RU2180336C2 - Diaryl ethers, method for their obtaining and diaryl ethers-containing herbicide compositions, intermediate compounds, method for their obtaining, method to protect against weeds and method of plant desiccation - Google Patents

Abstract

FIELD: agriculture. SUBSTANCE: the innovation refers to the new compounds of formula (1), or their salts, where X, Y represent, independently, hydrogen, halogen, Z represents oxygen, Q is chosen among

- Q₁-Q₉ described in the formula of innovation and which contain heterocycles with nitrogen and sulfur, Ar represents pyridyl, pyrimidyl, pyridazinyl, triazolyl, thiazolyl, isothiazolyl or phenyl, or pyridyl, pyrimidyl, pyridazinyl, triazolyl, thiazolyl, isothiazolyl or phenyl substituted by substituents to 5, when Q represents Q₃ or Q₆ substituted phenyl is excluded. It is, also, revealed several methods to obtain the mentioned compounds, intermediate ones and herbicide compositions based upon new diaryl ethers suggested. Moreover, the method to protect against weeds is put forward along with that of plant desiccation which include application of mentioned compounds in a locus. EFFECT: higher efficiency. 21 cl, 16 tbl, 21 ex

Description

где X, Y представляют водород, галоген, циано, нитро или C_1-6-галогеналкил;
Z представляет кислород или серу;
Q выбран среди

Ar является замещенным или незамещенным арильным или гетероарильным кольцом; а когда Q представляет Q₃ или Q₆, исключается замещенный фенил.The class of diaryl ethers, which, like compositions based on them, are used in weed control, has the general formula

where X, Y are hydrogen, halogen, cyano, nitro or C _1-6 haloalkyl;
Z represents oxygen or sulfur;
Q is selected among

Ar is a substituted or unsubstituted aryl or heteroaryl ring; and when Q is Q ₃ or Q ₆ , substituted phenyl is excluded.

Q может представлять пиразол, имидазол, имидазолидин-2,4-дион, триазолинон, тетразолинон, аминоурацил и т.п. R может представлять водород, алкил, циклоалкил, алкенил или алкинил. В патенте США 5496956 описываются арилпиразолы с группой R, выбранной среди пропаргила, аллила или замещенного алкила. В патенте Японии JP 6256312 описываются фенилимидазолы с группой R, выбранной среди водорода, C_1-10-алкила, C_1-5-галогеналкила, C_3-5-алкенила, C_3-5-алкинила или C_3-6-циклоалкила. В патенте США 5125958 описываются триазолиноны с замещенной фенильной группой, выбранной в качестве группы R. В патенте Японии JP 57197268 описываются гидантоины с низшей алкильной группой, выбранной в качестве группы R. В патенте США 4902337 списываются гидантоины с группой R, выбранной среди водорода, алкила, циклоалкила, алкенила или алкинила. В патенте Японии JP 525173 описываются пиримидиндионы с группой R, выбранной среди водорода, C_1-10-алкила, C_1-5-галогеналкила, C_3-5-алкенила, C_3-5-алкинила или C_3-6-циклоалкила. В патенте США 4985065 описываются фенилтетразолиноны с выбранной в качестве группы R замещенной фенильной группой. Производные с гетероарильными группами R не заявляются. В WO 9602523 описываются замещенные арилиминотиадиазолы с группой R, выбранной среди водорода, алкила, циклоалкила, алкенила или алкинила. В патенте США 4452981 описываются фенилуразолы с группой R, выбранной среди C_1-3-алкила, аллила или пропаргила. В ЕР-А-517181 (соответствующий патенту США 5280010) описываются аминоурацильные соединения, в которых Q представляет аминоурацил, а R представляет низшую алкильную группу. В WO 96/07323 и WO 96/08151 описываются некоторые известные соединения урацила. В WO 96/08151 общее представление значительно шире, чем то, что раскрывается в его формуле изобретения и в более ранних патентах. Специфические аминоурацилы формулы (I), указанные ниже, неизвестны и являются новыми.Various substituted phenyl ethers (I ') are known.

Q may be pyrazole, imidazole, imidazolidin-2,4-dione, triazolinone, tetrazolinone, aminouracil and the like. R may be hydrogen, alkyl, cycloalkyl, alkenyl or alkynyl. US Pat. No. 5,496,956 describes arylpyrazoles with an R group selected from propargyl, allyl, or substituted alkyl. Japanese Patent JP 6256312 describes phenylimidazoles with a R group selected from hydrogen, C _1-10 alkyl, C _1-5 haloalkyl, C _3-5 alkenyl, C _3-5 alkynyl or C _3-6 cycloalkyl. US Pat. No. 5,215,958 describes triazolinones with a substituted phenyl group selected as the R. group. Japan Patent JP 57197268 describes hydantoins with a lower alkyl group selected as the R. Group. US Patent No. 4,902,337 describes hydantoins with the R group selected from hydrogen, alkyl. cycloalkyl, alkenyl or alkynyl. Japanese patent JP 525173 describes pyrimidinediones with a group R selected from hydrogen, C _1-10 alkyl, C _1-5 haloalkyl, C _3-5 alkenyl, C _3-5 alkynyl or C _3-6 cycloalkyl. US Pat. No. 4,985,065 describes phenyltetrazolinones with a substituted phenyl group selected as the R group. Derivatives with heteroaryl groups R are not claimed. WO 9602523 describes substituted aryliminothiadiazoles with an R group selected from hydrogen, alkyl, cycloalkyl, alkenyl or alkynyl. US Pat. No. 4,452,981 describes phenyllurazoles with an R group selected from C _1-3 alkyl, allyl or propargyl. EP-A-517181 (corresponding to US Pat. No. 5,280,010) describes aminouracil compounds in which Q is aminouracil and R is a lower alkyl group. WO 96/07323 and WO 96/08151 describe some known uracil compounds. In WO 96/08151, the general idea is much broader than what is disclosed in its claims and in earlier patents. The specific aminouracils of formula (I) indicated below are unknown and are new.

 The present invention shows that some diaryl esters represented by the general formula (I) or their salts have a strong herbicidal effect with sufficient safety for cultivated plants.

 There remains a need for new and more effective herbicidal compounds and compositions. This invention relates to new diaryl ethers, compositions containing diaryl ethers, and to the use of diaryl ethers and compositions based on them as broad spectrum herbicides that are effective against both monocotyledonous and dicotyledonous weeds in pre-emergence and post-emergence applications, and , in some way, safe for cultivated plants. The compounds and compositions of the present invention can sometimes also be used as desiccants. The invention also includes methods for preparing these compounds and intermediates for them, as well as methods for using the compounds as herbicides.

где X, Y представляют, независимо, водород, галоген, циано, нитро или C_1-6-галогеналкил, и
Z представляет кислород или серу, и
Q выбирают среди

R₁ представляет галоген;
R₂, R₃, R₄ и R₅ представляют, независимо, водород, C_1-6-алкил или C_1-6-галогеналкил;
когда R₃ и R₄ взятые вместе с атомами, к которым они присоединены, образуют четырех-семичленное замещенное или незамещенное кольцо, необязательно прерываемое О, S(O)_n или N-R₄, и необязательно замещенное одной-тремя C_1-6-алкильными группами или одним или несколькими атомами галогена;
R₆ представляет водород, C_1-6-алкил, C_2-6-алкенил, C_2-6-алкинил, C_1-6-галогеналкил, C_2-6-галогеналкенил, C_2-6-галогеналкинил, C_1-6-цианоалкил, C_1-6-алкокси-C_1-6-алкил или C_1-6-алкилтио-C_1-6-алкил;
A₁ и A₂ представляют, независимо, кислород или серу;
В представляет СН или N;
каждый из R₇ и R₈ представляет, независимо, водород, C_1-6-алкил, необязательно замещенный одним или несколькими атомами галогена, или C_3-6-циклоалкил, необязательно замещенный одним или несколькими атомами галогена, и когда R₇ и R₈ взяты вместе с атомами, к которым они присоединены, они представляют четырех-семичленное замещенное или незамещенное кольцо, необязательно прерываемое О, S(O)_n или N-R₄, и необязательно замещенное одной-тремя C_1-6-алкильными группами или одним или несколькими атомами галогена;
n представляет целое число 0, 1 или 2;
R₉ и R₁₀ представляет водород, C_1-6-алкил, ацил или C_1-6-алкилсульфонил, или R₉ и R₁₀ могут образовывать кольцо, состоящее из полиметиленовой группы (СН₂)_m, где m является целым числом - 2, 3, 4 или 5, вместе с атомом азота группы NR₉R₁₀, которое может иметь или может не иметь C_1-6-алкильный заместитель.This invention relates to diaryl esters of the general formula I and their salts

where X, Y are independently hydrogen, halogen, cyano, nitro or C _1-6 haloalkyl, and
Z represents oxygen or sulfur, and
Q choose among

R ₁ represents halogen;
R ₂ , R ₃ , R ₄ and R ₅ are independently hydrogen, C _1-6 alkyl or C _1-6 haloalkyl;
when R ₃ and R ₄ taken together with the atoms to which they are attached form a four-membered seven-substituted or unsubstituted ring, optionally interrupted by O, S (O) _n or NR ₄ , and optionally substituted with one to three C _1-6 -alkyl groups or one or more halogen atoms;
R ₆ is hydrogen, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 haloalkyl, C _2-6 haloalkenyl, C _2-6 haloalkynyl, C _{1- 6-} cyanoalkyl, C _1-6 -alkoxy-C _1-6 -alkyl or C _1-6 -alkylthio-C _1-6 -alkyl;
A ₁ and A ₂ independently represent oxygen or sulfur;
B represents CH or N;
each of R ₇ and R ₈ is independently hydrogen, C _1-6 alkyl optionally substituted with one or more halogen atoms, or C _3-6 cycloalkyl optionally substituted with one or more halogen atoms, and when R ₇ and R ₈ taken together with the atoms to which they are attached, they represent a four-membered substituted or unsubstituted ring, optionally interrupted by O, S (O) _n or NR ₄ , and optionally substituted by one to three C _1-6 alkyl groups or one or several halogen atoms;
n represents an integer of 0, 1 or 2;
R ₉ and R ₁₀ represents hydrogen, C _1-6 alkyl, acyl or C _1-6 alkylsulfonyl, or R ₉ and R ₁₀ may form a ring consisting of a polymethylene group (CH ₂ ) _m , where m is an integer - 2, 3, 4 or 5, together with a nitrogen atom of the group NR ₉ R ₁₀ , which may or may not have a C _1-6 alkyl substituent.

 Some compounds of formula (I) and their intermediates can sometimes exist as geometric or optical isomers, and the present invention includes all of these isomeric forms.

 Some compounds of formula (I) and their intermediates may form salts with acidic or basic materials. The salt with an acidic substance may be a salt of an inorganic acid, such as hydrochloride, hydrobromide, phosphate, sulfate or nitrate. The salt with the basic substance may be an inorganic or organic base salt, such as a sodium salt, a potassium salt, a calcium salt, a quaternary ammonium salt, such as an ammonium salt or a dimethylamine salt.

Ar represents a substituted or unsubstituted aryl or heteroaryl ring; when Q is Q ₃ or Q ₆ , substituted phenyl is excluded.

 The present invention also relates to compositions containing these compounds, and to methods of using these compounds and compositions. The compounds and compositions of the present invention are particularly useful for selectively controlling undesirable plant species, sometimes in the presence of cultivated plants. The compounds and compositions of the present invention can also be used as desiccants.

 The present invention relates to a method for controlling undesirable plant species through pre-emergence or post-emergence applications.

где X, Y, Z, Аr и Q имеют указанные выше значения.The diaryl esters of this invention have the general formula I

where X, Y, Z, Ar and Q have the above meanings.

In the determination of Ar, aryl may represent phenyl or naphthyl, and heteroaryl in the definition of Ar may represent a five- or six-membered ring with at least one heteroatom from among nitrogen, oxygen or sulfur atoms and, for example, may represent pyridyl, pyrimidyl, pyridazinyl, triazolyl, thiazolyl or isothiazolyl. Substituents in the case of a substituted aryl or heteroaryl ring may be, for example, halogen, C _1-6 -alkyl, halogen-C _1-6 -alkyl, C _1-6 -alkoxy, halogen-C _1-6 -alkoxy, C _{1- 6-} alkylthio, C _1-6 -alkylsulfonyl, C _1-6 -alkylsulfinyl, C _1-6- dialkylaminocarbonyl, cyano, nitro, amino, hydroxy, C _1-6 -alkylsulfonylamino, C _1-6 -alkoxycarbonyl-C _{1- 6-} alkoxy, C _1-6 -alkylcarbonylamino, bisbenzoylamino, aminoacetyl, aminodifluoroacetyl or amino-C _1-6 -allyl sulfonate. The number of substituents is one or more, for example, up to five. When this number is two or more, the substituents may be the same or different.

The alkyl group and the alkyl part in the definition relating to X, Y, R ₂ -R ₁₀ and substituents in the case of a substituted aryl and heteroaryl ring as Ar contain straight or branched chains C _1-6 , preferably C _1-4 , such as methyl, ethyl, propyl, butyl, pentyl or hexyl. The alkenyl or acynyl group and parts thereof in the definition of R ₆ also contain straight or branched chains, C _2-6 , preferably C _2-4 chains, such as vinyl, propenyl, butenyl, pentenyl, hexenyl, ethynyl, propynyl, butynyl, pentinyl or hexynil.

The halogen atom and halogen component in the definition relating to X, Y, R ₁ -R ₈ represent fluorine, chlorine, bromine or iodine atoms. A haloalkyl, haloalkenyl or haloalkynyl group consists of an alkyl, alkenyl or alkynyl group and one or more halogen atoms as defined above. When the number of halogen atoms is two or more, halogen atoms may be the same or different.

Preferred compounds of formula I of the present invention are compounds
where X, Y are independently hydrogen or halogen;
Z represents oxygen or sulfur;
Q is selected from Q ₁ , Q ₂ , Q ₄ , Q ₆ , Q ₇ , Q ₈ or Q ₉ .

Ar represents pyridyl, pyrimidyl, triazolyl, thiazolyl, isothiazolyl or phenyl, or pyridyl, pyrimidyl, triazolyl, thiazolyl, isothiazolyl or phenyl substituted with up to five substituents independently selected from bromine, chlorine, fluorine, iodine atoms, (C ₁ -C ₄ ) -alkyl, halo-C _1-4 -alkyl, C _1-4 -alkoxy, C _1-4 -alkylthio, halogen-C _1-4 -alkoxy, C _1-4 -alkylsulfonyl, C _1-4 -alkylsulfinyl, di-C _1-4 -alkylaminocarbonyl, cyano, nitro, amino, hydroxy, C _1-4 -alkylsulfonylamino, C _1-4 -alkoxycarbonyl-C _1-4 -alkoxy or C _1-4 -alkoxycarbonylamino; when Q is Q ₆ , substituted phenyl is excluded.

The most preferred compounds of this invention are compounds of formula I,
where X is fluorine;
Y represents chlorine;
Z represents oxygen or sulfur;
Q is selected from Q ₁ , Q ₂ , Q ₄ , O ₆ , O ₇ , Q ₈ or Q ₉ ;
Ar is 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-bromo-2-pyridyl, 5-bromo-2-pyridyl, 6-bromo-2-pyridyl, 3-chloro-2-pyridyl, 5-chloro 2-pyridyl, 6-chloro-2-pyridyl, 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 6-fluoro-2-pyridyl, 3-cyano-2-pyridyl, 5-cyano-2- pyridyl, 6-cyano-2-pyridyl, 3-nitro-2-pyridyl, 5-nitro-2-pyridyl, 6-nitro-2-pyridyl, 3-trifluoromethyl-2-pyridyl, 4-trifluoromethyl-2-pyridyl, 5-trifluoromethyl-2-pyridyl, 6-trifluoromethyl-2-pyridyl, 5-amino-2-pyridyl, 3-dimethylaminocarbonyl-2-pyridyl, 3-methylsulfonyl-2-pyridyl, 3-isopropylsulfonyl-2-pyridyl, 6- chloro-3-trifluoromethyl-2-pyridyl, 3,5,6-trifluoropyridyl, 2 -pyrimidyl, 4-pyrimidyl, 5-bromo-2-pyrimidyl, 4-chloro-2-pyrimidyl, 4-trifluoromethyl-2-pyrimidyl, 4,6-dimethoxy-2-pyrimidyl, 2,6-dimethoxy-4-pyrimidyl 4,6-dimethoxy-2-triazinyl, phenyl, 2-iodophenyl, 2-trifluoromethoxyphenyl, 2-nitrophenyl, 4-nitrophenyl, 4-aminophenyl, 4-hydroxyphenyl, 4-methylsulfonylaminophenyl, 4- (1-ethoxycarbonylethoxy) phenyl, 2-cyanophenyl, 2-cyano-3-fluorophenyl, 2-cyano-4-fluorophenyl, 2-amino-4- (1-ethoxycarbonylethoxy) phenyl, 2-cyano-4-nitrophenyl, 4-amino-2-cyanophenyl, 4 nitro-2-trifluoromethylphenyl, 4-amino-2-trifluoromethylphenyl, 4-acetylamino-2-trifluoromethylphenyl, 4- (1-ethoxy carbonylethoxy) -2-nitrophenyl, 5-chloro-4- (1-ethoxycarbonylethoxy) -2-nitrophenyl, 3-methyl-4-nitro-5-isothiazolyl or 5-nitro-2-thiazolyl; when Q is Q ₆ , substituted phenyl is excluded.

 Intermediates II and III can be obtained by the methods described in the method (1).

Способ 1
Способ (1) осуществляется в две стадии. Первой стадией является взаимодействие аминофенола с арилгалогенидом или гетероарилгалогенидом с или без растворителей. Растворителями могут являться ацетонитрил, тетрагидрофуран, диметилимидазолидин, диметилсульфоксид, гексаметилфосфотриамид, N,N-диметилформамид, ацетон, бутан-2-он, бензол, толуол или ксилол, в присутствии основания, такого как карбонат калия, карбонат натрия, гидроксид калия, гидроксид натрия, трет-бутоксид калия, фторид калия или гидрид натрия. Катализаторы можно использовать, а можно и не использовать. К таким катализаторам относятся хлорид меди (1), оксид меди (1), медь, алкоксид меди (1), алкилкупрат, палладий (0), галогениды тетрабутиламмония или 8-хинолинол. Температура реакции обычно составляет от 0 до 250^oС, предпочтительно - от 20 до 120^oС. Время реакции составляет от 1 до 12 часов, предпочтительно - от 2 до 6 часов. Диарилэфиры (II) можно также получить посредством обработки аминофенола арилсодержащими трикарбоксилатами, диацетатом трифенилвисмута, трифторацетатом трифенилвисмута или дифенилйодиумгалогенидами в присутствии растворителей, таких как бензол, толуол, дихлорметан, дихлорэтан, хлороформ или вода, без или с катализаторами, такими как медь или переходный металл. Температура обычно составляет от 0^oС до температуры кипения смеси, а время реакции составляет от 10 минут до 72 часов. Предпочтительна температура от 20^oС до температуры кипения смеси, а время предпочтительно составляет от 2 до 6 часов.

Method 1
Method (1) is carried out in two stages. The first step is the reaction of aminophenol with an aryl halide or heteroaryl halide with or without solvents. The solvents may be acetonitrile, tetrahydrofuran, dimethylimidazolidine, dimethyl sulfoxide, hexamethylphosphotriamide, N, N-dimethylformamide, acetone, butan-2-one, benzene, toluene or xylene, in the presence of a base such as potassium carbonate, sodium carbonate, potassium hydroxide potassium tert-butoxide, potassium fluoride or sodium hydride. Catalysts may or may not be used. Such catalysts include copper chloride (1), copper oxide (1), copper, copper alkoxide (1), alkyl cuprate, palladium (0), tetrabutylammonium halides or 8-quinolinol. The reaction temperature is usually from 0 to 250 ^{° C.} , preferably from 20 to 120 ^° C. The reaction time is from 1 to 12 hours, preferably from 2 to 6 hours. Diaryl ethers (II) can also be obtained by treating aminophenol with aryl-containing tricarboxylates, triphenylbismuth diacetate, triphenylbismuth trifluoroacetate or diphenyl-iodium halides in the presence of solvents such as benzene, toluene, dichloromethane, dichloroethane, chloroform or water, or metal. The temperature is usually from 0 ^{° C.} to the boiling point of the mixture, and the reaction time is from 10 minutes to 72 hours. A temperature of from 20 ^{° C.} to a boiling point of the mixture is preferred, and the time is preferably from 2 to 6 hours.

The second step requires treating the amine (II) with phosgene or triphosgene in a solvent such as hexane, heptane, benzene, toluene, xylene or ethyl acetate. The reaction temperature is usually from 0 ^{° C.} to the boiling point of the mixture, with the boiling point of the mixture being preferred. The reaction time is usually from 30 minutes to 6 hours, preferably from 2 to 3 hours.

Способ 2
При способе (2) простая эфирная связь образуется в условиях, описанных в первой стадии способа (1).

Method 2
In the method (2), an ether linkage is formed under the conditions described in the first step of the method (1).

Способ 3
При способе (3) простая эфирная связь образуется с использованием условий, описанных на первой стадии способа (1).

Method 3
In the method (3), an ether bond is formed using the conditions described in the first step of the method (1).

Способ 4
Способ (4) осуществляется в три стадии. На первой стадии происходит образование диазониевой соли анилина (II), обычно, в кислой среде, такой как концентрированная соляная кислота, при обработке водным раствором нитрита натрия. Он восстанавливается в присутствии восстановителя с образованием соответствующего производного гидразина. Таким восстановителем может являться неорганическое соединение, такое как гидратированный хлорид олова(II). Смесь обрабатывается кетокислотой, такой как пировиноградная кислота, в водном растворе. Температура реакции составляет от -15 до 30^oС, а время реакции - от 30 минут до 4 часов. Предпочтительная температура сначала составляет от 0 до 5^oС, а позднее - 20-30^oС, и предпочтительное время составляет от 30 до 60 минут.

Method 4
Method (4) is carried out in three stages. In the first stage, the formation of the diazonium salt of aniline (II) occurs, usually in an acidic medium, such as concentrated hydrochloric acid, when treated with an aqueous solution of sodium nitrite. It is reduced in the presence of a reducing agent to form the corresponding hydrazine derivative. Such a reducing agent may be an inorganic compound, such as hydrated tin (II) chloride. The mixture is treated with a keto acid, such as pyruvic acid, in an aqueous solution. The reaction temperature is from -15 to 30 ^o C, and the reaction time is from 30 minutes to 4 hours. The preferred temperature is initially from 0 to 5 ^o C, and later 20-30 ^o C, and the preferred time is from 30 to 60 minutes.

In a second step, the resulting hydrazone (VIII) is treated with diphenylphosphoryl azide in an inert solvent such as benzene, toluene, xylene, hexane, in the presence of a base such as triethylamine or pyridine. The reaction temperature leaves from 20 ^o With up to the boiling point of the mixture, and the reaction time is from 30 minutes to 6 hours. Preferably, the temperature is the boiling point of the mixture, and the time is from 1 to 2 hours.

The final step is the alkylation of (IX) in an inert solvent such as diethyl ether, dioxane or tetrahydrofuran, an alkylating agent such as an alkyl halide, haloalkyl halide or alkyl sulfate in the presence of a base such as sodium or potassium hydroxide, sodium or potassium carbonate, pyridine or triethylamine , with or without a catalytic amount of tetraalkylammonium salt. The reaction temperature is from -40 to 50 ^o C, and the reaction time is from 30 minutes to 4 days. The preferred reaction temperature is from 20 to 30 ^{° C.} , the preferred reaction time is 2 days.

Способ 5
Способ (5) осуществляется в три стадии. Первой стадией является обработка изоцианата (IIIa) аммиаком в инертном растворителе, таком как гексан, бензол, толуол, ксилол, диэтиловый эфир, тетрагидрофуран или диоксан. Температура реакции составляет от -10 до 100^oС, и время реакции составляет от 15 минут до 6 часов. Предпочтительно температура реакции составляет от 0 до 10^oС, а время реакции - от 30 до 60 минут.

Method 5
Method (5) is carried out in three stages. The first step is the treatment of isocyanate (IIIa) with ammonia in an inert solvent such as hexane, benzene, toluene, xylene, diethyl ether, tetrahydrofuran or dioxane. The reaction temperature is from -10 to 100 ^o C, and the reaction time is from 15 minutes to 6 hours. Preferably, the reaction temperature is from 0 to 10 ^{° C.} and the reaction time is from 30 to 60 minutes.

The second stage is the treatment of urea (IX) with an acid catalyst, such as p-toluenesulfonic acid or amberlist resin, and a keto ester in an inert solvent, such as benzene, toluene, xylene, hexane, at a temperature of from 20 ^o C to the boiling point of the mixture , from 10 to 24 hours, with the formation of imidazolidinone (XII). The temperature is preferably the boiling point of the mixture, and the time is 12-16 hours.

The final step is the alkylation of (XII) in an inert solvent such as diethyl ether, dioxane, tetrahydrofuran, benzene, toluene, xylene or hexane, with an alkylating agent such as an alkyl halide or haloalkyl halide, in the presence of a base such as sodium or potassium hydroxide, sodium carbonate or potassium, pyridine or triethylamine. The reaction temperature is from 20 ^o C to the boiling point of the mixture, and the time is from 30 minutes to 20 hours. Preferably, the temperature is from 50 to 100 ^{° C.} and the time is from 12 to 16 hours.

Способ 6
Способ (6) осуществляется в три стадии. Первая стадия представляет обработку изоцианата (III-b) 2,2-диметил-5-(2-тетрагидропирролиден)-1,3-диоксан-4,6-дионом в присутствии основания, такого как метоксид натрия, этоксид натрия, трет-бутоксид калия или гидрид натрия, в растворителе, таком как толуол, N,N-диметилформамид или диметилсульфоксид. Температура реакции составляет от -40^oС до температуры кипения смеси, а время составляет от 30 минут до 14 часов. Предпочтительно начальная температура реакции присоединения составляет от -30 до -20^oС, а затем для реакции требуется температура от 100 до 120^oC. Предпочтительное время составляет от 4 до 5 часов.

Method 6
Method (6) is carried out in three stages. The first step is the treatment of isocyanate (III-b) with 2,2-dimethyl-5- (2-tetrahydropyrrolidene) -1,3-dioxan-4,6-dione in the presence of a base such as sodium methoxide, sodium ethoxide, tert-butoxide potassium or sodium hydride, in a solvent such as toluene, N, N-dimethylformamide or dimethyl sulfoxide. The reaction temperature is from -40 ^o C to the boiling point of the mixture, and the time is from 30 minutes to 14 hours. Preferably, the initial temperature of the addition reaction is from -30 to -20 ^{° C.} , and then the reaction requires a temperature of from 100 to 120 ^° C. A preferred time is from 4 to 5 hours.

The second step is the hydrolysis of an ether linkage under acidic conditions in an inert solvent such as chloroform or methylene chloride using concentrated sulfuric acid. The reaction temperature is from -20 to 50 ^o C, and the time is from 30 minutes to 6 hours. Preferably, the addition is carried out at 0-5 ^{° C.} , and then a reaction temperature of from 20 ^° C. to 30 ^° C. is required ^. The preferred time is from 1 to 2 hours.

 At the final stage, using the conditions described in the first stage of the method (1), an ether link is formed.

Способ 7
Способ (7) осуществляется в две стадии. На первой стадии происходит образование тетразольного кольца (XVIII) при обработке изоцианата (III) триметилсилилазидом с или без растворителя. Температура реакции составляет от 100^oС до температуры кипения смеси, а время составляет от 1 до 48 часов. Предпочтительно температурой реакции является температура кипения смеси, а время составляет 24 часа.

Method 7
Method (7) is carried out in two stages. At the first stage, the formation of the tetrazole ring (XVIII) occurs when the isocyanate (III) is treated with trimethylsilyl azide with or without a solvent. The reaction temperature is from 100 ^{° C.} to the boiling point of the mixture, and the time is from 1 to 48 hours. Preferably, the reaction temperature is the boiling point of the mixture and the time is 24 hours.

The final step is the alkylation (XVIII) in an inert solvent such as acetone, diethyl ether, dioxane, tetrahydrofuran, benzene, toluene, xylene, hexane, N, N-dimethylformamide or dimethyl sulfoxide, an alkylating agent such as an alkyl halide or a halide in the presence of such as sodium or potassium hydroxide, sodium or potassium carbonate, pyridine or triethylamine. The reaction temperature is from 50 to 150 ^o C, and the reaction time is from 30 minutes to 2 days. The preferred temperature range is from 70 to 90 ^o C, and the time is from 20 to 30 hours.

Способ 8
Способ (8) осуществляется в пять стадий. На первой стадии проводят обработку амина (II) тиофосгеном в растворителе, таком как гексан, гептан, бензол, толуол, ксилол или этилацетат. Температура реакции обычно составляет от 0^oC до температуры кипения смеси, предпочтительно присоединение осуществляется при температуре от 0 до 5^oС, а затем для реакции требуются температуры для нагревания смеси до кипения. Время реакции обычно составляет от 30 минут до 6 часов, предпочтительно - от 2 до 3 часов.

Method 8
Method (8) is carried out in five stages. In a first step, amine (II) is treated with thiophosgene in a solvent such as hexane, heptane, benzene, toluene, xylene or ethyl acetate. The reaction temperature is usually from 0 ^° C. to the boiling point of the mixture, preferably the addition is carried out at a temperature of from 0 ^{° C.} to 5 ^{° C.} , and then the reaction requires temperatures to heat the mixture to a boil. The reaction time is usually from 30 minutes to 6 hours, preferably from 2 to 3 hours.

In a second step, isothiocyanate (XX) is treated with formic hydrazide in an inert solvent such as toluene, tetrahydrofuran, dioxane or diethyl ether. The reaction temperature is usually from 0 ^{° C.} to the boiling point of the mixture, preferably represents ambient temperature. The reaction time is usually from 30 minutes to 10 hours, preferably from 3 to 4 hours.

Formylhydrazines (XXI) are treated with phosgene or triphosgene in a solvent such as hexane, heptane, benzene, toluene, xylene, acetone or ethyl acetate. The reaction temperature is usually from -20 to 50 ^{° C.} , preferably from 0 to 25 ^° C. The reaction time is usually from 30 minutes to 6 hours, preferably from 1 to 2 hours.

The hydrolysis of 3-formylthiadiazolidinones (XXII) is carried out under acidic conditions in solvents such as acetone, butan-2-one, methanol, ethanol, tetrahydrofuran or N, N-dimethylformamide. Acids may be sulfuric, hydrochloric or acetic acid and may be diluted. The reaction temperature is usually from -20 ^o C to 50, preferably from 0 to 25 ^o C. The reaction time is usually from 15 minutes to 6 hours, preferably from 30 minutes to 2 hours.

The final step is the alkylation (XXIII) in an inert solvent such as acetone, diethyl ether, dioxane, tetrahydrofuran, benzene, toluene, xylene, hexane, N, N-dimethylformamide or dimethyl sulfoxide, an alkylating agent such as an alkyl halide or a halide base such as sodium or potassium hydroxide, sodium or potassium carbonate, pyridine or triethylamine. The reaction temperature is from 30 ^o C to the boiling point of the mixture, and the time is from 30 minutes to 6 hours. The preferred temperature range is from 50 to 90 ^o C, and the time is from 1 to 3 hours.

Способ 9
По способу (9) амины (II) превращаются в 2,4-имидазолидиндионы (XXVII) в три стадии. На первой стадии обработка галогенангидридом галогенуксусной кислоты, таким как хлорацетилхлорид, и органическим основанием, таким как триэтиламин или пиридин, в инертном растворителе, таком как бензол, толуол, ксилол, тетаргидрофуран или N, N-диметилформамид, дает хлорамиды (XXV). Предпочтительным ацилирующим агентом является хлорацетилхлорид, а предпочтительным основанием - триэтиламин. Предпочтительным растворителем является толуол. Реакцию можно осуществить при температурах от -20 до 150^oС, предпочтительно - от 25 до 50^oС. Время реакции может составлять от 30 минут до десяти часов, предпочтительно - от 2 до 4 часов.

Method 9
According to method (9), amines (II) are converted into 2,4-imidazolidinediones (XXVII) in three stages. In a first step, treatment with a haloacetic acid halide such as chloroacetyl chloride and an organic base such as triethylamine or pyridine in an inert solvent such as benzene, toluene, xylene, tetrahydrofuran or N, N-dimethylformamide gives chloramides (XXV). Chloroacetyl chloride is the preferred acylating agent, and triethylamine is the preferred base. A preferred solvent is toluene. The reaction can be carried out at temperatures from -20 to 150 ^o C, preferably from 25 to 50 ^o C. The reaction time can be from 30 minutes to ten hours, preferably from 2 to 4 hours.

In a second step, the reaction of these chloramides (XXV) with suitable amines in a solvent such as C _1-5 alcohols, tetrahydrofuran or dioxane gives aminoamides (XXVI). Ethanol is the preferred solvent, and the reaction can be carried out at temperatures from -20 to 150 ^{° C.} , preferably from 25 to 70 ^° C. The reaction time can be from 30 minutes to ten hours, preferably from 2 to 3 hours.

In a third step, aminoamides (XXVI) are treated with 1,1'-carbonyldiimidazole in an inert solvent such as benzene, toluene, xylene, tetrahydrofuran or N, N-dimethylformamide, and 2,4-imidazolidinediones (XXVII) are formed. Toluene is the preferred solvent, and the reaction can be carried out at temperatures from -20 to 150 ^{° C.} , preferably from 100 to 120 ^° C. The reaction time can be from 30 minutes to ten hours, preferably from 2 to 3 hours.

Способ 10
Способ (10) осуществляется в три стадии. Первой стадией является взаимодействие изоцианатов (ХХа) с насыщенным гетероциклическим соединением (XXVIII), таким как 1-этилоксикарбонилгексагидропиридазин, где В=N, и f=2, которое, необязательно, можно осуществить в два этапа - (1) и (2). На этапе (1) реагенты перемешиваются вместе в инертном растворителе, таком как бензол, толуол, ксилол, диоксан, гексан, этилацетат, тетрагидрофуран, диэтиловый эфир или ацетон. Температура реакции обычно составляет от -70^oС до температуры кипения смеси, в зависимости от характера В, f и R₄. Время реакции обычно составляет от 30 минут до 20 часов, в зависимости от характера В, f и R₄. На этапе (2) после удаления растворителя может добавляться толуол, ксилол или диоксан, а также слабощелочное соединение, такое как ацетат натрия. Реакция протекает при температуре от 50^oС до температуры кипения смеси, а время составляет от 6 часов до 3 суток. Предпочтительной температурой является температура кипения смеси, а время составляет от 20 до 30 часов.

Method 10
Method (10) is carried out in three stages. The first stage is the interaction of isocyanates (XXa) with a saturated heterocyclic compound (XXVIII), such as 1-ethyloxycarbonylhexahydropyridazine, where B = N, and f = 2, which, optionally, can be carried out in two stages - (1) and (2). In step (1), the reagents are mixed together in an inert solvent such as benzene, toluene, xylene, dioxane, hexane, ethyl acetate, tetrahydrofuran, diethyl ether or acetone. The reaction temperature is usually from -70 ^{° C.} to the boiling point of the mixture, depending on the nature of B, f and R ₄ . The reaction time is usually from 30 minutes to 20 hours, depending on the nature of B, f and R ₄ . In step (2), after removal of the solvent, toluene, xylene or dioxane may be added, as well as a slightly alkaline compound such as sodium acetate. The reaction proceeds at a temperature of from 50 ^o C to the boiling point of the mixture, and the time is from 6 hours to 3 days. The preferred temperature is the boiling point of the mixture, and the time is from 20 to 30 hours.

The second step is hydrolysis of the ether linkage under acidic conditions in an inert solvent such as chloroform or methylene chloride using concentrated sulfuric acid. The reaction temperature is from -20 to 50 ^o C, and the time is from 30 minutes to 6 hours. A temperature of 0 ^{° C.} and a time of 1 to 2 hours are preferred.

 The final stage is the formation of a simple ether bond and receipt (XXXI). This is carried out under the conditions described in the first stage of the method (1).

Способ 11
Способ (11) является одностадийным способом, где соединение (ХХb), которое может представлять изоцианат или изотиоцианат, взаимодействует с насыщенным гетероциклическим соединением (XXVIII), с или без растворителей, с образованием продукта реакции (XXXI). Взаимодействие усиливается в присутствии растворителей, таких как гексан, пентан, бензол, толуол, ксилол, диэтиловый эфир, тетрагидрофуран, диоксан, ацетон, бутан-2-он, этилацетат, N, N-диметилформамид или диметилсульфоксид, и проводится при температуре от -70^oС до температуры кипения смеси за время от 15 минут до 20 часов. Температура предпочтительно составляет от 0 до 30^oС, а время - от 15 минут до 12 часов.

Method 11
Process (11) is a one-step process, wherein compound (XXb), which may be an isocyanate or isothiocyanate, is reacted with a saturated heterocyclic compound (XXVIII), with or without solvents, to produce a reaction product (XXXI). The interaction is enhanced in the presence of solvents such as hexane, pentane, benzene, toluene, xylene, diethyl ether, tetrahydrofuran, dioxane, acetone, butan-2-one, ethyl acetate, N, N-dimethylformamide or dimethyl sulfoxide, and is carried out at a temperature of from -70 ^o C to the boiling point of the mixture over a period of 15 minutes to 20 hours. The temperature is preferably from 0 to 30 ^o C, and the time is from 15 minutes to 12 hours.

Способ 12
По способу (12) тиадиазабициклононаноны (XXIV) обрабатываются каталитическим количеством основания, такого как метоксид натрия, этоксид натрия или трет-бутоксид калия, в спирте C_1-5, таком как метанол, этанол или трет-бутанол, при температуре от 0^oС до температуры кипения смеси за время от 15 минут до 3 часов. Предпочтительны температура кипения смеси и время от 30 до 60 минут.

Method 12
According to method (12), thiadiazabicyclononanones (XXIV) are treated with a catalytic amount of a base, such as sodium methoxide, sodium ethoxide or potassium tert-butoxide, in a C _1-5 alcohol such as methanol, ethanol or tert-butanol, at a temperature of from 0 ^o C to the boiling point of the mixture over a period of 15 minutes to 3 hours. The boiling point of the mixture and the time from 30 to 60 minutes are preferred.

Способ 13
Способ (13) осуществляется с использованием 0,5-10 эквивалентов (предпочтительно - 0,8-3) гидразинов по отношению к оксазинам (XXXII). Примерами гидразинов являются гидразин, алкилгидразины, такие как метил-, этил- или трет-бутилгидразин, и циклические гидразины, такие как 1-аминопирролидин. Реакция протекает без каких-либо растворителей, но обычно ускоряется при использовании растворителя.

Method 13
Method (13) is carried out using 0.5-10 equivalents (preferably 0.8-3) of hydrazines with respect to oxazines (XXXII). Examples of hydrazines are hydrazine, alkyl hydrazines such as methyl, ethyl or tert-butyl hydrazines, and cyclic hydrazines such as 1-aminopyrrolidine. The reaction proceeds without any solvents, but is usually accelerated by the use of a solvent.

 The reaction also requires solvents such as aliphatic hydrocarbons, for example hexane, heptane, naphtha and petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, and halogenated hydrocarbons such as chloroform and methylene chloride, ethers such as diethyl ether, dioxane and tetrahydrofuran, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile and isobutyronitrile, tertiary amines such as pyridine and N, N-dimethylaniline, acid amides such as N, N-dimethylacetamide, N, N- dime tilformamide and N-methylpyrrolidone, sulfur-containing compounds such as dimethyl sulfoxide and sulfolane, alcohols such as methanol, ethanol, propanol and butanol, water and mixtures thereof.

The reaction temperature is usually from -30 to 150 ^o C, preferably from -10 ^o C to the boiling point of the reaction mixture. The reaction usually takes from 10 minutes to 96 hours, preferably from 30 minutes to 48 hours.

Способ 14
По способу (14) простая эфирная связь образуется при использовании условий, описанных на первой стадии способа (1).

Method 14
According to the method (14), an ether bond is formed using the conditions described in the first stage of the method (1).

Способ 15
Способ (15) осуществляется в растворителе, таком как диоксан, диметилсульфоксид, гексаметилфосфотриамид или N,N-диметилформамид, в присутствии основания, такого как карбонат натрия, карбонат калия, гидроксид натрия, гидроксид калия или гидрид натрия. Можно использовать ряд агентов аминирования, таких как 2,4-динитрофеноксиамин; O-арилсульфонилгидроксиамины, такие как 2,3,6-триметил- и триизопропилфенилгидроксиамин; O-пикоилгидроксиамин и O-мезитилгидроксиамин. Температура реакции обычно составляет от -30 до 110^oС, а время реакции составляет от 12 часов до 7 суток, температура реакции предпочтительно составляет от 20 до 30^oС. Время реакции предпочтительно составляет от 12 часов до 3 суток.

Method 15
Method (15) is carried out in a solvent such as dioxane, dimethyl sulfoxide, hexamethylphosphotriamide or N, N-dimethylformamide, in the presence of a base such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or sodium hydride. A number of amination agents can be used, such as 2,4-dinitrophenoxyamine; O-arylsulfonylhydroxyamines such as 2,3,6-trimethyl- and triisopropylphenylhydroxyamine; O-picoylhydroxyamine and O-mesitylhydroxyamine. The reaction temperature is usually from -30 to 110 ^{° C.} , and the reaction time is from 12 hours to 7 days, the reaction temperature is preferably from 20 to 30 ^° C. The reaction time is preferably from 12 hours to 3 days.

Способ 16
С использованием способа (16) можно использовать изоцианат (III) для образования аминоурацила (XXXIIIа) при синтезе в одном реакторе без выделения урацила (XXXV). Урацильное кольцо образуется при взаимодействии полученного изоцианата (III) с алкил-3-амино-4,4,4-трифторкротонатом и основанием, таким как гидрид натрия, метоксид натрия или этоксид натрия, в растворителе, таком как диметилсульфоксид, N,N-диметилформамид, бензол, толуол, ксилол, тетрагидрофуран, диоксан или диэтиловый эфир, при температурах обычно от -50 до 50^oС, при времени реакции от 10 минут до 14 часов. Предпочтительны температура реакции от -30 до 30^oС и время реакции от 15 минут до 6 часов. Затем вводятся агенты аминирования, такие как 2,4-динитрофеноксиамин; O-арилсульфонилгидроксиамины, такие как 2,3,6-триметил- и триизопропилфенилгидроксиамин; O-пикоилгидроксиамин и O-мезитилгидроксиамин, как описано в способе (15). Температура реакции обычно составляет от -30 до 110^oС, а время реакции составляет от 12 часов до 7 суток. Температура реакции предпочтительно составляет от 20 до 30^oС. Время реакции предпочтительно составляет от 12 часов до 3 суток.

Method 16
Using method (16), isocyanate (III) can be used to form aminouracil (XXXIIIa) in synthesis in a single reactor without isolation of uracil (XXXV). The uracil ring is formed by reacting the resulting isocyanate (III) with an alkyl-3-amino-4,4,4-trifluorocrotonate and a base such as sodium hydride, sodium methoxide or sodium ethoxide in a solvent such as dimethyl sulfoxide, N, N-dimethylformamide , benzene, toluene, xylene, tetrahydrofuran, dioxane or diethyl ether, at temperatures usually from -50 to 50 ^o With the reaction time from 10 minutes to 14 hours. The reaction temperature is preferred from -30 to 30 ^{° C.} and the reaction time is from 15 minutes to 6 hours. Amination agents such as 2,4-dinitrophenoxyamine are then introduced; O-arylsulfonylhydroxyamines such as 2,3,6-trimethyl- and triisopropylphenylhydroxyamine; O-picoylhydroxyamine and O-mesitylhydroxyamine, as described in method (15). The reaction temperature is usually from -30 to 110 ^o C, and the reaction time is from 12 hours to 7 days. The reaction temperature is preferably from 20 to 30 ^° C. The reaction time is preferably from 12 hours to 3 days.

Способ 17
С использованием способа (17) соединение формулы (Q₉), где A₁ и/или A₂ представляют атом серы, можно получить посредством взаимодействия соединения указанной выше формулы (XXXIII) с агентом сульфуризации, таким как реагент Лоуссона или пентасульфид фосфора. Далее сульфуризация может происходить при длительном нагревании и с избытком реагента. Для реакции используются растворители, такие как бензол, толуол и ксилол. Время реакции обычно составляет от 2 до 12 часов, предпочтительно - 3-4 часа. Температура реакции обычно составляет от 0 до 150^oС, предпочтительно - от 60^oС до температуры кипения смеси.

Method 17
Using method (17), a compound of formula (Q ₉ ), where A ₁ and / or A ₂ represents a sulfur atom, can be prepared by reacting a compound of the above formula (XXXIII) with a sulfurization agent such as Lawsson's reagent or phosphorus pentasulfide. Further, sulfurization can occur with prolonged heating and with an excess of reagent. Solvents such as benzene, toluene and xylene are used for the reaction. The reaction time is usually from 2 to 12 hours, preferably 3-4 hours. The reaction temperature is usually from 0 to 150 ^o C, preferably from 60 ^o C to the boiling point of the mixture.

Способ 18
По способу (18) простая эфирная связь образуется в условиях, описанных на первой стадии способа (1).

Method 18
According to the method (18), a simple ether bond is formed under the conditions described in the first stage of the method (1).

Способ 19
По способу (19) требуется взаимодействие натриевой или калиевой соли ароматического или гетероциклического гидроксилсодержащего соединения с галогенароматическим урацилом (XXXVIII). Реакция протекает в отсутствие какого-либо растворителя, но обычно ускоряется при использовании растворителя. К таким растворителям относятся толуол, ксилол, N,N-диметилформамид и диметилсульфоксид, и используется катализатор, такой как медь, бронза или переходный металл. Температура обычно составляет от 0 до 150^oС, а время реакции - от 10 минут до 72 часов. Температура предпочтительно составляет от 150^oС до температуры кипения смеси, а время предпочтительно составляет от 2 до 6 часов.

Method 19
The method (19) requires the interaction of the sodium or potassium salt of an aromatic or heterocyclic hydroxyl-containing compound with halogenated aromatic uracil (XXXVIII). The reaction proceeds in the absence of any solvent, but is usually accelerated by the use of a solvent. Such solvents include toluene, xylene, N, N-dimethylformamide and dimethyl sulfoxide, and a catalyst such as copper, bronze or a transition metal is used. The temperature is usually from 0 to 150 ^o C, and the reaction time is from 10 minutes to 72 hours. The temperature is preferably from 150 ^{° C.} to the boiling point of the mixture, and the time is preferably from 2 to 6 hours.

Способ 20
Способ (20) показывает, что урацильное кольцо может образоваться при взаимодействии полученного изоцианата (III) с алкил-3-амино-4,4,4-трифторкротонатом и основанием, таким как гидрид натрия, метоксид натрия, этоксид натрия или трет-бутоксид калия, в растворителе, таком как диметилсульфоксид, N, N-диметилформамид, бензол, толуол, ксилол, тетрагидрофуран, диоксан или диэтиловый эфир, обычно, при температурах от -50 до 50^oС, при времени реакции от 10 минут до 14 часов. Предпочтительна температура от -30 до 30^oС при времени реакции от 15 минут до 6 часов.

Method 20
Method (20) shows that a uracil ring can be formed by reacting the resulting isocyanate (III) with alkyl 3-amino-4,4,4-trifluorocrotonate and a base such as sodium hydride, sodium methoxide, sodium ethoxide or potassium tert-butoxide in a solvent such as dimethyl sulfoxide, N, N-dimethylformamide, benzene, toluene, xylene, tetrahydrofuran, dioxane or diethyl ether, usually at temperatures from -50 ^° C to 50 ^° C, with a reaction time of 10 minutes to 14 hours. The preferred temperature is from -30 to 30 ^o With a reaction time of from 15 minutes to 6 hours.

Способ 21
Способ (21) осуществляется в две стадии. Первой стадией является получение N-фенилацетамида (XXXIX) с использованием обычной методологии.

Method 21
Method (21) is carried out in two stages. The first step is the preparation of N-phenylacetamide (XXXIX) using the usual methodology.

The second stage is cyclization with the formation of oxazines (XXXII). This step is carried out in solvents representing aliphatic hydrocarbons such as hexane, heptane, naphtha and petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, tertiary amines such as pyridine and N, N-dimethylaniline, acid amides, such as N, N-dimethylacetamide, N, N-dimethylformamide and N-methylpyrrolidone, sulfur-containing compounds such as dimethyl sulfoxide and sulfolane, and organic acids such as formic acid, acetic acid, lactic acid, and acetic anhydride. Preferably, the above aliphatic hydrocarbons, aromatic hydrocarbons and organic acids are used. The reaction temperature is usually from 0 to 200 ^o C, preferably from 20 ^o C to the boiling point of the mixture. The reaction time is from 10 minutes to 72 hours, preferably from 30 minutes to 24 hours.

Способ 22
Способ (22) осуществляется в две стадии. Первой стадией является образование фенолоксазина (XL) с использованием методики, описанной в способе (21). Процесс осуществляется в растворителях, представляющих алифатические углеводороды, такие как гексан, гептан, лигроин и петролейный эфир, ароматические углеводороды, такие как бензол, толуол, ксилол и хлорбензол, третичные амины, такие как пиридин и N,N-диметиланилин, амиды кислот, такие как N,N-диметилацетамид, N,N-диметилформамид и N-метилпирролидон, серусодержащие соединения, такие как диметилсульфоксид и сульфолан, и органические кислоты, такие как муравьиная кислота, уксусная кислота, молочная кислота, и уксусный ангидрид. Предпочтительно используются вышеуказанные алифатические углеводороды, ароматические углеводороды и органические кислоты. Температура реакции обычно составляет от 0 до 200^oС, предпочтительно - от 20^oС до температуры кипения смеси. Время реакции составляет от 10 минут до 72 часов, предпочтительно - от 30 минут до 24 часов.

Method 22
Method (22) is carried out in two stages. The first stage is the formation of phenoloxazine (XL) using the technique described in method (21). The process is carried out in solvents representing aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, tertiary amines such as pyridine and N, N-dimethylaniline, acid amides, such such as N, N-dimethylacetamide, N, N-dimethylformamide and N-methylpyrrolidone, sulfur-containing compounds such as dimethyl sulfoxide and sulfolane, and organic acids such as formic acid, acetic acid, lactic acid, and acetic anhydride. Preferably, the above aliphatic hydrocarbons, aromatic hydrocarbons and organic acids are used. The reaction temperature is usually from 0 to 200 ^o C, preferably from 20 ^o C to the boiling point of the mixture. The reaction time is from 10 minutes to 72 hours, preferably from 30 minutes to 24 hours.

 The second stage is carried out under the same conditions as described for method (13).

Способ 23
Способ (23) осуществляется в две стадии. Исходные вещества для первой стадии карбаматы (XLI) получаются по обычной методологии. Они обрабатываются алкил-3-амино-4,4,4-трифторкротонатом в условиях, описанных для способа (20). Вторая стадия осуществляется при тех же условиях, какие описаны для способа (15).

Method 23
Method (23) is carried out in two stages. The starting materials for the first stage carbamates (XLI) are obtained according to the usual methodology. They are treated with alkyl-3-amino-4,4,4-trifluorocrotonate under the conditions described for method (20). The second stage is carried out under the same conditions as described for method (15).

Способ 24
При способе (24) изоцианат (III) обрабатывается гидразоносоединением (XLIII) при тех же условиях, какие описаны для способа (20), с образованием нужного продукта реакции (XXXIII).

Method 24
In the method (24), the isocyanate (III) is treated with the hydrazono compound (XLIII) under the same conditions as described for the method (20) to form the desired reaction product (XXXIII).

 Although some embodiments of the present invention are described below, the scope of the present invention is not limited to such options.

 Examples of the preparation of the compounds of the present invention will be described. The preparation of 3- (4-chloro-2-fluoro-5-hydroxyphenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione is described in US Pat. No. 4,859,229. Lawson's reagent [2,4-bis (4-Methoxyphenyl) -1,3-dithia-2,4-diphosphethane-2,4-disulfide] obtained from Aldrich.

Examples
All temperature values are measured in ^o C, "conc." means "concentrated," and "mp." denotes the melting point. "Processing, treating" indicates that water and ethyl acetate are added, the solutions are separated, and the organic phase is dried over sodium sulfate, filtered, and the filtrate is evaporated under reduced pressure. Preparation of 5-amino-2-chloro-4-fluorophenol is described in U.S. Patent No. 4484941. The purity is estimated by TLC, HPLC, and monitored using the spectra of ¹ H and ¹³ C nuclear magnetic resonance (NMR), which is obtained on Varian instrument 300 MHz

Example 1
Synthesis of 4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenylisocyanate (intermediate IIIc)
(Method 1)
1.1.

2- (5-amino-2-chloro-4-fluorophenoxy) pyrimidine (intermediate IIp)
A mixture of 5-amino-2-chloro-4-fluorophenol (3.57 g), potassium carbonate (3.04 g) and 2-chloropyrimidine (3.20 g) is suspended in butan-2-one (100 ml) and dimethyl sulfoxide (10 ml), and refluxed overnight. The solution was treated and chromatographed on silica gel, eluting with a 1: 2 mixture of ethyl acetate and hexane, to give yellow crystals (4.0 g).

¹ H NMR (acetone-d ₆ , TMS): 4.75 (2H, br), 6.78 (1H, d, J = 8.4 Hz), 7.09 (1H, d, J = 10.6 Hz), 7.15 (1H, t, J = 4.8 Hz), 8.56 (2H, d, J = 4.8 Hz).

 In a similar manner, the following compounds can be prepared.

 2- (5-amino-2-chloro-4-fluorophenoxy) -4-chloropyrimidine (intermediate IIq).

 2- (5-amino-2-chloro-4-fluorophenoxy) -4,6-dimethoxypyrimidine (intermediate IIr).

 2- (5-amino-2,4-dichlorophenoxy) -4-chloropyrimidine (intermediate IIs).

 2- (5-amino-2-clop-4-fluorophenoxy) nitrobenzene (intermediate IIt).

 2- (5-amino-2-chloro-4-fluorophenoxy) benzonitrile (intermediate IIu).

 2- (5-amino-2-chloro-4-fluorophenoxy) -6-fluorobenzonitrile (intermediate IIv).

1.2
4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl isocyanate (intermediate IIIc)
A solution of triphosgene (1.21 g) in ethyl acetate (10 ml) was stirred at 0 ^{° C.} under a nitrogen atmosphere, and at this time a solution of 2- (5-amino-2-chloro-4-fluorophenoxy) pyrimidine (0, 96 g) and triethylamine (1.2 ml) in ethyl acetate (10 ml). The mixture was refluxed for 3.5 hours, cooled, filtered, and the filtrate was evaporated to give the corresponding isocyanate.

¹ H NMR (CDCl ₃ , TMS): 7.03 (1H, d, J = 7.2 Hz), 7.10 (1H, t, J = 4.8 Hz), 7.31 (1H, d, J = 8.9 Hz), 8.57 (2H, d, J = 4.8 Hz).

 In a similar manner, the following compounds can be prepared.

 4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyrimidyloxy) phenyl isocyanate (intermediate IIId).

 4-chloro-2-fluoro-5- (2-nitrophenoxy) phenylisocyanate (intermediate IIIe).

 4-chloro-2-fluoro-5- (2-cyanophenoxy) phenyl isocyanate (intermediate IIIf).

 4-chloro-2-fluoro-5- (6-fluoro-2-cyanophenoxy) phenyl isocyanate (intermediate IIIg).

Example 2
Synthesis of 4-chloro-3- (4-chloro-2-fluoro-5- (4,6-dimethoxy-2-triazinyl-oxy) phenyl) -1-methyl-5-trifluoromethyl-lH-pyrazole (compound 1-8) ( method 2)
4-chloro-3- (4-chloro-2-fluoro-5-hydroxyphenyl) -1-methyl-5-tritoromethyl-1H-pyrazole (obtained by the method described in US Pat. No. 5,281,571) (0.25 g, 0, 76 mmol) was dissolved in N, N-dimethylformamide (5 ml), and potassium carbonate (0.13 g, 0.91 mmol) and 2-chloro-4,6-dimethoxytriazine (0.16 g, 0.91 mmol) were added. ) The suspension is stirred at 90 ^{° C.} for 2 hours under a nitrogen atmosphere and treated. The residue was subjected to silica gel column chromatography, eluting with a mixture of methylene chloride and methanol, 99: 1, to obtain the title compound (0.29 g, 81.6%).

¹ H NMR (CDCl ₃ , TMS): 4.01 (6H, s), 4.07 (3H, m), 7.35 (1H, d, J = 9.1 Hz), 7.45 (1H, t, J = 6.6 Hz).

Example 3
Synthesis of 5-chloro-4- (4-chloro-2-fluoro-5- (4,6-dimethoxy-2-triazinyloxy) phenyl) -1-difluoromethyl-2-methylimidazole (compound 2-4) (method 3)
5-chloro-4- (4-chloro-2-fluoro-5-hydroxyphenyl) -1-difluoromethyl-2-methylimidazole (obtained by the method described in patent EP 590834) (0.31 g, 1 mmol) is dissolved in N , N-dimethylformamide (5 ml). Potassium carbonate (0.17 g, 1.2 mmol) and 2-chloro-4,6-dimethoxytriazine (0.21 g, 1.2 mmol) are added, and the suspension is stirred at 110 ^{° C.} for 2 hours under nitrogen. . The mixture was worked up and the residue was chromatographed on silica gel eluting with a mixture of methylene chloride and methanol 98: 2 to give the title compound (0.25 g, 55%).

¹ H NMR (CDCl ₃ , TMS): 2.61 (3H, br), 4.00 (6H, s), 7.17 (1H, t, J = 58.1 Hz), 7.29 (1H, d, J = 9.3 Hz), 7.53 (1H, d, J = 6.6 Hz).

Example 4
Synthesis of 1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -4-difluoromethyl-3-methyl-1,4-dihydro-1,2,4-triazolin-5-one ( compound 3-1) (method 4)
4.1
4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenylhydrazone pyruvic acid
A solution of sodium nitrite (2.01 g) in water (15 ml) was added dropwise over 10 minutes to a solution of 2- (5-amino-2-chloro-4-fluorophenoxy) pyrimidine (7.0) cooled to -10 ^{° C.} g) in concentrated hydrochloric acid (40 ml) and stirred in a nitrogen atmosphere. Stirring is continued for 30 minutes at this temperature, and a solution of tin (II) chloride dihydrate (16.3 g) in hydrochloric acid (20 ml) is added over 10 minutes. The resulting mixture was stirred for 2 hours at room temperature. Water (20 ml) was added and a solution of pyruvic acid (2.55 g) in water (10 ml) was added dropwise. The resulting mixture was stirred for 30 minutes, and the yellow precipitate formed was collected by filtration to obtain 11.24 g (wet weight) of the desired product.

4.2
1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -3-methyl-1,4-dihydro-1,2,4-triazolin-5-one
To a suspension of 4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenylhydrazone pyruvic acid (1.24 g) in toluene (30 ml) was added triethylamine (0.4 g) at room temperature. Diphenylphosphoryl azide (1.05 g) was added, and the resulting mixture was refluxed for 1 hour. The solution was treated and the residue was chromatographed on silica gel eluting with ethyl acetate to give a yellow solid (0.75 g).

4.3
1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -4-difluoromethyl-3-methyl-1,4-dihydro-1,2,4-triazolin-5-one (compound 3- 1)
Chlorodifluoromethane gas was bubbled for several hours with stirring at room temperature, until saturation, through a solution of 1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -3-methyl-1,4-dihydro-1 , 2,4-triazolin-5-one (0.43 g) in tetrahydrofuran (100 ml). Potassium hydroxide (0.4 g) and a catalytic amount of tetrabutylammonium bromide are added, and the cooling bath is removed. The mixture was stirred at room temperature for 48 hours. The solution was treated and the resulting oil was chromatographed on silica gel eluting with a mixture of ethyl acetate, hexane and methylene chloride, 1: 2: 2, and a colorless oil (0.25 g) was obtained.

Example 5
Synthesis of 3- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -5-isopropylidinimidazolidine-2,4-dione (compound 4-1) (method 5)
5.1
4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl urea
A solution of 4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylisocyanate (1.3 g) in toluene (30 ml) is cooled to 5 ^{° C.} and ammonia gas is bubbled through it for 15 minutes . Stirring was continued for another 30 minutes, and the mixture was filtered and the filtrate was evaporated to give a white solid (1.3 g).

¹ H NMR (CDCl ₃ ): 2.40 (3H, s), 7.20 (5H, m).

5.2
3- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -5-isopropylidinimidazolidin-2,4-dione (compound 4-1)
Solution of 4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylurea (1.24 g), ethyl 3-methyl-2-oxobutyrate (0.9 g) and p-toluenesulfonic acid ( 0.1 g) in toluene (30 ml) was refluxed for 14 hours and treated to give a white solid (0.55 g), mp > 220 ^o C.

¹ H NMR (CDCl ₃ ): 1.90 (3H, s), 2.30 (3H, s), 7.12 (1H, dd, J = 5.7 Hz), 7.30 (1H, d, J = 7 Hz), 7.40 (1H, d, J = 9 Hz), 8.00 (1H, d, J = 7 Hz), 8.25 (1H, m), 8.62 (1H, s )

Example 6
Synthesis of 2- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -6,7-dihydropyrrolo [1,2-c] pyrimidine-1,3- (2H, 5H) dione (compound 5-10) (method 6)
6.1
2- (4-chloro-2-fluoro-5-isopropyloxyphenyl) -6,7-dihydropyrrolo [1,2-c] pyrimidine-1,3 (2H, 5H) -dione
4-chloro-2-fluoro-5-isopropyloxyaniline (9.4 g) and triethylamine (9.4 g) in dry ethyl acetate (110 ml) were stirred at 0 ^{° C.} and a solution of triphosgene (13.8 g) was added dropwise. in ethyl acetate (110 ml). The mixture was refluxed for 2 hours, cooled to room temperature, filtered, and the filtrate was evaporated. The crude isocyanate was dissolved in N, N-dimethylformamide (70 ml), and dropwise added to a mixture of sodium hydride (1.2 g) and 2,2-dimethyl-5- (2-tetrahydropyrrolidene) -1,3-dioxane-4 , 6-dione (9.9 g) in N, N-dimethylformamide (50 ml) with stirring at -30 ^° C. The mixture was stirred at room temperature for 0.5 hours and at 110 ^{° C.} for 4 hours. The volume is reduced under reduced pressure, and the residue is treated. Column chromatography (silica gel, hexane: ethyl acetate, 2: 3) gives 2- (4-chloro-2-fluoro-5-isopropyloxyphenyl) -6,7-dihydropyrrolo [1,2-c] pyrimidine-1,3 (2H, 5H) -dione (9.0 g, 60%).

¹ H NMR (CDCl ₃ , TMS): 1.36 (6H, d, J = 6.1 Hz), 2.19 (2H, m), 2.99 (2H, t, J = 7.9 Hz) 3.99 (2H, m), 4.46 (1H, m), 5.74 (1H, s), 6.85 (1H, d, J = 6.6 Hz), 7.29 (1H, d, J = 6.6 Hz).

6.2
2- (4-chloro-2-fluoro-5-hydroxyphenyl) -6,7-dihydropyrrolo- [1,2-c] pyrimidin-1,3 (2H, 5H) -dione
This substance is synthesized from 2- (4-chloro-2-fluoro-5-isopropyloxyphenyl) -6,7-dihydropyrrolo [1,2-c] pyrimidin-1,3 (2H, 5H) -dione in 86% yield with the same conditions as described below for the preparation of 2- (4-chloro-2-fluoro-5-hydroxyphenyl) hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin-1- she (example 10.2).

¹ H NMR (CDCl ₃ , TMS): 2.22 (2H, m), 3.06 (2H, t, J = 7.5 Hz), 3.13 (1H, br), 4.01 (2H, t, J = 6.5 Hz), 5.71 (1H, s), 6.87 (1H, t, J = 6.9 Hz), 7.18 (1H, d, J = 9.3 Hz) .

6.3
2- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -6,7-dihydropyrrolo [1,2-c] pyrimidine-1,3 (2H, 5H) -dione ( compound 5-10) (method 1)
This substance is synthesized from 2- (4-chloro-2-fluoro-5-hydroxyphenyl) -6,7-dihydropyrrolo [1,2-c] pyrimidin-1,3 (2H, 5H) -dione and 2-chloro-3 trifluoromethylpyridine in 90% yield under the same conditions as described below to obtain 2- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] hexahydro-3-thioxo-1H- [1,2,4 ] triazolo [1,2-a] pyridazin-1-one (example 10.3) (compound 8-29).

Example 7
Synthesis of 1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -4- (3-fluoropropyl) -1,4-dihydro-5-oxo-5H-tetrazole (compound 6-10) ( method 7)
7.1
1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -1,4-dihydro-5-oxo-5H-tetrazole
4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenylisocyanate (0.96 g) and trimethylsilyl azide (5 ml) were refluxed under nitrogen overnight. The reaction mixture was worked up and the resulting oil was chromatographed on silica gel eluting with a 1: 4 mixture of ethyl acetate and methylene chloride to give a yellow semi-solid (0.54 g).

¹ H NMR (CDCl ₃ , TMS): 7.16 (1H, dd, J = 4.8 Hz), 7.49 (1H, d, J = 9.3 Hz), 7.64 (1H, d, J = 6.8 Hz), 8.59 (2H, d, J = 4.8 Hz).

7.2
1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -4- (3-fluoropropyl) -1,4-dihydro-5-oxo-5H-tetrazole (compound 6-10) (method 6-10) 1)
A suspension of potassium carbonate (0.36 g), 1- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -1,4-dihydro-5-oxo-5H-tetrazole 0.54 g) and 1-bromo-3-fluoropropane (0.37 g) in N, N-dimethylformamide (10 ml) was stirred in an oil bath at 80 ^{° C.} for 26 hours. The reaction mixture was worked up and the resulting oil was chromatographed on silica gel eluting with a 2: 1 mixture of hexane and ethyl acetate to give the reaction product, mp. 111-3 ^o C.

¹ H NMR (CDCl ₃ , TMS): 2.30 (2H, m), 4.20 (2H, t, J = 6.9 Hz), 4.59 (2H, dt, J = 46.9, 6 6 Hz), 7.13 (1H, dd, J = 4.8 Hz), 7.48 (1H, d, J = 9.3 Hz), 7.58 (1H, d, J = 6.8 Hz), 8.58 (2H, d, J = 4.8 Hz).

Example 8
Synthesis of 9- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylimino] -8-thia-1,6-diazabicyclo [4.3.0] nonan-7-one (compound 7 -1) (method 8)
8.1
N- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylaminothiocarbonyl] -N ¹ -formylhydrazine
Ant hydrazide (0.6 g) was added to a mixture of 4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylisothiocyanate (3.4 g) in tetrahydrofuran (20 ml), and the mixture was stirred for 3 hours at room temperature. The solvent was removed under reduced pressure, and the residue was treated. The resulting oil was dissolved in ethanol (30 ml) and hexane was added to cause crystallization. The crystals are filtered off and dried to give a reaction product (3.5 g, 69%).

8.2
5- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylimino] -3-formyl-1,3,4-thiadiazolidin-2-one
To a solution of N- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylaminothiocarbonyl] -N ¹ -formylhydrazine (2.8 g) in acetone (70 ml) was added with stirring at 0 ^{° C.} triphosgene (0.7 g) in toluene (20 ml). Stirring was continued at room temperature for 1 hour, and the solvents were removed under reduced pressure. Column chromatography (methylene chloride: ethyl acetate, 3: 1) gives the reaction product (3.3 g).

8.3
5- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylimino] -1,3,4-thiadiazolidin-2-one
To a solution of 5- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylimino] -3-formyl-1,3,4-thiadiazolidin-2-one (3.3 g) in acetone (60 ml) add a 10% solution of hydrogen chloride in methanol (8 ml). After stirring for 0.5 hours, the solvents were removed under reduced pressure. A minimal amount of ethanol was used to dissolve the residue, and hexane was added to cause crystallization. The crystals are filtered off and dried, and a reaction product is obtained (1.0 g, 36%).

8.4
9- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylimino] -8-thia-1,6-diazabicyclo [4.3.0] nonan-7-one (compound 7- 1)
1,4-dibromobutane (0.64 g) was mixed with 5- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylimino] -1,3,4-thiadiazolidin-2-one ( 1.0 g) in acetone (25 ml) and potassium carbonate (0.85 g) was added. The mixture was refluxed for 2 hours and the solvent was evaporated. The residue was taken up and the resulting oil was chromatographed (silica gel, hexane: ethyl acetate, 4: 1) to give the reaction product (0.65 g, 57%).

Example 9
Synthesis of 3- [4-chloro-2-fluoro-5- (trifluoromethyl-2-pyridyloxy) phenyl] -1-ethylimidazolidine-2,4-dione (compound 8-1) (method 9)
9.1
N- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -2-chloroacetamide
A solution of 2- (5-amino-2-chloro-4-fluorophenoxy) -3-trifluoromethylpyridine (1.32 g) and triethylamine (0.8 ml) in toluene (20 ml) is stirred at 0 ^{° C.} while a solution of chloroacetyl chloride is added (0.4 ml) in toluene (10 ml). The mixture was stirred overnight at room temperature and worked up. Column chromatography on silica gel using methylene chloride as eluent gave a white solid (1.4 g), mp 146-9 ^o C.

¹ H NMR (CDCl ₃ , TMS): 4.20 (2H, s), 7.12 (1H, dd, J = 5.8 Hz), 7.30 (1H, d, J = 9 Hz), 8 01 (1H, m), 8.22 (1H, m), 8.34 (1H, d, J = 7 Hz).

9.2
N- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -2-ethylaminoacetamide
A solution of N- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -2-chloroacetamide (1.4 g) and 70% ethylamine (5 ml) in ethanol (25 ml) is boiled under reflux for 3 hours and evaporated to dryness. The residue was taken up and a yellow solid (1.0 g) was obtained.

¹ H NMR (CDCl ₃ , TMC): 1.16 (3H, t, J = 7 Hz), 2.72 (2H, q, J = 7 Hz), 3.39 (2H, s), 7.10 (1H, dd, J = 6.8 Hz), 7.26 (1H, d, J = 8 Hz), 8.00 (1H, m), 8.24 (1H, m), 8.45 (1H d, J = 8 Hz), 9.86 (1H, s).

9.3
3- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -1-ethylimidazolidin-2,4-dione (compound 8-1)
A solution of N- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -2-ethylaminoacetamide (0.82 g) and 1.1 ¹ -carbonylimidazole (0.43 g) in toluene (20 ml) is refluxed for 2 hours, cooled and treated. Silica gel column chromatography, eluting with 2.5% methanol in methylene chloride, gives a tan solid (0.8 g), mp 162-3 ^o C.

¹ H NMR (CDCl ₃ , TMC): 1.24 (3H, t, J = 7 Hz), 3.53 (2H, q, J = 7 Hz), 4.05 (2H, s), 7.13 (1H, m), 7.30 (1H, d, J = 7 Hz), 7.38 (1H, d, J = 9 Hz), 8.01 (1H, m), 8.24 (1H, m )

Example 10
Synthesis of 2- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin-1-one ( compound 8-29) (method 10)
10.1
2- [4-chloro-2-fluoro-5- (isopropyloxy) phenyl] hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin-1-one
A solution of 4-chloro-2-fluoro-5-isopropyloxyaniline (12.1 g) and triethylamine (12.0 g) in ethyl acetate (120 ml) is cooled to 0 ^{° C.} and stirred until a solution of thiophosgene (6.8) is added dropwise. g) in ethyl acetate (100 ml). The reaction mixture was refluxed for 2 hours, and the mixture was filtered and the filtrate was evaporated. The crude isothiocyanate was dissolved in benzene (70 ml) and treated with a solution of 1-ethyloxycarbonylhexahydropyridazine (9.5 g) in benzene (10 ml). After stirring for 3 hours, the solvent was evaporated, and the residue was dissolved in m-xylene (250 ml) containing sodium acetate (1.6 g), and refluxed for 22 hours. The solvents were removed under reduced pressure and the residue was chromatographed (silica gel, hexane: ethyl acetate, 60:40) to give the reaction product (17.2 g, 81%).

¹ H NMR (CDCl ₃ , TMS): 1.37 (6H, d, J = 7.8 Hz), 1.96 (4H, m), 3.71 (2H, m), 4.02 (2H, m), 4.47 (1H, m), 6.95 (1H, d, J = 6.4 Hz), 7.30 (1H, d, J = 9.0 Hz).

10.2
2- (4-chloro-2-fluoro-5-hydroxyphenyl) hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin-1-one
To a solution of 2- [4-chloro-2-fluoro-5- (isopropyloxy) phenyl] hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin-1-one (17 , 2 g) in methylene chloride (120 ml) with stirring at 0 ^o With added dropwise concentrated sulfuric acid (22 ml). The mixture was stirred at room temperature for 1 hour, and ice water (200 g) was added. The aqueous phase was extracted with methylene chloride and the organic phases were combined, dried over sodium sulfate and chromatographed (silica gel, ethyl acetate) to give the reaction product (14.5 g, 96%).

¹ H NMR (CDCl ₃ , TMS): 1.84 (4H, m), 3.82 (4H, m), 7.06 (1H, d, J = 6.5 Hz), 7.58 (1H, d, J = 8.8 Hz), 10.6 (1H, s).

10.3
2- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin-1-one (compound 8-29)
2- (4-chloro-2-fluoro-5-hydroxyphenyl) hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin-1-one (0.5 g) are mixed with 2-chloropyrimidine (1 equiv.) and potassium carbonate (2 equiv.) in dimethyl sulfoxide (20 ml), and the resulting mixture was stirred at 100 ^{° C.} for 1.5 hours and at room temperature overnight. The mixture was worked up and the residue was subjected to column chromatography (silica gel, methylene chloride: ethyl acetate, 3: 1) to obtain the reaction product (0.34 g, 55%).

¹ H NMR (CDCl ₃ , TMS): 1.92 (4H, m), 3.69 (2H, m), 3.99 (2H, m), 7.05 (1H, m), 7.37 ( 1H, d, J = 6.5 Hz), 7.39 (1H, d, J = 9.0 Hz), 8.53 (2H, d, J = 4.8 Hz).

Example 11
Synthesis of 2- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] hexahydro-3-thioxo-1H- [1,2,4] triazolo [1,2-a] pyridazin- 1-one (compound 8-18) (method 11)
9- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenylimino] -8-thia-1,6-diazabicyclo [4.3.0] nonan-7-one (see example 8) (0.2 g) was mixed with methanol (18 ml) and a catalytic amount of sodium methoxide was added. The mixture was refluxed for 0.5 hours, and the solvent was removed under reduced pressure. Column chromatography (silica gel, hexane: ethyl acetate, 3: 2) gives the reaction product (0.2 g, 100%).

Example 12
(R, S) -2- [4-Chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8- 47) (method 11)
To a solution of 4-chloro-2-fluoro-5- (2-pyrimidyloxy) aniline (0.4 g) and triethylamine (0.34 g) in dry ethyl acetate (10 ml), thiophosgene (0.192 g) was added and the solution was boiled with reflux for 1.5 hours. After cooling, the solution was filtered, and the filtrate was evaporated under reduced pressure. The residue was dissolved in dry ethyl acetate (10 ml), and ethylpipecolinate (0.288 g) was added. The solution was refluxed for 1 hour and evaporated to give a brown solid. This material was purified using column chromatography eluting with dichloromethane to give white crystals (0.35 g). T. pl. 238-239 ^o C.

 The following compounds are prepared in a similar manner.

 (R, S) -2- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] hexahydroimidazo [1,5-a] pyridin-1,3-dione (compound 8-48).

 (S) -2- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8-49) .

 (S) -2- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] hexahydro-3-thioxopyrro [1,2-c] imidazole-1 (1H) -one (compound 8-50) .

 (R, S) -2- (4-chloro-2-fluoro-5-phenoxyphenyl) hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8-51).

 (R, S) -2- [4-chloro-2-fluoro-5- (2-nitrophenoxy) phenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8- 52).

 (R, S) -2- [4-chloro-5- (2-cyanophenoxy) -2-fluorophenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8-53 )

 (R, S) -2- [4-chloro-2-fluoro-5- (2-pyrazinyloxy) phenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8- 54).

 (R, S) -2- [4-chloro-2-fluoro-5- (2-pyridyloxy) phenyl] hexahydro-3-thioxoimidazo [l, 5-a] pyridin-1 (5H) -one (compound 8- 55).

 (R, S) -2- [4-chloro-5- (3-chloro-2-pyridyloxy) -2-fluorophenoxy] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8-56).

 (R, S) -2- [4-chloro-5- (3-chloro-5-trifluoromethyl-2-pyridyloxy) -2-fluorophenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H ) -one (compound 8-57).

 (R, S) -2- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) - he (compound 8-58).

 (R, S) -2- [4-chloro-2-fluoro-5- (3-nitropyridyloxy) phenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8- 59).

 (R, S) -2- [4-chloro-5- (3-cyano-2-pyridyloxy) -2-fluorophenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8-60).

Example 13
(R, S) -2- [5- (3-amino-2-pyridyloxy) -4-chloro-2-fluorophenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8-61).

 (R, S) -2- [4-chloro-2-fluoro-5- (3-nitropyridyloxy) phenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (0.21 d) dissolved in ethyl acetate (10 ml), is reduced in a hydrogen atmosphere using palladium-on-charcoal (10%, 50 mg) as a catalyst. After stirring at room temperature for 5 hours, the mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography eluting with a 9: 1 mixture of dichloromethane and ethyl acetate to give a yellow oil (0.28 g).

Similarly get
(R, S) -2- [5- (2-aminophenoxy) -4-chloro-2-fluorophenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one (compound 8-62 )

Example 14
(R, S) -2- [5- (3-acetylamino-2-pyridyloxy) -4-chloro-2-fluorophenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) -one ( connection 8-63)
To a solution of (R, S) -2- [5- (3-amino-2-pyridyloxy) -4-chloro-2-fluorophenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H) - it (0.22 g) and triethylamine (0.066 g) in dry ethyl acetate (10 ml), acetyl chloride (0.047 g) was added with stirring at 5 ^{° C.} The solution was stirred for 1 hour at room temperature, filtered, and the filtrate was evaporated. The residue was purified by column chromatography, eluting with a 8: 2 mixture of dichloromethane and ethyl acetate, and brown crystals (0.24 g) were obtained.

Similarly get
(R, S) -2- [5- [2 - [(bis-benzoyl) amino] phenoxy] -4-chloro-2-fluorenyl] hexahydro-3-thioxoimidazo [1,5-a] pyridin-1 (5H ) -one (compound 8-64).

Example 15
Synthesis of 1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione ( connection 9-1)
15.1
Synthesis of 2- (5-amino-2-chloro-4-fluorophenoxy) -3-nitropyridine (intermediate IIa) (method 1)
A mixture of 5-amino-2-chloro-4-fluorophenol (0.64 g), ground potassium hydroxide (0.24 g) and 2-chloro-3-nitropyridine (0.76 g) in dimethyl sulfoxide (15 ml) is heated at 110 ^o With stirring for 2 hours. The solution was treated and the resulting oil was chromatographed on silica gel eluting with a mixture of methanol and methylene chloride, 3:97 to give 2- (5-amino-2-chloro-4-fluorophenoxy) -3-nitropyridine (intermediate IIa) as a yellow semi-solid substances (0.45 g).

 The following compounds are prepared in a similar manner.

 2- (5-amino-2-chloro-4-fluorophenoxy) -5-bromopyridine (intermediate IIb).

 2- (5-amino-2-chloro-4-fluorophenoxy) -5-chloropyridine (intermediate IIc).

 2- (5-amino-2-chloro-4-fluorophenoxy) -6-fluoropyridine (intermediate IId).

 2- (5-amino-2-chloro-4-fluorophenoxy) -6-chloropyridine (intermediate IIe).

 2- (5-amino-2-chloro-4-fluorophenoxy) -3,5,6-trifluoropyridine (intermediate IIf).

 2- (5-amino-2-chloro-4-fluorophenoxy) -3-trifluoromethylpyridine (intermediate IIg).

 2- (5-amino-2-chloro-4-fluorophenoxy) -4-trifluoromethylpyridine (intermediate IIh).

 2- (5-amino-2-chloro-4-fluorophenoxy) -3-cyanopyridine (intermediate IIi).

 2- (5-amino-2-chloro-4-fluorophenoxy) -5-cyanopyridine (intermediate IIj).

 2- (5-amino-2-chloro-4-fluorophenoxy) -5-nitropyridine (intermediate IIk).

 2- (5-amino-2,4-difluorophenoxy) -3-trifluoromethylpyridine (intermediate IIl).

 2- (5-amino-2-chloro-4-fluorophenoxy) -3-ethylsulfonylpyridine (intermediate IIm).

 2- (5-amino-2-chloro-4-fluorophenoxy) -3-methyl-4-nitroisothiazole (intermediate IIn).

 2- (5-amino-2-chloro-4-fluorophenoxy) pyridine (intermediate IIo).

15.2
Synthesis of 3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11- 1) (method 20)
A solution of triphosgene (0.47 g) in ethyl acetate (10 ml) was stirred under nitrogen until a solution of 2- (5-amino-2-chloro-4-fluorophenoxy) -3-nitropyridine (0.45 g) was added dropwise and triethylamine (0.45 ml) in ethyl acetate (15 ml). The mixture was refluxed for 2 hours, cooled, filtered, and the filtrate was evaporated, and the corresponding isocyanate was obtained.

A suspension of sodium hydride (0.038 g) in N, N-dimethylformamide (2 ml) was stirred at 0 ^° C under nitrogen atmosphere, adding a solution of ethyl 3-amino-4,4,4-trifluorocrotonate (0) at that time. 26 g) in N, N-dimethylformamide (1 ml). After 15 minutes, a solution of the resulting isocyanate in N, N-dimethylformamide (5 ml) and toluene (5 ml) was gradually added, and the solution was stirred overnight at room temperature. Dilute hydrochloric acid was added and the solution was treated. The resulting solid is chromatographed on silica gel, eluting with a mixture of methanol and methylene chloride, 5:95 to give 3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1, 2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-1) as a white solid (0.32 g).

 The following compounds are prepared in a similar manner.

 3- [4-chloro-2-fluoro-5- (5-bromo-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-2 )

 3- [4-chloro-2-fluoro-5- (5-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-3 )

 3- [4-chloro-2-fluoro-5- (6-fluoro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-4 )

 3- [4-chloro-2-fluoro-5- (6-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-5 )

 3- [4-chloro-2-fluoro-5- (3,5,6-trifluoro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate compound 11-6).

 3- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-7 )

 3- [4-chloro-2-fluoro-5- (4-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-8 )

 3- [4-chloro-2-fluoro-5- (3-cyano-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-9 )

 3- [4-chloro-2-fluoro-5- (5-cyano-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-10 )

 3- [4-chloro-2-fluoro-5- (5-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-11 )

 3- [2,4-difluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-12).

 3- [4-chloro-2-fluoro-5- (3-ethylsulfonyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-13 )

 3- [4-chloro-2-fluoro-5- (3-methyl-4-nitro-5-isothiazolyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione ( intermediate 11-14).

 3- [4-chloro-2-fluoro-5- (4-chloro-2-pyrimidyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-16 )

 3- [4-chloro-2-fluoro-5- (4,6-dimethoxy-2-pyrimidyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11 -17).

15.3
Synthesis of 1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione ( compound 9-1) (method 15)
Potassium carbonate suspension (0.23 g), 3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine -2,4-dione (0.5 g) and 2,4-dinitrophenoxyamine (0.32 g) in N, N-dimethylformamide (10 ml) were stirred at room temperature overnight. The solution was treated and the resulting oil was chromatographed on silica gel, eluting with a mixture of methanol and methylene chloride, 2:98. The reaction product is isolated in the form of a yellow semi-solid (0.3 g), so pl. 90-6 ^o C.

 The following compounds are prepared in a similar manner.

 1-amino-3- [4-chloro-2-fluoro-5- (5-bromo-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-2).

 1-amino-3- [4-chloro-2-fluoro-5- (5-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-3).

 1-amino-3- [4-chloro-2-fluoro-5- (6-fluoro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-4).

 1-amino-3- [4-chloro-2-fluoro-5- (6-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-5).

 1-amino-3- [4-chloro-2-fluoro-5- (3,5,6-trifluoro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4 dione (compound 9-6).

 1-amino-3- [4-chloro-2-fluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-7).

 1-amino-3- [4-chloro-2-fluoro-5- (4-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-8).

 1-amino-3- [4-chloro-2-fluoro-5- (3-cyano-2-pyridyloxy) phenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-9).

 1-amino-3- [4-chloro-2-fluoro-5- (5-cyano-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-10).

 1-amino-3- [4-chloro-2-fluoro-5- (5-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-11).

 1-amino-3- [2,4-difluoro-5- (3-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9 -12).

 1-amino-3- [4-chloro-2-fluoro-5- (3-ethylsulfonyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-13).

 1-amino-3- [4-chloro-2-fluoro-5- (3-methyl-4-nitroisothiazol-5-yloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4 dione (compound 9-14).

 1-amino-3- [4-chloro-2-fluoro-5- (2-pyrimidyloxy) phenyl] -6-trifluoromethyl-l, 2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-16) .

 1-amino-3- [4-chloro-2-fluoro-5- (4-chloro-2-pyrimidyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-17).

 1-amino-3- [4-chloro-2-fluoro-5- (4,6-dimethoxy-2-pyrimidyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-18).

Example 16
Synthesis of 1-amino-3- [4-chloro-2-fluoro-5- (2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-15 ) (method 16)
A solution of triphosgene (0.5 g) in ethyl acetate (10 ml) was stirred under nitrogen until a solution of 2- (5-amino-2-chloro-4-fluorophenoxy) pyridine (0.4 g) and triethylamine (0) was added dropwise. 5 ml) in ethyl acetate (20 ml), the mixture is refluxed for 2 hours, cooled, filtered, and the filtrate is evaporated, and the corresponding isocyanate is obtained.

A suspension of sodium hydride (0.05 g) in N, N-dimethylformamide (2 ml) was stirred at 0 ^{° C.} under a nitrogen atmosphere, and a solution of ethyl 3-amino-4,4,4-trifluorocrotonate was added dropwise at this time. (0.32 g) in N, N-dimethylformamide (1 ml). After 15 minutes, a solution of the resulting isocyanate in N, N-dimethylformamide (5 ml) and toluene (5 ml) was gradually added. The solution was stirred at room temperature for 2 hours, and treated with a solution of 2,4-dinitrophenoxyamine (0.42 g) in N, N-dimethylformamide (4 ml). Stirring is continued for 3 days. The solution is treated and a solid is obtained which is chromatographed on silica gel eluting with a mixture of methanol and methylene chloride, 5:95. The title compound is obtained as a yellow solid (0.3 g).

 The following compounds are prepared in a similar manner.

 1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-1).

 1-amino-3- [4-chloro-2-fluoro-5- (5-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-3).

Example 17
Synthesis of 1-amino-3- [4-chloro-2-fluoro-5- (2-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-21 )
17.1
3- [4-chloro-2-fluoro-5- (2-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-18) (method 18 )
A mixture of 3- (4-chloro-2-fluoro-5-hydroxyphenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (2.2 g), 2-chloronitrobenzene (1.3 g) and potassium carbonate (1.4 g) in N, N-dimethylformamide (100 ml) are refluxed for 3 hours under nitrogen. The resulting mixture was poured into water (200 ml) and acidified by adding a small amount of concentrated hydrochloric acid. The solution was extracted with a mixed solvent (ethyl acetate: hexane, 1: 1, 400 ml), and the organic phase was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was chromatographed on silica gel eluting with a 1: 1 mixture of ethyl acetate and hexane to give 3- [4-chloro-2-fluoro-5- (2-nitrophenoxy) phenyl] -6-trifluoromethyl-1 , 2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-18) as an amorphous solid (1.0 g).

 The following compounds are prepared in a similar manner.

 3- [4-chloro-2-fluoro-5- (3-methylsulfonyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-19 )

 3- [4-chloro-2-fluoro-5- (3-isopropylsulfonyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-20 )

 3- [4-chloro-2-fluoro-5- (4-nitrofecoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-21).

 3- [4-chloro-2-fluoro-5- (4-nitro-2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-22 )

 3- [4-chloro-2-fluoro-5- (3-nitro-5-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-23 )

 3- [4-chloro-2-fluoro-5- (2-cyanophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-33).

 3- [4-chloro-2-fluoro-5- (2-cyano-3-fluorophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-34 )

17.2
1-amino-3- [4-chloro-2-fluoro-5- (2-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-21) (method 15)
Suspension of 3- (4-chloro-2-fluoro-5- (2-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione (1.0 g), potassium carbonate (0.37 g) and 2,4-dinitrophenoxyamine (0.54 g) in anhydrous N, N-dimethylformamide (20 ml) was stirred at room temperature for 20 hours, the solution was treated and the resulting oil was chromatographed on silica gel eluting with a mixture methylene chloride, hexane and ethyl acetate, 2: 3: 0.5 The reaction product is crystallized from a mixture of methylene chloride, hexane and ethyl acetate to give a white solid (0.45 g).

 The following compounds are prepared in a similar manner.

 1-amino-3- [4-chloro-2-fluoro-5- (3-methylsulfonyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-19).

 1-amino-3- [4-chloro-2-fluoro-5- (3-isopropylsulfonyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-20).

 1-amino-3- [4-chloro-2-fluoro-5- (4-nitro-2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-22).

 1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-5-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-23).

 1-amino-3- [4-chloro-2-fluoro-5- (2-cyanophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-30) .

 1-amino-3- [4-chloro-2-fluoro-5- (2-cyano-3-fluorophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-31).

Example 18
Synthesis of 1-amino-3- [4-chloro-2-fluoro-5- (2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-24 )
18.1
3- [4-chloro-2-fluoro-5- (4-amino-2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-24 )
Suspension of 10% Pd / C and 3- [4-chloro-2-fluoro-5- (4-nitro-2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4- dione (4.0 g) in ethyl acetate (100 ml) was stirred overnight in a hydrogen atmosphere. The mixture was filtered through celite, and the filtrate was concentrated. The resulting oil is chromatographed on silica gel, eluting with a mixture of ethyl acetate and hexane, 1: 0.8. 3- [4-chloro-2-fluoro-5- (4-amino-2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-24 ) is isolated as a solid amorphous substance (3.3 g).

 The following compounds are prepared in a similar manner.

 3- [4-chloro-2-fluoro-5- (4-aminophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-25).

 3- [4-chloro-2-fluoro-5- (3-amino-5-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-26 )

 3- [4-chloro-2-fluoro-5- (2-aminophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-27).

18.2
3- [4-chloro-2-fluoro-5- (2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-28)
3- [4-chloro-2-fluoro-5- (4-amino-2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (3.0 g) dissolved in anhydrous N, N-dimethylformamide (10 ml) is added to a solution of tert-butyl nitrite (1.28 g) in anhydrous N, N-dimethylformamide (40 ml), stored at 60-5 ^{° C.} under a nitrogen atmosphere. The resulting mixture was stirred for 30 minutes at this temperature. The solution was poured into water and extracted with a mixture of ethyl acetate and hexane, 1: 1 (300 ml). The organic phase is washed with brine and dried over anhydrous sodium sulfate. After removing the solvent, the residue was chromatographed on silica gel, eluting with a 1: 2 mixture of ethyl acetate and hexane. 3- [4-chloro-2-fluoro-5- (2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione (intermediate 11-28) is isolated as amorphous solid (1.64 g).

 The following compounds are prepared in a similar manner.

 3- [4-chloro-2-fluoro-5- (3-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-29).

 3- [4-chloro-2-fluoro-5-phenoxyphenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-30).

18.3
1-amino-3- [4-chloro-2-fluoro-5- (2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-24) (method 15)
Suspension of 3- [4-chloro-2-fluoro-5- (2-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-3,2,3,4-tetrahydropyrimidine-2,4-dione (0.7 g), potassium carbonate (0.27 g) and 2,4-dinitrophenoxyamine (0.39 g) in anhydrous N, N-dimethylformamide (20 ml) was stirred at room temperature for 72 hours. The solution is treated and the resulting oil is chromatographed on silica gel, eluting with a 4: 1 mixture of hexane and ethyl acetate containing 0.1% triethylamine. The reaction product (compound 9-24) was isolated as a pale yellow amorphous solid (0.6 g).

 The following compounds are prepared in a similar manner.

 1-amino-3- [4-chloro-2-fluoro-5- (3-trifluoromethylphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-25) .

 1-amino-3- [4-chloro-2-fluoro-5-phenoxyphenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-26).

Example 19
Synthesis of ethyl 2- [4- [2-chlorop-2-fluoro-5- (1-amino-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dion-3-yl) phenoxy] phenoxypropionate (compound 9-27)
19.1
3- [4-chloro-2-fluoro-5- (4-hydroxyphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (intermediate 11-31)
3- [4-chloro-2-fluoro-5- (4-aminophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (2.0 g) was mixed with hot 30 % sulfuric acid (5 ml), and ice water (5.0 g) was added. The mixture is kept at 10 ^{° C.} until a solution of sodium nitrite (0.45 g) in water (5 ml) is gradually introduced into the bottom of the mixture with stirring. After stirring for 10 minutes, urea (0.1 g) is added, followed by a solution of copper nitrate (2) (18.0 g) in water (170 ml) and copper oxide (1) (0.7 g). The mixture was stirred for 10 minutes, extracted with diethyl ether (50 ml x 3), and dried over sodium sulfate. The crude product was purified by column chromatography (hexane: ethyl acetate, 4; 1) to give 3- [4-chloro-2-fluoro-5- (4-hydroxyphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4- tetrahydropyrimidine-2,4-dione (intermediate 11-31) (1.0 g).

19.2
Ethyl 2- [4- [2-chloro-4-fluoro-5- (6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dion-3-yl) phenoxy] phenoxy] propionate (intermediate connection 11-32)
A solution of 3- [4-chloro-2-fluoro-5- (4-hydroxyphenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione (1.0 g) in butane- 2-one (20 ml) was mixed with ethyl 2-bromopropionate (1 equivalent) and potassium carbonate (1 equivalent) and refluxed for 4 hours. The mixture was filtered and evaporated. The crude product is chromatographed to give ethyl 2- [4- [2-chloro-4-fluoro-5- (6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dion-3-yl) phenoxy ] phenoxy] propionate (intermediate 11-32) (0.81 g).

19.3
Ethyl 2- [4- [2-chloro-4-fluoro-5- (1-amino-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dion-3-yl) phenoxy] phenoxy ] propionate (compound 9-27) (method 15)
Suspension of ethyl 2- [4- [2-chloro-4-fluoro-5- (4-trifluoromethyl-1,2,3,6-tetrahydropyrimidin-2,6-dion-3-yl) phenoxy] phenoxy] propionate (0.81 g), potassium carbonate (0.24 g) and 2,4-dinitrophenoxyamine (0.35 g) in anhydrous N, N-dimethylformamide (20 ml) were stirred at room temperature for 24 hours. The solution is treated and the resulting oil is chromatographed on silica gel, eluting with a 4: 1 mixture of hexane and ethyl acetate. The reaction product ethyl-2- [4- [2-chloro-4-fluoro-5- (1-amino-6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dion-3-yl) phenoxy ] phenoxy] propionate (compound 9-27) was isolated as a pale yellow amorphous solid (0.51 g).

Example 20
Synthesis of 1-amino-3- [4-chloro-2-fluoro-5- (5-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydro-2-oxo-4- thioxopyrimidine (compound 9-28) (method 17)
Mixture of 1-amino-3- [4-chloro-2-fluoro-5- (5-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione ( 0.27 g), sodium bicarbonate (0.19 g) and Lawsson's reagent (0.26 g) in dry toluene (10 ml) are refluxed for 4 hours. The mixture was cooled, filtered, and the residue was evaporated under reduced pressure. The resulting oil was chromatographed on silica gel, eluting with a 4: 6 mixture of ethyl acetate and hexane, to give a yellow viscous oil (0.18 g).

Similarly get
1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2-oxo-4-thioxopyrimidine (compound 9-29).

Example 21
Synthesis of 1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione ( connection 9-1)
21.1
1-amino-3- (4-chloro-2-fluoro-5-isopropyloxyphenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
A suspension of sodium hydride (1.0 g, 60% in oil) in N, N-dimethylformamide (30 ml) was stirred at 0 ^{° C.} under a nitrogen atmosphere, while a solution of ethyl 3-amino-4,4,4- was added dropwise. trifluorocrotonate (4.5 g) in N, N-dimethylformamide (20 ml). After stirring for 15 minutes at -35 ^{° C.} , a solution of 4-chloro-2-fluoro-5-isopropyloxyphenyl isocyanate (5.6 g) in toluene (25 ml) is gradually added. The solution was stirred at room temperature for 2 hours and treated with a solution of 2,4-dinitrophenoxyamine (5.8 g) in N, N-dimethylformamide (20 ml). Stirring is continued for 3 days. The solution is treated and a solid is obtained which is chromatographed on silica gel eluting with a 1: 5 mixture of ethyl acetate and hexane containing 0.1% triethylamine. 1-amino-3- (4-chloro-2-fluoro-5-isopropyloxyphenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione was obtained as a white solid (5.3 g )

21.2
1-amino-3- (4-chloro-2-fluoro-5-hydroxyphenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
To a solution of 1-amino-3- (4-chloro-2-fluoro-5-isopropyloxyphenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione (4.5 g) in methylene chloride ( 50 ml), with stirring at 0 ^{° C.} , concentrated sulfuric acid (3 ml) is added. After 1 hour, the mixture was diluted with water and treated. The oily product is chromatographed on silica gel eluting with a 2: 3 mixture of ethyl acetate and hexane to give 1-amino-3- (4-chloro-2-fluoro-5-hydroxyphenyl) -6-trifluoromethyl-1,2,3,4- tetrahydropyrimidine-2,4-dione as a pale yellow amorphous solid (3.6 g).

¹ H NMR (CDCl ₃ , TMS): 7.27 (1H, d, J = 8.8 Hz), 6.88 (1H, d, J = 6.5 Hz), 6.28 (1H, s) 5.86 (1H, broth); 4.61 (2H, s).

21.3
1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-1) (method 14)
Sodium hydride (75 mg, 60% in oil) was added at room temperature to a mixture of 1-amino-3- (4-chloro-2-fluoro-5-hydroxyphenyl) -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine -2,4-dione (0.5 g) and 2-chloro-3-nitropyridine (0.35 g) in anhydrous tetrahydrofuran (50 ml). After stirring for 36 hours, water was added and the reaction mixture was worked up. Silica gel chromatography, eluting with a 1: 2 mixture of ethyl acetate and hexane, gives compound 9-1 as a yellow semi-solid (0.1 g).

 The following compounds are prepared in a similar manner.

 1-amino-3- [4-chloro-2-fluoro-5- (5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-32).

 1-amino-3- [2,4-dichloro-5- (5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9- 33).

 1-amino-3- [2,4-difluoro-5- (5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9- 34).

 1-amino-3- [4-chloro-5- (5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-35) .

 1-amino-3- [4-bromo-2-fluoro-5- (5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-36).

 1-amino-3- [4-bromo-5- (5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-37) .

 1-amino-3- [4-chloro-2-fluoro-5- (3-amino-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-38).

 1-amino-3- [4-chloro-2-fluoro-5- (3-aminotrifluoroacetyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-39).

 1-amino-3- [4-chloro-2-fluoro-5- (3-aminoacetyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-40).

 1-amino-3- [4-chloro-2-fluoro-5- (3-aminomethylsulfonate-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-41).

 1-amino-3- [4-chloro-2-fluoro-5- (3-chloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-42).

 1-amino-3- [4-chloro-2-fluoro-5- (6-bromo-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-43).

 1-amino-3- [4-chloro-2-fluoro-5- (3-chloro-3-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4 dione (compound 9-44).

 1-amino-3- [4-chloro-2-fluoro-5- (3-nitro-5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4 dione (compound 9-45).

 1-amino-3- [4-chloro-2-fluoro-5- (3-chloro-5-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4 dione (compound 9-46).

 1-amino-3- [4-chloro-2-fluoro-5- (3,5-dichloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-47).

 1-amino-3- [4-chloro-2-fluoro-5- (3,5-dinitro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-48).

 1-amino-3- [4-chloro-2-fluoro-5- (4,6-bistrifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-49).

 1-amino-3- [4-chloro-2-fluoro-5- (6-chloro-4-cyano-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4 dione (compound 9-50).

 1-amino-3- [4-chloro-2-fluoro-5- (4,5-bistrifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-51).

 1-amino-3- [4-chloro-2-fluoro-5- (3,6-bistrifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-52).

 1-amino-3- [4-chloro-2-fluoro-5- (3,5,6-trichloro-4-trifluoromethyl-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine -2,4-dione (compound 9-53).

 1-amino-3- [4-chloro-2-fluoro-5- (3,4,5-trichloro-6-trifluoromethyl-2-pyridyloxy) phenyl] -1-methyl-6-trifluoromethyl-2,4- ( 1H, 3H) -pyrimidinedione (compound 9-54).

 1-amino-3- [4-chloro-2-fluoro-5- (3,5-dichloro-4,6-difluoro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine -2,4-dione (compound 9-55).

 1-amino-3- [4-chloro-2-fluoro-5- (3,5,6-trifluoro-4-bromo-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine -2,4-dione (compound 9-56).

 1-amino-3- [4-chloro-2-fluoro-5- (3,4,5,6-tetrachloro-2-pyridyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2 , 4-dione (compound 9-57).

 1-amino-3- [4-chloro-2-fluoro-5- (5-bromo-2-pyrimidyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-58).

 1-amino-3- [4-chloro-2-fluoro-5- (6-chloro-5-nitro-4-pyrimidyloxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4 dione (compound 9-59).

 1-amino-3- [4-chloro-2-fluoro-5- (6-chloro-2-pyridazinyl-oxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione (compound 9-60).

 1-amino-3- [4-chloro-2-fluoro-5- (2-chloro-6-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-61).

 1-amino-3- [4-chloro-2-fluoro-5- (4-fluoro-6-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-62).

 1-amino-3- [4-chloro-2-fluoro-5- (3-fluoro-6-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-63).

 1-amino-3- [4-chloro-2-fluoro-5- (3-fluoro-2-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-64).

 1-amino-3- [4-chloro-2-fluoro-5- (2-fluorophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-65) .

 1-amino-3- [4-chloro-2-fluoro-5- (3-fluorophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-66) .

 1-amino-3- [4-chloro-2-fluoro-5- (4-fluorophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-67) .

 1-amino-3- [4-chloro-2-fluoro-5- (2-chloro-4-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-68).

 1-amino-3- [4-chloro-2-fluoro-5- (4-cyano-2,3,5,6-tetrafluorophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2 , 4-dione (compound 9-69).

 1-amino-3- [4-chloro-2-fluoro-5- (3-chloro-4,6-dinitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-70).

 1-amino-3- [4-chloro-2-fluoro-5- (4-nitrophenoxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidine-2,4-dione (compound 9-71) .

 1-amino-3- [4-chloro-2-fluoro-5- (6-chloro-3-pyridazinyl-oxy) phenyl] -6-trifluoromethyl-1,2,3,4-tetrahydropyrimidin-2,4-dione (compound 9-72).

 Some of the compounds of the present invention obtained by the methods described above are shown in tables 1-9. Physical data on the intermediates, including NMR data, are shown in tables 10 and 11. NMR data for the compounds of the present invention are given in table. 12.

 The compounds of the present invention exhibit an excellent herbicidal effect when used as the active ingredient (s) of a herbicide. The herbicide can sometimes be used for widespread use, for example, on lands under cultivated plants, such as rice fields, irrigated land plots, lands under fruit orchards and mulberry trees, and on lands not occupied by cultivated plants, such as forests, agricultural roads, game sites and development sites by industrial enterprises. You can choose the appropriate method of application for application in soil tillage and for non-root use.

 The compounds of the present invention are used to control harmful weeds, including cereals (gramineae) such as millet rooster (Echinochola crus-galli), creeping weed (Digitaria sanguinalis), green bristle (Setaria viridis), Indian Elevine (Eleusine indica L.) , wild oatmeal (Avena fatua L), Johnson grass (Sorghum halepense), creeping wheatgrass (Agropyron repens), cowberry (Brachiaria piantaginea), purple millet (Panicum purpurascen), leptochloa (Leptochloa chinensloa) and leptochloa sedges (or Sureraseae), such as rice raw (Surerus iria L.), purple nutsedge (Cyperus rotondus L.), Japanese reeds (Scripus Juncoides), raw (Cyperus serotinus), long long flowered (Cyperus difformis), thin swamp ( Eleocharis acicularis) and water chestnut (Eleocharis kuroguwai); ditties, such as Japanese broad-leaved arrowhead (Sagittaria pygmaea), arrowhead (Sagittaria trifolia) and lanceolate (Alisma canaliculatum); pontedericeae such as monochoria (Monochoria vaginalis) and the species monochoria (Monochoria korsakovii); bumpy, such as the false femur (Lindernia pyxidaria) and abunome (Dopatrium Junceum); lythraceae such as Indian Rotala (Rotala indica) and red stem (Ammannia multiflora); and broadleaf, such as paniculate amaranth (Amaranthus retroflexus), Theophrastius tomose (Abutilon theophrasti), morning glory (Ipomoea hederacea), white gauze (Chenopodium album), prickly brisket (Sida spinosa L.), garden purslane (Portulaca oleracea L. fine thyme (Amaranthus viridis L.), cirrus (Cassia obtusifolia), black nightshade (Solanum nigrum L.), mountaineer pepper (Polygonum lapathifolium L.), woodlice (Stellaria media L.), common cockroach (Xanthium strumarium L.), corrugated core (Cardamine flexuosa WITH.), cedus (Lamium amplexicaule L.) and three-seeded pear (Acalypha australis L.). Accordingly, they are useful for indiscriminate or selective control of harmful weeds when growing crops such as corn (Zea mays L.), soybeans (Glycine max Merr.), Cotton (Gossypium spp.), Wheat (Triticum spp.), Rice (Oryza sativa L.), barley (Hordeum vulgare L.), oats (Avena sativa L.), sorghum (Sorghum bicolor Moench), canola (Brassica napus L.), sunflower (Helianthus annuus L.), sugar beets (Beta vulgaris L .), sugarcane (Saccharum officinarum L.), Japanese lawn grass (Zoysia Japonica stend), peanuts (Arachis hypogaea L.) or flax (Linum usitatissimum L.).

 For use as herbicides, the active ingredients of the present invention are formulated in herbicidal compositions by mixing the herbicidally active amounts thereof with inert ingredients known in the art to facilitate the suspension, dissolution or emulsification of the active ingredient for the desired application. The type of composition obtained, depending on the composition, culture and system of use, can affect the activity and usefulness of the active ingredient in practical use. Thus, for use in agriculture, the herbicidal compounds of the present invention can be made in the form of dispersible granules, granules for direct application to the soil, water-soluble concentrates, wettable powders, dusts, solutions, emulsion concentrates (CE), microemulsions, suspoemulsions, invert emulsions or other types depending on the desired target weeds, crops and methods of application.

 Such herbicidal compositions can be applied on the intended area (where suppression of undesirable vegetation is the goal) in the form of dusts, granules, or sprayable formulations diluted with water or a solvent. Such compositions may contain the active ingredient from as little as 0.1 wt.%, To as much as 97 wt.%.

 Dusts are mixtures of the active ingredient with finely ground materials such as clays (some examples of compositions include kaolins and montmorillonites), talc, granite dust, or other inorganic or organic solids that act as dispersants and carriers for the active ingredient; these finely ground materials have an average particle size of less than 50 microns. A typical dust composition will contain 1% active ingredient and 99% carrier.

 Wettable powders are made up of small particles that quickly disintegrate in water or other carriers for spray formulations. Typical carriers are kaolins, fuller’s earth, silicas and other absorbent wettable inorganic materials. Wettable powders can be prepared containing from 1 to 90% of the active ingredient, depending on the desired application and absorption capacity of the carrier. Wettable powders typically contain wetting or dispersing agents to aid dispersion in water or other carriers.

 Water-dispersible granules are granular solid materials that are readily dispersible when mixed with water. Such a composition typically consists of an active ingredient (0.1% -95% of the active ingredient), a wetting agent (1-15 wt.%), A dispersant (1-15 wt.%) And an inert carrier (1-95 wt.%). Water-dispersible granules can be obtained by thoroughly mixing the ingredients, followed by adding a small amount of water to a rotating disk (this mechanism is commercially available) and collecting agglomerated granules. Alternatively, the mixture of ingredients can be mixed with the optimum amount of liquid (water or other liquid) and passed through an extruder (this mechanism is commercially available) equipped with openings allowing small extruded granules to be obtained. Alternatively, the mixture of ingredients can be granulated using a high speed mixer (this mechanism is commercially available) by adding a small amount of liquid and mixing at high speeds to influence agglomeration. Alternatively, the mixture of ingredients can be dispersed in water and dried by spraying the dispersion through a hot nozzle in a process known as spray drying (spray drying equipment is commercially available). After granulation, the moisture content is brought to the optimum level (usually less than 5%), and the product is sieved to obtain particles of the desired size (in the mesh).

Granules are granular solids that do not crumble in water, but retain their physical structure when applied to the soil using a machine for applying dry granular materials. Such granular solid materials can be obtained from clay, plant material, such as flour from corncobs, agglomerated silicas, or from other agglomerated
organic or inorganic materials or compounds, such as calcium sulfate. The composition typically consists of the active ingredient (1-20%) sprayed onto or absorbed into the granule. A granule can be obtained by thoroughly mixing the active ingredient with granules with or without the addition of a bonding agent to facilitate adhesion of the active ingredient to the surface of the granule, or by dissolving the active ingredient in a solvent, spraying the dissolved active ingredient and solvent onto a granule, followed by drying to remove the solvent. Granular compositions are useful when furrowing or tape application is desired.

 Emulsion concentrates (CEs) are homogeneous liquids consisting of a solvent or mixture of solvents such as xylenes, heavy ligroin epaulets, isophorone or other proprietary commercial compositions derived from petroleum epaulets, active ingredient and emulsifier or emulsifiers. For herbicidal use, CE is added to water (or another carrier for the spray formulation) and is applied as a spray formulation in the intended area. The CE composition may contain 0.1-95% of the active ingredient, 5-95% of a solvent or mixture of solvents, and 1-20% of an emulsifier or mixture of emulsifiers.

 Suspension concentrate compositions (also known as flowable suspensions) are liquid compositions consisting of a thin suspension of the active ingredient in a carrier, typically in water or in a non-aqueous carrier, such as oil. Suspension concentrates usually contain the active ingredient (5-50 wt.%), Carrier, wetting agent, dispersant, antifreeze, viscosity modifiers and pH modifiers. For use, suspension concentrates are usually diluted with water and sprayed on the intended area.

 Solution concentrates represent solutions of the active ingredient (1-70%) in solvents that have sufficient solubility to dissolve the desired amount of active ingredient. Because they are simple solutions without other inert ingredients, such as wetting agents, additives to facilitate proper use are usually added to the spray tank for mixing before spraying.

 Microemulsions are solutions consisting of an active ingredient (1-30%) dissolved in a surfactant or emulsifier without the addition of solvents. No other solvents are added to this composition. Microemulsions are especially useful when a low-odor composition is needed, as is the case with lawn grass near residential buildings.

 Suspoemulsions are combinations of two active ingredients. One active ingredient is prepared in the form of a suspension concentrate (1-50% of the active ingredient), and the second active ingredient is prepared in the form of an emulsion concentrate (0.1-20%). The reason for obtaining this kind of composition is the inability to obtain the CE of the first ingredient due to poor solubility in organic solvents. Sustoemulsion composition allows a combination of two active ingredients that are packaged in one container, thereby minimizing packaging waste and creating more convenience for the user of the product.

 The herbicidal compounds of this invention can be formulated or used together with insecticides, fungicides, acaricides, nematicides, fertilizers, plant growth regulators or other agricultural chemicals. Some additives for mixing in the spray tank, such as binders, penetration aids, wetting agents, surfactants, emulsifiers, moisturizers and UV protectants, may be added in an amount of 0.01 to 5% to enhance biological activity, stability, wetting, spraying on foliage or absorption of active ingredients on the intended area, or to increase the possibility of formation of a suspension, dispersion, re-dispersion, emulsion, increase UV resistance or improving other physical or physico-chemical properties of the active ingredient in a spray tank, spray system, or target area.

 Examples of compositions of the present invention are given in table. 17-22.

Test examples
A conventional greenhouse screening system for herbicidal activity was used to evaluate the herbicidal efficacy and safety of these test compounds for cultivated plants. Six species of broad-leaved weeds, including paniculate amaranth (Amaranthus retroflexus, AMARE), Theophrastus abutus (Abutilon theophrasti, ABUTH), carapace (Cassia obtusifolia, CASOB), and ivy foliage (Ipomoa hederacea, IPOHE Chen, ) and ragweed (Ambrosia artemisiifolia L., AMBEL), are used as experimental species. Four types of cereal weeds are also used, including green bristle (Setaria viridis, SETVI), millet rooster (Echinochloa crusgalli, ECHCG), Johns grass (Sorghum halepense, SORHA) and creeping weed (Digitaria sanguinalis, DIGSA). In addition, three cultivars are included in the test - field corn (Zea mays L., Dekalb 535, CORN), soybeans (Glycine max L., Pella 86, SOY) and dry rice (Oryza, Tebonnet, RICE) .

 Test Example 1. Pre-emergence treatment.

 All plants are grown in 10-cm plastic pots filled with a mixture of sand and loamy soil. For pre-emergence testing, the seeds are sown the day before the test compounds are applied. Immediately after application, test pre-emergence test samples are watered with water from the surface of the soil to deposit test materials. Subsequently, these samples are watered from the pan.

 All test compounds are dissolved in acetone and applied to test samples in a volume of 187 l / ha. The test materials are applied at a rate in the range of 125 g ai / ha to 1000 g ai / ha using a crawler sprayer equipped with a leveling tip with a flat spray torch TJ8001E. Plants are put on the table so that the upper part of the plants (after emergence) or the soil surface (before emergence) is 40-45 cm below the tip. Compressed air is used to feed the test solution through the tip when it is moved mechanically (using an electrically controlled chain drive) over the tops of all test plants / pots. Such application mimics typical industrial application of herbicides in the field.

 Test Example 2. Post-emergence test.

 In a post-emergence test, a non-ionic surfactant (0.25%, v / v) is also included to enhance the wettability of the leaves of target plants at a rate of application in the range of 63 g ai / ha to 1000 g ai / ha. In the case of post-emergence tests, seeds are sown 8-21 days before the tests, so that seedlings appear and foliage develops well before the test substances are used. During post-emergence application, plants of all species are usually at the developmental stage of 2-3 leaves. Post-emergence test specimens are always watered from the pan.

 On the 14th day after the application of the test materials, phytotoxicity assessments are recorded. The 0-100 grading scale described previously in Research Methods in Weed Science, 2nd edition, B. Truelove, Ed., Southern Weed Science Society, Auburn University, Auburn, Alabama, 1977 is used. Briefly, “0” corresponds to no damage , and "100" corresponds to the complete death of all plants in this sample during testing. This scale is used to determine both the effectiveness against the weed species and the danger to the cultivated species. The herbicidal results of the various compounds of this invention, which are presented under the numbers indicated in the table. 1-9 are given in table. 13 and 14. The results show a significant difference between the compounds both in efficiency against weeds and in selectivity for the type of crop. For the selected compounds, excellent action against most weed species is observed with minimal damage to at least one crop species.

 The compositions of the present invention can be used in a mixture or in combination with other chemicals for agriculture, fertilizers or phytotoxicity-reducing agents. In this case, they can detect even the best action or activity. Other agricultural chemicals can be mentioned, for example, herbicides, fungicides, antibiotics, plant hormones, insecticides or acaricides. In particular, by using herbicidal compositions containing the compounds of the present invention used in a mixture or in combination with one or more active ingredients of other herbicides, it is possible to improve the herbicidal activity, extend the range of application time and the number of types of weeds to which they can be applied . In addition, the compounds of the present invention and the active ingredient of another herbicide can be incorporated into different compositions so that they can be mixed for use at the time of use, or they can be incorporated into a single composition. The present invention encompasses such herbicidal compositions.

 The ratio of the components when mixing the compounds of the present invention with the active ingredient of other herbicides cannot be determined in general, since it varies depending on the time and method of application, weather conditions, type of soil and type of composition. However, one active ingredient of another herbicide can usually be included in an amount of 0.01-100 mass parts per mass part of the compounds of the present invention. In addition, the total dose of all active ingredients is usually from 1 to 10,000 g / ha, preferably from 5 to 500 g / ha. The present invention encompasses such herbicidal compositions.

 As active ingredients of other herbicides, the following (common names) may be mentioned. Herbicidal compositions containing the compounds of the present invention, used in combination with other herbicides, can sometimes exhibit a synergistic effect.

 1. Active ingredients that are believed to exhibit a herbicidal effect by disrupting the action of plant auxins, including phenoxyacetic acid type ingredients such as 2,4-D, 2,4-DB, 2,4-DP, MCPA, MCPP, MCPB or naproanilide (including free acids, their esters or salts), such as aromatic carboxylic acids, such as 2,3,6 TBA, dicamba, dichlobenyl, type pyridines, such as picloram (including free acids and their salts), triclopyr or clopyralid, and others, such as naptalam, benazolin, or hinklorac.

 2. Active ingredients believed to be herbicidal by inhibiting plant photosynthesis, including urea-type ingredients such as diuron, linuron, isoproturon, chlortoluron, methobenzuron, tebutiuron or fluomethuron, such as triazines, such as simazine, atrazine, cyanazine, terbutylazine, atratone, hexazinone, metribuzin, simethrin, ametrine, prometrin or dimetamethrin, such as uracils such as bromacil, terbacyl or lenacyl, such as anilides such as propanyl or cypromide, carbamate type such as swap des £ dif or phenmedipham, a hydroxybenzonitrile type such as bromoxynil or ioxynil, and others such as pyridate, bentazon and methazole.

 3. The type of salts of the quaternary ammonium bases, such as paraquat, diquat or diphenzoquat, which are believed to themselves convert to free radicals to form active oxygen in the plant, and thus exhibit a quick herbicidal effect.

 4. Active ingredients that are believed to exhibit a herbicidal effect by inhibiting chlorophyll biosynthesis in plants and abnormally accumulating photosynthetic peroxide in the plant body, including diphenyl ether type ingredients such as nitrofen, lactofen, acifluorfen sodium, oxyfluorfen, bomefenfen, xomefenfen, xomefenfen such as cyclic amides, such as chlorophthalene, flumioxadine or flumicloracpentyl, and others, such as oxadiazone, sulfentrazone or thidiazimine.

 5. Active ingredients believed to exhibit a herbicidal effect characterized by etiolation activity by inhibiting plant chromogenesis, such as carotenoids, including ingredients such as pyridazinones, such as norflurazone, chloridazone or metflurazone, such as pyrazoles, such as pyrazolate, pyrazoxyphene or benzofenap, and others, such as fluridone, fluramon, diflufencam, methoxyphenone, chlomazone, amitrol, sulcotrione or isoxaflutol.

 6. Active ingredients that are believed to specifically affect cereal plants, including ingredients such as aryloxyphenoxypropionic acids, such as diclofopmethyl, pyrofenopnatrium, fluazifopbutyl, haloxifopmethyl, quisalofopetyl, phenoxapropethyl or cygalofopbutyl oxide, tsialofopbutiland alikit, tsiklofopilutilovid, tsiklofilutiklinda, tsiklofetilutilovid, tsiklofibutilanda, and celodime or thralkoxydim.

 7. The active ingredients, which are believed to exhibit herbicidal effects by inhibiting amino acid biosynthesis of plants, including a sulfonylurea type ingredients, such as chlorimuron-ethyl, nicosulfuron, metilsulfuronmetil, triasulfuron, primisulfuron, tibenuronmetil, chlorsulfuron, bensulfuronmetil, sulfometuron methyl, prosulfuron, galosulfuronmetil , tifensulfuronmethyl, rimsulfuron, azimsulfuron, flazasulfuron, imazosulfuron, cyclosulfamuron, flupirsulfuron, such as triazolopyrimidinesulfo amides such as flumetsulam or metosulam, such as imidazolinones, such as imazapyr, imaztapir, imazaquin, imazamox, imazamet, imazametabenzmetil such pirimidinsalitsilovoy acids such as pirtiobaknatry, bispiribaknatry or piriminobakmetil, and others such as glyphosate, glifosatammony, glifosatizopropilamin or sulfosate.

 8. Active ingredients that are believed to exhibit a herbicidal effect, interfering with normal metabolism during the absorption of inorganic nitrogen, such as glufosinate, glufosinate ammonium, phosphinotricin or bialophos.

 9. Active ingredients believed to exhibit a herbicidal effect by inhibiting cytogenesis of plant cells, including dinitroaniline-type ingredients such as trifuranyl, oryzaline, nitralin, pendamethalin, ethafluralin, benefin and prodiamine, and an amide type such as bensulide, napronamide and pronamide, such as carbamates, such as profam, chlorprofam, barbane, and asulam, such as organophosphorus compounds, such as amiprofosmethyl or butamiphos, and others, such as DCPA and dithiopyr.

 10. Active ingredients believed to exhibit herbicidal effects by inhibiting protein synthesis in plant cells, including ingredients such as acetanilides, such as alachlor, metolachlor, propachlor, acetochlor (including combinations with herbicides (safeners)) and dimethenamide.

 11. Active ingredients whose type of herbicidal effect is not yet known, including dithiocarbamates, such as thiobencarb, EPTC, diallate, triallate, molinate, pebulate, cyclolate, butylate, vernolate or prosulfocarb, and mixed herbicides such as MSMA , DSMA, endotal, etofumesate, sodium chlorate, pelargonic acid and fosamine.

 Examples of combinations with other herbicides (see tab. 23-26).

 (Note: abbreviations for weed names are taken from the Composite List of Weeds published by the American Society for the Study of Weeds in 1989).

 The following examples illustrate the use of combinations of the compounds of this invention with existing herbicides. The methods of application are identical to the methods of application of the individual compounds, except that industrial compositions of existing herbicides are added in an appropriate amount to the spray mixture before spraying.

 These compounds may also find useful as desiccants, which are used as an aid in harvesting crops such as cotton and potatoes. Preliminary studies are carried out in the greenhouse by spraying the foliage of potato plants with solutions containing various compounds of the invention. Within 1 week after application, the death of leaf tissue in excess of 90% is observed when the treatment is carried out with solutions containing from 100 g to 1000 g ai per ha. Similarly, when processing cotton plants, 100% die-off of leaf tissue is observed within 48 hours after application.

 Test Example 1.

 A greenhouse bioassay screening system is used to evaluate the defoliant ability of the test compounds.

 As the studied species, cotton (Gossyium hirsutum L.) is used. Cotton seeds are sown in 10-centimeter square plastic pots containing a mixture of sand: soil drainage: peat in a ratio of 3: 2: 1. To remove the foliage, the plants are treated at a time when 4-5 leaves are fully bloomed (not including the seven-leaf leaves). The treatment included experimental test material. The test material was either in the form of concentrates capable of processing the emulsion (EC), or in the form of a solution in acetone. A crop oil concentrate (1%) or non-ionic surfactant (0.25%) is added to the sprayed solution. The sprayer was calibrated so as to deliver material in a volume of 93 l / ha using a tracked sprayer equipped with a TJ800E flat spray nozzle with a spray tip at a pressure of 40 psi.

 After processing, the pots were returned to the greenhouse, in which they were watered and kept under favorable conditions for growth for two weeks.

 The defoliant effect of the plant was visually assessed by counting the number of fully bloomed leaves remaining on the plant, and calculating the percentage reduction of the number of fully bloomed leaves on the plant during spraying.

 The evaluation results on day 14 after processing are summarized in table. fifteen.

 Test Example 2

 Field trials were conducted on ripened cotton grown in 36 '' rows. Plants were treated at a time when approximately 60% of the boxes were opened using a tractor mounted sprayer with a capacity of 93 l / ha. Compounds 9-16 and 9-21 were applied in an amount of 25, 50, 100 and 200 g ai / ha with the addition of nonionic surfactant in an amount of 0.25%. Defoliation was evaluated on day 14 after treatment.

 The results are summarized in table. 16.

Claims (20)

1. The compound of formula (I) or its salt,

where X, Y independently is hydrogen, halogen;
Z is oxygen;
Q choose among

R ₁ is halogen;
R ₂ - R ₅ independently is hydrogen, C _1-6 alkyl or C _1-6 haloalkyl and R ₃ and R ₅ together with the atoms to which they are attached form a four-membered substituted or unsubstituted ring; R ₆ is hydrogen, C _1-6 haloalkyl, C _1-6 cyanoalkyl, C _1-6 alkoxy-C _1-6 alkyl;
A ₁ and A ₂ independently are oxygen or sulfur;
B is CH or N;
R ₇ and R _{8 are} each independently hydrogen, C _1-6 alkyl, and R ₇ and R _8, together with the atoms to which they are attached, form a four-seven-membered substituted or unsubstituted ring;
R ₉ and R ₁₀ are hydrogen;
Ar - pyridyl, pyrimidyl, pyridazinyl, triazolyl, thiazolyl, isothiazolyl, or phenyl or pyridyl, pyrimidyl, pyridazinyl, triazolyl, thiazolyl, isothiazolyl, or phenyl substituted with up to five substituents independently selected from halogen atoms, C ₁ -C ₆ alkyl, halogen-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylthio, halogen-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylsulfonyl, C ₁ -C ₆ - alkylsulfinyl, di-C ₁ -C ₆ -alkylaminocarbonyl, cyano, nitro, amino, hydroxy, C ₁ -C ₆ -alkylsulfonylamino, C ₁ -C ₆ -alkoxycarbonyl-C ₁ -C ₆ -alkoxy,
C ₁ -C ₆ alkoxycarbonylamino, bisbenzoylamino, aminoacetyl, aminotrifluoroacetyl or amino-C ₁ -C ₆ alkylsulfonate;
when Q is Q ₃ or Q ₆ , substituted phenyl is excluded. 2. The compound or its salt according to claim 1, where X is fluorine, Y is chlorine, Z is oxygen, Q is selected from Q ₁ - Q ₉ and Ar is 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-bromo -2-pyridyl, 5-bromo-2-pyridyl, 6-bromo-2-pyridyl, 3-chloro-2-pyridyl, 5-chloro-2-pyridyl, 6-chloro-2-pyridyl, 3-fluoro-2 -pyridyl, 5-fluoro-2-pyridyl, 6-fluoro-2-pyridyl, 3-cyano-2-pyridyl, 5-cyano-2-pyridyl, 6-cyano-2-pyridyl, 3-nitro-2-pyridyl 5-nitro-2-pyridyl, 6-nitro-2-pyridyl, 3-trifluoromethyl-2-pyridyl, 4-trifluoromethyl-2-pyridyl, 5-trifluoromethyl-2-pyridyl, 6-trifluoromethyl-2-pyridyl, 5 amino-2-pyridyl, 3-dimethylaminocarbonyl-2-pyridyl, 3-methylsulfonyl-2-pyridyl, 3-isoprop lsulfonyl-2-pyridyl, 6-chloro-3-trifluoromethyl-2-pyridyl, 3,5,6-trifluoropyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-bromo-2-pyrimidyl, 4-chloro-2-pyrimidyl, 4-trifluoromethyl-2-pyrimidyl, 4,6-dimethoxy-2-pyrimidyl, 2,6-dimethoxy-4-pyrimidyl, 4,6-dimethoxy-2-triazinyl, phenyl, 2-iodophenyl, 2-trifluoromethoxyphenyl, 2- nitrophenyl, 4-nitrophenyl, 4-aminophenyl, 4-hydroxyphenyl, 4-methylsulfonylaminophenyl, 4- (1-ethoxycarbonylethoxy) phenyl, 2-cyano-phenyl, 2-cyano-3-fluorophenyl, 2-cyano-4-fluorophenyl, 2 amino-4- (1-ethoxycarbonylethoxy) phenyl, 2-cyano-4-nitrophenyl, 4-amino-2-cyanophenyl, 4-nitro-2-trifluoromethylpheni , 4-amino-2-trifluoromethylphenyl, 4-acetylamino-2-trifluoromethylphenyl, 4- (1-ethoxycarbonylethoxy) -2-nitrophenyl, 5-chloro-4- (1-ethoxycarbonylethoxy) -2-nitrophenyl, 3-methyl-4 nitro-5-isothiazolyl or 5-nitro-2-thiazolyl;
when Q is Q ₆ , substituted phenyl is excluded. 3. The method of obtaining the compounds of formula (I) according to claim 1 or its salt, where X, Y, Z, Q, R ₁ - R ₈ , A ₁ , A ₂ , B and Ar have the meanings specified in paragraph 1, including the interaction of the compounds of formula

with a compound of the formula Ar-Hal, where Hal is a halogen atom in the presence of a base. 4. A method of obtaining a compound of formula (I) according to claim 1 or a salt thereof having the formula (XXXIII)

where Q is Q ₉ ;
X, Y, Z, R ₉ , R ₁₀ and Ar have the meanings indicated in paragraph 1,
comprising the interaction of the compounds of formula (XXXII)

with a hydrazine derivative of the formula

5. A method of obtaining a compound of formula (I) according to claim 1 or a salt thereof having the formula (XXXIII)

where Q is Q ₉ ;
X, Y, Z, R ₉ , R ₁₀ and Ar have the meanings indicated in paragraph 1,
comprising the interaction of the compounds of formula (III)

with alkyl-3-amino-4,4,4-trifluorocrotonate in the presence of a base and quenching of the reaction with an amination agent. 6. The method of obtaining the compounds of formula (XXXV)

or its salt,
where X, Y, Z and Ar have the meanings specified in paragraph 1,
comprising the interaction of halogenaryluracil of the formula (XXXVIII)

with a salt of an aryl or heteroaryl hydroxyl compound. 7. A method of obtaining a compound of formula (XXXII)

or its salt,
where X, Y, Z and Ar have the meanings specified in paragraph 1,
comprising treating a compound of formula (XXXIX)

where alkyl is an alkyl group,
acidic compounds. 8. The method of obtaining the compounds of formula (XXXVI)

or its salt,
where X, Y, Z, R ₉ and R ₁₀ have the meanings specified in paragraph 1,
comprising reacting a compound of formula (XL)

with hydrazine derivative. 9. A method of obtaining a compound of formula (I) according to claim 1 or a salt thereof having the formula (XXXIII)

where Q is Q ₉ , where R ₉ and R ₁₀ are hydrogen, A ₁ and A ₂ are oxygen;
X, Y, Z and Ar have the meanings specified in paragraph 1,
comprising the interaction of an isocyanate of the formula (III)

with a hydrazone ester of formula (XLIII)

where alkyl is an alkyl group.  10. A herbicidal composition containing an effective amount of a compound according to claim 1 and an adjuvant used in agriculture.  11. A method of controlling weeds, including applying at a locus that protects a herbicide, characterized in that the compounds according to claim 1 in an effective amount are used as the herbicide.  12. The method according to p. 11, characterized in that the protected locus is a field occupied by crops.  13. The method according to p. 11, characterized in that the protected locus is a field occupied by soy.  14. The method according to p. 11, characterized in that it comprises applying an effective amount of the compound according to p. 1 in combination with another herbicide to provide an additive or synergistic herbicidal action.  15. A weed control method according to claim 11, characterized in that the compound according to claim 1 is applied to the soil as a pre-emergence herbicide.  16. The method of weed control according to p. 11, characterized in that the compound according to p. 1 process the foliage of the plant.  17. The weed control method of claim 11, wherein the other herbicide is acetanilide, sulfonylurea or any other selected from phenoxyacetic acid, aromatic carboxylic acid, pyridine, urea, triazine, uracil, anilide, carbamate, hydroxybenzonitrile, quaternary ammonium , diphenyl ether of cyclic amide, pyridazinone, pyrazole, aryloxyphenoxypropionic acid, cyclohexanedione, sulfonylurea, triazolopyrimidinesulfonamide, imidazolinone, pyrimidinesalicylic acid, dinitroa niline, amide, organophosphorus compounds, acetanilide, dithiocarbamates.  18. A method of desiccation of a plant, comprising treating the plant with a compound according to claim 1.  19. The method of desiccation of a plant according to claim 18, characterized in that the plant that is treated with the compound is potato or cotton. 20. The compound of the formula

where X, Y is hydrogen, halogen;
Z is oxygen;
Ar has the same meaning as defined in paragraph 1;
A is hydrogen, —CS, —CO,
or its salt.  21. The compound or its salt according to claim 20, wherein Ar is 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-bromo-2-pyridyl, 5-bromo-2-pyridyl, 6-bromo-2-pyridyl, 3-chloro-2-pyridyl, 5-chloro-2-pyridyl, 6-chloro-2-pyridyl, 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 6-fluoro-2-pyridyl, 3- cyano-2-pyridyl, 5-cyano-2-pyridyl, 6-cyano-2-pyridyl, 3-nitro-2-pyridyl, 5-nitro-2-pyridyl, 6-nitro-2-pyridyl, 3-trifluoromethyl- 2-pyridyl, 4-trifluoromethyl-2-pyridyl, 5-trifluoromethyl-2-pyridyl, 6-trifluoromethyl-2-pyridyl, 6-amino-2-pyridyl, 3-dimethylaminocarbonyl-2-pyridyl, 3-methylsulfonyl-2- pyridyl, 3-isopropylsulfonyl-2-pyridyl, 6-chloro-3-trift trimethyl-2-pyridyl, 3,5,6-trifluoropyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-bromo-2-pyrimidyl, 4-chloro-2-pyrimidyl, 4-trifluoromethyl-2-pyrimidyl, 4,6- dimethoxy-2-pyrimidyl, 2,6-dimethoxy-4-pyrimidyl, 4,6-dimethoxy-2-triazinyl, phenyl, 2-iodophenyl, 2-trifluoromethoxyphenyl, 2-nitrophenyl, 4-nitrophenyl, 4-aminophenyl, 4- hydroxyphenyl, 4-methylsulfonylaminophenyl, 4- (3-ethoxycarbonylethoxy) phenyl, 2-cyanophenyl, 2-cyano-3-fluorophenyl, 2-cyano-4-fluorophenyl, 2-amino-4- (1-ethoxycarbonylethoxy) phenyl, 2- cyano-4-nitrophenyl, 4-amino-2-cyanophenyl, 4-nitro-2-trifluoromethylphenyl, 4-amino-2-trifluoromethylphenyl, 4-acet amylamino-2-trifluoromethylphenyl, 4- (1-ethoxycarbonylethoxy) -2-nitrophenyl, 5-chloro-4- (1-ethoxycarbonylethoxy) -2-nitrophenyl, 3-methyl-4-nitro-5-isothiazolyl or 5-nitro 2-thiazolyl. Priority on points:
03/14/1997 on pp. 4-9;
08/26/1997 on PP. 20 and 21;
01/14/1998 PP 1-3, 10-19.

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