPh 3-PrOPh C = O 768 3-BrPh 3-BuOPh C = O 769 3-BrPh 3-C ₅ H ₁₁ OPh C = O 770 3-BrPh 3-C ₆ H ₁₃ OPh C = O 771 3-BrPh 4-CH ₃ OPh C = O 772 3-BrPh 4-EtOPh C = O 773 3-BrPh 4-PrOPh C = O 774 3-BrPh 4-BuOPh C = O 775 3-BrPh 4-C ₅ H ₁₁ OPh C = O 776 3-BrPh 4-C ₆ H ₁₃ OPh C = O 777 3-BrPh 3-CH ₃ O- 4-EtO-Ph C = O 778 3-BrPh 3-CH ₃ O-4-PrO-Ph C = O 779 3-BrPh 3-CH ₃ O-4-BuO-Ph C = O 780 3-BrPh 3- EtO-4-CH ₃ O-Ph C = O 781 3-BrPh 3-PrO-4-CH ₃ O-Ph C = O 782 3-BrPh 3-BuO-4-CH ₃ O-Ph C = O 783 3 -BrPh 3,4-di-EtO-Ph C = O 784 3-BrPh 3,4-di-PrO-Ph C = O 785 3-BrPh 3-CH ₃ Ph C = O 786 3-BrPh 3-Et- Ph C = O 787 3-BrPh 4-CH ₃ Ph C = O 788 3-BrPh 4-EtPh C = O 789 3-BrPh 1-Np C = O 790 3-BrPh 2-Np C = O 791 3,5 -diClPh 3-CH ₃ OPh C = O 792 3,5-diClPh 3-PrOPh C = O 793 3,5-diClPh 4-CH ₃ OPh C = O 794 3,5-diClPh 4-PrOPh C = O 7953 , 5-diClPh 3-EtPh C = O 796 3,5-diClPh 4-EtPh C = O 797 3,5-diClPh 3-PrPh C = O 798 3,5-diClPh 4-PrPh C = O 799 3,5 -diClPh 4-EtOPh C = O 800 3,5-diClPh 3,4-diCH ₃ O-Ph C = O 801 2,3-diClPh 4-EtOPh C = O 802 2,5-diClPh 3-CH ₃ OPh C = O 803 2, 5-diClPh 4-CH ₃ OPh C = O 804 2,5-diClPh 3-EtOPh C = O 805 2,5-diClPh 4-EtOPh C = O 806 2,5-diClPh 3-PrOPh C = O 807 2, 5-diClPh 4-PrOPh C = O 808 2,5-diClPh 4-CH ₃ Ph C = O 809 2,5-diClPh 4-EtPh C = O 810 2,5-diClPh 4-PrPh C = O 811 2, 5-diClPh 3,4-diCH ₃ O-Ph C = O 812 2,6-diClPh 3-CH ₃ OPh C = O 813 2,6-diClPh 4-CH ₃ OPh C = O 814 2,6-diClPh 3 -EtOPh C = O 815 2,6-diClPh 4-EtOPh C = O 816 2,6-diClPh 3-PrOPh C = O 817 2,6-diClPh 4-PrOPh C = O 818 2,6-diClPh 3,4 -diCH ₃ O-Ph C = O 819 2,6-diClPh 4-CH ₃ Ph C = O 820 2,6-diClPh 4-EtPh C = O 821 2,6-diClPh 4-PrPh C = O 822 2, 4-diClPh 3-CH ₃ OPh C = O 823 2,4-diClPh 4-CH ₃ OPh C = O 824 2,4-diClPh 3-EtOPh C = O 825 2,4-diClPh 4-EtOPh C = O 826 2,4-diClPh 3-PrOPh C = O 827 2,4-diClPh 4-PrOPh C = O 828 2,4-diClPh 3,4-diCH ₃ O-Ph C = O 829 2,4-diClPh 4-CH ₃ Ph C = O 830 2,4-diClPh 4-EtPh C = O 831 2,4-diClPh 4-PrPh C = O 832 3,5-di CH ₃ Ph 4-CH ₃ OPh C = O 833 3,5-diCH ₃ Ph 4-EtOPh C = O 834 3,5-diCH ₃ Ph 4-PrOPh C = O 835 3,5-diCH ₃ Ph 3,4 -diCH ₃ O-Ph C = O 836 3,5-diCH ₃ Ph 4-CH ₃ Ph C = O 837 3,5-diCH ₃ Ph 4-EtPh C = O 838 3,5-diCH ₃ Ph 4-PrPh C = O 839 3,5-diCH ₃ Ph 3-ClPh C = O 840 3,5-diCH ₃ Ph 4-ClPh C = O 841 3,5-diCH ₃ Ph 3-FPh C = O 842 3,5- diCH ₃ Ph 4-FPh C = O 843 3,5-diCH ₃ Ph 3-BrPh C = O 844 3,5-diCH ₃ Ph 4-BrPh C = O 845 3,5-diCF ₃ Ph 4-CH ₃ OPh C = O 846 3,5-diCF ₃ Ph 4-EtOPh C = O 847 3,5-diCF ₃ Ph 4-PrOPh C = O 848 3,5-diCF ₃ Ph 3,4-diCH ₃ O-Ph C = O 849 3,5-diCF ₃ Ph 4-CH ₃ Ph C = O 850 3,5-diCF ₃ Ph 4-EtPh C = O 851 3,5-diCF ₃ Ph 4-PrPh C = O 852 3,5- diCF ₃ Ph 3-ClPh C = O 853 3,5-diCF ₃ Ph 4-ClPh C = O 854 3,5-diCF ₃ Ph 3-FPh C = O 855 3,5-diCF ₃ Ph 4-FPh C = O 856 3,5-diCF ₃ Ph 3-BrPh C = O 857 3,5-diCF ₃ Ph 4-BrPh C = O 858 3,5-diFPh 4-CH ₃ OPh C = O 859 3,5-diFPh 4 -EtOPh C = O 86 3,5-diFPh 4-PrOPh C = O 861 3,5-diFPh 4-CH 3 Ph C = O 862 3,5-diFPh 4-EtPh C = O 863 3,5-diFPh 4-PrPh C = O 864 3,5-diFPh 3-ClPh C = O 865 3,5-diFPh 4-ClPh C = O 866 3-Cl-5-F-Ph 4-CH ₃ OPh C = O 867 3-Cl-5-F- Ph 4-EtOPh C = O 868 3-Cl-5-F-Ph 4-EtPh C = O 869 3-Cl-5-F-Ph 4-PrPh C = O 870 3,5-diBrPh 4-CH ₃ OPh C = O 871 3-FPh 4-EtPh C = O 872 3-FPh 4-EtOPh C = O 873 3-CN-Ph 4-CH ₃ OPh C = O 874 3-CN-Ph 4-EtOPh C = O 875 3-CN-Ph 4-EtPh C = O 876 3-CN-Ph 4-PrPh C = O 877 3-Cl-5-CH ₃ Ph 4-CH ₃ OPh C = O 878 3-Cl-5-CH ₃ Ph 4-EtOPh C = O 879 3-Cl-5-CH ₃ Ph 4-EtPh C = O 880 3-Cl-5-CH ₃ Ph 4-PrPh C = O ─────────── 表 Table 2

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{Compound No. R ¹ R ² R ⁴ } ───────────────────────────────── 2-1 3-ClPh 3-ClPh 3,4-diCH ₃ OPh 2 -2 4-ClPh 4-ClPh 3,4-diCH ₃ OPh 2 -3 3-ClPh 2,3-diClPh 3,4-diCH ₃ OPh 2 -4 3-ClPh 3,4-diClPh 3,4-diCH ₃ OPh 2 -5 4-ClPh 2,3-diClPh 3,4-diCH ₃ OPh 2 -6 3-ClPh 3-CH ₃ OPh 3,4-diCH ₃ OPh 2 -7 3-ClPh 4-CH ₃ OPh 3, 4-diCH ₃ OPh 2 -8 3-ClPh 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh 2 -9 3-ClPh 3-CH ₃ O-3-PrOPh 3,4-diCH ₃ OPh 2-10 2,3-diClPh 3-CH ₃ OPh 3,4-diCH ₃ OPh 2-11 2,3-diClPh 4-CH ₃ OPh 3,4-diCH ₃ OPh 2-12 2,3-diClPh 3-CH ₃ Ph 3,4-diCH ₃ OPh 2-13 2,3-diClPh 4-CH ₃ Ph 3,4-diCH ₃ OPh 2-14 3,4-diClPh 3-CH ₃ OPh 3,4-diCH ₃ OPh 2-15 3,4-diClPh 4-CH ₃ OPh 3,4-diCH ₃ OPh 2-16 3,4-diClPh 4-PrOPh 3,4-diCH ₃ OPh 2-17 3,4-diClPh 4-i-BuOPh 3, 4-diCH ₃ OPh 2-18 3,4-diClPh 3-C H ₃ Ph 3,4-diCH ₃ OPh 2-19 3,4-diClPh 4-CH ₃ Ph 3,4-diCH ₃ OPh 2-20 3,4-diClPh 4-i-BuPh 3,4-diCH ₃ OPh 2-21 3-CH ₃ Ph 3-CH ₃ Ph 3,4-diCH ₃ OPh 2-22 3-CH ₃ Ph 4-CH ₃ Ph 3,4-diCH ₃ OPh 2-23 3-CH ₃ Ph 4- CH ₃ OPh 3,4-diCH ₃ OPh 2-24 3-CH ₃ Ph 3-PrOPh 3,4-diCH ₃ OPh 2-25 3-CH ₃ Ph 4-PrOPh 3,4-diCH ₃ OPh 2-26 3 -CH ₃ Ph 3-i-BuOPh 3,4-diCH ₃ OPh 2-27 3-CH ₃ Ph 4-i-BuOPh 3,4-diCH ₃ OPh 2-28 3-CH ₃ Ph 3,4-diCH ₃ Ph 3,4-diCH ₃ OPh 2-29 3-CH ₃ Ph 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh 2-30 3-CH ₃ Ph 3,4-diPrOPh 3,4-diCH ₃ OPh 2-31 3-CH ₃ Ph 3-CH ₃ O-4-PrOPh 3,4-diCH ₃ OPh 2-32 3-CF ₃ Ph 3-ClPh 3,4-diCH ₃ OPh 2-33 3-CF ₃ Ph 4-ClPh 3,4-diCH ₃ OPh 2-34 3-CF ₃ Ph 3-CH ₃ OPh 3,4-diCH ₃ OPh 2-35 3-CF ₃ Ph 4-CH ₃ OPh 3,4-diCH ₃ OPh 2-36 3-CF ₃ Ph 3-PrOPh 3,4-diCH ₃ OPh 2-37 3-CF ₃ Ph 4-PrOPh 3,4-diCH ₃ OPh 2-38 3-CF ₃ Ph 3-i-BuOPh 3 , 4-diCH ₃ OPh 2-39 3-CF ₃ Ph 4-i-BuOPh 3,4-diCH ₃ OPh 2-40 3-CF ₃ Ph 3,4-diCH ₃ OPh 3,4-diCH ₃ OPh 2- 41 3-ClPh 3-ClPh 3-CH ₃ OPh 2-42 3- ClPh 4-ClPh 3-CH ₃ OPh 2-43 3-ClPh 3-CH ₃ OPh 3-CH ₃ OPh 2-44 3-ClPh 4-CH ₃ OPh 3-CH ₃ OPh 2-45 3-ClPh 3,4 -diCH ₃ OPh 3-CH ₃ OPh 2-46 3,4-diClPh 4-CH ₃ OPh 3-CH ₃ OPh 2-47 3,4-diClPh 4-PrOPh 3-CH ₃ OPh 2-48 3,4- diClPh 4-i-BuOPh 3-CH ₃ OPh 2-49 3-CH ₃ Ph 3-CH ₃ Ph 3-CH ₃ OPh 2-50 3-CH ₃ Ph 4-CH ₃ OPh 3-CH ₃ OPh 2-51 3-CH ₃ Ph 4-PrOPh 3-CH ₃ OPh 2-52 3-CH ₃ Ph 4-i-BuOPh 3-CH ₃ OPh 2-53 3-CH ₃ Ph 3,4-diCH ₃ OPh 3-CH ₃ OPh 2-54 3-CH ₃ Ph 3,4-diClPh 3-CH ₃ OPh 2-55 3-CH ₃ Ph 3,4-diCH ₃ Ph 3-CH ₃ OPh 2-56 3-CF ₃ Ph 4-CH ₃ OPh 3-CH ₃ OPh 2-57 3-CF ₃ Ph 4-PrOPh 3-CH ₃ OPh 2-58 3-CF ₃ Ph 4-i-BuOPh 3-CH ₃ OPh 2-59 3-CF ₃ Ph 3 , 4-diCH ₃ OPh 3-CH ₃ OPh 2-60 3-CF ₃ Ph 3,4-diClPh 3-CH ₃ OPh 2-61 3-CF ₃ Ph 3,4-diCH ₃ Ph 3-CH ₃ OPh 2 -62 3-ClPh 3-ClPh 4-CH ₃ OPh 2-63 3-ClPh 4-ClPh 4-CH ₃ OPh 2-64 3-ClPh 3-CH ₃ OPh 4-CH ₃ OPh 2-65 3-ClPh 4 -CH ₃ OPh 4-CH ₃ OPh 2-66 3-ClPh 3,4-diCH ₃ OPh 4-CH ₃ OPh 2-67 3,4-diClPh 4-CH ₃ OPh 4-CH ₃ OPh 2-68 3, 4-diClPh 4-P rOPh 4-CH ₃ OPh 2-69 3,4-diClPh 4-i-BuOPh 4-CH ₃ OPh 2-70 3-CH ₃ Ph 3-CH ₃ Ph 4-CH ₃ OPh 2-71 3-CH ₃ Ph 4-CH ₃ OPh 4-CH ₃ OPh 2-72 3-CH ₃ Ph 4-PrOPh 4-CH ₃ OPh 2-73 3-CH ₃ Ph 4-i-BuOPh 4-CH ₃ OPh 2-74 3-CH ₃ Ph 3,4-diCH ₃ OPh 4-CH ₃ OPh 2-75 3-CH ₃ Ph 3,4-diClPh 4-CH ₃ OPh 2-76 3-CH ₃ Ph 3,4-diCH ₃ Ph 4-CH ₃ OPh 2-77 3-CF ₃ Ph 4-CH ₃ OPh 4-CH ₃ OPh 2-78 3-CF ₃ Ph 4-PrOPh 4-CH ₃ OPh 2-79 3-CF ₃ Ph 4-i-BuOPh 4 -CH ₃ OPh 2-80 3-CF ₃ Ph 3,4-diCH ₃ OPh 4-CH ₃ OPh 2-81 3-CF ₃ Ph 3,4-diClPh 4-CH ₃ OPh 2-82 3-CF ₃ Ph 3,4-diCH ₃ Ph 4-CH ₃ OPh 2-83 Ph 3,4-di-CH ₃ O-Ph 3,4-di-CH ₃ O-Ph 2-84 Ph 3,4-di-CH ₃ O-Ph 3-CH ₃ O-Ph 2-85 Ph 3,4-di-CH ₃ O-Ph 4-CH ₃ O-Ph 2-86 Ph 3,4-di-PrO-Ph 3,4-di -CH ₃ O-Ph 2-87 Ph 3,4-di-PrO-Ph 3-CH ₃ O-Ph 2-88 Ph 3,4-di-PrO-Ph 4-CH ₃ O-Ph 2-89 Ph 3-CH ₃ O-4-PrO-Ph 3,4-di-CH ₃ O-Ph 2-90 Ph 3-CH ₃ O-4-PrO-Ph 3-CH ₃ O-Ph 2-91 Ph 3- CH ₃ O-4-PrO-Ph 4-CH ₃ O-Ph 2-92 3-Cl-Ph 3,4-di-PrO-Ph 3,4-di-CH ₃ O-Ph 2-93 3-Cl -Ph 3,4-di-PrO-P h 3-CH ₃ O-Ph 2-94 3-Cl-Ph 3,4-di-PrO-Ph 4-CH ₃ O-Ph 2-95 3-Cl-Ph 3-PrO-4-CH ₃ O- Ph 3,4-di-CH ₃ O-Ph 2-96 3-Cl-Ph 3-PrO-4-CH ₃ O-Ph 3-CH ₃ O-Ph 2-97 3-Cl-Ph 3-PrO- 4-CH ₃ O-Ph 4-CH ₃ O-Ph 2-98 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph 3,4-di-CH ₃ O-Ph 2-99 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph 3-CH ₃ O-Ph 2-100 3-CH ₃ Ph 3-PrO-4-CH ₃ O-Ph 4-CH ₃ O-Ph 2-101 3 -CF ₃ Ph 3-CH ₃ O-4-PrO-Ph 3,4-di-CH ₃ O-Ph 2-102 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph 3-CH ₃ O -Ph 2-103 3-CF ₃ Ph 3-CH ₃ O-4-PrO-Ph 4-CH ₃ O-Ph 2-104 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph 3,4 -di-CH ₃ O-Ph 2-105 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph 3-CH ₃ O-Ph 2-106 3-CF ₃ Ph 3-PrO-4-CH ₃ O-Ph 4-CH ₃ O-Ph 2-107 3-CF ₃ Ph 3,4-di-PrO-Ph 3,4-di-CH ₃ O-Ph 2-108 3-CF ₃ Ph 3,4- di-PrO-Ph 3-CH ₃ O-Ph 2-109 3-CF ₃ Ph 3,4-di-PrO-Ph 4-CH ₃ O-Ph 2-110 3,4-diCH ₃ OPh Ph 3,5 -diCH ₃ O-4-PrSPh 2-111 3,4-diCH ₃ OPh Ph 4-CH ₃ SPh 2-112 3-CH ₃ O-4-PrOPh Ph 3-CH ₃ S-4,5-diCH ₃ OPh 2-113 3-CH ₃ O-4-PrOPh 3-CH ₃ Ph 3,4,5-triCH ₃ Ph 2-114 3-CH ₃ O-4-PrOPh 3-CH ₃ Ph 3,4,5-triEtPh 2-115 3-CH ₃ O-4-PrOPh 3-ClPh 3,4-diEtPh 2-116 3-CH ₃ O-4-PrOPh 3-CF ₃ Ph 4-EtPh 2-117 4-PrOPh 3,4-diClPh 4-ClPh 2-118 4-PrOPh 3-CH ₃ Ph 3,4-diClPh 2-119 3-PrOPh 3-CF ₃ Ph 3-ClPh 2-120 3-ClPh 3-ClPh 3-Cl-4-CH ₃ Ph 2-121 3-CH ₃ Ph 3-CH ₃ Ph 3-CH ₃ -4-ClPh 2-122 3-CH ₃ Ph 3-CH ₃ Ph Ph 2-123 3-CH ₃ OPh Ph 2-CF ₃ Ph 2-124 3-EtOPh Ph 3-CF ₃ Ph 2-125 4-CH ₃ OPh Ph 4-CF ₃ Ph 2-126 4-EtOPh Ph 3,4,5-triCF ₃ Ph 2-127 3,4-diCH ₃ OPh Ph 2-CF ₃ Ph 2-128 3,4-diEtOPh Ph 3-CF ₃ Ph 2-129 3-CH ₃ OPh 4-ClPh 4-CF ₃ Ph 2-130 3 -EtOPh 4-BrPh 3,4,5-triCF ₃ Ph 2-131 4-CH ₃ OPh 4-FPh 2-CF ₃ Ph 2-132 4-EtOPh 4-ClPh 3-CF ₃ Ph 2-133 3,4 -diCH ₃ OPh 4-FPh 4-CF ₃ Ph 2-134 3,4-diEtOPh 4-BrPh 3,4,5-triCF ₃ Ph 2-135 3-CH ₃ OPh 4-CH ₃ Ph 2-CF ₃ Ph 2-136 3-EtOPh 4-CH ₃ Ph 3-CF ₃ Ph 2-137 4-CH ₃ OPh 4-CH ₃ Ph 4-CF ₃ Ph 2-138 4-EtOPh 4-CH ₃ Ph 3,4,5 -triCF ₃ Ph 2-139 3,4-diCH ₃ OPh 4-CH ₃ Ph 2-CF ₃ Ph 2-140 3,4-diEtOPh 4-CH ₃ Ph 3-CF ₃ Ph 2-141 3-CH ₃ OPh Four- CF ₃ Ph 4-CF ₃ Ph 2-142 3-EtOPh 4-CF ₃ Ph 3,4,5-triCF ₃ Ph 2-143 4-CH ₃ OPh 4-CF ₃ Ph 2-CF ₃ Ph 2-144 4 -EtOPh 4-CF ₃ Ph 3-CF ₃ Ph 2-145 3,4-diCH ₃ OPh 4-CF ₃ Ph 4-CF ₃ Ph 2-146 3,4-diEtOPh 4-CF ₃ Ph 3,4,5 -triCF ₃ Ph 2-147 ₃ -CH ₃ OPh 3,4-diClPh 2-CF ₃ Ph 2-148 3-EtOPh 3,4-diFPh 3-CF ₃ Ph 2-149 4-CH ₃ OPh 3,4- diFPh 4-CF ₃ Ph 2-150 4-EtOPh 3,4-diClPh 3,4,5-triCF ₃ Ph 2-151 3,4-diCH ₃ OPh 3,4-diClPh 2-CF ₃ Ph 2-152 3 , 4-diEtOPh 3,4-diFPh 3-CF ₃ Ph 2-153 3-CH ₃ OPh Ph 2-EtOPh 2-154 3-EtOPh Ph 3-EtOPh 2-155 4-CH ₃ OPh Ph 4-EtOPh 2- 156 4-EtOPh Ph 2,3,4-triEtOPh 2-157 3,4-diCH ₃ OPh Ph 2-OHPh 2-158 3,4-diEtOPh Ph 3-OHPh 2-159 3-CH ₃ OPh 4-ClPh 4 -OHPh 2-160 3-EtOPh 4-BrPh 3,4,5-triOHPh 2-161 4-CH ₃ OPh 4-FPh 2-CH ₃ SPh 2-162 4-EtOPh 4-ClPh 3-CH ₃ SPh 2- 163 3,4-diCH ₃ OPh 4-FPh 4-CH ₃ SPh 2-164 3,4-diEtOPh 4-BrPh 3,4,5-triCH ₃ SPh 2-165 3-CH ₃ OPh 4-CH ₃ Ph 3 , 4,5-triEtSPh 2-166 3-EtOPh 4-CH ₃ Ph 2-EtOPh 2-167 4-CH ₃ OPh 4-CH ₃ Ph 3-EtOPh 2-168 4-EtOPh 4-CH ₃ Ph 4-EtOPh 2-169 3,4-diCH ₃ OPh 4-CH ₃ Ph 2,3,4-triEtOPh 2-170 3,4-diEtOPh 4-CH ₃ Ph 2-OHPh 2 -171 3-CH ₃ OPh 4-CF ₃ Ph 3-OHPh 2-172 3-EtOPh 4-CF ₃ Ph 4-OHPh 2-173 4-CH ₃ OPh 4-CF ₃ Ph 3,4,5-triOHPh 2 -174 4-EtOPh 4-CF ₃ Ph 2-CH ₃ SPh 2-175 3,4-diCH ₃ OPh 4-CF ₃ Ph 3-CH ₃ SPh 2-176 3,4-diEtOPh 4-CF ₃ Ph 4- CH ₃ SPh 2-177 3-CH ₃ OPh 3,4-diClPh 3,4,5-triCH ₃ SPh 2-178 3-EtOPh 3,4-diFPh 3,4,5-triEtSPh 2-179 4-CH ₃ OPh 3,4-diFPh 2-EtOPh 2-180 4-EtOPh 3,4-diClPh 3-EtOPh 2-181 3,4-diCH ₃ OPh 3,4-diClPh 4-EtOPh 2-182 3,4-diEtOPh 3 , 4-diFPh 2,3,4-triEtOPh 2-183 3-CH ₃ OPh Ph 2-ClPh 2-184 3-EtOPh Ph 3-ClPh 2-185 4-CH ₃ OPh Ph 4-ClPh 2-186 4- EtOPh Ph 3,4,5-triClPh 2-187 3,4-diCH ₃ OPh Ph 2-FPh 2-188 3,4-diEtOPh Ph 3-FPh 2-189 3-CH ₃ OPh 4-ClPh 4-FPh 2 -190 3-EtOPh 4-BrPh 3,4,5-triFPh 2-191 4-CH ₃ OPh 4-FPh 2-BrPh 2-192 4-EtOPh 4-ClPh 3-BrPh 2-193 3,4-diCH ₃ OPh 4-FPh 4-BrPh 2-194 3,4-diEtOPh 4-BrPh 3,4,5-triBrPh 2-195 3-CH ₃ OPh 4- CH ₃ Ph 2-ClPh 2-196 3-EtOPh 4-CH ₃ Ph 3-ClPh 2-197 4-CH ₃ OPh 4-CH ₃ Ph 4-ClPh 2-198 4-EtOPh 4-CH ₃ Ph 3,4 , 5-triClPh 2-199 3,4-diCH ₃ OPh 4-CH ₃ Ph 2-FPh 2-200 3,4-diEtOPh 4-CH ₃ Ph 3-FPh 2-201 3-CH ₃ OPh 4-CF ₃ Ph 4-FPh 2-202 3-EtOPh 4-CF ₃ Ph 3,4,5-triFPh 2-203 4-CH ₃ OPh 4-CF ₃ Ph 2-BrPh 2-204 4-EtOPh 4-CF ₃ Ph 3 -BrPh 2-205 3,4-diCH ₃ OPh 4-CF ₃ Ph 4-BrPh 2-206 3,4-diEtOPh 4-CF ₃ Ph 3,4,5-triBrPh 2-207 3-CH ₃ OPh 3, 4-diClPh 2-ClPh 2-208 3-EtOPh 3,4-diFPh 3-ClPh 2-209 4-CH ₃ OPh 3,4-diFPh 4-ClPh 2-210 4-EtOPh 3,4-diClPh 3,4 , 5-triClPh 2-211 3,4-diCH ₃ OPh 3,4-diClPh 2-FPh 2-212 3,4-diEtOPh 3,4-diFPh 3-FPh 2-213 4-CH ₃ OPh 3-ClPh 2 -Pyr 2-214 4-CH ₃ OPh 3-ClPh 3-Pyr 2-215 4-CH ₃ OPh 3-ClPh 4-Pyr 2-216 3-CH ₃ OPh 3-ClPh 3-Pyr 2-217 3,4 -diCH ₃ OPh 3-ClPh 3-Pyr 2-218 3-ClPh 3-ClPh 3-Pyr 2-219 4-EtOPh 3-ClPh 3-Pyr 2-220 4-PrOPh 3-ClPh 3-Pyr 2-221 3 -CH ₃ Ph 3-ClPh 3-Pyr 2-222 4-CH ₃ Ph 3-ClPh 3-Pyr 2-223 4-EtPh 3-ClPh 3-Pyr 2-224 3,4 -diCH ₃ Ph 3-ClPh 3-Pyr 2-225 3-CH ₃ OPh 3,5-diClPh 3-Pyr 2-226 4-CH ₃ OPh 3,5-diClPh 3-Pyr 2-227 3-EtOPh 3, 5-diClPh 3-Pyr 2-228 4-EtOPh 3,5-diClPh 3-Pyr 2-229 3-PrOPh 3,5-diClPh 3-Pyr 2-230 4-PrOPh 3,5-diClPh 3-Pyr 2- 231 3,4-diCH ₃ OPh 3,5-diClPh 3-Pyr 2-232 3-CH ₃ Ph 3,5-diClPh 3-Pyr 2-233 4-CH ₃ Ph 3,5-diClPh 3-Pyr 2- 234 3-EtPh 3,5-diClPh 3-Pyr 2-235 4-EtPh 3,5-diClPh 3-Pyr 2-236 3-PrPh 3,5-diClPh 3-Pyr 2-237 4-PrPh 3,5- diClPh 3-Pyr 2-238 3,4-diCH ₃ Ph 3,5-diClPh 3-Pyr 2-239 4-CH ₃ OPh 3,5-diClPh 2-Pyr 2-240 4-CH ₃ OPh 3,5- diClPh 4-Pyr 2-241 4-CH ₃ OPh 2,3-diClPh 3-Pyr 2-242 4-CH ₃ OPh 2,5-diClPh 3-Pyr 2-243 4-CH ₃ OPh 2,6-diClPh 3 -Pyr 2-244 4-CH ₃ OPh 3,5-diCH ₃ Ph 3-Pyr 2-245 3-ClPh 3,5-diCH ₃ Ph 3-Pyr 2-246 4-ClPh 3,5-diCH ₃ Ph 3 -Pyr 2-247 3-FPh 3,5-diCH ₃ Ph 3-Pyr 2-248 4-FPh 3,5-diCH ₃ Ph 3-Pyr 2-249 4-EtPh 3,5-diCH ₃ Ph 3-Pyr 2-250 4-CH ₃ OPh 3,5-diCF ₃ Ph 3-Pyr 2-251 3-ClPh 3,5-diCF ₃ Ph 3-Pyr 2-252 4-ClPh 3,5-diCF ₃ Ph 3-Pyr 2-253 3-FPh 3,5-diCF ₃ Ph 3-Pyr 2-254 4-FPh 3,5-diCF ₃ Ph 3-Pyr 2-255 4-CH ₃ OPh 3-FPh 3-Pyr 2 -256 4-EtOPh 3-FPh 3-Pyr 2-257 4-EtPh 3-FPh 3-Pyr 2-258 4-PrPh 3-FPh 3-Pyr 2-259 4-CH ₃ OPh 3,5-diFPh 3- Pyr 2-260 4-EtOPh 3,5-diFPh 3-Pyr 2-261 4-CH ₃ OPh 3-CN-Ph 3-Pyr 2-262 4-EtOPh 3-CN-Ph 3-Pyr 2-263 4- EtPh 3-CN-Ph 3-Pyr 2-264 4-PrPh 3-CN-Ph 3-Pyr 2-265 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3-Pyr 2-266 4-EtOPh 3 -Cl-5-CH ₃ Ph 3-Pyr 2-277 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ Pyr) 2-278 4-EtOPh 3-ClPh 3- (2-CH ₃ Pyr) 2 -279 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ Pyr) 2-280 4-EtOPh 3-FPh 3- (2-CH ₃ Pyr) 2-281 4-CH ₃ OPh 3,5-diClPh 3- (2-CH ₃ Pyr) 2-282 4-EtOPh 3,5-diClPh 3- (2-CH ₃ Pyr) 2-283 4-EtPh 3,5-diClPh 3- (2-CH ₃ Pyr) 2 -284 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ Pyr) 2-285 4-EtOPh 3,5-diFPh 3- (2-CH ₃ Pyr) 2-286 4-CH ₃ OPh 3 , 5-diClPh 3- (6-CH ₃ Pyr) 2-287 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 2-288 4-CH ₃ OPh 3,5-diClPh 3- (2 -288 4-CH ₃ OPh 3,5-diClPh 3- (6-ClPyr) 2-289 4-CH ₃ OPh 3,5-diClPh 3- (2-FPyr) 2-290 4-CH ₃ OPh 3,5-diClPh 3- (2,4-diCH ₃ Pyr) 2-291 4-CH ₃ OPh 3 , 5-diClPh 3- (2-CH ₃ SPyr) 2-292 4-CH ₃ OPh 3,5-diClPh 3- (2-EtSPyr) 2-293 4-EtOPh 3,5-diClPh 3- (6-CH ₃ Pyr) 2-294 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 2-295 4-EtOPh 3,5-diClPh 3- (2-ClPyr) 2-296 4-EtOPh 3,5-diClPh 3- (6-ClPyr) 2-297 4-EtOPh 3,5-diClPh 3- (2-FPyr) 2-298 4-EtOPh 3,5-diClPh 3- (2,4-diCH ₃ Pyr) 2-299 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 2-300 4-EtOPh 3,5-diClPh 3- (2-EtSPyr) 2-301 4-CH ₃ OPh 3-ClPh 3- (6 -CH ₃ Pyr) 2-302 4-CH ₃ OPh 3-ClPh 3- (5-BrPyr) 2-303 4-CH ₃ OPh 3-ClPh 3- (2-ClPyr) 2-304 4-CH ₃ OPh 3 -ClPh 3- (6-ClPyr) 2-305 4-CH ₃ OPh 3-ClPh 3- (2-FPyr) 2-306 4-CH ₃ OPh 3-ClPh 3- (2,4-diCH ₃ Pyr) 2 -307 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 2-308 4-CH ₃ OPh 3-ClPh 3- (2-EtSPyr) 2-309 4-EtOPh 3-ClPh 3- (6 -CH ₃ Pyr) 2-310 4-EtOPh 3-ClPh 3- (5-BrPyr) 2-311 4-EtOPh 3-ClPh 3- (2-ClPyr) 2-312 4-EtOPh 3-ClPh 3- (6 -ClPyr) 2-313 4-EtOPh 3-ClPh 3- (2-FPyr) 2-314 4-EtOPh 3-ClPh 3- (2,4-diCH ₃ Pyr) 2-315 4-EtOPh 3-ClPh 3- (2-CH ₃ SPyr) 2-316 4-EtOPh 3-ClPh 3- (2-EtSPyr ) 2-317 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 2-318 4-CH ₃ OPh 3,5-diFPh 3- (5-BrPyr) 2-319 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 2-320 4-CH ₃ OPh 3,5-diFPh 3- (6-ClPyr) 2-321 4-CH ₃ OPh 3,5-diFPh 3- (2 -FPyr) 2-322 4-CH ₃ OPh 3,5-diFPh 3- (2,4-diCH ₃ Pyr) 2-323 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 2 -324 4-CH ₃ OPh 3,5-diFPh 3- (2-EtSPyr) 2-325 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 2-326 4-EtOPh 3-FPh 3- (5 -BrPyr) 2-327 4-EtOPh 3-FPh 3- (2-ClPyr) 2-328 4-EtOPh 3-FPh 3- (6-ClPyr) 2-329 4-EtOPh 3-FPh 3- (2-FPyr ) 2-330 4-EtOPh 3-FPh 3- (2,4-diCH ₃ Pyr) 2-331 4-EtOPh 3-FPh 3- (2-CH ₃ SPyr) 2-332 4-EtOPh 3-FPh 3- (2-EtSPyr) 2-333 4-CH ₃ OPh 3-CN-Ph 3- (6-CH ₃ Pyr) 2-334 4-CH ₃ OPh 3-CN-Ph 3- (5-BrPyr) 2-335 4-CH ₃ OPh 3-CN-Ph 3- (2-ClPyr) 2-336 4-CH ₃ OPh 3-CN-Ph 3- (6-ClPyr) 2-337 4-CH ₃ OPh 3-CN-Ph 3- (2-FPyr) 2-338 4-CH ₃ OPh 3-CN-Ph 3- (2,4-diCH ₃ Pyr) 2-339 4-CH ₃ OPh 3 -CN-Ph 3- (2-CH ₃ SPyr) 2-340 4-CH ₃ OPh 3-CN-Ph 3- (2-EtSPyr) 2-341 4-EtOPh 3-CN-Ph 3- (6-CH ₃ Pyr) 2-342 4-EtOPh 3-CN-Ph 3- (5-BrPyr) 2-343 4-EtOPh 3-CN-Ph 3- (2-ClPyr) 2-344 4-EtOPh 3-CN-Ph 3- (6-ClPyr) 2-345 4-EtOPh 3-CN-Ph 3- (2-FPyr) 2-346 4-EtOPh 3-CN-Ph 3- (2,4-diCH ₃ Pyr) 2-347 4-EtOPh 3-CN-Ph 3- (2-CH ₃ SPyr) 2-348 4-EtOPh 3-CN-Ph 3- (2-EtSPyr) 2-349 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ Pyr) 2-350 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 2-351 4-CH ₃ OPh 3-Cl-5 -CH ₃ Ph 3- (5-BrPyr) 2-352 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 2-353 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-ClPyr) 2-354 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-FPyr) 2-355 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2,4-diCH ₃ Pyr) 2-356 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr) 2-357 4-CH ₃ OPh 3-Cl-5 -CH ₃ Ph 3- (2-EtSPyr) 2-358 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ Pyr) 2-359 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 2-360 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 2-361 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2 -ClPyr) 2-362 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-ClPyr) 2-363 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-FPyr) 2-364 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2 _{, 4-diCH 3 Pyr) 2-365} 4-EtOPh 3-Cl-5-CH 3 Ph 3- (2-CH 3 SPyr) 2-366 4-EtOPh 3-Cl-5-CH 3 Ph 3- (2 -EtSPyr) 2-367 4-CH ₃ OPh 3-ClPh 3- (5-CH ₃ OPyr) 2-368 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 2-369 4- CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 2-370 4-CH ₃ OPh 3,5-diFPh 3- (5-CH ₃ OPyr) 2-371 4-CH ₃ OPh 3-CN-Ph 3- (5-CH ₃ OPyr) 2-372 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 2-373 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr) 2-374 4-EtOPh 3,5-diClPh 3- (5-CH ₃ OPyr) 2-375 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 2-376 4-EtOPh 3,5 -diFPh 3- (5-CH ₃ OPyr) 2-377 4-EtOPh 3-CN-Ph 3- (5-CH ₃ OPyr) 2-378 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) ────────────────────────────────────Table 3

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━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Compound number R¹ R^Two R^Four ──────────────────────────────────── 3-1 Ph 3,4-diCH_ThreeOPh 3,4,5-triCH_ThreeOPh 3 -2 3-ClPh 3,4-diCH_ThreeOPh 3,4,5-triCH_ThreeOPh 3 -3 3-CF_ThreePh 3,4-diCH_ThreeOPh 3,4,5-triCH_ThreeOPh 3 -4 3-CH_ThreePh 3,4-diCH_ThreeOPh 3,4,5-triCH_ThreeOPh 3 -5 4-CH_ThreeOPh 3,4-diClPh 3,4,5-triCH_ThreeOPh 3 -6 4-CH_ThreeOPh 3,4-diCH_ThreePh 3,4,5-triCH_ThreeOPh 3 -7 3-ClPh 3-ClPh 3,4,5-triCH_ThreeOPh 3 -8 3-CH_ThreePh 3-CH_ThreePh 3,4,5-triCH_ThreeOPh 3 -9 3-ClPh 4-PrOPh 3,4,5-triCH_ThreeOPh 3-10 3-ClPh 4-i-BuOPh 3,4,5-triCH_ThreeOPh 3-11 3-CH_ThreePh 4-PrOPh 3,4,5-triCH_ThreeOPh 3-12 3-CH_ThreePh 4-i-BuOPh 3,4,5-triCH_ThreeOPh 3-13 3,4-diClPh 4-PrOPh 3,4,5-triCH_ThreeOPh 3-14 3,4-diClPh 4-i-BuOPh 3,4,5-triCH_ThreeOPh 3-15 3,4-diClPh 4-CH_ThreePh 3,4,5-triCH_ThreeOPh 3-16 3,4-diClPh 4-i-BuPh 3,4,5-triCH_ThreeOPh 3-17 Ph 3,4-diCH_ThreeOPh 3,4-diCH_ThreeOPh 3-18 3-ClPh 3,4-diCH_ThreeOPh 3,4-diCH_ThreeOPh 3-19 3-CF_ThreePh 3,4-diCH_ThreeOPh 3,4-diCH_ThreeOPh 3-20 3-CH_ThreePh 3,4-diCH_ThreeOPh 3,4-diCH_ThreeOPh 3-21 4-CH_ThreeOPh 3,4-diClPh 3,4-diCH_ThreeOPh 3-22 4-CH_ThreeOPh 3,4-diCH_ThreePh 3,4-diCH_ThreeOPh 3-23 3-ClPh 3-ClPh 3,4-diCH_ThreeOPh 3-24 3-CH_ThreePh 3-CH_ThreePh 3,4-diCH_ThreeOPh 3-25 3-ClPh 4-PrOPh 3,4-diCH_ThreeOPh 3-26 3-ClPh 4-i-BuOPh 3,4-diCH_ThreeOPh 3-27 3-CH_ThreePh 4-PrOPh 3,4-diCH_ThreeOPh 3-28 3-CH_ThreePh 4-i-BuOPh 3,4-diCH_ThreeOPh 3-29 3,4-diClPh 4-PrOPh 3,4-diCH_ThreeOPh 3-30 3,4-diClPh 4-i-BuOPh 3,4-diCH_ThreeOPh 3-31 3,4-diClPh 4-CH_ThreePh 3,4-diCH_ThreeOPh 3-32 3,4-diClPh 4-i-BuPh 3,4-diCH_ThreeOPh 3-33 Ph 3,4-diCH_ThreeOPh 4-CH_ThreeOPh 3-34 3-ClPh 3,4-diCH_ThreeOPh 4-CH_ThreeOPh 3-35 3-CF_ThreePh 3,4-diCH_ThreeOPh 4-CH_ThreeOPh 3-36 3-CH_ThreePh 3,4-diCH_ThreeOPh 4-CH_ThreeOPh 3-37 4-CH_ThreeOPh 3,4-diClPh 4-CH_ThreeOPh 3-38 4-CH_ThreeOPh 3,4-diCH_ThreePh 4-CH_ThreeOPh 3-39 3-ClPh 3-ClPh 4-CH_ThreeOPh 3-40 3-CH_ThreePh 3-CH_ThreePh 4-CH_ThreeOPh 3-41 3-ClPh 4-PrOPh 4-CH_ThreeOPh 3-42 3-ClPh 4-i-BuOPh 4-CH_ThreeOPh 3-43 3-CH_ThreePh 4-PrOPh 4-CH_ThreeOPh 3-44 3-CH_ThreePh 4-i-BuOPh 4-CH_ThreeOPh 3-45 3,4-diClPh 4-PrOPh 4-CH_ThreeOPh 3-46 3,4-diClPh 4-i-BuOPh 4-CH_ThreeOPh 3-47 3,4-diClPh 4-CH_ThreePh 4-CH_ThreeOPh 3-48 3,4-diClPh 4-i-BuPh 4-CH_ThreeOPh 3-49 Ph 3-CH_ThreeO-4-PrOPh 3,4,5-triCH_ThreeOPh 3-50 Ph 3,4-diPrOPh 3,4,5-triCH_ThreeOPh 3-51 Ph 3-PrO-4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-52 3-ClPh 3-CH_ThreeO-4-PrOPh 3,4,5-triCH_ThreeOPh 3-53 3-ClPh 3-PrO-4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-54 3-ClPh 3,4-diPrOPh 3,4,5-triCH_ThreeOPh 3-55 3-ClPh 3-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-56 3-CH_ThreePh 3-CH_ThreeO-4-PrOPh 3,4,5-triCH_ThreeOPh 3-57 3-CH_ThreePh 3-PrO-4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-58 3-CH_ThreePh 3,4-diPrOPh 3,4,5-triCH_ThreeOPh 3-59 3-CF_ThreePh 3-CH_ThreeO-4-PrOPh 3,4,5-triCH_ThreeOPh 3-60 3-CF_ThreePh 3-PrO-4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-61 3-CF_ThreePh 3,4-diPrOPh 3,4,5-triCH_ThreeOPh 3-62 3-BrPh 3-CH_ThreeO-4-PrOPh 3,4,5-triCH_ThreeOPh 3-63 3-BrPh 3-PrO-4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-64 3-BrPh 3,4-diPrOPh 3,4,5-triCH_ThreeOPh 3-65 3-BrPh 3-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-66 3-BrPh 3-PrOPh 3,4,5-triCH_ThreeOPh 3-67 3-BrPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-68 3-BrPh 4-EtOPh 3,4,5-triCH_ThreeOPh 3-69 3-BrPh 4-PrOPh 3,4,5-triCH_ThreeOPh 3-70 3-BrPh 4-BuOPh 3,4,5-triCH_ThreeOPh 3-71 3-CF_ThreePh 3-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-72 3-CF_ThreePh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-73 3-CF_ThreePh 3-PrOPh 3,4,5-triCH_ThreeOPh 3-74 3-CF_ThreePh 4-PrOPh 3,4,5-triCH_ThreeOPh 3-75 3-F-Ph 3-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-76 3-F-Ph 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-77 3-F-Ph 3-PrOPh 3,4,5-triCH_ThreeOPh 3-78 3-F-Ph 4-PrOPh 3,4,5-triCH_ThreeOPh 3-79 3,5-diClPh 3-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-80 3,5-diClPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-81 3,5-diClPh 3-PrOPh 3,4,5-triCH_ThreeOPh 3-82 3,5-diClPh 4-PrOPh 3,4,5-triCH_ThreeOPh 3-83 3-ClPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-84 2,3-diClPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-85 2,4-diClPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-86 2,5-diClPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-87 2,6-diClPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh 3-88 3,6-diClPh 4-CH_ThreeOPh 3,4,5-triCH_ThreeOPh ──────────────────────────────────── Table 4

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{Compound No. R ¹ R ² R ⁴ p} ４ 4-1 4-ClPh 4-ClPh 3,4,5-triCH ₃ OPh 1 4-2 4-ClPh 4-ClPh 3,4,5-triCH ₃ OPh 2 4-3 4-ClPh 3-ClPh 3,4,5-triCH ₃ OPh 1 4-4 4-CH ₃ OPh 4 -CH ₃ OPh 3,4,5-triCH ₃ OPh 14-5 4-CH ₃ OPh 4-CH ₃ OPh 3,4,5-triCH ₃ OPh 2 4-6 4-CH ₃ OPh 3-ClPh 3, 4,5-triCH ₃ OPh 14-7 4-CH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 24-8 4-CH ₃ OPh 2,3-diClPh 3,4,5-triCH ₃ OPh 14-9 4-CH ₃ OPh 2,3-diClPh 3,4,5-triCH ₃ OPh 24-10 4-CH ₃ OPh 2,4-diClPh 3,4,5-triCH ₃ OPh 14- 11 4-CH ₃ OPh 2,4-diClPh 3,4,5-triCH ₃ OPh 2 4-12 4-CH ₃ OPh 2,5-diClPh 3,4,5-triCH ₃ OPh 14-13 4-CH ₃ OPh 2,5-diClPh 3,4,5-triCH ₃ OPh 2 4-14 4-CH ₃ OPh 2,6-diClPh 3,4,5-triCH ₃ OPh 14-15 4-CH ₃ OPh 2, _{6-diClPh 3,4,5-triCH 3 OPh} 2 _{-16 4-CH 3 OPh 3,4-} diClPh 3,4,5-triCH 3 OPh 1 4-17 4-CH 3 OPh 3,4-diClPh 3,4,5-triCH 3 OPh 2 4-18 4- CH ₃ OPh 3,5-diClPh 3,4,5-triCH ₃ OPh 14-19 4-CH ₃ OPh 3,5-diClPh 3,4,5-triCH ₃ OPh 24-20 4-CH ₃ OPh 3 -FPh 3,4,5-triCH ₃ OPh 14-21 4-CH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-22 4-CH ₃ OPh 3,5-diFPh 3,4, 5-triCH ₃ OPh 1 4-23 4-CH ₃ OPh 3,5-diFPh 3,4,5-triCH ₃ OPh 2 4-24 4-CH ₃ OPh 3-CNPh 3,4,5-triCH ₃ OPh 1 4-25 4-CH ₃ OPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-26 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 14- 27 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 24-28 4-CH ₃ OPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 14- 29 4-CH ₃ OPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 2 4-30 4-EtOPh 3-ClPh 3,4,5-triCH ₃ OPh 1 4-31 4-EtOPh 3-ClPh 3 , 4,5-triCH ₃ OPh 2 4-32 4-EtOPh 2,3-diClPh 3,4,5-triCH ₃ OPh 14-33 4-EtOPh 2,3-diClPh 3,4,5-triCH ₃ OPh 2 4-34 4-EtOPh 2,4-diClPh 3,4,5-triCH ₃ OPh 1 4-35 4-EtOPh 2,4-diClPh 3,4,5-triCH ₃ OPh 2 4-36 4-EtOPh 2 , 5-di ClPh 3,4,5-triCH ₃ OPh 14-37 4-EtOPh 2,5-diClPh 3,4,5-triCH ₃ OPh 2 4-38 4-EtOPh 2,6-diClPh 3,4,5-triCH ₃ OPh 1 4-39 4-EtOPh 2,6-diClPh 3,4,5-triCH ₃ OPh 2 4-40 4-EtOPh 3,4-diClPh 3,4,5-triCH ₃ OPh 14-41 4- EtOPh 3,4-diClPh 3,4,5-triCH ₃ OPh 2 4-42 4-EtOPh 3,5-diClPh 3,4,5-triCH ₃ OPh 14-43 4-EtOPh 3,5-diClPh 3, 4,5-triCH ₃ OPh 2 4-44 4-EtOPh 3-FPh 3,4,5-triCH ₃ OPh 14-45 4-EtOPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-46 4 -EtOPh 3,5-diFPh 3,4,5-triCH ₃ OPh 14-47 4-EtOPh 3,5-diFPh 3,4,5-triCH ₃ OPh 2 4-48 4-EtOPh 3-CNPh 3,4 , 5-triCH ₃ OPh 14-49 4-EtOPh 3-CNPh 3,4,5-triCH ₃ OPh 24-4-50 4-EtOPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 14-51 4-EtOPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 24 4-52 4-EtOPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 14-53 4-EtOPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 2 4-54 4-CH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 34-55 4-CH ₃ OPh 3,5 -diClPh 3,4,5-triCH ₃ OPh 34-56 4-CH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 34-57 4-CH ₃ OPh 3,5-diFPh 3,4,5-triCH ₃ OPh 34-58 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 34-59 4-CH ₃ OPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 3 4-60 4-EtOPh 3-ClPh 3,4,5-triCH ₃ OPh 3 4-61 4-EtOPh 3,5-diClPh 3,4,5-triCH ₃ OPh 3 4-62 4-EtOPh 2,5-diClPh 3,4,5-triCH ₃ OPh 3 4-63 4-EtOPh 3-FPh 3,4,5-triCH ₃ OPh 34-64 4-EtOPh 3,5- diFPh 3,4,5-triCH ₃ OPh ₃ 4-65 4-EtOPh 3-CNPh 3,4,5-triCH ₃ OPh 3 4-66 4-EtOPh 3-Cl-5-CH ₃ Ph 3,4,5 -triCH ₃ OPh 34-67 4-EtOPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 34-68 4-CH ₃ OPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 14 -69 4-CH ₃ OPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-70 4-CH ₃ OPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 34-71 4- CH ₃ OPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 14-72 4-CH ₃ OPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-73 4- CH ₃ OPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 34-74 4-EtOPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 14-75 4-EtOPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-76 4-EtOPh 3-CH ₃ Ph 3,4,5-triCH ₃ OPh 34-77 4-EtOPh 3,5-diCH ₃ Ph 3,4, 5-triCH ₃ OPh 14-78 4-EtOPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-79 4-EtOPh 3,5-diCH ₃ Ph 3,4,5-triCH ₃ OPh 34-80 3,4-diCH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 14-81 3,4-diCH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 2 4-82 3,4- diCH ₃ OPh 3-ClPh 3,4,5-triCH ₃ OPh 3 4-83 3,4-diCH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 14-84 3,4-diCH ₃ OPh 3 -FPh 3,4,5-triCH ₃ OPh 2 4-85 3,4-diCH ₃ OPh 3-FPh 3,4,5-triCH ₃ OPh 3 4-86 3,4-diCH ₃ OPh 3-CNPh 3, 4,5-triCH ₃ OPh 14-87 3,4-diCH ₃ OPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-88 3,4-diCH ₃ OPh 3-CNPh 3,4,5- triCH ₃ OPh 3 4-89 3,4-diCH ₃ OPh 3-CF ₃ 3,4,5-triCH ₃ OPh 14-90 3,4-diCH ₃ OPh 3-CF ₃ 3,4,5-triCH ₃ OPh 2 4-91 3,4-diCH ₃ OPh 3-CF ₃ 3,4,5-triCH ₃ OPh 34-92 4-EtPh 3-ClPh 3,4,5-triCH ₃ OPh 14-93 4- EtPh 3-ClPh 3,4,5-triCH ₃ OPh 2 4-94 4-EtPh 3-ClPh 3,4,5-triCH ₃ OPh 34-95 4-EtPh 3,5-diClPh 3,4,5- triCH ₃ OPh 14-96 4-EtPh 3,5-diClPh 3,4,5-triCH ₃ OPh 24-97 4-EtPh 3,5-diClPh 3,4,5-triCH ₃ OPh 34-98 4 -EtPh 2,5-diClPh 3,4,5-triCH ₃ OPh 14-99 4-EtPh 2,5-diClPh 3,4,5-triCH ₃ OPh 24-100 4-EtPh 2,5-diClPh 3,4 , 5-triCH ₃ OPh 3 4-101 4-EtPh 3-FPh 3,4,5-triCH ₃ OPh 14-102 4-EtPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-103 4- EtPh 3-FPh 3,4,5-triCH ₃ OPh 34-104 4-EtPh 3,5-diFPh 3,4,5-triCH ₃ OPh 14-105 4-EtPh 3,5-diFPh 3,4, 5-triCH ₃ OPh 2 4-106 4-EtPh 3,5-diFPh 3,4,5-triCH ₃ OPh 34-107 4-EtPh 3-CNPh 3,4,5-triCH ₃ OPh 14-108 4 -EtPh 3-CNPh 3,4,5-triCH ₃ OPh 2 4-109 4-EtPh 3-CNPh 3,4,5-triCH ₃ OPh 34-110 4-EtPh 3-CF ₃ Ph 3,4,5 -triCH ₃ OPh 14-111 4-EtPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 24 4-112 4-EtPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 34-113 4-EtPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 14-114 4-EtPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 24 4-115 4-EtPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 34-116 4-PrPh 3-ClPh 3,4,5-triCH ₃ OPh 14-117 4-PrPh 3-ClPh 3,4,5-triCH ₃ OPh 2 4-118 4-PrPh 3,5-diClPh 3,4,5-triCH ₃ OPh 14-119 4-PrPh 3,5-diClPh 3,4,5-triCH ₃ OPh 2 4-120 4-PrPh 3-FPh 3,4,5-triCH ₃ OPh 14-121 4-PrPh 3-FPh 3,4,5-triCH ₃ OPh 2 4-122 4-PrPh 3,5 -diFPh 3,4,5-triCH ₃ OPh 14-123 4-PrPh 3,5-diFPh 3,4,5-triCH ₃ OPh 2 4-124 4-PrPh 3-CNPh 3,4,5-triCH ₃ OPh 14-125 4-PrPh 3-CNPh 3,4,5-triCH ₃ OPh 24-126 4-PrPh 3-CF ₃ Ph 3,4,5-triCH ₃ OPh 14-127 4-PrPh 3- CF ₃ Ph 3,4,5-triCH ₃ OPh 2 4-128 4-PrPh 3-Cl-5-CH ₃ Ph 3,4,5-triCH ₃ OPh 14-129 4-PrPh 3-Cl-5- CH ₃ Ph 3,4,5-triCH ₃ OPh 2 4-130 4-CH ₃ OPh 3-ClPh 3-Pyr 14-131 4-CH ₃ OPh 3-ClPh 3-Pyr 2 4-132 4-CH ₃ OPh 3-ClPh 3-Pyr 3 4-133 4-CH ₃ OPh 3-ClPh 3- (5-BrPyr) 14-134 4-CH ₃ OPh 3-ClPh 3- (5-BrPyr) 24 4-135 4 -CH ₃ OPh 3-ClPh 3- (5-BrPyr) 34-136 4-CH ₃ OPh 3-ClPh 3- (5-CH ₃ OPyr) 14-137 4-CH ₃ OPh 3-ClPh 3- ( 5-CH ₃ OPyr) 2 4-138 4-CH ₃ OPh 3-ClPh 3- (5-CH ₃ OPyr) 34-139 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 14 -140 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 2 4-141 4-CH ₃ OPh 3-ClPh 3- (2-CH ₃ SPyr) 34-142 4-CH ₃ OPh 3-ClPh 3- (6-CH ₃ Pyr) 14-143 4-CH ₃ OPh 3-ClPh 3- (6-CH ₃ Pyr) 24 4-144 4-CH ₃ OPh 3-ClPh 3- ( 6-CH ₃ Pyr) 34-145 4-CH ₃ OPh 3,5-diClPh 3-Pyr 14-146 4-CH ₃ OPh 3,5-diClPh 3-Pyr 2 4-147 4-CH ₃ OPh 3 , 5-diClPh 3-Pyr 3 4-148 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 14-149 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 2 4-150 4-CH ₃ OPh 3,5-diClPh 3- (5-BrPyr) 34-151 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 14-152 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 2 4-153 4-CH ₃ OPh 3,5-diClPh 3- (5-CH ₃ OPyr) 34-154 4-CH ₃ OPh 3, 5-diClPh 3- (2-CH ₃ SPyr) 14-155 4-CH ₃ OPh 3,5-diClPh 3- (2-CH ₃ SPyr) 24 4-156 4-CH ₃ OPh 3,5-diClPh 3 -(2-CH ₃ SPyr) 34-157 4-CH ₃ OPh 3,5-diClPh 3- (6-CH ₃ Pyr) 14-158 4-CH ₃ OPh 3,5-diClPh 3- (6- (CH ₃ Pyr) 2 4-159 4-CH ₃ OPh 3,5-diClPh 3- (6-CH ₃ Pyr) 34-160 4-CH ₃ OPh 3-FPh 3-Pyr 14-161 4-CH ₃ OPh 3-FPh 3-Pyr 2 4-162 4-CH ₃ OPh 3-FPh 3-Pyr ₃ 4-163 4-CH ₃ OPh 3-FPh 3- (2-ClPyr) 14-164 4-CH ₃ OPh 3-FPh 3- (2-ClPyr) 2 4-165 4-CH ₃ OPh 3-FPh 3- (2-ClPyr) 34-166 4-CH ₃ OPh 3-FPh 3- (5-BrPyr) 14-167 4-CH ₃ OPh 3-FPh 3- (5-BrPyr) 2 4-168 4-CH ₃ OPh 3-FPh 3- (5-BrPyr) 34-169 4-CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 1 4-170 4-CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 2 4-171 4-CH ₃ OPh 3-FPh 3- (5-CH ₃ OPyr) 34-172 4- CH ₃ OPh 3-FPh 3- (6-CH ₃ Pyr) 14-173 4-CH ₃ OPh 3-FPh 3- (6-CH ₃ Pyr) 24 4-174 4-CH ₃ OPh 3-FPh 3- (6-CH ₃ Pyr) 34-175 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ SPyr) 14-176 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ SPyr) 2 4-177 4-CH ₃ OPh 3-FPh 3- (2-CH ₃ SPyr) 34-178 4-CH ₃ OPh 3,5-diFPh 3-Pyr 14-179 4-CH ₃ OPh 3,5- diFPh 3-Pyr 2 4-180 4-CH ₃ OPh 3,5-diFPh 3-Pyr 3 4-181 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 14-182 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 2 4-183 4-CH ₃ OPh 3,5-diFPh 3- (2-ClPyr) 34-184 4-CH ₃ OPh 3,5-diFPh 3- (5-BrPyr) 1 4-185 4 -CH 3 OPh 3,5-diFPh 3- (5-BrPyr) 2 4-186 4-CH 3 OPh 3,5-diFPh 3- (5-BrPyr) 3 4- 187 4-CH ₃ OPh 3,5-diFPh 3- (5 -CH ₃ OPyr) 14-188 4-CH ₃ OPh 3,5-diFPh 3- (5-CH ₃ OPyr) 24 -189 4-CH ₃ OPh 3,5-diFPh 3- (5-CH ₃ OPyr ) 34-190 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 14-191 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 24 192 4-CH ₃ OPh 3,5-diFPh 3- (2-CH ₃ SPyr) 34-193 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 14-194 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 2 4-195 4-CH ₃ OPh 3,5-diFPh 3- (6-CH ₃ Pyr) 34-196 4-CH ₃ OPh 3- CNPh 3-Pyr 14-197 4-CH ₃ OPh 3-CNPh 3-Pyr 24-198 4-CH ₃ OPh 3-CNPh 3-Pyr 34-199 4-CH ₃ OPh 3-CNPh 3- (2 -ClPyr) 14-200 4-CH ₃ OPh 3-CNPh 3- (2-ClPyr) 24-201 4-CH ₃ OPh 3-CNPh 3- (2-ClPyr) 34-202 4-CH ₃ OPh 3-CNPh 3- (5-BrPyr) 14-203 4-CH ₃ OPh 3-CNPh 3- (5-BrPyr) 24 4-204 4-CH ₃ OPh 3-CNPh 3- (5-BrPyr) 34 -205 4-CH ₃ OPh 3-CNPh 3- (5-MeOPyr) 1 4-206 4-CH ₃ OPh 3-CNPh 3- (5-MeOPyr) 2 4-207 4-CH ₃ OPh 3-CNPh 3- (5-MeOPyr) 34-208 4-CH ₃ OPh 3-CNPh 3- (2-CH ₃ SPyr) 14-209 4-CH ₃ OPh 3-CNPh 3- (2-CH ₃ SPyr) 24 210 4-CH ₃ OPh 3-CNPh 3- (2-CH ₃ SPyr) 34- 211 4-CH ₃ OPh 3-CNPh 3- (6-CH ₃ Pyr) 14 4-212 4-CH ₃ OPh 3-CNPh 3- (6 _{-CH 3 Pyr) 2 4-213 4-} CH 3 OPh 3-CNPh 3- (6-CH 3 Pyr) 3 4-214 4-CH 3 OPh 3-Cl-5-CH 3 Ph 3-Pyr 1 4- 215 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3-Pyr 2 4-216 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3-Pyr 3 4-217 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (2-ClPyr) 14-218 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 24 4-219 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (2-ClPyr) 34-220 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 14-221 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (5-BrPyr) 2 4-222 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 34-223 4-CH ₃ OPh 3- Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 14-224 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 24 4-225 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPyr) 34-226 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr) 1 4- 227 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr) 24 228 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPyr ) 34-229 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 14-230 4-CH ₃ OPh 3-Cl- 5-CH ₃ Ph 3- (6-CH ₃ Pyr) 2 4-231 4-CH ₃ OPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 3 4-232 4-EtOPh 3- ClPh 3-Pyr 1 4-233 4-EtOPh 3-ClPh 3-Pyr 24 234 4-EtOPh 3-ClPh 3-Pyr 34-235 4-EtOPh 3-ClPh 3- (2-ClPyr) 14- 236 4-EtOPh 3-ClPh 3- (2-ClPyr) 2 4-237 4-EtOPh 3-ClPh 3- (2-ClPyr) 34-238 4-EtOPh 3-ClPh 3- (5-BrPyr) 14 -239 4-EtOPh 3-ClPh 3- (5-BrPyr) 24-240 4-EtOPh 3-ClPh 3- (5-BrPyr) 34-241 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr ) 1 4-242 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr) 2 4-243 4-EtOPh 3-ClPh 3- (5-CH ₃ OPyr) 34-244 4-EtOPh 3-ClPh 3 -(2-CH ₃ SPyr) 14-245 4-EtOPh 3-ClPh 3- (2-CH ₃ SPyr) 24 4-246 4-EtOPh 3-ClPh 3- (2-CH ₃ SPyr) 34-247 4-EtOPh 3-ClPh 3- (6-CH ₃ Pyr) 14-248 4-EtOPh 3-ClPh 3- (6-CH ₃ Pyr) 2 4-249 4-EtOPh 3-ClPh 3- (6-CH ₃ 4-250 4-EtOPh 3,5-diClPh 3-Pyr 14-251 4-EtOPh 3,5-diClPh 3-Pyr2 4-252 4-EtOPh 3,5-diClPh 3-Pyr 3 4 -253 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 1 4-254 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 2 4- 255 4-EtOPh 3,5-diClPh 3- (5-BrPyr) 3 4-256 4-EtOPh 3,5-diClPh 3- (5-CH ₃ OPyr) 14-257 4-EtOPh 3,5-diClPh 3 -(5-CH ₃ OPyr) 2 4-258 4-EtOPh 3,5-diClPh 3- (5-CH ₃ OPyr) 34-259 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 1 4-260 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 2 4-261 4-EtOPh 3,5-diClPh 3- (2-CH ₃ SPyr) 3 4-262 4-EtOPh 3 , 5-diClPh 3- (6-CH ₃ Pyr) 14-263 4-EtOPh 3,5-diClPh 3- (6-CH ₃ Pyr) 24-264 4-EtOPh 3,5-diClPh 3- (6 -CH ₃ Pyr) 34-265 4-EtOPh 3-FPh 3-Pyr 14-266 4-EtOPh 3-FPh 3-Pyr2 4-267 4-EtOPh 3-FPh 3-Pyr 34-268 4- EtOPh 3-FPh 3- (2-ClPyr) 14-269 4-EtOPh 3-FPh 3- (2-ClPyr) 24-270 4-EtOPh 3-FPh 3- (2-ClPyr) 34-271 4 -EtOPh 3-FPh 3- (5-BrPyr) 14-272 4-EtOPh 3-FPh 3- (5-BrPyr) 24-273 4-EtOPh 3-FPh 3- (5-BrPyr) 34-274 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 14-275 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 2 4-276 4-EtOPh 3-FPh 3- (5-CH ₃ OPyr) 3 4-277 4-EtOPh 3-FPh 3- (2-CH ₃ SPh) 1 4-278 4-EtOPh 3-FPh 3- (2-CH ₃ SPh) 2 4-279 4 -EtOPh 3-FPh 3- (2-CH ₃ SPh) 34-280 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 14-281 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 24-282 4-EtOPh 3-FPh 3- (6-CH ₃ Pyr) 34-283 4-EtOPh 3-CNPh 3-Pyr 14-284 4-EtOPh 3-CNPh 3-Pyr 24 285 4-EtOPh 3-CNPh 3-Pyr 3 4-286 4-EtOPh 3-CNPh 3- (5-BrPyr) 14-287 4-EtOPh 3-CNPh 3- (5-BrPyr) 2 4-288 4- EtOPh 3-CNPh 3- (5-BrPyr) 34-289 4-EtOPh 3-CNPh 3- (5-CH ₃ OPyr) 14-290 4-EtOPh 3-CNPh 3- (5-CH ₃ OPyr) 2 4-291 4-EtOPh 3-CNPh 3- (5-CH ₃ OPyr) 34-292 4-EtOPh 3-CNPh 3- (2-CH ₃ SPyr) 14-293 4-EtOPh 3-CNPh 3- ( 2-CH ₃ SPyr) 2 4-294 4-EtOPh 3-CNPh 3- (2-CH ₃ SPyr) 34-295 4-EtOPh 3-CNPh 3- (6-CH ₃ SPyr) 14-296 4- EtOPh 3-CNPh 3- (6-CH ₃ SPyr) 2 4-297 4-EtOPh 3-CNPh 3- (6-CH ₃ SPyr) 34-298 4-EtOPh 3-Cl-5-CH ₃ Ph 3- Pyr 14-299 4-EtOPh 3-Cl-5-CH ₃ Ph 3-Pyr 24-300 4-EtOPh 3-Cl-5-CH ₃ Ph 3-Pyr 34-301 4-EtOPh 3-Cl- 5-CH ₃ Ph 3- (2-ClPyr) 14-302 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 24-303 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-ClPyr) 34-304 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 14-305 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 2 4-306 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr) 34-306 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-BrPyr ) 34-307 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPh) 14-308 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (5-CH ₃ OPh ) 24-309 4-EtOPh 3-Cl-5-CH ₃ Ph3- (5-CH ₃ OPh) 34-310 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPh ) 1 4-311 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPh) 24-3-12 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (2-CH ₃ SPh ) 34-313 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 14-314 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr ) 24-315 4-EtOPh 3-Cl-5-CH ₃ Ph 3- (6-CH ₃ Pyr) 34-316 4-EtOPh 3,5-diCH ₃ Ph 3-Pyr 14-317 4-EtOPh 3,5-diCH ₃ Ph 3-Pyr 2 4-318 4-EtOPh 3,5-diCH ₃ Ph 3-Pyr 34-319 4-EtOPh 3,5-diCH ₃ Ph 3- (5-BrPyr) 14 -320 4-EtOPh 3,5-diCH ₃ Ph 3- (5-BrPyr) 2 4-321 4-EtOPh 3,5-diCH ₃ Ph 3- (5-BrPyr) 3 ───────── ────────────────── ──────── Among the exemplified compounds described in Table 1, suitable compounds, 1,2,3,4,6,14,16,17,1
8, 19, 20, 25, 26, 28, 29, 30, 4
1,45,46,53,76,83,91,116,1
17, 118, 120, 129, 130, 133, 13
4,141,154,155,207,220,29
8,300,313,325,327,342,34
3,388,411,412,419,420,42
4,425,426,431,433,441,44
5,452,453,454,455,456,45
7,458,459,460,461,462,46
3,466,467,468,469,470,47
1,472,473,474,475,476,47
7,478,479,480,481,482,48
3,484,485,486,487,488,48
9,490,491,492,496,498,50
1,505,507,510,511,512,51
3,514,515,516,517,518,51
9,520,521,522,523,524,52
5,528,529,530,531,536,53
7,539,541,546,551,552,55
3,556,557,558,559,560,56
1,562,563,564,565,566,56
7,568,569,570,571,572,57
3,574,580,581,582,583,58
4,585,586,587,588,589,59
0,591,592,593,594,595,59
6,598,601,602,603,604,60
5,606,607,608,609,610,61
1,612,616,621,622,623,62
4,625,626,627,628,629,63
0,631,632,633,634,635,63
6,637,638,639,640,641,64
2,643,644,645,646,647,64
9,650,651,652,655,659,66
0,661,662,663,664,665,66
6,667,668,669,670,671,67
2,673,674,675,676,677,67
8,679,680,681,682,683,68
4,685,686,687,688,689,69
0,691,692,693,694,695,69
6,697,699,700,701,702,70
3,704,705,706,707,708,70
9,710,711,712,713,714,71
5,716,717,718,719,720,72
1,722,723,724,725,726,72
7,728,729,730,731,732,73
3,734,735,736,737,738,73
9,740,741,742,743,744,74
5,746,747,748,749,750,75
1,752,753,754,755,756,75
7,758,759,760,761,762,76
3,764,766,771,772,773,77
4,777,778,779,780,781,78
2,783,784,785,787,788,78
9,790,793,795,796,798,79
9,801,803,805,807,809,81
0,813,815,817,820,821,82
3,825,832,833,845,846,85
0,851,858,859,860,862,86
3,866,867,871,872,873,87
4,875,876,877,879 and 880.

Of the compounds exemplified in Table 2 above,
Suitable compounds include 1,7,8,9,15,16,
19, 21, 23, 24, 25, 29, 30, 31, 3
2,35,37,41,44,45,46,47,5
1,53,57,59,62,65,66,67,6
8, 70, 72, 74, 75, 77, 78, 80, 8
3,84,85,86,87,88,89,90,9
1,92,93,94,101,102,103,10
4,107,108,109,110,112,16
3,255,256,257,258,259,26
0, 261, 265, 266, 278, 280, 28
2,285,291,292,294,299,30
0, 302, 310, 318, 323, 324, 32
5,326,331,332,334,340,34
6,351,355,360,364,365,36
8,369,371,372,374,375,377
And 378.

Of the compounds exemplified in Table 3 above,
Suitable compounds include 1,2,3,4,5,6,7,
8, 9, 11, 13, 18, 19, 23, 25, 29,
34, 35, 37, 49, 50, 51, 52, 54, 5
6, 58, 59, 61, 62, 64, 67 and 68 compounds.

Of the compounds exemplified in Table 4 above,
Suitable compounds include 1,2,4,5,7,8,1
0, 12, 13, 14, 16, 18, 19, 20, 2
1,22,24,25,26,27,28,30,3
2,36,37,38,42,43,44,45,4
6,48,49,50,51,63,65,83,8
6,101,102,107,118,121,12
4,130,131,134,145,148,16
0,166,167,169,178,184,19
4,202,205,214,220,223,23
2,238,241,250,253,265,26
6,271,274,283,286,289,29
8, 304 and 308 compounds.

Of the compounds exemplified in Table 1 above,
More preferred compounds include 28, 53, 419, 42
4,426,431,441,445,453,45
4,455,456,461,462,463,46
4,467,468,469,470,472,47
5,476,478,480,482,483,48
4,486,510,512,513,514,51
5,517,519,521,524,529,53
1,541,546,558,560,568,57
0,574,581,582,585,587,59
0,592,594,598,603,606,60
9,622,627,628,631,632,63
7,660,668,670,671,675,67
9,680,681,684,685,693,69
4,702,703,707,710,713,71
4,717,718,719,727,728,73
0,731,733,737,740,743,74
6,752,758,759,772,773,77
7,778,784,793,795,799,80
3,805,813,815,845,858,85
9,866,867,872,873,874,877
And 878.

Of the compounds exemplified in Table 2 above,
More preferred compounds include 255, 256, 260,
261,262,266,294,318,326,3
34, 351 and 360 compounds.

Of the compounds exemplified in Table 3 above,
More preferred compounds include 2,3,5,49,50,
Compounds 52, 54, 56 and 59 can be mentioned. Among the exemplified compounds described in Table 4 above, more preferred compounds include 12, 18, 20, 21, 24, and 2
5,26,27,36,42,44,45,48,13
0 and 286.

Among the exemplified compounds shown in Tables 1 to 4, the most preferred compounds are the compounds 28,419,424,426,453,454,4 described in Table 1.
55,467,468,469,470,482,48
3,484,513,515,529,557,55
9,574,590,594,603,606,62
2,627,685,710,740,743,79
3,803,805,858,859,872,87
The compounds of 3,874,877 and 878, the compounds of 256, 262 and 326 described in Table 2, and the compounds of 42, 44 and 48 described in Table 4 can be mentioned.

The N- (3,3-disubstituted acryloyl) piperazine derivative of the present invention can be produced by the method described below.

When a compound having a thiocarbonyl group in the molecule is produced, the compound is usually produced by the following reaction using a compound having a corresponding thiocarbonyl group as a raw material. The compound can be also produced by synthesizing a compound having a carbonyl group, followed by reacting the compound according to a conventional method using a reagent for converting a carbonyl group into a thiocarbonyl group, such as a Lawson reagent. At this time, when the molecule has two carbonyl groups, two or one carbonyl group can be selectively converted to a thiocarbonyl group by selecting conditions.

[Method A]

[0049]

Embedded image

In the above formula, R ¹ , R ² , R ³ , R ⁴ , X and A have the same meanings as described above, and B is a compound represented by the general formula

[0051]

Embedded image

Wherein R ⁵ , m and n are as defined above, and Y is a nucleophilic leaving group, for example, chlorine, bromine or iodine. A halogen atom; an azido group or a lower alkoxycarbonyloxy group such as methoxycarbonyloxy or ethoxycarbonyloxy.

[Method A] The compound of the present invention in the case where R ³ and R ⁵ together do not show the general formula-(CH ₂ ) _p- (wherein p represents 1 to 3) It is a manufacturing method of.

Step A-1 is a step of preparing a carboxylic acid derivative (A
This is the step of converting I) into its activated derivative (AII). The activation is carried out according to a conventional method. When an acid halide compound is produced, the activation is carried out using a phosphorus chloride such as phosphorus pentachloride or phosphorus trichloride or a sulfuric acid derivative such as thionyl chloride. In the case of producing a lower alkoxycarbonyloxy compound, for example, the reaction is carried out using an azidating agent such as diphenylphosphoryl azide (DPPA) and an organic base. This is performed using a lower alkyl carbonate and an organic base. The organic base used above is not particularly limited as long as it is used as a base in a usual reaction, but preferably triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N -Dimethylamino) pyridine, N,
N-dimethylaniline, 1,5-diazabicyclo [4.3.0] nona
-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,8-
Organic bases such as diazabicyclo [5.4.0] undec-7-ene (DBU) can be mentioned.

In step A-2 , the activated carboxylic acid derivative (AII) and compound (AIII) are dissolved in a solvent
This is a step of producing compound (I) of the present invention by reacting in the presence or absence of a base. When the activated carboxylic acid derivative (AII) is an acid halide compound, it is preferable to use a base.
There is no particular limitation as long as it is used as a base in a normal reaction. For example, as a base, an alkali metal carbonate such as sodium carbonate or potassium carbonate; an alkali metal bicarbonate such as sodium bicarbonate or potassium bicarbonate; an alkali metal such as lithium hydride, sodium hydride or potassium hydride Hydrides: sodium hydroxide, potassium hydroxide, when using an inorganic base such as an alkali metal hydroxide such as barium hydroxide,
Examples of the solvent include ethers such as ether, tetrahydrofuran, dioxane, and dimethoxyethane; amides such as dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; sulfoxides such as dimethyl sulfoxide; and acetonitrile. Nitriles; water or a mixed solvent of water and the above organic solvent is preferably used. As a base, triethylamine, diisopropylethylamine, N-methylmorpholine, pyridine, 4- (N, N-dimethylamino) pyridine, N, N- Dimethylaniline, 1,5-diazabicyclo [4.3.0] non-5-ene,
When using organic bases such as 1,4-diazabicyclo [2.2.2] octane and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), it is necessary to use benzene, toluene and xylene. It is preferable to use ethers such as ether, tetrahydrofuran, dioxane and dimethoxyethane, or halogenated hydrocarbons such as methylene chloride and chloroform.

Activated carboxylic acid derivative (AII)
Is an acid azide compound or a lower alkoxycarbonyloxy compound, the reaction proceeds even in the absence of a base, so the organic base is not necessarily required. The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the raw materials to some extent, but is preferably aromatic hydrocarbons such as benzene, toluene and xylene;
Halogenated hydrocarbons such as methylene chloride and chloroform; ethers such as ether, tetrahydrofuran, dioxane and dimethoxyethane; amides such as dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide; dimethyl sulfoxide And nitriles such as acetonitrile. The reaction is carried out at a temperature of 0 ° C. to 50 ° C., preferably at room temperature. The reaction time varies depending mainly on the reaction temperature, the type of the starting compound and the type of the solvent used, but is usually 15 minutes to 1 day. It is.

The compound (AIII) used in the step A-2 is a known compound [for example, 1- (3,4,5)
-Trimethoxybenzoyl) piperazine was prepared according to Toldi et al. (Acta. Chim. Acad. Sci. Hung., 49 (3), 265-285
66) and 1- (3,4,5-trimethoxythiobenzoyl) piperazine were prepared by Farina et al. (Eur. Med. Chem. Chemica Theica).
rapeutica, 14 (1), 27-31 (1979). Or a compound (BI) and a compound (BI)
II) is reacted according to step B-2.

[Method B]

[0059]

Embedded image

In the above formula, R ¹ , R ² , R ³ , R ⁴ , X,
Y, A and B are as defined above.

[Method B] The compound of the present invention in the case where R ³ and R ⁵ together do not show the general formula-(CH ₂ ) _p- (wherein p represents 1 to 3). Is a separate manufacturing method.

In step B-1 , the activated carboxylic acid derivative (AII) and the compound (BI) are reacted according to step A-2, and the formyl group substituted by a nitrogen atom is removed. This is a step of producing a compound (BII) by removal. The latter removal of the formyl group is achieved by treatment with a base in the presence of a solvent. The base is not particularly limited as long as it does not affect the other parts of the compound, but is preferably a metal alcoholate such as sodium methoxide; an alkali metal carbonate such as sodium carbonate and potassium carbonate. Salts; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; aqueous ammonia or concentrated ammonia-methanol. The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction, and water; methanol, ethanol,
Organic solvents such as alcohols such as n-propanol; ethers such as tetrahydrofuran and dioxane; or mixed solvents of water and an organic solvent are preferred. The reaction temperature and reaction time vary depending on the starting material, the base used, and the like, and are not particularly limited. In order to suppress side reactions, the reaction is usually performed at 0 ° C. to 150 ° C., preferably at room temperature, and the reaction time is preferably 1 to 24 hours.

Step B-2 is a step of producing compound (I) of the present invention by reacting compound (BII) with compound (BIII) in a solvent in the presence of a base. When B represents a group other than a lower alkylene group, the reaction is carried out according to step A-2. When B represents a lower alkylene group, lithium hydride, sodium hydride and potassium hydride are preferably used. There is no particular limitation on the solvent, as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably ether, tetrahydrofuran, dioxane, dimethoxy. Ethers such as ethane or amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide are used.

After completion of the reaction, the target compound of each reaction is collected from the reaction mixture according to a conventional method. For example, it can be obtained by adding an organic solvent immiscible with water to the reaction mixture, washing with water, and distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

[Method C]

[0066]

Embedded image

In the above formula, R ¹ , R ² , R ⁴ , X, A,
Y, m, n and p are as defined above.

[Method C] refers to the method of the present invention compound where R ³ and R ⁵ together represent the general formula-(CH ₂ ) _p- (wherein p represents 1 to 3). It is a manufacturing method.

Step C-1 is a step in which the bicyclic amine compound (C
The secondary amino group of I) is converted to a compound (BIII)
This is a method for producing a compound (CII) in which a nitrogen atom is substituted by reacting according to two steps.

In step C-2 , the compound (C)
II) is treated with a base in the presence of a solvent to generate an anion at the methylene group adjacent to the carbonyl group, and then reacted with compound (CIII) to carry out an aldol reaction to produce compound (CIV) This is the step of performing The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably an aliphatic hydrocarbon such as hexane, heptane, ligroin, or petroleum ether; Aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; formamide, dimethylformamide, dimethylacetamide, hexamethyl Examples include amides such as phosphorotriamide; and sulfoxides such as dimethyl sulfoxide and sulfolane. The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably, inorganic bases such as alkali metal hydrides such as sodium hydride and potassium hydride; Alkali metal alkoxides such as sodium methoxide and sodium ethoxide; 1,5-diazabicyclo [4.3.0] non-5-ene;
Organic bases such as 1,4-diazabicyclo [2.2.2] octane (DABCO) and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) or organic bases such as butyllithium and lithium diisopropylamide Metal bases can be mentioned. The reaction is carried out at a temperature ranging from -78 ° C to 0 ° C, preferably from -78 ° C to -50 ° C. The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of the solvent used, but is usually 1 hour to 2 hours.

In step C-3 , the compound (C
IV) is a step of producing a compound (CV) of the present invention by dehydrating the compound (IV) by treating it with an acid or a dehydrating agent such as phosphorus oxychloride in the presence or absence of a solvent. The solvent to be used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably aliphatic hydrocarbons such as hexane and heptane; benzene, toluene and xylene Aromatic hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and propyl acetate; ethers such as diethyl ether, tetrahydrofuran and dioxane; methano- Alcohols such as toluene and ethanol; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; nitriles such as acetonitrile and isobutyronitrile; formamide, dimethylformamide, dimethylacetamide and hexamethylphosphorotrile Amides such as amides; dimethyl sulfoxide Can be exemplified de, sulfoxides such as sulfolane. When phosphorus oxychloride is used as the dehydrating agent, a non-proton donating solvent must be used among the above solvents, and aliphatic hydrocarbons and aromatic hydrocarbons are preferably used. Or halogenated hydrocarbons. The acid to be used is not particularly limited as long as it is a donor of a hydrogen ion as a Bronsted acid.Tosic acid, organic sulfonic acids such as camphor-sulfonic acid, or hydrochloric acid, is preferably used. Inorganic acids such as sulfuric acid can be mentioned. The reaction is carried out at a temperature of from 0 ° C to 150 ° C, preferably from 80 ° C to 120 ° C.
The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of the solvent used, but is usually from 1 hour to 1 day. The product is obtained as a mixture of geometric isomers, and each isomer can be separated by conventional means of formation, such as various chromatography and recrystallization.

[Method D]

[0073]

Embedded image

In the above formula, R ¹ , R ² , R ⁴ , X, Y,
A, m, n and p are as defined above.

In the [Method D], the compound of the present invention in the case where R ³ and R ⁵ together represent a general formula-(CH ₂ ) _p- (wherein p represents 1 to 3) ( CV).

In the step D-1 , the compound (CII) is reacted with the aldehyde compound (DI) in the step C-2 and the step C-2.
In this step, compound (DII) is produced by reacting according to step-3.

In the step D-2 , the compound (DII) and the compound (DII) having the general formula R ² -Y are prepared according to the Heck reaction.
This is a step of producing a compound (CV) of the present invention by reacting the compound of the present invention with I) in the presence of a palladium salt such as palladium acetate and bis (triphenylphosphine) dichloropalladium. The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but is preferably a nitrile such as acetonitrile; or an aromatic such as benzene, toluene and xylene. Hydrocarbons; esters such as ethyl acetate and propyl acetate; ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane; amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide or Sulfoxides such as dimethyl sulfoxide can be mentioned. The reaction is carried out at a temperature of 50 ° C to 200 ° C, preferably at 80 ° C.
To 150 ° C. The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of the solvent used, but is usually 8 hours to 2 days. The product is obtained as a mixture of geometric isomers, each isomer is obtained by conventional means of formation, such as various chromatography and recrystallization.
Can be separated.

[Method E]

[0079]

Embedded image

In the above formula, R ¹ , R ² , R ⁴ , X, Y,
A, m, n and p are as defined above.

In the [Method E], the compound of the present invention in which R ³ and R ⁵ together represent a general formula-(CH ₂ ) _p- (wherein p represents 1 to 3) ( CV).

Step E-1 is a step of reacting the compound (CI) with an active derivative of formic acid (EI) according to Step C-1 to produce a compound (EII) substituted with a nitrogen atom. is there.

In step E-2 , the compound synthesized above (E
II) is reacted with a ketone compound (CIII) according to Steps C-2 and C-3 to give a compound (EIII)
This is the step of manufacturing.

In step E-3 , the compound (E
The formyl group of III) is removed according to the later stage of Step B-1, and then the compound (BI) is removed according to Step B-2.
II) to produce the compound (CV) of the present invention.

[Method F]

[0086]

Embedded image

In the above formula, R ¹ , R ² , X, Y, m, n and p are as defined above.

[Method F] The compound of the present invention wherein R ³ and R ⁵ together represent a general formula-(CH ₂ ) _p- (wherein p represents 1 to 3) CV), a synthetic intermediate (E
III) is a separate production method.

In the step F-1 , the compound (E
II) is reacted with the aldehyde compound (DI) according to the above-mentioned Step C-2 and Step C-3 to give a compound (FI)
This is the step of manufacturing.

In the step F-2 , the compound (FI) synthesized above is reacted with the compound (DIII) having the general formula R ² -Y according to the Heck reaction, and the intermediate compound (CV) of the present invention is synthesized. A process for producing the compound (EIII),
It is performed according to two steps.

After completion of the reaction, the target compound of each reaction in each of the above steps is collected from the reaction mixture according to a conventional method. For example, it can be obtained by adding an organic solvent immiscible with water to the reaction mixture, washing with water, and distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, recrystallization, reprecipitation or chromatography.

R ³ and R ⁵ together form a group of the general formula-(CH
_{2) p} -. (Wherein, p is a carboxylic acid derivative which is a starting compound of the present invention compounds when exhibiting no indicating) 1 to 3 (AI) is prepared in the following manner.

[Method G]

[0094]

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In the above formula, R ¹ , R ² and R ³ have the same meaning as described above, and R ⁷ represents the above “lower alkyl group”;
R ⁸ represents the “lower alkyl group” or the “optionally substituted aryl group”.

The step G-1 includes the step of ketone compound (CII)
I) and a Honer reagent (GI) [for example, the well-known Arbuzov
Produced by reaction. Is reacted in the presence of a base in a solvent to produce compound (GII). The base to be used is not particularly limited as long as it is used as a base in a usual reaction.
Alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and barium hydroxide, and 1,5-diazabicyclo [ 4.3.0] Nona-5-ene, 1,4-diazabicyclo [2.2.2] octane,
Examples thereof include organic bases such as 8-diazabicyclo [5.4.0] undec-7-ene (DBU) and organic metal bases such as butyllithium and lithium diisopropylamide. The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably an aromatic hydrocarbon such as benzene, toluene, or xylene; And ethers such as tetrahydrofuran, dioxane and dimethoxyethane; amides such as dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide; and sulfoxides such as dimethylsulfoxide.

In the step G-2 , the protecting group R ⁷ for the carboxylic acid of the compound (GII) is removed, and the starting compound (GI
II). Removal of the protecting group is generally accomplished by treatment with an acid or base by methods well known in the art. As the acid, hydrochloric acid, sulfuric acid, phosphoric acid, or hydrobromic acid is used, and the base is not particularly limited as long as it does not affect the other parts of the compound. It is carried out using an alkali metal carbonate such as potassium; an alkali metal hydroxide such as sodium hydroxide, potassium hydroxide or concentrated ammonia-methanol. The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction. Water or water and methanol, ethanol,
Preferred is a mixed solvent with an organic solvent such as alcohols such as toluene, n-propanol or ethers such as tetrahydrofuran and dioxane. The reaction temperature and the reaction time vary depending on the starting material, the base used, and the like, and are not particularly limited.
Time. The product is obtained as a mixture of geometrical isomers. At each stage of Step G-1 or Step G-2, by using chromatography or the like according to a conventional method,
The (E) -form and the (Z) -form can each be isolated.

The starting compound (CIII) is, for example,
A compound having the formula R ¹ -CHO (wherein R ¹ has the same meaning as described above) and a compound having the formula R ² -MgZ (wherein
R ² has the same meaning as described above, and Z represents a halogen atom. )
Or a compound having the formula R ² -Li (wherein, R ² is. Which as defined above) is reacted with a, or formula R ² -C
Compounds having HO (wherein, R ² is. Which as defined above) and a compound having the formula R ¹ -MgZ (wherein, R ¹ and Z are as defined above.) Or the formula R ¹ A compound having -Li (wherein R ¹ has the same meaning as described above), and then oxidizing the resulting alcohol compound to a carbonyl group according to a conventional method.

Further, utilizing the well-known Frydder-Crafts reaction, for example, a compound having the formula R ¹ -H (wherein R ¹ has the same meaning as described above) and a compound having the formula R ² -COZ ( Wherein R ² and Z have the same meanings as described above), or a compound having the formula R ² -H (wherein R ² has the same meanings as above) and a compound of the formula R ¹ -COZ. (Wherein, R ¹ and Z have the same meanings as described above).

[Method H]

[0101]

Embedded image

In the above formula, R ¹ , R ² and R ⁷ are as defined above, and R ^{3 ′} is a group other than a hydrogen atom in the definition of R ³ .

In the step preceding the step H-1 , the compound (HI)
Is treated according to Step C-2, and then the compound (C
III) to produce a starting compound (HIII).

The latter stage of the step H-1 is a step of treating the compound (HIII) prepared above according to the step C-3 to produce the starting compound (HIV) of the present invention.

In the step H-2 , the compound (CIII) and the compound (HV) were activated in the presence of a solvent according to the method of Kameya et al. (Pharmaceutical Magazine, Vol. 88, p. 911 (1968)). Using a zinc powder, a Reformat Matte-Ski reaction is carried out, and the obtained hydroxyester is subjected to dehydration and hydrolysis in the same manner as in Step H-1 to give the starting compound (HI
V) separately. In the previous step,
The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but is preferably hexane, heptane, ligroin, aliphatic hydrocarbons such as petroleum ether or Benzene, toluene, and aromatic hydrocarbons such as xylene,
More preferably, they are aromatic hydrocarbons. Reaction temperature is 0
C. to the boiling point, preferably from 80.degree.
0 ° C. The reaction time varies depending mainly on the reaction temperature, the starting compound and the kind of the solvent used, but is usually 1 to 24 hours, preferably 2 to 6 hours.

[Method I]

[0107]

Embedded image

In the above formula, R ¹ , R ³ and R ⁷ are as defined above, and R ^{2 ′} is the same as the “group having the formula —R ⁶ ” in the definition of R ² .

In the step I-1 , the compound (II) and a compound having the formula R ^{2 ′} -Y (wherein R ^{2 ′} and Y have the same meanings as described above) are obtained by the Heck reaction. After reacting according to Step D-2, the protecting group R ⁷ of the carboxylic acid is replaced with G-
This is a step of producing the starting compound (III) of the present application by removing the compound according to two steps.

The starting compound (II) has the formula R ¹ -CHO
Wherein R ¹ is as defined above.
Can be produced according to [Method G] or [Method H].

[J method]

[0112]

Embedded image

In the above formula, R ¹ , R ² , R ⁷ and Z are as defined above.

Step J-1 is a step of converting the compound (JI) to produce the starting compound (JII) of the present invention.

[0115] R ² is to indicate R ^{2 ',} the compound (J
I) and a compound having the formula R ^{2 ′} -MgZ (wherein R ^{2 ′} and Z have the same meanings as described above) in a solvent such as bis (diphenylphosphino) ethane nickel (II) chloride After reacting in the presence of such a divalent nickel complex,
The protecting group R ⁷ of the carboxylic acid is removed according to Step G-2 to produce the starting compound (JII) of the present application. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent.
Examples thereof include aromatic hydrocarbons such as benzene, toluene, and xylene, and ethers such as ether, tetrahydrofuran, dioxane, and dimethoxyethane.

When R ² represents a group other than R ^{2 ′} , a compound (JI) and a compound having the formula R ⁶ —CH = CH ₂ (wherein
R ⁶ has the same meaning as described above. Or a compound having the formula R ⁶ -C≡CH (wherein R ⁶ has the same meaning as described above) in a solvent, for example, a palladium complex such as bis (triphenylphosphine) palladium (II) chloride after reacting in the presence of, by removing the protecting group R ⁷ of the carboxylic acid, the starting compound of the present application (JII) is produced. In the former reaction, it may be preferable to carry out the reaction in the presence of an organic base such as triethylamine. The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, Halogenated hydrocarbons such as chloroform; ethers such as ether, tetrahydrofuran, dioxane, dimethoxyethane; amides such as dimethylformamide, dimethylacetamide, hexamethylphosphorotriamide or dimethylsulfoxide Sulfoxides can be mentioned.

The starting compound (JI) is obtained by adding a halogen atom such as chlorine or bromide to the compound in which R ³ is a hydrogen atom in the compound (II), and then adding hydrogen chloride or hydrogen bromide. It can be produced by desorbing hydrogen isomers to form a triple bond and further adding hydrogen halide such as hydrogen bromide.

R ³ and R ⁵ are taken together to have the general formula-(CH
_{2) p} -. (Wherein, p is the starting compound of the present invention compounds when indicating the indicating) 1 to 3 (CI) is produced, for example, as follows.

The starting compound (CI) of the compound of the present invention
Are mostly new compounds, but m = 1, n =
Compounds with 2 and p = 1 are described in WO 88/0313.
No. 8 discloses the structural formula. However, there is no general production method and examples in this publication, and it is not clear whether or not it was actually produced, and a third party cannot perform additional synthesis.

[Method K]

[0121]

Embedded image

In the above formula, X, m, n and p are as defined above, R ⁹ is the above “lower alkyl group”,
¹⁰ is, for example, tetrahydropyran-2-yl, 3-bromotetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, 4-
Tetrahydropyranyl or tetrahydrothiopyranyl groups such as methoxytetrahydrothiopyran-4-yl; tetrahydrofuran-2-yl, tetrahydrothiofuran-2
Tetrahydrofuranyl or tetrahydrothiofuranyl groups such as -yl; tri-lower alkylsilyl groups such as trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl, triisopropylsilyl A silyl group such as a tri-lower alkylsilyl group substituted by one or two aryl groups such as diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl, and phenyldiisopropylsilyl; methoxymethyl, 1,1-dimethyl -1- Lower alkoxymethyl group such as methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, t-butoxymethyl, lower alkoxylated lower alkyl such as 2-methoxyethoxymethyl Kishimechiru group, 2,
Alkoxymethyl groups such as halogeno lower alkoxymethyl such as 2,2-trichloroethoxymethyl and bis (2-chloroethoxy) methyl; lower alkoxylated ethyl groups such as 1-ethoxyethyl and 1- (isopropoxy) ethyl; 2,
Substituted ethyl groups such as halogenated ethyl groups such as 2,2-trichloroethyl; benzyl, α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl A lower alkyl group substituted with 1 to 3 aryl groups, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl,
Aliquots with lower alkyl, lower alkoxy, halogen, cyano groups such as 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl, 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, methyl, piperonyl A protecting group for a hydroxyl group typified by an aralkyl group such as a lower alkyl group substituted with 1 to 3 aryl groups in which the aryl ring is substituted, and preferably include
Preferably, it is a tetrahydropyranyl or tetrahydrothiopyranyl group.

In the K-1 step , the carboxy group of, for example, a pyroglutamic acid or a pyro-2-aminoadipic acid derivative represented by the general formula (KI) is converted to a carboxy group by the method of Saijo et al.
m. Pharm. Bull., 5, 1449 (1980)] to produce an alcohol compound (KII).

The K-2 step includes a Mitsunobu reaction [Synthesis, 19
81 , 1], compound (KII) is reacted with phthalimide in the presence of an azodicarboxylic acid ester such as diethyl azodicarboxylate and a trivalent phosphorus compound such as triphenylphosphine to produce compound (KIII) This is the step of performing The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably aromatic hydrocarbons such as benzene, toluene, xylene and diethyl ether. And ethers such as diisopropyl ether, tetrahydrofuran and dioxane. Reaction temperature is 0
C. to 50.degree. C., preferably 10.degree.
5 ° C. The reaction time mainly depends on the reaction temperature, the starting compound,
Depending on the type of reaction reagent or solvent used,
Usually 15 minutes to 1 day.

In step K-3 , compound (KIII) is converted to
In this step, a compound (KV) is produced by reacting with a compound (KIV) in a solvent in the presence of a base to alkylate a nitrogen atom. The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent, but is preferably aromatic hydrocarbons such as benzene, toluene and xylene; diethyl ether And ethers such as diisopropyl ether, tetrahydrofuran, and dioxane; amides such as dimethylformamide, dimethylacetamide, and hexamethylphosphorotriamide; and sulfoxides such as dimethylsulfoxide and sulfolane. The base used is not particularly limited as long as it is used as a base in a usual reaction, but is preferably an alkali metal hydride such as lithium hydride, sodium hydride or potassium hydride; Inorganic bases such as alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and barium hydroxide, and organic metal bases such as butyllithium and lithium diisopropylamide can be mentioned. The reaction is carried out at a temperature of 0 ° C to 100 ° C, preferably at room temperature. The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of the solvent used, but is usually 1 to 24 hours.

In the K-4 step , the R ¹⁰ group and the phthaloyl group of the compound (KV) are removed in no particular order, and the compound (KV) is removed.
This is the step of manufacturing I). The removal of the R ¹⁰ group depends on its type, but is generally carried out as follows by methods well known in the art.

When a silyl group is used as a protecting group for a hydroxyl group, it is usually removed by treating with a compound which generates a fluorine anion such as tetrabutylammonium fluoride. The reaction solvent is not particularly limited as long as it does not inhibit the reaction, but ethers such as tetrahydrofuran and dioxane are preferable. The reaction temperature and reaction time are not particularly limited, but the reaction is usually carried out at room temperature for 10 to 18 hours.

When the protecting group for the hydroxyl group is an aralkyl group, it is usually removed by bringing it into contact with a reducing agent in a solvent, preferably by catalytic reduction at room temperature under a catalyst. A method or a method of removing using an oxidizing agent is preferred. The solvent used in the removal by catalytic reduction is not particularly limited as long as it does not participate in the reaction, but alcohols such as methanol, ethanol, and isopropanol, diethyl ether, Ethers such as tetrahydrofuran and dioxane, toluene,
Aromatic hydrocarbons such as benzene and xylene; aliphatic hydrocarbons such as hexane and cyclohexane; esters such as ethyl acetate and propyl acetate; fatty acids such as acetic acid; Mixed solvents are preferred. The catalyst to be used is not particularly limited as long as it is usually used in a catalytic reduction reaction, but is preferably palladium carbon, Raney-nickel, platinum oxide, platinum black, rhodium-aluminum oxide, Phenylphosphine-rhodium chloride and palladium-barium sulfate are used. The pressure is not particularly limited, but it is usually 1 to 10 atm. The reaction temperature and the reaction time vary depending on the type of the starting material and the catalyst, but are usually 0 to 100 ° C.
For 5 minutes to 24 hours.

The solvent used in the removal by oxidation is not particularly limited as long as it does not participate in this reaction, but is preferably a water-containing organic solvent. Suitable examples of such organic solvents include ketones such as acetone, methylene chloride, chloroform, halogenated hydrocarbons such as carbon tetrachloride, nitriles such as acetonitrile, diethyl ether, tetrahydrofuran, and dioxane. And ethers, amides such as dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide, and sulfoxides such as dimethylsulfoxide. The oxidizing agent used is not particularly limited as long as it is a compound usually used for oxidation.Preferably, potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3-dichloro- 5,6-dicyano-p-benzoquinone (DDQ) is used. The reaction temperature and the reaction time vary depending on the type of the starting material and the catalyst, etc., but are usually from 0 to 150 ° C. for from 10 minutes to 24 hours.

Further, in liquid ammonia or methanol
In alcohols such as ethanol and ethanol, -78
It can also be removed by applying alkali metals such as metallic lithium and metallic sodium at a temperature of from -20 ° C to -20 ° C.

Further, it can be removed by using an aluminum silyl halide such as aluminum chloride-sodium iodide or trimethylsilyl iodide in a solvent. The solvent used is not particularly limited as long as it does not participate in the reaction, but is preferably a nitrile such as acetonitrile, a methylene chloride, a halogenated hydrocarbon such as chloroform, or a mixed solvent thereof. Is used. The reaction temperature and reaction time vary depending on the starting materials and the like, but are usually carried out at 0 to 50 ° C. for 5 minutes to 3 days.

When the reaction substrate has a sulfur atom,
Preferably, aluminum chloride-sodium iodide is used.

When the protecting group for the hydroxyl group is an alkoxymethyl group,
In the case of a tetrahydropyranyl group, a tetrahydrothiopyranyl group, a tetrahydrofuranyl group, a tetrahydrothiofuranyl group or a substituted ethyl group, they are usually treated with water or a lower alcohol in a solvent in the presence of an acidic catalyst. Removed by processing. The acidic catalyst to be used is not particularly limited as long as it is usually used as Bronsted acid, and is preferably an inorganic acid such as hydrochloric acid or sulfuric acid; or an organic acid such as acetic acid or p-toluenesulfonic acid. Alternatively, acid salts thereof such as pyridine salts of p-toluenesulfonic acid, but strongly acidic cation exchange resins such as Dowex 50W can also be used. The solvent used is not particularly limited as long as it is an organic solvent which does not participate in the present reaction and is miscible with water or a lower alcohol, and alcohols such as methanol and ethanol; dioxane;
Organic solvents such as acetone are preferred. The reaction temperature and reaction time vary depending on the starting material and the type of acid used, but are usually 0 to 100 ° C. and 1 to 48 hours.

Removal of the phthaloyl group can be achieved by treatment with a base in a solvent. The base to be used is not particularly limited as long as it is used as a base in a usual reaction, but preferably includes ammonia; hydrazine; and organic bases such as methylamine, ethylamine and butylamine. Can be. The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, but is preferably water; or methanol, ethanol, n-propanol, Isopropanol, n-butanol, isobutanol, t-butanol
And alcohols such as isoamyl alcohol or a mixed solvent thereof. Reaction temperature is 25 ° C to 120 ° C
The temperature is preferably 50 ° C. to 100 ° C. The reaction time varies depending mainly on the reaction temperature, the starting compound, the reaction reagent or the type of the solvent used, but is usually 1 to 48 hours.

In the K-6 step , the compound (KVI) is treated under the conditions of the Mitsunobu reaction described in the K-2 step and the ring is closed to produce (CI) which is a starting compound of the compound of the present invention. It is a process.

The compound (K
I) can be synthesized from the readily available glutamic acid or its homologous 2-aminoadipic acid because its (R) form and '(S) form can be synthesized from the compound (C).
I) can also be produced as each optically active substance.

After completion of the reaction in each of the above steps, the target compound is
It is collected from the reaction mixture according to a conventional method. For example, it can be obtained by appropriately neutralizing the reaction mixture, removing any insoluble matter by filtration, adding an organic solvent immiscible with water, washing with water, and distilling off the solvent. If necessary, the obtained target compound is subjected to a conventional method, for example, recrystallization,
It can be further purified by reprecipitation or chromatography.

[0138]

【The invention's effect】

[0139]

Test Example 1 Wistar Imodo rats (body weight: 350 to 450 g) anesthetized with inactin (90 mg / kg, intraperitoneally) were used as test animals for suppressing the blood pressure lowering effect of PAF . Blood pressure was continuously measured from the cannula inserted into the femoral artery, and the drug was intravenously injected through the cannula inserted into the femoral vein. First, 10 ng / kg of C ₁₆ -PAF was intravenously injected at intervals of 5 minutes, and was repeated until the magnitude of the antihypertensive reaction became constant. Next, the test drug was intravenously injected, and one minute later, the same dose of PAF was administered again. The test drug was administered cumulatively, and a 50% inhibitory dose (ID ₅₀ ) was determined from the inhibition rate of the PAF antihypertensive action, and used as an index of PAF antagonist activity. PAF is 0.
A saline solution containing 25% bovine serum albumin (BSA)
The test drug was dissolved in dimethylformamide before use. The results are shown below. ──────────────────────────────────── Test compound (Example No.) Antihypertensive ID ₅₀ (mg / kg) ──────────────────────────────────── 1 0.057 2 0.039 3 0.048 4 0.073 5 0.054 7 -1 0.014 7-2 0.058 7-9 0.022 7-10 0.074 7-11 0.0083 7-12 0.026 7-19 0.052 7-22 0.039 7-23 0.048 7-24 0.044 7-25 0.0067 7-27 0.0078 7-28 0.021 7-29 0.012 7-30 0.039 7-33 0.0080 7-35 0.0071 7-36 0.0050 7-37 0.0044 7-38 0.0075 7-39 0.0066 7-42 0.012 7-43 0.0080 7-46 0.0084 7-47 0.0074 7 -50 0.011 7-51 0.0033 7-52 0.0074 7-53 0.0097 7-54 0.0084 7-55 0.0055 7-56 0.0051 7-57 0.0092 7-58 0.0037 7 59 0.0073 7-61 0.0066 7-64 0.0065 7-66 0.013 7-68 0.011 7-69 0.0086 7-70 0.0061 7-71 0.015 22 0.011 23 0.092 25 0.028 28 0.049 29 0.071 30 0.062 Target compound (CV-3988) 0.42 ────────────────────────────────────

[0140]

[Test Example 2] PAF platelet aggregation inhibitory activity in vitro Blood was collected from a rabbit and immediately mixed with 1/9 volume of 3.8% sodium citrate. After centrifugation at 150 g for 15 minutes at room temperature, platelet-rich plasma (PRP) was obtained from the upper layer. The remaining blood was centrifuged at 1000 g for another 15 minutes, and platelet poor plasma (PP
P) was obtained. An appropriate amount of PRP and PPP were mixed to adjust the final platelet count of PRP to 600,000 per μl. Platelet aggregation was determined by the method of Born et al. (GVR Born, J. Physiol., 62, 67-
68 (1962)) using an aglycometer. 3 μl of a test drug in dimethyl sulfoxide was added to 272 μl of PRP, and 1 minute later, 25 μl of C
_16- PAF physiological saline (final concentration: 10 ^{-8 to} 3 × 10 ^-8 M) was added, and then observed for 5 minutes to observe the aggregation suppressing effect. The inhibition rate was determined based on the aggregation by PAF when dimethyl sulfoxide was used instead of the test solution.
IC ₅₀ was calculated. The results are shown below. ──────────────────────────────────── Test compound (Example No.) Platelet aggregation inhibitory IC ₅₀ (M ) １ 1 3.2 × 10 ^-7 2 2.0 × 10 ^-7 3 ^{2.2 × 10 -7 5 2.6 × 10} -7 7-1 2.8 × 10 -7 7-9 6.8 × 10 -8 7-11 6.3 × 10 -8 7-22 2.3 × 10 -7 7-23 1.8 × 10 - ⁷ 7-24 1.5 × 10 ^-7 7-25 4.4 × 10 ^-8 7-27 4.3 × 10 ^-8 7-29 1.1 × 10 ^-7 7-30 2.2 × 10 ^-7 7-31 1.1 × 10 ^-7 7 -34 1.1 × 10 ^-7 7-35 6.7 × 10 ^-8 7-39 3.9 × 10 ^-8 7-43 6.6 × 10 ^-8 7-46 3.0 × 10 ^-8 7-47 5.2 × 10 ^-8 7-51 3.0 × 10 ^-8 7-52 3.8 × 10 ^-8 7-54 8.6 × 10 ^-8 7-55 5.8 × 10 ^-8 7-56 9.9 × 10 ^-8 7-57 8.3 × 10 ^-8 7-58 2.6 × ^{10 -8 7-59 2.9 × 10 -8 7-64} 2.8 × 10 -8 7 ^{65 3.1 × 10 -8 7-66 9.9 ×} 10 -9 22 6.5 × 10 -8 25 3.0 × 10 -8 27 7.5 × 10 -9 control compounds (CV-3988) 9.8 × 10 -6 ────── ──────────────────────────────

[0141]

[Test Example 3] Inhibition of PAF receptor binding Heart blood was collected from rabbits, and immediately a 1/9 volume of 0.77 M EDTA •
Mix with 2 sodium solution. A platelet precipitate was obtained in substantially the same manner as in Test Example 2. Furthermore, the washed platelets were repeatedly freeze-thawed and disrupted, and then overlaid on top of two sucrose liquid layers of 0.25 M and 1.5 M. 4 ° C, 6
After centrifugation at 3,500 × g for 2 hours, the fraction collected at the interface between 0.25 M and 1.5 M sucrose was defined as the PAF receptor membrane fraction. The receptor binding experiment was performed according to the method of Huan et al. (San-BaoHwang e
t al., J.Biol.Chem., 260 , by approximately the same method as 15639-15645 (1985)), the specific binding of ³ H-PAF Whatman
It was measured using a GF / C filter. The compound was dissolved in dimethylsulfoxide, diluted 100-fold with a buffer containing 0.5% bovine serum albumin, and mixed so as to be 1/10 volume of the reaction solution of the receptor binding experiment. The binding inhibition rate (%) was plotted against the log of the compound concentration, and the 50% inhibitory concentration (IC ₅₀ ) was determined from a straight line connecting the points. The results are shown below. ──────────────────────────────────── Test compound (Example No.) Receptor binding inhibition IC ₅₀ ( M) ──────────────────────────────────── 1 4.7 × 10 ^-8 5 4.7 × 10 ^-8 7-9 4.3 × 10 ^-8 7-25 1.4 × 10 ^-8 7-35 1.7 × 10 ^-7 7-36 2.0 × 10 ^-8 7-37 1.3 × 10 ^-8 7-38 1.5 × 10 ^-8 7- 39 1.6 × 10 ^-8 7-43 2.1 × 10 ^-8 7-50 3.5 × 10 ^-8 7-53 2.6 × 10 ^-8 7-56 2.3 × 10 ^-8 7-58 1.4 × 10 ^-8 7-65 3.2 × 10 ^-8 7-68 1.4 × 10 ^-8 7-69 4.0 × 10 ^-8 7-70 2.0 × 10 ^-8 22 7.6 × 10 ^-8 27 2.0 × 10 ^-8 29 5.6 × 10 ^-8 30 6.0 × 10 ^-8 Control compound (CV-3988) 1.6 × 10 ^-6 ────────────────────────────────────

[0142]

[Test Example 4] Acute toxicity test Male ddY mice (5 weeks after birth, 3 mice in each group) were treated with Example 2,
Oral administration of compound 7-1 or 7-9 (dose 300 mg / kg
)did. After one week, no death was observed in any of the administration groups.

As described above, the novel N- (3,3) of the present invention
3-Disubstituted acryloyl) piperazine derivatives have an excellent PAF antagonistic activity and are not toxic, and therefore various diseases in which PAF is considered to be involved, for example, endotoxin shock, anaphylactic shock, nephritis, myocardial infarction , Angina, asthma, psoriasis, gastric ulcer and the like.

The administration form of the compound (I) of the present invention includes
For example, oral administration by tablets, capsules, granules, powders, syrups and the like, or parenteral administration by injections, suppositories and the like can be mentioned. These formulations are:
It is manufactured by a known method using additives such as excipients, binders, disintegrants, lubricants, stabilizers, and flavoring agents. The amount used depends on symptoms, age, etc., but 0.001-100 mg / k / day
g body weight, preferably 0.2-50 mg / kg body weight per day, can be usually administered to an adult once or several times a day.

Hereinafter, the present invention will be described more specifically with reference to Examples, Reference Examples, and Production Examples.

[0146]

Example 1 1- (3-Phenylcinnamoyl) -4- (3,4,5-trimethoxy
Benzoyl) piperazine 3-phenylcinnamic acid (4.485 g) in methylene chloride (90 ml)
The solution was cooled to 0-5 ° C. and phosphorus pentachloride (4.164 g) was added. After stirring the reaction solution at room temperature for 1 hour, the solvent was distilled off. The residue was dissolved in toluene (50 ml), and the solvent was distilled off again. When the same operation was repeated once, 3-phenylcinnamic acid chloride was obtained as a white solid. This crude product was used immediately in the following reaction. 1- (3,4,5-trimethoxybenzoyl) piperazine (1.401
To a solution of g) in tetrahydrofuran (30 ml) was added sodium hydrogen carbonate (0.840 g) dissolved in water (15 ml). In this mixture, 3-phenylcinnamic acid chloride (1.214
g) was added in one portion and stirred at room temperature for 30 minutes. Methylene chloride (50 ml) was added to the reaction solution to carry out liquid separation, and the aqueous layer was extracted with methylene chloride. Combine the methylene chloride layers,
Washed sequentially with 10% hydrochloric acid, 5% aqueous sodium hydrogen carbonate solution and saturated saline. After drying over sodium sulfate, the solvent was evaporated and the oily residue (2.70 g) was subjected to silica gel flash chromatography. The fractions eluted with methylene chloride-methanol (100: 1) were collected and the title compound
(2.150 g) was obtained as a white powder. Recrystallization from ethyl acetate-hexane gave white needles (melting point: 148-150 ° C). NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.65-3.80 (8
H, m); 3.84 (6H, s); 3.85 (3H, s); 6.30 (1H, s); 6.52 (2H,
s); 7.2-7.5 (10H, m ) Mass spectrum (m / z):. 486 (M +); 291 (M + -C 10 H 11 O 4); 27
9 (M ⁺ -C ₁₅ H ₁₁ O); 207 (C ₁₅ H ₁₁ O); 195 (C ₁₀ H ₁₁ O ₄ ) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 158
5. Elemental analysis (as C ₂₉ H ₃₀ N ₂ O ₅ ) Calculated: C; 71.59, H; 6.21, N; 5.76. Found: C; 71.54, H; 6.44, N; 5.71.

[0147]

Example 2 1- [3,3-Bis (4-methoxyphenyl) acryloyl] -4-
(3,4,5-trimethoxybenzoyl) piperazine 3,3-bis (4-methoxyphenyl) acrylic acid (0.500 g)
The title compound (0.362 g) was obtained in the same manner as in Example 1.
Was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.70-3.75 (8
H, m); 3.82 (3H, s); 3.84 (3H, s); 3.85 (9H, s); 6.14 (1H,
. s); 6.54 (2H, s); 6.80-6.93 (4H, m); 7.18-7.30 (4H, m) Mass spectrum (m / z): 546 ( M +); 351 (M + -C 10 H ₁₁ O ₄ ); 27
^{_{9 (M + -C 17 H 15}} O 3); 267 (C 1 7 H 15 O 3); 195 (C 10 H 11 O 4) Infrared absorption spectrum _{ν max (CHCl 3) cm-} 1:. 1625, 160
5, 1585.

[0148]

Embodiment 31- [3,3-bis (4-chlorophenyl) acryloyl] -4-
(3,4,5-trimethoxybenzoyl) piperazine 3,3-bis (4-chlorophenyl) acrylic acid (0.500 g)
The title compound (0.938 g) was obtained in the same manner as in Example 1.
Obtained as a white powder. NMR spectrum (270MHz, CDCl_Three) δ ppm: 2.90-3.70 (8
H, m); 3.86 (9H, s); 6.32 (1H, s); 6.56 (2H, s); 7.15-7.4
0 (8H, m). Mass spectrum (m / z): 554 (M⁺); 359 (M⁺-C_TenH₁₁O_Four); 27
9 (M⁺-C₁₅H₉Cl_TwoO); 275 (C₁₅H₉Cl_TwoO); 195 (C_TenH₁₁O_Four). Infrared absorption spectrum ν_max (CHCl_Three) cm-1: 1630, 159
0.

[0149]

Example 4 1- [3,3-Bis (2-thienyl) acryloyl] -4- (3,4,5-
The title compound (0.719 g) was obtained as a white powder from 3,3-bis (2-thienyl) acrylic acid (0.500 g) in the same manner as in Example 1 from trimethoxybenzoyl) piperazine . NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.90-3.75 (8
H, m); 3.85 (9H, s); 6.34 (1H, s); 6.57 (2H, s); 7.02 (1H,
dd, J = 5.13,3.66Hz); 7.08 (1H, dd, J = 5.13,3.66Hz); 7.13
(1H, dd, J = 1.10,3.66Hz); 7.26 (1H, dd, J = 1.10,3.66Hz);
7.32 (1H, dd, J = 5.13,1.10Hz); 7.42 (1H, dd, J = 5.13,1.10H)
z). Mass spectrum (m / z): 498 (M ⁺ ); 30
3 (M ⁺ -C ₁₀ H ₁₁ O ₄ ); 279 (M ⁺ -C
_{11 H 7 OS 2); 219} (C 1 1 H 7 OS 2);
_{195 (C 10 H 11 O 4} ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1620, 15
85. Elemental analysis _{(C 25 H 26 N 2 O} 5 as S ₂₎ Calculated: C; 60.22, H; 5.26 , N; 5.62, S; 12.86 Found:. C; 60.34, H; 5.43, N; 5.59, S; 12.97.

[0150]

Embodiment 51- [Z-3-phenyl-3- (2-thienyl) acryloyl] -4-
(3,4,5-trimethoxybenzoyl) piperazine Z-3-phenyl-3- (2-thienyl) α obtained in Reference Example 1
Example 1 from crylic acid (melting point: 144-147 ° C, 0.480 g)
In the same manner as above, the title compound (0.703 g) was converted to a white powder.
I got it. NMR spectrum (270MHz, CDCl_Three) δ ppm: 2.70-3.75 (8
H, m); 3.84 (3H, s); 3.85 (6H, s); 6.41 (1H, s); 6.53 (2H,
s); 6.88 (1H, dd, J = 3.67,1.10Hz); 6.98 (1H, dd, J = 5.13,
3.30Hz); 7.30 (1H, dd, J = 5.13,1.10Hz); 7.40 (5H, s-lik
e) .Mass spectrum (m / z): 492 (M⁺); 297 (M⁺-C_TenH₁₁O_Four); 27
9 (M⁺-C₁₃H₉OS); 213 (C₁₃H₉OS); 195 (C_TenH₁₁O_Four). Infrared absorption spectrum ν_max (CHCl_Three) cm-1: 1620, 158
5. Elemental analysis value (C₂₇H₂₈N_TwoO_Five(As S) Calculated: C; 65.83, H; 5.73, N; 5.69, S; 6.51. Found: C; 65.68, H; 5.97, N; 5.79, S; 6.51.

[0151]

Embodiment 61- [E-3-phenyl-3- (4-pyridyl) acryloyl] -4-
(3,4,5-trimethoxybenzoyl) piperazine E-3-phenyl-3- (4-pyridyl) a obtained in Reference Example 3
Crylic acid (melting point: 239-241 ° C, 0.224 g) and triethyl alcohol
To a solution of min (0.28 ml) in methylene chloride (5 ml)
Methylene chloride (1 ml) of phenylphosphoric azide (0.330 g)
Solution and 1- (3,4,5-trimethoxybenzoyl) piperazine
(0.280 g), and the mixture was stirred at room temperature for 4 hours. Remove the reaction solution
Dilute with Tylene chloride (20 ml) and add 5% sodium bicarbonate
And a saturated aqueous solution of sodium chloride. Organic layer with sodium sulfate
After drying with a solvent and evaporating the solvent, 0.686 g of an oily residue was obtained.
Silica gel flash column chromatography
Was. Methylene chloride-Dissolve in methanol (100: 2-100: 3)
Collect the obtained fractions to give the title compound (0.419 g) in white.
Obtained as a powder. NMR spectrum (60MHz, CDCl_Three) δ ppm: 3.05-3.70 (8H,
m); 3.84 (9H, m); 6.50 (1H, s); 6.58 (2H, s); 7.10-7.68
(7H, m); 8.45-8.85 (2H, m) .Mass spectrum (m / z): 487 (M⁺); 292 (M⁺-C_TenH₁₁O_Four); 27
9 (M⁺-C₁₄H_TenNO); 208 (C_{1 Four}H_TenNO); 195 (C_TenH₁₁O_Four). Infrared absorption spectrum ν_max (CHCl_Three) cm-1: 1630.

[0152]

Example 7 N- (3,3, -bis-substituted phenyl) acryloyl-N- (3,4,5-to
Synthesis of (Limethoxybenzoyl ) -piperazine Derivatives The following compounds 7-1 to 7-72 were prepared according to the general methods described below in Reference Examples 4-1 to 4-174, 11, 14 and 15.
Was synthesized from the above compound.

[ General Synthesis Method ] 3,3-Disubstituted acrylic acid derivatives (Reference Examples 4-1 to 4-174, 11, 14 and 1)
5) 1.60 mmol and 0.67 ml (4.80 mmol) of triethylamine
To a solution of methylene chloride (7 ml) were sequentially added diphenylphosphoric azide (0.793 g, 2.88 mmol) and N- (3,4,5-trimethoxybenzoyl) piperazine (0.449 g, 1.60 mmol). After stirring the reaction mixture at room temperature for 3 hours, it was diluted with methylene chloride (20 ml). The solution was washed successively with a saturated aqueous solution of sodium hydrogen carbonate, 10% hydrochloric acid and water, dried, and the solvent was distilled off. The residue was subjected to medium pressure liquid chromatography using two Roper B columns connected in series. Elution with ethyl acetate removes less polar impurities followed by methylene chloride-methanol (100: 1-1
00: 2) to give the desired N- (3,3-disubstituted acryloyl) -N- (3,4,5-trimethoxybenzoyl) piperazine derivative in 50-99% yield. Was. When these compounds were amorphous solids, they were pulverized and dried, and when obtained as crystals, they were recrystallized from a suitable solvent to obtain samples to be used in biological tests.

[0154]

Embedded image

[0155]

Example 7-1 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, Configuration = E Material (Reference Example Number) = 4-3. Yield (%) = 78. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.70-3.70 (8
H, m), 3.81 (3H, s), 3.84 (9H, s), 3.90 (3H, s), 6.25 (1H,
s), 6.52 (2H, s), 6.76-6.88 (3H, m), 7.27-7.42 (5H, m). Mass spectrum (m / z): 546 (M ⁺ ), 351; 279; 267; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1515, 1460, 1420, 1330, 1130.

[0156]

Example 7-2 Compound of R ¹ = Ph, R ² = 3,4-di-CH ₃ OPh, configuration = Z Raw material (reference example number) = 4-4. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.85 (3H, s), 3.86 (9H, s), 3.92 (3H, s), 6.22 (1H,
s), 6.55 (2H, s), 6.80 (1H, dd, J = 8.30,1.46Hz), 6.86 (1
H, d, J = 8.30Hz), 6.86-6.88 (1H, m), 7.28-7.40 (5H, m) .Mass spectrum (m / z): 546 (M ⁺ ), 351; 279; 267; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 158
5, 1515, 1460, 1420, 1335, 1130.

[0157]

Example 7-3 Compound of R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, Configuration = E Material (Reference Example No.) = 4-7. Yield (%) = 74. Melting point (recrystallization solvent) = 166-168 ° C (CH ₂ Cl ₂ -Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.70-3.70 (8
H, m), 3.78 (3H, s), 3.846 (9H, s), 3.850 (3H, s), 3.87 (3
H, s), 6.26 (1H, s), 6.47 (2H, s), 6.53 (2H, s), 7.28-7.4
2 (5H, m). Mass spectrum (m / z): 576 (M ⁺ ), 381; 297; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1505, 1460, 1415, 1330, 1125.

[0158]

Example 7-4 Compound of R ¹ = Ph, R ² = 3,4,5-tri-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-8. Yield (%) = 79. Mp (recrystallization _{solvent) = 149-151 ℃ (CH 2 Cl} 2 -Et 2 O-hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.77 (6H, s), 3.85 (3H, s), 3.86 (6H, s), 3.89 (3H,
s), 6.25 (1H, s), 6.53 (2H, s), 6.54 (2H, s), 7.28-7.40
(5H, m). Mass spectrum (m / z): 576 (M ⁺ ); 381; 297; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 1585,
1505, 1460, 1415, 1335, 1125.

[0159]

Example 7-5 Compound of R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, Configuration = E Raw Material (Reference Example Number) = 4-11. Yield (%) = 91. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.04 (3H, t, J =
7.32Hz), 1.88 (2H, m), 2.70-3.65 (8H, m), 3.79 (3H, s),
3.84 (6H, s), 3.85 (3H, s), 3.99 (2H, t, J = 6.83Hz), 6.24 (1
H, s), 6.53 (2H, s), 6.75-6.85 (3H, m), 7.27-7.43 (5H,
m) .Mass spectrum (m / z): 574 (M ⁺ ); 531; 379; 295; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1510, 1460, 1425, 1330, 1130.

[0160]

Example 7-6 Compound of R ¹ = Ph, R ² = 3-CH ₃ O-4-PrO-Ph, Configuration = Z Raw Material (Reference Example Number) = 4-12. Yield (%) = 91. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.06 (3H, t, J =
7.32Hz), 1.89 (2H, m), 2.80-3.70 (8H, m), 3.78 (3H, s),
3.85 (3H, s), 3.86 (6H, s), 4.00 (3H, t, J = 6.84Hz), 6.20 (1
H, s), 6.55 (2H, s), 6.78 (1H, dd, J = 8.30,1.46Hz), 6.85-
6.95 (2H, m), 7.27-7.40 (5H, m). Mass spectrum (m / z): 574 (M ⁺ ); 531; 379; 295; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1630, 1600, 1590, 151
5, 1465, 1420, 1335, 113
0.

[0161]

Example 7-7 Compound of R ¹ = 3,4-di-PrOPh, R ² = Ph, Configuration = E Material (Reference Example Number) = 4-15. Yield (%) = 87. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.01 (3H, t, J =
7.33Hz), 1.05 (3H, t, J = 7.33Hz), 1.85 (4H, m), 2.70-3.7
0 (8H, m), 3.84 (6H, s), 3.85 (3H, s), 3.88 (2H, t, J = 6.83H
z), 3.97 (2H, t, J = 6.84Hz), 6.23 (1H, s), 6.53 (2H, s),
6.80 (3H, s), 7.25-7.40 (5H, m) .Mass spectrum (m / z): 602 (M ⁺ ); 559; 517; 407; 323;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1590, 1510, 1460, 1425, 1330, 1130.

[0162]

Example 7-8 Compound of R ¹ = Ph, R ² = 3,4-di-PrOPh, Configuration = Z Raw Material (Reference Example Number) = 4-16. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.01 (3H, t, J =
7.32Hz), 1.06 (3H, t, J = 7.32Hz), 1.70-1.95 (4H, m), 2.7
0-3.70 (8H, m), 3.85 (9H, s), 3.85-3.92 (2H, m), 3.99 (2H, m)
H, t, J = 6.84Hz), 6.19 (1H, m), 6.55 (2H, s), 6.75-6.90 (3
H, m), 7.28-7.40 (5H, m) .Mass spectrum (m / z): 602 (M ⁺ ); 559; 517; 407; 323;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1510, 1460, 1420, 1330, 1130.

[0163]

Example 7-9 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-Cl-Ph, Configuration = E Material (Reference Example Number) = 4-19. Yield (%) = 89. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 3.90 (3H, s), 6.28 (1H,
s), 6.56 (2H, s), 6.75 (1H, br.s), 6.81 (2H, br.s), 7.20-
7.38 (4H, m, AB type). Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1510, 1460, 1420, 1330, 1130.

[0164]

Example 7-10 Compound of R ¹ = 4-ClPh, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-20. Yield (%) = 71. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.80 (3H, s), 3.86 (9H, s), 3.92 (3H, s), 6.20 (1H,
s), 6.55 (2H, s), 6.78 (1H, dd, J = 8.25,1.95Hz), 6.86 (1
H, d, J = 8.25Hz), 6.81-6.87 (1H, m), 7.20-7.36 (4H, m, AB
Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1635, 159
5, 1515, 1465, 1425, 1335, 1135.

[0165]

Example 7-11 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-23. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 3.90 (3H, s), 6.29 (1H,
s), 6.57 (2H, s), 6.77 (1H, br.s), 6.82 (2H, m), 7.15-7.
. 43 (4H, m) Mass spectrum (m / z): 580 ( M +, 35 Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1515, 1460, 1420, 1330, 1130.

[0166]

Example 7-12 Compound of R ¹ = 3-ClPh, R ² = 3,4-di-CH ₃ OPh, Configuration = E Material (Reference Example Number) = 4-24. Yield (%) = 90. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 3.92 (3H, s), 6.22 (1H,
s), 6.55 (2H, s), 6.78 (1H, dd, J = 8.30,1.95Hz), 6.85 (1H
. H, m), 6.87 ( 1H, d, J = 8.30Hz), 7.13-7.38 (4H, m) Mass spectrum (m / z): 580 ( M +, 35 Cl); 385; 301; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1515, 1460, 1420, 1330, 1260, 1130.

[0167]

Example 7-13 Compound of R ¹ = 2,3-di-CH ₃ OPh, R ² = 4-ClPh, Configuration = E Raw Material (Reference Example Number) = 4-27. Yield (%) = 85. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.57 (3H, s), 3.86 (9H, s), 3.87 (3H, s), 6.17 (1H,
s), 6.55 (2H, s), 6.75 (1H, dd, J = 7.81,1.46Hz), 6.93 (1
H, dd, J = 8.30,1.46Hz), 7.04 (1H, t, J = 8.30Hz), 7.25 (2H,
. dm, J = 8.79Hz), 7.29 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 580 ( M +, 35 Cl); 549; 301; 195. Infrared absorption spectrum [nu _max ( CHCl ₃ ) cm
-1: 1635, 1595, 1470, 143
0, 1335, 1135.

[0168]

Example 7-14 Compound of R ¹ = 4-ClPh, R ² = 2,3-di-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-28. Yield (%) = 94. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.90-3.70 (8
H, m), 3.855 (9H, s), 3.859 (6H, s), 6.38 (1H, s), 6.57 (2
H, s), 6.86 (1H, dd, J = 8.30,1.47Hz), 6.96 (1H, dd, J = 8.3
0,1.47Hz), 7.07 (1H, t, J = 8.30Hz), 7.20 (2H, dm, J = 8.79H
z), 7.29 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 580 (M ⁺ , ³⁵ Cl); 549; 301; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 1630, 158
5, 1460, 1420, 1330, 1125.

[0169]

Example 7-15 Compound of R ¹ = 4-i-BuOPh, R ² = 4-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-31. Yield (%) = 75. Melting point (recrystallization solvent) = 122-124 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.03 (6H, d, J =
6.83Hz), 2.09 (1H, m), 2.80-3.65 (8H, m), 3.73 (2H, d, J =
6.34Hz), 3.86 (9H, s), 6.26 (1H, s), 6.56 (2H, s), 6.84 (2
H, dm, J = 8.30Hz), 7.17 (2H, dm, J = 8.30Hz), 7.22 (2H, dm, J
= 8.30Hz), 7.34 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 592 (M ⁺ , ³⁵ Cl); 535; 397; 313;
279; 257; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1590, 1510, 1460, 1425, 1330, 1175, 1130.

[0170]

Example 7-16 Compound of R ¹ = 4-ClPh, R ² = 4-i-BuOPh, Configuration = E Raw Material (Reference Example Number) = 4-32. Yield (%) = 59. Melting point (recrystallization solvent) = 128-129 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.04 (6H, d, J =
6.84Hz), 2.10 (1H, m), 2.70-3.65 (8H, m), 3.75 (2H, d, J =
6.35Hz), 3.84 (6H, s), 3.85 (3H, s), 6.18 (1H, s), 6.54 (2
H, s), 6.88 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79Hz),
7.21 (2H, dm, J = 8.30Hz), 7.30 (2H, dm, J = 8.30Hz) Mass spectrum (m / z):. 592 (M +, 35 Cl); 535; 397; 313;
279; 257; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1490, 1460, 1425, 1330, 1285, 1175,
1130.

[0171]

Example 7-17 Compound of R ¹ = 4-PrOPh, R ² = 4-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-35. Yield (%) = 76. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.04 (3H, t, J =
7.32Hz), 1.75-1.90 (2H, m), 2.80-3.65 (8H, m), 3.86 (9
H, s), 3.93 (2H, t, J = 6.84Hz), 6.26 (1H, s), 6.56 (2H, s),
6.85 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79Hz), 7.22
. (2H, dm, J = 8.79Hz), 7.34 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 578 ( M +, 35 Cl); 535; 383; 299;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1425, 1330, 1130.

[0172]

Example 7-18 Compound of R ¹ = 4-ClPh, R ² = 4-PrOPh, Configuration = E Raw Material (Reference Example Number) = 4-36. Yield (%) = 74. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.06 (3H, t, J =
7.33Hz), 1.75-1.92 (2H, m), 2.80-3.70 (8H, m), 3.846 (6
H, s), 3.850 (3H, s), 6.18 (1H, s), 6.54 (2H, s), 6.88 (2
H, dm, J = 8.78Hz), 7.17 (2H, dm, J = 8.78Hz), 7.24 (2H, dm, J
= 8.30Hz), 7.30 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 535; 383; 299;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1130.

[0173]

Example 7-19 Compound of R ¹ = 4-FPh and R ² = 4-FPh Raw material = 3,3-bis (4-fluorophenyl) acrylic acid (known compound). Yield (%) = 76. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.70-3.70 (8
H, m), 3.85 (9H, s), 6.27 (1H, s), 6.56 (2H, s), 6.97-7.1
3 (4H, m), 7.20-7.33 (4H, m). Mass spectrum (m / z): 522 (M ⁺ ); 327; 279; 243; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 1630, 160
0, 1585, 1505, 1460, 1420, 1330, 1125.

[0174]

Example 7-20 Compound of R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, Configuration = E Raw Material (Reference Example Number) = 4-39. Yield (%) = 77. Melting point (recrystallization solvent) = 195-197 ° C (CH ₂ Cl ₂ -Et ₂ O-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.80-3.70 (8
H, m), 3.79 (6H, s), 3.86 (9H, s), 3.87 (3H, s), 6.27 (1H,
s), 6.45 (2H, s), 6.56 (2H, s), 7.05-7.13 (2H, m), 7.25-
7.33 (2H, m). Mass spectrum (m / z): 594 (M ⁺ ); 315; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1505, 1460, 1415, 1330, 1125.

[0175]

Example 7-21 Compound of R ¹ = 4-FPh, R ² = 3,4,5-tri-CH ₃ OPh, configuration = Z Raw material (Reference Example No.) = 4-40. Yield (%) = 78. Melting point (recrystallization solvent) = 130-132 ° C (CH ₂ Cl ₂ -Et ₂ O) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.80-3.70 (8
H, m), 3.77 (6H, s), 3.85 (3H, s), 3.86 (6H, s), 3.89 (3H,
s), 6.20 (1H, s), 6.51 (2H, s), 6.54 (2H, s), 7.00-7.09
(2H, m), 7.26-7.35 (2H, m). Mass spectrum (m / z): 594 (M ⁺ ); 315; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625 , 160
0, 1585, 1505, 1460, 1415, 1125.

[0176]

Example 7-22 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3,4-di-CH ₃ OPh Raw material = 3,3-bis (3,4-dimethoxyphenyl) acryl Acids (known compounds). Yield (%) = 74. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.82 (3H, s), 3.86 (9H, s), 3.91 (3H,
s), 3.92 (3H, s), 6.16 (1H, s), 6.56 (2H, s), 6.80-6.95
(6H, m). Mass spectrum (m / z): 606 (M ⁺ ); 411; 327; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1515, 1460, 1420, 1330, 1250, 1125.

[0177]

Example 7-23 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, Configuration = E Material (Reference Example Number) = 4-43. Yield (%) = 54. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.85 (12H, s), 3.90 (3H, s), 6.16 (1
H, s), 6.55 (2H, s), 6.76-6.85 (3H, m), 6.89 (2H, dm, J = 8.
78Hz), 7.22 (2H, dm, J = 8.78Hz). Mass spectrum (m / z): 576 (M ⁺ ); 381; 297; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625 , 160
0, 1585, 1510, 1460, 1420, 1330, 1130.

[0178]

Example 7-24 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-44. Yield (%) = 73. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.90-3.70 (8
H, m), 3.80 (3H, s), 3.83 (3H, s), 3.86 (9H, s), 3.92 (3H,
s), 6.15 (1H, s), 6.55 (2H, s), 6.78-6.91 (5H, m), 7.12-
7.26 (2H, m). Mass spectrum (m / z): 576 (M ⁺ ); 381; 297; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1585, 1510, 1460, 1420, 1330, 1130.

[0179]

Example 7-25 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3,4-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-47. Yield (%) = 85. Melting point (recrystallization solvent) = powder NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.10-3.70 (8
H, m), 3.83 (3H, s), 3.857 (3H, s), 3.861 (6H, s), 6.32 (1
H, s), 6.58 (2H, s), 6.87 (2H, dm, J = 8.79Hz), 7.13 (1H, d
d, J = 8.30,1.95Hz), 7.18 (2H, dm, J = 8.79Hz), 7.36 (1H, d,
. J = 1.95Hz), 7.45 ( 1H, d, J = 8.30Hz) Mass spectrum (m / z): 584 ( M +, 35 Cl); 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1125.

[0180]

Example 7-26 Compound of R ¹ = 3,4-di-ClPh, R ² = 4-CH ₃ OPh, Configuration = E Material (Reference Example Number) = 4-48. Yield (%) = 84. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.85 (12H, s), 6.21 (1H, s), 6.54 (2H, s), 6.90 (2
H, dm, J = 8.79Hz), 7.10 (1H, dd, J = 8.30,1.95Hz), 7.18 (2
H, dm, J = 8.79Hz), 7.38 (1H, d, J = 1.95Hz), 7.40 (1H, d, J =
8.30Hz). Mass spectrum (m / z): 584 (M ⁺ , ³⁵ Cl); 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1130.

[0181]

Example 7-27 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CF ₃ Ph, Configuration = E Material (Reference Example Number) = 4-51. Yield (%) = 74. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.90-3.70 (8
H, m), 3.82 (3H, s), 3.848 (6H, s), 3.853 (3H, s), 3.91 (3
H, s), 6.37 (1H, s), 6.56 (2H, s), 6.77 (1H, br.s), 6.79-
6.88 (2H, m), 7.47-7.60 (3H, m), 7.60-7.71 (1H, m). Mass spectrum (m / z): 614 (M ⁺ ); 419; 335; 307; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1625, 1600, 1585, 151
0, 1460, 1420, 1325, 130
0, 1170, 1125.

[0182]

Example 7-28 Compound of R ¹ = 3-CF ₃ Ph, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-52. Yield (%) = 50. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.81 (3H, s), 3.85 (3H, s), 3.86 (6H, s), 3.93 (3H,
s), 6.26 (1H, s), 6.56 (2H, s), 6.78 (1H, dd, J = 8.30,1.96
Hz), 6.86 (1H, m), 6.87 (1H, d, J = 8.30Hz), 7.43-7.53 (2
H, m), 7.53-7.67 (2H, m) .Mass spectrum (m / z): 614 (M ⁺ ); 419; 335; 307; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1515, 1460, 1420, 1325, 1255, 1165, 1125.

[0183]

Example 7-29 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, Configuration = E Material (Reference Example Number) = 4-55. Yield (%) = 89. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.39 (3H, s),
2.80-3.70 (8H, m), 3.81 (3H, s), 3.848 (6H, s), 3.851 (3
H, s), 3.89 (3H, s), 6.20 (1H, s), 6.54 (2H, s), 6.79 (1H,
br.s), 6.80-6.90 (2H, m), 7.17 (4H, s) .Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption spectrum ν _max ( CHCl ₃ ) cm-1: 1620, 160
0, 1585, 1510, 1460, 1420, 1330, 1125.

[0184]

Example 7-30 Compound of R ¹ = 4-CH ₃ Ph, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-56. Yield (%) = 99. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.37 (3H, s),
2.80-3.70 (8H, m), 3.80 (3H, s), 3.85 (3H, s), 3.86 (6H,
s), 3.91 (3H, s), 6.19 (1H, s), 6.55 (2H, s), 6.80 (1H, d
d, J = 8.30,1.46Hz), 6.84 (1H, m), 6.85 (1H, d, J = 8.30Hz),
7.14 (2H, d, J = 8.30Hz), 7.19 (2H, d, J = 8.30Hz). Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 158
5, 1510, 1460, 1420, 1330, 1255, 1125.

[0185]

Example 7-31 Compound of R ¹ = 3-CH ₃ Ph, R ² = 3,4-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-59. Yield (%) = 91. Melting point (recrystallization solvent) = powder NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
2.90-3.70 (8H, m), 3.857 (3H, s), 3.862 (6H, s), 6.36 (1
H, s), 6.58 (2H, s), 7.00-7.07 (2H, m), 7.13 (1H, dd, J = 8.
30Hz), 7.16-7.28 (2H, m), 7.36 (1H, d, J = 1.96Hz), 7.45
(1H, d, J = 8.30Hz). Mass spectrum (m / z): 568 (M ⁺ , ³⁵ Cl); 373; 289; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1635, 159
0, 1465, 1425, 1335, 1130.

[0186]

Example 7-32 Compound of R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, Configuration = E Material (Reference Example Number) = 4-60. Yield (%) = 92. Melting point (recrystallization solvent) = powder NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.35 (3H, s),
2.70-3.70 (8H, m), 3.84 (6H, s), 3.85 (3H, s), 6.27 (1H,
s), 6.53 (2H, s), 7.02-7.14 (3H, m), 7.18-7.32 (2H, m),
. 7.36-7.44 (3H, m) mass spectrum (m / z): 568 ( M +, 35 Cl); 373; 289; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1465, 1425, 1335, 1130.

[0187]

Example 7-33 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, Configuration = E Material (Reference Example Number) = 4-63. Yield (%) = 83. Melting point (recrystallization solvent) = powder NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
2.70-3.70 (8H, m), 3.81 (3H, s), 3.846 (6H, s), 3.850 (3
H, s), 3.90 (3H, s), 6.21 (1H, s), 6.54 (2H, s), 6.76-6.8
8 (3H, m), 7.06-7.13 (2H, m), 7.16-7.30 (2H, m). Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1515, 1465, 1425, 1330, 1130.

[0188]

Example 7-34 Compound of R ¹ = 3-CH ₃ Ph, R ² = 3,4-di-CH ₃ OPh, Configuration = Z Raw Material (Reference Example Number) = 4-64. Yield (%) = 83. Melting point (recrystallization solvent) = powder NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
2.80-3.70 (8H, m), 3.80 (3H, s), 3.85 (3H, s), 3.86 (6H,
s), 3.92 (3H, s), 6.20 (1H, s), 6.55 (2H, s), 6.77-6.90
(3H, m), 7.06-7.28 (4H, m). Mass spectrum (m / z): 560 (M ⁺ ); 365; 281; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1630, 1600, 1590, 151
5, 1465, 1425, 1330, 126
0, 1130.

[0189]

Example 7-35 Compound of R ¹ = 3-ClPh, R ² = 3-ClPh Raw Material (Reference Example Number) = 11. Yield (%) = 86. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.86 (9H, s), 6.36 (1H, s), 6.56 (2H, s), 7.10-7.2
0 (2H, m), 7.27-7.43 (6H, m) Mass spectrum (m / z):. 554 (M +, 35 Cl); 359; 279; 275;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1460, 1420, 1330, 1130.

[0190]

Example 7-36 Compound of R ¹ = 4-CH ₃ OPh, R ² = 2-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-66. Yield (%) = 91. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.80 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 6.54 (1H, s), 6.58 (2H,
s), 6.85 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.79Hz), 7.
29-7.45 (4H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 515; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1685, 1510, 1460, 1420, 1330, 1175, 1130.

[0191]

Example 7-37 Compound of R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-69. Yield (%) = 81. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.78 (3H, s), 3.85 (9H, s), 6.35 (1H, s), 6.56 (2H,
. s), 6.56-6.94 (3H, m), 7.16-7.40 (5H, m) Mass spectrum (m / z): 550 ( M +, 35 Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1460, 1420, 1330, 1125.

[0192]

Example 7-38 Compound of R ¹ = 3-ClPh, R ² = 3-CH ₃ OPh, Configuration = E Material (Reference Example No.) = 4-70. Yield (%) = 82. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.77 (3H, s), 3.85 (9H, s), 6.29 (1H, s), 6.54 (2H,
s), 6.80-6.87 (2H, m), 6.90-6.97 (1H, m), 7.12-7.19 (1
. H, m), 7.22-7.37 ( 4H, m) Mass spectrum (m / z): 550 ( M +, 35 Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1585, 1460, 1420, 1330, 1125.

[0193]

Working Example 7-39 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-73. Yield (%) = 81. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.85 (9H, s), 6.28 (1H, s), 6.56 (2H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.19 (2H, dm, J = 8.79Hz), 7.
26-7.40 (4H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1625, 1605, 1585, 151
0, 1460, 1420, 1330, 112
5.

[0194]

Example 7-40 Compound of R ¹ = 3-ClPh, R ² = 4-CH ₃ OPh, configuration = E Material (Reference Example No.) = 4-74. Yield (%) = 82. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.85 (12H, s), 6.21 (2H, s), 6.55 (2H, s), 6.90 (2
H, dm, J = 8.79Hz), 7.20 (2H, dm, J = 8.79Hz), 7.12-7.36 (4
H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 355; 279; 271;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1510, 1460, 1420, 1330, 1125.

[0195]

Example 7-41 Compound of R ¹ = Ph, R ² = 2-Np, Configuration = Z Raw Material (Reference Example Number) = 14. Yield (%) = 94. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.50-3.70 (8
H, m), 3.77 (3H, s), 3.82 (6H, s), 6.39 (3H, s), 7.28-7.4
0 (6H, m), 7.46-7.57 (2H, m), 7.78-7.90 (4H, m) Mass spectrum (m / z):. 536 (M +, 35 Cl); 341; 279; 257;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1460, 1425, 1330, 1130.

[0196]

Example 7-42 Compound of R ¹ = 2-Np, R ² = Ph, Configuration = E Material (Reference Example Number) = 15. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.60-3.70 (8
H, m), 3.85 (9H, s), 6.44 (1H, s), 6.54 (2H, s), 7.30-7.5
. 4 (8H, m), 7.71 (1H, br.s), 7.74-7.88 (3H, m) mass spectrum (m / z): 536 ( M +, 35 Cl); 341; 279; 257;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1595, 1460, 1420, 1330, 1125.

[0197]

Working Example 7-43 Compound of R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-77. Yield (%) = 84. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.04 (3H, t, J =
7.32Hz), 1.73-1.90 (2H, m), 3.10-3.70 (8H, m), 3.86 (9
H, m), 3.93 (2H, t, J = 6.35Hz), 6.31 (1H, s), 6.58 (2H, s),
6.86 (2H, dm, J = 8.79Hz), 7.13 (1H, dd, J = 8.30,1.46Hz),
7.17 (2H, dm, J = 8.79Hz), 7.36 (1H, d, J = 1.46Hz), 7.45 (1
H, d, J = 8.30Hz). Mass spectrum (m / z): 612 (M ⁺ , ³⁵ Cl); 569; 417; 333;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1130.

[0198]

Example 7-44 Compound of R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, Configuration = E Material (Reference Example Number) = 4-81. Yield (%) = 93. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.47 (3H, t, J =
6.84Hz), 2.50-3.70 (8H, m), 3.80 (3H, s), 3.84 (9H, s),
4.11 (2H, q, J = 6.84Hz), 6.25 (1H, s), 6.53 (2H, s), 6.79 (1
H, br.s), 6.80 (2H, br.s), 7.27-7.34 (2H, m), 7.34-7.41
(3H, m). Mass spectrum (m / z): 560 (M ⁺ , ³⁵ Cl); 545; 365; 281;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
0, 1590, 1510, 1460, 1420, 1330, 1130.

[0199]

Working Example 7-45 Compound of R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, Configuration = E Material (Reference Example No.) = 4-85. Yield (%) = 79. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 0.98 (3H, t, J =
7.32Hz), 1.45-1.58 (2H, m), 1.75-1.90 (2H, m), 2.60-3.
70 (8H, m), 3.79 (3H, s), 3.84 (9H, s), 6.24 (1H, s), 6.53
(2H, s), 6.76-6.86 (3H, m), 7.26-7.34 (2H, m), 7.34-7.4
2 (3H, m). Mass spectrum (m / z): 588 (M ⁺ ); 545; 531; 393; 309;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1590, 1510, 1460, 1420, 1330, 1130.

[0200]

Working Example 7-46 Compound of R ¹ = 4-EtPh, R ² = 3,4-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-88. Yield (%) = 81. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.25 (3H, t, J =
7.32Hz), 2.67 (2H, q, J = 7.32Hz), 3.00-3.70 (8H, m), 3.8
6 (9H, m), 6.36 (1H, s), 6.58 (2H, S), 7.13 (1H, dd, J = 8.3
0,1.96Hz), 7.12-7.22 (4H, m), 7.36 (1H, d, J = 1.96Hz),
7.45 (1H, d, J = 8.30 Hz). Mass spectrum (m / z): 582 (M ⁺ , ³⁵ Cl); 387; 303; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1460, 1420, 1330, 1130.

[0201]

Working Example 7-47 Compound of R ¹ = 4-PrOPh, R ² = Ph, Configuration = E Raw Material (Reference Example Number) = 4-92. Yield (%) = 78. Mp (recrystallization solvent) = powder NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.03 (3H, t, J =
7Hz), 1.50-2.15 (2H, m), 2.80-3.70 (8H, m), 3.83 (9H, s),
3.84 (2H, t, J = 7Hz), 6.26 (1H, s), 6.56 (2H, s), 6.86 (2
H, dm, J = 9Hz), 7.24 (2H, dm, J = 9Hz), 7.25-7.60 (5H, m).

[0202]

Example 7-48 R ¹ = 3,4-methylenedioxy-Ph, R ² = Ph, configuration = E
Compound raw material (Reference Example No.) = 4-93. Yield (%) = 94. Mp (recrystallization solvent) = powder NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 2.60-3.70 (8
H, m), 3.84 (9H, s), 5.98 (2H, s), 6.23 (1H, s), 6.55 (2H,
s), 6.78 (3H, s), 7.20-7.60 (5H, m).

[0203]

Working Example 7-49 Compound of R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = 3-CH ₃ Ph, Configuration = E Material (Reference Example Number) = 4-97. Yield (%) = 69. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.04 (3H, t, J =
7.33Hz), 1.80-1.95 (2H, m), 2.34 (3H, s), 2.70-3.70 (8
H, m), 3.80 (3H, s), 3.85 (9H, s), 3.99 (2H, t, J = 6.84Hz),
6.21 (1H, s), 6.54 (2H, s), 6.80 (3H, br.s), 7.05-7.13
(2H, m), 7.16-7.30 (2H, m) .Mass spectrum (m / z): 588 (M ⁺ ); 545; 393; 309; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1630, 1600, 1590, 151
0, 1460, 1425, 1330, 126
0, 1130.

[0204]

Example 7-50 Compound of R ¹ = 3-CH ₃ Ph and R ² = 3-CH ₃ Ph Raw Material (Reference Example No.) = 4-100. Yield (%) = 82. Melting point (recrystallization solvent) = powder NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.34 (6H, s),
2.60-3.70 (8H, m), 3.84 (9H, s), 6.24 (1H, s), 6.54 (2H,
. s), 7.02-7.12 (4H, m), 7.13-7.29 (4H, m) Mass spectrum (m / z): 514 ( M +, 35 Cl); 319; 279; 235;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1460, 1425, 1330, 1130.

[0205]

Example 7-51 Compound of R ¹ = 3-PrOPh, R ² = 3-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-103. Yield (%) = 90. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.02 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 2.80-3.70 (8H, m), 3.86 (9
H, s), 3.89 (2H, t, J = 6.84Hz), 6.34 (1H, s), 6.56 (2H, s),
6.76-6.85 (2H, m), 6.87-6.94 (1H, m), 7.16-7.40 (5H, m
m). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 383; 299; 279;
257; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1460, 1420, 1330, 1125.

[0206]

Example 7-52 Compound of R ¹ = 4-PrOPh, R ² = 3-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-106. Yield (%) = 78. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.04 (3H, t, J =
7.32Hz), 1.75-1.90 (2H, m), 3.00-3.70 (8H, m), 3.85 (9
H, m), 3.95 (2H, t, J = 6.35Hz), 6.28 (1H, s), 6.56 (2H, s),
6.85 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.79Hz), 7.18-
7.22 (1H, m), 7.26-7.40 (3H, m) mass spectrum (m / z):. 578 (M +, 35 Cl); 535; 515; 383;
299; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1510, 1460, 1425, 1330, 1130.

[0207]

Example 7-53 Compound of R ¹ = 3-CH ₃ OPh, R ² = 2-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-109. Yield (%) = 77. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.70 (8
H, m), 3.78 (3H, s), 3.86 (9H, s), 6.58 (2H, s), 6.61 (1H,
s), 6.76-6.80 (1H, m), 6.80-6.91 (2H, m), 7.21-7.44 (5
H, m). Mass spectrum (m / z): 550 (M ⁺ , ³⁵ Cl); 515; 271; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1465, 1425, 1330, 1290, 1130.

[0208]

Working Example 7-54 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, Configuration = Z Raw Material (Reference Example Number) = 4-112. Yield (%) = 76. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.28 (1H, s), 6.57 (2H,
s), 6.87 (2H, dm, J = 8.79Hz), 7.20 (2H, dm, J = 8.79Hz), 7.
23-7.30 (2H, m), 7.40-7.46 (1H, m), 7.48-7.57 (1H, m). Mass spectrum (m / z): 594 (M ⁺ , ⁷⁹ Br);
399; 315; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 16
10, 1590, 1515, 1475, 1430, 1335, 1180, 1130.

[0209]

Example 7-55 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-FPh, Configuration = Z Raw Material (Reference Example Number) = 4-116. Yield (%) = 76. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.85 (9H, s), 6.28 (1H, s), 6.56 (2H,
s), 6.86 (2H, dm, J = 8.79Hz), 6.94-7.03 (1H, m), 7.04-7.
13 (2H, m), 7.20 (2H, dm, J = 8.79Hz), 7.35 (1H, ddd, J = 7.8
1,7.81,5.86Hz). Mass spectrum (m / z): 535 (M ⁺ ); 339; 279; 255; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1515, 1465, 1430, 1335, 1180, 1130.

[0210]

Example 7-56 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-CF ₃ Ph, Configuration = Z Raw Material (Reference Example Number) = 4-120. Yield (%) = 79. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.80-3.70 (8
H, m), 3.83 (3H, s), 3.846 (6H, s), 3.851 (3H, s), 6.36 (1
H, s), 6.56 (2H, s), 6.87 (2H, dm, J = 8.79Hz), 7.19 (2H, d
m, J = 8.79Hz), 7.45-7.58 (3H, m), 7.62-7.69 (1H, m). Mass spectrum (m / z): 584 (M ⁺ ); 516; 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1425, 1320, 1180, 1130.

[0211]

Example 7-57 Compound of R ¹ = 3-PrOPh, R ² = Ph, Configuration = E Raw Material (Reference Example Number) = 4-123. Yield (%) = 89. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.02 (3H, t, J =
7.32Hz), 1.70-1.90 (2H, m), 2.70-3.70 (8H, m), 3.84 (6
H, s), 3.85 (3H, s), 3.88 (2H, t, J = 6.35Hz), 6.30 (1H, s),
6.53 (2H, s), 6.78-6.94 (3H, m), 7.19-7.40 (6H, m). Mass spectrum (m / z): 544 (M ⁺ ); 515; 501; 349; 279;
265; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1460, 1425, 1330, 1280, 1130.

[0212]

Example 7-58 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-ClPh, Configuration = Z Raw Material (Reference Example No.) = 4-127. Yield (%) = 88. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.70 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.33 (1H, s), 6.59 (2H,
s), 6.88 (2H, dm, J = 8.78Hz), 7.17 (2H, d, J = 1.95Hz), 7.2
0 (2H, dm, J = 8.78Hz), 7.38 (1H, t, J = 1.95Hz) Mass spectrum (m / z):. 584 (M +, 35 Cl); 389; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1560, 1510, 1460, 1420, 1330, 1180, 1130.

[0213]

Example 7-59 Compound of R ¹ = 4-CH ₃ OPh, R ² = 2,4-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-130. Yield (%) = 93. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.80 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 6.59 (1H, s), 6.61 (2H,
s), 6.85 (2H, dm, J = 8.79Hz), 7.16 (2H, dm, J = 8.79Hz), 7.
25 (1H, d, J = 8.30Hz), 7.30 (1H, dd, J = 8.30,1,95Hz), 7.44
(1H, d, J = 1.95Hz). Mass spectrum (m / z): 584 (M ⁺ , ³⁵ Cl); 549; 305; 279;
195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1515, 1465, 1415, 1335, 1180, 1130.

[0214]

Example 7-60 Compound of R ¹ = 4-CH ₃ OPh, R ² = 2,6-di-ClPh, configuration = Z Raw material (Reference Example No.) = 4-132. Yield (%) = 85. Mp (recrystallization _{solvent) = 162-164 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.40-3.80 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 6.62 (2H, s), 6.78 (1H,
s), 6.87 (2H, dm, J = 6.83Hz), 7.20-7.30 (3H, m), 7.32-7.
42 (2H, m). Mass spectrum (m / z): 584 (M ⁺ ); 549; 305; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1180, 1130.

[0215]

Example 7-61 Compound of R ¹ = 4-CH ₃ OPh, R ² = 2,5-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-134. Yield (%) = 85. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.10-3.80 (8
H, m), 3.82 (3H, s), 3.86 (9H, s), 6.60 (1H, s), 6.61 (2H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.79Hz), 7.
. 26-7.38 (3H, m) mass spectrum (m / z): 584 ( M +, 35 Cl); 549; 533; 305;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1630, 1605, 1585, 151
0, 1460, 1420, 1330, 117
5, 1130.

[0216]

Example 7-62 Compound of R ¹ = 4-CH ₃ OPh, R ² = 2,3-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-136. Yield (%) = 89. Mp (recrystallization _{solvent) = 119-122 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.20-3.80 (8
H, m), 3.81 (3H, s), 3.86 (9H, s), 6.58 (1H, br.s), 6.60
(2H, s), 6.85 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79H
. z), 7.23-7.31 (2H, m), 7.46-7.53 (1H, m) mass spectrum (m / z): 584 ( M +, 35 Cl); 549; 305; 279;
179. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1280, 1175, 1130.

[0219]

Example 7-63 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-CH ₃ Ph, Configuration = Z Raw Material (Reference Example Number) = 4-139. Yield (%) = 75. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.29 (6H, s),
2.60-3.70 (8H, m), 3.82 (3H, s), 3.846 (6H, s), 3.850 (3
H, s), 6.17 (1H, s), 6.54 (2H, s), 6.85 (2H, dm, J = 8.79H
z), 6.88 (2H, br.s), 7.01 (1H, br.s), 7.21 (2H, dm, J = 8.7
9Hz). Mass spectrum (m / z): 544 (M ⁺ ); 349; 279; 265; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1590, 1505, 1460, 1425, 1330, 1175, 1130.

[0218]

Example 7-64 Compound of R ¹ = 4-C ₂ H ₅ -Ph, R ² = 3-Cl-Ph, Configuration = Z Raw Material (Reference Example Number) = 4-144. Yield (%) = 78. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.25 (3H, t, J =
7.81Hz), 2.67 (2H, q, J = 7.81Hz), 2.80-3.70 (8H, m), 3.8
5 (9H, s), 6.33 (1H, s), 6.56 (2H, s), 7.14-7.23 (5H, m),
7.25-7.29 (1H, m), 7.31 (1H, dd, J = 7.82,7.82Hz), 7.37 (1
H, ddd, J = 7.82,1.47,1.47Hz). Mass spectrum (m / z): 548 (M ⁺ ); 353; 279; 269; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1465, 1430, 1235, 1130, 985.

[0219]

Example 7-65 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-CF ₃ Ph, Configuration = Z Raw Material (Reference Example Number) = 4-147. Yield (%) = 77. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.20-3.70 (8
H, m), 3.84 (3H, s), 3.86 (9H, s), 6.28 (1H, s), 6.59 (2H,
s), 6.90 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.79Hz), 7.
70-7.74 (2H, m), 7.88-7.92 (1H, m). Mass spectrum (m / z): 652 (M ⁺ ); 457; 373; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 161
0, 1590, 1515, 1460, 1425, 1330, 1280, 1180, 1130.

[0220]

Working Example 7-66 Compound of R ¹ = 4-EtOPh, R ² = 3,5-di-ClPh, Configuration = Z Raw Material (Reference Example Number) = 4-151. Yield (%) = 82. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.43 (3H, t, J =
6.84Hz), 3.20-3.70 (8H, m), 3.86 (9H, s), 4.05 (2H, q, J =
6.84Hz), 6.33 (1H, s), 6.59 (2H, s), 6.86 (2H, dm, J = 8.79
Hz), 7.166 (2H, d, J = 1.95Hz), 7.167 (2H, dm, J = 8.79Hz),
7.38 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 598 (M ⁺ ); 403; 319; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 160
5, 1590, 1510, 1460, 1420, 1330, 1220, 1175, 1130.

[0221]

Example 7-67 Compound of R ¹ = 4-EtPh, R ² = 3,5-di-ClPh, Configuration = Z Raw Material (Reference Example No.) = 4-155. Yield (%) = 91. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.25 (3H, t, J =
7.32Hz), 2.67 (2H, q, J = 7.32Hz), 3.00-3.75 (8H, m), 3.8
6 (9H, s), 6.38 (1H, s), 6.59 (2H, s), 7.1O-7.26 (4H, m),
7.17 (2H, d, J = 1.95Hz), 7.38 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 582 (M ⁺ ); 387; 303; 279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1630, 159
0, 1560, 1460, 1425, 1330, 1220, 1130.

[0222]

Working Example 7-68 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3,5-di-FPh, Configuration = Z Raw Material (Reference Example Number) = 4-159. Yield (%) = 95. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.05-3.75 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.33 (1H, s), 6.59 (2H,
s), 6.77-6.91 (3H, m), 6.87 (2H, dm, J = 8.79Hz), 7.19 (2H
H, dm, J = 8.79 Hz). Mass spectrum (m / z): 552 (M ⁺ ); 357; 279; 273; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1625, 1610, 1595, 151
5, 1465, 1430, 1335, 118
0, 1130.

[0223]

Working Example 7-69 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-CNPh, Configuration = Z Raw Material (Reference Example Number) = 4-162. Yield (%) = 89. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.00-3.80 (8
H, m), 3.83 (3H, s), 3.86 (9H, s), 6.41 (1H, s), 6.59 (2H,
s), 6.88 (2H, dm, J = 8.79Hz), 7.16 (2H, dm, J = 8.79Hz), 7.
45-7.60 (3H, m), 7.62-7.72 (1H, m). Mass spectrum (m / z): 541 (M ⁺ ); 346; 279; 262; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2220, 162
5, 1605, 1585, 1510, 1460, 1420, 1330, 1175, 1125.

[0224]

Example 7-70 Compound of R ¹ = 4-EtOPh, R ² = 3-FPh, Configuration = Z Raw Material (Reference Example Number) = 4-165. Yield (%) = 94. Mp (recrystallization solvent) = powder NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.42 (3H, t, J =
6.83Hz), 2.70-3.70 (8H, m), 3.85 (9H, s), 4.05 (2H, q, J =
6.83Hz), 6.28 (1H, s), 6.56 (2H, s), 6.85 (2H, dm, J = 8.79
Hz), 6.93-7.03 (1H, m), 7.03-7.13 (2H, m), 7.19 (2H, dm,
J = 8.79Hz), 7.35 (1H, ddd, J = 7.81,7.81,5.86Hz). Mass spectrum (m / z): 548 (M ⁺ ); 533; 519; 353; 279;
269; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
5, 1585, 1505, 1460, 1420, 1330, 1170, 1125.

[0225]

Example 7-71 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-Cl-5-Me-Ph, Configuration = Z Raw Material (Reference Example Number) = 4-169. Yield (%) = 91. Melting point (recrystallization solvent) = powder NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.33 (3H, s),
2.70-3.70 (8H, m), 3.83 (3H, s), 3.86 (9H, s), 6.25 (1H,
s), 6.57 (2H, s), 6.86 (2H, dm, J = 8.79Hz), 6.93-7.11 (2
. H, m), 7.14-7.25 ( 1H, m), 7.20 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 564 ( M +, 35 Cl); 549; 369; 285;
279; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1625, 160
0, 1585, 1510, 1460, 1420, 1330, 1170, 1125.

[0226]

Example 7-72 Compound of R ¹ = 4-EtOPh, R ² = 3-Cl-5-Me-Ph, Configuration = Z Raw Material (Reference Example Number) = 4-173. Yield (%) = 92. Mp (recrystallization solvent) = powder NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.40 (3H, t, J =
7Hz), 2.32 (3H, s), 2.90-3.75 (8H, m), 3.85 (9H, s), 4.0
4 (2H, q, J = 7Hz), 6.26 (1H, s), 6.59 (2H, s), 6.80-7.40 (3
. H, m), 6.86 ( 2H, dm, J = 9Hz), 7.22 (2H, q, J = 9Hz) Mass Spectrum (m / z): 578 ( M +, 35 Cl); 563; 383; 299;
279; 195.

[0227]

Example 8 1- [E-3,5-diphenylpent-2-en-4-inoyl] -4
-(3,4,5-Trimethoxybenzoyl) -piperazine Using the compound of Reference Example 6 (0.900 g), and in the same manner as in Example 1, the title compound (1.574 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.40-4.00 (8
H, m); 3.83 (3H, s); 3.85 (6H, s); 6.59 (2H, s); 6.74 (1H,
s); 7.3-7.8 (10H, m). Mass spectrum (m / z): 510 (M ⁺ ); 315; 279; 231; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
^-1 : 1615, 1590, 1490, 146
0, 1420, 1330, 1125. Elemental analysis (calculated as C ₃₁ H ₃₀ N ₂ O ₅ ) Calculated: C; 72.97, H; 5.92, N; 5.49. Found: C; 72.65, H; 6.10, N; 5.45.

[0228]

Example 9 1-[(2E, 4Z) -3,5-diphenylpent-2,4-dienoyl]-
4- (3,4,5-trimethoxybenzoyl) piperazine 10% palladium-barium sulfate (0.025 g) and quinoline (2 drops) were added to a solution of the compound of Example 8 (0.250 g) in methanol (5 ml). Hydrogen gas was passed at room temperature and normal pressure. After reacting for 15 hours, the catalyst was filtered off and the solvent was distilled off. The residue was subjected to medium pressure liquid chromatography using a Roper B column to give methylene chloride-ethyl acetate (3: 2-1: 3).
The title compound (0.153 g) was obtained as a powder from the fraction eluted with. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.90-3.80 (8
H, m), 3.86 (3H, s), 3.87 (6H, s), 6.38 (1H, br.s), 6.58
(2H, s) 6.61 (1H, dd, J = 12.20,1.95Hz).

[0229]

Example 10 1- [3,3-bis (4-methoxyphenyl) -2-methylacrylo
Yl] -4- (3,4,5-trimethoxybenzoyl) piperazine Using the compound of Reference Example 9 (0.511 g), the title compound (0.673 g) was obtained as a powder in the same manner as in Example 7. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.00 (3H, s);
2.95-3.45 (8H, m); 3.80 (3H, s); 3.82 (3H, s); 3.846 (6H,
s); 3.851 (3H, s); 6.53 (2H, s); 6.75-7.20 (8H, m) .Mass spectrum (m / z): 560 (M ⁺ ); 545; 365; 281; 279;
195.

[0230]

Example 11 1- (3,3-diphenylacryloyl) -4- (3,4,5-trimethoate
(Xybenzenesulfonyl ) piperazine 3-phenylcinnamic acid (0.400 g) in methylene chloride (8 ml)
Phosphorus pentachloride (0.371 g) was added to the solution under ice cooling. 0-5
After stirring at C for 1 hour, the reaction solution was concentrated. Dry toluene (10 ml) was added to the residue, which was concentrated and dried. The residue was dissolved in tetrahydrofuran (5 ml), and the compound of Reference Example 10 (0.
564 g), sodium bicarbonate (0.300 g), tetrahydrofuran (15 ml) and water (7.5 ml). After stirring at room temperature for 30 minutes, the reaction solution was poured into water and extracted twice with methylene chloride. Wash the extract with 10% hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine, and dry.
Concentrated. The residue was subjected to column chromatography using silica gel (20 g). The title compound (0.750 g) was obtained as crystals from the fraction eluted with methylene chloride-ethyl acetate. Melting point: 163-165 ° C (ethyl acetate-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.17 (2H, t, J =
4.76Hz); 2.81 (2H, t, J = 4.76Hz); 3.35 (2H, t, J = 4.76Hz);
3.64 (2H, t, J = 4.76Hz); 3.92 (6H, s); 3.97 (3H, s); 6.21
(1H, s); 6.80 (2H, s); 7.00-7.40 (10H, m) .Mass spectrum (m / z): 522 (M ⁺ ); 458; 315; 291; 231;
207. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 159
5, 1500, 1460, 1410, 1350, 1315, 1155, 1130. Elemental analysis (as C ₂₈ H ₃₀ N ₂ O ₆ S) Calculated: C; 64.35, H; 5.79, N; 5.36, S; 6.14. Found: C; 64.60, H; 5.94, N; 5.35, S; 6.27.

[0231]

Example 12 1- (3-phenylcinnamoyl) -4- (3,4,5-trimethoxy
Thiobenzoyl) piperazine 3-phenylcinnamic acid (0.900 g) in methylene chloride (18 ml)
Phosphorus pentachloride (0.836 g) was added to the solution under ice-cooling, and 0-5 ° C
For 1 hour. After the reaction solution was concentrated and dried, dry toluene (20 ml) was added, and the concentration and drying were repeated. The residue was dissolved in tetrahydrofuran (5 ml), and 1- (3,4,5-trimethoxythiobenzoyl) piperazine (1.189 g), sodium hydrogencarbonate (0.674 g), tetrahydrofuran (25 m
l) and water (12.5 ml) were added under water cooling.
After stirring at room temperature for 30 minutes, the reaction solution was poured into water and extracted twice with methylene chloride. The extract was washed successively with 10% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and water, dried and concentrated. The residue was subjected to column chromatography using silica gel (40 g) to give methylene chloride-ethyl acetate.
The fractions eluted at (3: 1) were collected and the title compound (1.860
g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.84 (1H, br.
s); 3.23 (1H, br.s); 3.39 (1H, br.s); 3.51 (2H, br.s);
3.69 (1H, br.s); 3.76 (1H, br.s); 3.82,3.84 (9H, s × 2);
4.17 (1H, br.s); 6.27,6.33 (1H, s × 2); 6.37,6.44 (2H, s
× 2); 7.20-7.50 (10H, m) .Mass spectrum (m / z): 502 (M ⁺ ); 469; 335; 295; 211;
207; 178; 167. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 158
0, 1460, 1425, 1340, 1280, 1125.

[0232]

Example 13 1- [3,3-bis (4-methoxyphenyl) acryloyl] -4-
(3,4,5-trimethoxythiobenzoyl) piperazine 3,3-bis (4-methoxyphenyl) acrylic acid (0.400
g), and in the same manner as in Example 12, the title compound (0.59
6 g) was obtained as a yellow powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.96,3.23,3.
45,3.51,4.20 (8H, br.s × 5); 3.82 (6H, s); 3.85 (9H, s);
6.11,6.16 (1H, s × 2); 6.38,6.45 (2H, s × 2); 6.80-6.95
(4H, m); 7.10-7.30 (4H, m) .Mass spectrum (m / z): 562 (M ⁺ ); 529; 335; 295; 267;
227; 211. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
^-1 : 1625, 1605, 1585, 151
0, 1460, 1425, 1340, 128
0, 1170, 1125. Elemental analysis _{(C 31 H 34 N 2 O} 6 as _S) Calculated: C; 66.17, H; 6.09 , N; 4.98, S; 5.70 Found:. C; 65.92, H; 6.37, N; 4.84, S ; 5.65.

[0233]

Example 14 1- [3,3-Bis (4-fluorophenyl) -4- (3,4,5-trime
Toxithiobenzoyl) piperazine 3,3-bis (4-fluorophenyl) acrylic acid (0.300 g)
And the title compound (0.574) as in Example 12.
g) was obtained as a yellow powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.04,3.25,3.
52, 3.78, 4.21 (8H, br.s × 5); 3.84 (9H, s); 6.28 (1H, br.
s); 6.45 (2H, s); 6.95-7.35 (8H, m) .Mass spectrum (m / z): 538 (M ⁺ ); 505; 335; 295; 243;
211. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
0, 1580, 1505, 1460, 1425, 1340, 1125.

[0234]

Example 15 1- (3-phenylcinnamoyl) -4- (3,4,5-trimethoxy
Benzyl) piperazine 3-phenylcinnamic acid (0.500 g) and 1- (3,4,5-trimethoxybenzyl) piperazine (0.653 g) were used as in Example 12 to give the title compound (0.897 g). g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.88 (2H, t, J =
5.13Hz); 2.25 (2H, t, J = 5.13Hz); 3.28 (2H, m); 3.28 (2H,
s); 3.55 (2H, t, J = 5.13Hz), 3.83 (3H, s); 3.84 (6H, s);
6.30 (1H, s); 6.46 (2H, s); 7.13-7,47 (10H, m). Mass spectrum (m / z): 472 (M ⁺ ); 457; 291; 265; 207;
181. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 159
5, 1460, 1440, 1345, 1125.

[0235]

Example 16 1- (3,3-diphenylthioacryloyl) -4- (3,4,5-tri
Methoxythiobenzoyl) piperazine Compound of Example 12 (1.000 g) and Lawesson
A solution of the reagent (0.805 g) in benzene (10 ml) was heated under reflux for 2 hours. After cooling, pour the reaction mixture into water and add
Extracted times. The extract was washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (30 g). The fractions eluted with hexane-ethyl acetate (3: 1) were collected to give the title compound (1.010 g) as a yellow powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.86-4.45 (8
H, m); 3.82,3.84 (9H, s × 2); 6.36,6.37 (2H, s × 2); 6.6
6,6.69 (1H, s × 2); 7.15-7.50 (10H, m). Mass spectrum (m / z): 518 (M ⁺ ); 485; 351; 307. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1580, 147
5, 1425, 1340, 1285,1130.

[0236]

Example 17 1- [3,3-Bis (4-methoxyphenyl) thioacryloyl
-4- (3,4,5-Trimethoxybenzoyl) piperazine 3,3-bis (4-methoxyphenyl) acrylic acid (3.00 g) and triethylamine (2.94 ml) in methylene chloride (6.
0 ml) was added with diphenylphosphate azide (3.41 ml) and 1-formylpiperazine (1.09 ml), and the mixture was stirred at room temperature for 2 hours.
The reaction solution was poured into a saturated aqueous solution of sodium hydrogen carbonate, and extracted twice with methylene chloride. The extract was washed with water, dried and concentrated, and the residue was dissolved in methanol (80 ml). After adding a 10% aqueous sodium hydroxide solution (40 ml) and stirring at room temperature for 18 hours, the reaction solution was poured into water and extracted twice with methylene chloride. The extract was washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (80 g). The fractions eluted with methylene chloride-methanol (19: 1-4: 1) were collected and 1- [3,3-bis (4-methoxyphenyl)
Acryloyl] piperazine (3.00 g) was obtained as a powder. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 2.0
8 (1H, s); 2.20-3.65 (8H, m);
3.80 (6H, s); 6.13 (1H, s);
6.70-7.40 (8H, m). The above compound (1.155 g) and Lawesson's reagent (1.3
A solution of 26 g) in benzene (12 ml) was heated to reflux for 2 hours. After cooling, the reaction solution was poured into water and extracted twice with ethyl acetate. The extract was washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (30 g).
The fractions eluted with methylene chloride-methanol (19: 1) were collected to give 1- [3,3-bis (4-methoxyphenylthioacryloyl] piperazine (1.177 g) as a powder NMR spectrum (60 MHz) , CDCl ₃ ) δ ppm: 2.30 (2H, m);
2.80 (2H, m); 2.86 (1H, s); 3.48 (2H, m); 3.80 (6H, s); 4.
16 (2H, m); 6.50 (1H, s); 6.70-7.50 (8H, m). The above thioamide (1.049 g) and triethylamine
(0.29 ml) in methylene chloride (30 ml) solution under ice-cooling
3,4,5-Trimethoxybenzoyl chloride (0.157 g) was added. After stirring for 1 hour at room temperature, the reaction solution was poured into water,
Extracted twice with methylene chloride. The extract was washed sequentially with 10% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and water, dried and concentrated. The residue was subjected to column chromatography using silica gel (40 g) and medium pressure liquid chromatography using a Rover B column. Methylene chloride
The fractions eluted with ethyl acetate (9: 1-4: 1) were collected to give the title compound (1.368 g) as a yellow powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.75-3.30 (2
H, m); 3.40-3.70 (4H, m); 3.83,3.846,3.850 (15H, s × 3);
6.53,6.55 (3H, s × 2); 6.80-6.95 (4H, m); 7.15-7.35 (4H,
m). Mass spectrum (m / z): 562 (M ⁺ ); 529; 455; 367. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
5, 1585, 1510, 1460, 1420, 1330, 1280, 1170, 1125.

[0237]

Example 18 1- [3,3-bis (4-methoxyphenyl) thio
Oacryloyl] -4- (3,4,5-trimethoxythiobenzoi
G ) Piperazine Using the compound of Example 17 (0.790 g), in the same manner as in Example 16, the title compound (0.792 g) was obtained as a yellow powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.99,3.46,
3.56,3.72,4.27,4.37 (8H, br.s × 6); 3.82,3.83,3.85 (15
H, s × 3); 6.39,6.46 (2H, s × 2); 6.51,6.55 (1H, s × 2);
. 6.80-6.95 (4H, m); 7.10-7.37 (4H, m) Mass spectrum (m / z): 578 ( M +); 545; 513; 367. Infrared absorption spectrum ν _max (CHCl ₃₎ cm ^{- 1} : 1605, 158
0, 1510, 1460, 1425, 1335, 1280, 1170, 1125. Elemental analysis (as C ₃₁ H ₃₄ N ₂ O ₅ S ₂ ) Calculated: C; 69.34, H; 5.92, N; 4.84, S; 11.08 Found: C; 64.21, H; 6.19, N; 4.64, S; 10.98.

[0238]

Embodiment 191- [3,3-bis (3-chlorophenyl) acryloyl] -4-
(3,4-dimethoxybenzoyl) piperazine 3,4-dimethoxybenzoic acid (0.250 g) and triethyl alcohol
Diffusion in a solution of min (0.38 ml) in methylene chloride (10 ml)
Phenylphosphoryl azide (0.44 ml) and Reference Example 12
The compound (0.545 g) was added, and the mixture was stirred at room temperature for 16 hours. reaction
The solution was successively added with 10% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and
It was washed with water, dried and concentrated. The residue is applied to a Lobar-B column (2
Medium-pressure liquid chromatography using
Collect fractions eluted with sun-ethyl acetate (1: 2-1: 4)
The title compound (0.682 g) was obtained as a white powder. NMR spectrum (270MHz, CDCl_Three) δ ppm: 2.90-3.70 (8
H, m); 3.890 (3H, s); 3.90 (3H, s); 6.36 (1H, s); 6.85 (1
H, d, J = 7.81Hz); 6.92 (1H, dd, J = 7.81,1.47Hz); 6.95 (1H,
d, J = 1.47Hz); 7.10-7.20 (2H, m); 7.24-7.42 (6H, m). Mass spectrum (m / e): 524 (M⁺,³⁵Cl); 359; 275; 249;
165.

[0239]

Example 20 1- [3,3-Bis (3-chlorophenyl) acryloyl] -4- (4
-Methoxybenzoyl) piperazine The compound of Reference Example 12 (0.529 g) and triethylamine (0.4
1 ml) in methylene chloride (10 ml) under ice cooling.
-Methoxybenzoic acid chloride (0.250 g)
Stirred for hours. Hereinafter, operating in the same manner as in Example 19,
The title compound (0.682 g) was obtained as a powder. NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.90-3.70 (8
H, m); 3.83 (3H, s); 6.36 (1H, s); 6.90 (1H, dm, J = 8.79H
. z); 7.10-7.19 (2H, m); 7.24-7.42 (8H, m) Mass spectrum (m / e): 494 ( M +, 35 Cl); 359; 275; 219;
135. Elemental analysis _{(C 27 H 24 Cl 2 N} 2 as O ₃₎ Calculated: C; 65.46, H; 4.88 , N; 5.65, Cl; 14.31 Found:. C; 65.19, H; 5.12, N; 5.64, Cl; 14.55.

[0240]

Example 21 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (4-acetoxy-3,5-dimethoxyben
Zoyl) piperazine The compound of Reference Example 23 (0.600 g) and the compound of Reference Example 22
(0.936 g) and in the same manner as in Example 19, the desired compound (1.072 g) was obtained as a powder. Melting point: 191-194 ° C NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.34 (3H,
s); 2.70-3.70 (8H, m); 3.82 (6H, s); 3.83 (3H, s); 6.28
(1H, s); 6.58 (2H, s); 6.87 (2H, dm, J = 8.79Hz); 7.16-7.2
3 (3H, m); 7.32 (1H, dd, J = 7.32,7.32Hz); 7.37 (1H, ddd, J =
7.81,1.95,1.95Hz). Mass spectrum (m / z): 578 (M ⁺ , ³⁵ Cl); 536; 355; 307;
271; 181. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1770, 163
0, 1600, 1515, 1460, 1430, 1370, 1340, 1285, 1180,
1135.

[0241]

Example 22 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (3,5-dimethoxy-4-hydroxyben
(Zoyl) piperazine To a solution of the compound of Example 21 (0.500 g) in methanol (20 ml) was added a saturated aqueous potassium carbonate solution (10 ml), and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into water and extracted three times with methylene chloride. The extract was washed with water, dried and concentrated.
The residue was subjected to medium pressure liquid chromatography using two R-B columns. Ethyl acetate-methanol (19:
The fractions eluted in 1) were collected to obtain the desired compound (0.464 g) as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.00-3.70
(8H, m); 3.83 (3H, s); 3.89 (6H, s); 5.72 (1H, s); 6.29 (1
H, s); 6.61 (2H, s); 6.87 (2H, dm, J = 9.27Hz); 7.16-7.23
(3H, m); 7.31 (1H, dd, J = 8.30,8.30Hz); 7.37 (1H, ddd, J =
8.30,1.95,1.95Hz). Mass spectrum (m / z): 536 (M ⁺ ); 356; 355; 271; 265;
181. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3550, 163
0, 1605, 1510, 1460, 1420, 1365, 1330, 1280, 1180,
1115, 980, 830.

[0242]

Example 23 1- [Z-3- (4-methoxyphenyl) -3- (3-trifluoromethyl
Ruphenyl) acryloyl] -4- (3,4,5-trimethoxybe
Condensation reaction of compound (0.516 g) of 1- (3,4,5-trimethoxybenzoyl) homopiperazine (0.471 mg) and the reaction product thereof (nzoyl ) hexahydro-1H-1,4-diazepine Was produced in the same manner as in Example 7 to obtain the desired compound (0.819 g) as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.60-2.10
(2H, m); 3.20-3.80 (8H, m); 3.82 (3H, s); 3.83 (3H, s);
3.85 (3H, s); 3.86 (3H, s); 6.46 (1H, br.s); 6.55 (2H, s);
6.81-6.92 (2H, m); 7.14-7.25 (2H, m); 7.40-7.52 (2H, m
m); 7.52-7.66 (2H, m). Mass spectrum (m / z): 598 (M ⁺ ); 403; 305; 293; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 161
0, 1590, 1510, 1465, 1420, 1320, 1180, 1130.

[0243]

Example 24 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] -4- (2-pyridinecarbonyl) piperazine The compound of Reference Example 22 (0.500 g) and triethylamine (0.4
4mg) in tetrahydrofuran (10 ml).
2-Carboxylic chloride hydrochloride (0.249 g) was added under ice cooling. After stirring at room temperature for 3 days, the solvent was distilled off. The residue was dissolved in methylene chloride, washed with water, dried and concentrated. The residue was subjected to medium pressure liquid chromatography using Rover B columns (two columns) to give methylene chloride-
Collect fractions eluted with methanol (49: 1)
(0.489 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.10-3.75
(8H, m); 3.83 (3H, s); 6.28,6.31 (1H, s × 2); 6.80-6.92
(2H, m); 7.15-7.40 (7H, m); 7.68 (1H, br.d, J = 7.81Hz);
7.80 (1H, br.dd, J = 7.81,7.81Hz); 8.50-8.62 (1H, m) mass spectrum (m / z):. 461 (M +, 35 Cl); 433; 355; 271;
190; 106. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 161
0, 1570, 1515, 1480, 1460, 1440, 1425, 1290, 1250,
1175, 1010, 830. Elemental analysis (C ₂₆ H ₂₄ ClN ₃ as O ₃₎ Calculated: C; 67.60, H; 5.24 , N; 9.10 Found:. C; 67.64, H; 5.58, N; 9.10.

[0244]

Example 25 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
[Acryloyl] -4- (3-pyridinecarbonyl) piperazine Using the compound of Reference Example 22 (0.500 g) and pyridine-3-carboxylic acid chloride hydrochloride (0.249 g), the same procedure as in Example 24 was carried out to obtain the desired compound ( 0.548 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.80-3.80
(8H, m); 3.83 (3H, s); 6.28 (1H, s); 6.87 (2H, dm, J = 8.78H
z); 7.15-7.42 (7H, m); 7.71 (1H, dm, J = 7.81Hz); 8.61 (1
. H, br.s); 8.65-8.72 ( 1H, m) mass spectrum (m / z): 461 ( M +, 35 Cl); 433; 355; 271;
190; 106. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
^-1 : 1630, 1605, 1510, 146
0, 1430, 1420, 1290, 125
0, 1180, 1140, 1005, 830. Elemental analysis (as C ₂₆ H ₂₄ ClN ₃ O ₃ ) Calculated: C; 67.60, H; 5.24, N; 9.10, Cl; 7.67. Found: C; 67.49, H; 5.54, N; 9.09, Cl; 7.44.

[0245]

Example 26 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
[Acryloyl] -4- (4-pyridinecarbonyl) piperazine Using the compound of Reference Example 22 (0.500 g) and pyridine-4-carboxylic acid chloride hydrochloride (0.299 g), the same procedure as in Example 24 was carried out to obtain the desired compound ( 0.612 g) was obtained as a powder. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.70-3.80
(8H, m); 3.83 (3H, s); 6.28 (1H, br.s); 6.87 (2H, dm, J = 8.
. 30Hz); 7.10-7.42 (8H, m); 8.70 (2H, dm, J = 4.88Hz) Mass spectrum (m / z): 461 ( M +, 35 Cl); 355; 271; 190;
106. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
5, 1510, 1460, 1430, 1285, 1240, 1175, 1010, 830. Elemental analysis (as C ₂₆ H ₂₄ ClN ₃ O ₃ ) Calculated: C; 67.60, H; 5.24, N; 9.10, Cl; 7.67 Found: C; 67.43, H; 5.48, N; 9.11, Cl; 7.50.

[0246]

Example 27 1- [Z-3- (3,5-dichlorophenyl) -3- (4-methoxyphenyl)
Le) acryloyl] -4- (3-pyridinecarbonyl) pipera
Gin The title compound (0.587 g) was obtained as a powder in the same manner as in Example 24 using the compound of Reference Example 28 (0.500 g) and pyridine-3-carboxylic acid chloride hydrochloride (0.250 g). NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 2.95-3.80
(8H, m); 3.84 (3H, s); 6.34 (1H, s); 6.88 (2H, dm, J = 8.79H
_Z ); 7.16 (2H, d, J = 1.96H _Z ); 7.18 (2H, dm, J = 8.79H _Z ); 7.3
2-7.43 (1H, m); 7.39 (1H, t, J = 1.96H Z); 7.74 (1H, ddd, J =
7.81,1.46,1.46H _Z ); 8.60-8.70 (1H, m); 8.69 (1H, dd, J =
4.88,1.46H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 160
5, 1510, 1460, 1430, 1415, 1285, 1250, 1175, 1005. Mass spectrum (m / z): 495 ( M +, 35 Cl); 389; 305; 190;
106.

[0247]

Embodiment 28dl-7-Bis (4-methoxyphenyl) methylene-2- (3,4,5
-Trimethoxy) benzoyloctahydropyrrolo [1,2-
a] pyrazine-6-one Under a nitrogen atmosphere, diisopropylamine (0.424 ml)
To a solution of lahydrofuran (24 ml) was added n-butyllithium.
A hexane solution (1.6M, 1.89 ml) was added dropwise at -78 ° C. Ice cold
After stirring under the above conditions for 30 minutes, the mixture was cooled to −78 ° C.
Compound (843.6 mg) and hexamethylphosphoric triamide (12 m
l) and tetrahydrofuran (16 ml)
did. After stirring at -78 ° C for 5 minutes, 4,4'-dimethoxybenzene was added.
Nzophenone (672.4 mg) and hexamethylphosphoric triamide
(4 ml) and tetrahydrofuran (16 ml).
Was. After stirring at -78 ° C for 1 hour, acetic acid (0.175 ml) was added.
A solution of lahydrofuran (0.4 ml) was added dropwise. Acetic acid
Poured into ethyl and water and washed three times with water. Saturate organic layer
Washed with brine, dried and concentrated. The residue was purified on silica gel (16
g) using column chromatography.
Chloridomethanol (99.5: 0.5-99: 1)
Collect the dl-7- {bis (4-methoxyphenyl)} hydro
Xymethyl-2- (3,4,5-trimethoxy) benzoylocta
Hydropyrrolo [1,2-a] pyrazin-6-one (730.3 mg, yield
50%) as an oil. The above compound (728.0 mg) and
And p-toluenesulfonic acid monohydrate (48.0 mg)
The mixture was refluxed for 3 hours in a solvent (15 ml). After cooling, the reaction
Poured into water and extracted three times with ethyl acetate. Combine the extracts
And saturated aqueous sodium bicarbonate, then saturated saline
Washed with. The residue obtained by drying and concentrating is dried over silica gel (14
g) using column chromatography.
-Collect the fractions eluted with ethyl acetate (1: 4-0: 1)
The title compound (662.9 mg, yield 94%) was obtained as a powder. NMR spectrum (270MH_Z , CDCl_Three) δ ppm: 2.50-3.10
(7H, m); 3.50-3.70 (1H, m); 3.81 (6H, s); 3.86 (9H, s);
4.10-4.25 (1H, m); 6.62 (2H, s); 6.84 (4H, dm, J = 8.79H_Z);
 7.10 (4H, dm, J = 8.79H_Z). Infrared absorption spectrum ν_max (CHCl_Three) cm^-1: 1685, 163
0, 1605, 1575, 1510, 1460, 1420, 1330, 1125. Mass spectrum (m / z): 558 (M⁺); 363; 195.

[0248]

Embodiment 29dl-7-bis (4-chlorophenyl) methylene-2- (3,4,5-to
Rimethoxy) benzoyloctahydro-2H-pyrido [1,2-
a] pyrazine-6-one Under a nitrogen atmosphere, diisopropylamine (0.194 ml)
To a solution of lahydrofuran (9 ml) was added hexane of n-butyllithium.
A sun solution (1.6M, 0.87 ml) was added dropwise at -78 ° C. Ice cold
After stirring under the above conditions for 30 minutes, the mixture was cooled to −78 ° C.
Compound (402.2 mg) and hexamethylphosphoric triamide (5 ml)
And a mixed solution of tetrahydrofuran (3 ml) was added dropwise.
After stirring the reaction solution under ice cooling for 30 minutes, it was cooled to -78 ° C,
4,4'-dichlorobenzophenone (318.8 mg) and hexamethy
Triphosphate triamide (1 ml) and tetrahydrofuran (6 ml)
Was added dropwise. After stirring at -78 ° C for 1 hour, acetic acid
(0.080 ml) in tetrahydrofuran (0.2 ml) was added dropwise.
Was. Hereinafter, the same procedures as in Example 28 were carried out to obtain the title compound.
(432.5 mg) was obtained as white crystals. Yield: 54% (2 steps). Melting point: 181.0-183.0 ° C (methylene chloride-hexane
NMR spectrum (270MH)_Z , CDCl_Three) δ ppm: 1.50-1.70
(1H, m); 2.00-2.20 (1H, m); 2.40-2.90 (6H, m); 2.95-3.2
0 (1H, m); 3.45-3.60 (1H, m); 3.87 (9H, s); 4.55-4.75 (1
H, m); 6.63 (2H, s); 7.00 (2H, dm, J = 2.93H_Z); 7.03 (2H, d
m, J = 2.93H_Z); 7.25 (2H, dm, J = 8.79H_Z); 7.30 (2H, dm, J = 8.7
9H_Z). Infrared absorption spectrum ν_max (CHCl_Three) cm^-1: 1625, 158
5, 1490, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 580 (M⁺,³⁵Cl); 385; 195. Elemental analysis: C₃₁H₃₀Cl_TwoN_TwoO_Five Calculated: C; 64.03, H; 5.20, Cl; 12.19, N; 4.82. Measured: C; 64.05, H; 5.38, Cl; 12.35, N; 4.87.

[0249]

Embodiment 30dl-7-Bis (4-methoxyphenyl) methylene-2- (3,4,5
-Trimethoxy) benzoyloctahydro-2H-pyrido
[1,2-a] pyrazin-6-one The compound of Reference Example 51 (524.5 mg) and 4,4′-dimethoxybe
Starting from nzophenone (401 mg),
Similarly, the title compound (486.4 mg) was converted to white crystals.
I got it. Yield: 58% (2 steps). Melting point: 163.0-164.0 ° C (methylene chloride-hexane
NMR spectrum (270MH)_Z , CDCl_Three) δ ppm: 1.50-1.70
(1H, m); 2.00-2.15 (1H, m); 2.40-2.90 (6H, m); 2.95-3.2
0 (1H, m); 3.45-3.60 (1H, m); 3.78 (3H, s); 3.81 (3H, s);
3.87 (9H, s); 4.60-4.80 (1H, m); 6.63 (2H, s); 6.80 (2H, d
m, J = 8.79H_Z); 6.84 (2H, dm, J = 8.79H_Z); 7.00 (2H, dm, J = 1.4
6H_Z); 7.03 (2H, dm, J = 1.46H_Z). Infrared absorption spectrum ν_max (CHCl_Three) cm^-1: 1630, 160
5, 1585, 1505, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 572 (M⁺); 377; 195.

[0250]

Example 31 (S) -7-{(Z)-(3,5-dichlorophenyl)-(4-methoxyphen)
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoylo
Kutahydropyrrolo [1,2-a] pyrazin-6-one The same procedure as in Example 28 was carried out using the compound of Reference Example 45 (2.010 g) and 3,5-dichloro-4'-methoxybenzophenone (1.859 g). did. The crude product was passed through a column (C
Column), and the low-polarity fraction eluted with methylene chloride-methanolsan (99: 1) was collected to obtain 0.314 g (8.1% in two steps) of the target compound as a powder. [Α] _D ²⁵ + 51.8 ° (c = 1.01, CHCl ₃ ) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.50-3.15 (7
H, m), 3.55-3.75 (1H, m), 3.82 (3H, s), 3.86 (9H, s), 4.05
-4.25 (1H, m), 6.63 (2H, s), 6.87 (2H, br.dm, J = 8.79Hz),
7.05 (2H, d, J = 1.95Hz), 7.10 (2H, br.dm, J = 8.79Hz), 7.29
(1H, t, J = 1.95Hz). Mass spectrum (m / z): 596 (M ⁺ , ³⁵ Cl); 401; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1680, 163
0, 1610, 1590, 1560, 1510, 1465, 1415, 1330, 1250,
1130.

[0251]

Example 32 (S) -7-{(E)-(3,5-dichlorophenyl)-(4-methoxyphen)
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoylo
Kutahydropyrrolo [1,2-a] pyrazin-6-one After elution of the compound of Example 31, elution was further continued and the highly polar fraction was collected to obtain 1.968 g of the target compound (55. 4%) was obtained as a powder. [Α] _D ²⁵ + 38.2 ° (c = 1.03, CHCl ₃ ) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.35-3.15 (7
H, m), 3.50-3.75 (1H, m), 3.81 (3H, s), 3.86 (3H, s), 3.87
(6H, s), 4.05-4.30 (1H, m), 6.63 (2H, s), 6.86 (2H, dm, J =
8.79Hz), 7.05 (2H, br.d, J = 1.95Hz), 7.10 (2H, dm, J = 8.79
Hz), 7.28-7.31 (1H, m). Mass spectrum (m / z): 596 (M ⁺ , ³⁵ Cl); 401; 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1680, 163
0, 1610, 1585, 1560, 1510, 1465, 1415, 1330, 1245,
1130.

[0252]

Example 33 (R) -7-{(Z)-(3,5-dichlorophenyl)-(4-methoxyphen)
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoylo
Kutahydropyrrolo [1,2-a] pyrazin-6-one Starting from the compound of Reference Example 46, in the same manner as in Example 31, the target compound was obtained as a powder. [Α] _D ²⁵ -51.3 ° (c = 1.05, CHCl ₃ )

[0253]

Example 34 (R) -7-{(E)-(3,5-dichlorophenyl)-(4-methoxyphen)
Nyl)} methylene-2- (3,4,5-trimethoxy) benzoylo
Kutahydropyrrolo [1,2-a] pyrazin-6-one Starting from the compound of Reference Example 46, the target compound was obtained as a powder in the same manner as in Example 32. [Α] _D ²⁵ −37.9 ° (c = 1.08, CHCl ₃ )

[0254]

Reference Example 1 Diethylphosphonoacetic acid was added to a suspension of (E)-and (Z) -3- (2-thienyl) sodium cinnamate (5.63 g, content 55%) in tetrahydrofuran (400 ml). ethyl
(26.30 g) in tetrahydrofuran (100 ml) under ice-cooling
It was added dropwise at 8-10 ° C over 15 minutes. After the reaction solution was stirred at room temperature for 1 hour, 2-benzoylthiophene (22.08 g) was added, and the mixture was further heated under reflux for 21 hours. The reaction solution was poured into water (300 ml) and extracted with ethyl acetate. After the extract was dried over sodium sulfate, the solvent was distilled off. Oily residue (26.56
g) was dissolved in methanol (450 ml), 10% aqueous sodium hydroxide solution (150 ml) was added, and the mixture was stirred at room temperature for 2 hours. The reaction was poured into water (500 ml) and washed with methylene chloride. The aqueous layer was adjusted to pH 2 by adding hydrochloric acid and extracted with methylene chloride. After the extract was dried over sodium sulfate, the solvent was distilled off, and the residue was subjected to column chromatography using silica gel. Methylene chloride-methanol (19:
When elution is performed in 1), isomer A having a lower polarity is obtained.
3.415 g of (Rf value: 0.48 (silica gel, methylene chloride-methanol (24: 1))] (presumed to be the (Z) -isomer) are eluted first and then the more polar isomer B ( (E) -isomer) [Rf value: 0.35 (silica gel, methylene chloride-
0.789 g of methanol (24: 1)) was eluted. [Isomer A] Light brown crystal Melting point: 144-147 ° C. NMR spectrum (90 MHz, CDCl ₃ ) δ ppm: 6.34 (1H, s);
6.80-7.10 (2H, m); 7.15-7.50 (6H, m); 9.93 (1H, br.s) .Mass vector (m / z): 230 (M ⁺ ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1685; 161
0; 1595. Elemental analysis (C ₁₃ H ₁₀ O as ₂ S) Calculated: C; 67.80, H; 4.38 , S; 13.92 Found:.. C; 67.71, H ; 4.12, N; 13.88 [ isomer B] light brown crystal Melting point: 152-155 ° C NMR spectrum (90MHz, CDCl ₃ ) δ ppm: 6.18 (1H, s);
6.95-7.15 (1H, m); 7.15-7.55 (7H, m); 10.66 (1H, br.s) .Mass spectrum (m / z): 230 (M ⁺ ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1690; 159
Five.

[0255]

Reference Example 2 Diethylphosphonate was added to a suspension of sodium (E)-and (Z) -3- (4-pyridyl) ethyl cinnamate (5.76 g, content 55%) in tetrahydrofuran (400 ml). Ethyl acetate
(26.92 g) in tetrahydrofuran (100 ml) under ice-cooling
It was added dropwise at 8-10 ° C over 20 minutes. After the reaction solution was stirred at room temperature for 1 hour, 4-benzoylpyridine (22.00 g) was added, and the mixture was further stirred for 3 hours. The reaction solution was poured into water (300 ml) and extracted with ethyl acetate. After the extract was dried over sodium sulfate and the solvent was distilled off, the residue was subjected to column chromatography using silica gel. After elution with hexane-methylene chloride (3: 1-1: 1), isomer C showing a lower polarity (estimated as (Z)-isomer) [Rf value: 0.63 (silica gel, methylene chloride-methano- (49: 1))] 10.047
g is eluted first, followed by elution with hexane-methylene chloride (1: 1-0: 1) to give the more polar isomer D (estimated (E) -isomer) [Rf value: 0.55 (silica gel,
16.603 g of methylene chloride-methanol (49: 1)) was eluted. [Isomer C] Colorless oil NMR spectrum (90 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.57); 4.07 (2H, q, J = 7.5Hz); 6.48 (1H, s); 7.05-7.55
(7H, m); 8.40-8.90 (2H, m). Mass spectrum (m / z): 253 (M ⁺ ); 208 (M ⁺ -C ₂ H ₅ O) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720. Elemental analysis (as C ₁₆ H ₁₅ NO ₂ ) Calculated: C; 75.87, H; 5.97, N; 5.53. Found: C; 75.91, H; 6.26, N; 5.48. Isomer D] colorless crystal Melting point: 101-102 ° C NMR spectrum (90MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.5Hz); 4.05 (2H, q, J = 7.5Hz); 6.46 (1H, s); 7.05-7.50
(7H, m); 8.50-8.85 (2H, m). Mass spectrum (m / z): 253 (M ⁺ ); 208 (M ⁺ -C ₂ H ₅ O) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715. Elemental analysis (as C ₁₆ H ₁₅ NO ₂ ) Calculated: C; 75.87, H; 5.97, N; 5.53. Found: C; 75.86, H; 5.86, N; 5.59.

[0256]

Reference Example 3 (E) -3- (4-Pyridyl) cinnamate (E) -3- (4-Pyridyl) methanoate of ethyl cinnamate (3.41 g)
(35 ml) solution with 10% aqueous sodium hydroxide solution (20 m
l) was added and the mixture was stirred at room temperature for 1 hour. The reaction solution was water (50 ml)
Poured in and washed with methylene chloride. The pH of the aqueous layer was adjusted to pH 2.8 by adding hydrochloric acid, and the resulting precipitate was collected to give the desired compound (2.131 g, melting point: 239-241 ° C) as a white powder. NMR spectrum (90 MHz, DMSO-d ₆ ) δ ppm: 6.51 (1H,
s); 7.15-7.55 (7H, m); 8.45-8.80 (2H, m). Mass vector (m / z): 225 (M ⁺ ); 180 (M ⁺ -COOH). Infrared absorption spectrum ν _max ( Nujol) cm-1: 169
7; 1625; 1602.

[0257]

[Reference Example 4] Synthesis of 3,3-diphenylacrylic acid derivative by Heck reaction
Synthetic Heck et al. [J. Org.chem., 43 , 2952, (1978
)], A coupling reaction between an E-acrylate having a 3-position substituent R ¹ and an iodide having a substituent R ² was carried out. That is, E having a 3-position substituent R ¹
Ethyl acrylate (20 mmol), aryl iodide of formula R ² -I (30 mmol), triethylamine (4.17 m
l), palladium acetate (0.270 g) and acetonitrile (8
ml) of the mixture in a sealed tube and placed on a 100 ° C. oil bath for 18 minutes.
Heated for hours. After cooling, the mixture was diluted with ethyl acetate (30 ml) and washed sequentially with 10% hydrochloric acid, a saturated aqueous solution of sodium hydrogen carbonate and brine. The organic layer is dried and concentrated, and the residue is subjected to flash column chromatography using silica gel (~ 400 mesh, 400 g) and Rover C column.
(Si-60 type) was applied to medium pressure liquid chromatography. Methylene chloride-ether-hexane (1: 1: 5-1:
Elution with the 1: 4) mixture separated the (E) and (Z) isomers of the 3,3-disubstituted ethyl acrylate.

In the following description of geometric isomers, isomers first eluted by the above-mentioned chromatography are described above.

The thus separated E- or Z-
Ethyl 3,3-diphenylacrylate (4 mmol) in dioxane
(12 ml) and methanol (12 ml).
An aqueous solution of sodium hydroxide (5 ml) was added for hydrolysis. After stirring at room temperature for 18 hours, the solvent was distilled off. The residue was diluted with water (20 ml) and washed with ethyl acetate. 10% in water layer
The pH was adjusted to 2 by adding hydrochloric acid, and the mixture was extracted twice with methylene chloride. The extract was washed with water and dried to obtain 3,3-disubstituted acrylic acid as a solid.

Compounds of Reference Examples 4-29 and 4-30, 4-
In the separation of 33 and 4-34, toluene was used as an elution solvent. The separation of the compounds 4-93 and 4-94 of the reference example was carried out as follows, since the corresponding ester mixture was not separated by the above chromatography. The E / Z-ester mixture was hydrolyzed as described above and the resulting E / Z-acid mixture was washed with methylene chloride. The insolubles were recrystallized from ether-tetrahydrofuran to give the compound of Reference Example 4-93 (estimated as E-isomer). The methylene chloride solution was concentrated, and the residue was recrystallized from methylene chloride-hexane to obtain the compound of Reference Example 4-94 (estimated as the Z-isomer).

[0261]

Embedded image

[0262]

[Reference Example 4-1] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement = E
Compound yield (%) = 14. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.10 (3H, t, J =
7.32Hz), 3.82 (3H, s), 3.88 (3H, s), 4.04 (2H, q, J = 7.32H
z), 6.32 (1H, s), 6.74-6.84 (2H, m), 6.89 (1H, br.s), 7.
16-7.25 (2H, m), 7.34-7.42 (2H, m). Mass spectrum (m / z): 312 (M ⁺ ), 297, 283, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1705, 1595, 1580, 151
0, 1465, 1160, 1135.

[0263]

[Reference Example 4-2] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 21. Melting point (recrystallization solvent) = 93-95 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 3.81 (3H, s), 3.92 (3H, s), 4.09 (2H, q, J = 7.32H
z), 6.29 (1H, s), 6.72 (1H, d, J = 1.95Hz), 6.82 (1H, dd, J =
8.30,1.95Hz), 6.88 (1H, d, J = 8.30Hz), 7.30-7.14 (5H,
m). Mass spectrum (m / z): 312 (M ⁺ ), 297, 283, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1585, 1515, 1465, 1445, 1160, 1135.

[0264]

[Reference Example 4-3] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = H, arrangement = E
Compound yield (%) = 98. Melting point (recrystallization solvent) = 178-181 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
3.88 (3H, s), 6.28 (1H, s), 6.75-6.83 (2H, m), 6.86 (1H, b
rs), 7.17-7.25 (2H, m), 7.33-7.43 (3H, m) .Mass spectrum (m / z): 284 (M ⁺ ), 269, 267, 239.Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1595, 1515, 1260, 1135.

[0265]

[Reference Example 4-4] R ¹ = 3,4-di-CH ₃ OPh, R ² = Ph, R ¹¹ = H, configuration = Z
Compound yield (%) = 99. Melting point (recrystallization solvent) = 162-164 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.80 (3H, s),
3.92 (3H, s), 6.26 (1H, s), 6.75 (1H, d, J = 1.95Hz), 6.80
(1H, dd, J = 8.30,1.95Hz), 6.87 (1H, d, J = 8.30Hz), 7.27-
7.43 (5H, m). Mass vector (m / z): 284 (M ⁺ ), 269, 267, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1605, 1515, 1255, 1135.

[0266]

[Reference Example 4-5] R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 19. Melting point (recrystallization solvent) = 119-121 ° C (Et ₂ O-CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 3.77 (6H, s), 3.87 (3H, s), 4.05 (2H, q, J = 7.32H
z), 6.32 (1H, s), 6.51 (2H, s), 7.18-7.24 (2H, m), 7.35-
7.41 (3H, m). Mass spectrum (m / z): 342 (M ⁺ ), 327, 313, 299, 297. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
5, 1580, 1500, 1460, 1415, 1160, 1125.

[0267]

Reference Example 4-6 R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 35. Melting point (recrystallization solvent) = 96-98 ° C (CH ₂ Cl ₂ -Et ₂ O) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.33Hz), 3.80 (6H, s), 3.90 (3H, s), 4.08 (2H, q, J = 7.33H
z), 6.32 (1H, s), 6.43 (2H, s), 7.31-7.40 (5H, m). Mass spectrum (m / z): 342 (M ⁺ ), 327, 313, 299, 297. Absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1585. 1500, 1460, 1410, 1300, 1170, 1125.

[0268]

[Reference Example 4-7] R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = H, configuration =
Compound of E Yield (%) = 100. Melting point (recrystallization solvent) = 202-206 ° C (Et ₂ O-CH ₂ Cl ₂ ) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.76 (6H, s),
3.87 (3H, s), 6.30 (1H, s), 6.49 (2H, s), 7.19-7.25 (2H,
m), 7.35-7.41 (3H, m). Mass spectrum (m / z): 314 (M ⁺ ), 299. Infrared absorption spectrum ν _max (KBr) cm-1: 2400-3400 (br
oad), 1688, 1610, 1578, 1502, 1241, 1200, 1129.

[0269]

[Reference Example 4-8] R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = Ph, R ¹¹ = H, configuration =
Compound of Z Yield (%) = 100. Melting point (recrystallization solvent) = 203-205 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.78 (6H, s),
3.91 (3H, s), 6.30 (1H, s), 6.44 (2H, s), 7.28-7.43 (5H,
m). Mass spectrum (m / z): 314 (M ⁺ ), 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1580, 1500, 1460, 1410, 1365,
1125.

[0270]

REFERENCE EXAMPLE 4-9 R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = Et, configuration =
Compound of E Yield (%) = 24. Melting point (recrystallization solvent) = 66-68 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.10 (3H, t, J = 7.33Hz), 1.80-1.95 (2H, m), 3.8
1 (3H, s), 3.98 (2H, t, J = 6.84Hz), 4.03 (2H, q, J = 7.33Hz),
6.31 (1H, s), 6.77 (1H, s), 6.78 (1H, s), 6.89 (1H, s),
7.16-7.25 (2H, m), 7.35-7.45 (3H, m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 269, 253, 226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1600, 1520, 147
0, 1375, 1260, 1160, 114
0.

[0271]

Reference Example 4-10 Compound of R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 37. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.05 (3H, t, J =
7.32Hz), 1.15 (3H, t, J = 7.32Hz), 1.80-2.00 (2H, m), 3.7
9 (3H, s), 4.01 (2H, t, J = 6.83Hz), 4.08 (2H, q, J = 7.32Hz),
6.27 (1H, s), 6.72 (1H, d, J = 1.95Hz), 6.78 (1H, dd, J = 8.3
0,1.95Hz), 6.87 (1H, d, J = 8.30Hz), 7.30-7.42 (5H, m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 269, 253, 226. Red External absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1515, 1470, 1375, 1260, 1170, 1140.

[0272]

Reference Example 4-11 R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = H, configuration =
Compound of E Yield (%) = 94. Melting point (recrystallization solvent) = 147-150 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.33Hz), 1.75-2.00 (2H, m), 3.79 (3H, s), 3.98 (2H, t, J =
6.84Hz), 6.28 (1H, s), 6.73-6.80 (2H, m), 6.85 (1H, br.
s), 7.15-7.25 (2H, m), 7.33-7.40 (3H, m). Mass spectrum (m / z): 312 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1595, 1580, 1510, 1465, 1260,
1180, 1135.

[0273]

Reference Example 4-12 R ¹ = 3-CH ₃ O-4-PrO-Ph, R ² = Ph, R ¹¹ = H, configuration =
Compound of Z Yield (%) = 93. Melting point (recrystallization solvent) = 139-142 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.33Hz), 1.80-2.00 (2H, m), 3.79 (3H, s), 4.01 (2H, t, J =
6.84Hz), 6.24 (1H, s), 6.29-6.79 (2H, m), 6.85 (1H, dd, J
= 8.33,1.47Hz), 7.25-7.45 (5H, m). Mass spectrum (m / z): 312 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1575, 1510, 1465, 1445, 1410,
1250, 1130.

[0274]

Reference Example 4-13 Compound of R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = E Yield (%) = 16. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.33Hz), 1.03 (3H, t, J = 7.33Hz), 1.10 (3H, t, J = 7.33Hz),
1.70-1.95 (4H, m), 3.90 (2H, t, J = 6.83Hz), 3.96 (2H, t, J
= 6.83Hz), 4.03 (2H, q, J = 7.33Hz), 6.30 (1H, s), 6.72-6.
80 (2H, m), 6.90 (1H, br, s), 7.15-7.25 (2H, m), 7.30-7.4
5 (3H, m). Mass spectrum (m / z): 368 (M ⁺ ), 326, 323, 284. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 159
5, 1510, 1470, 1370, 1260, 1160, 1130.

[0275]

Reference Example 4-14 Compound of R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 25. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.32Hz), 1.06 (3H, t, J = 7.32Hz), 1.15 (3H, t, J = 7.32Hz),
1.70-1.95 (4H, m), 3.89 (2H, t, J = 6.84Hz), 4.00 (2H, t, J
= 6.84Hz), 4.08 (2H, q, J = 7.32Hz), 6.26 (1H, s), 6.73 (1
H, d, J = 1.95Hz), 6.77 (1H, dd, J = 8.30,1.95Hz), 6.86 (1H,
d, J = 8.30 Hz), 7.25-7.40 (5H, m). Mass spectrum (m / z): 368 (M ⁺ ), 326, 323, 284. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1605, 1510, 147
0, 1445, 1370, 1260, 116
0, 1130.

[0276]

[Reference Example 4-15] R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = H, arrangement = E
Compound yield (%) = 92. Melting point (recrystallization solvent) = 102-103 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.32Hz), 1.03 (3H, t, J = 7.32Hz), 1.70-1.95 (4H, m), 3.8
9 (2H, t, J = 6.83Hz), 3.96 (2H, t, J = 6.84Hz), 6.26 (1H, s),
6.74 (1H, dd, J = 8.30,1.96Hz), 6.78 (1H, d, J = 8.30Hz),
6.86 (1H, d, J = 1.96Hz), 7.15-7.25 (2H, m), 7.30-7.40 (3
H, m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 256, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1595, 1580, 1510, 1425, 1260,
1135.

[0277]

Reference Example 4-16 Compound of R ¹ = 3,4-di-PrOPh, R ² = Ph, R ¹¹ = H, Configuration = Z Yield (%) = 94. Melting point (recrystallization solvent) = 120-123 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.33Hz), 1.06 (3H, t, J = 7.32Hz), 1.70-1.95 (4H, m), 3.8
9 (2H, t, J = 6.84Hz), 4.00 (2H, t, J = 6.84Hz), 6.23 (1H, s),
6.73-6.80 (2H, m), 6.83-6.87 (1H, m), 7.25-7.45 (5H, m
m). Mass spectrum (m / z): 340 (M ⁺ ), 298, 256, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1610, 1515, 1260, 1135.

[0278]

Reference Example 4-17 Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 14. Melting point (recrystallization solvent) = 83-84 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.84 (3H, s), 3.89 (3H, s), 4.06 (2H, q, J = 7.32H
z), 6.31 (1H, s), 6.76 (1H, dd, J = 8.79,1.95Hz), 6.80 (1H
H, d, J = 8.79Hz), 6.86 (1H, d, J = 1.95Hz), 7.15 (2H, dm, J =
8.79Hz), 7.36 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ Cl), 317, 301, 274. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 1705, 161
5, 1595, 1580, 1510, 1460, 1370, 1290, 1160, 1135.

[0279]

Reference Example 4-18 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = Et, Configuration = Z Yield (%) = 22. Melting point (recrystallization solvent) = 67-69 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 3.81 (3H, s), 3.91 (3H, s), 6.26 (1H, s), 6.70
(1H, d, J = 1.95Hz), 6.79 (1H, dd, J = 8.30,1.95Hz), 6.88 (1
H, d, J = 8.30Hz), 7.12-7.40 (4H, m). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ Cl), 317, 301, 274. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1590, 1515, 1490, 1460, 1255, 1170, 1135.

[0280]

Reference Example 4-19 Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = H, configuration = E Yield (%) = 85. Melting point (recrystallization solvent) = 164-165 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
3.89 (3H, s), 6.29 (1H, s), 6.76 (1H, dd, J = 8.30,1.95Hz),
6.80 (1H, d, J = 8.30Hz), 6.84 (1H, d, J = 1.95Hz), 7.15 (2
H, dm, J = 8.30Hz), 7.35 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 318 (M ⁺ ), 303, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 2400-3600 (broad), 169
0, 1610, 1595, 1515, 146
5, 1260, 1175, 1135.

[0281]

Reference Example 4-20 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 91. Melting point (recrystallization solvent) = 188-190 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.80 (3H, s),
3.92 (3H, s), 6.23 (1H, s), 6.72 (1H, d, J = 1.95Hz), 6.78
(1H, dd, J = 8.30,1.95Hz), 6.86 (1H, d, J = 8.30Hz), 7.23 (2
H, dm, J = 8.79Hz), 7.31 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 318 (M ⁺ ), 303, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1605, 1585, 1515, 1490, 1465, 1415,
1255, 1135.

[0282]

Reference Example 4-21 Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 13. Melting point (recrystallization solvent) = Oil NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J = 7H
z), 3.83 (3H, s), 3.88 (3H, s), 4.06 (2H, q, J = 7Hz), 6.35
(1H, s), 6.75-7.00 (3H, m), 7.00-7.50 (4H, m).

[0283]

Reference Example 4-22 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 20. Mp (recrystallization solvent) = oil NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.15 (3H, t, J = 7H
z), 3.81 (3H, s), 3.90 (3H, s), 4.08 (2H, q, J = 7Hz), 6.29
(1H, s), 6.70-7.00 (3H, m), 7.10-7.45 (4H, m).

[0284]

Reference Example 4-23 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 90. Melting point (recrystallization solvent) = 178-181 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
3.89 (3H, s), 6.30 (1H, s), 6.75 (1H, dd, J = 8.30,1.95Hz),
6.80 (1H, d, J = 8.30Hz), 6.85 (1H, d, J = 1.95Hz), 7.10 (1
H, dt, J = 7.81,1.46Hz), 7.20 (1H, t, J = 1.46Hz), 7.31 (1H,
t, J = 7.81Hz), 7.36 (1H, dt, J = 7.81,1.46 Hz). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 303. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1590, 1580, 1510, 1460, 1420,
1255, 1140.

[0285]

Reference Example 4-24 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = E Yield (%) = 91. Melting point (recrystallization solvent) = 158-160 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
3.92 (3H, s), 6.23 (1H, s), 6.73 (1H, d, J = 1.95Hz), 6.78
(1H, dd, J = 8.30,1.95Hz), 6.87 (1H, d, J = 8.30Hz), 7.15-
7.40 (4H, m). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 303. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1580, 1565, 1515, 1460, 1420,
1255, 1135.

[0286]

Reference Example 4-25 Compound of R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 4. Melting point (recrystallization solvent) = 82-84 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.39 (3H, s), 3.84 (3H, s), 4.10 (2H, q, J = 7.32H
z), 6.16 (1H, s), 6.82 (1H, dd, J = 8.30,1.46Hz), 6.93 (1
H, dd, J = 8.30,1.46Hz), 7.04 (1H, t, J = 8.30Hz), 7.20 (2H,
dm, J = 8.79 Hz), 7.29 (2H, dm, J = 8.79 Hz). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ C)
l), 315, 301, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 16
20, 1600, 1580, 1495, 1475, 1430, 1370, 1260, 117
0.

[0287]

Reference Example 4-26 Compound in which R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 37. Melting point (recrystallization solvent) = 90-92 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 3.58 (3H, s), 3.89 (3H, s), 4.04 (2H, q, J = 7.32H
z), 6.43 (1H, s), 6.69 (1H, dd, J = 8.30,1.47Hz), 6.95 (1
H, dd, J = 8.30,1.47Hz), 7.08 (1H, t, J = 8.30Hz), 7.28 (4H,
s). Mass spectrum (m / z): 346 (M ⁺ , ³⁵ Cl), 315, 301, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720, 162
5, 1590, 1580, 1495, 1480, 1430, 1370, 1260, 1170.

[0288]

Reference Example 4-27 Compound of R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = H, configuration = E Yield (%) = 98. Melting point (recrystallization solvent) = 129-131 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.39 (3H, s),
3.84 (3H, s), 6.16 (1H, s), 6.79 (1H, dd, J = 8.30,1.47Hz),
6.93 (1H, dd, J = 8.30,1.47Hz), 7.04 (1H, t, J = 8.30Hz),
7.20 (2H, dm, J = 8.79Hz), 7.28 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 287. Infrared absorption spectrum ν _max ( CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1620, 1600, 1580, 1495, 1475, 1425,
1260.

[0289]

Reference Example 4-28 Compound of R ¹ = 2,3-di-CH ₃ O-Ph, R ² = 4-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 98. Melting point (recrystallization solvent) = 147 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.57 (3H, s),
3.88 (3H, s), 6.38 (1H, s), 6.67 (1H, dd, J = 7.81,1.46Hz),
6.94 (1H, dd, J = 7.81,1.46Hz), 7.06 (1H, t, J = 7.81Hz),
7.20-7.33 (4H, m). Mass spectrum (m / z): 318 (M ⁺ , ³⁵ Cl), 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1620, 1590, 1580, 1495, 1480, 1425,
1265.

[0290]

Reference Example 4-29 R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 13. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.02 (6H, d, J =
6.83Hz), 1.14 (3H, t, J = 7.32Hz), 2.00-2.15 (1H, m), 3.7
2 (2H, d, J = 6.35Hz), 4.05 (2H, q, J = 7.32Hz), 6.30 (1H, s),
6.83 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.20
(2H, dm, J = 8.79Hz), 7.35 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 358 (M ⁺ , ³⁵ Cl), 313, 302. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1515, 1495, 1475, 1375, 1280, 1255, 1170.

[0291]

Reference Example 4-30 R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 16. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (6H, d, J =
6.83Hz), 1.17 (3H, t, J = 7.32Hz), 2.00-2.20 (1H, m), 3.
74 (2H, d, J = 6.35Hz), 4.09 (2H, q, J = 7.32Hz), 6.23 (1H,
s), 6.89 (2H, dm, J = 9.28Hz), 7.11 (2H, dm, J = 9.28Hz), 7.
22 (2H, dm, J = 8.79Hz), 7.29 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 358 (M ⁺ , ³⁵ Cl), 313, 302. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1510, 1490, 1470, 1370, 1285, 1160.

[0292]

Reference Example 4-31 R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = H, arrangement =
Compound of Z Yield (%) = 80. Mp (recrystallization _{solvent) = 172-174 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.02 (6H, d, J =
6.83Hz), 1.95-2.20 (1H, m), 3.72 (2H, d, J = 6.84Hz), 6.2
7 (1H, s), 6.83 (2H, dm, J = 8.30Hz), 7.13 (2H, dm, J = 8.30H
z), 7.18 (2H, dm, J = 8.79Hz), 7.34 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 330 (M ⁺ , ³⁵ Cl), 274, 257. Absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1600, 1590, 1510, 1295, 1250, 1175.

[0293]

Reference Example 4-32 R ¹ = 4-iso-BuOPh, R ² = 4-ClPh, R ¹¹ = H, arrangement =
Compound of E Yield (%) = 100. Melting point (recrystallization solvent) = 150-152 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.04 (6H, d, J =
6.35Hz), 2.00-2.20 (1H, m), 3.75 (2H, d, J = 6.34Hz), 6.1
9 (1H, s), 6.87 (2H, dm, J = 8.79Hz), 7.12 (2H, dm, J = 8.79H
. z), 7.21 (2H, dm, J = 8.78Hz), 7.30 (2H, dm, J = 8.78Hz) Mass spectrum (m / z): 330 ( M +, 35 Cl), 274, 257. Infrared Absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1590, 1515, 1290, 1245, 1175.

[0294]

Reference Example 4-33 Compound of R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = Et, Configuration = Z Yield (%) = 19. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.14 (3H, t, J = 7.33Hz), 1.74-1.90 (2H, m), 3.9
2 (2H, t, J = 6.83Hz), 4.05 (2H, q, J = 7.33Hz), 6.31 (1H, s),
6.83 (2H, dm, J = 9.28Hz), 7.14 (1H, dm, J = 8.79Hz), 7.20
(2H, dm, J = 9.28Hz), 7.36 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299, 272,
257, 230. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1595, 1510, 1370, 1275, 1250, 1160, 1150.

[0295]

Reference Example 4-34 Compound of R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 27. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.05 (3H, t, J =
7.33Hz), 1.16 (3H, t, J = 7.33Hz), 1.75-1.95 (2H, m), 3.
95 (2H, t, J = 6.84Hz), 4.09 (2H, q, J = 7.33Hz), 6.23 (1H,
s), 6.89 (2H, dm, J = 8.78Hz), 7.12 (2H, dm, J = 8.78Hz), 7.
22 (2H, dm, J = 8.79Hz), 7.29 (2H, dm, J = 8.79Hz) Mass spectrum (m / z):. 344 (M +, 35 Cl), 302, 299, 272,
257, 230. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1590, 1510, 1490, 1370, 1290, 1240, 1170, 1150.

[0296]

Reference Example 4-35 Compound of R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = H, Configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 159-161 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.70-1.90 (2H, m), 3.93 (2H, t, J = 6.84Hz), 6.2
7 (1H, s), 6.83 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.30H
. z), 7.19 (2H, dm, J = 8.79Hz), 7.34 (2H, dm, J = 8.30Hz) Mass spectrum (m / z): 316 ( M +, 35 Cl), 274, 257, 229. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 2400-3600 (broad), 169
5, 1600, 1595, 1510, 128
0, 1255, 1180.

[0297]

Reference Example 4-36 R ¹ = 4-PrOPh, R ² = 4-ClPh, R ¹¹ = H, arrangement = E
Compound yield (%) = 97. Melting point (recrystallization solvent) = 145-147 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.33Hz), 1.75-1.90 (2H, m), 3.95 (3H, t, J = 6.35Hz), 6.1
9 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.13 (2H, dm, J = 8.79H
. z), 7.21 (2H, dm, J = 8.79Hz), 7.30 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 316 ( M +, 35 Cl), 274, 257, 229. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1610, 1590, 1510, 1495, 1290, 1270,
1250, 1175.

[0298]

Reference Example 4-37 Compound in which R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = Et, configuration = E Yield (%) = 22. Melting point (recrystallization solvent) = 133-135 ° C (Et ₂ O) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.78 (6H, s), 3.87 (3H, s), 4.07 (2H, q, J = 7.32H
z), 6.31 (1H, s), 6.48 (2H, s), 7.03-7.13 (2H, m), 7.17-
7.25 (2H, m). Mass spectrum (m / z): 360 (M ⁺ ), 345, 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1580, 1505, 1465, 1415, 1355, 1165, 1155, 1130.

[0299]

Reference Example 4-38 Compound in which R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = Et, configuration = Z Yield (%) = 37. Melting point (recrystallization solvent) = 62-64 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.33Hz), 3.80 (6H, s), 3.90 (3H, s), 4.08 (2H, q, J = 7.33H
z), 6.26 (1H, s), 6.41 (2H, s), 6.98-7.08 (2H, m), 7.27-
7.36 (2H, m). Mass spectrum (m / z): 360 (M ⁺ ), 345, 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1585, 1505, 1465, 1415, 1370, 1310, 1160, 1130.

[0300]

Reference Example 4-39 Compound having R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = H, configuration = E Yield (%) = 98. Melting point (recrystallization solvent) = 201-204 ° C (CH ₂ Cl ₂ -Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.78 (6H, s),
3.87 (3H, s), 6.28 (1H, s), 6.46 (2H, s), 7.02-7.12 (2H,
m), 7.12-7.25 (2H, m). Mass spectrum (m / z): 332 (M ⁺ ), 317. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1580, 1505, 1130.

[0301]

Reference Example 4-40 Compound of R ¹ = 3,4,5-tri-CH ₃ OPh, R ² = 4-FPh, R ¹¹ = H, configuration = Z Yield (%) = 100. Melting point (recrystallization solvent) = 187-189 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.79 (6H, s),
3.91 (3H, s), 6.24 (1H, s), 6.42 (2H, s), 6.99-7.09 (2H,
m), 7.27-7.35 (2H, m). Mass spectrum (m / z): 332 (M ⁺ ), 317. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1585, 1505, 1415, 1125.

[0302]

Reference Example 4-41 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = E Yield (%) = 20. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 3.826 (3H, s), 3.848 (3H, s), 3.89 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.23 (1H, s), 6.77-6.89 (3H, m), 6.91
(2H, dm, J = 8.78Hz), 7.16 (2H, dm, J = 8.78Hz). Mass spectrum (m / z): 342 (M ⁺ ), 313, 297. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
5, 1580, 1510, 1465, 1290, 1165, 1135.

[0303]

Reference Example 4-42 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 30. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.81 (3H, s), 3.85 (3H, s), 3.92 (3H, s), 4.07
(2H, q, J = 7.32Hz), 6.24 (1H, s), 6.71 (1H, d, J = 1.95Hz),
6.77-6.94 (4H, m), 7.26 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 342 (M ⁺ ), 313, 297. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 1705, 160
0, 1510, 1465, 1250, 1170, 1135.

[0304]

Reference Example 4-43 Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 91. Melting point (recrystallization solvent) = 161-163 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
3.85 (3H, s), 3.89 (3H, s), 6.20 (1H, s), 6.74-6.82 (2H,
m), 6.84 (1H, br.s), 6.89 (2H, dm, J = 8.79Hz), 7.17 (2H, d
m, J = 8.79 Hz). Mass spectrum (m / z): 314 (M ⁺ ), 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 2400-3600 (broad), 168
5, 1605, 1595, 1510, 146
5, 1290, 1245, 1170, 113
5.

[0305]

[Reference Example 4-44] R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ OPh, R ¹¹ = H,
Compound of configuration = Z Yield (%) = 97. Melting point (recrystallization solvent) = 149-152 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
3.83 (3H, s), 3.92 (3H, s), 6.21 (1H, s), 6.74 (1H, d, J = 1.
95Hz), 6.80 (1H, dd, J = 8.30,1.95Hz), 6.82-6.93 (3H, m),
7.14-7.29 (2H, m). Mass spectrum (m / z): 314 (M ⁺ ), 299, 270. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1600, 1515, 1465, 1255, 1175, 1135.

[0306]

Reference Example 4-45 R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 62. Mp (recrystallization solvent) = oil NMR spectrum _{(60MHz, CDCl 3) δ ppm} : 1.15 (3H, t, J = 7H
z), 3.80 (3H, s), 4.06 (2H, q, J = 7Hz), 6.35 (1H, s), 6.8-
7.4 (7H, m).

[0307]

Reference Example 4-46 R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 23. Melting point (recrystallization solvent) = Oil NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J = 7H
z), 3.84 (3H, s), 4.06 (2H, q, J = 7Hz), 6.23 (1H, s), 6.7-
7.5 (7H, m).

[0308]

Reference Example 4-47 R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration =
Compound of Z Yield (%) = 84. Melting point (recrystallization solvent) = 181-184 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CD ₃ OD) δ ppm: 3.80 (3H, s),
6.36 (1H, s), 6.91 (2H, dm, J = 9.28Hz), 7.08 (1H, dd, J = 8.3
0,1.95Hz), 7.23 (2H, dm, J = 9.28Hz), 7.31 (1H, d, J = 1.95H
z), 7.51 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 277. Infrared absorption spectrum ν _max (KBr) cm-1: 2300 -3400 (br
oad), 1692, 1597, 1585, 1510, 1288, 1254, 1214, 11
78, 1162.

[0309]

Reference Example 4-48 R ¹ = 3,4-diClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration =
Compound of E Yield (%) = 95. Melting point (recrystallization solvent) = 193-196 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CD ₃ OD) δ ppm: 3.83 (3H, s),
6.30 (1H, s), 6.93 (2H, dm, J = 8.79Hz), 7.12 (2H, dm, J = 8.7
9Hz), 7.23 (1H, dd, J = 8.30,1.95Hz), 7.38 (1H, d, J = 1.95H)
z), 7.50 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 277. Infrared absorption spectrum ν _max (KBr) cm-1: 2300 -3400 (br
oad), 1688, 1662, 1602, 1512, 1407, 1281, 1253, 12
07, 1177.

[0310]

Reference Example 4-49 Compound of R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = Et, Configuration = E Yield (%) = 13. Melting point (recrystallization solvent) = 72-74 ° C (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.08 (3H, t, J =
7.32Hz), 3.84 (3H, s), 3.89 (3H, s), 4.03 (2H, q, J = 7.32H
z), 6.37 (1H, s), 6.72 (1H, dd, J = 8.30,1.96Hz), 6.80 (1H
H, d, J = 8.30Hz), 6.87 (1H, d, J = 1.96Hz), 7.35-7.70 (4H,
m). Mass spectrum (m / z): 380 (M ⁺ ), 361, 335. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1595, 1515, 146
0, 1370.

[0311]

Reference Example 4-50 Compound wherein R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = Et, configuration = Z Yield (%) = 16. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.18 (3H, t, J =
7.32Hz), 3.82 (3H, s), 3.93 (3H, s), 4.11 (2H, q, J = 7.32H
z), 6.30 (1H, s), 6.71 (1H, d, J = 1.95Hz), 6.81 (1H, dd, J =
8.30,1.96Hz), 6.89 (1H, d, J = 8.30Hz), 7.40-7.50 (2H,
m), 7.57-7.68 (2 H, m). Mass spectrum (m / z): 380 (M ⁺ ), 361, 335. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1515, 1460, 1370, 1325.

[0312]

Reference Example 4-51 Compound of R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 100. Melting point (recrystallization solvent) = 142-144 ° C (CH ₂ Cl ₂ -hexane)

[0313]

Reference Example 4-52 Compound of R ¹ = 3,4-diCH ₃ OPh, R ² = 3-CF ₃ Ph, R ¹¹ = H, configuration = Z Yield (%) = 100. Melting point (recrystallization solvent) = 140-143 ° C (CH ₂ Cl ₂ -hexane)

[0314]

Reference Example 4-53 Compound in which R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 21. Melting point (recrystallization solvent) = 75-77 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.32Hz), 2.39 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 4.06
(2H, q, J = 7.32Hz), 6.27 (1H, s), 6.77 (1H, d, J = 8.30Hz),
6.81 (1H, dd, J = 8.30,1.95Hz), 6.89 (1H, d, J = 1.95Hz), 7.
01-7.22 (4H, m). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1580, 1510, 1465, 1440, 1370, 1290, 1250, 1160,
1130.

[0315]

Reference Example 4-54 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 38. Melting point (recrystallization solvent) = 69-70 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 2.36 (3H, s), 3.81 (3H, s), 3.91 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.27 (1H, s), 6.72 (1H, d, J = 1.95Hz),
6.81 (1H, dd, J = 7.81,1.95Hz), 6.88 (1H, d, J = 7.81Hz), 7.
13 (2H, dm, J = 8.30Hz), 7.21 (2H, dm, J = 8.30Hz). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1510, 1465, 1415, 1370, 1250, 1160, 1135.

[0316]

REFERENCE EXAMPLE 4-55 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 97. Mp (recrystallization _{solvent) = 167-170 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.39 (3H, s),
3.88 (3H, s), 3.92 (3H, s), 6.24 (1H, s), 7.79 (1H, m), 6.
86 (1H, br.s), 7.08-7.22 (4H, m). Mass spectrum (m / z): 298 (M ⁺ ), 283. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400- 3600
(broad), 1690, 1600, 1580, 1510, 1465, 1440, 1420,
1325, 1290, 1250, 1175, 1135.

[0317]

Reference Example 4-56 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 4-CH ₃ Ph, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 185-188 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.36 (3H, s),
3.80 (3H, s), 3.92 (3H, s), 6.24 (1H, s), 6.75 (1H, d, J = 1.
95Hz), 6.79 (1H, dd, J = 8.30,1.95Hz), 6.86 (1H, d, J = 8.30
Hz), 7.10-7.23 (4H, m). Mass spectrum (m / z): 298 (M ⁺ ), 283. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1605, 1515, 1465, 1420, 1260, 1180,
1140.

[0318]

Reference Example 4-57 Compound of R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 52. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 2.33 (3H, s), 4.08 (2H, q, J = 7.32Hz), 6.36 (1H,
s), 7.03-7.13 (3H, m), 7.15-7.23 (2H, m), 7.30 (1H, d, J =
1.95Hz), 7.46 (1H, d, J = 8.30Hz). Mass spectrum (m / z): 334 (M ⁺ , ³⁵ Cl), 305, 289, 262. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 1715, 162
0, 1470, 1370, 1280, 1170, 1150.

[0319]

Reference Example 4-58 Compound in which R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 19. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 2.35 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.30 (1H,
s), 6.95-7.05 (2H, m), 7.12 (1H, dd, J = 8.79,1.95Hz), 7.
15-7.32 (2H, m), 7.379 (1H, d, J = 1.95Hz), 7.385 (1H, d, J =
8.79Hz). Mass spectrum (m / z): 334 (M ⁺ , ³⁵ Cl), 305, 289, 262. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720, 162
0, 1470, 1380, 1370, 1350, 1280, 1250, 1175.

[0320]

Reference Example 4-59 Compound of R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, Configuration = Z Yield (%) = 95. Mp (recrystallization _{solvent) = 163-165 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 2.33 (3H, s),
6.33 (1H, s), 7.00-7.10 (3H, m), 7.18-7.28 (2H, m), 7.29
(1H, d, J = 1.95Hz), 7.45 (1H, d, J = 7.81Hz). Mass spectrum (m / z): 306 (M ⁺ , ³⁵ Cl), 291, 261. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1600, 1585, 1475, 1290, 1125.

[0321]

Reference Example 4-60 Compound of R ¹ = 3,4-di-ClPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 92. Melting point (recrystallization solvent) = 152-154 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.34 (3H, s),
6.26 (1H, s), 6.94-7.03 (2H, m), 7.09 (1H, dd, J = 8.30,1.9
6Hz), 7.18-7.32 (2H, m), 7.35 (1H, d, J = 1.96Hz), 7.39 (1H
H, d, J = 8.30Hz). Mass spectrum (m / z): 306 (M ⁺ , ³⁵ Cl), 291, 261. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1620, 1470, 1410, 1285, 1180, 1130.

[0322]

Reference Example 4-61 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 23. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 2.36 (3H, s), 3.83 (3H, s), 3.88 (3H, s), 4.04
(2H, q, J = 7.32Hz), 6.29 (1H, s), 6.75-6.84 (2H, m), 6.90
(1H, br.s), 6.94-7.05 (2H, m), 7.15-7.31 (2H, m). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1515, 1470, 1445, 1330, 1295, 1255, 1160,
1145, 1130.

[0323]

Reference Example 4-62 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = Z Yield (%) = 33. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.33Hz), 2.33 (3H, s), 3.81 (3H, s), 3.92 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.72 (1H, d, J = 1.96Hz), 6.81 (1H, dd, J
= 8.30,1.96Hz), 6.88 (1H, d, J = 8.30Hz), 7.07-7.26 (4H,
m). Mass spectrum (m / z): 326 (M ⁺ ), 297, 281, 254. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 161
0, 1590, 1520, 1470, 1260, 1180, 1160, 1145, 1135.

[0324]

Reference Example 4-63 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 140-143 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.35 (3H, s),
3.82 (3H, s), 3.89 (3H, s), 6.27 (1H, s), 6.74-6.83 (2H,
m), 6.87 (1H, br.s), 6.99-7.06 (2H, m), 7.15-7.31 (2H,
m). Mass spectrum (m / z): 298 (M ⁺ ), 283, 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1600, 1580, 1515, 1470, 1260, 1170,
1145, 1130.

[0325]

Reference Example 4-64 Compound of R ¹ = 3,4-di-CH ₃ OPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 148-150 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.33 (3H, s),
3.81 (3H, s), 3.92 (3H, s), 6.24 (2H, s), 6.75 (1H, d, J = 1.
96Hz), 6.80 (1H, dd, J = 8.30,1.96Hz), 6.87 (1H, d, J = 8.30
Hz), 7.05-7.14 (2H, m), 7.16-7.24 (2H, m). Mass spectrum (m / z): 298 (M ⁺ ), 283, 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 2400-3600
(broad), 1690, 1605, 1585, 1515, 1450, 1440, 1420,
1255, 1175, 1135.

[0326]

Reference Example 4-65 Compound of R ¹ = 2-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = Z Yield (%) = 81. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.10 (3H, t, J =
7.33Hz), 3.81 (3H, s), 4.03 (2H, q, J = 7.33Hz), 6.48 (1H,
s), 6.85 (2H, dm, J = 9.28Hz), 7.11-7.20 (1H, m), 7.26 (2
H, dm, J = 9.28Hz), 7.26-7.37 (2H, m), 7.40-7.50 (1H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 281, 271, 253 . Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1575, 1515, 1465, 1370, 1355, 1280, 1255,
1160.

[0327]

Reference Example 4-66 Compound of R ¹ = 2-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 85. Melting point (recrystallization solvent) = 162-164 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.80 (3H, s),
6.44 (1H, s), 6.84 (2H, dm, J = 8.79Hz), 7.09-7.16 (1H,
m), 7.24 (2H, dm, J = 8.79Hz), 7.26-7.35 (2H, m), 7.37-7.
46 (1H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 253, 238. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1700, 1620, 1605, 1595, 1575, 1515, 1425,
1290, 1260, 1180, 1160.

[0328]

Reference Example 4-67 Compound of R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = Z Yield (%) = 8. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.13 (3H, t, J =
7.32Hz), 3.78 (3H, s), 4.06 (2H, q, J = 7.32Hz), 6.37 (1H,
s), 6.81 (1H, t, J = 1.96Hz), 6.86 (1H, ddd, J = 8.31,1.96,
0.98Hz), 6.91 (1H, ddd, J = 8.31,1.96,0.98Hz), 7.10 (1H,
dt, J = 7.81,1.95Hz), 7.20 (1H, t, J = 1.95Hz), 7.25 (1H, t,
J = 7.81Hz), 7.31 (1H, t, J = 7.81Hz), 7.35 (1H, dt, J = 7.81,
1.95Hz). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271, 243,
228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 162
0, 1600, 1580, 1490, 1470, 1435, 1370, 1350, 1290,
1280, 1170.

[0329]

Reference Example 4-68 Compound of R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 18. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.32Hz), 3.79 (3H, s), 4.06 (2H, q, J = 7.32Hz), 6.33 (1H,
s), 6.72 (1H, dd, J = 2.44,1.46Hz), 6.79 (1H, dt, J = 7.81,
1.46Hz), 6.93 (1H, ddd, J = 8.30,2.44,1.46Hz), 7.18 (1H,
dt, J = 7.32,1.46Hz), 7.22-7.36 (4H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271, 243,
228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1720, 162
0, 1590, 1580, 1570, 1490, 1470, 1430, 1370, 1350,
1290, 1260, 1170.

[0330]

Reference Example 4-69 Compound of R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 98. Melting point (recrystallization solvent) = 115-117 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.78 (3H, s),
6.35 (1H, s), 6.78 (1H, t, J = 1.47Hz), 6.84 (1H, dm, J = 7.81
Hz), 6.93 (1H, dm, J = 7.81Hz), 7.10 (1H, dt, J = 7.32,1.47H
z), 7.25 (1H, t, J = 7.81Hz), 7.30 (1H, t, J = 7.32Hz), 7.36
(1H, dt, J = 7.33,1.47 Hz). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400- 3600
(broad), 1695, 1620, 1600, 1580, 1490, 1435, 1410,
1345, 1290, 1150.

[0331]

Reference Example 4-70 Compound of R ¹ = 3-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, configuration = E Yield (%) = 96. Melting point (recrystallization solvent) = 140-142 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.79 (3H, s),
6.30 (1H, s), 6.72 (1H, dd, J = 2.44,1.47Hz), 6.78 (1H, dm,
J = 7.32Hz), 6.93 (1H, ddd, J = 8.30,2.44,0.97Hz), 7.16 (1
H, dt, J = 7.81,1.47Hz), 7.23-7.38 (4H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1620, 1600, 1590, 1570, 1490, 1470,
1460, 1430, 1350, 1285.

[0332]

Reference Example 4-71 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = Z Yield (%) = 10. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.32 (1H,
s), 6.85 (2H, dm, J = 9.28Hz), 7.09 (1H, dt, J = 7.30,1.96H
z), 7.18-7.39 (5H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ C
l), 287, 271, 244, 228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 16
05, 1600, 1570, 1515, 1465, 1420, 1370, 1350, 129
0, 1275, 1255, 1170, 1155.

[0333]

Reference Example 4-72 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 14. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.84 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.25 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.
15-7.36 (4H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271, 244,
228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 161
0, 1570, 1515, 1470, 1370, 1355, 1295, 1250, 1175.

[0334]

Reference Example 4-73 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, Configuration = Z Yield (%) = 94. Melting point (recrystallization solvent) = 158-160 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.29 (1H, s), 6.85 (2H, dm, J = 9.28Hz), 7.09 (2H, dt, J = 7.3
0,1.46Hz), 7.16-7.38 (5H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1605, 1590, 1570, 1515, 1425, 1285,
1255, 1180.

[0335]

Reference Example 4-74 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-ClPh, R ¹¹ = H, Configuration = E Yield (%) = 92. Melting point (recrystallization solvent) = 119-120 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.21 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.7
9Hz), 7.12-7.38 (4H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 271, 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1610, 1570, 1515, 1420, 1295, 1250,
1180.

[0336]

Reference Example 4-75 Compound in which R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 4. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.16 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.9
3 (2H, t, J = 6.84Hz), 4.07 (2H, q, J = 7.32Hz), 6.32 (1H, s),
6.84 (2H, dm, J = 8.79Hz), 7.06 (1H, dd, J = 8.30,1.95Hz),
7.20 (2H, dm, J = 8.79Hz), 7.29 (1H, d, J = 1.95Hz), 7.45 (1
H, d, J = 8.30Hz). Mass spectrum (m / z): 378 (M ⁺ , ³⁵ Cl), 336, 333, 308,
305, 291, 264.

[0337]

Reference Example 4-76 Compound in which R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = Et, configuration = E Yield (%) = 5. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.05 (3H, t, J =
7.32Hz), 1.17 (3H, t, J = 7.32Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.35Hz), 4.09 (2H, q, J = 7.32Hz), 6.22 (1H, s),
6.90 (2H, dm, J = 8.79Hz), 7.11 (2H, dm, J = 8.79Hz), 7.13
(1H, dd, J = 8.30,1.96Hz), 7.38 (1H, d, J = 1.96Hz), 7.39 (1
H, d, J = 8.30Hz). Mass spectrum (m / z): 378 (M ⁺ , ³⁵ Cl), 336, 333, 308,
305, 291, 264. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 163
0, 1515, 1470, 1390, 1370, 1350, 1290, 1280, 1245,
1170.

[0338]

Reference Example 4-77 Compound of R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 161-163 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.93 (2H, t, J = 6.84Hz), 6.2
9 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 7.06 (1H, dd, J = 8.30,
1.95Hz), 7.19 (2H, dm, J = 8.79Hz), 7.28 (1H, d, J = 1.95H)
z), 7.45 (1H, d, J = 8.30 Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 308, 291, 263. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 2400-3600
(broad), 1695, 1605, 1590, 1515, 1475, 1285, 1255,
1180.

[0339]

Reference Example 4-78 A compound in which R ¹ = 4-PrOPh, R ² = 3,4-di-ClPh, R ¹¹ = H, and configuration = E Yield (%) = 85. Melting point (recrystallization solvent) = 155-157 ° C (CH ₂ Cl ₂ -hexane)

[0340]

Reference Example 4-79 R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = Et, configuration =
Compound of E Yield (%) = 21. Melting point (recrystallization solvent) = 89-91 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.10 (3H, t, J =
7.33Hz), 1.46 (3H, t, J = 7.33Hz), 3.81 (3H, s), 4.03 (2H,
q, J = 7.33Hz), 4.10 (2H, q, J = 7.33Hz), 6.31 (1H, s), 6.77
(2H, br.s), 6.90 (1H, br.s), 7.16-7.25 (2H, m), 7.32-7.
41 (3H, m). Mass spectrum (m / z): 326 (M ⁺ , ³⁵ Cl), 297, 281, 253,
226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
5, 1600, 1580, 1515, 1480, 1470, 1370, 1320, 1290,
1250, 1160, 1135.

[0341]

Reference Example 4-80 R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = Et, configuration =
Compound of Z Yield (%) = 32. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 1.49 (3H, t, J = 7.32Hz), 3.80 (3H, s), 4.08 (2H,
q, J = 7.32Hz), 4.14 (2H, q, J = 7.32Hz), 6.28 (1H, s), 6.73
(1H, d, J = 1.95Hz), 6.79 (1H, dd, J = 8.30,1.95Hz), 6.87 (1
. H, d, J = 8.30Hz ), 7.29-7.40 (5H, m) Mass spectrum (m / z): 326 ( M +, 35 Cl), 297, 281, 253,
226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1580, 1515, 1480, 1470, 1450, 1410, 1370, 1355,
1320, 1250, 1160, 1130.

[0342]

Reference Example 4-81 R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = H, configuration =
Compound of E Yield (%) = 93. Melting point (recrystallization solvent) = 200-202 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 1.
45 (3H, t, J = 6.96Hz), 3.80 (3H, s), 4.11 (2H, q, J = 6.96H
z), 6.32 (1H, s), 6.80 (1H, dd, J = 8.43,1.83Hz), 6.84 (1
H, d, J = 8.43Hz), 6.88 (1H, d, J = 1.83Hz), 7.18-7.27 (2H,
m), 7.32-7.42 (3H, m). Mass spectrum (m / z): 298 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (KBr) cm-1: 2400-3600 (br
oad), 1692, 1660, 1605, 1587, 1514, 1479, 1421, 14
02, 1324, 1297, 1274, 1255, 1204, 1137.

[0343]

Reference Example 4-82 R ¹ = 3-CH ₃ O-4-EtO-Ph, R ² = Ph, R ¹¹ = H, configuration =
Compound of Z Yield (%) = 90. Melting point (recrystallization solvent) = 133-135 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.49 (3H, t, J =
7.33Hz), 3.80 (3H, s), 4.14 (2H, q, J = 7.32Hz), 6.25 (1H,
s), 6.72-6.86 (3H, m), 7.27-7.43 (5H, m). Mass spectrum (m / z): 298 (M ⁺ ), 270, 253, 225. Infrared absorption spectrum ν _max (CHCl ₃ ) Cm
-1: 2400-3600 (broad), 169
0, 1605, 1580, 1515, 147
0, 1450, 1415, 1255, 113
5.

[0344]

Reference Example 4-83 Compound in which R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, R ¹¹ = Et, Configuration = E Yield (%) = 21. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.43-1.54 (2
H, m), 1.78-1.86 (2H, m), 3.80 (3H, s), 4.02 (2H, t, J = 6.84
Hz), 4.03 (2H, q, J = 7.33 Hz), 6.31 (1H, s), 6.77 (2H, br.
s), 6.79 (1H, br.s), 7.17-7.24 (2H, m), 7.34-7.41 (3H,
m). Mass spectrum (m / z): 354 (M ⁺ ), 309, 298, 269, 226. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 169
0, 1610, 1595, 1580, 1510, 1465, 1370, 1290, 1270,
1250, 1160, 1135.

[0345]

Reference Example 4-84 R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 47. Melting point (recrystallization solvent) = Oil NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.98 (3H, t, J = 7H
z), 1.13 (3H, t, J = 7Hz), 1.30-2.20 (4H, m), 3.78 (3H, s),
4.02 (2H, t, J = 7Hz), 4.10 (2H, q, J = 7Hz), 6.30 (1H, s), 6.
70-7.05 (3H, m).

[0346]

Reference Example 4-85 R ¹ = 3-CH ₃ O-4-BuO-Ph, R ² = Ph, R ¹¹ = H, configuration =
Compound of E Yield (%) = 92. Melting point (recrystallization solvent) = 140-435 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 0.97 (3H, t, J =
7.33Hz), 1.40-1.60 (2H, m), 1.75-1.90 (2H, m), 3.79 (3
H, s), 4.02 (2H, t, J = 6.84Hz), 6.28 (1H, s), 6.75 (1H, dd,
J = 8.78,1.47Hz), 6.78 (1H, d, J = 8.78Hz), 6.85 (1H, d, J =
1.47 Hz), 7.17-7.24 (2H, m), 7.30-7.40 (3H, m). Mass spectrum (m / z): 326 (M ⁺ ), 2
70, 253, 237. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-360
0 (broad), 1690, 1610, 1595, 1580, 1510, 1500, 147
0, 1420, 1320, 1250, 1135.

[0347]

[Reference Example 4-86] R ¹ = 3,4-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 50. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 1.24 (3H, t, J = 7.32Hz), 2.66 (2H, q, J = 7.32Hz),
4.08 (2H, q, J = 7.32Hz), 6.37 (1H, s), 7.06 (1H, dd, J = 8.3
0,1.95Hz), 7.12-7.24 (4H, m), 7.30 (1H, d, J = 1.95Hz),
7.46 (1H, d, J = 8.30 Hz). Mass spectrum (m / z): 348 (M ⁺ , ³⁵ Cl), 319, 303, 276. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710 , 162
0, 1610, 1470, 1370, 1275, 1170, 1160.

[0348]

Reference Example 4-87 R ¹ = 3,4-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 14. Melting point (recrystallization solvent) = Oil NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.10 (3H, t, J = 7H
z), 1.27 (3H, t, J = 7Hz), 2.70 (2H, q, J = 7Hz), 4.05 (2H, q, J
= 7Hz), 6.27 (1H, s), 6.98-7.60 (7H, m).

[0349]

[Reference Example 4-88] R ¹ = 3,4-di-ClPh, R ² = 4-EtPh, R ¹¹ = H, configuration =
Compound of Z Yield (%) = 94. Mp (recrystallization _{solvent) = 172-174 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.24 (3H, t, J =
7.32Hz), 2.66 (2H, q, J = 7.32Hz), 6.35 (1H, s), 7.06 (1H,
dd, J = 7.82,1.95Hz), 7.12-7.24 (4H, m), 7.29 (1H, d, J = 1.
95Hz), 7.45 (1H, d, J = 7.82Hz). Mass spectrum (m / z): 320 (M ⁺ , ³⁵ Cl), 305, 291, 275. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 2400-3600
(broad), 1690, 1620, 1605, 1470, 1280, 1180, 1160,
1120.

[0350]

Reference Example 4-89 Compound of R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 35. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.05 (3H, t, J =
7.33Hz), 1.67 (3H, t, J = 7.33Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.60Hz), 4.09 (2H, q, J = 7.33Hz), 6.26 (1H, s),
6.89 (2H, dm, J = 8.80Hz), 7.14 (2H, dm, J = 8.80Hz), 7.26-
7.40 (5H, m). Mass spectrum (m / z): 310 (M ⁺ ), 268, 265, 238, 223,
196. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1370, 1290, 1260, 1240, 1170.

[0351]

Reference Example 4-90 Compound of R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = E Yield (%) = 35. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.33Hz), 1.10 (3H, t, J = 7.33Hz), 1.75-1.90 (2H, m), 3.9
2 (2H, t, J = 6.84Hz), 4.03 (2H, q, J = 7.33Hz), 6.30 (1H, s),
6.82 (2H, dm, J = 9.27Hz), 7.15-7.28 (2H, m), 7.23 (2H, d
m, J = 9.27Hz), 7.28-7.43 (3H, m) .Mass spectrum (m / z): 310 (M ⁺ ), 268, 265, 238, 223,
196. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1595, 1575, 1510, 1370, 1250, 1160, 1150.

[0352]

Reference Example 4-91 Compound of R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = H, Configuration = Z Yield (%) = 93. Melting point (recrystallization solvent) = 183-185 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.33Hz), 1.75-1.90 (2H, m), 3.95 (2H, t, J = 6.84Hz), 6.2
3 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.79H
z), 7.26-7.42 (5H, m). Mass spectrum (m / z): 282 (M ⁺ ), 240, 223, 195. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1695, 1610, 1515, 1290, 1280, 1250, 1175.

[0353]

Reference Example 4-92 Compound having R ¹ = 4-PrOPh, R ² = Ph, R ¹¹ = H, configuration = E Yield (%) = 92. Melting point (recrystallization solvent) = 138-140 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (60MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7Hz), 1.45-2.20 (2H, m), 3.90 (2H, q, J = 7Hz), 6.27 (1H,
s), 6.83 (2H, dm, J = 9Hz), 7.05-7.60 (7H, m), 10.00 (1H, b
rm).

[0354]

Reference Example 4-93 R ¹ = 3,4-methylenedioxy-Ph, R ² = Ph, R ¹¹ =
Compound of H, configuration = E Yield (%) = 22. Melting point (recrystallization solvent) = 222-224 ° C (Et ₂ O-tetrahydrofuran) NMR spectrum (60 MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 5.
99 (2H, s), 6.29 (1H, s), 6.79 (3H, s), 7.05-7.60 (5H, m).

[0355]

Reference Example 4-94 R ¹ = 3,4-methylenedioxy-Ph, R ² = Ph, R ¹¹ =
H, Configuration = Z Compound Yield (%) = 51. Melting point (recrystallization solvent) = 141-143 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 6.00 (2H, s),
6.26 (1H, s), 6.72-6.96 (3H, m), 7.15-7.55 (5H, m).

[0356]

Reference Example 4-95 Compound in which R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = E Yield (%) = 22. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.11 (3H, t, J = 7.32Hz), 1.80-1.95 (2H, m), 2.3
5 (3H, s), 3.81 (3H, s), 3.98 (2H, t, J = 6.84Hz), 4.04 (2H,
q, J = 7.32Hz), 6.29 (1H, s), 6.72-6.86 (2H, m), 6.90 (1H,
br.s), 6.98-7.05 (2H, m), 7.15-7.24 (1H, m), 7.30-7.42
(1H, m). Mass spectrum (m / z): 354 (M ⁺ ), 312, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1580, 1510, 1485, 1370, 1290, 1260, 1160, 1145,
1130.

[0357]

Reference Example 4-96 Compound in which R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = Et, configuration = Z Yield (%) = 40. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.05 (3H, t, J =
7.32Hz), 1.15 (3H, t, J = 7.32Hz), 1.80-1.95 (2H, m), 2.3
2 (3H, s), 3.80 (3H, s), 4.02 (2H, t, J = 6.84Hz), 4.08 (2H,
q, J = 7.32Hz), 6.26 (1H, s), 6.72 (1H, d, J = 1.96Hz), 6.78
(1H, dd, J = 7.82,1.96Hz), 6.87 (1H, d, J = 7.82Hz), 7.06-
7.25 (4H, m). Mass spectrum (m / z): 354 (M ⁺ ), 312, 267, 240. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1515, 1465, 1370, 1250, 1180, 1160, 1130.

[0358]

Reference Example 4-97 Compound in which R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, configuration = E Yield (%) = 98. Melting point (recrystallization solvent) = 123-126 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.33Hz), 1.75-1.95 (2H, m), 2.34 (3H, s), 3.80 (3H, s),
3.98 (2H, t, J = 6.84Hz), 6.26 (1H, s), 6.74 (1H, dd, J = 8.7
9,1.95Hz), 6.78 (1H, d, J = 8.79Hz), 6.86 (1H, d, J = 1.95H
z), 6.98-7.05 (2H, m), 7.14-7.30 (2H, m). Mass spectrum (m / z): 326 (M ⁺ ), 284, 267, 239. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1595, 1580, 1515, 1470, 1260, 1175,
1145, 1130.

[0359]

Reference Example 4-98 Compound of R ¹ = 3-CH ₃ O-4-PrOPh, R ² = 3-CH ₃ Ph, R ¹¹ = H, Configuration = Z Yield (%) = 97. Melting point (recrystallization solvent) = 132-135 ° C (CH ₂ Cl ₂ -hexane)

[0360]

Reference Example 4-99 Compound of R ¹ = 3-CH ₃ Ph, R ² = 3-CH ₃ Ph, R ¹¹ = Et Yield (%) = 78. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 2.32 (3H, s), 2.35 (3H, s), 4.03 (2H, q, J = 7.32H
z), 6.31 (1H, s), 6.98-7.30 (8H, m). Mass spectrum (m / z): 280 (M ⁺ ), 265, 251, 235, 208. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1600, 1580, 1370, 1350, 1280, 1190, 1160.

[0361]

Reference Example 4-100 Compound of R ¹ = 3-CH ₃ Ph, R ² = 3-CH ₃ Ph, and R ¹¹ = H Yield (%) = 94. Melting point (recrystallization solvent) = 133-135 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.32 (3H, s),
2.34 (3H, s), 6.28 (1H, s), 6.98-7.12 (4H, m), 7.14-7.30
(4H, m). Mass spectrum (m / z): 252 (M ⁺ ), 237, 235, 207. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600
(broad), 1690, 1615, 1600, 1580, 1430, 1285, 1170.

[0362]

Reference Example 4-101 Compound of R ¹ = 3-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = Z Yield (%) = 10. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.02 (3H, t, J =
7.33Hz), 1.12 (3H, t, J = 7.33Hz), 1.70-1.85 (2H, m), 3.8
8 (2H, t, J = 6.84Hz), 4.06 (2H, q, J = 7.33Hz), 6.37 (1H, s),
6.80-6.86 (2H, m), 6.90 (1H, ddd, J = 8.30,2.44,0.97Hz),
7.10 (1H, ddd, J = 6.84,1.47,1.47Hz), 7.19-7.38 (4H, m). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1600, 1580, 1485, 1475, 1440, 1370, 1350, 1290,
1170.

[0363]

Reference Example 4-102 Compound of R ¹ = 3-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 18. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.02 (3H, t, J =
7.33Hz), 1.12 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.8
9 (2H, t, J = 6.84Hz), 4.06 (2H, q, J = 7.33Hz), 6.32 (1H, s),
6.71 (1H, m), 6.77 (1H, ddd, J = 7.81,1.46,0.98Hz), 6.92
(1H, ddd, J = 8.30,2.93,0.98Hz), 7.16-7.35 (5H, m). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1600, 1580, 157
0, 1475, 1440, 1370, 135
0, 1280, 1260, 1170, 103
0.

[0364]

Reference Example 4-103 R ¹ = 3-PrOPh, R ² = 3-ClPh, R ¹¹ = H, configuration = Z
Compound yield (%) = 94. Melting point (recrystallization solvent) = 118-120 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.02 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.88 (2H, t, J = 6.84Hz), 6.3
4 (1H, s), 6.77-6.85 (2H, m), 6.92 (1H, ddd, J = 7.32,2.44,
0.98Hz), 7.10 (1H, ddd, J = 7.31,1.46,1.46Hz), 7.17-7.3
8 (4H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1695, 162
0, 1600, 1580, 1490, 1480, 1440, 1410, 1350, 1290,
1150.

[0365]

Reference Example 4-104 Compound of R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = Z Yield (%) = 10. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.12 (3H, t, J = 7.32Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.84Hz), 4.04 (2H, q, J = 7.32Hz), 6.31 (1H, s),
6.84 (2H, dm, J = 8.79Hz), 7.09 (1H, ddd, J = 6.84,1.95,1.9
5Hz), 7.17-7.20 (1H, m), 7.21 (2H, dm, J = 8.79Hz), 7.28-
7.40 (2H, m). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1590, 1570, 1510, 1470, 1370, 1275, 1255, 1170,
1155.

[0366]

Reference Example 4-105 Compound of R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = Et, Configuration = E Yield (%) = 14. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.05 (3H, t, J =
7.32Hz), 1.17 (3H, t, J = 7.32Hz), 1.75-1.90 (2H, m), 3.9
5 (2H, t, J = 6.84Hz), 4.09 (2H, q, J = 7.32Hz), 6.24 (1H, s),
6.89 (2H, dm, J = 8.79Hz), 7.12 (1H, dm, J = 8.79Hz), 7.17
(1H, ddd, J = 7.81,1.95,1.95Hz), 7.25 (1H, dd, J = 7.81,7.8
1Hz), 7.28 (1H, dd, J = 1.95,1.95Hz), 7.33 (1H, ddd, J = 7.8
1,1.95,1.95Hz). Mass spectrum (m / z): 344 (M ⁺ , ³⁵ Cl), 302, 299. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1470, 1290, 1240, 1170.

[0367]

Reference Example 4-106 Compound of R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = H, Configuration = Z Yield (%) = 92. Melting point (recrystallization solvent) = 174.5-176.5 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.03 (3H, t, J =
7.32Hz), 1.74-1.90 (2H, m), 3.93 (2H, t, J = 6.83Hz), 6.2
9 (1H, s), 6.84 (2H, dm, J = 9.28Hz), 7.09 (1H, ddd, J = 7.33,
1.95,1.95Hz), 7.16-7.20 (1H, m), 7.20 (2H, dm, J = 9.28H
z), 7.27-7.38 (2H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257, 229. Infrared absorption spectrum ν _max (KBr) cm-1: 3400- 2400, 1
665, 1600, 1585, 1510, 1305, 1260, 1245, 1180.

[0368]

Reference Example 4-107 Compound of R ¹ = 4-PrOPh, R ² = 3-ClPh, R ¹¹ = H, Configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 147-149 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.06 (3H, t, J =
7.32Hz), 1.75-1.90 (2H, m), 3.96 (2H, t, J = 6.34Hz), 6.2
0 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79H
z), 7.14-7.19 (1H, m), 7.23-7.38 (3H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 274, 257, 229. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1610, 1570, 1515, 1290, 1250, 1180.

[0369]

Reference Example 4-108 Compound of R ¹ = 2-ClPh, R ² = 3-CH ₃ OPh, R ¹¹ = Et, Configuration = Z Yield (%) = 63. Melting point (recrystallization solvent) = 82-84 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.10 (3H, t, J =
7.32Hz), 3.78 (3H, s), 4.04 (2H, q, J = 7.32Hz), 6.54 (1H,
s), 6.84-6.94 (3H, m), 7.14-7.19 (1H, m), 7.21-7.36 (3
H, m), 7.40-7.48 (1H, m). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 281, 271, 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1 : 1715, 161
5, 1600, 1580, 1490, 1470, 1435, 1370, 1350, 1290,
1170, 1050, 1035.

[0370]

Reference Example 4-109 Compound of R ¹ = 2-ClPh, R ² = 3-CH ₃ OPh, R ¹¹ = H, Configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 140-142 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.77 (3H, s),
6.51 (1H, s), 6.83 (1H, dd, J = 1.95,1.95Hz), 6.86-6.94 (2
H, m), 7.11-7.18 (1H, m), 7.21-7.35 (3H, m), 7.38-7.46
(1H, m). Mass spectrum (m / z): 288 (M ⁺ , ³⁵ Cl), 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1695, 1625, 1600, 1580, 1490, 1470, 1430, 1290,
1050.

[0371]

Reference Example 4-110 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = Et, Configuration = Z Yield (%) = 9. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.31 (1H,
s), 6.85 (2H, dm, J = 8.79Hz), 7.14 (1H, ddd, J = 7.81,1.47,
1.47Hz), 7.22 (2H, dm, J = 8.79Hz), 7.25 (1H, ddd, J = 7.81,
7.81,1.47Hz), 7.35 (1H, dd, J = 1.47,1.47Hz), 7.51 (1H, d
dd, J = 7.81,1.47,1.47Hz). Mass spectrum (m / z): 360 (M ⁺ , ⁷⁹ Br), 333, 315, 288. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710 , 160
0, 1510, 1370, 1290, 1270, 1250, 1165, 1025, 830.

[0372]

Reference Example 4-111 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = Et, Configuration = E Yield (%) = 12. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.84 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.24 (1H,
s), 6.90 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.
18-7.24 (2H, m), 7.43-7.52 (2H, m). Mass spectrum (m / z): 360 (M ⁺ , ⁷⁹ Br), 333, 315, 288. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 161
0, 1515, 1375, 1295, 1250, 1175, 1030, 840.

[0373]

Reference Example 4-112 Compound of R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = H, Configuration = Z Yield (%) = 97. Melting point (recrystallization solvent) = 169-171 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.29 (1H, s), 6.85 (2H, dm, J = 9.28Hz), 7.14 (1H, ddd, J = 7.
81,1.95,0.98Hz), 7.21 (2H, dm, J = 9.28Hz), 7.25 (1H, dd,
J = 7.81,7.81Hz), 7.33 (1H, dd, J = 1.95,1.95Hz), 7.51 (1
H, ddd, J = 7.81,1.95,0.98Hz). Mass spectrum (m / z): 332 (M ⁺ , ⁷⁹ Br), 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 2400-3600, 1685, 159
5, 1570, 1555, 1505, 142
0, 1275, 1250, 1170, 102
0,825.

[0374]

Reference Example 4-113 R ¹ = 4-CH ₃ OPh, R ² = 3-BrPh, R ¹¹ = H, configuration = E
Compound yield (%) = 96. Melting point (recrystallization solvent) = 131-132 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.20 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.7
9Hz), 7.18-7.24 (2H, m), 7.40-7.44 (1H, m), 7.46-7.54
(1H, m). Mass spectrum (m / z): 332 (M ⁺ , ⁷⁹ Br), 315. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1690, 1610, 1560, 1510, 1470, 1420, 1295, 1245, 1
175, 1030,835.

[0375]

Reference Example 4-114 Compound of R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = Z Yield (%) = 55. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.33Hz), 3.82 (3H, s), 4.04 (2H, q, J = 7.33Hz), 6.32 (1H, s
s), 6.85 (2H, dm, J = 8.79Hz), 6.91 (1H, ddd, J = 9.53,2.57,
1.47Hz), 6.99 (1H, dm, J = 7.69Hz), 7.03-7.11 (1H, m), 7.
23 (2H, dm, J = 8.79Hz), 7.35 (1H, ddd, J = 7.69,7.69,5.87H
z). Mass spectrum (m / z): 300 (M ⁺ ), 271, 255, 228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1585, 1510, 1440, 1370, 1275, 1250, 1160, 1030,
830.

[0376]

Reference Example 4-115 Compound of R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = E Yield (%) = 22. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.84 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.27 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 6.98 (1H, ddd, J = 10.25,2.4
4,1.96Hz), 7.05 (1H, dddd, J = 8.30,8.30,2.44,0.98Hz),
7.08-7.12 (1H, m), 7.15 (2H, dm, J = 8.79Hz), 7.29 (1H, ddd,
J = 8.30,8.30,5.86Hz). Mass spectrum (m / z): 300 (M ⁺ ), 271, 255, 228. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1585, 1510, 1485, 1440, 1370, 1295, 1280, 1245,
1170, 1030, 1030, 870, 830.

[0377]

Reference Example 4-116 Compound of R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 166-167 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.29 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 6.91 (1H, ddd, J = 9.
76,2.44,1.46Hz), 6.95-7.01 (1H, m), 7.07 (1H, dddd, J =
8.30,8.30,2.44,0.97Hz), 7.21 (2H, dm, J = 8.79Hz), 7.33
(1H, ddd, J = 8.30,8.30,5.86Hz). Mass spectrum (m / z): 272 (M ⁺ ), 255, 227. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600 ,
1695, 1600, 1515, 1440, 1285, 1255, 1180, 1120, 10
35.

[0378]

Reference Example 4-117 Compound of R ¹ = 3-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 133-135 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.23 (1H, s), 6.89 (2H, dm, J = 8.79Hz), 6.96 (1H, ddd, J = 9.
77,1.96,1.96Hz), 7.02-7.12 (2H, m), 7.15 (2H, dm, J = 8.7
9Hz), 7.30 (1H, ddd, J = 8.30, 8.30, 5.86Hz). Mass spectrum (m / z): 272 (M ⁺ ), 255, 227. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 2400-3600, 1690, 161
0, 1580, 1510, 1485, 1440,
1290, 1245.

[0379]

Reference Example 4-118 R ¹ = 3-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration =
Compound of Z Yield (%) = 56. Mp (recrystallization solvent) = oil NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 1.08 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.03 (2H, q, J = 7.32Hz), 6.37 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.21 (2H, dm, J = 8.79Hz), 7.
37-7.43 (1H, m), 7.44-7.47 (1H, m), 7.48-7.55 (1H, m),
7.61-7.67 (1H, m). Mass spectrum (m / z): 350 (M ⁺ ), 331, 321, 305, 278. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1510, 1325, 1255, 1165, 1130, 1070, 1030.

[0380]

Reference Example 4-119 R ¹ = 3-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement = E
Compound yield (%) = 15. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.18 (3H, t, J =
7.33Hz), 3.85 (3H, s), 4.11 (2H, q, J = 7.33Hz), 6.28 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 7.15 (2H, dm, J = 8.79Hz), 7.
37-7.53 (2H, m), 7.56-7.64 (2H, m). Mass spectrum (m / z): 350 (M ⁺ ), 331, 321, 305, 278. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1370, 1330, 1295, 1245, 1170, 1150, 1130,
1070, 1030.

[0381]

Reference Example 4-120 R ¹ = 3-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z
Compound yield (%) = 91. Mp (recrystallization _{solvent) = 165-167 ℃ (CH 2 Cl} 2 -hexane) NMR spectrum _{(270MHz, CDCl 3) δ ppm} : 3.82 (3H, s),
6.33 (1H, s), 6.86 (2H, dm, J = 8.79Hz), 7.19 (2H, dm, J = 8.7
9Hz), 7.37 (1H, br.d, J = 7.82Hz), 7.45 (1H, br.s), 7.48 (1H
H, br.dd, J = 7.82,7.82Hz), 7.63 (1H, br.d, J = 7.82Hz). Mass spectrum (m / z): 322 (M ⁺ ), 305, 277, 263. Infrared Absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1690, 1600, 1575, 1510, 1440, 1325, 1310, 1290, 1
260, 1180, 1150, 1130, 1070.

[0382]

Reference Example 4-121 Compound of R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = E Yield (%) = 23. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.32Hz), 1.10 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.8
7 (2H, t, J = 6.84Hz), 4.04 (2H, q, J = 7.32Hz), 6.35 (1H, s),
6.82-6.92 (3H, m), 7.16-7.40 (6H, m).

[0383]

Reference Example 4-122 Compound of R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = Et, Configuration = Z Yield (%) = 47. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.32Hz), 1.12 (3H, t, J = 7.32Hz), 1.70-1.90 (2H, m), 3.8
9 (2H, t, J = 6.84Hz), 4.06 (2H, q, J = 7.32Hz), 6.34 (1H, s),
6.72-6.96 (3H, m), 7.23-7.38 (6H, m).

[0384]

Reference Example 4-123 Compound of R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = H, Configuration = E Yield (%) = 51. Melting point (recrystallization solvent) = 120-122 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.00 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.86 (2H, t, J = 6.70Hz), 6.3
1 (1H, s), 6.78-6.85 (2H, m), 6.88-6.94 (1H, m), 7.16-7.
28 (3H, m), 7.28-7.40 (3H, m). Mass spectrum (m / z): 282 (M ⁺ ), 240,
223. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-360
0, 1690, 1610, 1600, 1580, 1485, 1440, 1400, 1285.

[0385]

Reference Example 4-124 Compound of R ¹ = 3-PrOPh, R ² = Ph, R ¹¹ = H, Configuration = Z Yield (%) = 67. Melting point (recrystallization solvent) = 120-122 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7.33Hz), 1.70-1.90 (2H, m), 3.89 (2H, t, J = 6.84Hz), 6.3
1 (1H, s), 6.73 (1H, dd, J = 2.44,1.47Hz), 6.78 (1H, ddd, J =
7.32,1.47,0.98Hz), 6.91 (1H, ddd, J = 8.30,2.44,0.98H
z), 7.22-7.40 (6H, m). Mass spectrum (m / z): 282 (M ⁺ ), 240, 223. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1680, 1590, 1570, 1480,1440, 1425, 1390, 1275, 11
00.

[0386]

Reference Example 4-125 Compound of R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 64. Melting point (recrystallization solvent) = 116-118 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.06 (2H, q, J = 7.32Hz), 6.33 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.09 (2H, d, J = 1.83Hz), 7.2
1 (2H, dm, J = 8.79Hz), 7.37 (1H, t, J = 1.83Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 321, 305, 278. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1585, 1560, 1510, 1370, 1345, 1290, 1270, 1250,
1170, 1160, 1030, 860, 830.

[0387]

Reference Example 4-126 Compound in which R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 19. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.85 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.23 (1H,
s), 6.91 (2H, dm, J = 8.79Hz), 7.13 (2H, dm, J = 8.79Hz), 7.
16 (2H, d, J = 1.96Hz), 7.35 (1H, t, J = 1.96Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 321, 305, 278. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1580, 1560, 1510, 1415, 1370, 1350, 1290, 1245,
1170, 1030, 860, 835.

[0388]

Reference Example 4-127 Compound of R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 71. Melting point (recrystallization solvent) = 214-216 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.78 (3H, s),
6.37 (1H, s), 6.94 (2H, dm, J = 8.79Hz), 7.17 (2H, d, J = 1.95
. Hz), 7.23 (2H, dm, J = 8.79Hz), 7.57 (1H, t, J = 1.95Hz) Mass spectrum (m / z): 322 ( M +, 35 Cl), 305, 277. Infrared Absorption spectrum ν _max (KBr) cm-1: 2400-3400, 1
695, 1670, 1600, 1580,1560, 1510, 1290, 1260, 121
5, 1185, 1170, 1035, 840, 800.

[0389]

Reference Example 4-128 Compound of R ¹ = 3,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = E Yield (%) = 80. Melting point (recrystallization solvent) = 169-171 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.19 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 7.13 (2H, dm, J = 8.7
9Hz), 7.14 (2H, d, J = 1.95Hz), 7.36 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 305, 277. Absorption spectrum ν _max (KBr) cm-
1: 2400-3400, 1700, 1675,
1610, 1580, 1560, 1510, 1
425, 1350, 1280, 1250, 12
20, 1175, 1030, 850, 835,
805.

[0390]

Reference Example 4-129 Compound of R ¹ = 2,4-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 83. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.33Hz), 3.81 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.48 (1H,
s), 6.85 (2H, dm, J = 8.80Hz), 7.09 (1H, d, J = 8.42Hz), 7.2
4 (2H, dm, J = 8.80Hz), 7.30 (1H, dd, J = 8.42,1.84Hz), 7.47
(1H, d, J = 1.84 Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 315, 305, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1590, 1510, 1280, 1255, 1170, 1030, 830.

[0391]

Reference Example 4-130 Compound of R ¹ = 2,4-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 90. Melting point (recrystallization solvent) = 162-164 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
6.44 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 7.07 (1H, d, J = 8.30
Hz), 7.22 (2H, dm, J = 8.79Hz), 7.28 (1H, dd, J = 8.30,1.95H
z), 7.45 (1H, d, J = 1.95 Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1700, 160
0, 1590, 1510, 1285, 1260, 1180, 1155, 830.

[0392]

Reference Example 4-131 Compound of R ¹ = 4-CH ₃ OPh, R ² = 2,6-di-ClPh, R ¹¹ = Et, configuration = Z Yield (%) = 60. Melting point (recrystallization solvent) = 119-121 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.13 (3H, t, J =
7.33Hz), 3.81 (3H, s), 4.06 (2H, q, J = 7.33Hz), 6.56 (1H,
s), 6.87 (2H, dm, J = 9.28Hz), 7.22-7.34 (1H, m), 7.30 (2H
H, dm, J = 9.27Hz), 7.35-7.41 (2H, m). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 315, 305, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
5, 1575, 1510, 1430, 1290, 1275, 1255, 1160, 1025,
830.

[0393]

Reference Example 4-132 Compound of R ¹ = 4-CH ₃ OPh, R ² = 2,6-di-ClPh, R ¹¹ = H, configuration = Z Yield (%) = 98. Melting point (recrystallization solvent) = 222-224 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
6.53 (1H, s), 6.87 (2H, dm, J = 8.79Hz), 7.20-7.40 (3H, m),
7.28 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 322 (M ⁺ , ³⁵ Cl), 307, 305, 287,
272. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1700, 1600, 1575, 1515,1430, 1290, 1260, 1180, 11
60, 835.

[0394]

Reference Example 4-133 Compound of R ¹ = 2,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = Z Yield (%) = 82. Melting point (recrystallization solvent) = 98-100 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.13 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.47 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.15 (1H, d, J = 2.44Hz), 7.2
5 (2H, dm, J = 8.79Hz), 7.29 (1H, dd, J = 8.30,2.44Hz), 7.37
(1H, d, J = 8.30Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 315, 305, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 160
5, 1515, 1470, 1295, 1280, 1260, 1170, 1165, 1100,
1030, 835.

[0395]

Reference Example 4-134 Compound of R ¹ = 2,5-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = Z Yield (%) = 97. Melting point (recrystallization solvent) = 201-203 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, d ₆ -DMSO) δ ppm: 3.77 (3H,
s), 6.53 (1H, s), 6.94 (2H, dm, J = 8.79Hz), 7.25 (2H, dm, J
= 8.79Hz), 7.29 (1H, d, J = 2.44Hz), 7.46 (1H, dd, J = 8.79,
. 2.44Hz), 7.53 (1H, d, J = 8.79Hz), 12.13 (1H, br.s) mass spectrum (m / z): 322 ( M +, 35 Cl), 305, 287, 272. Infrared Absorption spectrum ν _max (KBr) cm-1: 2200-3300, 1
690, 1595, 1580, 1510,1465, 1425, 1345, 1280, 126
0, 1210, 1185, 1160, 1030, 835.

[0396]

Reference Example 4-135 Compound of R ¹ = 2,3-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 70. Melting point (recrystallization solvent) = 88-90 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 3.81 (3H, s), 4.03 (2H, q, J = 7.32Hz), 6.47 (1H,
s), 7.07 (1H, dd, J = 7.70,1.47Hz), 7.20-7.40 (3H, m), 7.
49 (1H, dd, J = 8.06,1.47Hz). Mass spectrum (m / z): 350 (M ⁺ , ³⁵ Cl), 315, 305, 287. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1 : 1710, 160
0, 1575, 1510, 1455, 1410, 1370, 1350, 1280, 1255,
1160, 1030, 830.

[0397]

Reference Example 4-136 Compound of R ¹ = 2,3-di-ClPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 89. Melting point (recrystallization solvent) = 129-131 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.81 (3H, s),
6.44 (1H, s), 6.85 (2H, dm, J = 8.78Hz), 7.05 (1H, dd, J = 7.8
1,1.47Hz), 7.23 (1H, dd, J = 7.81,7.81Hz), 7.24 (2H, dm, J
= 8.78Hz), 7.47 (1H, dd, J = 7.81,1.47Hz) mass spectrum ^{(m / z):. 322} (M +, 35 Cl),
287.

[0398]

Reference Example 4-137 Compound of R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 57. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.11 (3H, t, J =
7.32Hz), 2.31 (6H, s), 3.81 (3H, s), 4.04 (2H, q, J = 7.32H
z), 6.26 (1H, s), 6.80 (2H, br.s), 6.83 (2H, dm, J = 9.16H
z), 6.99 (1H, t, J = 0.73Hz), 7.25 (2H, dm, J = 9.16Hz). Mass spectrum (m / z): 310 (M ⁺ ), 281, 265, 238. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1460, 1440, 1370, 1350, 1290, 1245, 1170,
1030, 850,840.

[0399]

Reference Example 4-138 Compound of R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = E Yield (%) = 24. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 2.27 (3H, s), 2.28 (3H, s), 3.84 (3H, s), 4.08
(2H, q, J = 7.32Hz), 6.24 (1H, s), 6.895 (2H, dm, J = 8.79H
z), 6.904 (2H, br.s), 6.99 (1H, br.s), 7.15 (2H, dm, J = 8.
79Hz). Mass spectrum (m / z): 310 (M ⁺ ), 281, 265, 238. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1510, 1460, 1440, 1370, 1350, 1290, 1245, 1170,
1030, 850,840.

[0400]

Reference Example 4-139 Compound of R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 156-158 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.31 (6H, s),
3.81 (3H, s), 6.24 (1H, s), 6.82 (2H, br.s), 6.84 (2H, dm,
J = 8.78Hz), 7.01 (1H, br.s), 7.22 (2H, dm, J = 8.78Hz). Mass spectrum (m / z): 282 (M ⁺ ), 267, 237. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2400-3600,
1690, 1600, 1570, 1510,1285, 1250, 1175, 1030, 83
Five.

[0401]

Reference Example 4-140 Compound of R ¹ = 3,5-di-CH ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 165-166 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.28 (6H, s),
3.85 (3H, s), 6.20 (1H, s), 6.86-6.90 (2H, m), 6.88 (2H, d
m, J = 8.79Hz), 7.01 (1H, br.s), 7.16 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 282 (M ⁺ ), 267, 237. Infrared absorption Spectrum ν _max (CHCl ₃ ) cm-1: 2200-3700,
1690, 1610, 1510, 1290,1240, 1175, 1030, 835.

[0402]

Reference Example 4-141 Compound of R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = Et, Configuration = E Yield (%) = 13. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.33Hz), 1.28 (3H, t, J = 7.69Hz), 2.70 (2H, q, J = 7.69Hz),
4.07 (2H, q, J = 7.33Hz), 6.29 (1H, s), 7.11 (2H, dm, J = 8.4
3Hz), 7.17 (1H, ddd, J = 7.69,2.20,1.47Hz), 7.21 (2H, dm,
J = 8.43Hz), 7.25 (1H, dd, J = 7.69,7.69Hz), 7.29 (1H, dd, J
= 1.47,1.47Hz), 7.32 (1H, ddd, J = 7.69,2.20,1.47Hz) mass spectrum (m / z):. 314 (M +, 35 Cl), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1610, 1570, 147
5, 1370, 1350, 1260, 117
0, 1030, 875, 840.

[0403]

Reference Example 4-142 Compound of R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = Et, Configuration = Z Yield (%) = 41. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.32Hz), 1.24 (3H, t, J = 7.69Hz), 2.66 (2H, q, J = 7.69Hz),
6.36 (1H, s), 7.10 (1H, ddd, J = 6.96,1.83,1.83Hz), 7.16
(2H, dm, J = 8.43Hz), 7.18-7.21 (1H, m), 7.21 (2H, dm, J = 8.
43Hz), 7.27-7.34 (1H, m), 7.35 (1H, ddd, J = 8.06,1.83,1.
83Hz). Mass spectrum (m / z): 314 (M ⁺ , ³⁵ Cl), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1610, 1595, 1565, 1370, 1350, 1270, 1170, 1030,
880, 835.

[0404]

Reference Example 4-143 Compound of R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = H, configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 99-100 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.28 (3H, t, J =
7.32Hz), 2.70 (2H, q, J = 7.32Hz), 6.26 (1H, s), 7.11 (2H,
dm, J = 8.30Hz), 7.15 (1H, ddd, J = 7.81,1.46,1.46Hz), 7.2
0 (2H, dm, J = 8.30Hz), 7.26 (1H, dd, J = 7.81,7.81Hz), 7.34
(1H, ddd, J = 7.81,1.46,0.98Hz). Mass spectrum (m / z): 286 (M ⁺ , ³⁵ Cl), 271, 257, 241. Infrared absorption spectrum ν _max (CHCl ₃ ) cm- 1: 1690, 161
0, 1570, 1420, 1270, 1180, 840.

[0405]

Reference Example 4-144 Compound of R ¹ = 3-ClPh, R ² = 4-EtPh, R ¹¹ = H, Configuration = Z Yield (%) = 96. Melting point (recrystallization solvent) = 146-148 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.23 (3H, t, J =
7.82Hz), 2.66 (2H, q, J = 7.82Hz), 6.34 (1H, s), 7.10 (1H,
ddd, J = 6.84,1.47,1.47Hz), 7.13-7.22 (5H, m), 7.27-7.3
4 (1H, m), 7.35 (1H, ddd, J = 8.30,1.47,1.47Hz). Mass spectrum (m / z): 286 (M ⁺ , ³⁵ Cl), 271, 257, 241. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1690, 161
0, 1570, 1420, 1270, 1180, 840.

[0406]

Reference Example 4-145 Compound of R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = Z Yield (%) = 62. Melting point (recrystallization solvent) = 104-105 ° C (Et ₂ O-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.08 (3H, t, J =
7.33Hz), 3.83 (3H, s), 4.02 (2H, q, J = 7.33Hz), 6.42 (1H,
s), 6.88 (2H, dm, J = 8.80Hz), 7.18 (2H, dm, J = 8.80Hz), 7.
64-7.69 (2H, m), 7.88-7.92 (1H, m). Mass spectrum (m / z): 418 (M ⁺ ), 399, 390, 373, 346. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1510, 1460, 1390, 1330, 1280, 1175, 1140.

[0407]

Reference Example 4-146 Compound in which R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = E Yield (%) = 14. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.19 (3H, t, J =
7.33Hz), 3.86 (3H, s), 4.12 (2H, q, J = 7.33Hz), 6.31 (1H,
s), 6.93 (2H, dm, J = 8.79Hz), 7.14 (2H, dm, J = 8.79Hz), 7.
71-7.75 (2H, m), 7.85-7.89 (1H, m). Mass spectrum (m / z): 418 (M ⁺ ), 399, 389, 373, 346. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1720, 1610, 1515, 146
0, 1370, 1350, 1280, 124
5, 1175, 1140.

[0408]

Reference Example 4-147 Compound of R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = Z Yield (%) = 92. Melting point (recrystallization solvent) = 197-199 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
6.40 (1H, s), 6.88 (2H, dm, J = 8.79Hz), 7.18 (2H, dm, J = 8.7
9Hz), 7.62-7.67 (2H, m), 7.87-7.92 (1H, m). Mass spectrum (m / z): 390 (M ⁺ ), 373, 345. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 3700-2200,
1690, 1600, 1510, 1460, 1420, 1390, 1330, 1280, 1
180, 1140.

[0409]

Reference Example 4-148 Compound of R ¹ = 3,5-di-CF ₃ Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 144-146 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.87 (3H, s),
6.27 (1H, s), 6.93 (2H, dm, J = 8.79Hz), 7.16 (2H, dm, J = 8.7
9Hz), 7.69-7.74 (2H, m), 7.87-7.91 (1H, m). Mass spectrum (m / z): 390 (M ⁺ ), 373, 345. Infrared absorption spectrum ν _max (CHCl ₃ ) cm -1: 3200-2400,
1700, 1610, 1515, 1460, 1380, 1350, 1280, 1250, 1
180, 1140.

[0410]

Reference Example 4-149 Compound of R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = Et, Configuration = Z Yield (%) = 41. Melting point (recrystallization solvent) = 104-106 ° C (Et ₂ O) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.14 (3H, t, J =
7.33Hz), 1.42 (3H, t, J = 6.96Hz), 4.05 (2H, q, J = 6.96Hz),
4.06 (2H, q, J = 7.33Hz), 6.32 (1H, s), 6.85 (2H, dm, J = 8.7
9Hz), 7.09 (2H, d, J = 1.83Hz), 7.20 (2H, dm, J = 8.79Hz),
7.37 (1H, t, J = 1.83Hz). Mass vector (m / z): 364 (M ⁺ , ³⁵ Cl), 319, 292. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 160
5, 1590, 1565, 1515, 1370, 1350, 1275, 1255, 1160,
1040.

[0411]

Reference Example 4-150 Compound of R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = Et, Configuration = E Yield (%) = 12. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 1.44 (3H, t, J = 7.33Hz), 4.07 (2H, q, J = 7.33Hz),
4.09 (2H, q, J = 7.32Hz), 6.22 (1H, s), 6.90 (2H, dm, J = 8.7
9Hz), 7.11 (2H, dm, J = 8.79Hz), 7.16 (2H, d, J = 1.95Hz),
7.34 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 364 (M ⁺ , ³⁵ Cl), 319, 292. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 161
0, 1590, 1560, 1515, 1395, 1370, 1350, 1290, 1245,
1175.

[0412]

Reference Example 4-151 Compound of R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = H, configuration = Z Yield (%) = 86. Melting point (recrystallization solvent) = 220-222 ° C (MeOH-Et ₂ O) NMR spectrum (270 MHz, DMSO-d ₆ ) δ ppm: 1.32 (3H, t,
J = 6.84Hz), 4.04 (2H, q, J = 6.84Hz), 6.37 (1H, s), 6.92 (2H
H, dm, J = 8.79Hz), 7.18 (2H, d, J = 1.95Hz), 7.21 (2H, dm, J =
. 8.79Hz), 7.60 (1H, t, J = 1.95Hz), 12.18 (1H, br.s) mass spectrum (m / z): 336 ( M +, 35 Cl), 308, 291. Infrared absorption spectrum ν _max (KBr) cm-1: 3400-2200, 1
695, 1670, 1625, 1600,1585, 1560, 1515, 1440, 129
0, 1260, 1215, 1185, 1165, 840.

[0413]

Reference Example 4-152 Compound of R ¹ = 3,5-di-ClPh, R ² = 4-EtOPh, R ¹¹ = H, configuration = E Yield (%) = 89. Melting point (recrystallization solvent) = 174-176 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.44 (3H, t, J =
6.83Hz), 4.08 (2H, q, J = 6.83Hz), 6.19 (1H, s), 6.89 (2H,
dm, J = 8.79Hz), 7.12 (2H, dm, J = 8.79Hz), 7.15 (2H, d, J = 1.
95Hz), 7.36 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 336 (M ⁺ , ³⁵ Cl), 308, 291. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2200,
1690, 1610, 1585, 1560, 1510, 1420, 1390, 1290, 1
245, 1175.

[0414]

Reference Example 4-153 R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 44. Melting point (recrystallization solvent) = 73-75 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 1.24 (3H, t, J = 7.32Hz), 2.66 (2H, q, J = 7.32Hz),
4.07 (2H, q, J = 7.32Hz), 6.38 (1H, s), 7.10 (2H, d, J = 1.95
. Hz), 7.13-7.23 (4H, m), 7.37 (1H, t, J = 1.95Hz) Mass spectrum (m / z): 348 ( M +, 35 Cl), 319, 303, 276. Infrared Absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1710, 162
0, 1605, 1585, 1560, 1410, 1370, 1345, 1270, 1160.

[0415]

Reference Example 4-154 R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 13. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.13 (3H, t, J =
7.32Hz), 1.28 (3H, t, J = 7.32Hz), 2.70 (2H, q, J = 7.32Hz),
4.07 (2H, q, J = 7.32Hz), 6.27 (1H, s), 7.09 (2H, dm, J = 8.3
0Hz), 7.17 (2H, d, J = 1.95Hz), 7.22 (2H, dm, J = 8.30Hz),
7.34 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 348 (M ⁺ , ³⁵ Cl),
319, 303, 276. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 16
10, 1585, 1560, 1410, 1370, 1350, 1260, 1170.

[0416]

Reference Example 4-155 R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = H, configuration =
Compound of Z Yield (%) = 90. Melting point (recrystallization solvent) = 206-208 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, DMSO-d ₆ ) δ ppm: 1.17 (3H, t,
J = 7.32Hz), 2.61 (2H, q, J = 7.32Hz), 6.43 (1H, s), 7.16-
7.28 (4H, m), 7.20 (2H, d, J = 1.95Hz), 7.61 (1H, t, J = 1.95H
z), 12.32 (1H, br.s). Mass spectrum (m / z): 320 (M ⁺ , ³⁵ Cl), 291, 275. Infrared absorption spectrum ν _max (KBr) cm-1: 3400-2200, 1
695, 1670, 1620, 1605,1580, 1560, 1415, 1275, 122
0, 835, 805.

[0417]

Reference Example 4-156 R ¹ = 3,5-di-ClPh, R ² = 4-EtPh, R ¹¹ = H, configuration =
Compound of E Yield (%) = 99. Melting point (recrystallization solvent) = 162-164 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.28 (3H, t, J =
7.32Hz), 2.70 (2H, q, J = 7.32Hz), 6.23 (1H, s), 7.09 (2H,
dm, J = 8.30Hz), 7.14 (2H, d, J = 1.95Hz), 7.21 (2H, dm, J = 8.
30Hz), 7.36 (1H, t, J = 1.95Hz). Mass spectrum (m / z): 320 (M ⁺ , ³⁵ Cl), 291, 275. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1610, 1595, 1560,1415, 1265, 1180, 860, 83
Five.

[0418]

[Reference Example 4-157] R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of Z Yield (%) = 48. Melting point (recrystallization solvent) = 65-66 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.82 (3H, s), 4.07 (2H, q, J = 7.32Hz), 6.33 (1H,
s), 6.69-6.89 (3H, m), 6.86 (2H, dm, J = 9.16Hz), 7.22 (2
H, dm, J = 9.16Hz). Mass spectrum (m / z): 318 (M ⁺ ), 289, 273, 246. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 160
5, 1515, 1435, 1375, 1290, 1255, 1170, 1120.

[0419]

[Reference Example 4-158] R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, arrangement =
Compound of E Yield (%) = 20. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.32Hz), 3.85 (3H, s), 4.09 (2H, q, J = 7.32Hz), 6.26 (1H,
s), 6.75-6.88 (3H, m), 6.91 (2H, dm, J = 8.79Hz), 7.13 (2
H, dm, J = 8.79Hz). Mass spectrum (m / z): 318 (M ⁺ ), 289, 273, 246. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1715, 162
0, 1610, 1595, 1515, 1435, 1370, 1295, 1250, 1170,
1120.

[0420]

Reference Example 4-159 R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration =
Compound of Z Yield (%) = 87. Melting point (recrystallization solvent) = 170-172 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.82 (3H, s),
6.30 (1H, s), 6.67-6.90 (3H, m), 6.86 (2H, dm, J = 9.28Hz),
7.21 (2H, dm, J = 9.28 Hz). Mass spectrum (m / z): 290 (M ⁺ ), 273, 245. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 3600-2400, 1695, 162
5, 1600, 1515, 1430, 1290,
1260, 1180, 1120.

[0421]

Reference Example 4-160 Compound of R ¹ = 3,5-di-FPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = E Yield (%) = 90. Melting point (recrystallization solvent) = 140-142 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.85 (3H, s),
6.22 (1H, s), 6.75-6.94 (3H, m), 6.90 (2H, dm, J = 8.79Hz),
7.14 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 290 (M ⁺ ), 273, 245. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1695, 1625, 1610, 1595, 1515, 1435, 1295, 1250, 1
175, 1125.

[0422]

Reference Example 4-161 Compound of R ¹ = 3-CNPh, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = Z Yield (%) = 43. Melting point (recrystallization solvent) = 105-106 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.15 (3H, t, J =
7.32Hz), 3.83 (3H, s), 4.05 (2H, q, J = 7.32Hz), 6.38 (1H,
s), 6.86 (2H, dm, J = 8.79Hz), 7.19 (2H, dm, J = 8.79Hz), 7.
45 (1H, ddd, J = 7.69,1.47,1.47Hz), 7.48-7.52 (1H, m), 7.
51 (1H, ddd, J = 7.69,7.69,0.73Hz), 7.68 (1H, ddd, J = 7.69,
1.47,1.47Hz). Mass spectrum (m / z): 307 (M ⁺ ), 278, 262, 235. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 2240, 171
5, 1610, 1515, 1375, 1280, 1260, 1170, 1030, 835.

[0423]

Reference Example 4-162 Compound of R ¹ = 3-CNPh, R ² = 4-CH ₃ OPh, R ¹¹ = H, configuration = Z Yield (%) = 8. Melting point (recrystallization solvent) = 193-194 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 3.83 (3H, s),
6.34 (1H, s), 6.86 (2H, dm, J = 8.79Hz), 7.17 (2H, dm, J = 8.7
9Hz), 7.44 (1H, ddd, J = 7.82,1.47,1.47Hz), 7.45-7.50 (1
H, m), 7.48 (1H, dd, J = 7.82,7.82Hz), 7.67 (1H, ddd, J = 7.8
Mass spectrum (m / z): 279 (M ⁺ ), 262,
234. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
2240, 1690, 1600, 1570, 1510, 1425, 1285, 1260, 1
180, 1035,835.

[0424]

Reference Example 4-163 Compound of R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = Et, Configuration = Z Yield (%) = 16. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.33Hz), 1.41 (3H, t, J = 6.96Hz), 4.038 (2H, q, J = 6.96H
z), 4.042 (2H, q, J = 7.33Hz), 6.32 (1H, s), 6.83 (2H, dm, J
= 8.79Hz), 6.91 (1H, ddd, J = 9.53,2.56,1.46Hz), 6.95-7.
02 (1H, m), 7.07 (1H, dddd, J = 8.43,8.43,2.56,1.10Hz),
7.22 (2H, dm, J = 8.79Hz), 7.34 (1H, ddd, J = 8.43,8.43,5.86
Hz). Mass spectrum (m / z): 314 (M ⁺ ), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1580, 1510, 1475, 1370, 1270, 1250, 1160, 1115,
1035.

[0425]

Reference Example 4-164 Compound of R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = Et, Configuration = E Yield (%) = 8. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 1.43 (3H, t, J = 6.83Hz), 4.07 (2H, q, J = 6.83Hz),
4.09 (2H, q, J = 7.32Hz), 6.26 (1H, s), 6.89 (2H, dm, J = 8.7
9Hz), 6.94-7.13 (3H, m), 7.13 (2H, dm, J = 8.79Hz), 7.28
(1H, ddd, J = 8.30,8.30,5.86Hz). Mass spectrum (m / z): 314 (M ⁺ ), 285, 269, 242. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 1710, 1605, 1580, 151
0, 1485, 1475, 1440, 137
0, 1240, 1170, 1130, 103
5.

[0426]

Reference Example 4-165 R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = H, arrangement = Z
Compound yield (%) = 91. Melting point (recrystallization solvent) = 154-155 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.41 (3H, t, J =
6.83Hz), 4.04 (2H, q, J = 6.83Hz), 6.28 (1H, s), 6.83 (2H,
dm, J = 8.79Hz), 6.90 (1H, ddd, J = 9.28,2.44,1.46Hz), 6.9
4-7.00 (1H, m), 7.06 (1H, dddd, J = 8.30,8.30,2.44,0.98H
z), 7.20 (2H, dm, J = 8.79Hz), 7.33 (1H, ddd, J = 8.30,8.30,
5.86Hz). Mass spectrum (m / z): 286 (M ⁺ ), 269, 257, 241. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1595, 1510, 1435,1285, 1250, 1175, 1115, 10
35.

[0427]

Reference Example 4-166 Compound of R ¹ = 3-FPh, R ² = 4-EtOPh, R ¹¹ = H, Configuration = E Yield (%) = 95. Melting point (recrystallization solvent) = 148-149 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.44 (3H, t, J =
6.83Hz), 4.07 (2H, q, J = 6.83Hz), 6.22 (1H, s), 6.88 (2H,
dm, J = 8.79Hz), 6.92-7.00 (1H, m), 7.01-7.12 (2H, m), 7.
14 (2H, dm, J = 8.79Hz), 7.29 (1H, ddd, J = 8.30,8.30,5.86H
z). Mass spectrum (m / z): 286 (M ⁺ ), 269, 257, 241. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400,
1690, 1605, 1580, 1510, 1485, 1440, 1285, 1265, 1
240, 1170,1035.

[0428]

Reference Example 4-167 Compound of R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, configuration = Z Yield (%) = 49. Melting point (recrystallization solvent) = 83-85 ° C (hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.33Hz), 2.33 (3H, s), 3.82 (3H, s), 4.05 (2H, q, J = 7.33H
z), 6.29 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 6.86-6.90 (1
H, m), 6.98-7.03 (1H, m), 7.14-7.20 (1H, m), 7.23 (2H, d
m, J = 8.79Hz). Mass spectrum (m / z): 330 (M ⁺ , ³⁵ Cl), 301, 285, 258. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 160
0, 1575, 1510, 1290, 1275, 1250, 1165, 1030, 830.

[0429]

Reference Example 4-168 Compound of R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = Et, Configuration = E Yield (%) = 17. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.17 (3H, t, J =
7.33Hz), 2.30 (3H, s), 3.85 (3H, s), 4.09 (2H, q, J = 7.33H
z), 6.23 (1H, s), 6.90 (2H, dm, J = 8.79Hz), 6.95-7.02 (1
H, m), 7.04-7.09 (1H, m), 7.13-7.19 (1H, m), 7.14 (2H, d
m, J = 8.79Hz). Mass spectrum (m / z): 330 (M ⁺ , ³⁵ Cl), 301, 285, 258. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 1710, 161
0, 1570, 1510, 1290, 1280, 1245, 1170, 1140, 1030.

[0430]

Reference Example 4-169 Compound of R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H, Configuration = Z Yield (%) = 93. Melting point (recrystallization solvent) = 190-192 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.33 (3H, s),
3.82 (3H, s), 6.26 (1H, s), 6.85 (2H, dm, J = 8.79Hz), 6.85
-6.90 (1H, m), 6.96-7.01 (1H, m), 7.14-7.20 (1H, m), 7.2
1 (2H, dm, J = 8.79 Hz). Mass spectrum (m / z): 302 (M ⁺ , ³⁵ Cl), 285, 257. Infrared absorption spectrum ν _max (CHCl ₃ ) cm
-1: 3600-2400, 1690, 160
0, 1570, 1510, 1280, 1250,
1175, 1030, 830.

[0431]

Reference Example 4-170 R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-CH ₃ OPh, R ¹¹ = H,
Compound of configuration = E Yield (%) = 91. Melting point (recrystallization solvent) = 156-158 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 2.30 (3H, s),
3.85 (3H, s), 6.18 (1H, s), 6.89 (2H, dm, J = 8.79Hz), 6.94
-6.99 (1H, m), 7.00-7.06 (1H, m), 7.14-7.20 (1H, m), 7.1
4 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 302 (M ⁺ , ³⁵ Cl), 285, 257. Infrared absorption spectrum ν _max (CHCl ₃ ) cm-1: 3600-2400 ,
1690, 1605, 1570, 1510, 1290, 1245, 1170, 1030, 8
70, 850, 830.

[0432]

Reference Example 4-171 Compound of R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = Et, Configuration = Z Yield (%) = 17. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.12 (3H, t, J =
7.32Hz), 1.41 (3H, t, J = 6.96Hz), 2.33 (3H, s), 4.04 (2H,
q, J = 6.96Hz), 4.05 (2H, q, J = 7.32Hz), 6.29 (1H, s), 6.83
(2H, dm, J = 8.79Hz), 6.85-6.91 (1H, m), 6.98-7.02 (1H,
. m), 7.15-7.19 (1H, m), 7.21 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 344 ( M +, 35 Cl), 315, 299, 272. Infrared Absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
0, 1570, 1510, 1475, 1365, 1270, 1250, 1160, 1035,
850, 830.

[0433]

Reference Example 4-172 Compound of R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = Et, configuration = E Yield (%) = 6. Melting point (recrystallization solvent) = Oil NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.16 (3H, t, J =
7.32Hz), 1.43 (3H, t, J = 6.84Hz), 2.30 (3H, s), 4.07 (2H,
q, J = 6.84Hz), 4.08 (2H, q, J = 7.32Hz), 6.22 (1H, s), 6.89
(2H, dm, J = 8.79Hz), 6.95-7.01 (1H, m), 7.04-7.09 (1H,
. m), 7.12-7.18 (1H, m), 7.12 (2H, dm, J = 8.79Hz) Mass spectrum (m / z): 344 ( M +, 35 Cl), 315, 299, 272. Infrared Absorption Spectrum ν _max (CHCl ₃ ) cm-1: 1705, 160
5, 1570, 1510, 1475, 1365, 1280, 1240, 1165, 1140,
1110, 1035, 850.

[0434]

Reference Example 4-173 Compound of R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = H, Configuration = Z Yield (%) = 89. Melting point (recrystallization solvent) = 197-199 ° C (tetrahydrofuran
-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.41 (3H, t, J =
6.84Hz), 2.32 (3H, s), 4.04 (2H, q, J = 6.84Hz), 6.26 (1H,
s), 6.83 (2H, dm, J = 9.28Hz), 6.85-6.91 (1H, m), 6.96-7.
02 (1H, m), 7.14-7.20 (1H, m), 7.20 (2H, dm, J = 9.28Hz). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271.

[0435]

Reference Example 4-174 Compound of R ¹ = 3-Cl-5-CH ₃ -Ph, R ² = 4-EtOPh, R ¹¹ = H, Configuration = E Yield (%) = 86. Melting point (recrystallization solvent) = 163-165 ° C (CH ₂ Cl ₂ -hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.44 (3H, t, J =
6.84Hz), 2.30 (3H, s), 4.07 (2H, q, J = 6.84Hz), 6.17 (1H,
s), 6.87 (2H, dm, J = 8.79Hz), 6.93-7.00 (1H, m), 7.00-7.
07 (1H, m), 7.14-7.20 (1H, m), 7.13 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 316 (M ⁺ , ³⁵ Cl), 287, 271.

[0436]

[Reference Example 5] (E) Methyl 3,3-diphenylpent-2-ene-4 -inoate Z-3-bromocinnamate (1.000 g) and bis (triphenylphosphine) dichloropalladium (0.029 g) To a solution of this in diethylamine (25 ml) was added cuprous iodide (0.158 g) and phenylacetylene (0.424 g), and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off, water was added to the residue, and the mixture was extracted twice with benzene.The extract was washed with water, dried and concentrated.
(70-230 mesh, 25 g). The fractions eluted with hexane-ethyl acetate (39: 1) were collected to give the title compound (1.043 g). Melting point: 73-75 ° C (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 3.84 (3H,
s); 6.60 (1H, s); 7.34-7.82 (10H, m). Mass spectrum (m / z): 262 (M ⁺ ); 247; 231. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 2200, 171
0, 1600, 1590, 1575, 1490, 1450, 1435, 1365, 1275,
1165.

[0437]

REFERENCE EXAMPLE 6 (E) -3,5-Diphenylpent-2-ene-4-inoic acid The compound of Reference Example 5 (1.000 g), methanol (15 ml), tetrahydrofuran (7.5 ml) and 10% hydroxide A mixture of aqueous sodium solution (15 ml) was stirred at room temperature for 18 hours. After evaporating the solvent, the residue was diluted with water and extracted twice with ether. The extract is washed with water, dried and concentrated to give the title compound
(0.912 g) was obtained. Melting point: 124-126 ° C (methylene chloride-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 6.65 (1H,
s); 7.30-7.90 (10H, m). Mass spectrum (m / z): 248 (M ⁺ ); 231; 220. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 2400-3600
(broad), 2200, 1685, 1600, 1590, 1575, 1490, 1450,
1280, 1180.

[0438]

[Reference Example 7] 3,3-bis (4-methoxyphenyl) -3-hydroxy-2-methyl
Ethyl rupropionate A mixture of ethyl 2-bromopropionate (8.25 g), 4,4'-dimethoxybenzophenone (11.81 g), zinc (7.16 g) and benzene (70 ml) was heated to reflux on an oil bath for 4 hours. . After cooling, the reaction solution was filtered, and the filtrate was washed with 10% sulfuric acid, water and saturated saline. After drying, the solvent was distilled off, and the residue was subjected to flash column chromatography using silica gel (-400 mesh, 300 g). Hexane-ethyl acetate (10
The title compound (7.92 g) was obtained as white crystals from the fraction eluted with (0: 2). Melting point: 67-69 ° C (methylene chloride-hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.14 (6H,
t, J = 6.84Hz); 3.54 (1H, q, J = 6.84Hz); 3.75 (6H, s); 3.95
-4.15 (2H, m); 4.61 (1H, s); 6.80 (4H, dm, J = 8.79Hz); 7.3
3 (2H, dm, J = 8.79Hz), 7.44 (2H, dm, J = 8.79Hz). Mass spectrum (m / z): 344 (M ⁺ ); 326; 299; 281; 243. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1710, 161
0, 1510, 1460, 1375, 1340, 1245, 1170. Elemental analysis (as C ₂₀ H ₂₄ O ₅ ) Calculated: C; 69.75, H; 7.02. Found: C; 69.89, H; 7.10.

[0439]

[Reference Example 8] 3,3-bis (4-methoxyphenyl) -2-methylacrylic acid
Phosphorus oxychloride (4.10 ml) was added dropwise to a solution of the compound of Reference Example 7 in ethyl (7.02 g) in benzene (140 ml) at 5-10 ° C under ice-cooling. After stirring at room temperature for 3 hours, the reaction solution was poured into water and extracted three times with ether. The extract was washed with a saturated aqueous solution of sodium hydrogen carbonate, water and saturated saline, dried and concentrated.
The residue (6.72 g) was subjected to flash column chromatography on silica gel (100 g). Hexane-The title compound (6.04 g) from the fraction eluted with ethyl acetate (95: 5)
Was obtained as an oil. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 0.95 (3H,
t, J = 7.32Hz); 2.05 (3H, s); 3.78 (3H, s); 3.81 (3H, s);
3.97 (2H, q, J = 7.32Hz); 6.79 (2H, dm, J = 8.30Hz); 6.85 (2
H, dm, J = 8.30Hz); 7.03 (2H, dm, J = 8.30Hz); 7.08 (2H, dm, J
= 8.30Hz). Mass spectrum (m / z): 326 (M ⁺ ); 297; 281; 279; 252. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1700, 161
0, 1510, 1465, 1315, 1300, 1280, 1240, 1175, 1125. Elemental analysis (as C ₂₀ H ₂₂ O ₄ ) Calculated: C; 73.60, H; 6.79. Found: C; 73.39, H; 6.82.

[0440]

Reference Example 9 3,3-bis (4-methoxyphenyl) -2-methylacrylic acid The compound of Reference Example 8 (6.019 g), ethanol (120 ml) and
A mixture of 10% aqueous sodium hydroxide (80 ml) was added at room temperature.
Stir for 14 hours. After heating in a 100 ° C oil bath for 4 hours,
The ethanol was distilled off. The residue was diluted with ice water and washed with ethyl acetate. The aqueous layer was adjusted to pH 2 by dropwise addition of concentrated hydrochloric acid under ice cooling, and extracted twice with methylene chloride. Wash the extract with water
After drying and concentration, the title compound (5.117 g) was obtained as white crystals. Melting point: 134-135 ° C (methylene chloride-hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.06 (3H,
s); 3.80 (3H, s); 3.81 (3H, s); 6.79 (2H, dm, J = 8.79Hz);
6.86 (2H, dm, J = 8.79Hz); 7.06 (2H, dm, J = 8.79Hz); 7.07 (2
H, dm, J = 8.79Hz). Mass spectrum (m / z): 298 (M ⁺ ); 281; 253. Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 2400-3600
(broad), 1680, 1610, 1510, 1245, 1175. Elemental analysis (as C ₁₈ H ₁₈ O ₄ ) Calculated: C; 72.47, H; 6.08. Found: C; 72.11, H; 15.

[0441]

[Reference Example 10]N- (3,4,5-trimethoxybenzenesulfoni
Le) piperazine N-formylpiperazine (3.80 g) and triethyleneamine
(7.73 ml) and methylene chloride (150 ml) solution under ice-cooling.
3,4,5-trimethoxybenzenesulfonyl chloride
(7.40 g) in methylene chloride (75 ml) was added dropwise.
After stirring at 0-5 ° C for 30 minutes, pour the reaction solution into water and add methyl
Extracted twice with lenchloride. Extract the solution with 10% hydrochloric acid and
Washed with brine, dried and concentrated. The residue (9.86 g)
Hydrofuran (150 ml), methanol (75 ml) and 10% water
Dissolve in a mixture of aqueous sodium oxide (50 ml) and allow
Stirred at warm for 14 hours. Pour the reaction mixture into water and add
Extracted four times with Loride. The extract is washed with water, dried and concentrated,
The residue was recrystallized from hexane-ethyl acetate,
A compound (7.02 g) was obtained. Melting point: 131-133 ° C NMR spectrum (270MHz, CDCl_Three) δ ppm: 2.90-3.10
(8H, m); 3.91 (9H, s); 6.96 (2H, s) .Mass spectrum (m / z): 316 (M⁺); 232; 85. Elemental analysis (C₁₃H₂₀N_TwoO_Five(As S) Calculated: C; 49.35, H; 6.37, N; 8.85, S; 10.13. Found: C; 49.62, H; 6.30, N; 8.55, S; 10.11.

[0442]

[Reference Example 11] The same reaction as in Reference Example 1 was carried out using 3,3-bis (3-chlorophenyl) acrylic acid 3,3'-dichlorobenzophenone (10.85 g), and the crude product was converted from methylene chloride-hexane. Recrystallization gives the title compound (12.32
g) was obtained. Melting point: 114-115 ° C

[0443]

[Reference Example 12] 1- [3,3-bis (3-chlorophenyl) acryloyl] pipe
The compound of Razine Reference Example 11 (5.00 g) and triethylamine (4.75 g)
ml) in methylene chloride (100 ml), diphenylphosphoryl azide (5.51 ml) and N-formylpiperazine (1.91 ml).
3 ml) were added sequentially. The reaction mixture was stirred at room temperature for 18 hours, washed with a saturated aqueous solution of sodium hydrogen carbonate and water, dried and concentrated. The residue was dissolved in a mixture of ethanol (100 ml) and tetrahydrofuran (50 ml), 10% aqueous sodium hydroxide solution (50 ml) was added, and the mixture was stirred at room temperature for 8 hours.
The reaction solution was poured into water and extracted twice with methylene chloride. The extracts were combined, washed with water, dried and concentrated, and the residue was subjected to column chromatography using silica gel (150 g). The fractions eluted with methylene chloride-methanol (49: 1-9: 1) were collected to give the title compound (5.23 g) as a viscous oil. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 2.21 (1H,
s); 2.00-2.95 (4H, m); 3.00-3.85 (4H, m); 6.38 (1H, s);
6.90-7.50 (8H, m). Mass spectrum (m / e): 360 (M ⁺ , ³⁵ Cl); 325; 292; 275.

[0444]

Reference Example 13 (Z)-and (E) -3-phenyl-3- (2-naphthy
G) Reference Example 1 using ethyl acrylate 2-naphthyl phenyl ketone (10.10 g)
The same reaction as in the first half was performed. The crude product was subjected to column chromatography using silica gel (200 g) and medium pressure liquid chromatography using Lobar-C column. The fractions eluted with hexane-ethyl acetate were collected to give the Z-isomer (2.48 g). Melting point: 91-92 ° C (hexane) Elution with the same solvent was continued to obtain E-isomer (4.44 g). Melting point: 84-85 ℃ (hexane)

[0445]

REFERENCE EXAMPLE 14 (Z) -3-phenyl-3- (2-naphthyl) acrylic acid The Z-isomer of Reference Example 13 (2.411 g) was converted to ethanol (48 ml).
And tetrahydrofuran (24 ml).
% Aqueous sodium hydroxide solution (24 ml) was added, and the mixture was stirred at room temperature for 15 hours. Pour the reaction solution into water, add
And extracted twice with methylene chloride. The extract was washed with water, dried and concentrated, and the residue was recrystallized from methylene chloride-hexane to obtain the desired compound (2.005 g). Melting point: 170-172 ° C NMR spectrum (270 MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 6.
44 (1H, s); 7.28-7.42 (6H, m); 7.44-7.54 (2H, m); 7.71 (1
H, d, J = 0.73Hz); 7.76-7.91 (3H, m). Mass spectrum (m / e): 274 (M ⁺ ); 257; 229. Elemental analysis (calculated as C ₁₉ H ₁₄ O ₂ ) Value: C; 83.19, H; 5.14. Found: C; 83.39, H; 5.35.

[0446]

REFERENCE EXAMPLE 15 ( E) -3-Phenyl-3- (2-naphthyl) acrylic acid The E-isomer of Reference Example 13 (2.219 g) was hydrolyzed in the same manner as in Reference Example 14 to give the target compound ( 1.685 g) was obtained. Melting point: 229-231 ° C. (ether-tetrahydrofuran) NMR spectrum (270 MHz, CDCl ₃ -CD ₃ OD = 1: 1) δ ppm: 6.
50 (1H, s); 7.23-7.32 (2H, m); 7.36-7.43 (3H, m); 7.43-
7.54 (3H, m); 7.67 (1H, d, J = 1.83Hz); 7.70-7.88 (3H, m). Mass spectrum (m / e): 274 (M ⁺ ); 257; 229. Elemental analysis ( C ₁₉ H ₁₄ as O ₂₎ calculated: C; 83.19, H; 5.14 . Found: C; 83.45, H; 5.33.

[0447]

Reference Example 16 Ethyl (E) -p -isobutyloxycinnamate (E) -Ethyl p-hydroxycinnamate (9.61 g) and isobutyl bromide (8.22 g) were dissolved in dimethyl sulfoxide (100 ml), and potassium carbonate ( 13.8 g) and sodium iodide (7.50 g)
Was added and the mixture was heated and stirred at 60 ° C. for 20 hours. After cooling, the reaction solution was poured into 1 liter of water and extracted twice with ethyl acetate. The extract is washed with water, dried and concentrated, and the residue is silica gel (3
(00 g). The fractions eluted with hexane-ethyl acetate (5: 1) were collected to give the target compound as a colorless oil (10.71 g, which solidified at low temperature). NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.98 (6H, d, J =
7Hz); 1.28 (3H, t, J = 7Hz); 1.60-2.50 (1H, m); 3.70 (2H,
d, J = 7Hz); 4.24 (2H, q, J = 7Hz); 6.26 (1H, d, J = 16Hz); 6.8
6 (2H, dm, J = 9Hz); 7.45 (2H, dm, J = 9Hz); 7.66 (1H, d, J = 16H
z).

[0448]

[Reference Example 17] The same reaction as in Reference Example 16 was carried out using (E) -ethyl ethyl p-propoxycinnamate (E) -ethyl ethyl p-hydroxycinnamate (9.61 g) and propyl iodide (10.20 g). . However, sodium iodide was not used. Reference Example 1
By operating in the same manner as in 6, the target compound (11.00 g) was obtained as a solid. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.98 (3H, t, J =
7Hz); 1.26 (3H, t, J = 7Hz); 1.20-2.20 (2H, m); 3.88 (2H,
t, J = 6.5Hz); 4.21 (2H, q, J = 7Hz); 6.24 (1H, d, J = 16Hz);
6.85 (2H, dm, J = 8Hz); 7.44 (2H, dm, J = 8Hz); 7.62 (1H, d, J =
16Hz).

[0449]

[Reference Example 18] Ethyl (E) -3,4 -dipropoxycinnamate (E) -3,4-dihydroxycinnamate (10.41 g) and propyl iodide (20.40 g) were used. The reaction was performed to obtain the desired compound (10.20 g) as a solid. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.02 (6H, t, J =
7Hz); 1.32 (3H, t, J = 7Hz); 1.50-2.20 (4H, m); 3.99 (4H,
t, J = 7Hz); 4.26 (2H, q, J = 7Hz); 6.30 (1H, d, J = 16Hz); 6.7
0-7.35 (3H, m); 7.65 (1H, d, J = 16Hz).

[0450]

[Reference Example 19] Ethyl (E) -4 -ethoxy-3-methoxycinnamate (E) -4-hydroxy-3-methoxycinnamate (5.83 g) and ethyl iodide (5.61 g) were used as reference examples. The same reaction as in 17 was performed to obtain the desired compound (5.55 g) as a solid. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.30 (3H, t, J =
7Hz); 1.44 (3H, t, J = 7Hz); 3.89 (3H, s); 4.14 (2H, q, J = 7H
z); 4.24 (2H, q, J = 7Hz); 6.30 (1H, d, J = 16Hz); 6.75-7.35
(3H, m); 7.66 (1H, d, J = 16Hz).

[0451]

Reference Example 20 Ethyl ( E) -3-methoxy-4-propoxycinnamate Ethyl (E) -4-hydroxy-3-methoxycinnamate (11.11 g)
And propyl iodide (10.20 g), and the reaction was carried out in the same manner as in Reference Example 17 to obtain the desired compound (12.08 g). NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 1.01 (3H, t, J =
7 Hz); 1.30 (3H, t, J = 7Hz); 1.50-2.20 (2H, m); 3.88 (3H,
s); 3.98 (2H, t, J = 7Hz); 4.24 (2H, q, J = 7Hz); 6.28 (1H, d,
J = 16Hz); 6.70-7.35 (3H, m); 7.65 (1H, d, J = 16Hz).

[0452]

[Reference Example 21] Ethyl (E) -4 -butoxy-3-methoxycinnamate (E) -4-Hydroxy-3-methoxycinnamate (6.66 g) and butyl iodide (6.62 g) were used as Reference Examples. The same reaction as in 17 was performed to obtain the desired compound (7.00 g) as a solid. NMR spectrum (60 MHz, CDCl ₃ ) δ ppm: 0.96 (3H, t, J =
7Hz); 1.30 (3H, t, J = 7Hz); 1.20-2.10 (4H, m); 3.88 (3H,
s); 4.03 (3H, t, J = 7Hz); 4.24 (2H, q, J = 7Hz); 6.28 (1H, d,
J = 16Hz); 6.75-7.35 (3H, m); 7.65 (1H, d, J = 16Hz).

[0453]

Reference Example 22 1- [Z-3- (3-chlorophenyl) -3- (4-methoxyphenyl)
Acryloyl] piperazine Using the compound of Reference Example 4-73 (5.65 g), the same reaction and purification as in Reference Example 12 were performed to obtain the desired compound (6.37 g) as a powder. Melting point: 108-110 ° C NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.75 (1H,
s); 2.35-2.45 (2H, m); 2.65-2.75 (2H, m); 3.25-3.35 (2
H, m); 3.45-3.55 (2H, m); 3.82 (3H, s); 6.28 (1H, s), 6.86
. (2H, dm, J = 8.79Hz), 7.16-7.36 (6H, m) Elemental analysis _{(C 20 H 21 ClN 2 O} 2 ) Calculated value: C; 67.32, H; 5.93 , N; 7.85, Cl 9.93. Found: C; 67.09, H; 5.81, N; 7.81, Cl; 10.10.

[0454]

[Reference Example 23] A mixture of 4-acetoxy-3,5-dimethoxybenzoic acid 3,5-dimethoxy-4-hydroxybenzoic acid (3.00 g) and acetic anhydride (30 ml) was ice-cooled, and pyridine (15 ml) was obtained. 5
It was added dropwise over a period of minutes. After stirring at room temperature for 30 minutes, the reaction solution was poured into water and stirred at room temperature for 30 minutes. Extract with ethyl acetate three times, wash the extract with 10% hydrochloric acid, then dry,
Concentrated. The residue was recrystallized from methylene chloride-hexane to obtain the desired compound (3.13 g). 1. Melting point: 192-194 ° C. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm:
36 (3H, s); 3.90 (6H, s); 7.4
0 (2H, s). Elemental analysis (as C ₁₁ H ₁₂ O ₆ ) Calculated: C; 55.00, H; 5.04. Found: C; 55.02, H; 5.04.

[0455]

[Reference Example 24] Ethyl diethyl 3,5-dichlorocinnamate (0.84 g, 55% mineral oil suspension) in a mixture of tetrahydrofuran (40 ml) and ethyl diethylphosphonoacetate (4.33 g) in tetrahydrofuran (20 ml) solution was added dropwise over 12 minutes at 6-12 ° C under ice-cooling. At room temperature, 30
After stirring for 3 minutes, 3,5-dichlorobenzaldehyde (3.07
g) in tetrahydrofuran (20 ml) was added under ice cooling (8-11
(C) over 10 minutes. After stirring at room temperature for 4 hours, the reaction solution was poured into water and extracted twice with ethyl acetate.
The extract was washed with water, dried and concentrated.
Was subjected to flash column chromatography using 00 g). The fraction eluted with hexane-ethyl acetate (99: 1) was collected to obtain the desired compound (3.33 g). Melting point: 71-73 ° C (cold hexane) NMR spectrum (270MHz, CDCl ₃ ) δ ppm: 1.34 (3H, t,
J = 7.32Hz); 4.27 (2H, q, J = 7.32Hz); 6.43 (1H, d, J = 16.11H
z); 7.36 (1H, t, J = 1.95Hz); 7.38 (2H, d, J = 1.95Hz); 7.54
(1H, d, J = 16.11Hz). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1770, 164
0, 1580, 1560, 1415, 1360, 1310, 1280, 1270, 1170,
1020, 970, 845. Mass spectrum (m / z): 244 (M ⁺ , ³⁵ Cl); 216; 199; 171. Elemental analysis (as C ₁₁ H ₁₀ O ₂ Cl ₂ ) Calculated: C; 53.90, H; 4.11, Cl; 28.93. Found: C; 54.01, H; 4.16, Cl; 28.76.

[0456]

Reference Example 25 Ethyl 2,5-dichlorocinnamate 2,5-Dichlorobenzaldehyde (9.74 g) was used to obtain the target compound (12.17 g) in the same manner as in Reference Example 24. Melting point: 34-36 ° C NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.35 (3H, t,
J = 7.32Hz); 4.29 (2H, q, J = 7.32Hz); 6.42 (1H, d, J = 16.12H
z); 7.27 (1H, dd, J = 8.31,2.44Hz); 7.35 (1H, d, J = 8.30H
. z); 7.59 (1H, d, J = 2.44Hz); 7.99 (1H, d, J = 16.12Hz) Mass Spectrum (m / z): 244 ( M +, 35 Cl); 209; 199. Elemental analysis value (C ₁₁ H ₁₀ O ₂ as Cl ₂₎ calculated: C; 53.90, H; 4.11 , Cl; 28.93 Found:. C; 54.14, H; 4.24, Cl; 28.77.

[0457]

Reference Example 26 The target compound (23.46 g) was obtained in the same manner as in Reference Example 24 using ethyl 2,3-dichlorocinnamate 2,3-dichlorobenzaldehyde (20.00 g). Melting point: 69-70 ° C (hexane) NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.35 (3H, t,
J = 7.32Hz); 4.29 (2H, q, J = 7.32Hz); 6.41 (1H, d, J = 16.12H
z); 7.22 (1H, dd, J = 8.30,8.30Hz); 7.48 (1H, dd, J = 8.30,
1.47Hz); 7.51 (1H, dd, J = 8.30,1.47Hz); 8.08 (1H, d, J = 1
6.12Hz). Mass spectrum (m / z): 244 (M ⁺ , ³⁵ Cl); 209; 199. Elemental analysis (as C ₁₁ H ₁₀ O ₂ Cl ₂ ) Calculated: C; 53.90, H; 4.11, Cl; 28.93. Found: C; 54.10, H; 4.31, Cl; 28.65.

[0458]

Reference Example 27 The reaction was carried out in the same manner as in Reference Example 24 using ethyl 3,5-dimethylcinnamate 3,5-dimethylbenzaldehyde (11.44 g). The crude product was subjected to flash column chromatography on silica gel (300 g), and the fraction eluted with hexane-ethyl acetate (9: 1) was collected to give the desired compound (15.22 g) as an oil. Was. NMR spectrum (270 MHz, CDCl ₃ ) δ ppm: 1.33 (3H, t,
J = 7.32Hz); 2.33 (6H, s); 4.26 (2H, q, J = 7.32Hz); 6.41 (1
H, d, J = 16.12Hz); 7.02 (1H, br.s); 7.14 (2H, br.s); 7.63
(1H, d, J = 16.12Hz). Mass spectrum (m / z): 204 (M ⁺ ); 189; 175; 159. Elemental analysis (as C ₁₃ H ₁₆ O ₂ ) Calculated: C; 76.44, H; 7.90. Found: C; 76.67, H; 8.14.

[0459]

[Reference Example 28] 1- [Z-3- (3,5-dichlorophenyl) -3- (4-methoxyphenyl)
Ru) acryloyl] piperazine Reference Example 1 using the compound of Reference Example 4-127 (1,000 g).
Perform the same reaction and purification as in Example 2 to give the title compound (1.073
g) was obtained as a powder. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.89 (1H,
s); 2.45-2.65 (2H, m); 2.65-2.85 (2H, m); 3.25-3.45 (2H, m
m); 3.45-3.65 (2H, m); 3.83 (3H, s); 6.33 (1H, s); 6.87 (2
H, dm, J = 8.79H _Z ); 7.17 (2H, d, J = 1.95H _Z ); 7.19 (2H, dm, J =
8.79H _Z ); 7.35 (1H, t, J = 1.95H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 161
0, 1565, 1515, 1465, 1445, 1250, 1180. Mass spectrum (m / z): 390 (M ⁺ , ³⁵ Cl); 305; 85. Elemental analysis (C ₂₀ H ₂₀ Cl ₂ N ₂ O ₂ ) Calculated: C; 61.39, H; 5.15, N; 7.16, Cl; 18.12. Found: C; 61.44, H; 5.39, N; 7.04, Cl; 17.93.

[0460]

Reference Example 29 Method of dl-5- (N-phthaloylaminomethyl) -2-pyrrolidone Saijo et al. [Chem. Pharm. Bull., 5 , 1449 (198
0)], dl-5-hydroxymethyl-2-pyrrolidone (33.63 g), phthalimide (51.57 g) and triphenylphosphine (91.91 g) in tetrahydrofuran (600
ml) solution in diethyl azodicarboxylate (61.05 g, 0.
(350 mol) in tetrahydrofuran (80 ml) was added at room temperature. After stirring at room temperature for 1 hour, the reaction solution was concentrated to dryness. The residue was subjected to column chromatography using silica gel (1000 g), and ethyl acetate-methanol (1: 0-9: 1)
The fractions eluted in were collected and 62.55 g of the title compound (8
8%) as white needles. Mp: 178.0-180.0 ℃ - NMR spectrum (methylene chloride recrystallized from ethyl _{acetate) (270MH Z, CDCl 3)} δ ppm: 1.85-2.05
(1H, m); 2.20-2.40 (3H, m); 3.73 (1H, dd, J = 13.68,5.37
_{H Z); 3.88 (1H,} dd, J = 13.68,4.88H Z); 3.95-4.05 (1H, m);
6.05 (1H, br.s); 7.70-7.90 (4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3450, 178
0, 1720, 1705, 1495. Mass spectrum (m / z): 245 (M ⁺ +1); 160; 84. Elemental analysis (as C ₁₃ H ₁₂ N ₂ O ₃ ) Calculated: C; 63.93, H ; 4.95, N; 11.47. Found: C; 63.65, H; 4.69, N; 11.17.

[0461]

Reference Example 30 Method of (S) -5- (N-phthaloylaminomethyl) -2-pyrrolidone Silverman et al. [J. Org. Chem., 45 , 815 (1980)]
L-pyroglutamic acid ethyl ester synthesized from L-glutamic acid according to the method of Saijo et al. [Chem. Pharm.
ull., 5 , 1449 (1980)] to give (S) -5-hydroxymethyl-2-pyrrolidone. Using this compound,
By operating in the same manner as in Reference Example 1, the title compound was obtained as white needle crystals. Melting point: 190.0-191.0 ° C (reconstituted from methylene chloride-ethyl acetate) [α] _D ²⁵ + 3.24 ° (C = 1.08, CHCl ₃ ). Elemental analysis (as C ₁₃ H ₁₂ N ₂ O ₃ ) Calculated: C; 63.93, H; 4.95, N; 1
1.47. Found: C; 64.00, H; 4.91, N; 11.57.

[0462]

[Reference Example 31] Starting from (R) -5- (N-phthaloylaminomethyl) -2-pyrrolidone D-glutamic acid, in the same manner as in Reference Example 30,
The title compound was obtained as white needles. Melting point: 191.0-192.0 ° C (reconstituted from methylene chloride-ethyl acetate) [α] _D ²⁵ -3.23 ° (C = 1.02, CHCl ₃ ). Elemental analysis (as C ₁₃ H ₁₂ N ₂ O ₃ ) Calculated: C; 63.93, H; 4.95, N; 11.47. Found: C; 64.19, H; 4.87, N; 11.47.

[0463]

Reference Example 32 dl-5- (N-phthaloylaminomethyl) -1- (2-tetrahydro
In a mixture of sodium (pyranyloxyethyl ) -2-pyrrolidone hydride (55% mineral oil suspension, 12.29 g) and dimethylformamide (600 ml) under ice cooling (5-8 ° C), A solution of the compound (62.52 g) in dimethylformamide (600 ml) was added dropwise. After stirring at room temperature for 30 minutes, 2-tetrahydropyranyloxyethyl bromide (58.
96 g) in dimethylformamide (100 ml) under ice cooling (5
° C). After stirring at room temperature for 4 hours, the reaction solution was poured into ice water (2 l) and extracted three times with ethyl acetate. The extracts were combined, dried and concentrated, and the resulting residue was purified on silica gel.
(700 g) was subjected to column chromatography.
The fractions eluted with hexane-ethyl acetate (1: 1-0: 1) were collected to give 53.11 g (56%) of the title compound as a viscous oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.45-1.90
(6H, m); 1.90-2.50 (4H, m); 3.33-3.67 (3H, m); 3.75-4.0
0 (5H, m); 4.08-4.20 (1H, m), 4.58-4.63 (1H, m); 7.70-7.
90 (4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1775, 172
0, 1680, 1490. Mass spectrum (m / z): 373 (M ⁺ +1); 372 (M ⁺ ); 287; 271;
128.

[0464]

Reference Example 33 (S) -5- (N-phthaloylaminomethyl) -1- (2-tetrahydride
Starting from the compound of Reference Example 30 (lopyranyloxyethyl) -2-pyrrolidone , the title compound was obtained as a viscous oil in the same manner as in Reference Example 32.

[0465]

Reference Example 34 (R) -5- (N-phthaloylaminomethyl) -1- {2- (2-tetrahi
Starting from mud pyranyl) ethyl} -2-pyrrolidone compound of Reference Example 31 and following the procedure of Reference Example 32 to give the title compound as a viscous oil.

[0466]

[Reference Example 35] dl-1- (2-hydroxyethyl) -5- (N-phthaloylaminomethyl
(Tyl ) -2-pyrrolidone The compound of Reference Example 32 (53.05 g) was treated with acetic acid (300 ml) and water.
(150 ml) and stirred at room temperature for 15 hours.
Acetic acid and water were distilled off under reduced pressure, and the resulting oily residue was subjected to column chromatography using silica gel (600 g). The fractions eluted with methylene chloride-methanol (5: 95-7: 93) were collected and 32.75 g of the title compound (80
%) As white crystals. Mp: 121.0-123.0 ℃ (methylene chloride - recrystallized from hexane) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.98-2.55
(4H, m); 3.11 (1H, br.s); 3.40-3.50 (1H, m); 3.70-3.95 (5
H, m); 3.95-4.05 (1H, m); 7.70-7.90 (4H, m) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 177
5, 1720, 1670, 1495. Mass spectrum (m / z): 289 (M ⁺⁺ 1);
288 (M ⁺ ); 257;

[0467]

Reference Example 36 (S) -1- (2-hydroxyethyl) -5- (N-phthalo
(Ilaminomethyl) -2-pyrrolidone Starting from the compound of Reference Example 33, the title compound was obtained as white crystals in the same manner as in Reference Example 35. Melting point: 132.0-133.0 ° C (reconstituted from methylene chloride-hexane) [α] _D ²⁵ -43.4 ° (C = 1.01, CHCl ₃ ). Elemental analysis (as C ₁₅ H ₁₆ N ₂ O ₄ ) Calculated: C ; 62.49, H; 5.59, N; 9.72. Found: C; 62.66, H; 5.51, N; 9.75.

[0468]

Reference Example 37 (R) -1- (2-hydroxyethyl) -5- (N-phthaloylamino
Methyl) -2-pyrrolidone Starting from the compound of Reference Example 34, the title compound was obtained as white crystals in the same manner as in Reference Example 35. Melting point: 131.0-133.0 ° C (reconstituted from methylene chloride-hexane) [α] _D ²⁵ + 43.1 ° (C = 1.03, CHCl ₃ ). Elemental analysis (as C ₁₅ H ₁₆ N ₂ O ₄ ) Calculated: C ; 62.49, H; 5.59, N; 9.72. Found: C; 62.59, H; 5.58, N; 9.73.

[0469]

[Reference Example 38] dl-5-aminomethyl-1- (2-hydroxyethyl) -2-pyrroli
It was suspended the compound of Dong Reference Example 35 (32.59 g) in ethanol (500 ml), n-butylamine (67 ml) and the mixture was stirred under heating at 80 ° C. 24 hours. The residue obtained by evaporating the solvent was subjected to column chromatography using silica gel (300 g). Methylene chloride-methanol-water (9: 1: 0-60: 3
The fractions eluted at (5: 5) were collected and the title compound (15.70 g) was collected.
(88%) as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.40-2.00
(3H, br.s); 1.75-1.93 (1H, m); 2.12-2.27 (1H, m); 2.32-
2.57 (2H, m); 2.88 (1H, dd, J = 13.18,3.91H _Z ); 3.02 (1H, d
d, J = 13.18,4.89H _Z ); 3.37 (1H, ddd, J = 14.16,7.81,2.98
H _Z ); 3.56 (1H, ddd, J = 14.16,5.85,2,93H _z ); 3.70 (1H, dd
d, J = 11.71,5.85,2.93H _Z ); 3.65-3.75 (1H, m); 3.91 (1H, d
dd, J = 11.71,7.81,2.93H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 167
0. Mass spectrum (m / z): 159 (M ⁺ +1); 128.

[0470]

Reference Example 39 (S) -5-Aminomethyl-1- (2-hydroxyethyl) -2-pyrroli
Starting from the compounds of Don Reference Example 36 and following the procedure of Reference Example 38 to give the title compound as an oil. [Α] _D ²⁵ -32.7 ° (C = 1.06, CHCl ₃ ).

[0471]

[Reference Example 40] (R) -5-aminomethyl-1- (2-hydroxyethyl) -2-pyrroli
Starting from the compounds of Don Reference Example 37 and following the procedure of Reference Example 38 to give the title compound as an oil. [Α] _D ²⁵ + 32.3 ° (C = 1.07, CHCl ₃ ).

[0472]

Reference Example 41 dl-octahydropyrrolo [1,2-a] pyrazin-6-one A solution of the compound of Reference Example 38 (15.59 g) and triphenylphosphine (51.67 g) in tetrahydrofuran (280 ml) was prepared.
A solution of diethyl azodicarboxylate (34.31 g) in tetrahydrofuran (40 ml) was added at room temperature. After stirring at room temperature for 1 hour, the reaction solution was concentrated and dried. The residue was silica gel (260
The fraction eluted with methylene chloride methanol (95: 5-60: 35) was collected by column chromatography using g) to give 8.012 g (58%) of the title compound as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.58 (1H, dd
dd, J = 12.69,9.77,9.77,7.32H _Z ); 1.99 (1H, br.s); 2.16
(1H, dddd, J = 12.69,7.32,7.32,5.37H Z); 2.32-2.45 (3H,
m); 2.60 (1H, ddd, J = 11.72,11.72,3.41H _Z ); 2.75-2.90 (1
H, m); 2.97-3.06 (1H, m); 3.16 (1H, dd, J = 11.72,3.90H _Z );
3.55 (1H, dddd, J = 10.75,7.32,7.32,3.90H _Z ); 3.97-4.06
(1H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3350, 168
5. Mass spectrum (m / z): 140 (M ⁺ ); 98.

[0473]

Reference Example 42 (S) -Octahydropyrrolo [1,2-a] pyrazin-6-one From the compound of Reference Example 39, the title compound was obtained as an oil in the same manner as in Reference Example 41. [Α] _D ²⁵ -25.8 ° (C = 1.28, CHCl ₃ ).

[0474]

Reference Example 43 (R) -Octahydropyrrolo [1,2-a] pyrazin-6-one From the compound of Reference Example 40, the title compound was obtained as an oil in the same manner as in Reference Example 41. [Α] _D ²⁵ + 25.2 ° (c = 1.35, CHCl ₃ ).

[0475]

Reference Example 44 dl-2- (3,4,5-trimethoxybenzoyl) octahydropi
Loro [1,2-a] pyrazin-6-one The compound of Reference Example 41 (2.023 g) in tetrahydrofuran (1
0 ml) solution, add sodium bicarbonate (2.425 g) and water (20 ml).
ml), and then 3,4,5-trimethoxybenzoyl chloride (3.986 g) in tetrahydrofuran (10 ml) was added dropwise. After stirring at room temperature for 30 minutes, the reaction solution was poured into water and extracted three times with methylene chloride. After combining the extracts and washing with a saturated aqueous solution of sodium hydrogen carbonate and saturated saline,
It was dried and concentrated. The residue was subjected to column chromatography using silica gel (200 g), and the fraction eluted with methylene chloride-methanol (1: 0-98: 2) was collected to give 3.37 g (70%) of the title compound as a powder Obtained. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.55-1.75
(1H, m); 2.15-2.35 (1H, m); 2.40-2.50 (3H, m); 2.55-2.7
5 (1H, m); 2.75-3.10 (3H, m); 3.50-3.70 (1H, m); 3.88 (9
H, s); 4.00-4.20 (1H, m); 6.63 (2H, s) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1680, 163
0, 1585, 1460, 1420, 1330, 1220, 1130. Mass spectrum (m / z): 334 (M ⁺ ); 237; 195.

[0476]

Reference Example 45 (S) -2- (3,4,5-trimethoxybenzoyl) octahydro
Pyrrolo [1,2-a] pyrazin-6-one From the compound of Reference Example 42, the title compound was obtained as a powder in the same manner as in Reference Example 44. [Α] _D ²⁵ -15.5 ° (C = 1.08, CHCl ₃ ).

[0477]

Reference Example 46 (R) -2- (3,4,5-trimethoxybenzoyl) octahydro
Pyrrolo [1,2-a] pyrazin-6-one From the compound of Reference Example 43, the title compound was obtained as a powder in the same manner as in Reference Example 44. [Α] _D ²⁵ + 15.1 ° (C = 1.08, CHCl ₃ ).

[0478]

Reference Example 47 Method of dl-6- (N- phthaloylaminomethyl ) -2-piperidone Szirtes et al. [J. Med. Chem., 29 , 1654 (1986)]
Dl-pyro-2-aminoadipic acid (36.
0 g) was reduced by the method of Saijo et al. To obtain dl-6-hydroxymethyl-2-piperidone (26.71 g). Mp: 81-83 ° C. - NMR spectrum (methylene chloride recrystallized from ethyl _{acetate) (270MH Z, CDCl 3)} δ ppm: 1.28-1.42
(1H, m); 1.65-2.00 (3H, m); 2.20-2.46 (2H, m); 3.45 (1H,
dd, J = 10.25,8.30H _Z ); 3.68 (1H, dd, J = 10.25,2.44H _Z ); 3.
88 (1H, br.s); 7.18 (1H, br.s) Elemental analysis (C ₆ H ₁₁ NO ₂₎ Calculated values:. C; 55.80, H; 8.58, N; 10.84 Found:. C; 55.60, H; 8.39, N; 10.77. Using the above compound (3.06 g), in the same manner as in Reference Example 29, 4.59 g (75%) of the title compound was obtained as white crystals. Mp: 197-199 ° C. (chloroform - hexane to) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.40-1.60
(1H, m); 1.60-1.80 (1H, m); 1.85-2.05 (2H, m); 2.20-2.4
2 (2H, m); 3.65-4.90 (3H, m); 6.13 (1H, br.s); 7.70-7.90
(4H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 177
5, 1720, 1680, 1490. Mass spectrum (m / z): 259 (M ⁺ +1); 258 (M ⁺ ); 160; 98.

[0479]

Reference Example 48 dl-1- (2-hydroxyethyl) -6- (N-phthaloylaminomethyl
(Tyl ) -2-piperidone The title compound (16.74 g) was obtained as an oil using the compound of Reference Example 47 (35.62 g) in the same manner as in Reference Examples 32 and 35. Yield: 40% (two steps) NMR spectra _{(270MH Z, CDCl 3) δ} ppm: 1.45-2.62
(6H, m); 3.40-4.05 (8H, m); 7.70-7.90 (4H, m) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3400, 177
5, 1720, 1650, 1620, 1495. Mass spectrum (m / z): 303 (M ⁺⁺ 1);
285;

[0480]

Reference Example 49 dl-6-aminomethyl-1- (2-hydroxyethyl) -2
-Using the compound (16.69 g) of piperidone reference example 48 and in the same manner as in reference example 38, 6.94 g (73%) of the title compound was obtained as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.66-2.00
(4H, m); 1.95-2.25 (3H, br.s); 2.37-2.48 (2H, m); 2.85-
2.95 (2H, m); 3.35-3.45 (1H, m); 3.53 (1H, ddd, J = 14.16,
6.83,3.42H _Z ); 3.63 (1H, ddd, J = 14.16,5.86,3.42H _Z ); 3.
74 (1H, ddd, J = 11.23,5.86,3.42H _Z ); 3.87 (1H, ddd, J = 11.2
3,6.83,3.42H _Z ). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3380, 161
5. Mass spectrum (m / z): 173 (M ⁺ +1); 155; 142.

[0481]

Reference Example 50 dl-octahydro-2H-pyrido [1,2-a] pyrazin-6-one Using the compound of Reference Example 49 (6.91 g), the same procedure as in Reference Example 41 was carried out to obtain the title compound. 4.01 g (65%) of the compound was obtained as an oil. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.35-1.50
(1H, m); 1.60-1.77 (1H, m); 1.77-2.03 (2H, m); 2.10-2.4
0 (1H, br.s); 2.25-2.77 (5H, m); 2.93-3.12 (2H, m); 3.28-
3.45 (1H, m); 4.60-4.75 (1H, m). Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 3350, 162
5. Mass spectrum (m / z): 154 (M ⁺ ); 112.

[0482]

Reference Example 51 dl-2- (3,4,5-trimethoxybenzoyl) octahydro-2
H-pyrido [1,2-a] pyrazin-6-one Starting from the compound of Reference Example 50 (3.98 g) and operating as in Reference Example 44, 6.17 g (69%) of the title compound
Was obtained as a powder. NMR spectrum _{(270MH Z, CDCl 3) δ} ppm: 1.40-2.15
(6H, m); 2.28-2.83 (4H, m); 2.90-3.20 (1H, m); 3.32-3.5
0 (1H, m); 3.87 (9H, s); 4.63-4.80 (1H, m); 6.63 (2H, s) .Infrared absorption spectrum ν _max (CHCl ₃ ) cm ^-1 : 1630, 158
5, 1460, 1410, 1330, 1125. Mass spectrum (m / z): 348 (M ⁺ ); 237; 195; 153.

[0483]

[Reference Example 52]dl- (Z) -7- (3,4-dimethoxyphenyl) methylene-2- (3,4,
5-trimethoxy) benzoyloctahydro-2H-pyrido
[1,2-a] pyrazin-6-one Compound of Reference Example 51 (447.8 mg) and 3,4-dimethoxyben
The same as in Example 29 with the use of
Was operated in the same manner. The crude product is transferred to a rover column (B column)
And collect the low-polarity fraction eluted with ethyl acetate.
The title compound (41.6 mg) was obtained as white crystals. Yield: 6.5% (2 steps). Melting point: 73.0-76.0 ° C (from methylene chloride-hexane)
Reconnection) NMR spectrum (270MH_Z , CDCl_Three) δ ppm: 1.60-1.85
(1H, m); 2.10-2.33 (1H, m); 2.50-2.90 (6H, m); 2.90-3.2
0 (1H, m); 3.40-3.60 (1H, m); 3.88 (9H, s); 3.89 (6H, s);
4.65-4.85 (1H, m); 6.60 (1H, s); 6.64 (2H, s); 6.81 (1H,
d, J = 8.06H_Z); 7.14 (1H, dd, J = 8.06,1.83H_Z); 7.38 (1H, d,
J = 1.83H_Z). Infrared absorption spectrum ν_max (CHCl_Three) cm^-1: 1625, 158
5, 1510, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 496 (M⁺); 301; 195.

[0484]

[Reference Example 53]dl- (E) -7- (3,4-dimethoxyphenyl) methylene-2- (3,4,
5-trimethoxy) benzoyloctahydro-2H-pyrido
[1,2-a] pyrazin-6-one After elution of the compound of Reference Example 52, elution is further continued.
The highly polar fraction was collected and the title compound (525.3 mg)
Obtained as colored crystals. Yield: 82.3% (2 steps). Melting point: 166.0-168.0 ° C (methylene chloride-hexane
NMR spectrum (270MH)_Z , CDCl_Three) δ ppm: 1.45-1.70
(1H, m); 1.90-2.20 (1H, m); 2.45-3.30 (7H, m); 3.50-3.7
0 (1H, m); 3.880 (3H, s); 3.884 (9H, s); 3.91 (3H, s); 4.6
5-4.85 (1H, m); 6.65 (2H, s); 6.87 (1H, dd, J = 1.83H_Z); 6.
88 (1H, d, J = 8.43H_Z); 6.95 (1H, dd, J = 8.43,1.83H_Z); 7.75
(1H, s). Infrared absorption spectrum ν_max (CHCl_Three) cm^-1: 1625, 158
5, 1510, 1460, 1420, 1325, 1125. Mass spectrum (m / z): 496 (M⁺); 301; 195.

[0485]

[Production Example 1] (Tablets) Mix for 30 minutes other than magnesium stearate,
Magnesium stearate was added through a sieve. The mixture was mixed for an additional 5 minutes and compressed into tablets of 8 mm diameter.

[0486]

[Production Example 2] (Capsule) Mix for 5 minutes and fill in No. 3 capsules.

[0487]

[Production Example 3] (Granules) Combine the above 3 types and add 10 parts of hydroxypropyl cellulose.
% Wet with aqueous solution. The mixture was granulated by a conventional method using a cylindrical condyle, dried at 60 ° C., and sized with a No. 16 sieve.

[0488]

[Production Example 4] (Suppository) The compound was dispersed in a Witopsol base at 50 ° C. and poured into a mold for production.

[0489]

[Production Example 5] (Syrup) Per 100 ml of the compound of Example 3 1 g Sucrose 50 sodium carboxymethylcellulose 0.25 citric acid 0.15 sodium citrate 1 benzoic acid 0.5 purified water 100 ml sucrose, citric acid, sodium citrate, benzoic acid Was dissolved in purified water, and sodium carboxymethylcellulose and the compound were dispersed therein. Adjust the volume with purified water,
A syrup was produced.

[0490]

Production Example 6 (Injection) Compound of Example 3 1 mg Polyethylene glycol 150 polysorbate 80 0.5 Sodium dihydrogen phosphate (dihydrate) 1.6 Sodium monohydrogen phosphate (anhydrous) 1.4 Purified water for injection 1 ml Glycol and polysorbate 8
0 and mixed with purified water for injection. In this, sodium dihydrogen phosphate (dihydrate) and sodium monohydrogen phosphate (anhydrous) were dissolved, and the liquid volume was adjusted. The ampoules were filled, sealed and sterilized at 121 ° C. for 20 minutes.

──────────────────────────────────────────────────の Continued on front page (51) Int.Cl. ⁷ Identification code FI A61P 9/10 A61P 9/10 11/06 11/06 43/00 111 43/00 111 C07D 243/08 C07D 243/08 243 / 10 243/10 295/16 295/16 Z 471/04 116 471/04 116 487/04 140 487/04 140 (72) Inventor Masaaki Miyamoto 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (72) Inventor Yasuki Iijima 1-2-58 Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd. (56) References JP-A-3-72457 (JP, A) JP-A-4-342579 (JP, A JP-A-3-232864 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 241/04 A61K 31/495 A61K 31/4985 A61K 31/551 A61P 1/04 A61P 9 / 10 A61P 11/06 A61P 43/00 C07D 243/08 C07D 243/10 C07D 295/16 C07D 471/04 C07D 487/04 CA (STN) REGI TRY (STN)

Claims (2)

(57) [Claims] 1. A compound of the general formula In the formula, R ¹ and R ² are the same or different and each have a group having the formula —R ⁶ [wherein, R ⁶ is an aryl group which may be substituted (the substituent is a group A shown below) 1 to 5 substituents selected from the above.) Or a heteroaryl which may be substituted.
(The substituents are 1 to 5 substituents selected from Group A below.) ], Group (wherein, R ⁶ is as defined above.) Having the formula -CH = CH-R ^6, or the formula -C
And a group having ≡C—R ⁶ (wherein R ⁶ has the same meaning as described above). R ³ represents a hydrogen atom, a lower alkyl group, a cyano group, or a group having the formula —R ⁶ (wherein R ⁶ has the same meaning as described above), or together with R ⁵ , And a general formula-(CH ₂ ) _p- (where p represents 1 to 3). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituent is 1 to 5 substituents selected from the following groups A and B) or an optionally substituted heteroaryl group (The substituent is
1 to 5 substituents selected from the following group A. )
Is shown. R ⁵ represents a hydrogen atom or a lower alkyl group, or together with R ³ , represents a general formula — (CH ₂ ) _p −
(Where p represents 1 to 3). m represents 1 or 2. n represents 1 or 2. However, when R ⁴ represents a phenyl group or a substituted phenyl group,
In this case, R ⁵ does not represent a hydrogen atom, R ⁴ represents a 3-pyridyl group, R ³ represents a hydrogen atom or a lower alkyl group, R ⁵ represents a hydrogen atom or a lower alkyl group, and m and When n is 1 each, R ¹ and R
² is the same or different and has a group having the formula -R6 ^' [wherein,
R ^{6 ′} is a substituted aryl group (the substituent is 1 to 5 substituents selected from the following group A) or an optionally substituted heteroaryl group (the substituted aryl group) The group is
1 to 5 substituents selected from the following group A. )
Is shown. ], Group (wherein having the formula ^{-CH = CH-R 6, R} 6
Is as defined above. ) Or a group having the formula —C≡C—R ⁶ (wherein R ⁶ has the same meaning as described above). And a salt thereof. [Group A] a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a hydroxyl group, an alkylenedioxy group having 1 to 4 carbon atoms, an acyloxy group, a halogen atom, a cyano group and a nitro group. [Group B] Lower alkylsulfonyl, lower alkylsulfinyl and lower alkylthio groups. 2. A compound of the general formula In the formula, R ¹ and R ² are the same or different and each have a group having the formula —R ⁶ [wherein, R ⁶ is an aryl group which may be substituted (the substituent is a group A shown below) 1 to 5 substituents selected from the above.) Or a heteroaryl which may be substituted.
(The substituents are 1 to 5 substituents selected from Group A below.) ], Group (wherein, R ⁶ is as defined above.) Having the formula -CH = CH-R ^6, or the formula -C
And a group having ≡C—R ⁶ (wherein R ⁶ has the same meaning as described above). R ³ represents a hydrogen atom, a lower alkyl group, a cyano group, or a group having the formula —R ⁶ (wherein R ⁶ has the same meaning as described above), or together with R ⁵ , And a general formula-(CH ₂ ) _p- (where p represents 1 to 3). X represents an oxygen atom or a sulfur atom. A represents a lower alkylene group, a carbonyl group, a thiocarbonyl group, a sulfinyl group or a sulfonyl group. R ⁴ is a phenyl group, a substituted phenyl group (the substituent is 1 to 5 substituents selected from the following groups A and B), or an optionally substituted heteroaryl group (The substituent is
1 to 5 substituents selected from the following group A. )
Is shown. R ⁵ represents a hydrogen atom or a lower alkyl group, or together with R ³ , represents a general formula — (CH ₂ ) _p −
(Where p represents 1 to 3). m represents 1 or 2. n represents 1 or 2. However, when R ⁴ represents a phenyl group or a substituted phenyl group,
In that case, R ⁵ does not represent a hydrogen atom. Platelet-activating factor (PA) containing the compound represented by｝ or a salt thereof
An agent for preventing or treating a disease caused by F). [Group A] a lower alkyl group, a halogeno lower alkyl group, a lower alkoxy group, a hydroxyl group, an alkylenedioxy group having 1 to 4 carbon atoms, an acyloxy group, a halogen atom, a cyano group and a nitro group. [Group B] Lower alkylsulfonyl, lower alkylsulfinyl and lower alkylthio groups.