"Diamine Derivatives, Process For Producing The Same, And Plant Disease Control Agents Containing The Same As Active Ingredients"
Abstract:
Abstract: A diamine derivative, a process for producing the derivative, and a plant disease control agent containing the compound as an active ingredient. The diamine derivative is represented by the formula (1): (1) (wherein Rl represents C1-6 halogenated hydrocarbon, etc.; R2 and R7 each independently represents hydrogen, C1-6 hydrocarbon, etc.; R3 and R4 each independently represents hydrogen, optionalty substituted C1-6 hydrocarbon, eTc. or R3 and R4 represent C3-6 cycloalkyl containing the carbon atom bonded thereto; R5 and R6 each independently represents hydrogen, a C1-6 hydrocarbon group, etc.; and R8 represents optionally substituted arylalkyl, optionally substituted aryl, or optionally substituted heteroaryl).
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13-13, Nishinogawa 3-chome, Komae-shi, Tokyo 201-0001 (Japan).
Specification
DESCRIPTION
DIAMINE DERIVATIVES, PROCESS FOR PRODUCING THE SAME, AND PLANT DISEASE CONTROL AGENTS CONTAINING THE SAME AS ACTIVE
INGREDIENTS
TECHNICAL FIELD
The present invention relates to new diamine derivatives, process for producing them, and plant disease control agents containing them as active ingredients.
BACKGROUND ART
The pest control plays an important role in cultivating paddy rice. In particular, a rice blast is a significant disease. Therefore, various plant disease control agents have been developed and put into use. However, every agent does not have a satisfactory plant disease control activity, nor is at a satisfactory level with respect to harm to useful crops. In recent years, fungi having resistance to chemical agents have appeared due to a heavy use of plant disease control agents and, sometimes, known chemical agents do not have satisfactory activities. Accordingly, a new plant disease control agent capable of controlling harmful fungi at a low agent concentration has been required. Japanese Unexamined Patent Application Publication No. 2003-096046 discloses diamine
derivatives different from the compounds of the present invention and plant disease control agents containing them as active ingredients. However, in this document, there is no description on the usefulness of diamine derivatives including an oxycarbonyl group having a halogenated hydrocarbon.
Patent Document 1: Japanese Unexamined Patent Application Publication No. 2003-096046 (W02003008372)
DISCLOSURE OF' THE INVENTION
It is an object of the present invention to provide a diamine denivative exerting an excellent effect of controlling a rice blast.
Recently, the inventors of the present invention found out that diamine derivatives, in particular, diamine derivatives including an oxycarbonyl group having a halogenated hydrocarbon, exerted a high effect of controlling the rice blast. It was found out that this control effect was significantly higher than the effect: exerted by other diamine derivatives disclosed in Japanese Unexamined Patent Application Publication No. 2003-096046, fot example, and the present invention has been completed.
The present invention is as described below. [1]. A di.atnine derivative represented by Formula (1):
[In Formula, Rl represents a halogenated hydrocarbon having the carbon number of 1 to 6; R2 and R7 independently represent a hydrogen atom, a hydrocarbon having the carbon number of 1 to 6, or an acyl group; R3 and R4 independently represent a hydrogen atom, a hydrocarbon which has the carbon number of 1 to 6 and which may be substituted, or a heteroaryl group which may be substituted, or represent a cycloalkyl group having the carbon number of 3 to 6 including a carbon atom bonding to R3 and R4; R5 and R6 independently represent a hydrogen atom or a hydrocarbon having the carbon number of 1 to 6; and R8 represents an arylalkyl group which may be substituted, an aryl group which may be substituted, or a heteroaryl group which may be substituted. ] .
[2]. A plant disease control agent characterized in containing the diamine derivative according to the above-described [1] as an active ingredient.
[3] . A process for producing the diamine derivative according to the above-described [1], comprising reacting a compound represented by Formula (2) :
[In Formula, Rl, R2, R3, R4 , R5, R6, and R7 represent the same substances as those in [1]] with a compound represented by
Formula (3):
[In Formula, R8 represents the same substance as that in [1], and X represents a leaving group.].
[4]. A process for producing the diamine derivative according to [1], comprising condensing a compound represented by Formula (2) and a compound represented by Formula (4):
[In Formula, R8 represents the same substance as that in [1].]. [5]. A process for producing the diamine derivative according to the above-described [I], comprising reacting a compound represented by Formula (5):
[In Formula, R2, R3, R4, R5, R6, R7, and R8 represent the same substances as those in [1].] with a compound represented by Formula (6}:
[In Formula, Rl represents the same substance as that in [1] , and X represents a leaving group.].
The di-imine derivative according to the present invention includes an oxycarbonyl group having a halogenated hydrocarbon and, thereby, exerts an excellent effect of controlling the rice blast.
BEST MODE FOR CARRYING OUT THE INVENTION
The present: invention will be described below in detail.
In the diamine derivative represented by Formula (1) and the process for producing the same, typical examples of substituernts include the following groups, although not limited to them. Examples of halogenated hydrocarbons having the carbon number of 1 to 6 include chlorinated alkyl groups, e.g., a chloromethyl group, a 2-chloroethyl group, a 2,2,2-trichloroethyl group, a 3-chloro-l-propyl group, and a 4-chloro-1-butyl group; fluorinated alkyl groups, e.g., a 2-fluoroethyl group, a 2,2,2-trifluoroethyl group, a 1,1,1,3,3,3-hexafluoro-2-propyl group, a 1,3-difluoro-2-propyl group, a 5-fluoro-1-pentyl group, a 6,6,6,5,5,4,4,3,3-nonafluoro-1-hexyl group, and a 1-ethoxy-2,2,2-trifluoroethyl group; brominated alkyl groups, e.g., a 2-bromoethyl group and a 1,3-dibromo-2-propyl group; iodized alkyl groups, e.g., a 2-iodoethyl group; alkyl groups containing at least two types of halogen, e.g., a 3-bromo-l,1,1-trifluoro-2-propyl group; chlorinated cycloalkyl groups, e.g., a chlorocycli propyl group, a 2-chloro cyclobutyl group, a 2-
chlorocyclopentyl group, a 2-chlorocyclohexyl group, a 3-chlorocyclohexyl group, and a 4-chlorocyclohexyl group; fluorinated cycloalkyl groups, e.g., a 2-fluorocyclohexyl group and a 2,2,3,3-tetrafluorocyclopropyl group; brominated cycloalkyl groups, e.g., a 2-bromocyclohexyl group; iodized cycloalkyl groups, e.g., a 2-iodocyclohexyl group; chlorinated alkenyl groups, e.g., a 2-chloro-2-propenyl group and a 5-chloro-4-pentenyl group; fluorinated alkenyl groups, e.g., a 4,4,4-trifuoro-2-butenyl group and a 6,6,6-trifluoro-5-hexenyl group; chlorinated cycloalkenyl groups, e.g., a 2-chloro-2-cyclopropenyl group, a 3-chloro-3-cyclopentenyl group, and a 2-chloro-2-cyclohexenyl group; and fluorinated cycloalkenyl groups, e.g., a 2-.f luoro-2-cyclobutenyl group.
Examples of hydrocarbons having the carbon number of 1 to 6 include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a vinyl group, a properiyl group, a butenyl group, a pentenyl group, a hexerny] group, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, an ethynyl group, a propynyl gnoup, a butynyl group, a pentynyl group, a hexynyl group, a pheny] group, and a naphthyl group. Examples of heteroaryl groups include a pyridyl group, a pyrimidyl group, a thienyl group, a furanyl group, a pyrazolyl group, an imidazolyl group, an .sothiazolyl group, an isoxazolyl group, an indolyl group, a quinolyl group, a benzofuranyl group, a benzothienyl group, a bonzoxazolyl group, a benzisoxazolyl group, a
benzimidazoLyl group, a benzothiazolyl group, and a benzisothiazolyI group. Examples of acyl groups include alkylcarbonyl groups, e.g., an acetyl group; and arylcarbonyl group, e.g., a benzoyl group. Examples of substituents in the aryl group and the heteroaryl group include alkyl groups, e.g., a methyl group, an ethyl group, a propyl group, and a butyl group; cycloalkyl groups, e.g., a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group; halogenated alkyl groups, e.g., a trifluoromethyl group, a difluoromethyl group, a bromodifluoromethyl group, and a trifluoroethyl group; alkoxy groups, e.g., a methoxy group, an ethoxy group, a propoxy group, and a butoxy group; halogenated alkoxy groups, e.g., a trifluoromethoxy group, a difluoromethoxy group, and a trifluoroethoxy group; alkoxycarbonyl groups, e.g., a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, and a butoxycarbonyl group; aryloxycarbonyl groups, e.g., a phenoxycarbonyl group; alkylamino groups, e.g., a methylamino group, an ethylamino group, a propylamino group, a butylamino group, and a dimethylami no group; cycloalkylamino groups, e.g., a cyclopropylamino group, a cyclobutylamino group, a cyclopentyiamino group, a cyclohexylamino group, and a dicyclopropylamino group; alkylcarbamoyl groups, e.g., a methylcarbamoyl group, an ethylcarbamoyl group, a propylcarbamoyl group, a butylcarbamoyl group, and a dimethyl catbamoyl group; cycloalkylcarbamoyl groups, e.g., a cyclopropylcarbamoyl group, a cyclobutylcarbamoyl group, a
cyclopentylcarbamoyl group, a cyclohexylcarbamoyl group, and a
dicyclopropylcarbamoyl group; alkylcarbonylamino groups, e.g., a
methylcarbonylamino group, an ethylcarbonylamino group, a
propylcarbonylamino group, and a butylcarbonylamino group;
cycloalkyJcarbonylamino groups, e.g., a cyclopropylcarbonylamino
group, a cyclobutylcarbonylamino group, a
cyclopenty.lcarbonylamino group, and a cyclohexylcarbonylamino
group; alkyloxycarbonylamino groups, e.g., a
methyloxycarboriylamino group, an ethyloxycarbonylamino group, a
propyloxyca rbonylamirio group, and a butyloxycarbonylamino group;
cycloalkyloxycarbonylamino groups, e.g., a
cyclopropyjoxycarbonylamino group, a cyclobutyloxycarbonylamino
group, a cyclopentyloxycarbonylamino group, and a
cyclohexyJoxycarbonylamino group; alkylthio groups, e.g., a
methylthio group, an ethylthio group, a propylthio group, and a
butylthio group; halogenated alkylthio groups, e.g., a
trifluoromethylthio group, a difluoromethylthio group, and a
trifluoroethylthio group; alkylsulfinyl groups, e.g., a
methanesulfinyl group, an ethanesulfinyl group, a
propanesuliinyl group, and a butanesulfinyl group; halogenated
alkylsulfinyl groups, e.g., a trifluoromethanesulfinyl group, a
difluoromethanesulfinyl group, and a trifluoroethanesulfinyl
group; alkyIsulfonyl groups, e.g., a methanesulfonyl group, an
ethanesulfonyl group, a propanesulfonyl group, and a
butanesul i c.nyl group; halogenated alkylsulfonyl groups, e.g., a
trifluoromethanesulfonyl group, a difluoromethanesulfonyl group,
and a trif1uoroethanesulfonyl group; alkylsulfonamide groups,
e.g., a metiianesulfonamide group, an ethanesulfonamide group, a propanesulfonami.de group, and a butanesulfonamide group; halogenated alkylsulfonamide groups, e.g., a
trifluoromethanesulfonamide group, a difluoromethanesulfonamide group, and a trifluoroethanesulfonamide group; halogen atoms, e.g., a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom; and acyl groups, e.g., an acetyl group and a benzoyl group.
In the1 compounds represented by Formula (3) and Formula (6), examples of groups which are represented by X and which are to be eliminated can include halogen atoms typified by a chlorine atom, alkoxy groups typified by a methoxy group and an ethoxy group, aryloxy groups typified by a phenoxy group and a 4-nitrophenyl group, acyloxy groups typified by an acetyloxy group and a benzoyloxy group, alkoxycarbonyloxy groups typified by a methoxycarbonyloxy group, arylcarbonyloxy groups typified by a phenylcarbonyloxy group, alkylthio groups typified by a methylthio group, a 2,5-dioxopyrrolidinyloxy group, a benzotriazoLyloxy group, and an imidazolyl group.
The compound represented by Formula (I) of the present invention is a new compound, and the compound represented by Formula (Is can be produced by a process described as Reaction formula (1). Reaction formula (1)
[In Reaction formula (I), Rl, R2, R3, R4, R5, R6, and R7 represent the same substances as those in Formula (2), and R8 and X represent the same substances as those in Formula (3)]
In Reaction formula (1), a diamine derivative represented by Formula (2) or a salt thereof is reacted with a known carbonyl compound represented by Formula (3) in a solvent or without solvent in the presence of a base or without base and, thereby, a diamine derivative represented by Formula (1) can be produced.
Examples of bases used in the reaction represented by Reaction formula (1) can include alkali metal hydroxides, e.g., sodium hydroxide and potassium hydroxide; alkaline-earth metal hydroxide, e.g., magnesium hydroxide and calcium hydroxide; alkali metal hydrides, e.g., sodium hydride and potassium hydride; alkali metal alcoholates, e.g., sodium methoxide and sodium ethoxide; alkali metal oxides, e.g., sodium oxide; carbonates, e.g., potassium carbonate and sodium carbonate; phosphates, e.g., tripotassium phosphate, trisodium phosphate, dipotassium monohydrogen phosphate, and disodium monohydrogen phosphate; acetates, e.g., sodium acetate and potassium acetate; and organic bases, e.g., pyridine, 4-
(dimethylamino)pyridine(DMAP) , triethylamine, and 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU).
The amounts of use of these bases are not specifically limited. When the above-described organic bases are used, these can also be used as solvents.
Examples of solvents used in the reaction represented by
Reaction formula (1) can include water; halogenated hydrocarbons, e.g., dichJ.oromethane and chloroform; aromatic hydrocarbons, e.g., benzene, toluene, and xylene; aliphatic hydrocarbons, e.g., hexane and heptane; aprotic polar solvents, e.g., dimethylformamide (DMF), dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), 1,3-dimethyl-2-imidazolidinone (DMI), and I-methyl-2-pyrrolidone (NMP); ethers, e.g., diethyl ether, diisopropyl ether, 1,2-dimethoxyethane, tetrahydrofuran (THF), and dioxane; and nitriles, e.g., acetonitrile and propionitrile, as long as the solvents do not react with compounds represented by, in particular, Formula (1), Formula (2), and Formula (3).
Preferably, the equivalent of the carbonyl compound represented by Formula (3) is 1 to 2 equivalent relative to the compound represented by Formula (2), and more preferably is 1 to 1.2 equivalent.
The reaction temperature and the reaction time of the above-described reaction can be varied within a wide range. In general, preferably, the reaction temperature is -20°C to 200°C, and more preferably is 0°C to 100°C. Preferably, the reaction time is 0.01 to 50 hours, and more preferably is 0.1 to 15 hours.
The arnine derivative and a salt thereof represented by Formula (2: in Reaction Formula (1) other than commercially available compounds can be readily produced by known amine synthesis methods, e.g., the Gabriel method, the Delepine method, and reduction of a cyano group, amide, imine, oxime, and the likes, and •:-, method described in Tetrahedron Asymmetry, Vol. 11, page 1907 ;2000) .
The compound represented by Formula (3) in Reaction Formula (1) can be produced by a common method in which a known carboxylic acid derivative represented by Formula (4) is reacted with thionyi chloride, oxalyl chloride, phosgene, phosphorous oxychloride, phosphorous trichloride, phosphorous pentachloride, thionyi bromide, phosphorous tribromide, diethylaminosulfur trifluoride, 1,1' -carboriylbis-lH-imidazole, or the like.
The compound represented by Formula (3) in Reaction Formula (1) can also be produced by a common method in which a known carboxylic acid derivative represented by Formula (4) is reacted with alcohols, e.g., methyl alcohol or ethyl alcohol, or phenols, e.g., phenol or nitrophenol.
The compound represented by Formula (3) in Reaction Formula (1) can also be produced by a common method in which a known carboxylic acid derivative represented by Formula (4) is reacted with chloroformates, e.g., methyl chloroformate or phenyl chloroformate.
The compound represented by Formula (3) in Reaction Formula (1) can also be produced by a common method in which a known carboxylic acid derivative represented by Formula (4) is reacted with N-hydroxysuccinic acid imide, 1-hydroxybenzotriazole, or the like.
The compound represented by Formula (1) of the present invention can also be produced by a method described as Reaction formula (2] . Reaction formula (2)
[In Reaction formula (2), Rl, R2, R3, R4, R5, R6, and R7 represent the same substances as those in Formula (2) (Chemical formula 2), and R8 represents the same substance as that in Formula (4) j
In Reaction formula (2), a diamine derivative represented by Formula (2) or a salt thereof and a known carboxylic acid derivative represented by Formula (4) are condensed in a solvent or without solvent and, thereby, a diamine derivative represented by Formula (1) can be produced.
Examples of condensing agents in this case can include N,N'-dicyciohexylcarbodiimide, 1,1'-carbonylbis-lH-imidazole, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, and 2-chloro-l,3-dimethylimidazolium chloride.
The amount of use of the condensing agent is 1 to 2 equivalent relative to the compound represented by Formula (4), and preferably is 1 to 1.2 equivalent.
In this case, an organic solvent similar to that used in the method represented by Reaction formula (I) can be used as long as the solvent: do not react with compounds represented by, in particuiii, Formula (1), Formula (2), and Formula (4).
The amount of use of the carboxylic acid derivative represented by Formula (4) is 1 to 2 equivalent relative to the diamdne deiivative represented by Formula (2), and preferably is
to 1.2 equi va 1 ent .
The reaction temperature and the reaction time of the above-described reaction can be varied within a wide range. In general, the reaction temperature is -20°C to 200°C, and preferably is 0°C to 100°C. The reaction time is 0.01 to 50 hours, and preferably is 0.1 to 15 hours.
The compound represented by Formula (1) of the present invention can also be produced by a method described as Reaction formula (3) . Reaction formula (3)
[In Reaction formula (3), R2, R3, R4, R5, R6, R7, and R8 represent the same substances as those in Formula (5) , and Rl and X represent the same substances as those in Formula (6)]
In Reaction formula (3), a diamine derivative represented by Formula :5) or a salt thereof is reacted with a known compound represented by Formula (6) in a solvent or without solvent; in the presence of a base or without base and, thereby, a diamine derivative represented by Formula (1) can be produced.
The compound represented by Formula (6) in Reaction Formula (3) can he [: reduced by a common method in which a corresponding alcohols arc- reacted with, for example, phosgenes, e.g., phosgene anci t.riphosgene or chloroformates, e.g., phenyl ch 1 o r < ; formate .
In this case, bases similar to those used in the method represented by Reaction formula (1) can be used.
The amounts of use of these bases are not specifically limited. When the above-described organic bases are used, these can also be used as solvents.
In thns case, an organic solvent similar to that used in the method represented by Reaction formula (1) can be used as long as the solvent do not react with compounds represented by, in particular, Formula (1), Formula (5), and Formula (6).
The amount of use of the compound represented by Formula (6) is 1 to 4 equivalent relative to the diamine derivative represented by Formula (5), and preferably is 1 to 2 equivalent.
The reaction temperature and the reaction time of the above-described reaction can be varied within a wide range. In general, tho reaction temperature is -20°C to 200°C, and preferably 'is 0°C to 100°C. The reaction time is 0.01 to 50 hours, and preferably is 0.1 to 15 hours.
The diamine derivative represented by Formula (1) may include an ,:. epresented by Formula (1), which is the compound of the present invention, as an active ingredient exerts an excellent ertect of controlling the rice blast (Pyricularia
oryzae) and the like.
The diairdne derivative represented by Formula (1), which is the compound of the present invention, can be used as a mixture with other plant disease control agents; pesticides, e.g., insecticides, herbicides, and plant growth regulators; soil conditioners; or fertilizable materials, as a matter of course, and in addition, can be formulated together with them.
The compound of the present invention may be used alone, but preferably is put to use in the form of a composition prepared by mixing with a carrier including a solid or liquid diluent. Here, the carrier refers to a synthesized or natural, inorganic or organic substance blended in order to accelerate an active ingredient to reach sites to be treated or to smooth the way to store, transport, and handle the active ingredient.
Examples of appropriate solid carriers include clay, e.g., montmorillonite, kaolinite, and bentonite; inorganic materials, e.g., diatomaceous earth, kaolin, talc, vermiculite, gypsum, calcium carbonate, amorphous silicon dioxide, and ammonium sulfate; vegetable organic materials, e.g., soybean meal, and wheat floui; and urea.
Examples of appropriate liquid carriers include aromatic hydrocarbons, e.g., toluene, xylene, and cumene; paraffin hydrocarbons, e.g., kerosene and mineral oil, halogenated hydrocarbons, e.g., carbon tetrachloride, chloroform, and dichloroethane; ketones, e.g., acetone and methyl ethyl ketone; ethers, e.g., dioxane, tetrahydrofuran, and diethylene glycol dimethyl ether; alcohols, e.g., methanol, ethanol, propanol, and
ethylene q. ycol; aprotic polar solvents, e.g., dimethylformamide, dimethyl su i. roxide, and l-methyl-2-pyrrolidone; and water.
Furthermore, in order to enhance the effect of the compound of the present invention, the following inert ingredients can also be used alone or in combination according to purposes in consideration of types of formulation, situations of application, and the 1 i k«;j.
Examp.l es of inert .ingredients for the purposes of emulsifies! ion, dispersion, spread, wetting, bonding, stabilization, and the like include anionic surfactants, e.g., lignin suli.onat.es, alkylbenzene sulfonates, alkylsulfuric acid ester salt.-, polyoxyalkylene alkyl sulfates, and polyoxyalkylene alkylphosphoric acid ester salts; nonionic surfactants, e.g., polyoxyalkylene alkyl ethers, polyoxyalkylene alkylaryl ethers, polyoxyalky ..ene aikylamines, polyoxyalkylene alkylamides, polyoxyalkyIene aLkylthioethers, polyoxyalkylene aliphatic acid esters, glycerin aliphatic acid esters, sorbitan aliphatic acid esters, poiyoxyalkylene sorbitan aliphatic acid esters, and polyoxypropylene polyoxyethylene block polymers; lubricants, e.g., calcium stearate and wax; stabilizers, e.g., isopropylhydrodiene phosphate; and furthermore, methyl cellulose, carboxymeth/I cellulose, casein, and gum arable. However, these component.-:; -.tie not limited to the above-described substances. In q--?nerdl, the amount of the active ingredient in the compound oi the present invention is 0.5 to 20 percent by weight with respec' to a dust, b to 50 percent by weight with respect to an emul:, ;fdbIe concentrate, 10 to 90 percent by weight with
respect to a wettable powder, 0.1 to 20 percent by weight with respect to a granule, and 10 to 90 percent by weight with respect to a flowable formulation. On the other hand, in general, the amount of the carrier in each type of formulation is 60 to 99 percent by weight with respect to a dust, 40 to 95 percent by weight with respect to an emulsifable concentrate, 10 to 90 percent by weight with respect to a wettable powder, 80 to 99 percent by weight with respect to a granule, and 10 to 90 percent by weight with respect to a flowable formulation. In general, the amount of the inert ingredient is 0.1 to 20 percent by weight with respect to a dust, 1 to 20 percent by weight with respect to an emulsifable concentrate, 0.1 to 20 percent by weight with respect to a wettable powder, 0.1 to 20 percent by weight with respect to a granule, and 0.1 to 20 percent by weight with respect to a flowable formulation.
The present invention will be described below in further detail with reference to examples and test examples. [Example Ij
Process for synthesizing N-(chloromethyloxycarbonyl)-N'-(4-methylbenzoyl)-3-methyl-l,2-butanediamine (Compound No. 1)
To a mixture(6ml) of 0.50 g of N-(4-methylbenzoyl)-3-methyl-1,2-butanediamine hydrochloride in dichloromethane was added 0.39 g of triethylamine under an ice-cooled condition. And then, a solution (2ml) of 0.25 g of chloromethyl chloroformate in dichloromethane was added under an ice-cooled condition, and the mixture was stirred for 4 hours at room temperature. The
mixture was -purified by column chromatography on silica gel (ethyl acetate/hexane), so that 0.43 g of the —title compound was prepared as white crystals.
[Example 21
Process for synthesizing N-(2,2,2-
trifluoroethyloxycarbonyl)-N1-(4-methylbenzoyl)-3-methyl-l,2-butanediamine (Compound No. 6)
Under an ice-cooled condition, a solution (6ml) of 0.78 g of 4-nitrophenyl chloroformate in dichloromethane was added to a mixed solution of 0.42 g of 2,2,2-trifluoroethanol and 0.43 g of triethylamine. After the reaction solution was stirred for 1 hour under an ice-cooled condition, 0.50 g of N-(4-methylbenzoyl)-3-methyl-l,2-butanediamine hydrochloride was added under an ice-cooled condition. After 0.21 g of triethylamine was added under an ice-cooled condition, the reaction solution was stirred for 1 hour under an ice-cooled condition and for 2 hours at room temperature. The reaction solution was stood for one night at room temperature and, subsequent.!-/, was concentrated under a reduced pressure. 50ml of ethyl acetate was added to the residue and the resulting mixture was washed with water. The organic layer was dried over anhydrous magnesium sulfate, and was concentrated under a reduced pressure so as to produce a solid. The resulting solid was washed with diisopropyl ether and, subsequently, was purified by column chromatography on silica gel (ethyl acetate/hexane), so that 0.34 g of the title compound was
prepared as white crystals.
[Example 3]
Process for synthesizing N-(2,2,2-
trichloroethyloxycarbonyl)-N'-(4-methylbenzoyl)-3-methyl-l, 2-butanediamlne (Compound No. 7)
To a mixture(5ml) of 0.50 g of N-(4-methylbenzoyl)-3-methyl-1,2-butanediamine hydrochloride in dichloromethane was added 0.43 g of triethylamine under an ice-cooled condition. And then, u.41 g of 2,2,2-trichloroethyl chloroformate was added under an ice-cooled condition, and the mixture was stirred for 4 hours at room temperature. The mixture was purified by column chromatography on silica gel (ethyl acetate/hexane), so that 0.52 g of she title compound was prepared as white crystals.
[Example 4]
Process for synthesizing N-(1,1,1,3,3,3-hexafluoro-2-propyloxycarbonyl)-N'-(4-methylbenzoyl)-3-methyl-l,2-butanediamine (Compound No. 8)
Under an ice-cooled condition, a mixed solution of 0.65 g of 1, 1,1, 3, 3, 3-hexafluoro-2-propanol and 0.43 g of triethylamine was added to a solution (6ml) of 0.78 g of 4-nitrophenyl chloroformate in dichloromethane. After the reaction solution was stirred for 1 hour under an ice-cooled condition, 0.50 g of N-(4-methy;benzoyl)-3-methyl-l,2-butanediamine hydrochloride was added under an ice-cooled condition. After the reaction solution WHS stirred for 15 minutes under an ice-cooled
condition, 0.21 g of triethylamine was added under an ice-cooled condition. The reaction solution was stirred for 1 hour under an ice-cooled condition and for 1 hour at room temperature and, subsequently, was stood for one night. 50ml of dichloromethane was added to the solution and the solution was washed with water. The organic: layer was dried over anhydrous magnesium sulfate and, subsequently, was concentrated under a reduced pressure. The resulting solid was purified by column chromatography on silica gel (ethyl acetate/hexane), so that 0.38 g of the title compound was prepared as white crystals.
[Example 5]
Process for synthesizing of N-(2-
chlorocyclohexyloxycarbonyl)-N'-(4-methylbenzoyl)-3-methyl-l, 2-butanediamine (Compound No. 17)
Under an ice-cooled condition, a solution (25ml) of 5.00 g of 4-nitrophenyl chloroformate in dichloromethane was added to a solution (hOml) of 1.96 g of pyridine and 3.33 g of 2-chlorocyclohexanol in dichloromethane. After the reaction solution was stirred for 3.5 hours at room temperature, 100 ml of dichloromethane was added, and washed with a saturated sodium hydrogencarbonate aqueous solution. The organic layer was dried over anhydrous magnesium sulfate and, subsequently, was concentrated under a reduced pressure. The resulting oil was purified by column chromatography on silica gel (dichloronuvthane/hexane) , so that 4.43 g of (2-chlorocyc.l ohexyl)-(4-nitrophenyl) carbonate was prepared as a
yellow oil.
Under an ice-cooled condition, 2.00 g of N-(4-methylbenzoyi)-3-methyl-l,2-butanediamine hydrochloride was added to a solution (50ml) of 4.43 g of (2-chlorocyclohexyl)-(4-nitrophenyl)carbonate in tetrahydrofuran. After 0.78 g of triethylamine was added under an ice-cooled condition, the reaction solution was stirred for 1 hour under an ice-cooled condition arid for 2 hours at room temperature. The reaction solution was stood for one night at room temperature and, subsequently, was concentrated under a reduced pressure. 200ml of ethyl acetate was added to the residue and the resulting mixture was washed with water. The organic layer was dried over anhydrous magnesium sulfate and, subsequently, was concentrated under a reduced pressure. The resulting oil was purified by column chromatography on silica gel (ethyl acetate/hexane), so that 1.38 g of the title compound was prepared as white crystals.
Compounds represented by Formula 4*£ which can be produced as in Examples 1 to 5 are shown in Table 1 (Table 1-1 to Table 1-3) below. The values of some properties thereof are shown in Table 2 (Table 2-1 to Table 2-9). In Table 1, Me represents a methyl group, Et represents an ethyl group, n-Pr represents a normal propyi group, i-Pr represents an isopropyl group, and cyclohexyl represents a cyclohexyl group.
(Table Removed)
represented by Formula
1H NMR (CDCI3, ppm): 1.00 (3H, d, J=7.3 Hz), 1.02 (3H, d, J=7.1 Hz), 1.85-1.94 (1H, m), 2.39 (3H, s), 3.45-3.51 (1H, m), 3.63-3.76 (2H, m), 5.24 (1H, d, J=8.5 Hz), 5.66 (1H, d, J=6.1 Hz), 5.72 (1H, d, J= 6.1 Hz), 6.59 (1 H, br-s), 7.22 (2H, d, J=7.8 Hz), 7.66 _________________ (2H, d, J=8.1 Hz). ___
1H NMR (CDCI3, ppm): 1.00 (3H, d, J=7.3 Hz), 1.02 (3H, d, J=6.8 Hz), 1.88-1.89 (1H, m), 2.39 (3H, s), 3.52-3.72 (2H, m), 3.69-3.72 (1H, m), 4.23-4.25 (1H, m), 4.30-4.45 (1H, m), 4.44-4.80 (1H, m), 4.56^.60 (1H, m), 4.97 (1H, br-d, J=8.8 Hz), 6.78 (1H, br-s), 7.23 (2H, _____________ d, J=8.0 Hz), 7.67 (2H, d, J=8.3Hz). __
1H NMR (CDCI3, ppm): 0.97 (3H, d, J=6.3 Hz), 0.99 (3H, d, J=6.3 Hz), 1.83-1.88 (1H, m), 2.38 (3H, s), 3.43-3.71 (5H, m), 4.19-4.24 (2H, m), 5.38 (1H, br-d, J=6.8 Hz), 7.06 (1H, br-s), 7.17 (2H, d, J=7.8 Hz), 7.66 __________________________ (2H, d, J=7.8 Hz). _ _ __
1H NMR (CDCb,
: 100 (3H, d, J=6.8 Hz), 1.02 (3H, d, J=6.9 Hz), 1.87-1.89 (1H, m), 2.40 (3H, s), 3.38-3.41 (2H, m), 3.51-3.71 (3H, m), 4.25-4.33 (2H, m), 4.98 (1H, br-d, J=7.8Hz), 6.75 (1H, br-s), 7.23 (2H, d, J=7.8 Hz), 7.67 (2H, d, J=8.3 Hz).
Table 2-2 Property value of Compound (21H NMR (CDCI3, ppm): 1.00 (3H, d, J=7.6 Hz), 1.02 (3H, d, J=6.8 Hz), 1.87-2.05 (1H, m), 2.41 (3H, s), 3.13-3.17 (2H, m), 3.46-3.50 (1H, m), 3.59-3.70 (2H, m), 4.22-4.28 (2H, m), 4.93 (1H, br-d, J=8.8 Hz), 6.73 (1H, br-s), 7.23 (2H, d, J=7.8 Hz), 7.67 (2H, d, J=8.3 Hz).
1H NMR (CDCI3, ppm): 0.96-1.03 (6H, m), 1.85-1.91 (1H, m), 2.39(3H, s),
3.46-3.51 (1H, m), 3.61-3.72 (2H, m), 4.35^.46 (2H, m), 5.26 (1H, d, J=8.3 Hz), 6.62 (1H, br-s), 7.21-7.23 (2H, m),
7.63-7.65 (2H, m)
1H NMR
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2096-DELNP-2006-PROOF OF ALTERATION [13-12-2023(online)].pdf