WO1999025700A1 - Triazole derivatives, intermediates for the production thereof, processes for producing the both, and herbicides containing the derivatives as the active ingredient - Google Patents

Abstract

Triazole derivatives represented by general formula (I), processes for producing the same, intermediates for the production thereof, and herbicides containing the derivatives as the active ingredient. The herbicides exhibit excellent herbicidal activities in small doses and are reduced in damages to crops.

Description

 Specification

Triazole derivatives, intermediates for their production, methods for their production, and herbicides containing them as active ingredients

Technical field

 The present invention relates to novel triazole derivatives, intermediates for producing the same, methods for producing them, and herbicides containing them as active ingredients.

Background art

 Conventionally, as triazole derivatives having a herbicidal activity at the 1-position having a rubamoyl group, for example, Japan Kokai Tokkyo Koho JP 57/148606, Japan Kokai Tokkyo Koho JP 59/39880, EP 422369 (Japan Kokai Tokkyo Koho JP 03 / Compounds described in Japanese Patent No. 99066), Japan Kokai Tokkyo Koho JP 05/140124 (Chemical Abstracts 119: 271169) and Japan Kokai Tokkyo Koho JP 05/194432 (Chemical Abstracts 119: 175893) are known. The triazole derivatives described in these patent specifications have inferior herbicidal effects on weeds as shown in the test examples below, or those with strong activity have low safety on crops. It is not always a satisfactory compound.

On the other hand, as shown in the general formula (1) of the present invention, a triazole in which the sulfur atom at the 3-position of the triazole ring is substituted by an alkyl group having a cyano group or an alkoxycarbonyl group at the 1-position. There are no reports on derivatives. In addition, a carbamoyltriazole derivative having insecticidal activity is known as an approximate compound of the compound of the present invention (US Pat. No. 3,308,131), but there is no description about a compound having a sulfur atom oxidized. Disclosure of the invention

 The present invention provides a novel triazole derivative having excellent herbicidal activity and high crop selectivity, a method for producing the same, and a herbicide containing these derivatives as an active ingredient.

 Means for Solving the Problems The present inventors have conducted intensive studies for a herbicide having excellent herbicidal activity and crop selectivity. As a result, the triazole derivative of the present invention represented by the following general formula (1) causes harm to crops. The present invention has been found to have excellent herbicidal activity without application at a low dose, and to have a simple production method for these.

 That is, the present invention provides a compound represented by the general formula (1):

 0

R ^1,. People

(Wherein R ¹ and R ² are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, halogen) An alkenyl group having 3 to 12 carbon atoms which may be substituted by an atom, an alkynyl group having 3 to 6 carbon atoms which may be substituted by a halogen atom, an aralkyl group having 7 to 11 carbon atoms which may be substituted or Represents an optionally substituted phenyl group, or R ¹ and R ² may form an optionally substituted heterocyclic ring together with the nitrogen atom to which they are bonded R ³ represents a cyano group or C00R Represents ¹ and R ⁷ is a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, optionally substituted by a halogen atom An alkenyl group having 3 to 12 carbon atoms or In. And R ⁵ each independently represents an Ararukiru group with carbon number ~ 11, hydrogen atom, a substituted optionally alkyl group of good 1 to 12 carbon atoms, the optionally substituted number 3 of 8 carbon Charcoal optionally substituted by cycloalkyl group or halogen atom An alkenyl group having 3 to 12 carbon atoms, an alkynyl group having 3 to 6 carbon atoms which may be substituted with a halogen atom, an aralkyl group having 7 to 11 carbon atoms which may be substituted, a phenyl group which may be substituted Or an alkyloxycarbonyl group having 1 to 12 carbon atoms which may be substituted. Further, Γ and R ⁵ may be combined with the bonded carbon atom to form an optionally substituted ring. Further, R ⁴ or R ⁵ may be combined with an atomic group bonded together with R ⁷ to form an optionally substituted ring. Represents a hydrogen atom, a halogen atom or an alkyl group having 1 to 6 carbon atoms. n represents an integer of 0 to 2. However, when n is 0 and R ³ is a cyano group or R ⁷ is C00R ⁷ which is an alkyl group having 1 to 12 carbon atoms, and R ⁵ cannot be hydrogen atoms at the same time. ), And a production intermediate, represented by general formula (2)

(Wherein, R ³ , R \ R ⁵ and R ⁶ represent the same meaning as described above. R ^s represents a hydrogen atom or a group represented by R ^s C0, R ⁹ represents a chlorine atom, and has 1 to 1 carbon atoms. And 6 represents an alkyloxy group or a phenyloxy group which may be substituted.).

Further, the present invention provides a compound represented by the following general formula (3):

(Wherein, R ³ , R ⁴ and R ⁵ represent the same meaning as described above; Y represents a leaving group); and a compound represented by the general formula (4)

HN'V ^SH ,

( ⁴⁾

R ⁶ (Wherein, R ^s has the same meaning as described above) with a 3-mercapto-1,2,4-triazole derivative represented by the following formula:

()

(Wherein, R ³ , R \ R ⁵ and R ⁶ have the same meanings as described above), and then a triazole derivative represented by the general formula (5) 0

^R1 , N ^A Y ( ⁵ )

(Wherein R ′, R ² and Y have the same meanings as described above), and reacted in the presence of a base to obtain a compound represented by the general formula (la):

(Wherein, R ² , R ³ , RR ⁵ and the same meaning as described above).

 Further, the present invention provides a compound represented by the general formula (2a):

, NY, .S ^. R ³

 HN γ (2a)

> = Ν RR ⁵

R ⁶

(Wherein, R ³ , RR ^5, and R ⁶ have the same meanings as described above), and a general formula (6)

 0

₉ Λ (6)

R ⁹ X

(Wherein, X represents the same meaning as described above. X represents a chlorine atom, an alkyloxy group having 1 to 6 carbon atoms, or a phenoxy group which may be substituted.) Reacting the indicated acylating agent with a base in the presence of a base;

(Wherein R ³ , R \ R ⁵ , R ^s and R ⁹ have the same meanings as described above), and a triazole derivative represented by the general formula (7):

R ¹ R ² NH (7)

(Wherein R ¹ and R ² have the same meanings as described above), wherein the amine represented by the general formula (la) is reacted in the presence of a base.

, N (1a)

(Wherein, RR, RR \ R ⁵ and R ^s have the same meaning as described above.) The present invention relates to a method for producing a triazole derivative represented by the formula:

Further, the present invention provides a compound represented by the general formula (2a):

A triazole derivative represented by R ⁶ (wherein R ³ , R \ R ⁵ and R ^s have the same meanings as described above);

R ¹ CO (8)

(Wherein, ir is an alkyl group having 1 to i2 carbon atoms which may be substituted, a cycloalkyl group having 3 to 8 carbon atoms which may be substituted, or a carbon atom which may be substituted with a halogen atom having 3 to 8 carbon atoms. 12 alkenyl groups, an alkynyl group having 3 to 6 carbon atoms which may be substituted by a halogen atom, D also represents an aralkyl group having 7 to 11 carbon atoms or a phenyl group which may be substituted. ) Is reacted with an isocyanate represented by the general formula (lb)

0

 R, ヽ people,

 Ν Ν ^ (1 b)

'= NR ⁴ R ⁵

R ⁶

(Wherein, R ¹ ′ R ³ R \ R ⁵ and R ⁶ have the same meanings as described above.)

Further, the present invention provides a compound represented by the general formula (la):

(Wherein, R ² R ³ R \ R ⁵ and R ^s have the same meaning as described above.) By oxidizing a triazol derivative represented by the following general formula (lc):

 0

R ¹ヽ people, N SO m, R ³

 N N (1 c)

R ² > = NR ⁴ R ⁵

R ⁶

(Wherein, R ² R \ R \ R ⁵ and R ^s have the same meaning as described above. M represents 1 or 2.) The present invention also relates to a method for producing a triazolyl derivative represented by the formula:

 Further, the present invention provides a compound represented by the general formula (Id)

R ¹⁰ ,

R ⁶

(In the formula, R ⁴ , R \ R ⁵ and n represent the same meaning as described above, and R is an optionally substituted alkyl group having 1 to 12 carbon atoms, and an optionally substituted 3 to 8 carbon atoms. A cycloalkyl group, an alkenyl group having 3 to 12 carbon atoms which may be substituted by a halogen atom, or an alkenyl group having 7 to 11 carbon atoms which may be substituted Represents an aralkyl group. R ^ie represents Karubamo I le group represented by hydrogen or RHCO, R ¹ and R ² are as defined above. However, when ^Ri is a hydrogen atom, n is 0. ) By hydrolyzing the ester bond of the triazole derivative represented by the general formula (le)

(Wherein, R ⁴ R \ R ^s ° and n have the same meaning as described above. However, when R ^{1 D} is a hydrogen atom, n is 0.) The method and the carboxylic acid moiety of this method are represented by the general formula (9)

R ⁷ OH (9)

(Wherein, R ⁷ ′ represents the same meaning as described above.) By esterification using an alcohol represented by the general formula (Id)

(Wherein, R ⁴ R \ R ^s R ⁷ ′ and n represent the same meaning as described above. However, when R ¹ ″ is a hydrogen atom, n is 0.) It relates to a method of manufacturing.

 Further, the present invention provides a compound represented by the general formula (If):

 0

N ^N , 丫 ( ^1f >

R ² > = NR ⁴

R ⁶

(Wherein, RR ² R \ R \ R ^s and m represent the same meaning as described above), and a general formula (10) „

R ⁵ — Y (10)

(In the formula, R ⁵ ′ is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, and a carbon atom optionally substituted with a halogen atom. An alkenyl group having 3 to 12 carbon atoms, an alkynyl group having 3 to 6 carbon atoms which may be substituted with a halogen atom, an optionally substituted aralkyl group having 7 to 11 carbon atoms, or an Represents an alkyloxycarbonyl group of the formulas 1 to 12, and Y represents a leaving group.) In the presence of a base;

R ⁶

(Wherein, R ² , R ³ , R \ R ³ ′, R ^s and m have the same meanings as described above).

 Further, the present invention provides a compound represented by the general formula (lc):

R ¹ ,

(Wherein, RR ² , R ³ , R \ R ⁵ , R ⁶ and m have the same meanings as described above.) The present invention relates to a herbicide comprising a triazole derivative represented by the following formula: BEST MODE FOR CARRYING OUT THE INVENTION

In the compounds belonging to the present invention, the alkyl group having 1 to 12 carbon atoms represented by R ¹ , R ² , R \ R \ V, R ⁷ and R ⁷ ′ may be linear or branched. Methyl, ethyl, propyl-isopropyl, butyl, isobutyl, sec-butyl, tert-butyl Lithyl, pentyl, isoamyl, neopentyl, toluenepropyl, 1-methylbutyl, 2-methylbutyl, hexyl, isohexyl, heptyl, 1-methylhexyl, octyl, etc. Can be exemplified. These alkyl groups include a halogen atom, a cycloalkyl group having 3 to 8 carbon atoms, a cyano group, a nitro group, an alkylthio group having 1 to 6 carbon atoms, an alkyloxy group having 1 to 6 carbon atoms, and an alkyl group having 1 to 6 carbon atoms. May be substituted by one or more of a carbonyl group, an acyl group having 1 to 6 carbon atoms, and more specifically, a 2-chloroethyl group, a 3-chloropropyl group, a 3-fluoropropyl group, and a cycloalkyl group. Propylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyanomethyl, 2-cyanoethyl, 3-cyanopropyl, nitromethyl, 2-methylthioethyl, methoxymethyl, ethoxymethyl, methoxyethyl, methoxy Carbonylmethyl group, ethoxycarbonylmethyl group, 1-methoxycarbonylethyl group, 1-ethoxycarbonyl Group, 2-ethoxycarbonyl E butyl group, Asetoniru group, 1-Asechiruechiru group, can be exemplified 3-Asechi Rupuropiru group.

R \ R ¹ Examples of the cycloalkyl group ^{', R 2, R \ R} \ R 5', R 7 and R ⁷ carbon atoms 3 represented by '1-8, cyclopropyl group, cyclobutyl group, shea Kuropenchiru group, Examples thereof include a cyclohexyl group and a cyclooctyl group. Further, these cycloalkyl groups may be substituted with a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, a cyano group, or the like. More specifically, trimethylcycloalkyl Propyl, 2,2-dimethylcyclopropyl, 2-chlorocyclopropyl, 2,2-dichlorocyclopropyl, 2-methoxycarbonylcyclopropyl, 2-cyanonechloropropyl, 2-methylcyclopentyl And a 3-methylcyclopentyl group.

^{R \ R:, R 2,} RヽR \ R, the number 3-12 carbons represented by R 'and R ^7' 丄_Q

The alkenyl group may be linear, branched or cyclic, or may be displaced, and may be a 1-propenyl group, an aryl group, a 2-methyl-2-propenyl group, a 2-butenyl group. , 3-butenyl, 2-pentenyl, 3-pentenyl, 1-cyclopentenyl, 2-hexenyl, 3-hexenyl, 1-cyclohexenyl, 2-heptenyl, tricyclooctenyl And the like. These alkenyl groups may be substituted with a halogen atom or the like, for example, a 2-chloro-2-propenyl group, a 3-chloro-2-propenyl group, a 4-chloro-2-butenyl group. And the like.

The alkynyl group having 3 to 6 carbon atoms represented by RR ¹ ′, R ² , R \ R ⁵ and R ⁵ ′ may be linear or branched, and may be a propargyl group, 1 Examples thereof include -butyn-3-yl group, 3-methyl-1-butyn-3-yl group, 2-butynyl group, 2-pentynyl group, and 3-pentynyl group. These alkynyl groups may be substituted with a halogen atom or the like, for example, 3-fluoro-2-propynyl group, 3-chloro-2-propynyl group, 3-bromo-2-propynyl group, -Bromo-2-butynyl group, 4-bromo-3-butynyl group and the like.

R ', R ^1', as the Ararukiru groups ^{R 2, R \ R \ R} 5 ', carbon atoms represented by R ¹ and R ⁷ 7 to 11, benzyl group, 1-Fuweniruechiru group, 2-phenylene Examples thereof include a rutile group, a 1-phenylpropyl group, a 1-naphthylmethyl group, and a 2-naphthylmethyl group. On the aromatic ring of these aralkyl groups, a halogen atom, an alkyl group having 1 to 12 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkyloxy group having 1 to 6 carbon atoms, and an alkyloxycarbonyl having 1 to 6 carbon atoms It may be substituted one or more times with a group, carboxy group, cyano group, nitro group and the like.

R \ R ^1, R \ IT and ^ substituted by a substituent on Fuweniru ring which may Fuweniru group optionally halogen atom represented, § alkyl group having 1 to 12 carbon atoms, the number 1-6 carbons Haloalkyl group, alkyl having 1 to 6 carbon atoms 丄 丄

Examples thereof include an alkoxy group, an alkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, a cyano group, and a nitro group.

R \ R ⁵ and 1-12 carbon atoms represented by IT alkyl O carboxymethyl carbonylation as Le group main butoxycarbonyl group, ethoxy Kin carbonyl group, propylidene Ruo alkoxycarbonyl group, an isopropyl O alkoxycarbonyl group, butoxy carbonyl group And a pentyloxycarbonyl group, a hexyloxycarbonyl group, an octyloxycarbonyl group and the like. The alkyl groups on these alkyloxycarbonyl groups include a halogen atom, a cycloalkyl group having 3 to 8 carbon atoms, a cyano group, a nitro group, an alkylthio group having 1 to 6 carbon atoms, and an alkylthio group having 1 to 6 carbon atoms. May be substituted by one or more of an alkyloxy group of 1 to 6 carbon atoms, an alkyloxycarbonyl group of 1 to 6 carbon atoms, and an acyl group of 1 to 6 carbon atoms. Propyl, 3-fluoropropyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyanomethyl, 2-cyanoethyl, 3-cyanopropyl, nitromethyl, 2-methylthioethyl, methoxymethyl, Ethoxymethyl group, methoxyethyl group, methoxycarbonylmethyl group, ethoxycarbonylmethyl group, 1-methoxycarbonyl Examples thereof include an ethyl group, a 1-ethoxyquinethyl group, a 2-ethoxycarbonylethyl group, an acetonyl group, a 1-acetylethyl group, and a 3-acetylpropyl group.

Examples of the halogen atom represented by R ^s include a fluorine atom, a chlorine atom, and a bromine atom. Examples of the alkyl group having 1 to 6 carbon atoms represented by R ⁶ include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, and a pentyl group. it can.

The Arukiruokishi group having a carbon number of 1-6 represented by R ^¾, main butoxy group, an ethoxy group, Puropiruokishi group, an isopropyl O alkoxy group, butyl W

Examples thereof include an oxy group, an isobutyloxy group, a sec-butyloxy group, a tert-butyloxy group, and a pentyloxy group.

The substituent on the phenyl ring of the optionally substituted phenoxy group represented by R ^& is a halogen atom, an alkyl group having 1 to 12 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, and a haloalkyl group having 1 to 6 carbon atoms. Examples thereof include an alkyloxy group, an alkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, a cyano group, and a nitro group.

Examples of the heterocyclic group formed integrally with the nitrogen atom to which R ¹ and R ² are bonded include a piperidino group, a piperazino group, a morpholino group, a pyrrolidino group, and the like. One or more alkyl groups such as 1 to 6 may be substituted.

Examples of the ring formed integrally with the carbon atom to which R ⁴ and R ⁵ are bonded include cyclopropane, cyclobutane, cyclopentane, cyclohexane, and the like. These include a halogen atom and a carbon atom having 1 carbon atom. It may be substituted with one or more alkyl groups such as 6 to 6.

Or, as the ring formed integrally with the atomic group in which R ⁵ is bonded together with R ⁷ , an a-ptyrolactone ring, an a-pa'relolactone ring, a p-a-lactolactone ring, etc. should be exemplified. These may be substituted one or more times with a halogen atom, an alkyl group having 1 to 6 carbon atoms, or the like.

 As the leaving group represented by Y in the general formulas (3), (5) and (10), a halogen atom such as a chlorine atom, a bromine atom and an iodine atom, or a methanesulfonyloxy group or a trifluoromethanesulfonyloxy group And benzenesulfonyloxy, p-toluenesulfonyloxy and the like, or arenesulfonyloxy and the like.

In the general formula (6), the alkyloxy group having 1 to 6 carbon atoms represented by X includes methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, sec-butyloxy. And a tert-butyloxy group, a pentyloxy group and the like.Examples of the substituent on the phenyl ring of the phenyl group which may be substituted include a halogen atom, an alkyl group having 1 to 12 carbon atoms, Examples thereof include a haloalkyl group having 1 to 6 carbon atoms, an alkyloxy group having 1 to 6 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, a cyano group, and a nitro group.

 Next, a method for producing a compound belonging to the present invention will be described. The triazole derivative of the present invention can be produced, for example, by the following production method.

 [Production method 1]

(3)

 Ο

FT

R ⁶ (1a)

(Wherein, R ² , R ³ , R ", R ⁵ , R ⁶ and Y have the same meanings as described above.) Production method 1 is 3-mercapto-1,2,4-triazole. The derivative (4) is reacted with the compound (3) to produce the triazole derivative (2a) of the present invention, and then the triazole derivative (2a) is reacted with the tribasyl compound (5).

The method for producing the triazolyl derivative (la) of the present invention having a carbamoyl group at the 1-position of the ring is shown below.

 Step 1 consists of a 3-mercapto-1,2,4-triazole derivative (4) and a compound

And (3) in the presence of a base to produce the triazol derivative (2a) of the present invention.

The reaction must be carried out in the presence of a base, and usable bases include triethylamine, tributylamine, and N-methylmorpholine. Organic amines such as phosphorus, pyridine and dimethylaniline, potassium carbonate, sodium carbonate, sodium bicarbonate, sodium bicarbonate, sodium hydroxide, sodium hydroxide, sodium hydroxide, sodium hydride and sodium amide An example of the metal base can be exemplified. The amount of the base to be used is not particularly limited, but it is preferable to use the base in an amount equal to or more than that of the reaction substrate in terms of good yield.

 The reaction is preferably carried out in a solvent, and any solvent that does not harm the reaction can be used.Examples include aromatic hydrocarbon solvents such as benzene, toluene, xylene, and benzene, methyl ether, and the like. Ether solvents such as tetrahydrofuran, dioxane, 1,2-dimethoxetane (DME), halogen solvents such as dichloromethane, chloroform, carbon tetrachloride, etc., ketones such as acetone and methylethylketone, and acetonitrile , Nitriles such as propionitrile, esters such as ethyl acetate and ethyl propionate, amides such as N, N-dimethylformamide (MF), N-methylpyrrolidone, dimethyl sulfoxide (DMS0); Water or a mixed solvent thereof can be used.

 The reaction temperature varies depending on the base used, and is selected from the range of -10 to 150 ° C. It is preferable to carry out the reaction in the range of around 0 ° C to the reflux temperature of the reaction mixture in terms of good yield.

 After the completion of the reaction, if necessary, it can be purified by column chromatography or the like, if necessary, to obtain the desired product by a normal extraction operation. Further, the triazole derivative (2a) can be used as it is in the next step 12 without isolation.

Part of the compound (3) used in Step 1 is commercially available and can be easily obtained. The compound (3) in which R ³ is an ester is obtained by reacting a 2-halocarboxylic acid chloride derivative with an alcohol, or forming a hydroxyl group of a 2-hydroxycarboxylic acid derivative into a halogen atom or an alkane. ,

 15 can be produced by converting to an arenesulfonyloxy group according to a conventional method.

 The 2-hydroxycarboxylic acid derivative serving as a raw material can be produced by a method of hydrolyzing a cyano group of a cyanohydrin derivative obtained by reacting a carbonyl compound with cyanuric acid or a method of alcoholysis. The / 3, α-unsaturated -hydroxycarboxylic acid derivative contained in the raw material 2-hydroxycarboxylic acid derivative can be obtained by the method described in EP 153692 (Japan Kokai Tokkyo Koho JP 60/179147) or the method described therein. The 2-hydroxycarboxylic acid derivative can also be produced by reducing the double bond of this ^, α-unsaturated-hydroxy-carboxylic acid derivative. Can be manufactured.

Further, the compound (3) in which R ³ is a cyano group can be produced by converting the hydroxyl group of the above-mentioned cyanohydrin derivative into a halogen atom or an alkane or arenesulfonyloxy group according to a conventional method. Step 12 is a step of reacting the triazole derivative (2a) with the carbamoyl compound (5) in the presence of a base to produce the triazole derivative (la) of the present invention.

 The reaction must be carried out in the presence of a base, and usable bases include organic amines such as triethylamine, triptylamine, N-methylmorpholine, pyridine and dimethylaniline, potassium carbonate, and sodium carbonate. , Hydrogen bicarbonate, sodium hydrogen carbonate, sodium hydroxide, sodium hydroxide, sodium hydride, sodium amide, and the like. The amount of the base used is not particularly limited, but it is preferable to use the base in an amount equal to or more than that of the reaction substrate in terms of a good yield.

The reaction is preferably performed in a solvent, and any solvent that does not harm the reaction can be used. For example, benzene, toluene, xylene, ,

 1 Aromatic hydrocarbon solvents such as benzene, etc., ether solvents such as dimethyl ether, tetrahydrofuran, dioxane, DME, etc., halogen solvents such as dichloromethane, chloroform, carbon tetrachloride, etc. Ketones such as tilethyl ketone; nitriles such as acetonitrile and propionitrile; esters such as ethyl acetate and ethyl propionate; amides such as DMF and N-methylpyrrolidone; DMS0; water; or a mixture thereof. Solvents can be exemplified.

 The reaction temperature varies depending on the base used, and is selected from the range of -10 to 150 ° C. However, it is preferable to carry out the reaction in the range from around 0 ° C to the reflux temperature of the reaction mixture, since the yield is good. preferable.

 After completion of the reaction, the desired product can be obtained by a usual extraction operation. If necessary, purification can be performed by column chromatography or the like.

 The rubamoyl compound (5) used in the step 2 can be easily produced by reacting a commercially available amine corresponding to a part of the corresponding amine with phosgene or a phosgene equivalent according to a conventional method.

 [Manufacturing method 1]

, N, ^{R4 0}

 HN, People X «-3

 >

R ³ 'X

 R ° (2a) (6)

(Wherein, R ^;, R ² , R ³ , R \ R \ R \ R ^&, and X have the same meanings as described above.) The production method 2 comprises a triazole derivative (2a), an acylating agent (6) To produce the triazole derivative (2b) of the present invention, and then reacting this with an amine (7) to obtain the triazole derivative of the present invention. 2 shows a method for producing the body (la).

 Step-3 is a step of reacting the triazole derivative (2a) with the acylating agent (6) to produce the triazole derivative (2b) of the present invention.

 Examples of the acylating agent (6) used in this reaction include phosgene, phosgene equivalents, and haloformates. Although some haloformate esters are commercially available, they can be easily produced by reacting the corresponding alcohol with phosgene or a phosgene equivalent according to a conventional method.

 The reaction between the triazole derivative (2a) and phosgene or a phosgene equivalent is preferably performed in an organic solvent, and any solvent that does not harm the reaction can be used. For example, benzene, toluene, xylene Examples thereof include aromatic hydrocarbon solvents such as benzene and ethyl ester, esters such as ethyl acetate and ethyl propionate, and mixed solvents thereof.

 The reaction temperature is selected from the range of −10 to 150 ° C., but it is preferable to carry out the reaction in the range of 0 ° C. to the reflux temperature of the reaction mixture from the viewpoint of good yield. After the completion of the reaction, a force product capable of obtaining the desired product by a usual isolation operation can be used in the next step without isolation.

It is essential that the reaction of the triazole derivative (2a) with the haloformates be carried out in the presence of a base. Examples of usable bases include triethylamine, tributylamine, N-methylmorpholine and pyridine. , Organic amines such as dimethylaniline, sodium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium hydroxide, sodium hydroxide, sodium hydride, sodium hydroxide, etc. A group can be exemplified. The amount of the base used is not particularly limited, but it is preferable to use the base in an amount equal to or more than the amount of the reaction substrate in terms of good yield. The reaction is preferably carried out in an organic solvent. Any solvent can be used, for example, aromatic hydrocarbon solvents such as benzene, toluene, xylene, and chlorobenzene, ether solvents such as dimethyl ether, tetrahydrofuran, dioxane, and DME, dichloromethane, and the like. Halogen solvents such as carbon form, carbon tetrachloride, etc., ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile and propionitrile, esters such as ethyl acetate and ethyl propionate, DMF, N Examples include amides such as -methylpyrrolidone, DMS0, or a mixed solvent thereof.

 The reaction temperature varies depending on the base to be used and is selected from the range of -10 to 150 ° C. It is preferable to carry out the reaction in the range of around 0 ° C to the reflux temperature of the reaction mixture from the viewpoint of good yield.

 After completion of the reaction, the product can be purified by a column chromatography or the like, if necessary, by an ordinary extraction operation. The product can be used in the next step without isolation.

Step 14 is a step in which the triazole derivative (2b) is reacted with the amine (7) in the presence of a base to produce the triazole derivative (la) of the present invention. It is essential that the reaction is carried out in the presence of a base, and usable base groups include triethylamine, triptylamine, N-methylmorpholine, pyridine, dimethylaniline, 1,8-diazabicyclo.4.0] ゥOrganic amines such as ndecene-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane, potassium carbonate, Examples thereof include alkali metal bases such as sodium carbonate, sodium bicarbonate, sodium bicarbonate, sodium hydroxide, sodium hydroxide, sodium hydride, and sodium amide. The amount of the base to be used is not particularly limited, but it is preferable to use the base in an amount equal to or more than that of the reaction substrate in terms of good yield. The reaction is preferably carried out in an organic solvent, and any solvent that does not harm the reaction can be used. For example, aromatic hydrocarbon solvents such as benzene, toluene, xylene, and benzene, Ether solvents such as mono-ter, tetrahydrofuran, dioxane, DME, etc .; halogen solvents such as dichloromethane, chloroform, carbon tetrachloride, etc .; ketones such as acetone and methyl ethyl ketone; acetonitrile, propionitrile etc. Examples thereof include nitriles, esters such as ethyl acetate and ethyl propionate, amides such as DMF and N-methylpyrrolidone, DMS0, and a mixed solvent thereof.

 The reaction temperature varies depending on the base used, and is selected from the range of -10 to 150 ° C. However, it is preferable to carry out the reaction in the range from around 0 ° C to the reflux temperature of the reaction mixture, since the yield is good. preferable.

 After completion of the reaction, the product can be purified by column chromatography or the like, if necessary, to obtain the desired product by a normal extraction operation.

 [Production method 1]

^{(Wherein, R; ', R 3,} R \ R 5 and R ^s are as defined above.)

 Production method 13 (step 15) is a method for producing a triazole derivative (lb) of the present invention by reacting a triazole derivative (2a) with an isocyanate (8).

The reaction is preferably performed in an organic solvent, and any solvent that does not harm the reaction can be used. For example, aromatic hydrocarbon solvents such as benzene, toluene, xylene, and benzene Ether solvents such as tyl ether, tetrahydrofuran, dioxane, DME, etc. Halogen solvents such as dichloromethane, chloroform, carbon tetrachloride, etc., ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile and propionitol, and esters such as ethyl acetate and ethyl propionate. Kind,

Examples include amides such as DMF and N-methylpyrrolidone, DMS0, and a mixed solvent thereof.

 In the reaction, it is not necessary to add a base because the triazole derivative (2a) itself as a raw material acts as a base, but triethylamine, tributylamine, N-methylmorpholine, pyridine, dimethylaniline and the like can be used. Bases such as organic amines, potassium carbonate, sodium carbonate, hydrogen carbonate, sodium hydrogen carbonate, sodium hydroxide, sodium hydroxide, hydroxide hydroxide, alkali metal bases such as sodium hydride, sodium amide By conducting the reaction in the presence of, the reaction can be further promoted, and the desired product can be obtained in a short time and with high yield. The amount of the base used is not particularly limited, and it is preferable to use 0.01 to 2.0 equivalents, preferably 0.1 to 0.5 equivalents, based on the reaction substrate in terms of good yield.

 The reaction temperature is selected from the range of −10 to 150 ° C., but it is preferable to carry out the reaction in the range from around 0 ° C. to the reflux temperature of the reaction mixture from the viewpoint of good yield.

 After completion of the reaction, the desired product can be obtained by a usual extraction operation, but if necessary, it can be purified by column chromatography or the like.

Some of the raw material isocyanates (8) are commercially available and can be easily obtained. In addition, it can be produced from the corresponding amine using phosgene or an equivalent thereof according to a conventional method. [Production method 1 4]

(Wherein, R ² , \ R \ R ⁵ , R ⁶ and m have the same meanings as described above.) Production method 4 (step 1-6) involves oxidizing the sulfur atom of the triazole derivative (la). Is a step of producing the triazole derivative (lc) of the present invention.

 Oxidation can be carried out using an oxidizing agent. Examples of oxidizing agents that can be used include hydrogen peroxide, m-chloroperbenzoic acid, potassium permanganate, sodium metaperiodate, sodium hypochlorite, and oxidation. Osmium and the like can be exemplified.

 The reaction is preferably performed in a solvent, for example, an aromatic solvent such as benzene, toluene, xylene, and benzene, an aliphatic hydrocarbon solvent such as hexane, pentane, and heptane; dichloromethane; A halogen solvent such as carbon chloride, an alcohol solvent such as methanol and ethanol, a carboxylic acid such as acetic acid and propionic acid, water, or a mixed solvent thereof can be used.

 The reaction temperature varies depending on the oxidizing agent used, and is selected from the range of -10 to 150 ° C. Performing the reaction in the range of around 0 ° C to the reflux temperature of the reaction mixture provides a good yield. Is preferred.

After completion of the reaction, the desired product can be obtained by a usual extraction operation, but if necessary, it can be purified by column chromatography or the like. [Production method 1 5]

^R 1'0 ^u, N. .SOn. R E species one R 10, N, Roh SOn R

^N : YR ⁵ NY V- R

 N / COORT COOH

R ⁶ (1d) R. (1e) _n i

R

(Wherein, R ⁴ , R \ R ^s and n represent the same meaning as described above. R ⁷ ′ is an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, and 3 to 12 carbon atoms. Represents an alkenyl group or an aralkyl group having 7 to 11 carbon atoms, ° represents a hydrogen atom or a radical group represented by R CO, and R ¹ and R ² have the same meanings as described above, provided that R ¹ When "is a hydrogen atom, n is 0.)

The production method-5 includes a method for producing the triazole derivative (le) of the present invention by hydrolyzing an ester bond of the triazole derivative (Id), and a method for preparing a carboxylic acid of the triazole derivative (le) by a desired method. By esterification using the alcohol (9), the triazole derivative (1a), (lb) or (lc) of the present invention is a triazole derivative wherein R ³ is C00R ⁷ ′, or ³ shows a method for producing a triazole derivative in which R ^s is a hydrogen atom and R ³ is C00R ¹ ′ in the triazole derivative (2) of the present invention.

Step 7 by hydrolyzing the ester bonds of the triazole derivative (Id), are known various methods for hydrolysis of _c ester is a step for preparing a triazole Ichiru derivative (le) of the present invention However, any method that does not harm other functional groups of the raw material substrate can be used in this step. Usually, hydrolysis is carried out using an aqueous alkaline solution-specifically, sodium hydroxide, hydroxide hydroxide, sodium carbonate, sodium carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, etc. An aqueous solution of a genus base can be exemplified.

 The reaction can be carried out in an organic solvent, for example, a solvent capable of forming a homogeneous solution with water, such as methanol, ethanol, propyl alcohol, butyl alcohol, tetrahydrofuran, dioxane, acetonitrile, or a mixed solvent thereof. can do.

 The reaction temperature is selected from the range of 0 to 100 ° C., but it is preferable to carry out the reaction in the range of room temperature to the reflux temperature of the reaction mixture in terms of good yield.

 After completion of the reaction, the desired product can be obtained by an extraction operation, but if necessary, it can be purified by column chromatography or the like. Step-8 is a step of producing a triazole derivative (Id) by esterifying the carboxylic acid of the triazole derivative (le) with an alcohol (9).

In this step, for example, a general method used for esterification of carboxylic acid, such as a method of reacting a carboxylic acid with an alcohol in the presence of an acid catalyst such as sulfuric acid or p-toluenesulfonic acid (Protection). ive Groups in Organic synthesis, TW Greene, John Wiley & Sons, 1981; Protective Groups in Organic Synthesis, Second Edition, T. Greene and PGM Wuts, John Wiley & Sons, 1991). The desired ester (Id) can be produced. Alternatively, the carboxylic acid (le) is converted to an acid chloride using a chlorinating agent such as thionyl chloride and then reacted with an alcohol (9), or an alcohol (9) is reacted with a thionyl chloride. The method of reacting the reactive species prepared by the above reaction with carboxylic acid (le) is preferred in that the desired product can be obtained in a simple and high yield. [Production method 1]

(Wherein RR \ R ³ , R \ R ⁵ ′, R ⁶ , Y and m represent the same meaning as described above.) Production method—6 (Step-9) is a process in which a triazole derivative (If) and an alkylating agent are used. (10) is reacted in the presence of a base to produce a triazole derivative (lg) of the present invention.

 The reaction must be carried out in the presence of a base, and usable bases include organic amines such as triethylamine, triptylamine, N-methylmorpholine, and pyridine; lithium carbonate, sodium carbonate, and acetic acid. Examples thereof include alkali metal bases such as sodium, potassium acetate, sodium hydride, and sodium amide, and organic metal bases such as lithium diisopropylamide, among which sodium hydride, sodium amide, and lithium diisopropylamide. By using a base such as chloride, the desired product can be obtained in good yield. The amount of the base used is not particularly limited, but it is preferable to use the base in an amount equal to or more than that of the reaction substrate in terms of good yield.

 The reaction is preferably performed in an organic solvent, and any solvent that does not harm the reaction can be used. For example, aromatic hydrocarbon solvents such as benzene, toluene, xylene, and benzene Examples include ether solvents such as tyl ether, tetrahydrofuran, dioxane, and DME, halogen solvents such as dichloromethane, chloroform, carbon tetrachloride, etc., amides such as MF and -methylpyrrolidone, and DMS0 or a mixture thereof. Can be shown.

The reaction temperature varies depending on the base used, and is selected from the range of -100 ° C to 150 ° C. Is preferred in terms of good yield.

 After completion of the reaction, the desired product can be obtained by a usual extraction operation, but can be purified by column chromatography if necessary. The alkylating agent (10) used in this step is partially commercially available Can be produced by converting the hydroxyl group of the corresponding alcohol derivative into a halogen atom or an alkane or arenesulfonyloxy group according to a conventional method.

 Hereinafter, the present invention will be described in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto. Example Example-1

Et

To a solution of methyl (thiodecylcarbamoyl-1H-1,2,4-triazol-3-yl) thioate (0.409 g, 1.5 mmol) in chloroform (10 mL) under ice-cooling and stirring. Metaclo mouth perbenzoic acid (0.273 g, 1.58 mmol) was added. Then, the reaction solution was heated to room temperature, and further stirred for 24 hours. After the completion of the reaction, the reaction solution was added to a saturated aqueous solution of sodium hydrogen carbonate (10 mL), the organic layer was separated, and the aqueous layer was further extracted with chloroform (10 mL × 2). The organic layers were combined, washed with a saturated aqueous sodium chloride solution (10 mL), and dried over anhydrous magnesium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain a crude product. The product was purified by silica gel column chromatography (一 -gel C-200, ethyl acetate: hexane = 2: 1) to give (1-getylcarbamoyl-1H-1,2,4- Triazol-3-yl) sulfinyl acetate methyl To give a white solid (0.380 g 87.9%). mp: 57.3 58.5 ° C; - NMR (CDC1 3, TMS, ppm): (51.31 (6H, t, J = 6.6Hz), 3.45 3.70 (4H m), 3.78 (3H s), 4.24 (1H, d, J = 14.7Hz), 4.34 (1H, d J = 14.7Hz), 8.92 (1H, s).

The reaction was carried out in the same manner as in Example 1 except that (1-dimethylcarbamoyl-1H-1,24-triazol-3-yl) methyl thioacetate (2.44 g, 9.99 mmol) was used as the starting material. As a result, a colorless transparent oily product of methyl (1-dimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfinyl acetate (2.04 g, 73.9%) was obtained. 'Η-title R (CDC1 ₃ TMS, pm): 53.20 (3H, s), 3.35 (3H, s), 3.78 (3H, s), 4.23 (1H, d J = 14.7Hz), 4.34 (1H, d , J = 14.7Hz), 8.9K1H, s).

α-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) methyl thioacetate (1.08 g, 3.96 mmol) in chloroform Benzoic acid (2.56 g, 14.8 mmol) was added, and the reaction solution was warmed to room temperature and stirred for another 24 hours After the reaction was completed, the reaction solution was added to a saturated aqueous sodium hydrogen carbonate solution (50 mL), and the organic solution was added. The layers were separated, and the aqueous layer was further extracted with chloroform (20 mL x 2) The organic layers were combined, washed with an aqueous saturated sodium chloride solution (20 mL), and dried over anhydrous sulfuric acid: _2?

Dried. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain a crude product. The product was purified by silica gel column chromatography (Cogel C-200, ethyl acetate: hexane = 1: 3) to give (1-Getylcarbamoyl-1H-12,4-triazole- A white solid (1.08 g 89.6%) of methyl 3-yl) sulfonylacetate was obtained. mp: 58.5 59.0 ° C; - R (CDC1 3 T MS, ppm): 61.25 (6H, t J = 7.3Hz), 3.61 (4H, q, J = 7.3Hz), 3.75 (3 H, s), 4.44 C2H, s), 9.0K1H, s).

Et

The reaction was carried out in the same manner as in Example 1 except that (1-getylcarbamoyl-1H-1 2,4-triazolyl-3-yl) thioacetonitrile (0.479 g 2.Ommol) was used as a raw material. A white solid (0.470 g, 92.1%) of (1-getylcarbamoyl-111-124-triazolyl-3-yl) sulfinylacetonitrile was obtained. _{^{; H-NMR (CDC1 3,}} TMS, ppm): (1.33 (6H, br s), 3. 50 3.80 (4H m), 4.10 (1H, d J = 15.6Hz), 4.35 (1H d J = 15.6Hz ),

8.98 (1H, s). Example 5

The reaction was performed in the same manner as in Example 3 except that (1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) thioacetonitrile (2.57 g 11. Ommol) was used as a raw material. To give (1-Jetylcarbamoyl-1H- 1 2,4- Triazol-3-yl) sulfonylacetonitrile as a white solid (2.54 g,

E E

85.1%). ^{mp: 93.3~94.3 ° C; J H} -NMR (CDC1 3, TMS, ppm): (1.34

N NBEII tAA O O

(6H, br s), 3.54 to 3.74 (4H, m), 4.41 (2H, s), 8.99 (1H, s).

 Et,, Ns, NO COOH

 , N, ヽ N ^

 Et N

 In-sodium hydroxide solution in a solution of methyl carbamoyl-1H-1,2,4-triazol-3-yl) thioate (8.49 g, 31.2 mmol) in 1,4-dioxane (30 mL) (45 mL) and stirred at room temperature for 3 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, 1N-hydrochloric acid (20 OmL) and ethyl acetate (80 mL) were added to the obtained residue, the organic layer was separated, and the aqueous layer was further separated with ethyl acetate (80 mL × 2). Extracted. The organic layers were combined, washed with a saturated aqueous sodium chloride solution (20 mL), and dried over anhydrous magnesium sulfate. After filtering off the desiccant, the filtrate was concentrated under reduced pressure to give a white solid (6.92 g, 85.9%) of (1-methylethylcarbamoyl-1H-1,2,4-triazol-3-yl) thioacetic acid. ). mp: 112-113. C; 'H-NMRCCDCl ,, TMS, ppm): <51.27 (6H, t, J = 7.0Hz), 3.59 (4H, q, J-7.0Hz), 3.89 (2H, s), 6.20 (1H , Br s), 8.80 (1H, s).

S ^^ COOH O

 Et, person, N S COOEt

 rjj N

 Et N

Thionyl chloride (0.2 mL, 2.74 IMO1) was added dropwise to ethanol (5 mL) under ice-cooling and stirring, and (1-Getylcarbamoyl-1H-1,2,4-tria) was added to the resulting solution. (Zol-3-yl) thioacetic acid (0.645 g, 2.5 mmol) was added, and the temperature was raised to room temperature. After stirring at room temperature for 5.5 hours, toluene (2 mL) was added to the reaction solution, and the mixture was concentrated under reduced pressure to distill off excess thionyl chloride. (1-Jetyl sorbamoyl-1H-1,2,4 Thus, yellow oil (0.580 g, 81.0%) of -triazol-3-yl) ethyl thioacetate was obtained. _{- NMR (CDC1 3, TMS,} ppm):.. (5 1. 28 (6H, t, J = 7 0Hz), 1. 34 (3H, t, J = 7 0Hz), 3. 60 (4H, q , J = 7.0 Hz), 3.92 (2H, s), 4.2K2H, q, J = 7.0 Hz), 8.74 (1H, s).

 0

 Et, N-. People

 I

 Et

Reaction was performed in the same manner as in Example 13 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) ethyl thioacetate (0.580 g, 2.03 mmol) was used as a raw material. To give a white solid (0.610 g, 94.4%) of (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate. . Soku:... 53 0~53 5 ° C; 'Η- NMR (CDC1 3, TMS, ppra): (5 1. 25 (3H, t, J = 7 0Hz), 1. 32 (6H, t, J = 7.0Hz), 3.6K4H, q, J = 7.0Hz), 4.20 (2H, q, J = 7.0Hz), 4.40 (2H, s), 8.9K1H, s Example-9 s _C00Pr

The reaction was performed in the same manner as in Example 17 except that propyl alcohol was used instead of ethanol as the alcohol to give (1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) thio. Propyl acetate white solid Body (76.6%) was obtained. Soku: 56.8 57.4 ° C; - NMR (CDC1 3 TMS, ppm): δ 0. 92 (3Η t J = 7.0Hz), 1.27 (. 6Η t, J = 7 OHz), 1.54 1.70 (2H m), 3 .59 (4H, q, J-7. OHz), 3.93 (2H, s), 4.10 (2H, t, J = 7. OHz), 8.74 (1 H, s).

Et

The reaction was carried out in the same manner as in Example 3 except that propyl thioacetate (0.460 g, 1.53 iMol) was used as the starting material (1-getylcarbamoyl-lH-l, 24-triazol-3-yl). As a result, a white solid (0.450 g, 88.5 ») of (1 -getylcarbamoyl-1H-1 2,4-triazol-3-yl) sulfonylacetate was obtained.mp: 46.8 47.1 ° C ; 'H-NMRCCDCl ₃ , TMS, ppm): δθ.90 (3Η, t, J = 7.OHz), 1.31 (6H, t J = 7.OHz), 1.45 1.60 (2H m), 3.60 (4H q J = 7. OHz), 4.10 (2H, t J = 6.6Hz), 4.4K2H, s), 8.90 (1H, s).

The reaction was carried out in the same manner as in Example 17 except that isopropyl alcohol was used instead of ethanol as the alcohol to give (1-Jetyl carbamoyl-1H-1,2,4-triazol-3-yl). A white solid (70, 9%) of isopropyl thioacetate was obtained. mp:. 56.2 56.8 ° C; NMR (CDC1 3, TMS, p pm): (51.24 (6H, d J = 6.5Hz), 1.30 (6H, t, J = 7 OHz), 3.50 3.70 (4 H, m ), 3.90 (2H, s), 5.05 (1H, sep, J = 6.5Hz), 8.74 (1H, s). Example 1 1 2

Et.

Same as Example 13 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) isopropyl thioacetate (2.13 g, 7.09 mmol) was used as a raw material. To give a white solid (2.28 g, 96.9%) of (trimethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonylacetate. . .. mp: 44 6~45 5 ° C; 'Η- NMR (CDC1 3, TMS, ppm): δ 1. 22 (6H, d, 6. 4Hz), 1. 32 (6H, t, J = 7 0 Hz), 3.45 to 3.70 (4H, m), 4.38 (2H, s), 5.02 (1H, sep, J = 6.4Hz), 8.92 (1H, s). Example 1 1 3

By performing the reaction in the same manner as in Example 7 except that butyl alcohol was used instead of ethanol as the alcohol, (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) A white solid of butyl thioacetate (79.5%) was obtained. mp: 68. 7~69 6 ° C; :.. Η- NMR (CDC1 3, TMS, ppm): δ θ 91 (. 3H, t, J = 5 9Hz), 1. 28 (6H, t, J = 7.0 Hz), 1.22 to 1.59 (4H, m), 3.59 (4H, q, J = 7.0 Hz), 3.92 (2H, s), 4.14 (2H, t , J = 6.5Hz), 8.74 (1H, s). Example 14

 E

NEI

 t people. O

Et,, ^N ,, SS; i NO COOBu

N People Bruno ^N

 Ha N '

 I

 Et N

The reaction was performed in the same manner as in Example 3 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) butyl thioacetate (0.500 g, 1.59 mmol) was used as the starting material. As a result, a colorless transparent oil (0.430 g, 78.1%) of (trimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate was obtained. ^ -NMRCCDC, TMS, ppm): 50.90 (3H, t, J = 6.4 Hz), 1.32 (6H, t, J = 7.0 Hz), 1.27 to 1.58 (4H, m), 3.60 (4H, q, J-7.0Hz), 4.14 (2H, t, J = 6.4Hz), 4.4K2H, s), 8.9K1H, s).

The reaction was carried out in the same manner as in Example 7 except that isobutyl alcohol was used instead of ethanol as the alcohol to give (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl). ) A colorless transparent oily product of isobutyl thioacetate (55.7%) was obtained. ^ -NMRCCDCl. ,, TMS, ppm): δ ΰ.90 (6Η, d, J = 6.8Hz), 1.27 (6Η, t, J = 7.ΟΗζ), 1.80-2.00 (1Η, m), 3.59 ( 4Η, q, J = 7.ΟΗζ), 3.92 (2Η, d, J = 6.8Hz), 3.94 (2Η, s), 8.73 (1Η, s). Example 1 16 oo _w o

^Ε 1, Ν ^Α Ν '^ ^C00 - ^BU

Et Reaction was carried out in the same manner as in Example 3 except that (1_getylcarbamoyl-1H-1,2,4-triazol-3-yl) isobutyl thioacetate (0.350 g, 1. llmmol) was used as a raw material. Was carried out to obtain a colorless transparent oil (0.355 g, 92.3%) of (1-getylcarbamoyl-1H_1,2,4-triazol-3-yl) sulfonyl acetate isobutyl acetate. _{^{! HN R (CDC1 3, TMS}} , ppm): (50.89 (6H, d, J = 6 • 5Hz), 1.32 (6H, t, J = 7.0Hz), 1 · 80~2.00 (1H, m), 3.45 ~ 3.70 (4H, m), 3.93 (2H, d, J = 6.5Hz), 4.44 (2H, s), 8.92 (1H, s).

Et

By performing the reaction in the same manner as in Example 7 except that pentanol was used in place of ethanol as the alcohol, (1-getylcarbamoyl-1H-1,2,4-triazole-3 -Yl) A colorless transparent oil (88.3%) of pentyl thioacetate was obtained.

TMS, ppm): δ 0.89 (3H, t, J = 7. OHz), 1.26 (6H, t, J = 7. OHz), 1.25 to 1.35 (4H, m), 1.60 to 1.70 (2H, m), 3 · 40 to 3 · 70 (4H, m), 3.93 (2H, s), 4.14 (2H, t, J = 6.7Hz), 8.75 (1H, s).

 o

Et, A., S COO-pentyl

Same as Example 3 except that pentyl thioacetate (2.38 g, 7.25 mmol) was used as the starting material (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl). By carrying out the reaction in the same manner as described above, a colorless transparent oily substance (1.74 g, 66) of (1-getylcarbamoyl-1H-1,2,4-tria ZE-zol-3-yl) sulfonylacetate was obtained. 6%). 'H-NMRCCDCh, TMS, ppra): δ ΰ. 89 (3H, t, J = 7.0 Hz), 1.24 to 1.35 (4H, in), 1.32 C6H, t, J = 7. 0Hz), 1.59 (2H, tt, J = 6.7 and 7.0Hz), 3.45 to 3.70 (4H, m), 4.13 (2H, t, J = 6.7Hz), 4.42 (2H, s), 8.92 (1H, s).

(1 -Getylcarbamoyl-1H-1,2,4-triazol-3-yl) thioacetic acid (L 03 g, 4.00 ol) was added to a solution of thionyl chloride (0. 32 mL, 4.39 mmol) was added, and the mixture was stirred under reflux for 2.5 hours. Subsequently, the solvent and excess thionyl chloride were distilled off using Evapore overnight, and THF (10 mL), triethylamine (0.6 mL, 4.30 mmol) and ethyl ethyl glycolate were added to the obtained residue. 0.4 mL, 4.23 mmol) was added at 0 ° C, and the mixture was stirred for 4 hours. After completion of the reaction, 1N-hydrochloric acid (20 mL) and ethyl acetate (20 mL) were added to the reaction solution, the organic layer was separated, and the aqueous layer was further extracted with ethyl acetate (20 mL × 2). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride (40 mL), and dried over anhydrous magnesium sulfate. After filtering off the desiccant, the filtrate was concentrated under reduced pressure to obtain a crude product. This was purified by silica gel column chromatography (一 -gel C-200, ethyl acetate: hexane = 1: 1) to give (1-getylcarbamoyl-1H-1,2 There was obtained a brown oil (0.143 g, 10.4%) of ethoxycarbonylmethyl 4-, 4-triazol-3-yl) thio. _{^{; H-NMR (CDC1 3,}} TMS, ppm): δ I.27 (. 3H, t, J = 7 OHz), 1.28 (6H, t, J: 7.0Hz), 3.50~3.70 (4H, m), 4.05 (2H, s), 4.22 (2H, q, J = 7.OHz), 4.66 (2H, s), 8.75 (1H, s).

Example 1 20

Et,

 Same as Example 13 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) ethoxycarbonylmethyl thioacetate (0.143 g, 0.415 mmol) was used as a raw material. The reaction was carried out to give a clear, colorless oil (0.120 g, 76.8%) of (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetoxyethoxycarbonylmethyl. 'H-NMR (CDC1 TMS, ppm): 51.26 (3H, t, J = 7.OHz), 1.3K6H, t, J = 7.OHz), 3.5

0 to 3.70 (4Η, m), 4.20 (2H, q, J-7. OHz), 4.56 (2H, s), 4.64 (2H, s), 8.93 (1H, s).

Example 1 2 1

COO e on Et. N 义 N'V ^S

 Et then N

The reaction was carried out in the same manner as in Example 19 except that methyl 2-hydroxypropionate was used in place of ethyl glycolate to give (1-ethylcarbamoyl-1H-1,2,4-triazole- 3-yl) thioacetic acid (1-methoxy) A brown oil of (cycarbonyl) ethyl was obtained (5.88%). 'H-NMI CDCla, TM S, pm): δ \ .28 (6Η, t, J = 7.ΟΗζ), 1.50 (3Η, d, J = 7.ΟΗζ), 3.50 to 3.70 (4Η, m ), 3.73 (3Η, s), 4.02 (2Η, s), 5.15 (1Η, q, J = 7.ΟΗζ), 8.7 5 (1Η, s).

Example 1 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) ethyl thioacetate (1-methoxycarbonyl) ethyl (0.081 g, 0.235 mmol) was used as a raw material. By carrying out the reaction in the same manner as in 3, a colorless and transparent oily product of (1-methoxyethyl) -1-sulfonylacetic acid (1-methoxycarbonyl) ethyl is obtained. (0.050 g, 56.5%). ^ -NMRCCDCl. ,, TMS, ppm): δ \ .31 (6H, t, J = 7.0Hz), 1.47 (3H, d, J = 7.0Hz), 3.550 to 3.70 (4H, m), 3.72 (3H, s), 4.52 (2H, s), 5.12 (1H, q, J = 7.0Hz), 8.93 (1H, s).

Acetonitrile (60 mL) solution of 3-mercapto-1,2,4-triazole (5.06 g, 50.0 ol), methyl 2-chloropropionate (5.75 mL, 50.4 mmol) and potassium carbonate (5.20 g, 37.6 mmol) Was heated to reflux for 2 hours. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (50 mL), and this was extracted with getyl ether (30 mL × 3 times). Combine the organic layers and add a saturated aqueous sodium chloride solution And dried over anhydrous magnesium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain a crude product. The product was purified by silica gel column chromatography (Co-gel C-200, ethyl acetate: hexane = 2: 1) to give 2-[(1H-1,2,4-triazo-monophenol). A milky white solid of (-3-yl) thio] methyl propionate (5.50 g, 62.8%) was obtained. _{^{: H-NMR (CDC1 3,}} TMS, ppm): δ \ .6Κ3Η, d, J = 7.3Hz), 3.78 (3H, s), 4.20 (1H, q, J = 7 • 3Hz), 7.25 (1H, br s), 8.18 (1H, s).

Acetate of 3-mercapto-1,2,4-triazole (2.53 g, 25.Ommol), methyl 2-bromopropionate (4.18 g, 25 bandol) and potassium carbonate (2.59 g, 18.7 mmol) The nitrile (60 mL) solution was heated to reflux for 1 hour. After allowing to cool to room temperature, potassium carbonate (2.59 g, 18.7 mmol) and getylcarbamoyl chloride (3.48 mL, 27.6 mmol) were added to the reaction mixture, and the mixture was stirred for 6 hours. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (30 mL) and extracted with getyl ether (30 mL × 2). The organic layers were combined, washed with a saturated aqueous sodium chloride solution (20 mL), and dried over anhydrous magnesium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain a crude product. The product was purified by silica gel column chromatography (一 -gel C-200, ethyl acetate: hexane = 1: 3) to give 2-[(1-getylcarbamoyl-1H-1,2,4). A white solid (1.31 g, 76.2%) of methyl [-triazole-3-yl) thio] propionate was obtained. ^{mp:! 48.5~49.0 ° C; H} -NMR (CDC1 3, TMS, ppm): δ I.28 (6H, t, J = 7.3Hz), 1.65 (3H, d, J = 7.3Hz), 3.64 (4H, q, J-7.3Hz), 3.74 (3H, s), 4.39 (1H, q J = 7.3Hz), 8.75 ( 1H, s). Example 2 5

COOMe

Performed except that methyl 2-[(1-getylcarbamoyl-1H-124-triazolyl-3-yl) thio] propionate (0.43 NEI 0 g 1.5 mmol) was used as a raw material.

 t people.

By conducting the reaction in the same manner as in Example 1, the colorless methyl 2-[(1-getylcarbamoyl-ΙΗ-1,2,4-triazol-3-yl) sulfinyl] propionate is obtained. A clear oil (0.426 g, 93.9%) was obtained. 'H- osnN τMRCCDCla, TMS, ppm) (51.30 (6H, t J = 7.3Hz), 1.46 and 1.65 (total 3H each d J = 7.3 Hz), 3.64 (4H, q, J = 7.3Hz), 3.76 and 3.79 (total 3H, each s), 4.30 (1H, q, J = 7.3Hz), 8.9K1H, s).

Example 1 except that methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] propionate (0.859 g, 3.0 mmol) was used as a raw material. By carrying out the reaction in the same manner as in 3, a colorless transparent oil (0.880 g, 91.2%) of methyl 2- [α-getylcarbamoyl-1H-1,24-triazol-3-yl) sulfonyl] propionate is obtained. Obtained. ^ -NMRCCDCh, TMS, ppm): (51.3K6H, t, J = 7.3Hz), 1.73 (3H, d, J = 7.3Hz), 3.63 (4H, q J = 7.3Hz), 3.75 (3H, s ), 4.19 (1H, q, J = 7.3Hz), 8.92 (1H, s). Example 1 2 7

 0

 Et, person, COOMe 9

 N Y Ύ.

Et N ¹

 To a solution of methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] propionate (1.00 g, 3.49 mmol) in 4-dioxane (4 mL) An IN-sodium hydroxide solution (4.5 mL) was added dropwise, and the mixture was stirred at room temperature for 2.5 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, 1N-hydrochloric acid (10 mL) and ethyl acetate (10 mL) were added to the residue, the organic layer was separated, and the aqueous layer was further extracted with ethyl acetate (10 mL × 2). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. After the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] propionic acid as a white solid ( 0.788 g, 82.9%). Immediately: 115 116 ° C; 'H-NMRCCDCla, TMS, ppm) δ 1.28 (6H, t, J = 7.3Hz), 1.66 (3H, d, J = 7.3Hz), 3.62 (4H, q, J = 7.3) Hz), 4.28 (1H, q, J = 7.3Hz), 7.12 (1H, br s), 8.83 (1H, s).

2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] propionic acid (0.5545 g, 2.Ommol) Under ice-cooled stirring, metabenzo-perbenzoic acid (0.812 g, 4.70 mmol) was added, stirred for 4 hours under ice-cooling, then heated to room temperature, and further stirred at room temperature for 24 hours. Was added to 1N hydrochloric acid (20 mL), the organic layer was separated, and the aqueous layer was further extracted with chloroform (20 mL × 2). The extract was washed with an aqueous solution of sodium chloride (20 mL) and dried over anhydrous magnesium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain a crude product. Purification of this product by silica gel gel column chromatography (ヮ Kogel C-200, ethyl acetate: hexane = 4: 1 → ethyl acetate: methanol = 7: 3) yielded 2-[(1-gel A colorless transparent oil (0.157 g, 25.8%) of tylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propionic acid was obtained. 'HN RCCDCh, TMS, pm): 61.31 (6Η, t, J = 7.3Hz), 1.78 (3H, d, J = 7.3Hz), 3.63 (4H, q, J = 7.3Hz), 4.20 (1H, q, J = 7.3Hz), 6.52 (1H, br s), 8.97 (1H, s).

HN'V ^SH-

COO e

The reaction was carried out in the same manner as in Example 24 except that dimethylcarbamoylc-oleide was used instead of getylcarbamoylc-oleide, to give 2-[(1-dimethylcarbamoyl- 1H-1,2,2 A colorless, transparent oil (0.865 g, 50.3%) of methyl 4-pion-3-yl) thio] propionate was obtained. '.Eta. title _{R (CDC1 3, TMS, ppm} ): δ I.65 (3H, d, J = 7.3Hz), 3.25 (6H, s), 3.74 (3H, s), 4.38 (1H, q, J = 7.3Hz), 8.74 (1H, s). Example 1 30 e

Example 1 except that methyl 2-[(l-dimethylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] propionate (0.388 g, 1.5 mmol) was used as a raw material. The reaction was carried out in the same manner as described above to obtain a colorless transparent oily substance of methyl 2-[(tridimethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfinyl] propionate (0.280 g, 68.1% ). ^ -NMRCCDCh, TMS, ppm) δ 1.49 and 1.65 (total 3H each t, J = 7.3Hz), 3.27 (6H, s), 3.77 and 3.79 (total 3H each s), 4.30 (1H, q, J = 7.3Hz), 8.89 (1H, s)

The reaction was carried out in the same manner as in Example 24 except that morpholinocarbonylclip was used in place of getylcarbamoylcclide, to give 2-[(1-morpholinocarbonyl-1H-12,4- A colorless transparent oil (68.3%) of methyl triazolp-3-yl) thio] propionate was obtained. -NMI CDCla, T MS, ppm): δ \ .64 (3Η, d J = 7.4Hz), 3.73 (3Η, s), 3.85 (8Η, br s), 4.33 (1H, q, J = 7.4Hz) , 8.73 (1H, s).

The raw material is 2-[(1-morpholinocarbon-1H-1 2 4-triazole-3- L) thio] propionate (0.601 g, 2.0 mmol) was used to carry out the reaction in the same manner as in Example 13 to give 2-[(trimorpholinocarbonyl -ΙΗ-1,2,4- A colorless transparent oil (0.660 g, 99.3%) of methyl triazol-3-yl) sulfonyl] propionate was obtained. ^ -NMRCCDCh, TS, ppm): (5 1.72 (3H, d, J = 7.3 Hz), 3.74 (3H, s), 3.85 (8H, br s), 4.45 (1H , q, J = 7.3 Hz), 8.90 (1H, s).

H

The reaction was carried out in the same manner as in Example 24 except that disopropyl rubamoyl chloride was used instead of getyl carbamoyl chloride, to give 2-[(tolisopropyl propyl lbamoyl-1H-1, 2 There was obtained a colorless transparent oil (10.8%) of methyl 4-, 3-triazol-3-yl) thio] propionate. _{- NMR (CDC1 3, TMS,} ppm):.. Ό 1. 38C12H, d, J = 6 8Hz), 1. 65 (3H, d, J = 7 3Hz), 3. 73 (3H, s), 3 80 to 4.20 (2H, m), 4.4K1H, q, J = 7.3Hz), 8.64 (1H, s).

Except that methyl 2-[(l-diisopropylpropyllubamoyl-1H-1,2,4-triazol-3-yl) thio] propionate (0.340 g, 1.08 mmol) was used as the raw material Was reacted in the same manner as in Example 3 to give colorless and transparent methyl 2-[(1-diisopropyl-potamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] propionate. An oil (0.300 g, 86.6%) was obtained.

_{'H-NMR (CDC1 3,} TMS, ppm): 51.30~; I.50 (12H, m), 1.72 (. 3H, d, J = 7 3Hz), 3.74 (3H, s), 3.80-4.20 (2H , m), 4.40 (1H, q, J = 7.3Hz), 8.79 (1H, s).

The reaction was performed in the same manner as in Example 23 except that methyl 2-bromobutanoate was used in place of methyl 2-propionate to obtain 2-[(1Η-1,2,4-triazo-yl- A colorless transparent oil (72.1%) of methyl 3-yl) thiobutenoate was obtained. ^ -NMRCCDCh, TMS, ppm): δ 1.06 (3Η, t, J = 7.1 Hz), 1.9 4 (2H, dq, J = 7.6 and 7.1 Hz), 3.76 (3H, s), 4.08 (1H, t, J = 7.6Hz), 8.23 (1H, s), 12.4 (1H, br s).

Acetonitrile (10 mL) solution of methyl 2-[(lH-1,2,4-triazol-3-yl) thio] butanoate (0.403 g, 2.000 mmol) and carbonated carbonate (0.208 g, 1.50 mmol) To the mixture was added morpholinocarbonyl chloride (0.28 mL, 2.40 mmol), and the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (10m in water and extracted with geethylether (8raL x 3 times). The extract was washed with an aqueous sodium solution (8 mL) and dried over anhydrous magnesium sulfate. After the desiccant is removed by filtration, the filtrate is concentrated under reduced pressure to give methyl 2-[(1-morpholinocarbonyl-1H-1 2,4-triazol-3-yl) thio] butanoate A colorless transparent oil (0.563 g, 89.5%) was obtained. _{'H-NMR (CDC1 3,} TMS, pp m): 51.07 (3H, t, J = 7.3Hz), 1.99C2H, m), 3.73 (3H, s), 3.77 3. 93 (8H, m), 4.2 K1H, t J = 7.3Hz), 8.73 (1H, s).

Same as Example 13 except that methyl 2-[(1-morpholinocarbonyl-1H-124-triazol-3-yl) thio] butanoate (0.563 g, 1.79 mmol) was used as a raw material. By carrying out the reaction, a white solid of methyl 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) sulfonyl] butanoate (0.511 g, 82.4%) was obtained. . ^{mp:! 147 148C; H-} NMR (CDC1 3, TMS, pm): δ \ .06C3H, t, J = 7.5Hz), 2.22 (2H, dq, J = 5.9 and 7.5Hz), 3.76 (3H s) , 3.93 (8H, br s), 4.2K1H, t, J = 5.9Hz), 8.90 (1H s).

 O

 , Et, person, NS COO

 I

 Et N

By performing the reaction in the same manner as in Example 24 except that pentyl bromoacetate was used in place of methyl 2-propionate, (1-J A colorless transparent oily substance (35.1%) of tylcarbamoyl-1H-1,2,4-triazole-3-yl) cyclopentyl thioacetate was obtained. _{NMR (CDC1 3, TMS, ppm} ):.. 5 1. 2 called, t, J = 7 5Hz) , 1. 40~1 85 (8H, m), 3. 61 (4H, q, J = 7. 5 Hz), 3.89 (2H, s), 5.2K1H, m), 8.58 (1H, s).

 Reaction was performed in the same manner as in Example 3 except that (1-getylcarbamoyl-lH-l, 2,4-triazol-3-yl) cyclopentyl thioacetate (4.29 g, 13.lmmol) was used as a raw material. To give a colorless transparent oil (3.50 g, 74.5%) of (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate cyclopentyl. . 'H-NMRCCDCh, TMS, ppm): 5 1.32 (6H, t, J = 7.0 Hz), 1.42-1.81 (8H, m), 3.61 (4H, q, J-7 0 Hz), 4.37 (2 H, s), 5.15 to 5.2 2K 1H, m), 8.9K1H, s).

HN'V ^{S 00} small

 O

 Et, person no N S ^^ COO-t-Bu

 N N

I

 Et N

The reaction was carried out in the same manner as in Example 24 except that t-butyl acetate was used in place of methyl 2-propionate, to give (1-getylcarbamoyl-1H-1,2,4-triazole). -3-yl) White color of t-butyl thioacetate A solid (75.2%) was obtained. ^{mp:! 53.7 54.7 C; H} -NMR (CDC1 3, TMS, ppm) δ 1.28 (6H, t J = 7.0Hz), 1.45 (9H, s), 3.50 3.70 (4H, m), 3.86 (2H, s ), 8.74C1H, s).

 Reacted in the same manner as in Example 3 except that t-butyl thioacetate (10.0 g 31.8 IM101) was used as the starting material (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) Was carried out to obtain a white solid (10.75 g, 97.5%) of (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate. mp: 66.8 67.1 ° C; 'H-NMRCCDC, TMS, ppm): 61.24 (6H, t, J = 7.0Hz), 1.33 (9H, s), 3.40 3.70 (4H, m), 4.26 (2H, s) , 8.85 (1H, s).

 , N s COO-benzyl

The reaction was carried out in the same manner as in Example 23 except that benzyl 2-bromoacetate was used instead of methyl 2-chloropropionate to give (1H-12-triazole-3-yl). A yellow oil (79.9%) of benzyl thioacetate was obtained. H-NMR (CDC13 ₎ TMS, ppm): 53.94 (2H, s), 5.17 (2H, s), 7.25 to 0.35 (5H, m), 8.13 (1Hs), 10.50 (1H, br s ). _Λ

 47 Example 1 4 3

 ^ N. ^ S. .COO-benzyl

HN 丫 ^ 'O

 ^ = N _► Et, N s COO'benzyl

 Et N

Example-By the same reaction operation as in 36, benzyl (1H-12-triazol-3-yl) thioate (4.99 g, 20. Ommol) and getylcarbamoyl chloride (3.0 mL, 23.8 dragons) were obtained. ol) to give a colorless transparent oil (4.54 g, 65.1%) of benzyl (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) thioacetate. 'Eta -賺_{(CDC1 3, TMS ppm):} δ 1.24 (6H, t J = 7.0Hz), 3.50 3.60 (4H m), 3.97 (2H, s), 5.18 (2H, s), 7.30 7.40 (5H m ), 8.73 (1H, s).

 o

 Et, person, N

 丄 \

Et N

Same as Example 13 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) benzyl thioacetate (4.53 g, 13.Ommol) was used as a raw material. To give a white solid (4.39 g, 88.7%) of benzyl (1-getylcarbamoyl-1H-1,24-triazol-3-yl) sulfonylacetate. mp: 72.5 72.9 ° C; '' H- NMR (CDC1 3 TMS, ppm): (51.29 (6H, t J = 6.0Hz), 3.50 3.60 (4H, m), 4.47 (2H, s), 5.14 (2H , s), 7.33 to 7.35 (2H, m), 7.25 7.28 (3H m), 8.85 (1H, s). Example 1 45 l

Example-By the same reaction procedure as in 36, benzyl (1H-1,2,4-triazol-3-yl) thioacetate (4.99 g, 20. Ommol) and dimethylcarbamoyl chloride (2.0 mL, 22.0 dragonol) to give a clear, colorless oily product of benzyl (tridimethylcarbamoyl-1H-1,2,4-triazol-3-yl) thioacetate (4.64 g, 72.3 %). _{NMR (CDC1 3, TS, ppm} ):. 53.10~3.20 (6H, m), 3.96 (2H, s), 5.18 (2H, s), 7.26~7.35 (5H, m), 8.70 (1H, s) carried Example 1 46

O O

 , N S ゝ ノ COO-benzyl

N

The reaction was carried out in the same manner as in Example 13 except that (1-dimethylcarbamoyl-1H-1,2,4-triazol-3-yl) benzyl thioacetate (4.63 g, 14.5 mmol) was used as the starting material. Thereby, a white solid (5.00 g, 97.9%) of benzyl (1-dimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate was obtained. mp: 97.2~98.2 ° C; - NMR (CDC1 3, TMS, ppm): 53.18 (3H, s), 3.24 (3H, s), 4.47 (2H, s), 5.14 (2H, s), 7.26~7.28 (2H, m), 7.34 to 7.35 (3Η, m), 8.83 (1H, s). Example 1 4 7

By the same reaction procedure as in Example 36, benzyl (1H-1,2,4-triazol-3-yl) thioacetate (4.90 g, 19.7 minol) and morpholinocarbonyl chloride (4.9 g) were used. 2.30 mL, 19.7 mmol), and the colorless transparent oily substance of benzyl (trimorpholinocarbonyl-1H-1,2,4-triazol-3-yl) thioacetate (5.46 g, 76.5%). - Anonymous _{(CDC1 3, TMS, ppm)} :.. S 3. 60~3 95C10H, m), 5. 18 (2H, s), 7. 25~7 40 (5H, m), 8. 7K1H, s Example 1 4 8

Same as Example 3 except that (1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) benzyl thioacetate (5.46 g, 15.1 mmol) was used as a raw material. To give a colorless transparent oil (4.21 g, 70.7%) of (1-morpholinocarbonyl-1H_1,2,4-triazol-3-yl) sulfonylacetate. Obtained. _{^{! H-NMR (CDC1 3,}} TMS, ppm): 5 3. 50~4 · 00 (8H, m), 4 - 47 (2H, s), 5. 14 (2H, s), 7. 26~7 35 (5H, m), 8.84 (1H, s). Example 1 4 9

 (1-Jetylcarbamoyl-1H-1,2,4-triazolyl) was obtained by carrying out the reaction in the same manner as in Example 24, except that arginyl acetate was used in place of methyl 2-propionate. 3-yl) A clear and colorless oily substance of aryl thioacetate (62.6%) was obtained. ^ -NMRCCDCU, TMS, ppm): δ I.28 (6H, t, J = 7.0 Hz), 3.50 to 3.70 (4H, m), 3.96 (2H, s), 4.64 (2H, d, J = 5.5 Hz), 5.25 (1H, d, J = 10.4Hz), 5.33 (1H, d, J = 17.4Hz), 5.85-5.94 (1H, m), 8.75 (1H, s).

Et,

 allyl

The reaction was performed in the same manner as in Example 3 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) aryl thioacetate (6.54 g, 21.9 mmol) was used as a raw material. As a result, a colorless transparent oil (1.22 g, 16 • 9%) of (1-methylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate was obtained. _{- NMR (CDC1 3, TMS,} ppm): δ I.32 (6H, t, J = 7.0Hz), 3. 50~3.70 (4H, m), 4.45 (2H, s), 4.62 (2H, ddd, J = l.2, 1.5 and 5.8 Hz), 5.26 (1H, ddd, J = l.2, 1.5 and 10.4Hz), 5.32 (1H, ddd, J = l.2, 1.5 and 17.4Hz), 5.83 ( 1H, tdd, J = 5.8, 10.4 and 17.4Hz), 8.92 (1H, s). Example 1 5 1

Me

By performing the reaction in the same manner as in Example 24 except that chloroacetic acid (2-methoxetinole) was used instead of methyl 2-propionic acid propionate, (1-methylethylcarbamoyl-1H-1, A white solid (41.3%) of 2,4-triazol-3-yl) thioacetic acid (2-methoxethyl) was obtained. mp:.. 68. 8~69 6 ° C; -NMR (CDC1 3, TMS, ppm): (5 1. 28 (6H, t, J = 7 0Hz), 3. 37 (3H, s), 3 50 to 3.70 (6H, m), 3.98 (2H ₍ s), 4.28 to 4.31 (2H, m), 8.74 (1H, s).

Example 3 except that (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) thioacetic acid (2-methoxethyl) (1.63 g, 5.16 mmol) was used as a raw material. By carrying out the reaction in the same manner as described above, a colorless and transparent oily substance (1.51 g) of (1-methylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate (2-methoxethyl) was obtained. , 83.9%). ^ -NMRCCDCh, TMS, ppm): δ 1.32 (6H, t, J = 7.0 Hz), 3.34C3H, s), 3.53-3.70 (6H, m), 4.26-4 28 (2H, m), 4.46 (2H, s), 8.9K1H, s). Example 1 53

The reaction was carried out in the same manner as in Example 24 except that sec-butyl chloroacetate was used in place of methyl 2-chloropropionate to obtain (1-getyl sorbamoyl-1H-1,2,4-triazolyl). -3-yl) A colorless transparent oily substance (69.4%) of sec-butyl thioacetate was obtained.

TMS, ppm): δθ.87 (3Η, t, J = 7.3Hz), 1.2K3H, d, J = 6.4Hz), 1.28 (6H, t, J = 7.0Hz), 1.4 9 ~ 1 65 (2Η , M), 3.550 to 3.70 (4H, m), 3.92 (2H, s), 4.88 (1H, tq, J = 6.1 and 6.4Hz), 7.78 (1H, s).

Et,

The same as in Example 13 except that sec-butyl thioacetate (1.81 g, 5.75 mmol) was used as the raw material (1-getylcarbamoyl-lH-1,2,4-triazol-3-yl). By carrying out the reaction, a colorless transparent oil (1.96 g, 98.4%) of sec-butyl (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate was obtained. Was. ^ -NMRCCDCh, TMS, ppm): άθ.86 (3Η, t, J = 7.3 Hz), 1.18 (3H, d, J = 6.1 Hz), 1.32 (6H, t, J = 7.0 Hz), L46 ~ l.60 (2H, m), 3.50〜3 ・ 70 (4H, m), 4.38 (2H, s), 4.86 (1H, tq, J = 6.1 and 6.4Hz), 8.9K1H, s). Example 1 5 5

The reaction was carried out in the same manner as in Example 24 except that α-bromo-α-butyrolactone was used instead of methyl 2-chloropropionate to obtain-[(1-Getylcarbamoyl-1H-1, 2,4-Triazol-3-yl) thio] -r-butyrolactone was obtained as a white solid (72.1%). ^{mp: 58.9~59.7 ° C;: H} -NM R (CDC1 3, TMS, ppm): δ I.28 (6H, t, J = 7.0Hz), 2.70 (2H, m), 3.60 (4 H, q , J = 7.0Hz), 4.42 (2H, t, J = 8.8Hz), 4.45 (, m), 8.75 (1H, s).

Except for using [-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -a-butyrolactone (0.569 g, 2.0 mmol) as the raw material, The reaction was carried out in the same manner as in Example 3 to give a-[(1-Gethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -a-butyrolactone. A clear oil (0.400 g, 63.2%) was obtained.

TMS, pp m): (51.31 (6H, t, J = 7.0Hz), 3.05C2H, m), 3.59 (4H, q, J = 7.0Hz), 4.50 (1H, t, J = 8.8Hz), 4.56 (2H, t, J = 8.1Hz), 8.93 (1H, s). Example 57

, N S

 HN

The reaction was carried out in the same manner as in Example 24 except that methyl 2-chloro-2- (1-methylcyclopropyl) acetate was used instead of methyl 2-chloropropionate to give 2-[(1-ge Chi carbamoyl-1H-1, 2, 4-triazole Ichiru I le) Chio] - ₂ - ₍₁ - Mechirushiku port propyl - give 1-I le) No color clear oil acetate Echiru a (34.2%). ^ -NMRCCDCh, TMS, ppm): (50.47 to 0.52 (1H, m), 0.53 to 0.58 (1H, m), 0.62 to 0.68 (1H, m), 0.87 to 0.93 (1H, m) , 1.2K3H, s), 1.26 and 1.27 (total 9H, each t, J = 7.0Hz), 3.50 to 3.70 (5H, m), 4.18 and 4.23 (total 2H, each dq, J-7.0 and 10. 7Hz), 8.72 (1H, s).

Example _ 5 8

 o O

 Et

N 'V ^S丫 咖

The raw material is 2-[(l-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2- (1-methylcyclopropyl-1-yl) ethyl acetate (0.400 g, 1.08 mmol), and the reaction was carried out in the same manner as in Example 3 to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl). ) Sulfonyl] -2- (1-methylcyclopropyl-1-yl) colorless transparent oil (0.469 g, 94.1%) of ethyl acetate was obtained. - title _{R (CDC1 3, TMS, ppm} ): (50 · 52~0.5 6 (1H, in), 0 · 60~0 · 68 (2H, m), 0.70~0.77 (1H, m), 1.23 (3H , t, J 7.0Hz), 1.32 (6H, t, J = 7.0Hz), 1.42 (3H, s), 3.50 to 3.70 (4H, m), 3.80 (1H, s), 4.2K2H, q, J = 7.0Hz), 8.89 (1H, s). Example 1 5 9 OOMe

The reaction was carried out in the same manner as in Example 24 except that methyl 2-cyclopropyl-2-cyclopropylacetate (0.701 g, 4.72 mmol) was used instead of methyl 2-chloropropionate to obtain 2-[( A colorless transparent oil (0.173 g, 11.7%) of methyl tert-carbamoyl-1H-1,2,4-triazol-3-yl) thio] -2-cyclopropylacetate was obtained. _{^{: H-NMR (CDC1 3,}} TS, ppm): S 0 · 45~0 · 52 (1H, m), 0.58~0.63 (1H, m), 0.72~0 · 75 (2H, m), 1.27 (6H , t, J = 7.0 Hz), 1.30 to 1.38 (1H, m), 3.50 to 3.70 (4H, m), 3.72 (1H, d, J = 10.1 Hz), 3.75 (3H, s), 8.74 (1H , s). Example 1 60

Except for using 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -methyl 2-cyclopropylacetate (0.173 g, 0.55 mmol) as the raw material The reaction was carried out in the same manner as in Example 3 to give 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-cyclopropyl A colorless transparent oil (0.177 g, 93.4%) of methyl pyracetate was obtained. _{NMR (CDC1 3, TMS, ppm} ): δθ.37~0.43 (1H, m), 0 · 52~0 · 58 (1H, m), 0.72 ~0.85 (2H, m), 1.32 (6H, t, J = 7.3Hz), L47 ~ 1.55 (1H, m), 3.50-3.70 (5H, m), 3.79 (3H, s), 8.92 (1H, s).

 The reaction was performed in the same manner as in Example 24 except that methyl 2-chloropropionate was replaced by 2-ethyl-2-ethyl-2-ethylhexyl acetate (1.85 g, 9.93 mmol). [(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio]-colorless transparent oil of ethyl 2-cyclohexylacetate (0.736 g, 21.3%) ). 'H-NMRCCDCla, TMS, ppm): 51.10 to 1.30 (14H, m), 1.65 to 1.70 (1H, m), 1.74 to 1.80 (3H, m), 1.90 to 2.04 (2H, m), 3.50 to 3.80 ( 4H, m), 4.10-4.25 (3H, m), 8.73 (1H, s).

Ethyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2-cyclohexylacetate (0.431 g, 1.23 mmol) was used as a raw material. Other than the above, the reaction was carried out in the same manner as in Example 13 to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-cyclohexyl A colorless transparent oil (0.458 g, 97.4%) of ethyl acetate was obtained. _{-NMR (CDC1 3, TMS, ppm} ): δ 1.14-1.35 (14H, in), 1 · 64~1 · 80 (4H, m), 2.1 0~2 · 15 (1Η, m), 2.32~2.40 ( 1H, m), 3.50 to 3.70 (4H, m), 4.16 to 4.22 (3H, m), 8.89 (1H, s).

 , N S cOOMe

 HN J ― HN Y 丫

^N COOMe

Hydrogenated sodium (0.40 g, 10.0 ol) was placed in a two-necked eggplant flask (25 m) at 0 ° C in an argon atmosphere at 3 ° -mercapto-1,2,4-triazole (1.1 Olg, 9.99 ol). After stirring for 30 minutes at 0 ° C, dimethyl chloroformate (1.27mL, 9.95mmol) was added, and the temperature was gradually raised from 0 ° C to room temperature. After completion of the reaction, the reaction solution was added to 1N hydrochloric acid (15 mL), extracted with ethyl acetate (15 mL × 3), and the organic layers were combined, washed with a saturated aqueous sodium chloride solution (15 mL), and dried over anhydrous water. The desiccant was separated by filtration, and the filtrate was concentrated under reduced pressure to obtain a crude product, which was subjected to silica gel column chromatography (Co-gel C-200, ethyl acetate: ethyl acetate). By purifying with hexane = 2: 1), a white solid (1.19 g) of dimethyl (1H-1,2,4-triazol-3-yl) thiomalonate was obtained. To give ^{51.3%); H-NMR (} CDC1 3, TMS, ppm):. Δ 82 (6Η, s), 5.14 (1Η, s), 8. 26 (1Η, s), 12.65 (1Η, br s). Example-64

 Enter OOMe

 HN

COO e

Sodium hydride (0.090 g, 2.25 mmol) was placed in a two-necked eggplant flask (25 m), and dimethyl (1H-1,2,4-triazol-3-yl) thiomalonate (0H) was placed in an argon atmosphere at 0 ° C. A solution of 0.506 g, 2.19 bandol) in DMF (5 mL) was added.After stirring at 0 V for 40 minutes, getylcarbamoyl chloride (0.28 mL, 2.22 mmol) was added, and the temperature was gradually raised from 0 ° C to room temperature. After the completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (5 mL) and extracted with ethyl acetate (10 mL × 3) The organic layers were combined, and saturated aqueous sodium chloride solution (10 mL) was added. The extract was washed, dried over anhydrous magnesium sulfate, the desiccant was filtered off, and the filtrate was concentrated under reduced pressure to obtain a crude product, which was subjected to silica gel column chromatography (CO-gel C-200). And ethyl acetate: hexane = 1: 2) to give (1-Getylcarbamoyl-1H-.1,2,4). - Toriazo Ichiru - 3 - I le) Chiomaron dimethyl colorless clear oil (0.234 g, was obtained 32.3%) 'H- NMR (CDC1 3, TMS, ppm):. <51.28 (6H, t, J = 7.0Hz), 3.50 to 3.70 (4H, m), 3.82 (6H, s), 5.25 (1H, s), 8.76 (1H, s). Example 65 C _00Me

The reaction was carried out in the same manner as in Example 3 except that dimethyl thiomalonate (0.268 g, 0.81 iol) was used as the starting material (1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl). By doing so, the colorless and transparent oil of dimethyl (tridecylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylmalonate is obtained. (1.74 g, 66.6%).

TMS, ppm): 51.32 (6H, t, J = 7. OHz), 3.50 to 3.70 (4H, m), 3.86 (6H, s), 5.42 (1H, s), 8.93 (1H, s). One 6 six

The reaction was carried out in the same manner as in Example 23 except that 2-toluenesulfonyloxy-4-methylpenisobutanoate was used in place of methyl 2-propionate, to obtain 2-[(1H- A colorless, transparent oil (79.0%) of isopropyl 1,2,4-triazol-3-yl) thio] -4-methylpentanoate was obtained. _{'Η - NMR (CDC1 3,} TMS, ppm): δ 0.93 (3H, d, J = 6.4Hz), 0.95 (3H, d, J = 6.1Hz), 1.24 (6H, d, J = 6.1Hz), 1.63 to 1.70 (1H, m), 1.73 to L88 (2H, m), 3.98 to 4.08 (1H, m), 5.06 (1H, qq, J = 6.1 and 6.4Hz), 8.

12 (1H, s), 12.2K1H, br s).

According to the same reaction procedure as in Example 1-36, 2-[(1H-1,2,4-triazol-3-yl) thio] -4-methylpenoisobutyrate (3.49 g, 14.000 mmo) Reaction of 1) with getylcarbamoyl chloride (1.80 mL, 14.25 mmol) yields 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) thio] Colorless and transparent oily product of isopropyl-4-methylpentanoate (2.14 g, 42 E9%). _{^{: H-NMR (CDC1 3,}} TMS, ppm): ά 0.95 (3H, d, J = 6.4Hz), 0. 98 (3H, d, J = 6.1Hz), 1.20 (3H, d, J = 6.1Hz ), 1.2K3H, d, J = 6.4Hz), 1.29 (6H, t, J = 7.0Hz), 1.7 to 1.84 (2H, m), 1.86 to 1.92 (1H, m), 3.40 to 3.80 (4H , M), 4.26 to 4.30 (1H, m), 5.02 (1H, qq, J = 6.1 and 6.4Hz), 8.75 (1H, s).

2-[(l-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -4-methylpenisonate (0.903 g, 2.59 mmol) was used as the starting material. Except for the above, the reaction was carried out in the same manner as in Example 3 to give 2-[(1-methylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -4-methylpentene A colorless transparent oily product of isopropyl isobinate (0.985 g, 97.9%) was obtained.

6.7Hz), 1.22 (3Η, d, J = 6.4Hz), 1.23 (3Η, d, J = 6.4Hz), 1.32 (6H, t, J = 7.0Hz), 1.6 ~ 1.7 (1H, m), 1.98 (1H, ddd, J = 3.4, 9.2 and 13.4H z), 2.13 (1H, ddd, J = 5.2, 11.3 and 13.4Hz), 3.50-3.70 (4H, m), 4.24 (1H, dd J = 3.4 and 11.3Hz), 5.03 (1H, sep, J = 6.4Hz), 8.9K1H, s). Example 1 69

 Example 3 By the same reaction procedure as in 36, 2-[(1H-1,2,4-triazol-3-yl) thio] -4-propylmethylpentanoate (0.750 g, 2.91 bandages 0 1 ) And dimethylcarbamoyl chloride (0.281 mL, 3.06 mmol) to give 2-[(1-dimethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) thio] -4- A colorless and transparent oily product of isopropyl methyl penisonate (0.903 g, 94.5%) was obtained. ^ -NMRCCDCh, TMS, ppra): (50.95 (3H, d, J = 6.7 Hz), 0.98 (3H, d, J = 6.1 Hz), 1.2K3H, d, J = 6.1 Hz), 1.22 (3H , d, J = 6.4 Hz), 1.71 to 1.83 (2H, m), 1.85 to 1.92 (1H, m), 3.01 to 3.08 (6H, m), 4.25 (1H, t, J = 7.6Hz), 5.02 (1H, sep, J = 6.3Hz), 8.72 (1H, s).

Except that 2-[(l-dimethylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -4-methylpentanoate (0.903 g, 2.75 ol) was used as the raw material By carrying out the reaction in the same manner as in Example-3, 2-[(1-dimethylcarbamoyl-1H-1,2,4-triazoyl-3-yl) sulfonyl] -isopropyl 2-methylpentanoate (0.914 g, 92. 'H-NMRCCDCla, TMS, ppm): δ 0.94 (3Η, d, J = 6.7 Hz), 0.96 (3H, d, J = 6.4 Hz), 1.22 (3H, d, J = 5.2Hz), 1.23C3H, d, J = 5.9Hz), 1.62 to 1.71 (1H, m), 1.97 (1H, ddd, J = 3.4, 9.2 and 14.3Hz), 2.15 (1H, ddd, J = 5.2, 11.6 and 13.7Hz), 3.20 (3H, br s), 3.33C3H, br s), 4.26 (1H, dd, J = 3.4 and 11.6Hz), 5.04 (1H, sep, J = 6.1Hz), 8.90 (1H, s).

By the same reaction procedure as in Example 1, 36, 2-[(1H-1,2,4-triazolyl-3-yl) thio] -4-methylpentisopropyl citrate (0.500 g, 1.94 mmol 1 ) Was reacted with diisopropylcarbamoyl chloride (0.381 g, 2.33 mmol) to give 2-[(todisopropyl-lubamoyl-1H-1,2,4-triazolyl-3-yl) thio] -4 A colorless transparent oily substance of isopropyl methylpentanoate (0.742 g, 99.0%) was obtained. Title _{R (CDC1 3, TMS, ppm} ): δ 0.95 (3Η, d, J = 6.4Hz), 0.97 (3H, d, J = 6.4Hz), 1. 0 (3H, d, J = 6.1Hz), 1.21 (3H, d, J = 6.1Hz), 1.32-1.42 (12H, m), 1.71-1.82 (2H, m), 1.85-1.92 (1H, m), 3.80-4.20 (2H, m), 4.27 (1H, dd, J = 7.3 and 8.4Hz), 5.02 (1H, sep, J = 6.1Hz), 8.63 (1H, s).

The raw material is 2-[(1-diisopropylpropyl-lvamoyl-1H-1,2,4-triazol-3-yl) thio] -4-methylpentylisopropyl (0.500 g, 1.30 mmol) The reaction was carried out in the same manner as in Example 13 except that was used, to give 2-[(tolisopropyl-caproluvamoyl-1H-1,2,4-triazol-3-yl) sulfonyl]- A colorless transparent oily product of isopropyl 4-methylpentanoate (0.337 g, 61.5%) was obtained. _{- NMR (CDC1 3, TMS,} ppm): 50.94 (3H, d, J = 6.4Hz), 0.9 6 (3H, d, 6. Hz), 1.20 (3H, d, J = 6.1Hz), 1.2K3H, d, J = 5.8Hz), 1.30 to 1.58 (12H, br s), 1.63 to 1.71 (1H, m), 1.99 (1H, ddd, J = 3.4, 9.2 and 13.7Hz), 2.15 (1H, ddd, J = 5.2, 11.6 and 13.4Hz), 3.80 to 4.20 (2H, m), 4.25 (1H, dd, J = 3.4 and 11.3Hz), 5.03 (1H, sep, J = 6.4Hz), 8.80 (1H, s) Example 1 7 3

By the same reaction procedure as in Example 1, 36, 2-[(1H-1,2,4-triazolyl-3-yl) thio] -4-propyl pentanoate (0.500 g, 1.94 mmo 1) And morpholinocarbonyl chloride (0.232 mL, 2.33 mmol) to give 2-[(1-morpholinocarbon-1H-1,2,4-triazolyl-3-yl) thio] -4 A colorless and transparent oily product of iso-methylpenisobutyrate (0.671 g, 93.3%) was obtained. _{^{1 H-NMR (CDC1 3,}} TMS, ppm): δ 0.95 (3Η, d, J = 6.4Hz), 0 .98 (3H, d, J = 6.4Hz), 1.2K3H, d, J = 6.4Hz) , 1.22 (3H, d, J = 6.1 Hz), 1.71 to 1.82 (2H, m), L86 to 1.91 (1H, m), 3.66 to 4,000 (8H, m), 4.24 (1H, t, J = 7.3Hz), 5.0K1H, sep, J = 6.4Hz), 8.73 (1H, s). Example 1 Ί 4

Performed except using 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) thio] -4-methylpentanoate (0.671g, 1.81MIO1) as the raw material The reaction was carried out in the same manner as in Example 3 to give isopropyl 2-[(1-morpholinocarbonyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -4 methylpentanoate. A clear yellow oil (0.492 g, 93.4%) was obtained.

0.96 (3H, d, J = 6.7 Hz), 1.22 (3H, d, J = 6.1 Hz), 1.23 (3H, d, J = 6.4 Hz), 1.62 to 1.72 (1 H, m), 1.97 ( 1H, ddd, J = 3.3, 9.2 and 13.7Hz), 2.13 (1H, ddd, J = 5.2, 11.6 and 13.4Hz), 3.68 to 4.05 (8H, m), 4.25 (1H, dd, J = 3.7 an d 11.4Hz), 5.03 (1H, sep, J = 6.1Hz), 8.9K1H, s).

By the same reaction procedure as in Example 36, 2-[(1H-1,2,4-triazol-3-yl) thio] -4-isopropylpentanoate (0.200 g, 0.78 mmol 1) was used. Reaction with N-methyl-N-phenylcarbamoyl chloride (0.146 g, 0.86 mmol) yields 2- (N-methyl-N-phenylcarbamoyl) -1H-1,2,4-triazole [-3-yl} thio] Colorless and transparent oil (isopropyl) -4-methylpentanoate (0.297 g, 97.9%) was obtained. _{- NMR (CDC1 3, TMS,} ppm): δ 0.87 (3H, d, J = 6.4Hz), 0.92 (3H, d, J = 6.4Hz), 1.20 (3H, d J = 6.1Hz), 1.2K3H, d, J = 6.4Hz, 1.50 1.62 ( 1H, m), 1.68 1.77 (2H, m), 3.53 (3H, s), 3.85 3.90 (1H, m), 4.99 (1H, sep, J = 6.3Hz), 7.11 7.16 (2H, m), 7.20 7.50 (3H, m), 8.59 (1H, s).

The raw material is 2-[{1- (N-methyl-N-phenylcarbamoyl) -1H-1,24-triazol-3-yl} thio] -4-propylmethylpentanoate (0.297 g, 0.76 imol) except that the reaction was carried out in the same manner as in Example 3 to give 2- (N-methyl-N-phenylcarbamoyl) -1H-1,2,4-triazo-1-yl. A colorless transparent oil (0.317 g, 98.7%) of [l-3-yl} sulfonyl] -4-methylpenisobutanoate was obtained. _{'HN R (CDC1 3, TMS} , ppm): 50.88 (3Η, d J = 6.7Hz), 0.92 (3H, d, J = 6.7Hz), 1.20 (3H, d, J = 6.1Hz), 1.21 (3H , d J = 6. lHz), L50 l.64 (1H m), 1.67 1.80 (1H m), 1.88 2.06 (1H, m), 3.57 (3H, s), 3.93 4.06 (1H m), 5.0 K1H, sep, J = 6.3 Hz), 7.11 7 ・ 22 (2H m), 7.31 7 ・ 43 (3H, m), 8.75 (1H, s). Example 1 7 7

2-[(lH-1,2,4-triazol-3-yl) thio] -4-propylmethylpentanoate (3.35 g, 13. Ommol) and triethylamine (0.119 mL, 1.36 mmol) ) Of toluene ((S)-(-)-methylbenzylisocyanoate (1.85 mL, 13.1 mmol) was added to a 20-m solution at 0 ° C, and the mixture was stirred for 1 hour. A saturated aqueous solution of citric acid (5 mL) was added to the liquid, and the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (20 mL × 2) .The obtained organic layers were combined, washed with saturated saline (20 mL), and dried over anhydrous sodium chloride. The resultant was dried over magnesium sulfate, the desiccant was filtered off, and the filtrate was concentrated under reduced pressure to obtain a crude product, which was subjected to silica gel column chromatography (ク ロ マ ト グ ラ フ ィ co-gel C-200, chloroform: hexane). = 1: 1) to give 2-[{1- (N- (1-phenylethyl) -lubamoyl) -1H-1,2,4-triazolyl-3-y } Chio = -4 - give colorless oil main Chirupentan acid Isopuropi a (3.97g, 75.5%).

, 0.97 (3H, d, J2 6.4Hz), 1.19 (3H, d, J = 6.7Hz), 1.2K3H, d, J = 6.7Hz), 1.62 and 1.63 (total 3H, each d, J = 7.0Hz), 1.70 to 1.84 (2H, m), 1.85 to 1.92 (1H, m), 4.28 (1H, t, J = 7.3Hz), 5.02 (1H, qq, J = 6.1 and 6.4Hz), 5 12 (1H, dq, J = 7.0 and 7.9Hz), 7.07C1H, d, J = 7.9Hz), 728 to 7.40 (5H, m), 8.73 (1H, s). Example 7 8

 The raw material is 2- [U- (N- (1-phenylethyl) capsulebamoyl) -lH-l, 2,4-triazol-3-yl} thio] isopropyl -4-methylpentanoate (0.196g , 2- (U- (N- (1-phenylethyl) ylrubamoyl) -1H-1,2,4-triazoyl) by performing the reaction in the same manner as in Example 3 except that A colorless, transparent oil (0.107 g, 50.8%) of [l-3-yl} sulfonyl] -4-methylpenisobutanoate was obtained. 'H-NMRCCDCh, TS, ppm): (50.93 (3H, d, J = 6.4Hz), 0.96 (3H, d, J = 6.1Hz), 1.15 and 1.20 (total 3H, eac hd, J = 6.lHz ), 1.18 and 1.19 (total 3H, each d, J = 6.4Hz), 1.65 to 1.7K4H, m), 1.93 to 1.99 (1H, m), 2.15 to 2.22 (1H, m), 4.26 to 4 3 0 (1H, m), 5.02 and 5.04 (total 1H, esch qq, J = 6.4 and 6.1Hz), 5 • 15 (1H, dq, J = 7.0 and 7.9Hz), 7.24 (1H, d, J = 7.9Hz), 7, 28-7.40 (5H, m), 8.95 and 8.96 (total 1H, each s).

Example—By the same reaction procedure as in Ί7, 2-[(1Η-1,2,4-triazol-3-yl) thio] -4-methylpentanoate isopropyl (3.OOg, 11.7 mmol) ) And cyclohexyl isocyanate (1.75 g, 14.0 title ol) to give 2-[{1- (N-cyclohexylcarbamoyl) -1H-1,2,4-triazol-3- A clear colorless oily product of (isopropyl) -4-methylpentanoate (4.26 g, 95.2%) was obtained. ^ -NMRCCDCU, TMS, ppm): (50.96 (3H, d, J-6.4 Hz), 0.99 (3H, d, J = 6.4 Hz), 1.22 to 1.46 (10H, m), 1.62 to 1.83 (6H, m ), 1 86-1.93 (1Η, m), 1.96-2.08 (2H, m), 3 74-3.82 (1H, m), 4.28 (1H, dd, J = 7.2 and 8.1Hz), 5.03 ( 1H, sep, J = 6.4Hz), 6.69 (1H, d, J = 7.9Hz), 8.74 (1H, s).

The raw material is 2-[{(N-cyclohexylcarbamoyl) -1H-1,2,4-triazo-l-3-yl) thio] -4-isopropylmethylpentanoate (0.50 g, 1.31 mmol) The reaction was carried out in the same manner as in Example 13 except for using 2-({1- (N-cyclohexylcarbamoyl) -1H-1,2,4-triazolyl-3-yl). A colorless and transparent oily product of [sulfonyl] -4-methylpenoisobutyrate (0.202 g, 37.2%) was obtained. _{- NMR (CDC1 3, TMS,} ppm): 50.94 (3H, d, J-6.4 Hz), 0.97 (3H, d, J = 6.7Hz), 1.18~1.51 (10H, m), L 68~1.85 (5H , M), 1.94 to 2.07 (3H, m), 2.19 (1H, ddd, J = 5.2, 11.3 and 13.7Hz), 3 • 76 to 3.90 (1H, m), 4.29 (1H, dd, J = 3.4 and 11.3Hz), 5.05 (1H, sep J = 6.3Hz), 6.83 (1H, d, J = 7.9Hz), 8.97C1H, s). Example 1 81

To a solution of 3-mercapto-5-methyl-1H-1,2,4-triazol (1.30 g, 11.5 marl) in acetonitrile (80 mL) was added 2-isomethyl-4-isopropanol (2.43 g). , 12.61M0I), potassium carbonate (1.75 g, 12.7 mmol) and potassium iodide (10 mg), and the mixture was heated under reflux. Six hours later, lithium carbonate (1.75 g, 12.7 mmol) and getylcarbamoyl chloride (2.34 g, 17.3 mmol) were added, and the mixture was further heated under reflux for 6 hours. After completion of the reaction, the reaction solution was poured into 1N hydrochloric acid (150 mL), and extracted with ethyl acetate (150 mL × 2). The organic layer was washed with a saturated saline solution (150 mL), and then dried and dried over anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give 2-[(1-getylcarbamoyl-5-methyl-1H-1,2, A yellow oil (378 mg, 8.9%) of 4-isotripropyl-3-yl) thio] -4-methylpentanoate was obtained. _{'H- NMR (CDC1 3, TMS} , ppm): 50.94 (3H, d, J = 6.5Hz), 0.97 (3H, d, J = 6.5Hz), 1.20~1.29 (12H, m), 1.6 0~1.99 (3H, m), 2.58 (3H, s), 3.61 (4H, m), 4.23 (1H, m), 5.0K1H, m). Example 1 8 2

The mouth of 2-[(l-Getylcarbamoyl-5-methyl-1H-1,2,4-triazol-3-yl) thio] -4-methylpentanoate (370 mg, 1.000 mmol) To the mouth form solution (20 mL) was added metacro-perbenzoic acid (430 mg, 2.49 mmol), and the mixture was stirred at room temperature overnight. After the completion of the reaction, ethyl acetate (70 mL) and 1N aqueous sodium hydroxide were added. After liquid separation of the organic layer, the aqueous layer was extracted with ethyl acetate (5 OmL). The organic layers were combined, washed with saturated saline, and then dehydrated and dried with anhydrous sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to give 2-[(1-Jetyl sorbamoyl-5-methyl-1H-1,2, A colorless oil (120 mg, 29.8%) of 4-triazole-3-yl) sulfonyl] -4-methylpentanoate was obtained. _{^ -NMR (CDC1 3, TMS,} ppm): 60.93 (3H, d, J = 6.7Ηζ), 0.96 (3H, d, J = 6.7Hz), 1.21~L 31 (12H, m), 1.58~1.74 ( 1H, m), L 89 ~ 2.03 (1H, m), 2.08 ~ 2.23 (1H, m), 2.58 (3H, s), 3.37C2H, q, J = 7.0Hz), 3.54 (2H, q, J = 7.0Hz), 4.2K1H, dd, J = 3.5 and 11.4Hz), 5.04 (1H

, sep, J = 6.3Hz).

2-[(lH-l, 2,4-triazol-3-yl) thio] -4-methylpentanoic acid A 1N-sodium hydroxide solution (20 mL, 20 mmol) was added to a solution of isopropyl (2.69 g, 10.5 marl) in 1,4-dioxane (15 mL) at room temperature, and the mixture was stirred for 26 hours. After completion of the reaction, 1N-hydrochloric acid (25 mL) and ethyl acetate (25 mL) were added to the reaction solution, the organic layer was separated, and the aqueous layer was further extracted with ethyl acetate (25 mL × 2). The organic layers were combined, washed with a saturated saline solution (25 mL), and dried over anhydrous magnesium sulfate. The desiccant is filtered off, and the filtrate is concentrated under reduced pressure to give 2-[(1H-1,2,4-triazol-3-yl) thio] -4-methylpentanoic acid as a colorless transparent oil ( 2.16 g, 95.3%). 'H-NMRCCDCla + DMSO- d TMS, p pm): δ θ.96 (3H, d, J = 6.5Hz), 0.98 (3H, d, J = 6.5Hz), 1.68 to 1.74 (1 H, m) , 1.80 to 1.88 (1H, nO, 1.89 to 1.95 (1H, m), 4.29 (1H, t, J = 7.5 Hz), 4.74 (1H, br s), 8.78 (1H, s).

2-[(1H-1,2,4-triazol-3-yl) thio] -4-methylpentanoic acid (2.16 g, 10.0 liter), potassium carbonate (1.04 g, 7.52 mmol) and getylcarba A solution of moyl chloride (1.28 mL, 10. Ommol) in acetonitrile (45 mL) was heated and stirred at 70 ° C for 4 hours. After completion of the reaction, the reaction solution was allowed to cool to room temperature, IN-hydrochloric acid (40 mL) and ethyl acetate (30 mL) were added, the organic layer was separated, and the aqueous layer was further extracted with ethyl acetate (30 mL × 2). The organic layers were combined, washed with saturated saline, and dried over anhydrous magnesium sulfate. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure to obtain a crude product. Then, ethyl acetate was added to the obtained crude product, and insolubles were removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ヮ co-gel 0200, ethyl acetate). To give 2-[(tridecylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -4-methylpentenoic acid as a colorless transparent oil (1.97 g, 62 .5%).

TMS, ρρηι): δ ΰ.95 (3Η, d, J = 6.4 Hz), 0.98 (3H, d, J = 6.4 Hz), 1.28 (6H, t, J = 7.0 Hz), 1.70 to 1.76 (1 H, m), 1.83 to 1.97 (2H, m), 3.50 to 3.70 (4H, m), 4.17 (1H, t, J = 7.5 Hz), 5.57 (1H, br s), 8.82 (1H, s). Example-8 5

Et,

 Except that 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -4-methylpentanoic acid (0.633 g, 2. Olmmol) was used as the raw material The reaction was carried out in the same manner as in Example 3 to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -4- A brown oil (0.05 g, 7.1%) of methyl penic acid was obtained. 'H-NMRCCDCh, TMS, ppm): δ 0.95 (3H, d, J = 6.7Hz), 0.98 (3H, d, J = 6.4Hz), 1.3K6H, t, J = 7.0Hz, 1.66 to L78 (1H, m), L 90 ~ 2.02 (1H, in), 2.08 ~ 2.22 (1H, m), 3.56 (4H, br s), 4.30 (1H, dd, J = 3.4 and 11.3Hz), 5.57 (1H , br s), 8.95 (1H, s).

COO-i-Pr

2-[(1H-1,2,4-triazol-3-yl) thio] isopropyl (-4-methylpentanoate) (2.00 g, 7.77 ol) in ethyl acetate (30 mL) Trichloromethyl chloroformate (1.03 mL, 8.55 mmol) was added dropwise to the mixture at 0 ° C. After stirring at 0 ° C. for 30 minutes, the temperature was raised to room temperature, and the mixture was further stirred under heating and reflux for 3 hours. After the completion of the reaction, the solvent and excess phosgene gas are distilled off under atmospheric pressure to give 2-[(1-chloro-carbonyl-1H-1,2,4-triazol-3-yl) thio]-. An orange oil of isopropyl 4-methylpentanoate (2.44 g, 98.2%) was obtained. ^ -NMRCCDCh, TMS, pm): δ ΰ. 97 (3H, d, J = 5.8 Hz), 1.0K3H, d, J = 6.4 Hz), 1.25 (6H, d, J = 6. 4Hz), 1.72 to 1.85 (2H, m), 1.88 to 1, 96 (1H, m), 4.36 (1H, t, J = 7.3Hz), 5.06 (1H, sep, J = 6. lHz), 9.39 (1H, s).

2-[(1-Chlorocarbonyl-lH-l, 2, 4-triazol-3-yl) thio] -4-methylpentisopropyl citrate (1.86 g, 5.83 mmol) and carbonic acid rim ( To a solution of 0.463 g (2.92 mmol) in acetonitrile (20 mL) was added dropwise N-cyclohexyl-N-ethylamine (0.742 g, 5.83 bandol) at 0 ° C. After the addition, the reaction solution was heated to room temperature, and further stirred at room temperature for 4 hours. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (30 mL), and extracted with ethyl acetate (20 mL × 3). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride (30 mL), and dried over anhydrous magnesium sulfate. After filtering off the desiccant, the filtrate was concentrated under reduced pressure to obtain a crude product. This was purified by silica gel column chromatography (ヮ Kogel C-200, ethyl acetate: hexane = 1: 10). 2- [U- (N-cyclohexyl-N-ethylcarbamoyl) -1H-1,2,4-triazol-3-yl) thio] -2-butyl iso-4-butylpentanoate An oil (L 04 g, 43.4%) was obtained. 'H-NMRCCDCl. ,, TMS, ppm): δ ΰ.95 (3Η, d, J = 6.4 Hz), 0.98 (3H, d, J = 6.4 Hz), 1.06 to 1.40 (14H, m), 1.50 to 1.94 (8H, m), 3.46 to 3.66 (2H, m), 4.09 to 4.22 (1H, m), 4.27 (1H, t, J = 7.5Hz), 5.02 (1H, sep, J = 6.3Hz), 8.70 (1H, s). Example 1 8 8

The raw material is 2-[{1- (N-cyclohexyl-N-ethylcarbamoyl) -1H-1,2,4-triazol-3-yl} thio] -4-isobutyl isobutyl benzoate (0.400 g, 0.97 mmol) except that 2- [U- (N-cyclohexyl-N-ethylcarbamoyl) -1H-1, There was obtained a colorless transparent oil (0.393 g, 91.8%) of 2,4-triazol-3-yl) sulfonyl] -4-methylpentisobutyl citrate. _{'H-NMR (CDC1 3,} TMS, ppm): δ 0. 94 (3H, d, J = 6.7Hz), 0.96 (3H, d, J-6.7Hz), 1 · 20~1 · 42 (14H, m), 1.48-1.75 (3H, m), 1.78-1.95 (3H, m), 1.98 (1H, ddd, J = 3.6, 9.2 and 13.7Hz), 2.16 (1H, ddd, J = 5.2, 11.3 and 13.7 Hz), 3.56 (2H, br s), 394-416 (1H, m), 4.24 (1H, dd, J = 3.6 and 11.3Hz), 5.03 (1H, sep, J = 6.3Hz), 8.87 (1H, s). Example 1 8 9

Example 1 By a reaction operation similar to that of 87, 2-[(1-chlorocarbonyl-1H-1,2,4-triazoI-3-yl) thio] -4-methylpentyne 2-((topyrrolidinocarbonyl-1H-1,2,4-triazol-3-yl) is reacted with pyrrolidine (0.74 g, 10.4 bandol). ) Thio] -4-iso-methylpentanoate as a colorless transparent oil (0.21 g, 11.4%) was obtained. _{- NMR (CDC1 3, TMS,} ppm): (50.95 (3H, d, J = 6.4Hz), 0.98 (3H, d, J = 6.4Hz), 1.2K6H, d, J = 6.4Hz), 1.71~2.03 (7H, m), 3.64 to 3.70 (2H, m), 3.90 to 4.00 (2H, m), 4.25 (1H, t, J = 7.6Hz), 5.02 (1H, sep, J = 6.4Hz), 8.8K1H, s).

Performed except using 2- [G-pyrrolidinocarbonyl-1H-1,2,4-triazol-3-yl} thio] -4-methylpentanoate (0.24 g, 0.67 mmol) as the raw material The reaction was carried out in the same manner as in Example 3 to give 2-[(topyrrolidinocarbonyl-1H-1,2,4-triazoyl-3-yl) sulfonyl] -4-methylisopropyl pentanate To give a colorless transparent oil (0.25 g, 96.5%). _{^ - N MR (CDC1 3,} TMS, ppm): δ 0.93 (3Η, d, J = 6.4Hz), 0.96 (3Η, d, J = 6.4Η ζ), 1.2Κ3Η, d, J = 6.1Hz), 1.23 (3H, d, J = 6.1Hz), 1.60 ~ L 74 (1H, m), 1.93 ~ 2.06 (5H, m), 2.16 (1H, ddd, J = 5.2, 11.6 and 13.4Hz), 3.69 ~ 3.73 (2H, m), 3.94 ~ 3.99 (2H, m), 4.26 ( 1H, dd, J = 3.4 and 11.6Hz), 5.04 (1H, sep, J = 6.1Hz), 8.99 (1H, s).

 The reaction was carried out in the same manner as in Example 23 except that methyl 2-propanol-2- (tricyclohexenyl) acetate was used in place of methyl 2-chloropropionate. A white solid (28.7%) of (1H-1,2,4-triazol-3-yl) thio] -2- (1-cyclohexenyl) ethyl acetate was obtained. mp: 89.6 to 90.3 ° C; 'H-NMRCCDCh, TMS, ppm): 51.20 to 1.30 (3H, m), 1.51 to 1.62 (4H, m), 1.98 to 2.18 (4H, m), 4.19 (2H, br s), 4.8K1H, s), 5.78 (1H, br s), 8.05C1H, s), 13.3 (1H, br s).

By the same reaction procedure as in Example 36, 2-[(1H-1,2,4-triazol-3-yl) thio] -2- (1-cyclohexenyl) ethyl ester (0.95 g, The reaction between 3.55 tmol) and getylcarbamoyl chloride (0.50 mL, 3.96 mmol) was performed, and 2-[(getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) thio] was obtained. 2- (1-cyclohexenyl) ethyl acetate colorless and transparent oil (0.85 g, 65.3%). ^ -NMRCCDC, TMS, ppm): δ I.26 (3H, t, J = 7.1Hz), 1.27 (6H, t, J = 7.0Hz), 1.53-1.58 (2H, m), 1.63-1.68 (2H , M), 2.01 to 2.23 (4H, m), 3.60 (4H, q, J = 7.OHz), 4.2K2H, q, J = 7.1 Hz), 4.86 (1H, s), 5.88 (1H, br s), 8.73 (1H, s).

The reaction was carried out in the same manner as in Example 13 except that methyl octafluorophenylacetate was used in place of methyl 2-chloropropionate to give 2-[(1Η-1,2,4-triazo monomethyl acetate). Le-3-yl) thio] -2-phenylmethyl acetate was obtained as a white solid (77.6%). mp: 106.6~107.8 ° C; - NMR (CDC1 3 ten _{DMSO- d 6, TM S, ppm} ): 53.72 (3H, s), 5.50 (1H, s), 7.30~7.45 (5H, m), 8.06 ( 1H, s), 13.5 (1H, br s).

By the same reaction procedure as in Example 36, methyl 2-[(1H-1,2,4-triazolyl-3-yl) thio] -2-phenylacetate (0.624 g, 2.5 mmol) and dimethyl carbamoyl Reaction with chloride (0.26 mL, 2.82 mmol) yields colorless methyl 2-[(1-dimethylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2-phenylacetate A clear oil (0.76 g, 94.8 «was obtained. ^ -NMRCCDC _{1 3, TMS, ppm):} . (5 3. 19 (6H, s), 3. 73 (3H, s), 5. 48 (1H, s), 7. 30 '50 (5H, m), 8 7K1H, s). Example 1 9 5

Me

 Same as Example 13 except that methyl 2-[[(tridimethylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] phenylacetate (0.76 g, 2.37iMiol) was used as a raw material. To give a white solid of methyl 2-[(1-dimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-phenylacetate (0.46 g, 55%). 3%). Immediate: 127.5 to 128.0 ° C; ^ -NMRCCDCl a, TMS, ppm): 5 3.15 (6H, s), 3.80 (3H, s), 5.56 (1H, s), 7. 30 to 7.50 (5H, m), 8.83 (1H, s).

The reaction was performed in the same manner as in Example 24 except that methyl 2-chloropropionate phenylacetate was used instead of methyl 2-chloropropionate to obtain 2-[(1-methyl-carbamoyl-1H-1, There was obtained a white solid (74.9%) of methyl 2,4-triazol-3-yl) thio] -2-phenylacetate. _{NMR (CDC1 3, TMS, ppm} ) : (51.28 (6H, t, J = 7.5Hz), 3.64 (4H, q, J = 7.5Hz), 3.73 (3H, s), 5.47 (1H, s), 7.32 (3H, m), 7.47 (2H, m), 8.72 (1H, s).

^Et , Et

The procedure was carried out except that methyl 2-[(l-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2-phenylacetate (1.75 g, 5.02iMiol) was used as the starting material. The reaction was carried out in the same manner as in Example 13 to give 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-methyl acetate. A white solid (0.995 g, 57.9%) was obtained. mp:. 95.0~95.5 ° C; ^ -NMRCCDC 1 3, TMS, ppm): (51.2K6H, t, J = 7 OHz), 3.46 (4H, q, J = 7.0Hz), 3.7 9 (3H, s ), 5.55 (1H, s), 7.20 to 7.50 (5H, m), 8.86 (1H, s).

Performed except that methyl 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) thio] -2-phenylacetate (0.750 g, 2.07 mmol) was used as a raw material. The reaction was carried out in the same manner as in Example 3 to give methyl 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-phenylphenylacetate. A white solid (0.546 g, 66.9%) was obtained. ^{mp: 15L 5~152.5 ° C;:} H- NMR (CDC1 3, TMS, ppm): δ3 · 66~3.73 (8H, m), 3.77 (3H, s), 5.6K1H, s ), 7.42 (5H, m), 8.95 (1H, s).

Example 1 99

The reaction was carried out in the same manner as in Example 24 except that 2-ethyl phenylacetate was used instead of methyl 2-chloropropionate to obtain 2-[(1-methylethylcarbamoyl-1H-1,2 , 4-Bok Riazo Ichiru - 3-I le) Chio] -2-phenyl acetate Echiru of a yellow oil (yield the _{74.9 NMR (CDC1 3, TMS,} pp m.): (51.22 and 1.23 (total 9H , each t, J = 7.0Hz), 3.57 (4H, q, J = 7.0Hz), 4.19 (2H, q, J = 7.0Hz), 5.48 (1H, s), 7.31〜7.46 (5H, m) , 8.72 (1H, s).

Example 100

 o

^E N ^A

t

Except that 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2-phenylacetate (4.31 g, 11.9 marl) was used as the raw material The reaction was carried out in the same manner as in Example 13 to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazoyl-3-yl) sulfonyl] -2-phenylacetic acid An ethyl white solid (3.86 g, 92.9%) was obtained. mp: 96~97 ° C; - NMR (CDC1 3, T MS, ppm): (51.23 and 1.5 (total 9H, t, J = 7.3Hz), 3.48 (4H, q, J:

7.3Hz), 4.25 (2H, q, J = 7.0Hz), 5.52 (1H, s), 731 to 7.56 (5H, m),

8.85 (1H, s). Example 1 1 0 1

Et.

1,4-Dioxane of 2-[(l-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-phenylacetate (0.591 g, 1.5 ol) (3 mL), 1N-sodium hydroxide solution (1.7 mL) was added to the solution at room temperature, and the mixture was stirred for 23 hours. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (15 mL), and the precipitated white solid was collected by filtration, washed successively with hexane and water, and thoroughly dried to obtain 2-[(1-diethyl-2-chlorobenzene). A white solid (0.407 g, 74.1%) of rucarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-phenylacetic acid was obtained. mp: 193 ~ 194 ° C; ; H-NMR (CDCl 3 + DMS0-d 6, TMS, ppm): δ \ .24 (. 6H, t, J = 7 0Hz), 3.57 (4H, q, J = 7.0 Hz), 5.45 (1H, s), 6.45 (1H, br s), 7.28 to 7.50 (5H, m), 8.72 (1H, s).

Perform the reaction in the same manner as in Example 23 except that methyl 2,2-dichlorophenylacetate was used instead of methyl 2-propionate propionate. As a result, a white solid (39.3%) of methyl 2-[(1H-1,2,4-triazol-3-yl) thio] -2- (2,4-dichloromethyl) acetate was obtained. _{NMR (CDC1 3, TMS, ppm} ): 53.76 (3H, s), 5.88 (1H, s), 7.22 (1H, dd, J = 2.0 and 8.4Hz), 7.4K1H, d, J = 2.0Hz), 7.5 K1H, d, J = 8.4Hz), 8.15 (1H, s), 12.5 (1H, br s).

By the same reaction procedure as in Example 1, 36, methyl 2-[(1H-1,2,4-triazol-3-yl) thio] -2- (2,4-dichlorophenyl) acetate (0.255 g) , 0.80 bandol ol) and getylcarbamoyl chloride (0.12 mL, 0.95 mmol) to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazoyl-3- [Yl] thio] -methyl 2- (2,4-dichlorophenyl) acetate was obtained as a colorless transparent oil (0.300 g, 89.6%). ^ -N RCCDCh, TMS, ppm): δ \ .25 (6Η, t, J = 7.0Hz), 3.61 (4H, q, J = 7.0Hz), 3.77 (3H ₍ s), 6.0K1H, s) , 7.30 (1H, dd, J = 2.0 and 8.8Hz), 7.33 (1H, d, J = 2.0Hz), 7.6K1H, d, J = 8.8Hz, 8.77 (1H, s). Example 1 104

The raw material was methyl 2-[(tridecylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2- (2,4-dichloromethyl) acetate (0.300 g, 0.72 g). The reaction was carried out in the same manner as in Example 3 except that ol (ol) was used to give 2-[(todiethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] A white solid (0.240 g, 74.2%) of methyl 2- (2,4-dichlorophenyl) acetate was obtained. mp: 127~127.5 ° C; NMR ( CDC1 3, TMS, ppm): 61.27 (6H, t, J = 7 .0Hz), 3.53 (4H, q, J = 7.0Hz), 3.79 (3H, s), 6.22 (1H, s), 7.31 to 7.42 (2H, m), 7.98 (1H, d, J = 8.1 Hz), 8.89 (1H, s).

 Example 1 By the same reaction procedure as in 36, methyl 2-[(1H-1,2,4-triazol-3-yl) thio] -2- (2,4-dichlorophenyl) acetate (0.300 g, 0.94 mmol) and morpholinocarbonyl chloride (0.14 mL, 1.20 mmol) are reacted to give 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) thio]- Methyl 2- (2,4-dichlorophenyl) acetate (0.340 g,

86.7%). _{'H-NMR (CDC1 3,} TMS, ppm): 53.70~3.78 (11H, m), 5.97 (1H, s), 7.26 (1H, dd, J-2.0 and 8.4Hz), 7.43 (1H, d, J = 2.OHz), 7.58 (1H, d, J = 8.4Hz), 8.72 (1H , s). Example 1 10 6

The raw material was methyl 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-ynole) thio] -2- (2,4-dichlorophenyl) acetate (0.340 g, 0.81 mmol). Except for using, the reaction was carried out in the same manner as in Example 3 to give 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2 -A white solid (0.343 g, 94.2%) of methyl (2,4-dichlorophenyl) acetate was obtained. mp: 129~130 ° C; NMR ( CDC1 3, TMS, ppm): 53.71~3 · 89 (11H, m), 6.23 (1H, s), 7.30~7.45 (2H, m), 7.95 (1H, d , J = 8.4Hz), 8.87 (1H, s).

The reaction was carried out in the same manner as in Example 23 except that methyl -chloro-α- (4-methylphenyl) acetate was used instead of methyl 2-chloropropionate to obtain 2-[(1Η-1,2 A pale yellow solid (58.5%) of methyl 2,4-triazole-3-yl) thio] -2- (4-methylphenyl) acetate was obtained. _{'Η- NMR (CDC1 3, TMS} , ppm): <52.38 (3H, s), 3.46 (3H, s), 5.50 (1H, s), 7.28 (2H, d, J = 84 Hz), 7.45 (2H, d, J = 8.4 Hz), 8.26 (1H, s), 12.9 (1H, br s).

Example 2 By the same reaction procedure as 36, methyl 2-[(1H-1,2,4-triazol-3-yl) thio] -2- (4-methylphenyl) acetate (0.380 g, 1.44 bandage) 0 1) is reacted with getylcarbamoyl chloride (0.20 mL, 1.58 mmol) to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazol-3-yl) thio. [O] -Methyl 2- (4-methylphenyl) acetate was obtained as a yellow oil (0.512 g, 98.1%). _{'H-NMR (CDC1 3,} TMS, ppm): δ \ .25 (. 6Η, t, J-7 ΟΗζ), 2.33 (3 Η, s), 3.58 (. 4Η, q, J = 7 ΟΗζ), 3.72 (3Η, s), 5.46 (1Η, s), 7.15 (2Η, d, J = 7.9Ηζ), 7.38 (2Η, d, J = 7.9 Hz), 8.73 (1Η, s).

Et

The raw material used was methyl 2- [α-getylcarbamoyl-1Η-1,2,4-triazo-1-yl-3-yl) thio] -2- (4-methylphenyl) acetate (0.512 g, 1,41 mmol). Except for the above, the reaction was carried out in the same manner as in Example 3 to give 2-[(1-ethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2- (4- A white solid (0.460 g 82.7%) of methyl phenylacetate was obtained. mp: l 15 116 ° C; - NMR (CDC1 3 TMS, ppm) (51.24 (6H, t, J = 7.0Hz), 2.3 4 (3H, s), 3.50 (4H, q, J = 7.0Hz), 3.79 (3H, s), 5.5K1H, s), 7.16 (2H, dJ = 8.1Hz), 7.39 (2H, dJ = 8.1Hz), 8.85 (1H, s).

By the same reaction procedure as in Example 36, methyl 2-[(1H-12,4-triazol-3-yl) thio] -2- (4-methylphenyl) acetate (0.350 g, 1.33 g) mmo 1) is reacted with morpholinocarbonyl chloride (0.16 mL, 1.37 mmol) to give 2-[(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl) thio. A colorless and transparent oily substance of methyl 2- (4-methylphenyl) acetate (0.490 g, 97.9%) was obtained. 'H-NMRCCDC, TMS, ppm) 62.33 (3H, s), 3.78 (3H, s),

3.80 (8H, br s), 5.43 (1H, s), 7.15 (2H, d, J = 8.4Hz), 7.38 (2H, d, J = 8.4Hz), 8.7K1H, s). 1

2 _ [(1-morpholinocarbonyl-1H-1,2,4-triazol-3-yl L) thio] -2- (4-Methylphenyl) acetate (0.490 g, 1.30 mmol) except that methyl 2-((1-morpholinocarbonyl-1H-) was reacted in the same manner as in Example 3. There was obtained a white solid (0.330 g, 62.0%) of methyl 1,2,4-triazol-3-yl) sulfonyl] -2- (4-methylphenyl) acetate. mp: l 58~159 ° C; NMR (CDC1 3, TMS, ppm): 62.34 (3H, s), 3.75 (8H, br s), 3.79 (3H, s), 5.52 (1H, s), 7.16 ( 2H, d, J = 8.4Hz), 7.38 (2H, d, J = 8.4Hz), 8.85 (1H, s).

The reaction was carried out in the same manner as in Example 24 except that propyl α-chlorophenylpropionate was used in place of methyl 2-propionate, to obtain 2-[(1-ethylethylcarbamoyl-1H-1 , 2, 4-triazol-3-yl) thio]-2-propylacetonate as a yellow oil (84.2%). -膽_{(CDC1 3, T MS, ppm} ): (50.83 (3H, t, J = 7.0Hz), 1.24 (6H, t, J = 7.0Hz), 1.56 (2H, m), 3.67 (4H, q, J = 7.0Hz), 4.09 (2H, t, J = 6.6Hz), 5.49 (1H, s),

7.25 to 7.80 (5H, m), 8.72 (1H, s). Example 1 1 1 3

Example 3 except that 2-[(tridecylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2-phenylacetate (0.460 g, 1.66 mmol) was used as a raw material. By carrying out the reaction in the same manner as described above, a white solid of propyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-phenylacetate (0.430 g, 83.7%). ^{mp: 82.5~83 ° C;: H} -NMR (CDCL 3, TMS, ppm): (50.90 (3H, t, J = 7.0Hz), 1.23 (3H, t, J = 7.0Hz), 1.25 (3H, t, J = 7.0Hz), 1.6K2H, qt, J-7.0 and 6.6Hz), 3.49 (4H, q, J = 7.0Hz), 4.16 (2H, t, J = 6.6Hz), 5.54 (1H, s), 7.32 to 7.56 (5H, m), 8.85 (1H, s).

The reaction was carried out in the same manner as in Example 24 except that butanol butyl acetate was used in place of methyl 2-chloropropionate, to give 2-[(trimethylcarbamoyl-1H-1,2,4 -Triazole-3-yl) thio: A yellow oily substance (78.1%) of butyl-2-phenylacetate was obtained. -膽(CDC1 _3, TMS, ppm): (50.85 (3H, t J = 6.2Hz), 1.24 (6H t J = 7.0Hz), 1.49 (4H, m) 3.57 (4H, q, J = 7.0Hz), 4.13 (2H, t, J = 6.4Hz), 5.48 (1H, s), 7.2 4 7.67 (5H m), 8.72C1H, s).

Example 1 except that 2-[(l-Getylcarbamoyl-1H-124-triazol-3-yl) thio] -2-phenylacetate (0.330 g, 1.13 mmol) was used as a raw material. By carrying out the reaction in the same manner as in 3, a white solid of 2-[(trimethylcarbamoyl-1H-124-triazolyl-3-yl) sulfonyl] -2-phenylacetate (0.320 g) was obtained. 87.6%). Soku: 68.5 69 ° C; 'H -NMR (CDC 1 3, TS, ppm): (50.89 (3H, t J = 6.3Hz), 1.23 (3H, t J = 7.0Hz), 1. 25 (3H t J = 7.0Hz), 1.35 1.68 (4H, m), 3.48 (4H, q, J = 7.0Hz), 4.20 (2H, t, J = 6.4Hz), 5.54 (1H, s), 7.21 7.63 ( 5H, m), 8.85 (1H, s).

■ I o

Et, person II _K , O _s

 N eight Et, person, N.S COOMe

 I N— N 丫

Under an argon atmosphere, sodium hydride (0.1OOg, 2.50mmol) in DMF (2m suspension was added to 2-[(1-Gethylcarbamoyl-1H-124-triazolyl-3-yl) sulfonyl ] A solution of methyl acetate (0.761 g, 2.50 MIO1) in DMF (2 mL) was added at 0 ° C. After stirring at 0 ° C. for 30 minutes, isopropyl iodide (0.25 mL) was added. The mixture was stirred for 3 hours while gradually warming to room temperature, and further stirred at 80 ° C for 2.5 hours. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (20 mU, extracted with getyl ether (10 mL × 3). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride (10 mL), and dried over anhydrous magnesium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure to obtain a crude product, which was subjected to silica gel column chromatography (P-gel C-200, ethyl acetate: hexane = 2). : 5) to give a light yellow solid of methyl 2-[(1-methylethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -3-methylbutanoate (0.340). mp: 79-80 ° C; 'H-NMRCCDCla, TMS, pm): <1.1 K3H, d, J = 6.8 Hz), 1.23 (3 H, d, J = 6.8 Hz). ), 1.3K6H, t, J = 7.0Hz), 2.69 (1H, m), 3.60 (4H, q,

J = 7.0Hz), 3.74 (3H, s), 4.17 (1H, d, J-7.5Hz), 8.89 (1H, s).

Example 1 By the same reaction procedure as in 116, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propyl (0.83 lg, 2.50 mmol) ) With isopropyl iodide (0.25 mL, 2.51 bandol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -3 A colorless transparent oily substance of propyl methylbutanoate (0.347 g, 37.1%) was obtained. 'H-NMRCCDCla, TMS, ppm): δ 0.92 (3Η, t, J = 7.3Hz), 1.13 (3Η, d, J = 6.7Hz), 1.24 (3Η, d, J = 6.7Hz), 1.32 (6Η, t, J = 7.ΟΗζ), 1.64 (2Η, tq, J = 6.7 and 7.3 Hz), 2.67 (1H, dsep, J = 6.7 and 7.6 Hz), 3.50 to 3.70 (4H, m), 4.10 (2H, t, J = 6.7Hz), 4.18 (1H, d, J = 7.6Hz), 8.90 (1H, s). Example

Et,

.N one

 S, NO COO Small Pr

 丫 '

^ = N people

 Example-By the same reaction operation as in 116, 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] isopropyl acetate (

0.831 g, 2.50 bandol ol) and isopropyl iodide (0.25 mL, 2.51 mmol) were reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-y). L) sulfonyl] -3-isopropyl methyl-3-butyrate

0.292 g, 31.2%). _{^{l H - NMR (CDC1 3,}} TMS, pm): 51.13 (3H, d, J =

6.7Hz), 1.22 (3H, d, J = 6.1Hz), 1.23 (3H, d, J = 6.lHz), 1.24 (3H, d

, J = 6.7Hz), 1.32 (6H, t, J = 6.7Hz), 2.64 (1H, dsep, J = 6.7 and 7.3

Hz), 3.50-3.70 (4H, m), 4.14 (1H, d, J = 7.3Hz), 5.03 (1H, sep, J =

6.1Hz), 8.93 (1H, s).

By the same reaction procedure as in Example 116, methyl 2-[(1-methylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.761 g, 2.50 MIO1) With propyl iodide (0.245 mL, 2.51 mmol) to give methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] pentanoate A white solid (0.260 g, 30.0%) was obtained. mp: 77.0 -77.5 ° C; ^ -NMRCCDCh, TMS, ppm): 50.96 (3H, t, J = 7.0Hz), 1.29 (2H, m), 1.31 (6H, t, J = 7.0Hz), 2.07 ( 2H, m), 3.60 (4H, q, J = 7.OH 9 z), 3.75 (3H, s), 4.24 (1H, t, J = 7.5Hz), 8.90 (1H, s).

 9 o.o J)

Et, _{N N} , NS _C00Me Et, _N

Example 1-1 By the same reaction operation as in 116, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.608 g, 2. OOmmol) and butyl iodide (0.23mL, 2.02 ol) and react with 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl ] A colorless transparent oily product of methyl hexanoate (0.500 g, 69.4%) was obtained. _{-Ν MR (CDC1 3, TMS,} ppm): 50.90 (3H, t, J = 6.8Hz), 1.20~1.40 (10H, m), 2.10~2.20 (2H, m), 3.45~3.60 (4H, m) , 3.76 (3H, s), 4.20 to 4.30 (1H, m), 8.93 (1H, s).

Et

Example 1 By a reaction operation similar to that of 116, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.761 g, 2.50 bandol) With isobutyl iodide (0.29 mL, 2.52 dragonol) to give 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -A white solid of methyl 4-methylpenanoate (0.580 g, 64.4%) was obtained. mp: 65 ~ 66 ° C; NMR (CDC1 3, TMS, ppm): δθ.92 (3H, d, J = 6.2Hz), 0.95 (3H, d, J = 6.4Hz), L20~1.30 (1H, m), 1.3H6H, t, J = 7.0Hz), 1.96 to 2.12 (2H, m), 3.60 (4H, q, J = 7.0Hz), 3.75 (3H, s), 4.30 (1H, dd, J = 4.6 and 11.3Hz), 8.90 (1H, s). Example _ 1 2 2

Et,

 Example 1 By the same reaction procedure as in 116, 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] ethyl ester (0.796 g, 2.50 bandages) ol) and isobutyl iodide (0.290 mL, 2.52 ol) to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl]-4- A colorless transparent oily substance of methyl ethylpentanoate (0.305 g, 32.6%) was obtained. 'H-NMRCCDCla, TMS, ppm): 60.93 (3H, d, J = 6.7 Hz), 0.96 (3 H, d, J = 6.7 Hz), 1.24 (3H, t, J = 7.3 Hz), 1.32 (6H , t, J = 7.0Hz), 1.6-1.7 (1H, m), 1.98 (1H, ddd, J = 13.7, 9.15 and 3.4Hz), 2.14 (1H, ddd, J = 13.7, 11.3 and 5.2Hz ), 3.50-3.70 (4H, m), 4.20 and 4.2 total 2H, each q, J = 7.3Hz), 4.28 (1H, dd, J = 3.4 and 11.3Hz), 8.9K1H, s). twenty three

Example 1 By the same reaction procedure as in 116, 2- [α-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propyl acetate (0.99) „

 94

7g, 3. OOmmol) and isobutyl iodide (0.35mL, 3.04mmol) were reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfur. A colorless and transparent oily substance of propyl [ruphonyl] -4-methylpentanoate (0.425 g, 36.5%) was obtained. _{'H-NMR (CDC1 3,} TMS, ppm): δ ΰ.92 (3H, t, J = 7.3Ηζ), 0 .94 (3H, d, J = 6.4Hz), 0.96 (3H, d, J = 6.7Hz), 1.32C6H, t, J = 7.0Hz), 1.60-1.69 (3H, m), 1.97 (1H, ddd, J = 13.7, 9.46 and 3.5Hz), 2 • 15 (1H, ddd, J = 13.7, 11.6 and 4.9Hz), 3.50 to 3.70 (4H, m), 4.IK 2H, t, J = 6.7Hz), 4.29 (1H, dd, J = ll.6 and 3.5Hz), 8.9K1H, s ). Example—1 24

Example 1 By a reaction operation similar to that of 16, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] isopropyl acetate (0.997 g, 3. OOmmol) and isobutyl iodide (0.350 mL, 3.04 butylol) were reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl. ]-A yellow oily substance of isopropyl 4-methylpenanoate (0.435 g, 37.3%) was obtained.

TMS, ppm): δΰ.94 (3Η, d, J = 6.7Hz), 0.96 (3Η, d, J = 6.7Hz), 1.22 (3Η, d, J = 6.4Hz), 1.23 (3Η, d, J = 6.4Hz), 1.32 (6Η, t, J = 7.ΟΗζ), 1.6 to 1.7 (1Η, m), 1.98 (1Η, ddd, J = 3.4, 9.2 and 13.4Hz), 2.13 (1Η, ddd , J = 5.2, 11.3 and 13.4Hz), 3.50〜3 70 (4H, m), 4.24 (1H, dd J = 3.4 and 11.3Hz), 5.03 (1H, sep, J = 6.4Hz), 8.9K1H, s). ^ "

 95

Example 1 1 25

 O

 0,, 0

 Et, A N, s

N

Example 1 By a reaction operation similar to that of 16, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] butyl acetate (0.762 g, 2.50 bandages) ol) and isobutyl iodide (0.260 mL, 2.26 ol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] A colorless and transparent oily product of butyl-4-methylpentanoate (0.474 g, 53.5%) was obtained. 'H-NMRCCDCl ,, TMS, ppm): <50.92 (3H, t, J = 7.5Hz), 0.93 (3H, d, J = 6.4Hz), 0.96 (3H, d, J = 6.4Hz), 1.32 (6H, t, J = 7.0Hz), 1.30-1.38 (2H, m), 1.60 (2H, tt, J-6.7 and 7.0Hz), 1.60-1.70 (1H, m), 1.97 (1H, ddd , J = 3.4, 9.2 and 13.4Hz), 2.15 (1H, ddd, J = 5.1, 11.3 and 13.4Hz), 3.50-3.70 (4H, m), 4.14 (2H, t, J = 6.7Hz), 4.29 (1H, dd, J = 3.4 and 11.3Hz), 8.9K1H, s).

Example 1 By the same reaction operation as in 116, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] isobutyl acetate (1.04 g, 3.00 g) Ol) and isobutyl iodide (0.350 mL, 3.04 mmol) to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] Yellow oil of isobutyl 4-methylpentanoate (0.541 g, 4 _n

 9 6

4.8%). ^ -N RCCDC, TMS, ppm): 50.92 (3H, d, J = 6.7 Hz), 0.94 (3H, d, J = 6.7 Hz), 1.22 (3H, d, J = 6.4 Hz), 1.23 (3H, d, J = 6.4 Hz), 1.32 (6H, t, J = 7.0 Hz), 1.60 to 1.70 (1H, m), 1 90-1.94 (1H, m), 1.97 (1H, ddd, J = 3, 4, 9.5 and 13.7 Hz), 2.16 (1H, ddd, J = 5.0, 11 6 and 13.7Hz), 3.50 to 3.70 (4H, m), 3.93 (2H, d, J = 6.4Hz), 4.31 (1H, dd, J = 3.4 and 11.6Hz), 8.9K1H, s).

^E

Example 1 By a reaction operation similar to that of 16, sec-butyl 2-[(1-methylethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetate (0. 866 g, 2.50 mmol) and isobutyl iodide (0.32 mL, 2.78 mmol) were reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazoIl-3- A colorless transparent oil (0.625 g, 62.1%) of sec-butyl 4-methylpentanoate) was obtained. 'H-NMRCCDCl s, TMS, pm): δ 0.88 and O. 90 (total 3H, each t, J = 7.6 Hz), 0.94 (3H, d, J = 6.7 Hz), 0.95 and 0.96 (tota 13H, each d, J = 6.7 and 6.4Hz), 1.19 and 1.20 (total 3H, each d, J = 6.4Hz), 1.3K6H, t, J = 7.0 Hz), 1.48 to 1.70 (3H, m), 1.93 to 2.00 (1H, m), 2.12 to 2.19 (1H, in), 3.50 ~ 3.70 (4H, m), 4.27 and 4.28 (total IH, each dd, J = l l. 3 and 3.4Hz), 4.87 and 4.88 (total IH, each tq, J = 6.1 and 6.4Hz), 8.90 and 8.91 (total IH, each s). Example 1 2 8

 Example 1 By a reaction operation similar to that of 16, t-butyl 2-[(trimethylcarbamoyl-1H-1 2,4-triazol-3-yl) sulfonyl] acetate (1.04 g, 3. OOmmol) and isobutyl iodide (0.35mL 3.04mmol) to react with 2--2-[(tridecylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl]- A colorless transparent oily product of t-butyl 4-methylpentanoate (0.594 g, 49.2%) was obtained. 'H-NMRCCDC ^, TMS, ppm) (50.94 (3H, d, J = 6.4Hz), 0.96 (3H, d, J = 6.7Hz), 1.32 (6H t J = 7.0Hz), 1.42 (9H, s ), 1.64 1.7 3 (1H, m), 1.96 (1H, ddd, J = 13.4, 9.2 and 3.4Hz), 2.12 (1H, ddd, J = 13.4, 11.6 and 5.2Hz), 3.50 3.70 (4H, m) , 4.19 (1H, dd J = ll. 6 and 3.4Hz), 8.92 (1H, s).

Example 1 By a reaction operation similar to that of 16, pentyl 2-[(1-getylcarbamoyl-1H-124-triazolyl-3-yl) sulfonyl] acetate (1.08 g, 3.000 mmol) With isobutyl iodide (0.350 mL, 3.04 mmol) to give 2-[(trimethylcarbamoyl-1H-1,24-triazol-3-yl) sulfonyl] -4-methylpentenoic acid Pentyl yellow oil (0.695g, 55.6% ). _{^{; H-NMR (CDC1 3,}} TMS, ppm): 50.90 (3H, t, J = 7.0Hz), 0.94 (3H, d, J = 6.4Hz), 0.96 (3H, d, J = 6.4Hz), 1.32 (6H, t, J = 7.0Hz), 1.2g 1.34 (4H, m), 1.6K2H, tt, J = 6.7 and 7.0Hz), 1.60-1.70 (1H, m), 1.97 (1H, ddd, J = 3.4, 9.2 and 13.7Hz), 2.15 (1H, ddd, J = 5.1, 11.3 and 13.7Hz), 3.50-3.70 (4H, m), 4.13 (2H, t, J = 6.7Hz), 4.29 ( 1H, dd, J = 3.4 and 11.3Hz), 8.9K1H, s).

Example 1- [2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetic acid (2-methoxyethyl) (0.871 g, 2.50 mmol) and isobutyl iodide (0.29 mL, 2 · 521) to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3- [Yl] sulfonyl] -4-methylpentanoic acid (2-methoxethyl) as a colorless transparent oil (0.411 g, 53.8%). _{'H-NMR (CDC1 3,} TMS, ppm): 50.9 4 (3H, d, J = 6.7Hz), 0.96 (3H, d, J = 6.7Hz), 1.32 (6H, t, J = 7.0Hz 1.64~ L 73 (1H, m), 1.99 (1H, ddd, J = 13.7, 9.2 and 3.4Hz), 2.16 (1H, ddd, J = 13.7, 11.3 and 5.2Hz), 3.33 (3H, s), 3.54 (2H , dd, J = 4.6 and 4.9 Hz), 3.50 to 3.70 (4H, m), 4.26 (1H, dt, J = ll.9 and 4.6 Hz), 4.30 (1H, dt, J = ll.9) and 4.9Hz), 4.33 (1H, dd, J = ll.3 and 3.4Hz), 8.9K1H, s). 99 Example 1 1 3 1

Example 1 By a reaction operation similar to that of 16, a 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] aryl (0.702 g, 2.12 01) and isobutyl iodide (0.30 mL, 2.61 mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -A colorless transparent oily product of acrylyl 4-methylpenanoate (0.281 g, 34.3%) was obtained. _{- NMR (CDC1 3, TMS,} ppm): 60.94 (3H, d, J-6.7Hz), 0.96 (3 H, d, J = 6.7Hz), 1.32 (6H, t, J = 7.0Hz), 1 · 63 to 1.70 (1H, m), 1.95 to 2.02 (1H, m), 2.13 to 2.20 (1H, m), 3.55 to 3.65 (4H, m), 4.32 (1H, dd, J = ll.3 and 3.4Hz ), 4.63 (2H, dt, J = l.2 and 5.8Hz), 5.26 (1H, dq, J = l.2 and 10.4Hz), 5.32 (1H, dq, J = l.2 and 17.1Hz), 5.83 (1 H, ddt, J = 5.8, 10.4 and 17.1 Hz), 8.9K1H, s).

Example 1 By a reaction operation similar to that of 16, a mixture of 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] benzyl (0.95 lg, 2 · 50 mmol) and isobutyl iodide (0.29 mL, 2.52 mmol) are reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl]- Benzyl 4-methylpentanoate as a colorless transparent oil (0.689 g, 63.1%). 'H-NMRCCDCh, TMS, ppm): 50.9K3H, d, J = 6.7Hz), 0.92EI (3H, d, J = 6.7Hz), 1.28 (6H, t, J = 7.0Hz), 1.59 (1H, m), 1.96 to 2.04 (1H, m), 2.13 to 2.20 (1H, m), 3.48 to 3.58 (4H, m), 4.36 (1H, dd, J = ll.3 and 3.35Hz), 5.15 (2H, s), 7.25 to 7.40 (5H, m), 8.84 (1H, s).

Example 1 1 33

 O

 0,, 0

 Et, M

N people N, SC

According to the same reaction procedure as in Example-116, 2-[(trimethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetonitrile (1.00 g, 3.69 mmol) And isobutyl iodide (0.467 mL, 4.05 mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -4 A colorless transparent oil of -methylpentanenitrile (0.618 g, 51.2%) was obtained. 'H-NMRCCDCh, TMS, ppm): δ I.00 (3Η, d,

, 1.08 (3H, d, J = 6.4Hz), 1.34 (6H, brs), 1.94 ~ 2.05 (2H, m), 2.12 (1H, ddd, J = 4.6, 11.3 and 13.4Hz), 3.50 ~ 3.74 ( 4H, m), 4.38 (1H, dd, J = 6.4 and 11.3Hz), 8.98 (1H, s).

Example 1 1 34

Example 1 2-[(1-Jetylcarbamo 丄_Q丄

Reaction of Methyl [1H-1,2,4-triazol-3-yl) sulfinyl] acetate (0.72 lg, 2.50 mmol) with Isobutyl iodide (0.290 mL, 2.52 ol) To give a yellow oil of methyl 2-[(1-getylcarbamoyl-1H-1,2,2,4-triazol-3-yl) sulfinyl] -4-methylpentanoate (0. 372 g, 43.2%). 'H-NMRCCDCh, TS, ppm): (5 0.91, 0.94, 0.95 and 0.98 (total 6H, each d, J = 6.4 Hz), 1.32 (6H, t, J = 7.0 Hz), 1.52 to 1.78 (1H, m), 1, 89 to 2.11 (2H, m), 3 50 to 3 70 (4H, m), 3.68 and 3.77 (tota 13H, each s), 4.25 and 4.29 (total 1H, each dd, J = 4.0 and 10.5 Hz), 8.90 and 8.91 (total 1H, each s). Example 1 1 3 5

 By the same reaction procedure as in Example 11, 16-methyl [2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetate (1.22 g,

4. OOmmol) and sec-butyl iodide (0.48mL, 4.03mmol) are reacted to give 2-[(tridecylcarbamoyl-1H-1,2,4-triazolyl-3-yl ) Sulfonyl] -3-methyl-methylpyrunoate as a colorless transparent oil (0.365 g, 25.3%) was obtained. ^ -NMRCCDC, TMS, ppm): S O. 92 and 0.93 (total 3H, each t, J = 7.4Hz), 1.23 and 1.32 (total 3H, each d, J = 6.8Hz) ), 1.32 (6 H, t, J = 7.1 Hz), 1.45 to 1.73 (2H, m), 2.47 (1H, m), 3.60 (4H, q, J = 7.1 Hz), 3.73 and 3.74 (total 3H, each s), 4.25 and 4.36 (total 1H, each d, J = 8.0 and 5.6 Hz), 8.90 and 8 90 (total 1H, each s). _{Q g}

Example— 1 36 Et,

 ,

Example 1 By the same reaction operation as in 116, methyl 2-[(trimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.913 g, 3.000 mmol) ) And 3-bromopentane (0.380 mL, 3.06 bandol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -3 A colorless and transparent oily product of methyl-ethylpentenoate (0.056 g, 5.0%) was obtained. _{^ - NMR (CDC1 3, TMS} , ppm): (50.90 (3H, t, J = 7.3Hz), 0.92 (3H, t, J = 7.3Hz), 1.32 (6H, t, J = 7.0Hz), 1.59 Up to 1.68 (1H, m), 1.71 to 1.84 (3H, m), 2.20 to 2.30 (1H, m), 3.50 to 3.70 (4H, m), 3.73 (3H, s),

4.44 (1H, d, J = 6.1Hz), 8.90 (1H, s).

Et

Example 1 By the same reaction operation as in 116, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetate (0.913 g, 3. OOmmol) and (s)-(+)-1-bromo-2-methylbutane (0.375 mL, 3.04 bandages 1) to react with 2-[(1-Jetylcarbamoyl-1H-1,2,4 -Triazo-l-3-yl) sulfonyl] -4-methylhexanoate was obtained as a colorless transparent oil (0.308 g, 27.4%). ^ -NMRCCDCl ,, TMS, ppm): (50.87 and 0.88 (total 3H, each t, J = 7.6Hz), 0.90 and 0.91 (total 3H, each d 丄 U ϊ3

, J = 6.4Hz), 1 10-1.20 (1Η, m), 1.32 (6Η, t, J = 7.ΟΗζ), 1.35-115 0 (1Η, m), 1.90 and 2.25 (total 1Η, each ddd, J = 3.6, 9.5, 13.7 and 3.6, 11.9, 13.7Hz), 2.00-2.10 (1H, m), 2.13 and 2.16 (total 1H, each ddd, J = 3.6, 7.9, 13.7 and 3.6, 11.9 , 13.7Hz), 3.50 to 3.70 (4H, m), 3.76 (3H, s), 4.29 and 4.33 (total 1H, dd, J = 3.6, 11 • 9 and 3.6, 11. OHz), 8.9K1H, s). Example 1 38

Example 1 By the same reaction operation as in 116, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.913 g, 3 OOmmol) and cyclopentylmethyl tosylate (0.93g, 3.66mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl A colorless, transparent oil (0.102 g, 8.80%) of methyl 3-pentyl pentyl propionate was obtained. 'H-NMRCCDCh, TMS, ppm): 51.08 to 116 (1 (, m), 1.28 to 135 (7H, m), 1.48 to: L 58 (2H, m), 1.58 to 1.68 (2H, m), 1, 73 to 1.83 (3H, m), 2.06-2.13 (1H, m), 2.21 to 2.29 (1H, m), 3.50 to 3.70 (4H, m), 3.77 (3H, s), 4.26 (1H, dd, J = 3.4 and 11.6Hz), 8.93 (1H, s). , „

 104 Example 1 1 39

 Example 1 By a reaction operation similar to that of 16, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] isopropyl acetate (0.997 g, 3 · OO mmol) and cyclopentylmethyl tosylate (0.93 g, 3.66 mmol) to give 2-[(togetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl A colorless transparent oil (0.062 g, 4.99%) of isopropyl-3-cyclopentylpropionate was obtained. HMI CDCls, TMS, ppm): SI.08 to 1.18 (2H, m), 1.23 (3H, d, J = 6.4 Hz), 1.23 (3H, d, J = 6. lHz), 1.32 (6H, t, J = 7.0Hz), 1.48 to 1.58 (2H, m), 1.58 to 1.68 (2H, m), 1.72 to 1.87 (3H, m), 2.07 to 2.14 (1H, m), 2.23 to 2.30 (1H, m) , 3.50-3.70 (4H, m), 4.2K1H, dd, J-3.4 and 11.3Hz), 5.04 (1H, qq

, J = 6.1 and 6.4Hz), 8.9K1H, s).

By the same reaction procedure as in Example-116, methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.913 g, 3.000 mmol) And bromomethylcyclohexane (0.42 mL, 3,04 mmol) to give 2- acetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -3-cyclohexane Methyl xylpropionate white solid ₁

 1 05

(0.280 g, 23.3%). mp: 79, 2~80.3 ° C; NMR (CDC1 3, TMS, ppin): 50.84~L 02 (2H, m), 1.10~1.30 (3H, m), 1.32 (6H, t, J = 7.0Hz) , 1.60 to 1.77 (6H, m), 1.96 to 2.14 (2H, m), 3.50 to 370 (4H, m), 3.76 (3H, s), 4.33 (1H, dd, J = 3.4 and 11.3Hz ), 8.9K1H, s).

Example 1 By the same reaction operation as in 116, 2-[(trimethylcarbamoyl-1H-1,2,4-triazo-1-yl-3-sulfonyl) sulfonyl] isopropyl acetate (0.997 g, 3.00 ol) ) And bromomethylcyclohexane (0.42 mL, 3.04 ol) to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazo-l-3-yl) sulfo A colorless, transparent oil (0.102 g, 7.93%) of [isopropyl] -3-cyclohexylpropionate was obtained. _{^{! H-NMR (CDC1 3,}} TMS, pp ra): 50.82~1.06 (2H, m), 1.08~1 · 24 (9H, m), 1.3K6H, t, J = 7.0Hz), 1.62~1.76 (6H , M), 1.98 to 2.04 (1H, m), 2.08 to 2.14 (1H, m), 3.50 to 3.70 (4H, m), 4.28 (1H, dd, J = ll.3 and 3.4Hz), 5.04 (1H, qq, J = 6.4 and 6.1Hz), 8.92 (1H, s).

By the same reaction procedure as in Example-116, 2-[(1-Jetylcarbamo _{Q g}

Yl-1H-1,2,4-triazol-3-yl) sulfonyl] acetonitrile (1.00 g, 3.69 mmol) and bromomethylcyclohexane (0.613 mL, 4.43 mmol) ) To give 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -3-colorless transparent 3-cyclohexylpropionitrile An oil (0.711 g, 58.3%) was obtained. _{'H-NMR (CDC1 3,} TMS, ppm):. 5 0. 91 ~ 1. 38 C11H, m), 1. 52~L 82 (6H, m), 2. 02~2 10 (2H, m) , 3.50-3.74 (4H, m), 4.36-4.46 (1Η, in), 8.98 (1H, s).

Example 1 By a reaction operation similar to that of 16, a mixture of methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.913 g, 3 · The reaction between 00 ol) and 2-chloroethylmethyl sulfide (0.300 mL, 3.0 OO mmol) was carried out to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazo-1-yl). A colorless transparent oil (0.415 g, 36.5%) of methyl 3--3-yl) sulfonyl] -4-methylthiobutanoate was obtained. _{'H-NMR (CDC1 3,} TMS, ppm):. Δ ΐ 32 (. 6H, t, J = 7 0Hz), 2. 08 (3H, s), 2. 42~2 58 (3H, m), 2.67 to 2.74 (1H, m), 3.50 to 3 70 (4H, m), 3.75 (3H, s), 4.57 (1H, dd, J = 3.7 and 9 8Hz), 8.92 (1H, s).

^E

Example 1 By the same reaction operation as in 16, (1-Jetylcarbamoy The reaction between methyl 1H-1,2,4-triazol-3-yl) sulfonylacetate (0.761 g, 2 • 50 mmol) and 4-bromobutyronitrile (0.25 mL, 2.52 mmol) is carried out. A colorless, transparent oil (0.35 g, 37.7%) of methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -5-cyanopentanoate Obtained. _{- NMR (CDC1 3, TMS,} ppm): ό 1.26 (6Η, t, J = 7.0Hz), 1.8 0 (2H, m), 2. 14~2.47 (4H, m), 3.53 (4H, q, J = 7.0Hz), 3.70 (3H ₍ s), 4.26 (1H, t, J = 6.8Hz), 8.88 (1H, s).

 o

^Et , N

, Person N ' ^N

v /, ^{S C00Me} _ Et

Et N,

Example 1 By a reaction operation similar to that of 16-methyl, 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] methyl acetate (0.913 g, 3.000 mmol ) With cyclopropylmethyl bromide (0.300 mL, 3.09 butylol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl]- A colorless, transparent oil of methyl 3-cyclopropylpropionate (0.591 g, 55.0%) was obtained. 'H-NMRCCDCls, TMS, ppm): δ 0.10 to 0.20 (2H, m), 0.50 to 0.60 (2H, m), 0.70 to 0.90 (1H, m), 1.32 (6H, t, J = 7.0Hz ), 2.05 (1H, ddd, J = 4.0, 7.3 and 13.7Hz), 2.14 (1H, dd d, J = 7.0, 10.7 and 13.7Hz), 3.50-3.70 (4H, m), 3.78 (3H, s) , 4.35 (1H, dd, J = 4.0 and10.7Hz), 8.9K1H, s). Example 1 1 4 6

 O 0,

^EU N ^A N'V ^{S C0} ° ^Me SM. ,, ⁰

 Et

 Et Example— By the same reaction operation as in 116, methyl 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetate (0.761 g, 2.50 g) Reaction with cyclopentyl bromide (0.27 mL, 2.52 mmol) to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl. [2-cyclopentyl acetate] (0.127 g, 13.6%). : H-NMR (CDC, TS, ppm): 51.30-1.35 (7H, m), 1.37-1.46 (1H, m), 1.52-L85 (5H, m), 2-13-2.21 (1H, m), 2.5 2 to 2.65 (1H, m), 3.50 to 3.70 (4H, m), 3.74 (3H, s), 4.19 (1H, d, J = 10.4 Hz), 8.92 (1H, s) .

Example 1 1 4 7

 Example 1 By the same reaction procedure as in 116, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazo-1-yl) sulfonyl] ethyl (0.96 g, 3. Ommol) and cyclopentyl bromide (0.33 mL, 3.1 mmol) to give 2-[(togetylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl. ]-Colorless and transparent oil of 2-cyclopentyl acetate (0.056 g,

5.33%). ^ -NMRCCDC, TMS, ppm): (51.25 (3H, t, J = 7.0Hz), 1.30 to 1.35 (7Η, m), 1.37 to 1.46 (1H, m), 1.52 to 1.85 ( 5H, ra), 2.13 ~ 2.2K1H, m), 2.58-2.70 (1H, m), 3.50-3.70 (4H, m), 4.16 (1H, d, J = 10.4Hz), 4.19 (2H, q, J = 7.0Hz), 8.92 ( 1H, s). Example 1 1 4 8

Example-By the same reaction procedure as in 116, 2-[(Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] propyl acetate (1.00 g, 3.0 bandol) And cyclopentyl bromide (0.35 mL, 3.26 bandol) to give 2- [α-Getylcarbamoyl-1H-1,2,4-triazoyl-3-yl) sulfonyl]- A colorless transparent oil (0.149 g, 12.4%) of propyl 2-cyclopentylacetate was obtained.

.0Hz), 1.30 to 1.45 (8H, m), 1.50 to 1.75 (6H, m), 1.78 to 1.88 (1H, m), 2.12 to 2.20 (1H, m), 2.58 to 2.70 (1H, m), 3.50 ~ 3.70 (4H, m), 4.09 (1H, t, J = 6.7Hz), 4.10 (1H, t, J = 6.7Hz), 4.18 (1H, d, J = 10.4Hz), 8.92 (1H, s ). Example—1 4 9

Example 1 By the same reaction procedure as in 116, 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] isopropyl acetate (1.00 g, 3.0 liters) ol) and cyclopentyl bromide (0.35 mL, 3.26 mmol) The reaction was carried out to give a colorless, transparent oily substance of 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-cyclopentylacetate (0.100 g , 8.32%). 'HN RCCDCla, TMS, ppm): 51.22 (3H, d, J = 6.1Hz), 1.23C3H, d, J = 6.1Hz), 1.30-1.48 (8H, m), 1.52-1.90C5H, m), 2.12 to 2.24 (1H, m), 2.56 to 2.70 (1H, m), 3.50 to 3.70 (4H, m), 4.13 (1H, d, J = 10.4Hz), 5.02 (1H, sep, J = 6.1Hz) , 8.9K1H, s).

According to the same reaction procedure as in Example-116, cyclopentyl 2-[[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (L 07g, 3. Ommol) and cyclopentyl bromide (0.32 mL, 3.0 ol) to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl A colorless transparent oil (0.145 g, 11.3%) of pentyl 2-cyclopentylacetate was obtained. ^ -NMRCCDCl ^ TMS, ppm): 51.30-1.45 (8H, m), 1.52-1.88 (13H, m), 2.10-2.20 (1H, m), 2.52-2.65 (1H, m), 3.50-3 70 (4H, m), 4.14 (1H, d, J = 10.0Hz), 5.18 to 5.25 (1H, m), 8.90 (1H, s). 丄

Example 1 1 5 1

 O o ,, 0

 Et, ΛN, s'

y N '

By the same reaction operation as in Example 11, 16- [2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] butyl acetate (1.04 g,

3. OO mmol) and cyclopentyl bromide (0.40 mL, 3.73 mmol) are reacted to give 2-[(torgethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl ] Butyl 2-cyclopentylacetate (0.141g,

11.3%). ^ -NMRCCDCU, TMS, ppm): <50.92 (3H, t, J = 7.3Hz), 1.28 to 1.48 (employment, m), 1.54 to 1.85 (7H, m), 2.1 to 2.22 (1H, m), 2.55 ~ 2.70 (1H, m), 3.50 ~ 3.70 (4H, m), 4.12 and 4.13 (total 2H, each t, J = 6.7Hz), 4.18C1H, d, J = 10.1Hz), 8.92 (1H, s). Example 1 1 52

Example 1-1 By the same reaction operation as in 116, 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] isobutyl acetate (1.04 g, 3 • OO mmol) and cyclopentyl bromide (0.38 mL, 3.54 mmol) were reacted to obtain 2-[(tridecylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfo. A colorless, transparent oil (isobutyl) -2-yl-2-pentylacetate (0.109 g, 8.76%) was obtained. 'H-NMRCCDCla, TMS, ppm): c50.92 and 0.93 (total 6H, each d, J = 6.7Hz), 1.28-L46 (8H, m), 150-2.00 (6 H, m), 2.12-2.24 (1H, m), 2.58-2.68 (1H, m), 3.50-3.70 (4H, m), 3.91 and 3.92 (total 2H, each d, J = 6.7Hz), 4.20 ( 1H, d, J = 10.1 Hz), 8.92 (1H, s).

Example 1 By a reaction operation similar to that of 116, t-butyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (1.04 g, 3. OOmmol) is reacted with cyclopentyl bromide (0.38mL, 3.54 bandol) to give 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) Sulfonyl] -t-butyl 2-cyclopentylacetate was obtained as a colorless transparent oil (0.083 g, 6.67%). _{^ - NMR (CDC1 3, TMS} , ppm): δ ΐ.32 (6H, t, J = 7.

0Hz), 1.36 to L 46 (10H, m), 1.52 to 1.74 (4H, m), 1.82 to 1.88 (1H, m), 213 to 2.20 (1H, m), 2.54 to 2.65 (1H, m) , 3.50-3.70 (5H, m), 4.0 6 (1H, d, J = 10.1Hz), 8.9K1H, s).

Example 1 By the same reaction operation as in 116, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetonitrile (1.50 g, 5.53 bandits) ol) and cyclopentyl bromide (1.09 g, 7.19 mmol) 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-cyclopentylacetonitrile as an orange oil (0.341 g, 20.4% ). _{^{! H-NMR (CDC1 3,}} TMS, ppm): 61.33 (6H, br s), 1.50~1 · 70 (4H, m), 1.72~1.83 (2H, m), 2.07~2.17 (2H, m), 2.78 to 2.84 (1H, m), 3.58 to 3.72 (4H, m), 4.50 (1H, d, J = 5.5Hz), 8.97 (1H, s).

Example 1 1 55

Example 1 By a reaction operation similar to that of 16-, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.913 g, 3. OOmmol) and 3-methylcyclopentyl iodide (0.882g, 4.20mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) A colorless transparent oil (0.132 g, 11.4%) of methyl sulfonyl] -2- (3-methylcyclopentyl) acetate was obtained. 'H-NMRCCDCh, TMS, ppm): <50.9 5 to 1.60 (12H, m), 1.65 to 2.40 (4H, m), 2.65 to 2.85 (1H, m), 3.50 to 3.70 (4H, m), 3.73 (3H, s), 4.16 to 418 (1H, m), 8.9K1H, s).

Example 1 56

^Et , Miao

Et

By the same reaction procedure as in Example-116, 2-[(1-Jetylcarbamo Reaction of ethyl 1H-1,2,4-triazol-3-yl) sulfonyl] ethyl acetate (0.955 g, 3.00 mmol) with 3-methylcyclopentyl iodide (0.830 g, 3.95 mmol) The colorless and transparent oily substance of 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2- (3-methylcyclopentyl) ethyl acetate (0.125 g, 10.4%). 'H-NMRCCDCla, TMS, ppm): 50.9 4 to 1.02 (3H, m), 1.20 to 1.52 (12H, m), 1.68 to 2.40 (4H, m), 2.62 to 2.88 (1H, m), 3.45 3.73.75 (4H, m), 416〜4.22 (3H, m), 8.90 (1H, s).

Example 1 By a reaction operation similar to that of 16, a mixture of methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetate (0.761 g, 2.50 MIO1 ) And ^ -phenethyl bromide (0.35 mL, 2.56 mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -A colorless transparent oily product of methyl 4-phenylbutanoate (0.576 g, 56.4%) was obtained. _{- NMR (CDC1 3, TMS,} ppm): δ 1. 8 (. 6Η, t, J = 7 ΟΗζ), 2.43~2 · 57 (2Η, in), 2.67 (1Η, dt, J = 8.2 and 13.7Hz ), 2.80 (lH, dt, J = 4.3 and 13.7Hz), 3.50-3.70 (4H, m), 3.74 (3H, s), 4.2K1H, dd, J = 10.4 and 4.3Hz), 7.15 (2H, m ), 7.2K1H, m), 7.29 (2H, m), 8.88 (1H, s). Example 1 1 58

 O

^ET , N ^A NV ^S v ^C00Me

E • t N ―

Example 1 By a reaction operation similar to that of 116, methyl 2-[((1-ethylethylcarbamoyl-1H-1, 2,4-triazol-3-yl) sulfonyl] acetate (0.761 g, 2.50 mmol) ) And phenethyl bromide (0.35 mL, 2.56 mmol) to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -3 A white solid of methyl-phenylbutanoate (0.482 g, 47.2%) was obtained. mp: 99.1~100.4 ° C; - NMR (CDC1 3, TMS, ppm): δ I.26 (. 6Η, t, J = 7 ΟΗζ), 1.36 and 1.60 (total 3H, each d, J = 7.0Hz) , 3.38 and 3.89 (total 3H, each s), 3.50 to 3.70 (4H, m), 3.73 and 3.79 (tota 1 IH, each dq, J = 7.0, 11.0Hz and 7.0, 10.lHz), 4.55 and 4.83 ( total IH, each d, J = ll.0 and 10.0Hz), 7.09 to 7.30 (5H, m), 8.62 and 8.93 (total IH, each s).

Example 1 1 59

Example 1 By a reaction operation similar to that of 16, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propyl acetate (0.83 lg, 2.50 minol) ) And polyphenylbromide (0.35 mL, 256 mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -Colorless transparent oily substance of propyl 3-phenylbutanoate (0.63 Og, 57.7%). _{^{: H-NMR (CDC1 3,}} TS, ppm): <50.68 and 0.99 (tota

13H, each t, J = 7.3Hz), 1.20-1.36 (6H, m), 1.38 and 1.60 (total 3H, each d, J = 7.0Hz), 1.75 and 3.47 (total 2H, each tq, J = 7.0 and 7.3Hz), 3.50-3.86 (7H, m), 4.54 and 4.81 (total 1H, each d

, J = 10.1 and 11.0Hz), 7.04 to 7.28 (5H, m), 8.63 and 8.93 (total 1

H, each s).

Example 1 By a reaction operation similar to that of 16, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] isopropyl acetate (0.831 g, 2.50 mmol) ) And 3-phenethyl bromide (0.35 mL, 2.56 mmol) to give 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -A colorless transparent oily product of isopropyl 3-phenylbutanoate (0.568 g, 52.0%) was obtained. ^ -NMRCCDC, TMS, ppm): (50.76 and 0.94 (total 3H, each d, J = 6.1 and 6.4Hz), 1.20-1.34 (9H, m), 1.38 and 1.60 (total 3H, each d, J = 7.0Hz), 3.40 to 3.84 (5H, m), 4.62 and 5.20 (total 1H, each qq, J = 6.1 and 6.4Hz), 4.50 and 4.75 (total 1H, each d, J = ll.0 and 10.0 Hz), 7.05--28. (5H, m), 8.63 and 8.93 (total 1H, each s). Example 6 1

Example 1 By a reaction operation similar to that of 16, methyl 2-[(trimethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.913 g, 3. Ommol ) And 1- (2-trifluoromethylphenyl) ethyl iodide (1,08 g, 3.55 mmol) to give 2-[(1-getylcarbamoyl-1H-1,2,4- A white solid (0.102 g, 7.14%) of methyl triazole-3-yl) sulfonyl] -3- (2-trifluoromethylphenyl) butanoate was obtained. mp: 150.5 ~ 151.3 ° C;

7.0Hz), 3.51 (4H, m), 3.84 (3H, s), 4.26 (1H, dq, J = 7.0 and 7.9Hz), 4.80 (1H, d, J = 7.9Hz), 7.22 to 7.28 (2H, m), 7.30 to 7.35 (1H, m), 7.59 (1H, d, J = 7.9Hz), 8.76 (1H, s).

Example 1 By a reaction operation similar to that of 16, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.761 g, 2.50 imnol ) And benzyl chloride (0.29 mL, 2.52 mmol) were reacted to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazoyl-3-yl) sulfonyl] -3 A colorless transparent oily substance of methyl-phenylpropionate (0.840 g, 84.8%) was obtained. _{^{! H-NMR (CDC1 3,}} TMS, ppm): δ \ .32 (. 6Η, t, J = 7 OHz), 3.4 2 (1H, dd, J = ll.3 and 13.7Hz), 3.55 (1H, dd, J = 3.7 and 13.7Hz), 3.5-3.7 (4H, m), 3.65 (3H, s), 4.52 ( 1H, dd, J = ll.3 and 3.7Hz), 7.15 to 7.30 (5H, m), 8.92 (1H, s).

Example 1 By a reaction operation similar to that of 16, a mixture of methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.761 g, 2.50 bandages) was obtained. ol) and 4-fluorobenzyl chloride (0.32 mL, 2.57 mmol) to give 2-[(Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) A colorless transparent oil (0.540 g, 52.4%) of methyl sulfonyl] -3- (4-fluorophenyl) propionate was obtained. _{NMR (CDC1 3, TMS, ppm} ): δ 1 .32 (. 6Η, t, J = 7 ΟΗζ), 3.40 (1Η, dd, J = ll.6 and 14. OHz), 3.53 (1H, dd, J = 3.9 and 13.7Hz), 3-50 to 70 (4H, m), 3.65 (3H, s), 4.47 (1H, dd, J = ll.6 and 3.9Hz), 6.95 to 7.0 (2H , M), 7-1 to 7.2 (2H, m), 8.93 (1H, s).

^Et ,

Example 1 By the same reaction operation as in 116, 2-[(t Reaction of Methyl 1H-1, 2,4-Triazol-3-yl) sulfonyl] acetate (0.913g, 3.OOmmol) with 2- (bromomethyl) naphthalene (0.664g, 3.OOmmol) To a colorless, transparent oily product of methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -3- (2-naphthyl) propionate ( 0.536 g, 40.2%). _{- NMR (CDC1 3, TMS,} ppm): 51.31 (6H, t, J = 7.0Hz), 3.46~3 · 75 (9H, m), 4.64 (1H, dd, J = 4.0 and 11.3Hz), 7.27 ( 1H, d, J = 9.7Hz), 7.44 to 7.48 (2H, m), 7.64 (1H, s), 7.75 to 7.80 (3H, m), 8.93 (1H, s).

Example 1 By a reaction operation similar to that of 16, a mixture of methyl 2-[(1-acetylethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetate (1.22 g, 4. OO mmol) and 1-phenylpropyl iodide (1.20 g, 4.57 mmol) to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) A colorless transparent oil (0.536 g, 30.4%) of methyl sulfonyl] -3-phenylpenate was obtained. _{'Η - NMR (CDC1 3,} TMS, pm): δΰ.65 and 0.71 (tota 1 3H, each t, J = 7.0Hz), 1.10~1.20 (6H, m), 1.55~1.72 and 2.30 ~ 2.45 (total 2H, each m), 3.34 and 3.92 (total 3H, each s), 3.40 to 3.65 (5Η, m), 4.63 and 4.88 (total 1H, each d, J = 10.7Hz), 7.00 to 740 (5Η, m), 8.61 and 8.92 (total 1H, each s). Example 1 1 6 6

 Example 1 By a reaction operation similar to that of 16, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] ethyl (0.955 g, 3.00 g) Ol) and 1-phenylpropyl iodide (0.865 g, 3.30 IMO1) were reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl). Sulfonyl]-colorless transparent oil of ethyl 3-phenylpentanoate (0.

564 g, 31.5%).

TMS, ppm): 50.62 to 0.98 (6H, m), 1.24 to 1.40 (6H, m), 1.58 to 1.72 and 2.20 to 2.60 (total 1H, each m), 3,40 to 3.70 (5H, m), 3.75 ~ 3.84 (1H, m), 4.38 (2H, q, J = 7.3Hz), 4.61 and 4.81 (total 1H, each d, J = ll.0 and 10.7Hz), 7000 ~ 7.40 (5H, m), 8.60 and 8.92 (total 1H each s).

Example 1 By a reaction operation similar to that of 16, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propyl acetate (0.998 g, 3. OO mmol) and 1-phenylpropyl iodide (0.950 g, 3.62 mmol) are reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) A colorless transparent oily product of propyl sulfonyl] -3-fluoropentanoate (0.581 g, 41.5%) was obtained. _{^{! H-NMR (CDC1 3,}} TMS, ppm): 50.64~0.72 an _{1 g}

d 1.00 ~ 1.03 (total 6H, each m), 1.22 ~ 1.34 (6H, m), 1.60 ~ 1.82 and 2.38 ~ 2.47 (total 4H, each m), 3.40 ~ 3.74 (6H, m), 4.24 ~ 4.3 2 ( 1H, m), 4.62 and 4.86 (total 1H, each d, J = ll.0 and 10.7Hz), 7.00 to 7.28 (5H, m), 8.60 and 8.92 (total 1H, each s). 1 6 8

 ί?

 N

Et

Example 1 By the same reaction operation as in 116, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] isopropyl acetate (0.998 g, 3. OOmmol) and -trifluoropropyl iodide (0.865g, 3.30mmol) to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl A colorless, transparent oil of isopropyl 3-phenylpentanoate (0.578 g, 41.3%) was obtained. 'H-NMRCCDCla, TMS, ppm): 50.66 and 0.71 (total 3H, each t, J = 7.0Hz), 0.76 and 0.91 (total 3H, each d, J = 6.1Hz), 1.20 to 1.38 (9H, m ), 1.58 to 1.80 and 2.35 to 2.50 (total 2H, each m), 3.40 to 3.70 (5H, m), 4.58 and 5.23 (total 1H, each sep, J = 6.1Hz), 4.58 and 4.80 (total 1H, each d, J = ll.0 and 1 0.4Hz), 7.00 ~ 7.42 (5H, m), 8.61 and 8.92 (total 1H, each s).

Example 1 By the same reaction operation as in 116, 2-[(t Reaction of methyl yl-1H-1,2,4-triazolyl-3-yl) sulfonyl] acetate (0.612 g, 2. Olmmol) with aryl bromide (0.175 mL, 2.02 mmol) Colorless transparent oil of methyl 2-, ([tetethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -4-pentenoate (0.210 g, 30.5%) I got

_{NMR (CDC1 3, TMS, ppm} ):.. Δ 1. 32 (. 6Η, t, J = 7 1Hz), 2. 85~3 00 (2H, m), 3. 50~3 70 (4H, m ), 3.74C3H, s), 4.22 (1H, dd, J = 4.0 and 10.8 Hz), 5.10 to 5.20 (2H, m), 5.65 to 5.78 (1H , m), 8.92 (1H, s).

 Example 1 By a reaction operation similar to that of 116, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] acetate (0.761 g, 2 50 marl ol) and 3-chloro-2--2-methyl-1-propene (0.25 mL, 2.53 mmol) to give 2-[(1-Jetylcarbamoyl-1H-1,2,4 -Triazol-3-yl) sulfonyl] -4-methyl-4-pentenoate was obtained as a colorless transparent oil (0.664 g, 74.1%). 'H-NMRCCDCl a, TMS, ppm): δ I. 32 (6Η, t, J = 7.0 Hz), 1.75 (3H, s), 2.85 to 2.90 (2H, m), 3 50 to 3.70 (4H, m), 3.74 (3H, s), 4.44 (1H, dd, J = 6.4 and 9.1 Hz), 4.74 (1H, s), 4 84 (1H, s), 8.92 (1H, s).

 {} o ,, o o o o

· S 'COO e _Et IJ N COOMe

Et—human Example—1—Jetylcarbamoy Methyl -1H-1,2,4-triazol-3-yl) sulfonylacetate (0.761 g, 2 • 50 mmol) and 3-chloro-1-butene (0.26 mL, 2.58 bandol) To give 2-[(1-Gethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -3-methyl-4-methyl 4-pentenoate as a colorless transparent oil (0.425 g, 47.4%). - title _{R (CDC1 3, TMS, ppm} ): 51.32 (. 6H, t, J = 7 OHz), 1.6 2~L67 (3H, m), 2.78~3.00 (2H, m), 3 · 50~3.70 ( 4H, m), 3.74 (3H, s), 4.24 and 4.26 (total 1H, each d, J = 4.8 and 4.2Hz), 5.25 to 5.45 (1H, m), 5.55 to 5.65 (1H, m), 8.92 (1H, s). Example 1 1 72

 COOMe

Example 1 By the same reaction operation as in 116, methyl (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonylacetate (0.761 g, 2 • 50 mmol) was obtained. ) And methyl bromoacetate (0.24 mL, 2.53 mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] -A white solid of methyl 3-methoxycarbonylpropionate (0.340 g, 36.1%) was obtained. mp:. 96.0~97 · 5 ° C ; - NMR (CDC1 3, TMS, ppm): (51.32 (6H, t, J = 7 OHz), 3.27 (2H, d, J = 7.3Hz), 3.60 (4H , q, J = 7. OHz), 3.72 (3H, s), 3.75 (3H, s), 4.78 (1H, t, J = 7.3Hz), 8.9K1H, s).

^Et

Example 1 By the same reaction operation as in 16, (1-Jetylcarbamoy , _Λ

Reaction of dimethyl 124-l-1Η-1,2,4-triazol-3-yl) thiomalonate (0.661 g, 2.0 mmol) with isobutyl iodide (0.26 mL, 2.26 mmol) To a colorless, transparent oily product of methyl 2-[[1- (1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) thio] -2 -methoxycarbonyl-4-methylpentanoate ( 0.411 g, 53.2%). 'H-NMRCCDCh, TMS, ppm): <5 0.90 (6H, d, J = 6.4 Hz), 1.28 (6H, t, J = 7.0 Hz), 2.02 to 2.20 ( 3H, m), 3.40 to 3.85 (10H, m), 8.76 (1H, s).

Example 1 By a reaction operation similar to that of 16, methyl 2-[[alpha] -ethylmethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propionate (0.637 g, After reacting 2.00 ol ol) with iodide chill (0.20 mL, 2.46 marl ol), 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3 -Yl) sulfonyl]-methyl 2-methylbutanoate as a white solid (0.280 g, 40.4%) was obtained. mp: 72.5 to 73 ° C; ^ -NMRCCDC, TMS, ppm): δ 0.96 (3H, t, J = 7.5Hz), 1.31 (6H, t, J = 7.0Hz) ), 1.68 (3H, s), 2.40 (2H, q, J = 7.5 Hz), 3.60 (4H, q, J = 7.0 Hz), 3.73 (3H, s) , 8.89 (1H, s).

By the same reaction procedure as in Example-116, 2- [α-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] methionate was used. _Λ _ _

丄 ^ b (0.796 g, 2.50 mmol) was reacted with propyl bromide (0.225 mL, 2.75 mmol) to give 2-[(tridecylcarbamoyl-1H-1,2,4-triazole). A colorless transparent oil (0.325 g, 36.1%) of methyl -3-yl) sulfonyl] -2-methylpentenoate was obtained. _{- NMR (CDC1 3, TMS,} ppm): 50.91 (3H, t, J = 7.3Hz), 1.08~1.22 (1H, m), 1.30~1.40 (7H, m), 1.68 (3H, s), 1.98~ 2. 06 (1H, m), 2.34 to 2.42 (1H, m), 3.50 to 3.70 (4H, m), 3.73 (3H, s), 8.90 (1H, s).

^Et ,

Example 1 By the same reaction procedure as in 116, methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propionate (0.796 g, 2.50 2-((1-Jetylcarbamoyl-1H-1,2,4-triazol-3-ynole) sulfonyl] was reacted with butyl bromide (0.32 mL, 2.98 mmol). A colorless, clear oily product of methyl 2--2-methylhexanoate (0.329 g, 35.1%) was obtained. _{^ -NMR (CDC1 3, TMS,} ppm): 50.96 (3H, t, J = 7.3Hz), 1.12~1.35 (9H, m), 1.40~1.52 (1H, m), 1.68 (3H, s), 1.96 Up to 2.0 4 (1H, m), 2.30 to 2.37 (1H, m), 3.50 to 3.70 (4H, m), 3.73 (3H, s), 8 • 90 (1H, s).

^Et , "people

 N

 Et

Example 1 2-[(1-Jetylcarbamo Reaction of methyl -1H-1,2,4-triazole-3-yl) sulfonyl] propionate (0.796 g, 2.50 mmol) and isobutyl iodide (0.29 mL, 2.52 mmol) Colorless and transparent oily substance of methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2,4-dimethylpentenoate (0.628 g , 67.1%). 'H-NMRCCDCls, TMS, ppm): δθ.77C3H, d, J = 6.6 Hz), 0.99 (3H, d, J = 6.6 Hz), 1.32 (6H, t, J = 7.0 Hz), 1.70 (3H, s), 1.70-1.80 (1H, m), 2.1K1H, dd, J = 4.6 and 13.7Hz), 2.23 (1H, dd, J = 9.2 and 13.7Hz), 3.50-3.70 (4H, m), 3.73 ( 3H, s), 8.91 (1H, s).

Example 1 By a reaction operation similar to that of 16, meth-2-one [0.7-g of 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] propionate , 2.50 mmol) and benzyl chloride (0.330 mL, 2.60 mmol) were reacted to give 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl). A white solid of methyl [sulfonyl] -2-methyl-3-phenylpropionate (0.709 g, 69.4%) was obtained. mp: 100~100.5 ° C; MR ( CDC1 3, TMS, p pm): (51.32 (6H, t, J = 7.0Hz), 1.58 (3H, s), 3.17C1H, s), 3.32 (1H, s ), 3.61 (4H, q, J = 7.0Hz), 3.7K3H, s), 7.03-7.31 (5H, m), 8.94 (1H, s). Example 1 1 9

Example 1 By a reaction operation similar to that of 16, methyl 2-[(1-ethylethylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propionate (0.800 g, 2.5111111101) and 2,4-dimethylbenzyl chloride (0.37111 2.53 dragonol) were reacted to give 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazole-3- [Yl] sulfonyl] -2-methyl-3- (2,4-dimethylphenyl) colorless transparent oil (0.810 g, 73.9%) of methyl propionate was obtained. _{^ - NM R (CDC1 3,} TMS, ppm): δ 1.32 (6Η, t, J = 7.1Hz), 1.54 (3H, s), 2.27 (3 H, s), 2.28 (3H, s), 3.5K1H , s), 3.55 (1H, s), 3.60 (4H, q, J = 7.1 Hz), 3.74 (3H, s), 6.82 (1H, d, J = 7.9 Hz), 6.89 (1H, d, J = 7.9Hz), 6.99 (1H, s), 8.94 (1H, s).

Example 1 By a reaction operation similar to that of 16, methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propionate (0.797 g, 2.50 iMol) and 4- 1-butylbenzyl chloride (0.46 mL, 2.50 mmol) were reacted to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazole-3- A white solid (0.950 g, 81.8%) of methyl [yl] sulfonyl] -2-methyl-3- (4-t-butylphenyl) propionate was obtained. mp: 105.5~106.0 ° C; - NMR (CDC1 3, TMS, ppm): δ 1.28 (9H, s), 1.32 (6H, t, J = 7.0Hz ), 1.57 (3H, s), 3.13 (1H, s), 3.28 (1H, s), 3.60 (4H, q, J = 7.0Hz), 3.72 (3H, s), 7.00 (2H, d, J = 8.4Hz), 7.28 (2H, d, J = 8.4Hz), 8.93 (1H, s).

Example 1 18 1 f? O, o

 Et, .s OOMe

N ^ν , r γ

 Et He N

Example 1 By a reaction operation similar to that of 16, methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propionate (0.797 g, 2.50 mmol) ) And aryl bromide (0.22 mL, 2.54 bandol) to give 2-[(1-getylcarbamoyl-1H-1,2,4-triazolyl-3-inole) sulfonyl]- A white solid of methyl 2-methyl-4-pentenoate (0.836 g, 93.3%) was obtained. mp: 60, 0~61.0 ° C; MR (CDC1 3, TMS, ppm): 61.32 (. 6 H, t, J = 7 lHz), 2.17 (3H, s), 2.73C1H, dd, J = 8.2 and 13.7Hz), 3.18 (1H, dd, J = 6.7 and 13.7Hz), 3.50 to 3.70 (4H, m), 3.73 (3H, s), 5.18 to 5.23 (2H, m), 5.58 to 5.68 (1H , m), 8.9K1H, s).

Example 1 1 82

 ο ο,, ο

^ET , N people N ' ^{NS C00Me} f! 0 ^,, 0

 ^, T ^ ,, 义 ^ :, S COOMe

 Et N ► N N Get X

 Et ^ =, ^ ~ =

By the same reaction operation as in Example _116, methyl 2-[(1-getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] propionate (0.797 g, The reaction between 2.5 MIO1) and propargyl bromide (0.225 mL, 2.52 mmol) was carried out to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl. ]-Colorless clear oil of methyl 2--2-methyl-4-pentate (0.697 g, 78.2%) was obtained. _{^{: H - NMR (CDC1 3 TMS}} , ppm) 51.32 (6H, t J = 7.0Hz), 1.84 (3H, s), 2.08 (1H, t, J = 2.8Hz), 2.92 (1H, dd J = 2.8 and 16.5Hz), 3.39 (1H, dd J = 2.5 and 16.5Hz), 3.50 3.70 (4H, m), 3.76 (3H, s), 8.92 (1H, s).

Et.

Example 1 By a reaction operation similar to that of 16, methyl 2-[(trimethylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] butanoate (0.832 g 2.50 mmol ) And propyl bromide (0.28 mL, 3.08 mmol) to give 2-[(1-Getylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2- A colorless transparent oily product of methyl ethylpentanoate (0.242 g, 25.8%) was obtained. _{- NMR (CDC1 3, TMS,} ppm) 60.97 (3H, t J = 7.3Hz), 1 .08 (3H, t, J = 7.3Hz), L 16 1.40 (7H, m), 1.58 1.68 (1H, m ), 2.0 6 2.13 (1H m), 2.14 2.28 (2H m), 2.30 2.39 (1H m), 3.50 3.70C4H, m), 3.7K3H, s), 8.89 (1H, s). 1 84

^Et

Example 1-1 By the same reaction procedure as in 116, methyl 2-[(1-ethylethylcarbamoyl-1H-1 2,4-triazol-3-yl) sulfonyl] butanoate (0.832 g, 2.50 mmol) and butyl bromide (0.32 mL, 2.98 mmol) to give 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfur A colorless and transparent oily product of methyl [ruphonyl] -2-ethylhexanoate (0.229 g, 23.6%) was obtained. 'H-NMRCCDCb, TMS, ppm): ό 0.93 (3H, t, J = 7.3 Hz), 1.09 (3H, t, J = 7.3 Hz), L 16-1.60 (10H, m), 2.10-2.40 ( 4H, m), 3.50 to 3.70 (4H, m), 3.71 (3H, s), 8.89 (1H, s).

 S o, 'o? , 0 0

^Eu N ^A N

Et -VN ^s rk ^C0

^{0Me E} N ^A N

Et-VN ^s V ^C0 ? ^Me By the same reaction procedure as in Example 116, 2-[(1-Getylcarbamoyl-1H-1,2,4-triazolyl-3-yl) sulfonyl] butane The reaction between methyl citrate (0.831 g, 2.50 mmol) and isobutyl iodide (0.29 mL, 2.52 mmol) was carried out to give 2-[(trimethylcarbamoyl-1H-1,2,4-triazole-3- (Inore) Sulfonyl] -2-ethyl-4-methylpentanoate as a white solid (0.768 g, 79.0%) was obtained. mp: 51.1~51.5 ° C; - NMR (CDC1 3, TMS, ppm): ά 0.8 0 (3H, d, J = 6.6Hz), 1.02 (3H, d, J = 6.7Hz), 1.2K3H, t, J = 7.3Hz), 1.32 (6H, t, J = 6.7Hz), 1.81 ~ 1.90 (1H, m), 2.05 ~ 2.15 (2H, ra), 2.29 (1H, dd, J = 4.6 and 14.0Hz ), 2.41 to 2.50 (1H, m), 3.50 to 3.70 (4H, m), 3.70 (3H, s), 8.90 (1H, s).

Et. •

Under an argon atmosphere, a suspension of hydrogenated sodium (0.197 g, 4.93 tmol) in DMF (lm L) was added with (1-getylcarbamoyl-1H-1,2,4-triazol-3-). I F) A solution of methyl sulfonyl acetate (0.761 g, 2. Olmmol) in F (7 mL) was added at 0 ° C. After stirring at 0 ° C for 15 minutes, propargyl bromide (0.485 mL, 5.44 mmol) was added, and the mixture was stirred for 1.5 hours while gradually warming to room temperature. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (15 mL), and extracted with getyl ether (15 mL × 3 times). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride (10 mL), and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to obtain a crude product. Purification of this product by silica gel column chromatography (Co-gel C-200, ethyl acetate: hexane = 1: 2) yielded 2-[(tragetylcarbamoyl-1H-1,2,4- Triazole-3-yl) sulfonyl] -2-prono. A yellow solid of lugyl-4-pentinate (0.230 g, 24.2%) was obtained. mp: 98.0~99.0 ° C; NMR ( CDC1 3, TMS, ppm): SI.33 (6H, t, J = 7.0Hz), 2.03 (2H, t, J = 2.6Hz), 3.36 (4 H, d , J = 2.6Hz), 3.51 (4H, q, J = 7.0Hz), 3.8K3H, s), 8.90 (1H, s).

Et _ti

Under an argon atmosphere, a suspension of sodium hydride (0.060 g, 1.50 mmol) in DMF (lm L) was added to (1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl). ) A solution of methyl sulfonyl acetate (0.295 g, 0.97 mmol) in DMF (2 mL) was added at 0 ° C. After stirring at 0 ° C for 30 minutes, thiol iodide (0.08 mL, 0.984 mmol) was added, and the mixture was stirred for 4.5 hours while gradually warming to room temperature. After completion of the reaction, the reaction solution was added to 1N-hydrochloric acid (15 mL) and extracted with getyl ether (8 mL × 3). Combine the organic layers and wash with saturated aqueous sodium chloride solution (10) And dried over anhydrous magnesium sulfate. After the desiccant was filtered off, the filtrate was concentrated under reduced pressure to obtain a crude product. This product was purified by silica gel column chromatography (Co-gel C-200, ethyl acetate: hexane = 1: 2) to give 2-[(1-methylethylcarbamoyl-1H-1 Colorless transparent oil (0.160 g, 49.6%) of methyl 2,2,4-triazol-3-yl) sulfonyl] butanoate and 2-[(trimethylcarbamoyl-1H-1,2,4-triazo There was obtained a white solid (0.025 g, 7.15%) of methyl (l-3-yl) sulfonyl] -2-ethylethylbutyrate.

Methyl 2-[(1-Jetylcarbamoyl-1H-1,2,4-triazolyl- _3- yl) sulfonyl] butanoate: ¹ !!-NMR (CDC13, TMS, ppm): δ ΐ .05 (3H, t, J = 7.

3Hz), 1.32 (6H, t, J = 7.0Hz), 2.26 (2H, m), 3.60 (4H, q, J = 7.0Hz), 3.76 (3H, s), 4.16 (1H, t, J = 7.6 Hz), 8.90 (1H, s).

2-[(1-Jetylcarbamoyl-1H-1,2,4-triazol-3-yl) sulfonyl] -2-ethylmethylbutanoate: mp: 72.5-73.0 ° C; 'H-NMR _{(CDC1 3, TM S, ppm} ): δ ΐ.07 (6H, t, J = 7.3Hz), 1.3K6H, t, J = 7.0Hz), 2.24 (2H, q, J = 7.3Hz), 2.30 ( 2H, q, J = 7.3Hz), 3.60 (4H, q, J = 7.0Hz), 3.71 (

3H, s), 8.88 (1H, s).

HM ' ^N ^ ^SH , NS ^ COOMe

3-mercapto-1,2,4-triazole (5.06 g, 50. Ommol), methyl bromoacetate (4.74 mL, 50 lmmol) and potassium carbonate (5.18 g, 37.4 mmol) in acetonitrile (100 mL) The solution was heated at reflux for 1.5 hours. After completion of the reaction, the reaction mixture was allowed to cool to room temperature, added to water (50 mL), and extracted with getyl ether (40 mL × 3). The organic layers were combined, washed with a saturated aqueous sodium chloride solution (300 mL), and dried over anhydrous magnesium sulfate. Filter the dried 剂 After separation, the filtrate was concentrated under reduced pressure to obtain a white solid (6.06 g, 70.0%) of methyl (1H-1,2,4-triazol-3-yl) thioacetate. mp:. 112~ 113 ° C; - NMR (CDC1 3, TMS, ppm): 53.78 (3H, s), 3.90 (2H, s), 8.1 3 (1H, s), 12.4C1H, br s) Reference Example One two

Acetonitrile of 3-mercapto-1,2,4-triazole (3.04 g, 30.1 leaked ol), methyl bromoacetate (2.85 mL, 30.lmmol) and potassium carbonate (3.llg, 22.5 mmol) (90 mL) The solution was heated to reflux for 2 hours. Next, the reaction solution was allowed to cool to room temperature, and then potassium carbonate (3.1 g, 22.5 mmol) and getylcarbamoyl chloride (4.2 mL, 33.3 mmol) were added. After stirring at 50 to 60 ° C for 1.5 hours, the reaction solution was added to 1N-hydrochloric acid (100 mL), and extracted with ethyl acetate (40 inL x 3 times). The organic layers were combined, washed with a saturated aqueous solution of sodium chloride (20 mL), and dried over anhydrous magnesium sulfate. After filtering off the dried product, the filtrate was concentrated under reduced pressure to obtain a crude product. The product was purified by silica gel column chromatography (一 -gel C-200, ethyl acetate: hexane = 1: 2) to give (1-getylcarbamoyl-1H-1,2,4-triglyceride). A white solid (5.85 g, 71.4%) of methyl azo-3-yl) thioacetate was obtained. mp: 90~90.5 ° C; - NMR (CDC1 3, TMS, ppm): ό 1.27 (6H, t, J = 6.8Hz),

3.59 (4H, q, J = 6.8Hz), 3.75 (3H, s), 3.93 (2H, s), 8.74 (1H, s). Reference Example-3

 SH CN HN HN ^

 : N N

According to the same reaction procedure as in Reference Example 1, 3-mercapto-1,2,4-triazole (4.00 g, 39.6 · 1) and chloroacetonitrile (2.75 mL, 43.6 mmol) were reacted. A brown solid of 1H-1,2,4-triazol-3-yl) thioacetonitrile (2.66 g, 48.0%) was obtained. mp:. 106.6~107.1 ° C; ' H-NMR (CDC1 3, TMS, ppm): 53.95 (2H, s), 8.22 (1H, s), 13.87 (1H, br s) Reference example of 4

 O

^Et , N people N'N

 N

By performing the reaction in the same manner as in Reference Example 2 except that chloroacetonitrile was used instead of methyl bromoacetate, (1-getylcarbamoyl-1H-1,2,4-triazole-3-y L) A white solid (49.7%) of thioacetonitrile was obtained. Soku: 124.9~125.3 ° C; - NMR ( CDC1 3, TMS, ppm): (1.32 (6H, t, J = 6.5Hz), 3.63 (4H, br s), 3.89 (2H, s), 8.8K1H, s). Reference Example 1 5

Ethyl 2-hydroxy-2- (1-cyclohexenyl) acetate (9.21 g, 50.0 orchid 01) and trifidylphosphine (17.2 g, 65.6 mmol) in carbon tetrachloride (450 m "

The 13ο solution was heated to reflux for 1.5 hours. After the completion of the reaction, the reaction mixture was allowed to cool to room temperature, pentane (20 raL) was added, and the insoluble matter was filtered off. The filtrate was concentrated under reduced pressure, pentane (20 mL) was added again to the obtained residue, the insoluble matter was filtered off, and the filtrate was concentrated under reduced pressure. This operation was repeated once more to obtain a crude product. The product was purified by silica gel column chromatography (Co-gel C-200, ethyl acetate: hexane = 1: 3) to give 2-chloro-2- (1-cyclohexenyl) ethyl acetate. A yellow oil (9.40 g, 92.8%) was obtained. ^ -NMRCCDCl, TMS, ppm): δ I.29 (3H, t, J = 7.5Hz), 1.61 (4H, m), 2.1K4H, m), 4.24 (2H, q, J = 7.5Hz), 4.8K1H, s), 5.92 (1H, m). Reference Example 6

A solution of ethyl 2- (1-hydroxyhexenyl) acetate (1.85 g, 10.Ommol) in ethanol (10 mL) in the presence of Pd / C (50¾wet, 0.925 g) in a hydrogen atmosphere was used. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, the catalyst was separated by filtration, and the filtrate was concentrated under reduced pressure to obtain an oily substance of 2-hydroxy-2-cyclohexylethyl acetate (1.853 g, 99.5%). Then, a solution of the obtained 2-hydroxy-2-ethyl-2-cyclohexylacetate (1.85 g, 9.93 ol) and trifluorophosphine (3.38 g, 12.9 mmol) in carbon tetrachloride (10 mL) was added for 2.5 hours. Heated to reflux. After the completion of the reaction, the reaction mixture was allowed to cool to room temperature, pentane (1 OmL) was added, and insolubles were separated by filtration. The filtrate was concentrated under reduced pressure, pentane (10 mL) was added again to the obtained residue, insolubles were separated by filtration, and the filtrate was concentrated under reduced pressure. By repeating this operation once again, a colorless and transparent oily substance of ethyl 2-ethyl-2-cyclohexylacetate as a target substance was quantitatively obtained. -NMR (CDCI3, TMS, ppm): (1.05 ~ L 34 (9H, m), 1.60 ~ 1.72 (2H, m), 1.75 ~ 1.82 (2H, m), 1.86 ~ 1.97 (1H, m), 4.06 (1H, m d, J = 7. OHz), 4.24 (2 H, q, J = 7. OHz).

A mixture of 2-hydroxy-2- (4-methylphenyl) acetonitrile (5.01 g, 34.0 mmol) and 6N-hydrochloric acid (60 mL) was heated under reflux for 15 hours. After the reaction is completed, add 4N-sodium hydroxide aqueous solution to the reaction solution to adjust pH. ~ 8 and washed with dimethyl ether (40 mL). Next, 1N-hydrochloric acid was added to the obtained aqueous layer to adjust the pH to 1, followed by extraction with ether (40 mL × 3). The organic layers were combined, washed with saturated saline (50 mL), and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure to obtain a crude product. This was recrystallized from ethyl acetate / hexane to give a white solid of 2-hydroxy-2- (4-methylphenyl) acetic acid (1.49 g, 26.4%). Next, the obtained 2-hydroxy-2- (4-methylphenyl) acetic acid (0.5 g, 3. Ommo 1) was added to a solution of thionyl chloride (0.25 mL, 3.43 marl) in methanol (5 mL) with ice cooling. It was added under stirring. After the reaction solution was stirred for 4 hours while gradually warming to room temperature, the solvent was distilled off under reduced pressure. Toluene (10 mL) was added to the obtained residue, and toluene was distilled off under reduced pressure to remove excess thionyl chloride by azeotropy. Thus, white methyl 2-hydroxy-2- (4-methylphenyl) acetate was obtained. A solid (0.53 g, 98.6%) was obtained. Next, the obtained methyl 2-hydroxy-2- (4-methylphenyl) acetate (1.13 g, 6.27 mmol) and triphenylphosphine (2.1 丄 <5

A solution of 6 g, 8.24 mmol) in carbon tetrachloride (5 mL) was heated to reflux for 1.5 hours. After completion of the reaction, the reaction mixture was allowed to cool to room temperature, hexane (10 mL) was added, and insolubles were filtered off. The filtrate was concentrated under reduced pressure to obtain an oily substance of methyl 2-chloro-2- (4-methylphenyl) acetate (1.14 g, 91.6%). 'H-NMRCCDCl s, TMS, ppm): (5 2.23 (3H, s), 3.77 (3H, s), 5.34 (1H, s), 7.19 (2H, d, J = 8.0 Hz), 7.38 (2H, d, J = 8.0 Hz). Reference Example 8

To a solution of ethyl 2-hydroxy-3-methyl-3-butenoate (10. Og, 69.4 mmol) in anhydrous dichloromethane (200 mL) at 0 ° C under an argon atmosphere at 0 ° C was added methyl zinc (1M hexane solution). , 242 mL, 242 bandol ol), and then jod methane (81.4 g, 278 mmol). After stirring the reaction solution at 0 ° C. for 30 minutes, it was heated to room temperature and further stirred at room temperature for 14 hours. After completion of the reaction, I-hydrochloric acid (400 mL) was added to the reaction solution, the organic layer was separated, and the aqueous layer was further extracted with dichloromethane (100 mL × 2). The organic layers were combined, washed with a saturated saline solution (200 mL), and dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and the filtrate was concentrated under reduced pressure to obtain 2-hydroxy-2- (1-methylcyclopropyl) ethyl acetate as a pale yellow oil (10.3 g, 93.7%). . 'H-NMRCCDCl. ,, TMS, ppm): S O. 39 ~ 0.43 (2H, m), 0.58 ~ 0.62 (1H, m), 0.71 ~ 0.75 (1H, m ), 1.02 (3H, s), 1.32 (3H, t, J = 7.lHz), 2.87 (1H, d, J = 5.0 Hz), 3.52 (1H, d, J = 5.0 Hz), 4.26 to 4.34 (2H, m). Reference Example-9

2-Hydroxy-2- (1-methylcyclopropyl) ethyl acetate (0.95 g, 6.0 rninol) and trifenylphosphine (2.05 g, 7.8 mmol) in carbon tetrachloride (6 mL) are heated at reflux for 4 hours. did. After the completion of the reaction, the reaction mixture was allowed to cool to room temperature, pentane (10 mL) was added, and insolubles were filtered off. The filtrate was concentrated under reduced pressure, pentane (10 mL) was added again to the obtained residue, and the insoluble material was separated by filtration. The filtrate was concentrated under reduced pressure to give 2-chloro-2- (1-methylcyclopropyl) acetic acid. A yellow oil of chill (0.84 g, 79.5%) was obtained. ^: H - title _{R (CDC1 3, TMS, ppm} ): SO.5 Doo 0.58 (1H, m), 0.61~0.66 (2H, m), 0.84~0.91 (1H, m), LI 8 (3H, s) , 1.31 (3H, t, J = 7.0 Hz), 3.80 (1H, s), 4.25 (2H, q, J = 7.0 Hz). Inventive compounds are shown in Tables 1 and 2 including the compounds synthesized in the above Examples, but the present invention is not limited thereto. The reaction formulas shown in Examples and Reference Examples, and the abbreviations for the substituents used in Tables 1 and 2 have the following meanings. Me: methyl; Et: ethyl; Pr: propyl; i-Pr: isopropyl; Bu: butyl; i-Bu: isobutyl; sec-Bu: secondary monobutyl; t-Bu: tertiary butyl

ν τ7 n D 2 n 7 D

Compound Example K K n

 = ∑Ι £. Ρ = Ι

Turn—

 Lt bt H H H H 2

4 L Me Me Me H H H 1 r

 5 Me Me Me H H Me l

6 Me Me Me H H H 2

7 Me Me Me H H Me 2

8 1 Et Et Me H H H l

9 Et Et Me H H Me 2

10 3 Et Et Me H H H 2

1 1 Et Et Et H H H l

12 8 Et Et Et H H H 2

13 Et Et Et H H Me 2

14 Et Et Pr H H H l

15 10 Et Et Pr H H H 2

16 Et Et Pr H H Me 2

17 Et Et i-Pr H H H l

18 12 Et Et i-Pr H H H 2

19 Et Et i-Pr H H Me 2

20 Et Et Bu H H H l

21 14 Et Et Bu H H H 2

22 Et Et Bu H H Me 2

23 Et Et i-Bu H H H l

24 16 Et Et i-Bu H H H 2

25 Et Et i-Bu H H Me 2

26 Et Et sec-Bu H H H l

27 54 Et Et sec-Bu H H H 2

28 Et Et Pentyl H H H l

29 18 Et Et Pentyl H H H 2

30 Et Et Pentyl H H Me 2

31 Et Et Cyclopentyl H H H l

32 Et Et Cyclopentyl H H Mel

33 39 bt bt Cyclopentyl H H H 2

 T

 34 Lt Et t-Bu H H H 1

35 41 ht ht t-Bu H H H 2 t t t-Bu H H Me

37 43 dani t t benzyl H H H 0 ο

 00 44 bt t benzyl TT TT

 H H

 40 Me Me benzyl H H u u

 Benzyl 0

4υ 4b Me Me H H H L

41 47 - teeth 2 H ϋ and ₂ H r benzyl HHH Y

 O r »TT

42 48 - teeth ₂ H benzyl HHH

 A ft I

4ο 49 / ΐ / Lil Hatsatsu Tu IT

 n Π U

44 50 Et Et Araryl H H H 2

45 51 Et Et MeO (CH ₂ ) ₂ HHH 0

46 52 Et Et Me0 (CH ₂ ) ₂ HHH 2

47 19 Et Et Et0C0CH ₂ HHH 0

48 Et Et Et0C0CH ₂ HHH 1

49 20 Et Et Et0C0CH _? HHH 2

50 21 Et Et Me0C0C (CH ₃ ) HHHH 0 Table 1 continued

 Treasure υ υ D 2 D 7

 Ι \ 1 K K p p 5 p 6

¾t n

 QQ 丄 1 丄 1 71 Et Et Pr i-Pr u n u n L n yn u 丄 丄 0 Et Et i-Pr i-Pr u n u n L

0 y 1

 丄 Et Et Bu i-Pr n n 0

 L

 0 oL9 Et Et i-Bu i-Pr u n u n 9

93 Et Et Pentyl i-Pr H H 2

94 120 Et Et Me Bu H H 2

95 176 Et Et Me Bu Me H 2

96 Et Et Me Bu Me Me 2

97 184 Et Et Me Bu Et H 2

98 69 Me Me i-Pr i-Bu H H 0

99 70 Me Me i-Pr i-Bu H H 2

100 84 Et Et H i-Bu HH 0 Continuation of 1

^ I 2 D 4 D 6 mouth 夹 她 WJ ϋ 7

 K n number

丄 Ul

丄 li

 1 no

 1 (Λ

丄 3D l b Et Et l-Bu i-Bu H H 2 丄 3 丄 Et Et sec-Bu -Bu H H 0

 Et * D ..

丄 Et sec-Bu l-DU H H L 丄 Et Et t-DU i-Bu H H

1 A 10 Ω Et Et. / • D,

 Nonal l-DU n Π L

 u loo Et Et // y / ί n 口 口 ノ ナ ル il • D

 l-DU n xl 丄 db Et Et • D

 ぺ Nonl l-DU n Π

Et Et Ma Π 11] 1,

 Le l-DU rl Π 0

100

ids 1 'D,, u

 丄 oSnU Et Et ιτ ΠΡ

 U3 U then 2 Π4 1 ~ DU n 0

 Π L

 1 on ec-Bu 0

 丄 Et Et Me s n n

1 n

14U Et Et Me 0d. /

 —Heno: Na £ le ii, H n u

141 0

 丄 dt) Et Et Me 0. , /) 1,

 d—Henonal il Π

1 A 0 Et Et L and go to 0 d—. , Nominal, n Π

143 Et Et Pr 3-Pentyl H H 2

144 Et Et i-Pr 3-pentyl H H 2

145 137 Et Et Me 2-methylbutyl H H 2

146 172 Et Et Me CH ₃ OCOCH ₂ HH 2

147 143 Et Et Me CH ₃ SCH ₂ CH ₂ HH 2

148 Et Et Me CH ₃ OCH ₂ HH 2

149 144 Et Et Me NC (CH ₂ ) s HH 2

150 Et Et Me NCCH ₂ HH 2 Table 1

Chemical compound R ¹ R ² R 'R ⁵ R ⁶ n

151 Et Et Me Ciclop n-Pyrmethyl H H 2

152 Et Et Me Cyclopropyl H H 0

153 Serial Number Et Et Me Cyclopropyl H H 2

Et Et Me 1 -Methyl sig π-Provir H H 0

155 Italy 5 Et Et Me 1-Methylcycl π-propyl H H 1

156 Et Et Me 1 -Methylcycl π-propyl H H 2

157 57 Et Et Et 1-Methylc D-propyl H H 0

158 Et Et Et 1-Methyl cycl D propyl H H 1

159 58 Et Et Et 1-Methylcyclopropyl H H 2

160 146 Et Et Me Cyclopentyl H H 2

161 147 Et Et Et Cyclopentyl H H 2

162 148 Et Et Pr Cyclopentyl H H 2

163 149 Et Et i-Pr Cyclopentyl H H 2

164 151 Et Et Bu Cyclopentyl H H 2

165 152 Et Et i-Bu Cyclopentyl H H 2

166 153 Et Et t-Bu Cyclopentyl H H 2

167 150 Et Et Cyclopentyl Cyclopentyl H H 2

168 155 Et Et Me 3-Methyl π pentyl H H 2

169 156 Et Et Et 3 -Methyl π-pentyl H H 2

170 Et Et Pr 3-Methyl π pentyl H H 2

171 Et Et i-Pr 3-methylcycl πpentyl H H 2

172 61 Et Et Et Cyclohexyl H H 0

173 62 Et Et Et Cyclohexyl H H 2

174 138 Et Et Me Cyclopentylmethyl H H 2

175 139 Et Et i-Pr Cyclopentylmethyl H H 2

176 140 Et Et Me Cyclohexylmethyl H H 2

177 141 Et Et i-Pr Cyclohexylmethyl H H 2

178 169 Et Et Me Aryl H H 2

179 170 Et Et Me Metharyl H H 2

180 171 Et Et Me 3-butene-2-yl H H 2

181 92 Et Et Et 1 -Cyclohexenyl H H 0

182 Et Et Me Propargyl H H 2

183 186 Et Et Me Propargyl Propargyl H 2

184 64 Et Et Me MeOCO H H 0

185 173 Et Et Me MeOCO i-Bu H 0

186 Et Et Me MeOCO H H 1

187 65 Et Et Me MeOCO H H 2

188 94 Me Me Me shi (i H 5 H H 0

189 Me Me Me then sHs H H 1

Table 1 continued

Compound Example R ¹ R ⁵ R ⁶ n number

Table 2

Compound Example R ¹ V

 #Mouth mouth

 228 4 Et Et H H 1

 229 5 Et Et H H 2

 230 Et Et H Me 1

 231 Et Et H Me 2

 232 Me Me H H H 1

 233 Me Me H H H 2

 234 Et Et Me H H 0

 235 Et Et Me H H 2

 236 Et Et Me H Me 2

237 Et Et Me Me H Table 2 continued

Compound Example R ¹ VR ⁴ VR ⁵ n

 ¾ "

 238 Et Et Me Et H 2

 239 Et Et Pr H H 2

 240 Et Et i-Pr H H 2

 241 Et Et Bu H H 2

 242 133 Et Et i-Bu H H 2

 243 Et Six Hexyl i-Bu H H 2

 244 Et Et sec-Bu H H 2

 245 Et Et 3-Pentyl H H 2

 246 154 Et Et Cyclobentil H H 2

 247 Et Et 3—Methylcyclopentyl H H 2

 248 Et Et Cyclohexyl H H 2

 249 Et Et Cyclopentylmethyl H H 2

 250 142 Et Et Cyclohexylmethyl H H 2

 251 Et Et 0;

 252 Et Et then s H ii then (a a n H H 2

When the compound of the present invention is used as a herbicide, it can be used as it is, but in general, one or more adjuvants can be mixed and used as a herbicide. Usually, as an auxiliary, various carriers, extenders, solvents, surfactants, stabilizers, etc. are blended and formulated in the usual manner, for example, into wettable powders, emulsions, powders, granules, flowables, etc. It is preferable to use them.

 Examples of the solvent that is one of the auxiliary agents in the herbicide containing the compound of the present invention as an active ingredient include water, alcohols, ketones, ethers, aliphatic and aromatic hydrocarbons, halogenated hydrocarbons, Suitable are acid amides, esters, nitriles and the like, and one or a mixture of two or more of these are used.

As fillers, mineral powders such as clays such as kaolin and bentonite, talcs such as talc and pyrophyllite, oxides such as diatomaceous earth and white carbon and vegetable powders such as soybean powder and CMC Etc. are used. Further, a surfactant may be used as a spreading agent, a dispersant, an emulsifier, or a penetrant. Examples of the surfactant include a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant. These surfactants are- , _Λ

 1 4 5 It is utilized as one kind or a mixture of two or more kinds depending on the application.

 Preferred methods of using the herbicide containing the compound of the present invention as an active ingredient include soil treatment, water surface treatment, foliage treatment, and the like, and particularly excellent effects are obtained by application at the time of germination of the control weeds before germination. be able to.

 Herbicides containing the compound of the present invention as an active ingredient include other active ingredients that do not inhibit the herbicidal activity of the active ingredient, such as other herbicides, insecticides, fungicides, plant growth regulators, and the like. Next, the present invention will be described in more detail with reference to examples of herbicide preparations containing the compound of the present invention as an active ingredient and examples in which the herbicidal effect of the present herbicide was examined. You. The parts are by weight. Formulation example-1 (emulsion)

 An emulsion was obtained by uniformly mixing 20 parts of the compound of the present invention, 35 parts of xylene, 40 parts of cyclohexanone, and 5 parts of Sorbol 900Α (manufactured by Toho Chemical). Formulation Example 1 (Wetting powder)

 A mixture of 50 parts of the compound of the present invention, 25 parts of diatomaceous earth, 22 parts of clay, and 3 parts of Lunox R100C (manufactured by Toho Chemical) was uniformly mixed and pulverized to obtain a wettable powder. Formulation example _ 3 (granules)

 A mixture of 5 parts of the compound of the present invention, 35 parts of bentonite, 55 parts of talc, and 5 parts of lignin sulfonate is uniformly mixed and pulverized, followed by adding water, kneading, and granulating with an extruder. After drying, the granules were dried and sized to obtain granules.

Using the preparations prepared according to the methods exemplified above, the herbicidal effect of the compound of the present invention was investigated in accordance with the method shown in the following Test Examples. Table 3 and Table 3 show the herbicidal effect on the test weeds and the phytotoxicity on the test crops. Table 3-Herbicidal effect determined according to the criteria shown in 4

As a control compound, comparative drugs 薬 剤 and で which are the compounds described in JP-A-5-140125 described below were used in each test, and the results are shown in the table based on the same criteria.

 Comparative drug A Comparative drug B Test example 1 (Effect on paddy weeds)

Fill a pot of 1 / 10,000 ares with paddy soil, and after shaking, put Tainubie, Tamagayari, Konagi, Hoyurui, Matsubai, etc. The seeds of annual broadleaf weeds were sown, and rice at the 2.5 leaf stage (variety: Koshihikari) was transplanted and kept in an irrigated state. One day later, a wettable powder or an emulsion of the compound of the present invention prepared according to Formulation Examples was diluted and processed to give a prescribed dose per are. Fifteen days after the treatment, the herbicidal effect on the test weeds and the phytotoxicity on the paddy rice were investigated according to the 0 to 5 criteria, and the results are shown in Table-5 and Table-6.

Table-5 Soil treatment effect before weed emergence by paddy soil 权 Sanae

 Ceremony test amount

 ¾ l

 丄 / d ノ 々 々

 Noise

 No Nugas Miscellaneous

 Beer grass

 Ding, Noso

 • J

 QQ 1 1

 0.5 5 5 5 5 5 4 5 0

 104 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 5 5 0

 108 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 5 0

 110 1 5 5 4 5 5 5 0

 0.5 5 5 5 4 5 5 5 0

 137 1 5 5 5 5 4 5 0

 0.5 5 5 5 5 5 4 5 0

 141 1 5 5 4 5 5 5 0

 0.5 5 5 5 4 5 4 5 0

 151 1 5 5 4 5 5 5 0

 0.5 5 5 5 4 5 3 5 0

 160 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 5 5 0

 161 1 5 5 5 5 5 5 0

a 5 5 5 5 5 5 5 0 Table 6 Soil treatment effects before weed emergence by paddy soil Soil or grass activity I or ρα

 Compound compound gai / a

No

 -± r ヽ 早 早 早 早

 'J

 162 1 5 5 4 5 5 5 0

 0.5 5 5 5 4 5 5 5 0

163 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 5 5 0

168 1 5 5 5 5 4 5 0

 0.5 5 5 5 4 5 4 5 0

169 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 5 5 0

174 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 4 5 0

175 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 4 5 0

217 1 5 5 5 5 5 5 0

 0.5 5 5 5 4 5 4 5 0

220 1 5 5 5 5 5 5 0

 0.5 5 5 5 5 5 2 5 0

221 1 5 5 5 5 4 5 0

 0.5 5 5 5 4 5 2 5 0

223 1 5 5 5 5 4 5 0

 0.5 5 5 5 5 5 2 5 0

242 1 5 5 5 5 5 5 0

 0.5 4 5 4 4 4 5 0 Comparative drug 1 1 1 0 0 0 0 0

A 0.5 0 0 0 0 0 0 0 Comparative drug 1 0 0 0 0 0 0 0

B 0.5 0 0 0 0 0 0 0 Industrial applicability

 The triazole derivative of the present invention has an excellent effect as a herbicide. In particular, the herbicide containing the triazole derivative of the present invention as an active ingredient is problematic in soil treatment and foliage treatment in paddy fields. It shows an excellent herbicidal effect on various weeds such as weeds such as foxtail, eel, azaena, california and firefly, and does not show any phytotoxicity to rice.

Claims

1 5 0

1. General formula (1)

 Yo blue

(Wherein ^ and R ² are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl having 3 to 8 carbon atoms,

 Alkyl group, alkenyl group having 3 to 12 carbon atoms which may be substituted by halogen atom, alkynyl group having 3 to 6 carbon atoms which may be substituted by halogen atom

Represents an optionally substituted aralkyl group having 7 to 11 carbon atoms or an optionally substituted phenyl group, or R ¹ and R ² may be substituted together with the nitrogen atom to be bonded. It may form a good heterocycle. R ³ represents a cyano group or C00R ⁷ ; R ⁷ represents a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, An alkenyl group having 3 to 12 carbon atoms which may be substituted by a halogen atom or a carbon number which may be substituted? Represents an aralkyl group of 1 to 11. R ⁴ and R ⁵ are each independently substituted with a hydrogen atom, an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, or a halogen atom. An alkenyl group having 3 to 12 carbon atoms, an alkynyl group having 3 to 6 carbon atoms which may be substituted with a logen atom, an aralkyl group having 7 to 11 carbon atoms which may be substituted, It represents a good phenyl group or an optionally substituted alkyloxy group having 1 to 12 carbon atoms. And and R ⁵ may be combined with the carbon atom to form a ring which may be substituted. Further, IT or may be combined with the atomic group bonded together with R ¹ to form an optionally substituted ring. R ^s represents a hydrogen atom, a halogen atom or an alkyl group having 1 to 6 carbon atoms. n represents an integer of 0 to 2. Where n is 0 and R ³ is cyano When the group or R ⁷ is C00IT which is an alkyl group having 1 to 12 carbon atoms, and R ^; cannot simultaneously be hydrogen atoms. A triazole derivative represented by).

 2. —General formula (2)

_R8

R ⁶

(Wherein, R ³ , R \ R ⁵ and R ^s represent the same meaning as described above. R ⁸ represents a hydrogen atom or a group represented by R ^s C0, R ⁹ represents a chlorine atom, and has 1 to 6 carbon atoms. Represents an alkyloxy group or a funonoxy group which may be substituted.).

3. General formula (3)

(Wherein, R ³ and R ⁵ have the same meanings as described above; Y represents a leaving group.) And a compound represented by the general formula (4)

(Wherein represents the same meaning as described above.) With a 3-mercapto-1,2,4-triazole derivative in the presence of a base to obtain a compound represented by the general formula (2a):

(Wherein R ³ , R \ R ⁵ and R ⁶ represent the same meaning as described above), and then a triazole derivative represented by the general formula (5) (Five)

(Wherein, RR ² and Y represent the same meaning as described above.) Wherein the compound is reacted in the presence of a base.

0

R ¹ ,, N, S, R ³

 , To N N Y (1 a)

R ²

R ⁶

(Wherein, R \ R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above).

 4. General formula (2a)

( ^2a )

(Wherein, R ³ , R ⁵ and R ⁶ represent the same meaning as described above), and a general formula (6)

R Λ ⁹ X ( ⁶ )

(Wherein ^ represents the same meaning as described above. X represents a chlorine atom, an alkyloxy group having 1 to 6 carbon atoms or a phenyloxy group which may be substituted.) Reacting in the presence of

(Wherein, R ³ , R \ R \ R ⁵ and R ^& have the same meanings as described above), and then a triazole derivative represented by the following general formula (7): ΡΈ ² Η (7)

(Wherein Κ ¹ and R ² have the same meanings as described above.) Wherein the amine represented by the general formula (la) (1a) is reacted in the presence of a base.

(Wherein, R ² , RRR ⁵ and R ⁶ represent the same meaning as described above.).

5. General formula (2a)

(Wherein, R ³ , R \ R ⁵ and R ⁶ have the same meanings as described above), and a compound represented by the general formula (8)

R ¹ NCO (8)

(In the formula, R ¹ ′ is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, a carbon atom optionally substituted with a halogen atom. An alkenyl group having 3 to 12 carbon atoms, an alkynyl group having 3 to 6 carbon atoms which may be substituted with a halogen atom, an aralkyl group having 7 to 11 carbon atoms which may be substituted, or a phenyl group which may be substituted A) reacting with an isocyanate represented by the general formula (lb)

 0

^R1, _N people ^N, y ^s丫^R3)

H> = NR ⁴ R ⁵

R ⁶ (Wherein, R ^: ', R ³ RR ⁵ and ^ have the same meanings as described above).

 6. General formula (la)

(1a)

R ⁶

(Wherein, Γ, R ² , R ³ , R ⁴ , R ⁵ and R ^s have the same meanings as described above.) Wherein the triazole derivative represented by the general formula (lc )

R ¹ .

(Wherein, \, R \ R ³ , R \ R ⁵ and R ^s have the same meaning as described above. M represents 1 or 2).

7. General formula (Id)

 R.

(Wherein, Γ, R ^r \ R ^s and n have the same meanings as described above, and R ⁷ ′ is an alkyl group having 1 to 12 carbon atoms which may be substituted, 3 carbon atoms which may be substituted. Represents a cycloalkyl group having up to 8 carbon atoms, an alkenyl group having 3 to 12 carbon atoms which may be substituted by a halogen atom, or an aralkyl group having 7 to 11 carbon atoms which may be substituted. And R ¹ and R ^z have the same meanings as described above, provided that when R ¹ ″ is a hydrogen atom, n is 0.) An ester bond of a triazole derivative represented by Wherein the general formula (le) is hydrolyzed R ^1. , Λ OOH

 n; Y X: (1e)

NR ⁴ R ⁵

 R

(Wherein, R \ R ^{6 Rie} and n have the same meanings as described above. However, when R ¹ "is a hydrogen atom, n is 0.) A method for producing a triazole derivative represented by the formula: .

8. General formula (le)

R ⁶

(In the formula, R ⁴ R \ R ⁶ R ^{1 Q} and n have the same meanings as described above. However, when R ¹⁸ is a hydrogen atom, n is 0.) The carboxylic acid moiety is represented by the general formula (9)

R ⁷ 'OH (9)

(Wherein R ⁷ ′ has the same meaning as described above.) Wherein the esterification is carried out using an alcohol represented by the following general formula (Id):

R ¹⁰ヽ No ^SOn .COOR ⁷ R ⁶

(Wherein, R ⁴ R ⁵ R ⁶ RR and n represent the same meaning as described above. However, when R ¹ is a hydrogen atom, n is 0.) A method for producing a triazole derivative represented by R ¹ .

 9. General formula (If)

 0

R ¹ SOm _p 3

, To NY _Y ^R (1f)

R ² > = NR ⁴

R ⁶ (Wherein RR ² , R ³ , R ⁴ , R ^s and m represent the same meaning as described above), and a general formula (10)

R ⁵ '— Y (10)

(In the formula, R ⁵ ′ is an optionally substituted alkyl group having 1 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 8 carbon atoms, a carbon atom optionally substituted with a halogen atom. An alkenyl group having 3 to 12 carbon atoms, an alkynyl group having 3 to 6 carbon atoms which may be substituted with a halogen atom, an aralkyl group having 7 to 11 carbon atoms which may be substituted or a carbon number which may be substituted Wherein Y represents an alkyloxycarbonyl group of 1 to 12, and Y represents a leaving group.) In the presence of a base;

R ¹

(Wherein, R ² , R ³ , R \ R ⁵ ′, R ^s and m represent the same meaning as described above).

10. General formula (lc)

(Wherein, RR ² , R ³ , R \ R ⁵ , R ⁶ and m have the same meanings as described above.).