CN101023078A

CN101023078A - 5-heterocyclyl pyrimidines

Info

Publication number: CN101023078A
Application number: CNA2005800312591A
Authority: CN
Inventors: O·格保尔; H·盖尔; U·海涅曼; S·赫尔曼; S·希勒布兰德; R·埃伯特; K·伊尔格; U·瓦克亨多夫-诺伊曼; P·达门; K-H·库克
Original assignee: Bayer CropScience AG
Current assignee: Bayer CropScience AG
Priority date: 2004-09-16
Filing date: 2005-09-15
Publication date: 2007-08-22
Also published as: KR20070052324A; JP2008513399A; CA2580243A1; EP1791834A1; BRPI0515385A; MX2007003057A; WO2006029867A1; DE102004044829A1

Abstract

The invention relates to novel 5-heterocyclyl pyrimidines, several methods for the production thereof, and the use thereof for controlling unwanted microorganisms. The invention also relates to novel intermediate products and methods for the production thereof.

Description

The 5-heterocyclyl pyrimidines

The present invention relates to new 5-heterocyclyl pyrimidines, relate to its preparation method with and be used to prevent and treat the purposes of unwanted microorganisms.In addition, the invention still further relates to new intermediate and their method of preparation.

Known some 5-phenyl pyrimidine has fungicidal properties (contrast WO 03/070721, WO02/074753, WO 01/96314, WO 03/43993).These compounds active good, but its rate of application is also unsatisfactory sometimes when low.

Yet, because mycocide is now improved constantly in the requirement aspect ecological and the environment, for example form and suitable manufacture method aspect at activity profile, toxicity, selectivity, rate of application, residue, but also may there be other problems, resistance problem for example, therefore, need to develop the new mycocide that has advantage at least in some respects than prior art always.

The present invention now provides the new 5-heterocyclyl pyrimidines of following formula

Wherein

R ¹Represent hydrogen, C ₁-C ₈Alkyl, C ₂-C ₈Thiazolinyl, C ₃-C ₈Alkynyl, C ₃-C ₈Cycloalkyl or C ₃-C ₈Cycloalkenyl group, wherein R ¹Can be by one to three identical or different radicals R ^aReplace, and

R ^aRepresent halogen, hydroxyl, cyano group, C ₁-C ₄Alkoxyl group and/or C ₃-C ₆Cycloalkyl, perhaps

R ¹Represent five yuan to ten yuan saturated, unsaturated or fragrant monocycle or bicyclic heterocycles, described heterocycle contains one to four heteroatoms that is selected from O, N and S, wherein R ¹Can be by one or two identical or different radicals R ^bReplace, and

R ^bRepresent halogen, C ₁-C ₆Alkyl, cyano group, nitro and/or C ₃-C ₆Cycloalkyl;

R ²Represent hydrogen or C ₁-C ₆Alkyl, perhaps

R ¹And R ²The nitrogen-atoms that is connected with them represents ternary to hexavalent saturated, unsaturated or fragrant monocycle or bicyclic heterocycles jointly, wherein said heterocycle can contain the other heteroatoms that is selected from O, N and S, and described heterocycle can be by one to three identical or different radicals R ^cReplace, and

R ^cRepresent halogen, C ₁-C ₆Alkyl and/or C ₁-C ₆Haloalkyl,

R ³Represent saturated, the monocycle or the bicyclic heterocycles that part is unsaturated or fragrant of ternary to ten yuan, described heterocycle contains one to four heteroatoms that is selected from O, N and S, wherein R ³Can be by one to four identical or different radicals R ^dReplace, and

R ^dRepresent halogen, hydroxyl, cyano group, oxo, nitro, amino, sulfydryl, C ₁-C ₆Alkyl, C ₁-C ₆Haloalkyl, C ₂-C ₆Thiazolinyl, C ₂-C ₆Alkynyl, C ₃-C ₆Cycloalkyl, C ₁-C ₆Alkoxyl group, C ₁-C ₆Halogenated alkoxy, carboxyl, C ₁-C ₇Alkoxy carbonyl, formamyl, C ₁-C ₇Alkyl amino-carbonyl, C ₁-C ₆Alkyl-C ₁-C ₆Alkyl amino-carbonyl, morpholino carbonyl, pyrrolidyl carbonyl, C ₁-C ₇Alkyl-carbonyl-amino, C ₁-C ₆Alkylamino, two-(C ₁-C ₆Alkyl) amino, C ₁-C ₆Alkylthio, C ₁-C ₆Alkyl sulphinyl, C ₁-C ₆Alkyl sulphonyl, hydroxyl alkylsulfonyl, amino-sulfonyl, C ₁-C ₆Alkyl amino sulfonyl and/or two-(C ₁-C ₆Alkyl) amino-sulfonyl;

R ⁴Represent halogen or C ₁-C ₈Alkyl, C ₁-C ₈Alkoxyl group, C ₁-C ₈Haloalkyl, C ₁-C ₈Alkylthio, C ₁-C ₈Alkyl sulphinyl, C ₁-C ₈Alkyl sulphonyl or cyano group,

R ⁵Represent five yuan or saturated, unsaturated or fragrant monocycle or the bicyclic heterocycles of hexavalent, described heterocycle contains one to four heteroatoms that is selected from O, N and S, wherein R ⁵Can be by one to four identical or different radicals R ^eReplace, and

R ^eRepresent halogen, hydroxyl, cyano group, nitro, C ₁-C ₆Alkyl, C ₁-C ₆Haloalkyl, C ₂-C ₆Thiazolinyl, C ₂-C ₆Alkynyl, C ₃-C ₆Cycloalkyl, C ₁-C ₆Alkoxyl group, C ₁-C ₆Halogenated alkoxy, carboxyl, C ₁-C ₇Alkoxy carbonyl, formamyl, C ₁-C ₇Alkyl amino-carbonyl, C ₁-C ₆Alkyl-C ₁-C ₆Alkyl amino-carbonyl, C ₁-C ₆Alkylthio, C ₁-C ₆Alkyl sulphinyl, C ₁-C ₆Alkyl sulphonyl, oxyimino-C ₁-C ₆Alkyl and/or C ₁-C ₆Alkyl alkoxy imino--C ₁-C ₆Alkyl.

Formula I compound has good activity for unwanted microorganisms.

Formula I compound can obtain by different approaches.All group definition here as above.

1) Fig. 1 has shown Compound I ' synthetic, R wherein ³The heterocycle that representative connects by nitrogen.

Fig. 1: synthetic (the heterocycle R of compound (I ') ³Connect by nitrogen)

Thiocarbamide (XIV) obtains XVI type pyrimidine (process 1) by carrying out cyclisation with XVII type malonic ester), perhaps obtain XI type pyrimidine (process i)) by carrying out cyclisation with XIII type acetic ester.Obtain XV type compound (process k) by methylthio group being carried out alkylation) or X type compound (process h)).Halogenation is an IX type pyrimidine (process j) or g)) after, compound is converted into II type amine (process f)).Obtain III type compound (process a)) by oxidation, with the nitrogen heterocyclic ring reaction, finally obtain formula I ' compound of the present invention (process b) again).

2) with the page 3 of WO2004/103978 and page 4 on described synthetic similar, thereby can at first generate XXI type compound preparation formula I_ by the sulfo group pyrimidine (see figure 1) of formula III with hydrazine reaction " compound.

Fig. 2:

Further synthetic can carrying out as shown in Figure 3:

Fig. 3:

Hydrazine compound XXI and dicarbonyl compound XXII condensation are obtained formula XXIII compound, wherein substituent R ¹, R ², R ⁴, R ⁵, R ⁶And R ^dDefine as above, R ' represents alkyl, aryl or benzyl (see figure 3).The dicarbonyl compound of formula XXII is known in Angew.Chem.Int.Ed.Engl.1989 28, p.500.Condensation reaction is carried out according to description more detailed in DE 19627002.According to cyclization of the present invention be Compound I _ " be reflected under the condition that for example has alkali to exist and carry out, described alkali is alkali alcoholate particularly for example.(Synlett 1996,667-8) clearly description to have been carried out in the reaction that has sodium methylate to exist.At alkylating reagent R ^dX and alkaline exist down, obtain Compound I of the present invention _ ", R wherein ^dDefinition as above, X represents leavings group, for example halogen or sulfate radical, described highly basic is sodium hydride or Anhydrous potassium carbonate for example.

3) Fig. 4 has shown Compound I " synthetic, R wherein ³The heterocycle that representative connects by carbon.

Fig. 4: synthetic (the heterocycle R of compound (I ") ³Connect by carbon)

(market is on sale for the heterocyclically substituted amidine of XIX type, for example from Chemstep (www.chemstep.com)) carry out cyclisation with the malonic ester of XVII type and obtain XX type pyrimidine (process p)), perhaps carry out cyclisation and obtain XVIII type pyrimidine (process n) with XIII type acetic ester).Here also can use the amidine of salt form and use alkali that its original place (in situ) discharged.Generate V-type pyrimidine (process o) or m) by halogenation), this V-type pyrimidine and amine reaction generation Compound I of the present invention " (process c).

4) by make halogenated pyrimidine (I ' a or I " a) and R ⁴M ¹Shaped metal compound or Grignard compound VIII reaction generate of the present invention on the 6-position by R ⁴The I_ type pyrimidine (see figure 5) that replaces.

Fig. 5: compound (I_) synthetic

Now find and can a) use oxygenant oxidation formula (II) by process if compound---this reaction is suitably under the thinner existence to be carried out, with process b) formula (III) compound that will obtain like this and formula (IV) be if the compound reaction---and if this reaction is suitably in thinner and exists and carries out down and be suitably under the alkali existence carrying out, thereby the 5-heterocyclyl pyrimidines of preparation formula (I ')

R wherein ¹, R ²And R ⁵Define as above R ³The heterocycle that representative connects by nitrogen, R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

R wherein ¹, R ²And R ⁵Define as above R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ⁶Represent C ₁-C ₆Alkyl,

R wherein ¹, R ², R ⁵And R ⁶Define as above R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, n=1 or 2,

R ³-H(IV)

R wherein ³Define as above, condition is R ³Must have at least one nitrogen-atoms, group is connected on the pyrimidine ring of formula (I ') compound by this nitrogen-atoms.

The 5-heterocyclyl pyrimidines of formula (I ") can be by process c) make formula V compound and formula (VI) compound prepared in reaction; exist down and carry out if this reaction is suitably in thinner; carry out under existing, and if be suitably under the acid acceptor existence and carry out if be suitably in catalyzer

R wherein ¹, R ²And R ⁵Define as above R ³The heterocycle that representative connects by carbon, R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

R wherein ³, R ⁵Define as above, condition is R ³Be the heterocycle that is connected with the pyrimidine ring of (V) type compound by carbon atom, R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

HNR ¹R ² (VI)

R wherein ¹And R ²Definition as above.

But through type (I ' a) or in the formula (I " a) compound is at process d) with formula (VII) if the compound reaction---this reaction is suitably in the presence of the thinner to be carried out; perhaps at process e) in the presence of thinner with formula (VIII) if Grignard compound reacts---this reaction is suitably in the presence of the catalyzer to be carried out; thus the 5-heterocyclyl pyrimidines of preparation formula (I_)

R wherein ¹, R ²And R ⁵Define as above R ³The heterocycle that representative connects by nitrogen or carbon, R ⁴Represent C ₁-C ₈Alkyl, C ₁-C ₈Alkoxyl group, C ₁-C ₈Alkylthio, C ₁-C ₈Alkyl sulphonyl or cyano group,

R wherein ¹, R ², R ³And R ⁵Define as above: Hal represents halogen,

R ⁴-M ¹(VII)

R wherein ⁴Represent C ₁-C ₈Alkoxyl group, C ₁-C ₈Alkylthio, C ₁-C ₈Alkyl sulphinyl, C ₁-C ₈Alkyl sulphonyl or cyano group, and

M ¹Represent sodium or potassium,

R ⁴-MgHal(VIII)

R wherein ⁴Represent C ₁-C ₈Alkyl and

Hal represents chlorine or bromine.

At last, the 5-heterocyclyl pyrimidines of discoverable type (I) is very suitable for preventing and treating unwanted microorganisms.This compounds particularly has strong Fungicidally active, and can be used for Crop protection and material protection.

Surprisingly, the most similar and compound that effective object is identical of structure is compared in the 5-heterocyclyl pyrimidines of formula of the present invention (I) and the prior art, its microbiocidal activity excellence many.

If it is suitable, formula of the present invention (I) compound can be used as different possible mixture of isomers and exists, described isomer is steric isomer particularly, for example E isomer and Z isomer, threo isomer and erythro isomer, and optically active isomer, if for example R isomer and S isomer or atropisomer are and the suitable tautomer that also comprises.

In the definition to the symbol in the above-mentioned formula, the collective term of use is the following substituting group of representative usually:

Halogen: fluorine, chlorine, bromine and iodine; Halogen is preferably represented chlorine or bromine, preferred especially chlorine;

Alkyl: have the saturated straight or branched alkyl of 1 to 4,6 or 8 carbon atom, for example C ₁-C ₆Alkyl, methyl for example, ethyl, propyl group, the 1-methylethyl, butyl, the 1-methyl-propyl, the 2-methyl-propyl, 1, the 1-dimethyl ethyl, amyl group, the 1-methyl butyl, the 2-methyl butyl, the 3-methyl butyl, 2, the 2-dimethyl propyl, the 1-ethyl propyl, hexyl, 1, the 1-dimethyl propyl, 1, the 2-dimethyl propyl, the 1-methyl amyl, the 2-methyl amyl, the 3-methyl amyl, the 4-methyl amyl, 1, the 1-dimethylbutyl, 1, the 2-dimethylbutyl, 1, the 3-dimethylbutyl, 2, the 2-dimethylbutyl, 2, the 3-dimethylbutyl, 3, the 3-dimethylbutyl, the 1-ethyl-butyl, the 2-ethyl-butyl, 1,1,2-trimethylammonium propyl group, 1,2,2-trimethylammonium propyl group, 1-ethyl-1-methyl-propyl and 1-ethyl-2-methyl-propyl;

Haloalkyl: have the straight or branched alkyl (as mentioned above) of 1 to 8 carbon atom, wherein part or all hydrogen atom in these groups can be replaced by above-mentioned halogen atom, for example C ₁-C ₃Haloalkyl, for example chloro methyl, bromomethyl, dichloromethyl, trichloromethyl, fluoro methyl, difluoromethyl, trifluoromethyl, chloro fluoro methyl, dichloro one methyl fluoride, a chlorodifluoramethyl-, 1-chloroethyl, 1-bromotrifluoromethane, 1-fluoro ethyl, 2-fluoro ethyl, 2,2-two fluoro ethyls, 2,2,2-trifluoroethyl, 2-chloro-2-fluoro ethyl, 2-chloro-2,2-two fluoro ethyls, 2,2-two chloro-2-fluoro ethyls, 2,2,2-three chloroethyls, pentafluoroethyl group and 1,1,1-trifluoropropyl-2-base;

Thiazolinyl: have the unsaturated alkyl of the straight or branched of the two keys on 2 to 4,6 or 8 carbon atoms and the optional position, for example C ₂-C ₆Thiazolinyl, vinyl for example, the 1-propenyl, the 2-propenyl, the 1-methyl ethylene, the 1-butylene base, crotyl, the 3-butenyl, 1-methyl isophthalic acid-propenyl, 2-methyl isophthalic acid-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, the 1-pentenyl, pentenyl, the 3-pentenyl, the 4-pentenyl, 1-methyl isophthalic acid-butenyl, the 2-methyl-1-butene thiazolinyl, the 3-methyl-1-butene base, 1-methyl-2-butene base, 2-methyl-2-butene base, 3-methyl-2-butene base, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, the 1-hexenyl, the 2-hexenyl, the 3-hexenyl, the 4-hexenyl, the 5-hexenyl, 1-methyl-1-pentene thiazolinyl, 2-methyl-1-pentene thiazolinyl, 3-methyl-1-pentene thiazolinyl, the 4-methyl-1-pentene base, 1-methyl-pentenyl, 2-methyl-pentenyl, 3-methyl-pentenyl, 4-methyl-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-crotyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butylene base, 1,2-dimethyl-crotyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-1-butylene base, 1,3-dimethyl-crotyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butylene base, 2,3-dimethyl-crotyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butylene base, 3,3-dimethyl-crotyl, 1-ethyl-1-butylene base, 1-ethyl-crotyl, 1-ethyl-3-butenyl, 2-ethyl-1-butylene base, 2-ethyl-crotyl, 2-ethyl-3-butenyl, 1,1,2-trimethylammonium-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl isophthalic acid-propenyl and 1-ethyl-2-methyl-2-propenyl;

Alkynyl: have the alkyl of the straight or branched of three key on 2 to 4,6 or 8 carbon atoms and the optional position, for example C ₂-C ₆Alkynyl, ethynyl for example, the 1-proyl, 2-propynyl, the ethyl acetylene base, the 2-butyne base, the 3-butynyl, 1-methyl-2-propynyl, the 1-pentynyl, the valerylene base, the 3-pentynyl, the 4-pentynyl, 1-methyl-2-butyne base, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl isophthalic acid-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexin base, 2-hexin base, 3-hexin base, 4-hexin base, 5-hexin base, 1-methyl-valerylene base, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1-pentene alkynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentene alkynyl, 4-methyl-valerylene base, 1,1-dimethyl-2-butyne base, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-ethyl acetylene base, 1-ethyl-2-butyne base, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and 1-ethyl-1-methyl-2-propynyl;

Cycloalkyl: have the monocyclic saturated hydrocarbon group base of 3 to 8 carboatomic ring atoms, for example cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl;

Cycloalkenyl group: have the monocycle non-aromatic hydrocarbon base of the two keys of 3 to 8 carboatomic ring atoms and at least one, for example cyclopentenes-1-base, tetrahydrobenzene-1-base, ring heptan-1,3-diene-1-base;

Alkoxy carbonyl: by carbonyl (the alkoxyl group (as mentioned above) that CO-) links to each other with 1 to 6 carbon atom with skeleton;

Oxygen base alkene oxygen base: by 1 to 3 CH ₂The non-side chain chain of divalence that group is formed, wherein two valence links all are connected on the skeleton by Sauerstoffatom, for example OCH ₂O, OCH ₂CH ₂O and OCH ₂CH ₂CH ₂O;

Five yuan to ten yuan saturated or part is undersaturated to contain one to four heteroatomic heterocycle that is selected from oxygen, nitrogen and sulphur: except carboatomic ring atom, also contain the monocycle or the bicyclic heterocycles (heterocyclic radical) of one to three nitrogen-atoms and/or Sauerstoffatom or sulphur atom or one or two Sauerstoffatom and/or sulphur atom; If described ring contains a plurality of Sauerstoffatoms, then these Sauerstoffatoms are non-conterminous; Oxyranyle for example, aziridinyl, the 2-tetrahydrofuran base, the 3-tetrahydrofuran base, the 2-tetrahydro-thienyl, the 3-tetrahydro-thienyl, the 2-pyrrolidyl, the 3-pyrrolidyl, the 3-isoxazole alkyl, the 4-isoxazole alkyl, the 5-isoxazole alkyl, 3-isothiazole alkyl, 4-isothiazole alkyl, 5-isothiazole alkyl, the 3-pyrazolidyl, the 4-pyrazolidyl, the 5-pyrazolidyl, the 2-oxazolidinyl, the 4-oxazolidinyl, the 5-oxazolidinyl, the 2-thiazolidyl, the 4-thiazolidyl, the 5-thiazolidyl, the 2-imidazolidyl, the 4-imidazolidyl, 1,2,4-oxadiazole alkane-3-base, 1,2,4-oxadiazole alkane-5-base, 1,2,4-thiadiazolidine-3-base, 1,2,4-thiadiazolidine-5-base, 1,2,4-triazolidine-3-base, 1,3,4-oxadiazole alkane-2-base, 1,3,4-thiadiazolidine-2-base, 1,3,4-triazolidine-2-base, 2,3-dihydrofuran-2-base, 2,3-dihydrofuran-3-base, 2,4-dihydrofuran-2-base, 2,4-dihydrofuran-3-base, 2,3-dihydro-thiophene-2-base, 2,3-dihydro-thiophene-3-base, 2,4-dihydro-thiophene-2-base, 2,4-dihydro-thiophene-3-base, 2-pyrroline-2-base, 2-pyrroline-3-base, 3-pyrroline-2-base, 3-pyrroline-3-base, 2-isoxazoline-3-base, 3-isoxazoline-3-base, 4-isoxazoline-3-base, 2-isoxazoline-4-base, 3-isoxazoline-4-base, 4-isoxazoline-4-base, 2-isoxazoline-5-base, 3-isoxazoline-5-base, 4-isoxazoline-5-base, 2-isothiazoline-3-base, 3-isothiazoline-3-base, 4-isothiazoline-3-base, 2-isothiazoline-4-base, 3-isothiazoline-4-base, 4-isothiazoline-4-base, 2-isothiazoline-5-base, 3-isothiazoline-5-base, 4-isothiazoline-5-base, 2,3-pyrazoline-1-base, 2,3-pyrazoline-2-base, 2,3-pyrazoline-3-base, 2,3-pyrazoline-4-base, 2,3-pyrazoline-5-base, 3,4-pyrazoline-1-base, 3,4-pyrazoline-3-base, 3,4-pyrazoline-4-base, 3,4-pyrazoline-5-base, 4,5-pyrazoline-1-base, 4,5-pyrazoline-3-base, 4,5-pyrazoline-4-base, 4,5-pyrazoline-5-base, 2,3-dihydro-oxazole-2-base, 2,3-dihydro-oxazole-3-base, 2,3-dihydro-oxazole-4-base, 2,3-dihydro-oxazole-5-base, 3,4-dihydro-oxazole-2-base, 3,4-dihydro-oxazole-3-base, 3,4-dihydro-oxazole-4-base, 3,4-dihydro-oxazole-5-base, 3,4-dihydro-oxazole-2-base, 3,4-dihydro-oxazole-3-base, 3,4-dihydro-oxazole-4-base, the 2-piperidyl, the 3-piperidyl, the 4-piperidyl, 1,3-diox-5-base, the 2-THP trtrahydropyranyl, the 4-THP trtrahydropyranyl, the 2-tetrahydro-thienyl, 3-hexahydro-pyridazine base, 4-hexahydro-pyridazine base, 2-hexahydropyrimidine base, 4-hexahydropyrimidine base, 5-hexahydropyrimidine base, the 2-piperazinyl, 1,3,5-Hexahydrotriazine-2-base and 1,2,4-Hexahydrotriazine-3-base;

Five yuan to ten yuan contain one to four heteroatomic aromatic heterocycle that is selected from oxygen, nitrogen and sulphur: monocycle or bicyclic heteroaryl, for example

- Contain one to four nitrogen-atoms or one to three nitrogen-atoms and sulphur atom or Sauerstoffatom 5 yuan of heteroaryls: except carbon atom, also can contain one to four nitrogen-atoms or one to three nitrogen-atoms and sulphur atom or Sauerstoffatom 5 yuan of heteroaryls as annular atoms, 2-furyl for example, the 3-furyl, the 2-thienyl, the 3-thienyl, the 2-pyrryl, the 3-pyrryl, the 3-isoxazolyl, the 4-isoxazolyl, the 5-isoxazolyl, the 3-isothiazolyl, the 4-isothiazolyl, the 5-isothiazolyl, the 3-pyrazolyl, the 4-pyrazolyl, the 5-pyrazolyl, the 2-oxazolyl, the 4-oxazolyl, the 5-oxazolyl, the 2-thiazolyl, the 4-thiazolyl, the 5-thiazolyl, the 2-imidazolyl, the 4-imidazolyl, 1,2,4-oxadiazole-3-base, 1,2,4-oxadiazole-5-base, 1,2,4-thiadiazoles-3-base, 1,2,4-thiadiazoles-5-base, 1,2,4-triazole-3-base, 1,3,4-oxadiazole-2-base, 1,3,4-thiadiazoles-2-base and 1,3,4-triazole-2-base;

- The benzene that contains one to three nitrogen-atoms or nitrogen-atoms and Sauerstoffatom or sulphur atom And 5 yuan of heteroaryls of condensed: except carbon atom, also can contain one to four nitrogen-atoms or one to three nitrogen-atoms and sulphur atom or Sauerstoffatom 5 yuan of heteroaryls as annular atoms, two adjacent carboatomic ring atoms or a nitrogen-atoms and an adjacent carboatomic ring atom can be by fourths-1 in the described heteroaryl, 3-diene-1,4-two basic bridgings, described fourth-1,3-diene-1, one or two carbon atom can be replaced by nitrogen-atoms in 4-two bases;

- Contain one to four nitrogen-atoms and by 5 yuan of heteroaryls that nitrogen connects, perhaps contain one to Three nitrogen-atoms and the 5 yuan of benzo-fused heteroaryls that connect by nitrogen: except carbon atom, also can contain one to four nitrogen-atoms or one to three nitrogen-atoms 5 yuan of heteroaryls as annular atoms, two adjacent carboatomic ring atoms or a nitrogen-atoms and an adjacent carboatomic ring atom can be by fourths-1 in the described heteroaryl, 3-diene-1,4-two basic bridgings, described fourth-1,3-diene-1, one or two carbon atom can be replaced by nitrogen-atoms in 4-two bases, these rings are connected on the skeleton by an azo-cycle atom, 1-pyrryl for example, the 1-pyrazolyl, 1,2, the 4-triazol-1-yl, the 1-imidazolyl, 1,2, the 3-triazol-1-yl, 1,3, the 4-triazol-1-yl;

- 6 yuan of heteroaryls that contain one to three or one to four nitrogen-atoms:Except carbon atom, also can contain one to three nitrogen-atoms or one to four nitrogen-atoms 6 yuan of heteroaryls, for example 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 2-pyrazinyl, 1 as annular atoms, 3,5-triazine-2-base and 1,2,4-triazine-3-base.

For various distortion, the intermediate particularly preferred embodiment is corresponding to the R in formula (I) compound ¹To R ⁵The particularly preferred embodiment of group.

For final product formula (I) compound, and correspondingly, for raw material required among every kind of preparation method and intermediate, preferred especially following substituting group implication, these implications provide or provide its combination separately.

Preferred R wherein ¹Formula (I) compound of the following group of representative

Wherein # represents tie point.

Especially preferred R wherein ¹Formula (I) compound of the following group of representative

Preferred R wherein ²Represent formula (I) compound of hydrogen, methyl, ethyl or propyl group.

Equally, also preferred such formula (I) compound, wherein R ¹And R ²Represent pyrrolidyl, piperidyl, morpholinyl, thio-morpholinyl, piperazinyl, 3 with the nitrogen-atoms that they connected, 6-dihydro-1 (2H)-piperidyl or tetrahydrochysene-1 (2H)-pyridazinyl, wherein above-mentioned group can be replaced by 1 to 3 fluorine atom, 1 to 3 methyl and/or trifluoromethyl.

Equally, also preferred such formula (I) compound, wherein R ¹And R ²Represent following group with the nitrogen-atoms that they connected

Or

Wherein

R ₇Represent hydrogen or methyl,

R ⁸Represent methylidene, ethyl, fluorine, chlorine or trifluoromethyl,

M represents numeral 0,1,2 or 3, and wherein m represents 2 or 3 o'clock R ⁸Represent identical or different group,

R ⁹Represent methylidene, ethyl, fluorine, chlorine or trifluoromethyl,

And

O represents numeral 0,1,2 or 3, and wherein n represents 2 or 3 o'clock R ⁹Represent identical or different group.

Preferred R wherein ³Formula (I) compound for aromatic heterocycle.

In addition, preferred R wherein also ³Formula (I) compound for ternary, five yuan or hexa-member heterocycle, particularly five-membered ring.

Especially preferably R wherein ³Be nitrogenous heterocyclic formula (I) compound.

In addition, preferred R wherein also ³Be heterocyclic formula (I) compound that is connected with pyrimidine ring by nitrogen.

Equally, also preferred such formula (I) compound, wherein R ³Represent following group: pyrroles, pyrazoles, imidazoles, 1,2,4-triazole, 1,2,3-triazole, tetrazolium, 1,2,3-triazine, 1,2,4-triazine, oxazole, isoxazole, 1,3,4-oxadiazole, 1,3,4-thiadiazoles, furans, thiophene, thiazole, isothiazole, wherein heterocycle can be connected on the pyrimidine ring by carbon or nitrogen.

Also preferably wherein encircle R ³Represent formula (I) compound of pyridazine, pyrimidine or pyrazine.

Equally, also preferred such formula (I) compound, wherein R ³Represent following group: pyrazoles, pyrroles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazoles, tetrazolium, 2-pyridine, 2-pyrimidine, pyrazine or 3-pyridazine, each above-mentioned group is optional by maximum four radicals R ^dReplace.

Equally, also preferred such formula (I) compound, wherein R ³Represent following group: pyrazoles, pyrroles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazoles, tetrazolium, 2-pyridine, 2-pyrimidine, pyrazine or 3-pyridazine, each above-mentioned group is optional by maximum three radicals R ^dReplace.

Especially preferred R wherein ³Represent pyrazoles, 1,2,3-triazoles, 1,2, the formula of 4-triazole or pyridazine (I) compound.

In addition, also especially preferably wherein encircle R ³By one to three identical or different following radicals R ^dFormula (I) compound that replaces:

Halogen, hydroxyl, cyano group, nitro, amino, sulfydryl, C ₁-C ₆Alkyl, C ₁-C ₆Haloalkyl, C ₂-C ₆Thiazolinyl, C ₂-C ₆Alkynyl, C ₃-C ₆Cycloalkyl, C ₁-C ₆Alkoxyl group, C ₁-C ₆Halogenated alkoxy, carboxyl, C ₁-C ₇Alkoxy carbonyl, formamyl, C ₁-C ₇Alkyl amino-carbonyl, C ₁-C ₆Alkyl-C ₁-C ₆Alkyl amino-carbonyl, morpholino carbonyl, oxo, pyrrolidyl carbonyl, C ₁-C ₇Alkyl-carbonyl-amino, C ₁-C ₆Alkylamino, two-(C ₁-C ₆Alkyl) amino, C ₁-C ₆Alkylthio, C ₁-C ₆Alkyl sulphinyl, C ₁-C ₆Alkyl sulphonyl, hydroxyl alkylsulfonyl, amino-sulfonyl, C ₁-C ₆Alkyl amino sulfonyl or two-(C ₁-C ₆Alkyl) amino-sulfonyl.

In particular, especially preferably wherein encircle R ³By one to three identical or different following radicals R ^dFormula (I) compound that replaces:

Halogen, cyano group, nitro, hydroxyl, amino, C ₁-C ₆Alkyl, C ₁-C ₆Haloalkyl, C ₁-C ₆Alkoxyl group, carboxyl, C ₁-C ₇Alkoxy carbonyl, formamyl, C ₁-C ₇Alkyl amino-carbonyl, two-(C ₁-C ₆Alkyl) aminocarboxyl or C ₁-C ₇Alkyl-carbonyl-amino or oxo.

Especially preferred R wherein ³Be not substituted or by the mono-substituted formula of halogen, cyano group, nitro, methyl, hydroxyl, oxo or methoxyl group (I) compound.

In addition, especially preferred R wherein also ⁴Represent halogen, C ₁-C ₆Alkyl, C ₁-C ₆Haloalkyl or C ₁-C ₆Alkoxyl group, particularly represent formula (I) compound of halogen.

Especially preferred R wherein ⁴Represent formula (I) compound of chlorine.

In addition, preferred R wherein also ⁵Represent the pyrimidine of the formula (I) of pyridyl, described pyridyl connects on its 2-position or 4-position, and can be replaced by identical or different following substituting group list to four replacements: fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

Preferred R wherein equally, also ⁵Represent the pyrimidine of the formula (I) of pyrimidyl, described pyrimidyl connects on its 2-position or 4-position, and can be replaced by identical or different following substituting group list to three replacements: fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

Preferred R wherein equally, also ⁵Represent the pyrimidine of the formula (I) of thienyl, described thienyl connects on its 2-position or 3-position, and can be replaced by identical or different following substituting group list to three replacements: fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

Preferred R wherein equally, also ⁵Represent the pyrimidine of the formula (I) of thiazolyl, described thiazolyl connects on its 2-position, 4-position or 5-position, and can be replaced or two replacement by identical or different following substituting group list: fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

Consider purposes especially, the Compound I of listing in the preferred following table.The substituent group of the conduct that provides in the table itself is independent of the combination of addressing it, also is this substituting group particularly preferred embodiment.

Table 1

Formula (I-1) compound, wherein R ⁵Representative

And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 2

Formula (I-1) compound, wherein R ⁵Representative

Table 3

Formula (I-1) compound, wherein R ⁵Representative

Table 4

Formula (I-1) compound, wherein R ⁵Representative

Table 5

Formula (I-1) compound, wherein R ⁵Representative

Table 6

Formula (I-1) compound, wherein R ⁵Representative

Table 7

Formula (I-1) compound, wherein R ⁵Representative

Table 8

Formula (I-1) compound, wherein R ⁵Representative

Table 9

Formula (I-1) compound, wherein R ⁵Representative

Table 10

Formula (I-1) compound, wherein R ⁵Representative

Table 11

Formula (I-1) compound, wherein R ⁵Representative

Table 12

Formula (I-1) compound, wherein R ⁵Representative

Table 13

Formula (I-1) compound, wherein R ⁵Representative

Table 14

Formula (I-1) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 15

Formula (I-1) compound, wherein R ⁵Representative

Table 16

Table 17

Formula (I-1) compound, wherein R ⁵Representative

Table 18

Formula (I-1) compound, wherein R ⁵Representative

Table 19

Formula (I-1) compound, wherein R ⁵Representative

Table 20

Formula (I-2) compound, wherein R ⁵Representative

Table 21

Formula (I-2) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 22

Formula (I-2) compound, wherein R ⁵Representative

Table 23

Formula (I-2) compound, wherein R ⁵Representative

Table 24

Formula (I-2) compound, wherein R ⁵Representative

Table 25

Formula (I-2) compound, wherein R ⁵Representative

Table 26

Formula (I-2) compound, wherein R ⁵Representative

Table 27

Formula (I-2) compound, wherein R ⁵Representative

Table 28

Formula (I-2) compound, wherein R ⁵Representative

Table 29

Formula (I-2) compound, wherein R ⁵Representative

Table 30

Formula (I-2) compound, wherein R ⁵Representative

Table 31

Formula (I-2) compound, wherein R ⁵Representative

Table 32

Table 33

Formula (I-2) compound, wherein R ⁵Representative

Table 34

Formula (I-2) compound, wherein R ⁵Representative

Table 35

Formula (I-2) compound, wherein R ⁵Representative

Table 36

Formula (I-2) compound, wherein R ⁵Representative

Table 37

Formula (I-2) compound, wherein R ⁵Representative

Table 38

Table 39

Formula (I-3) compound, wherein R ⁵Representative

Table 40

Formula (I-3) compound, wherein R ⁵Representative

Table 41

Formula (I-3) compound, wherein R ⁵Representative

Table 42

Formula (I-3) compound, wherein R ⁵Representative

Table 43

Formula (I-3) compound, wherein R ⁵Representative

Table 44

Formula (I-3) compound, wherein R ⁵Representative

Table 45

Formula (I-3) compound, wherein R ⁵Representative

Table 46

Formula (I-3) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 47

Formula (I-3) compound, wherein R ⁵Representative

Table 48

Formula (I-3) compound, wherein R ⁵Representative

Table 49

Formula (I-3) compound, wherein R ⁵Representative

Table 50

Formula (I-3) compound, wherein R ⁵Representative

Table 51

Formula (I-3) compound, wherein R ⁵Representative

Table 52

Formula (I-3) compound, wherein R ⁵Representative

Table 53

Formula (I-3) compound, wherein R ⁵Representative

Table 54

Formula (I-3) compound, wherein R ⁵Representative

Table 55

Formula (I-3) compound, wherein R ⁵Representative

Table 56

Formula (I-3) compound, wherein R ⁵Representative

Table 57

Table 58

Formula (I-4) compound, wherein R ⁵Representative

Table 59

Formula (I-4) compound, wherein R ⁵Representative

Table 60

Formula (I-4) compound, wherein R ⁵Representative

Table 61

Formula (I-4) compound, wherein R ⁵Representative

Table 62

Formula (I-4) compound, wherein R ⁵Representative

Table 63

Formula (I-4) compound, wherein R ⁵Representative

Table 64

Formula (I-4) compound, wherein R ⁵Representative

Table 65

Formula (I-4) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 66

Formula (I-4) compound, wherein R ⁵Representative

Table 67

Formula (I-4) compound, wherein R ⁵Representative

Table 68

Formula (I-4) compound, wherein R ⁵Representative

Table 69

Formula (I-4) compound, wherein R ⁵Representative

Table 70

Formula (I-4) compound, wherein R ⁵Representative

Table 71

Formula (I-4) compound, wherein R ⁵Representative

Table 72

Table 73

Formula (I-4) compound, wherein R ⁵Representative

Table 74

Formula (I-4) compound, wherein R ⁵Representative

Table 75

Formula (I-4) compound, wherein R ⁵Representative

Table 76

Formula (I-4) compound, wherein R ⁵Representative

Table 77

Formula (I-5) compound, wherein R ⁵Representative

Table 78

Formula (I-5) compound, wherein R ⁵Representative

Table 79

Formula (I-5) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 80

Formula (I-5) compound, wherein R ⁵Representative

Table 81

Formula (I-5) compound, wherein R ⁵Representative

Table 82

Formula (I-5) compound, wherein R ⁵Representative

Table 83

Formula (I-5) compound, wherein R ⁵Representative

Table 84

Formula (I-5) compound, wherein R ⁵Representative

Table 85

Formula (I-5) compound, wherein R ⁵Representative

Table 86

Formula (I-5) compound, wherein R ⁵Representative

Table 87

Formula (I-5) compound, wherein R ⁵Representative

Table 88

Formula (I-5) compound, wherein R ⁵Representative

Table 89

Formula (I-5) compound, wherein R ⁵Representative

Table 90

Formula (I-5) compound, wherein R ⁵Representative

Table 91

Formula (I-5) compound, wherein R ⁵Representative

Table 92

Formula (I-5) compound, wherein R ⁵Representative

Table 93

Formula (I-5) compound, wherein R ⁵Representative

Table 94

Formula (I-5) compound, wherein R ⁵Representative

Table 95

Table 96

Formula (I-6) compound, wherein R ⁵Representative

Table 97

Formula (I-6) compound, wherein R ⁵Representative

Table 98

Formula (I-6) compound, wherein R ⁵Representative

Table 99

Formula (I-6) compound, wherein R ⁵Representative

Table 100

Formula (I-6) compound, wherein R ⁵Representative

Table 101

Formula (I-6) compound, wherein R ⁵Representative

Table 102

Formula (I-6) compound, wherein R ⁵Representative

Table 103

Formula (I-6) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 104

Formula (I-6) compound, wherein R ⁵Representative

Table 105

Formula (I-6) compound, wherein R ⁵Representative

Table 106

Formula (I-6) compound, wherein R ⁵Representative

Table 107

Formula (I-6) compound, wherein R ⁵Representative

Table 108

Formula (I-6) compound, wherein R ⁵Representative

Table 109

Formula (I-6) compound, wherein R ⁵Representative

Table 110

Formula (I-6) compound, wherein R ⁵Representative

Table 111

Formula (I-6) compound, wherein R ⁵Representative

Table 112

Formula (I-6) compound, wherein R ⁵Representative

Table 113

Formula (I-6) compound, wherein R ⁵Representative

Table 114

Formula (I-6) compound, wherein R ⁵Representative

Table 115

Formula (I-7) compound, wherein R ⁵Representative

Table 116

Formula (I-7) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 117

Formula (I-7) compound, wherein R ⁵Representative

Table 118

Table 119

Formula (I-7) compound, wherein R ⁵Representative

Table 120

Formula (I-7) compound, wherein R ⁵Representative

Table 121

Formula (I-7) compound, wherein R ⁵Representative

Table 122

Formula (I-7) compound, wherein R ⁵Representative

Table 123

Formula (I-7) compound, wherein R ⁵Representative

Table 124

Formula (I-7) compound, wherein R ⁵Representative

Table 125

Formula (I-7) compound, wherein R ⁵Representative

Table 126

Table 127

Formula (I-7) compound, wherein R ⁵Representative

Table 128

Formula (I-7) compound, wherein R ⁵Representative

Table 129

Formula (I-7) compound, wherein R ⁵Representative

Table 130

Formula (I-7) compound, wherein R ⁵Representative

Table 131

Formula (I-7) compound, wherein R ⁵Representative

Table 132

Table 133

Formula (I-7) compound, wherein R ⁵Representative

Table 134

Formula (I-8) compound, wherein R ⁵Representative

Table 135

Formula (I-8) compound, wherein R ⁵Representative

Table 136

Formula (I-8) compound, wherein R ⁵Representative

Table 137

Formula (I-8) compound, wherein R ⁵Representative

Table 138

Formula (I-8) compound, wherein R ⁵Representative

Table 139

Formula (I-8) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 140

Formula (I-8) compound, wherein R ⁵Representative

Table 141

Formula (I-8) compound, wherein R ⁵Representative

Table 142

Formula (I-8) compound, wherein R ⁵Representative

Table 143

Formula (I-8) compound, wherein R ⁵Representative

Table 144

Table 145

Formula (I-8) compound, wherein R ⁵Representative

Table 146

Formula (I-8) compound, wherein R ⁵Representative

Table 147

Formula (I-8) compound, wherein R ⁵Representative

Table 148

Table 149

Formula (I-8) compound, wherein R ⁵Representative

Table 150

Formula (I-8) compound, wherein R ⁵Representative

Table 151

Formula (I-8) compound, wherein R ⁵Representative

Table 152

Formula (I-8) compound, wherein R ⁵Representative

Table 153

Formula (I-9) compound, wherein R ⁵Representative

Table 154

Formula (I-9) compound, wherein R ⁵Representative

Table 155

Formula (I-9) compound, wherein R ⁵Representative

Table 156

Formula (I-9) compound, wherein R ⁵Representative

Table 157

Formula (I-9) compound, wherein R ⁵Representative

Table 158

Formula (I-9) compound, wherein R ⁵Representative

Table 159

Formula (I-9) compound, wherein R ⁵Representative

Table 160

Formula (I-9) compound, wherein R ⁵Representative

Table 161

Formula (I-9) compound, wherein R ⁵Representative

Table 162

Formula (I-9) compound, wherein R ⁵Representative

Table 163

Formula (I-9) compound, wherein R ⁵Representative

Table 164

Formula (I-9) compound, wherein R ⁵Representative

Table 165

Formula (I-9) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 166

Formula (I-9) compound, wherein R ⁵Representative

Table 167

Formula (I-9) compound, wherein R ⁵Representative

Table 168

Formula (I-9) compound, wherein R ⁵Representative

Table 169

Formula (I-9) compound, wherein R ⁵Representative

Table 170

Formula (I-9) compound, wherein R ⁵Representative

Table 171

Formula (I-9) compound, wherein R ⁵Representative

Table 172

Formula (I-10) compound, wherein R ⁵Representative

Table 173

Formula (I-10) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 174

Formula (I-10) compound, wherein R ⁵Representative

Table 175

Formula (I-10) compound, wherein R ⁵Representative

Table 176

Formula (I-10) compound, wherein R ⁵Representative

Table 177

Table 178

Formula (I-10) compound, wherein R ⁵Representative

Table 179

Formula (I-10) compound, wherein R ⁵Representative

Table 180

Table 181

Formula (I-10) compound, wherein R ⁵Representative

Table 182

Formula (I-10) compound, wherein R ⁵Representative

Table 183

Formula (I-10) compound, wherein R ⁵Representative

Table 184

Formula (I-10) compound, wherein R ⁵Representative

Table 185

Formula (I-10) compound, wherein R ⁵Representative

Table 186

Formula (I-10) compound, wherein R ⁵Representative

Table 187

Formula (I-10) compound, wherein R ⁵Representative

Table 188

Formula (I-10) compound, wherein R ⁵Representative

Table 189

Formula (I-10) compound, wherein R ⁵Representative

Table 190

Formula (I-10) compound, wherein R ⁵Representative

Table 191

Formula (I-11) compound, wherein R ⁵Representative

Table 192

Formula (I-11) compound, wherein R ⁵Representative

Table 193

Formula (I-11) compound, wherein R ⁵Representative

Table 194

Formula (I-11) compound, wherein R ⁵Representative

Table 195

Formula (I-11) compound, wherein R ⁵Representative

Table 196

Formula (I-11) compound, wherein R ⁵Representative

Table 197

Formula (I-11) compound, wherein R ⁵Representative

Table 198

Formula (I-11) compound, wherein R ⁵Representative

Table 199

Formula (I-11) compound, wherein R ⁵Representative

Table 200

Formula (I-11) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 201

Formula (I-11) compound, wherein R ⁵Representative

Table 202

Formula (I-11) compound, wherein R ⁵Representative

Table 203

Formula (I-11) compound, wherein R ⁵Representative

Table 204

Formula (I-11) compound, wherein R ⁵Representative

Table 205

Formula (I-11) compound, wherein R ⁵Representative

Table 206

Formula (I-11) compound, wherein R ⁵Representative

Table 207

Formula (I-11) compound, wherein R ⁵Representative

Table 208

Table 209

Formula (I-11) compound, wherein R ⁵Representative

Table 210

Formula (I-12) compound, wherein R ⁵Representative

Table 211

Formula (I-12) compound, wherein R ⁵Representative

Table 212

Formula (I-12) compound, wherein R ⁵Representative

Table 213

Formula (I-12) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 214

Formula (I-12) compound, wherein R ⁵Representative

Table 215

Formula (I-12) compound, wherein R ⁵Representative

Table 216

Formula (I-12) compound, wherein R ⁵Representative

Table 217

Formula (I-12) compound, wherein R ⁵Representative

Table 218

Formula (I-12) compound, wherein R ⁵Representative

Table 219

Formula (I-12) compound, wherein R ⁵Representative

Table 220

Formula (I-12) compound, wherein R ⁵Representative

Table 221

Formula (I-12) compound, wherein R ⁵Representative

Table 222

Formula (I-12) compound, wherein R ⁵Representative

Table 223

Formula (I-12) compound, wherein R ⁵Representative

Table 224

Formula (I-12) compound, wherein R ⁵Representative

Table 225

Formula (I-12) compound, wherein R ⁵Representative

Table 226

Formula (I-12) compound, wherein R ⁵Representative

Table 227

Formula (I-12) compound, wherein R ⁵Representative

Table 228

Formula (I-12) compound, wherein R ⁵Representative

Table 229

Formula (I-13) compound, wherein R ⁵Representative

Table 230

Formula (I-13) compound, wherein R ⁵Representative

Table 231

Formula (I-13) compound, wherein R ⁵Representative

Table 232

Formula (I-13) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 233

Formula (I-13) compound, wherein R ⁵Representative

Table 234

Formula (I-13) compound, wherein R ⁵Representative

Table 235

Formula (I-13) compound, wherein R ⁵Representative

Table 236

Formula (I-13) compound, wherein R ⁵Representative

Table 237

Table 238

Formula (I-13) compound, wherein R ⁵Representative

Table 239

Formula (I-13) compound, wherein R ⁵Representative

Table 240

Formula (I-13) compound, wherein R ⁵Representative

Table 241

Formula (I-13) compound, wherein R ⁵Representative

Table 242

Formula (I-13) compound, wherein R ⁵Representative

Table 243

Formula (I-13) compound, wherein R ⁵Representative

Table 244

Formula (I-13) compound, wherein R ⁵Representative

Table 245

Formula (I-13) compound, wherein R ⁵Representative

Table 246

Formula (I-13) compound, wherein R ⁵Representative

Table 247

Formula (I-13) compound, wherein R ⁵Representative

Table 248

Formula (I-14) compound, wherein R ⁵Representative

Table 249

Formula (I-14) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 250

Formula (I-14) compound, wherein R ⁵Representative

Table 251

Formula (I-14) compound, wherein R ⁵Representative

Table 252

Formula (I-14) compound, wherein R ⁵Representative

Table 253

Formula (I-14) compound, wherein R ⁵Representative

Table 254

Formula (I-14) compound, wherein R ⁵Representative

Table 255

Formula (I-14) compound, wherein R ⁵Representative

Table 256

Formula (I-14) compound, wherein R ⁵Representative

Table 257

Table 258

Formula (I-14) compound, wherein R ⁵Representative

Table 259

Formula (I-14) compound, wherein R ⁵Representative

Table 260

Formula (I-14) compound, wherein R ⁵Representative

Table 261

Formula (I-14) compound, wherein R ⁵Representative

Table 262

Formula (I-14) compound, wherein R ⁵Representative

Table 263

Formula (I-14) compound, wherein R ⁵Representative

Table 264

Formula (I-14) compound, wherein R ⁵Representative

Table 265

Formula (I-14) compound, wherein R ⁵Representative

Table 266

Table 267

Formula (I-15) compound, wherein R ⁵Representative

Table 268

Formula (I-15) compound, wherein R ⁵Representative

Table 269

Formula (I-15) compound, wherein R ⁵Representative

Table 270

Formula (I-15) compound, wherein R ⁵Representative

Table 271

Formula (I-15) compound, wherein R ⁵Representative

Table 272

Formula (I-15) compound, wherein R ⁵Representative

Table 273

Formula (I-15) compound, wherein R ⁵Representative

Table 274

Formula (I-15) compound, wherein R ⁵Representative

Table 275

Formula (I-15) compound, wherein R ⁵Representative

Table 276

Formula (I-15) compound, wherein R ⁵Representative And R in the compound ¹And R ²Every kind of situation of combination under corresponding to the delegation in the Table A.

Table 277

Formula (I-15) compound, wherein R ⁵Representative

Table 278

Formula (I-15) compound, wherein R ⁵Representative

Table 279

Formula (I-15) compound, wherein R ⁵Representative

Table 280

Formula (I-15) compound, wherein R ⁵Representative

Table 281

Formula (I-15) compound, wherein R ⁵Representative

Table 282

Formula (I-15) compound, wherein R ⁵Representative

Table 283

Formula (I-15) compound, wherein R ⁵Representative

Table 284

Table 285

Table 286

Formula (I-16) compound, wherein R ⁵Representative

Table 287

Table 288

Formula (I-15) compound, wherein R ⁵Representative

Table 289

Formula (I-15) compound, wherein R ⁵Representative

Table 290

Formula (I-15) compound, wherein R ⁵Representative

Table 291

Formula (I-15) compound, wherein R ⁵Representative

Table 292

Table 293

Formula (I-15) compound, wherein R ⁵Representative

Table 294

Formula (I-15) compound, wherein R ⁵Representative

Table 295

Formula (I-15) compound, wherein R ⁵Representative

Table 296

Formula (I-15) compound, wherein R ⁵Representative

Table 297

Formula (I-15) compound, wherein R ⁵Representative

Table 298

Formula (I-15) compound, wherein R ⁵Representative

Table 299

Formula (I-15) compound, wherein R ⁵Representative

Table 300

Formula (I-15) compound, wherein R ⁵Representative

Table 301

Formula (I-15) compound, wherein R ⁵Representative

Table 302

Formula (I-15) compound, wherein R ⁵Representative

Table 303

Formula (I-15) compound, wherein R ⁵Representative

Table 304

Formula (I-15) compound, wherein R ⁵Representative

Table A

Sequence number	R ¹	R ²
Sequence number	R ¹	R ²	A-1	CH ₂CH ₃	H
A-2	CH ₂CH ₃	CH ₃	A-1	CH ₂CH ₃	H
A-2	CH ₂CH ₃	CH ₃	A-3	CH ₂CH ₃	CH ₂CH ₃
A-4	CH ₂CH ₂CH ₃	H	A-3	CH ₂CH ₃	CH ₂CH ₃
A-4	CH ₂CH ₂CH ₃	H	A-5	CH ₂CH ₂CH ₃	CH ₃
A-6	CH ₂CH ₂CH ₃	CH ₂CH ₃	A-5	CH ₂CH ₂CH ₃	CH ₃
A-6	CH ₂CH ₂CH ₃	CH ₂CH ₃	A-7	CH ₂CH ₂CH ₃	CH ₂CH ₂CH ₃
A-8	CH ₂CH ₂F	H	A-7	CH ₂CH ₂CH ₃	CH ₂CH ₂CH ₃
A-8	CH ₂CH ₂F	H	A-9	CH ₂CH ₂F	CH ₃
A-10	CH ₂CH ₂F	CH ₂CH ₃	A-9	CH ₂CH ₂F	CH ₃
A-10	CH ₂CH ₂F	CH ₂CH ₃	A-11	CH ₂CF ₃	H
A-12	CH ₂CF ₃	CH ₃	A-11	CH ₂CF ₃	H
A-12	CH ₂CF ₃	CH ₃	A-13	CH ₂CF ₃	CH ₂CH ₃
A-14	CH ₂CF ₃	CH ₂CH ₂CH ₃	A-13	CH ₂CF ₃	CH ₂CH ₃
A-14	CH ₂CF ₃	CH ₂CH ₂CH ₃	A-15	CH ₂CCl ₃	H
A-16	CH ₂CCl ₃	CH ₃	A-15	CH ₂CCl ₃	H
A-16	CH ₂CCl ₃	CH ₃	A-17	CH ₂CCl ₃	CH ₂CH ₃
A-18	CH ₂CCl ₃	CH ₂CH ₂CH ₃	A-17	CH ₂CCl ₃	CH ₂CH ₃
A-18	CH ₂CCl ₃	CH ₂CH ₂CH ₃	A-19	CH(CH ₃) ₂	H
A-20	CH(CH ₃) ₂	CH ₃	A-19	CH(CH ₃) ₂	H
A-20	CH(CH ₃) ₂	CH ₃	A-21	CH(CH ₃) ₂	CH ₂CH ₃
A-22	CH(CH ₃) ₂	CH ₂CH ₂CH ₃	A-21	CH(CH ₃) ₂	CH ₂CH ₃
A-22	CH(CH ₃) ₂	CH ₂CH ₂CH ₃	A-23	CH ₂C(CH ₃) ₃	H
A-24	CH ₂C(CH ₃) ₃	CH ₃	A-23	CH ₂C(CH ₃) ₃	H
A-24	CH ₂C(CH ₃) ₃	CH ₃	A-25	CH ₂C(CH ₃) ₃	CH ₂CH ₃
A-26	CH ₂CH(CH ₃) ₂	H	A-25	CH ₂C(CH ₃) ₃	CH ₂CH ₃
A-26	CH ₂CH(CH ₃) ₂	H	A-27	CH ₂CH(CH ₃) ₂	CH ₃
A-28	CH ₂CH(CH ₃) ₂	CH ₂CH ₃	A-27	CH ₂CH(CH ₃) ₂	CH ₃
A-28	CH ₂CH(CH ₃) ₂	CH ₂CH ₃	A-29	(±)CH(CH ₂CH ₃)CH ₃	H
A-30	(±)CH(CH ₂CH ₃)CH ₃	CH ₃	A-29	(±)CH(CH ₂CH ₃)CH ₃	H
A-30	(±)CH(CH ₂CH ₃)CH ₃	CH ₃	A-31	(±)CH(CH ₂CH ₃)CH ₃	CH ₂CH ₃

Sequence number	R ¹	R ²
Sequence number	R ¹	R ²	A-32	(R)CH(CH ₂CH ₃)CH ₃	H
A-33	(R)CH(CH ₂CH ₃)CH ₃	CH ₃	A-32	(R)CH(CH ₂CH ₃)CH ₃	H
A-33	(R)CH(CH ₂CH ₃)CH ₃	CH ₃	A-34	(R)CH(CH ₂CH ₃)CH ₃	CH ₂CH ₃
A-35	(S)CH(CH ₂CH ₃)CH ₃	H	A-34	(R)CH(CH ₂CH ₃)CH ₃	CH ₂CH ₃
A-35	(S)CH(CH ₂CH ₃)CH ₃	H	A-36	(S)CH(CH ₂CH ₃)CH ₃	CH ₃
A-37	(S)CH(CH ₂CH ₃)CH ₃	CH ₂CH ₃	A-36	(S)CH(CH ₂CH ₃)CH ₃	CH ₃
A-37	(S)CH(CH ₂CH ₃)CH ₃	CH ₂CH ₃	A-38	(±)CH(CH ₃)-CH(CH ₃) ₂	H
A-39	(±)CH(CH ₃)-CH(CH ₃) ₂	CH ₃	A-38	(±)CH(CH ₃)-CH(CH ₃) ₂	H
A-39	(±)CH(CH ₃)-CH(CH ₃) ₂	CH ₃	A-40	(±)CH(CH ₃)-CH(CH ₃) ₂	CH ₂CH ₃
A-41	(R)CH(CH ₃)-CH(CH ₃) ₂	H	A-40	(±)CH(CH ₃)-CH(CH ₃) ₂	CH ₂CH ₃
A-41	(R)CH(CH ₃)-CH(CH ₃) ₂	H	A-42	(R)CH(CH ₃)-CH(CH ₃) ₂	CH ₃
A-43	(R)CH(CH ₃)-CH(CH ₃) ₂	CH ₂CH ₃	A-42	(R)CH(CH ₃)-CH(CH ₃) ₂	CH ₃
A-43	(R)CH(CH ₃)-CH(CH ₃) ₂	CH ₂CH ₃	A-44	(S)CH(CH ₃)-CH(CH ₃) ₂	H
A-45	(S)CH(CH ₃)-CH(CH ₃) ₂	CH ₃	A-44	(S)CH(CH ₃)-CH(CH ₃) ₂	H
A-45	(S)CH(CH ₃)-CH(CH ₃) ₂	CH ₃	A-46	(S)CH(CH ₃)-CH(CH ₃) ₂	CH ₂CH ₃
A-47	(±)CH(CH ₃)-C(CH ₃) ₃	H	A-46	(S)CH(CH ₃)-CH(CH ₃) ₂	CH ₂CH ₃
A-47	(±)CH(CH ₃)-C(CH ₃) ₃	H	A-48	(±)CH(CH ₃)-C(CH ₃) ₃	CH ₃
A-49	(±)CH(CH ₃)-C(CH ₃) ₃	CH ₂CH ₃	A-48	(±)CH(CH ₃)-C(CH ₃) ₃	CH ₃
A-49	(±)CH(CH ₃)-C(CH ₃) ₃	CH ₂CH ₃	A-50	(R)CH(CH ₃)-C(CH ₃) ₃	H
A-51	(R)CH(CH ₃)-C(CH ₃) ₃	CH ₃	A-50	(R)CH(CH ₃)-C(CH ₃) ₃	H
A-51	(R)CH(CH ₃)-C(CH ₃) ₃	CH ₃	A-52	(R)CH(CH ₃)-CH(CH ₃) ₃	CH ₂CH ₃
A-53	(S)CH(CH ₃)-C(CH ₃) ₃	H	A-52	(R)CH(CH ₃)-CH(CH ₃) ₃	CH ₂CH ₃
A-53	(S)CH(CH ₃)-C(CH ₃) ₃	H	A-54	(S)CH(CH ₃)-C(CH ₃) ₃	CH ₃
A-55	(S)CH(CH ₃)-C(CH ₃) ₃	CH ₂CH ₃	A-54	(S)CH(CH ₃)-C(CH ₃) ₃	CH ₃
A-55	(S)CH(CH ₃)-C(CH ₃) ₃	CH ₂CH ₃	A-56	(±)CH(CH ₃)-CF ₃	H
A-57	(±)CH(CH ₃)-CF ₃	CH ₃	A-56	(±)CH(CH ₃)-CF ₃	H
A-57	(±)CH(CH ₃)-CF ₃	CH ₃	A-58	(±)CH(CH ₃)-CF ₃	CH ₂CH ₃
A-59	(R)CH(CH ₃)-CF ₃	H	A-58	(±)CH(CH ₃)-CF ₃	CH ₂CH ₃
A-59	(R)CH(CH ₃)-CF ₃	H	A-60	(R)CH(CH ₃)-CF ₃	CH ₃
A-61	(R)CH(CH ₃)-CF ₃	CH ₂CH ₃	A-60	(R)CH(CH ₃)-CF ₃	CH ₃
A-61	(R)CH(CH ₃)-CF ₃	CH ₂CH ₃	A-62	(S)CH(CH ₃)-CF ₃	H
A-63	(S)CH(CH ₃)-CF ₃	CH ₃	A-62	(S)CH(CH ₃)-CF ₃	H
A-63	(S)CH(CH ₃)-CF ₃	CH ₃	A-64	(S)CH(CH ₃)-CF ₃	CH ₂CH ₃

Sequence number	R ¹	R ²
Sequence number	R ¹	R ²	A-97	-(CH ₂) ₂-O-(CH ₂) ₂-
A-98	-CH ₂-CH(CH ₃)-O-CH(CH ₃)-CH ₂-		A-97	-(CH ₂) ₂-O-(CH ₂) ₂-
A-98	-CH ₂-CH(CH ₃)-O-CH(CH ₃)-CH ₂-		A-99	(suitable)-CH ₂-CH(CH ₃)-O-CH(CH ₃)-CH ₂-
A-100	(instead)-CH ₂-CH(CH ₃)-O-CH(CH ₃)-CH ₂-		A-99	(suitable)-CH ₂-CH(CH ₃)-O-CH(CH ₃)-CH ₂-
A-100	(instead)-CH ₂-CH(CH ₃)-O-CH(CH ₃)-CH ₂-		A-101	-(CH ₂) ₂-NH-(CH ₂) ₂-
A-102	-(CH ₂) ₂-N(CH ₃)-(CH ₂) ₂-		A-101	-(CH ₂) ₂-NH-(CH ₂) ₂-
A-102	-(CH ₂) ₂-N(CH ₃)-(CH ₂) ₂-		A-103	-(CH ₂) ₂-S-(CH ₂) ₂-
A-104	-(CH ₂) ₂-CHF-(CH ₂) ₂-		A-103	-(CH ₂) ₂-S-(CH ₂) ₂-
A-104	-(CH ₂) ₂-CHF-(CH ₂) ₂-		A-105	-(CH ₂) ₃-CHF-CH ₂-
A-106	-(CH ₂) ₂-CH(CF ₃)-(CH ₂) ₂-		A-105	-(CH ₂) ₃-CHF-CH ₂-
A-106	-(CH ₂) ₂-CH(CF ₃)-(CH ₂) ₂-		A-107	-(CH ₂) ₂-CH(CH ₂F)-(CH ₂) ₂-
A-108	-(CH ₂) ₂-CF ₂-(CH ₂) ₂-		A-107	-(CH ₂) ₂-CH(CH ₂F)-(CH ₂) ₂-

Be applicable to that implementing process of the present invention thinner a) is acid, for example acetate, formic acid; Alcohol, for example methyl alcohol; And water or halohydrocarbon, for example methylene dichloride or chloroform.Can also use the mixture of these solvents.The preferred acetate that uses perhaps uses methanol/water mixture when using oxygenant oxone (Oxone).

Be applicable to that implementing process of the present invention oxygenant a) is, for example hydrogen peroxide, pertungstic acid, peracetic acid, 3-chlorine peroxybenzoic acid, mistake phthalic acid, chlorine, oxygen and Oxone_ (KHSO ₅).

When implementing process of the present invention a) time, temperature of reaction can change in the scope of broad relatively.In general, this process is carried out under 0 ℃ to 100 ℃ temperature, preferably carries out (referring to WO 02/074753 and the document wherein quoted) under 10 ℃ to 50 ℃ temperature.

When implementing process b of the present invention) during with preparation formula (I ') compound, the formula with respect to every mole (III) compound generally uses 1 to 5 mole, preferably uses 1 to 2 mole formula (IV) compound.

Formula (II) provides as the broad definition of implementing process of the present invention starting compound a).In the formula, R ¹, R ²And R ⁵Preferably or especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed; R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ⁶Represent C ₁-C ₆Alkyl.

Raw material formula (II) compound is a new compound, and also constitutes the part of theme of the present invention.

Formula (III) provides as implementing process b of the present invention) the broad definition of starting compound.In the formula, R ¹, R ²And R ⁵Preferably or especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed; R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ⁶Represent C ₁-C ₆Alkyl, n can be 1 or 2.

Be applicable to and implement process b of the present invention) acid acceptor be used for the mineral alkali or the organic bases of this class reaction for all routines.Preferred that use alkaline-earth metal or alkali-metal hydride, oxyhydroxide, aminocompound, alkoxide, acetate, carbonate or supercarbonate, for example sodium hydride, sodium amide, lithium diisopropylamine, sodium methylate, sodium ethylate, potassium tert.-butoxide, sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, lime acetate, yellow soda ash, salt of wormwood, saleratus and sodium bicarbonate; And ammonium compound, for example ammonium hydroxide, ammonium acetate and volatile salt; And tertiary amine, for example Trimethylamine 99, triethylamine, Tributylamine, N, accelerine, N, N-dimethyl benzyl amine, pyridine, N-methyl piperidine, N-methylmorpholine, N, N-Dimethylamino pyridine, diazabicyclooctane (DABCO), Diazabicyclononene (DBN) or diazabicylo undecylene (DBU).

Raw material formula (III) compound is a new compound, and also constitutes the part of theme of the present invention.

Formula (IV) provides also as implementing process b of the present invention) the definition of starting compound.In the formula, R ³Preferably or especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed, condition is R ³Must have at least one nitrogen-atoms, and R ³Group is connected by the pyrimidine ring of described nitrogen-atoms and formula (I ') compound.

Raw material formula (IV) compound is known and/or can prepare by currently known methods.

Raw material formula (II) compound is by process f) reaction of formula (IX) compound and formula (VI) compound obtains, exists down and carries out if this reaction is suitably in thinner, if if being suitably in catalyzer carries out and is suitably under the acid acceptor existence carrying out under existing,

Wherein

R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ⁶Represent C ₁-C ₆Alkyl, Hal represents halogen,

HNR ¹R ² (VI)

Wherein

R ¹And R ²Definition as above.

Formula (IX) compound is a new compound, and also constitutes the part of theme of the present invention.

Formula (VI) provides also as implementing process f of the present invention) the broad definition of raw material amine.In the formula, R ¹And R ²Preferably have and the R that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed ¹And R ²Implication.

The amine of formula (VI) is known or can prepares by currently known methods.

Be suitable for implementing process f of the present invention) thinner be all conventional organic solvents.Preferred halohydrocarbon, for example chlorobenzene, dichlorobenzene, methylene dichloride, chloroform, tetracol phenixin, ethylene dichloride or the trichloroethane of using; Ether, for example ether, diisopropyl ether, methyl tertiary butyl ether, tert amyl methyl ether(TAME), diox, tetrahydrofuran (THF), 1,2-glycol dimethyl ether, 1,2-diethoxyethane or methyl-phenoxide; Nitrile, for example acetonitrile, propionitrile, n-Butyronitrile or isopropyl cyanide or benzonitrile; Acid amides, N for example, dinethylformamide, N,N-dimethylacetamide, N-methyl formyl aniline, N-Methyl pyrrolidone or hexamethyl phosphoric triamide; Ester, for example methyl acetate or ethyl acetate; Sulfoxide, for example dimethyl sulfoxide (DMSO); Sulfone, for example tetramethylene sulfone; And alcohol, for example ethanol.

Be applicable to and implement process f of the present invention) acid acceptor be used for the mineral alkali or the organic bases of this class reaction for all routines.Preferred that use alkaline-earth metal or alkali-metal hydride, oxyhydroxide, aminocompound, alkoxide, acetate, carbonate or supercarbonate, for example sodium hydride, sodium amide, lithium diisopropylamine, sodium methylate, sodium ethylate, potassium tert.-butoxide, sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, lime acetate, yellow soda ash, salt of wormwood, saleratus and sodium bicarbonate; And ammonium compound, for example ammonium hydroxide, ammonium acetate and volatile salt; And tertiary amine, for example Trimethylamine 99, triethylamine, Tributylamine, N, accelerine, N, N-dimethyl benzyl amine, pyridine, N-methyl piperidine, N-methylmorpholine, N, N-dimethylamino piperidine, diazabicyclooctane (DABCO), Diazabicyclononene (DBN) or diazabicylo hendecene (DBU).

Be applicable to and implement process f of the present invention) catalyzer be used for the reaction promotor that this class is reacted for all routines.Preferred fluorinated thing, for example Sodium Fluoride, Potassium monofluoride or Neutral ammonium fluoride.

When implementing process f of the present invention) time, temperature of reaction can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 150 ℃ temperature, preferably carries out under 0 ℃ to 80 ℃ temperature.

When implementing process f of the present invention) time, the formula with respect to every mole (IX) halogenated pyrimidine generally uses 0.5 to 10 mole, preferably uses the amine of 0.8 to 2 mole formula (VI).Aftertreatment is undertaken by ordinary method.

Formula (IX) compound is by process g) formula (X) compound and halogenating agent reaction are obtained, if if this reaction is suitable can carried out in the presence of the acid acceptor and suitable can carrying out in the presence of thinner,

R wherein ⁵And R ⁶Define as above R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

Wherein

R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ⁵And R ⁶Definition as above.

Be applicable to and implement process g of the present invention) halogenating agent be used for the composition of halogen replacement hydroxyl for all routines.Preferred mixture or phosgene, trichloromethylchloroformate or the triphosgene of using phosphorus trichloride, phosphorus tribromide, phosphorus pentachloride, phosphoryl chloride, thionyl chloride, thionyl bromide or these materials.Corresponding fluorine cpd can be by making chlorine compound or bromine compounds and Potassium monofluoride prepared in reaction.

Be applicable to and implement process g of the present invention) thinner be used for the solvent of this class halogenating reaction for all routines.Preferred halogenated aliphatic hydrocarbon or halogenated aromatic, for example chlorobenzene of using.Yet, halogenating agent itself, for example the mixture of phosphoryl chloride or halogenating agent also can be used as thinner.

Be applicable to and implement process g of the present invention) acid acceptor be used for the organic bases of this class reaction for all routines.The preferred tertiary amine that uses, for example triethylamine, tri-n-butylamine and N, accelerine.

When implementing process g of the present invention) time, temperature can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 150 ℃ temperature, preferably carries out under 10 ℃ to 120 ℃ temperature.

When implementing process g of the present invention) time, the halogenating agent reaction that formula (X) compound is common and excessive.Aftertreatment is undertaken by ordinary method.

Formula (X) provides implements process g of the present invention) definition of the raw material of needs in addition.In the formula, R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ⁵And R ⁶Definition as above.

Formula (X) compound is a new compound, and also constitutes the part of theme of the present invention.

R wherein ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl and R ⁵Definition formula (X) compound as above is by process h) the alkylating reagent reaction of formula (XI) compound and formula (XII) is obtained, can in thinner, in the presence of alkali, carry out if this reaction is suitable,

Wherein

R ⁴Represent C ₁--C ₄Alkyl or C ₁-C ₄Haloalkyl, R ⁵Define as above,

R ⁶-X(XII)

Wherein

R ⁶Represent C ₁-C ₆Alkyl, the leavings group that X representative can be removed by nucleophile.

Formula (XII) is represented conventional alkylating reagent, for example C usually ₁-C ₆Alkylogen, particularly methyl chloride and monobromomethane, two-C ₁-C ₆Alkyl sulfuric ester is methyl-sulfate for example, or C ₁-C ₆The alkyl methanesulfonates is methyl mesylate for example.

Be applicable to and implement process h of the present invention) thinner be water, alcohol or dipolar aprotic solvent, N for example, dinethylformamide (referring to US 5,250,689).

Be applicable to and implement process h of the present invention) acid acceptor be oxyhydroxide, supercarbonate, carbonate and the alkoxide of alkali-metal or alkaline-earth metal, for example KOH, NaOH, NaHCO ₃, Na ₂CO ₃, sodium methylate and sodium ethylate, and nitrogen base, for example pyridine.

When implementing process h of the present invention) time, temperature can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 100 ℃ temperature, preferably carries out under 10 ℃ to 60 ℃ temperature.

Each component is used with the ratio near stoichiometric ratio usually.But also can advantageously use excessive alkylating reagent (XII).

Raw material formula (XII) compound is known and/or can prepare by currently known methods.

Formula (XI) has defined implements process h of the present invention) other required raw material.In the formula, R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl; R ⁵Definition as above.

Formula (XI) compound is a new compound, and also constitutes the part of theme of the present invention.

R wherein ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl and R ⁵Definition formula (XI) compound as above is by process i) the thiocarbamide reaction of formula (XIII) compound and formula (XIV) is obtained, if if this reaction is suitable can be carried out in thinner and suitable can carrying out in the presence of alkali,

Wherein

R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

R ⁷Represent C ₁-C ₄Alkyl,

And

R ⁵Define as above,

Be applicable to and implement process i of the present invention) thinner be protonic solvent, for example alcohol, particularly ethanol.But aprotic solvent, for example pyridine, N, the mixture of dinethylformamide, N,N-dimethylacetamide or these materials, also be suitable for (referring to US 4,331,590; Org.Prep.and Proced.Int., Vol.10, pp.21-27 Heteroat.Chem., Vol.10, pp.17-23 (1999); Czech.Chem.Commun., Vol.58, pp.2215-2221).

The acid acceptor that is fit to is oxyhydroxide, supercarbonate, carbonate and the alkoxide of alkali-metal or alkaline-earth metal, for example KOH, NaOH, NaHCO ₃, Na ₂CO ₃, sodium methylate and sodium ethylate, and nitrogen base, for example pyridine and Tributylamine.

When implementing process i of the present invention) time, temperature can change in the scope of relative broad.In general, this process is carried out under 20 ℃ to 250 ℃ temperature, preferably carries out under 70 ℃ to 220 ℃ temperature.

Each component is used with the ratio near stoichiometric ratio usually.But also can advantageously use excessive thiocarbamide (XIV).

Thiocarbamide (XIX) is known.

Raw material formula (XIII) compound is known (referring to EP-A-1002 788; DE3942952) and/or can prepare by currently known methods.

R wherein ⁵Heterocycle and R that representative connects by nitrogen ⁴Formula (IX) compound of representing halogen is by process j) formula (XV) compound and halogenating agent reaction are obtained, if if this reaction is suitable can carried out in the presence of the acid acceptor and suitable can carrying out in the presence of thinner,

Wherein

R ⁵And R ⁶Definition as above.

Formula (XV) compound also can following form exist:

Be applicable to implementation process j) halogenating agent for all as being applicable to implementation process g) the halogenating agent mentioned of halogenating agent.

Be applicable to and implement process j of the present invention) thinner for all as being applicable to implementation process g) the thinner mentioned of thinner.

Be applicable to and implement process j of the present invention) acid acceptor for all as being applicable to implementation process g) the acid acceptor mentioned of acid acceptor.

When implementing process j of the present invention) time, temperature can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 150 ℃ temperature, preferably carries out under 10 ℃ to 120 ℃ temperature.

When implementing process j of the present invention) time, the halogenating agent reaction that formula (XV) compound is common and excessive.Aftertreatment is undertaken by ordinary method.

Formula (XV) has defined implements process j of the present invention) other required raw material.In the formula, R ⁵And R ⁶Preferably or especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed.

Formula (XV) compound is a new compound, and also constitutes the part of theme of the present invention.

R wherein ⁵And R ⁶Definition formula (XV) compound as above is by process k) the alkylating reagent reaction of formula (XVI) compound and formula (XII) is obtained, can in thinner, in the presence of acid acceptor, carry out if this reaction is suitable,

Wherein

R ⁵Define as above,

R ⁶-X(XII)：

Wherein

Formula (XII) is represented conventional alkylating reagent, for example C usually ₁-C ₆Alkylogen, particularly methyl chloride and monobromomethane are represented two-C ₁-C ₆Alkyl sulfuric ester is methyl-sulfate for example, or C ₁-C ₆The alkyl methanesulfonates is methyl mesylate for example.

Formula (XVI) compound also can following form exist:

Be applicable to and implement process k of the present invention) thinner be water, alcohol or dipolar aprotic solvent, N for example, dinethylformamide (referring to US 5,250,689).

Be applicable to and implement process k of the present invention) acid acceptor be oxyhydroxide, supercarbonate, carbonate and the alkoxide of alkali-metal or alkaline-earth metal, for example KOH, NaOH, NaHCO ₃, Na ₂CO ₃, sodium methylate or sodium ethylate, and nitrogen base, for example pyridine.

As implementation process k) time, temperature can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 100 ℃ temperature, preferably carries out under 10 ℃ to 60 ℃ temperature.

Formula (XVI) has defined implements process k of the present invention) other required raw material.In the formula, R ⁵Preferably or especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed.

Formula (XVI) compound is a new compound, and also constitutes the part of theme of the present invention.

R wherein ⁵Definition formula (XVI) compound as above is by process 1) the thiocarbamide reaction of formula (XVII) compound and formula (XIV) is obtained, if if this reaction is suitable can be carried out in thinner and suitable can carrying out in the presence of acid acceptor,

Wherein

R ⁷Represent C ₁-C ₄Alkyl and R ⁵Define as above,

Be applicable to the process 1 of the present invention of implementing) thinner be protonic solvent, for example alcohol, particularly ethanol.But aprotic solvent, for example pyridine, N, the mixture of dinethylformamide, N,N-dimethylacetamide or these materials, also be suitable for (referring to US 4,331,590; Org.Prep.and Proced.Int., Vol.10, pp.21-27 Heteroat.Chem., Vol.10, pp.17-23 (1999); Czech.Chem.Commun., Vol.58, pp.2215-2221).

The acid acceptor that is fit to is oxyhydroxide, supercarbonate, carbonate and the alkoxide of alkali-metal or alkaline-earth metal, for example KOH, NaOH, NaHCO ₃And Na ₂CO ₃, and nitrogen base, for example pyridine and Tributylamine.

When implementation process 1) time, temperature can change in the scope of relative broad.In general, this process is carried out under 20 ℃ to 250 ℃ temperature, preferably carries out under 70 ℃ to 220 ℃ temperature.

Each component is used with the ratio near stoichiometric ratio usually.But also can advantageously use excessive thiocarbamide (XIX).

Thiocarbamide (XIV) is known.

Raw material formula (XVII) compound is known (referring to DE-103575707 and/or can prepare by currently known methods.

R wherein ⁵Raw material formula (XVII) compound of=(2-chlorine or 2-methyl) thiene-3-yl-also can prepare according to the method for following Fig. 1:

Fig. 1

2-(2-chlorothiophene-3-yl)-dimethyl malonate also can be prepared by (2-chlorothiophene-3-yl) acetate by last two steps that are similar to above building-up process.

Be applicable to and implement process c of the present invention) thinner be all conventional organic solvents.Preferred halohydrocarbon, for example chlorobenzene, dichlorobenzene, methylene dichloride, chloroform, tetracol phenixin, ethylene dichloride or the trichloroethane of using; Ether, for example ether, diisopropyl ether, methyl tertiary butyl ether, tert amyl methyl ether(TAME), diox, tetrahydrofuran (THF), 1,2-glycol dimethyl ether, 1,2-diethoxyethane or methyl-phenoxide; Nitrile, for example acetonitrile, propionitrile, n-Butyronitrile or isopropyl cyanide or benzonitrile; Acid amides, N for example, dinethylformamide, N,N-dimethylacetamide, N-methyl formyl aniline, N-Methyl pyrrolidone or hexamethyl phosphoric triamide; Ester, for example methyl acetate or ethyl acetate; Sulfoxide, for example dimethyl sulfoxide (DMSO); Sulfone, for example tetramethylene sulfone; And alcohol, for example ethanol.

Be applicable to and implement process c of the present invention) acid acceptor be used for the mineral alkali or the organic bases of this class reaction for all routines.Preferred that use alkaline-earth metal or alkali-metal hydride, oxyhydroxide, aminocompound, alkoxide, acetate, carbonate or supercarbonate, for example sodium hydride, sodium amide, lithium diisopropylamine, sodium methylate, sodium ethylate, potassium tert.-butoxide, sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, lime acetate, yellow soda ash, salt of wormwood, saleratus and sodium bicarbonate; And ammonium compound, for example ammonium hydroxide, ammonium acetate and volatile salt; And tertiary amine, for example Trimethylamine 99, triethylamine, Tributylamine, N, accelerine, N, N-dimethyl benzyl amine, pyridine, N-methyl piperidine, N-methylmorpholine, N, N-Dimethylamino pyridine, diazabicyclooctane (DABCO), Diazabicyclononene (DBN) or diazabicylo undecylene (DBU).

Be applicable to and implement process c of the present invention) catalyzer be used for the reaction promotor that this class is reacted for all routines.Preferred fluorochemical, for example Sodium Fluoride, Potassium monofluoride or the Neutral ammonium fluoride of using.

When implementing process c of the present invention) time, temperature of reaction can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 150 ℃ temperature, preferably carries out under 0 ℃ to 80 ℃ temperature.

When implementing process c of the present invention) time, the halogenated pyrimidine of the formula V with respect to every mole generally uses 0.5 to 10 mole, preferably uses 0.8 to 2 mole formula (VI) amine.Aftertreatment is undertaken by ordinary method.

Formula V provides implements process c of the present invention) broad definition of required starting compound.In the formula, R ³, R ⁴And R ⁵And halogen preferably and especially has and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed, and condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula V compound.

Raw material formula V compound is a new compound, and also constitutes the part of theme of the present invention.

The formula V compound is by process m) formula (XVIII) compound and halogenating agent reaction are obtained, if can carry out in the presence of the acid acceptor and suitable can in the presence of thinner, carrying out, wherein R in the formula V if this reaction is suitable ³And R ⁵Define as above, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula V compound R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

Wherein

R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ³And R ⁵Define as above, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula (XVIII) compound.

Be applicable to implementation process m) halogenating agent for all as being applicable to implementation process g) the halogenating agent mentioned of halogenating agent.

Be applicable to and implement process m of the present invention) thinner for all as being applicable to implementation process g) the thinner mentioned of thinner.

Be applicable to and implement process m of the present invention) acid acceptor for all as being applicable to implementation process g) the acid acceptor mentioned of acid acceptor.

As implementation process m) time, temperature also can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 150 ℃ temperature, preferably carries out under 10 ℃ to 120 ℃ temperature.

As implementation process m) time, the halogenating agent reaction that formula (XVIII) compound is common and excessive.Aftertreatment is undertaken by ordinary method.

Formula (XVIII) has defined implements process m of the present invention) same required raw material.In the formula, R ³, R ⁴And R ⁵Preferably and especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula (XVIII) compound.

Formula (XVIII) compound is a new compound, and also constitutes the part of theme of the present invention.

Formula (XVIII) compound is by process n) formula (XIII) compound and the reaction of formula (XIX) compound are obtained, if if this reaction is suitable can be carried out in thinner and suitable can carrying out in the presence of acid acceptor, R in its Chinese style (XVIII) ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, R ³And R ⁵Define as above, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula (XVIII) compound,

Wherein

R ⁴Represent C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

R ⁷Represent C ₁-C ₄Alkyl

And

R ⁵Define as above,

Be applicable to and implement process n of the present invention) thinner be protonic solvent, for example alcohol, particularly ethanol.But aprotic solvent, for example pyridine, N, the mixture of dinethylformamide, N,N-dimethylacetamide or these materials, also be suitable for (referring to US 4,331,590; Org.Prep.and Proced.Int., Vol.10, pp.21-27 Heteroat.Chem., Vol.10, pp.17-23 (1999); Czech.Chem.Commun., Vol.58, pp.2215-2221).

The acid acceptor that is fit to is oxyhydroxide, supercarbonate and the carbonate of alkali-metal or alkaline-earth metal, for example KOH, NaOH, NaHCO ₃, Na ₂CO ₃, sodium methylate and sodium ethylate, and nitrogen base, for example pyridine and Tributylamine.

As implementation process n) time, temperature also can change in the scope of relative broad.In general, this process is carried out under 20 ℃ to 250 ℃ temperature, preferably carries out under 70 ℃ to 220 ℃ temperature.

Each component is used with the ratio near stoichiometric ratio usually.But also can advantageously use excessive formula (XIX) compound.

Raw material formula (XIII) compound is known (referring to EP-A-1002 788) and/or can prepare by currently known methods.

Raw material formula (XIX) compound is known and/or can prepare by currently known methods.

The formula V compound is by process o) formula (XX) compound and halogenating agent reaction are obtained, if can carry out in the presence of the acid acceptor and suitable can in the presence of thinner, carrying out, wherein R in the formula V if this reaction is suitable ³And R ⁵Define as above, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula V compound R ⁴Represent halogen,

Wherein

R ³And R ⁵Define as above, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula (XX) compound.

Be applicable to and implement process o of the present invention) halogenating agent for all as being applicable to implementation process g) the halogenating agent mentioned of halogenating agent.

Be applicable to and implement process o of the present invention) thinner for all as being applicable to implementation process g) the thinner mentioned of thinner.

Be applicable to and implement process o of the present invention) acid acceptor for all as being applicable to implementation process g) the acid acceptor mentioned of acid acceptor.

As implementation process o) time, temperature also can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 150 ℃ temperature, preferably carries out under 10 ℃ to 120 ℃ temperature.

As implementation process o) time, the halogenating agent reaction that formula (XX) compound is common and excessive.Aftertreatment is undertaken by ordinary method.

Formula (XX) has defined implements process o of the present invention) other required raw material.In the formula, R ³And R ⁵Preferably and especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula (XX) compound.

Formula (XX) compound is a new compound, and also constitutes the part of theme of the present invention.

Formula (XX) compound is by process p) formula (XVII) compound and the reaction of formula (XIX) compound are obtained, if if this reaction is suitable can be carried out in thinner and suitable can carrying out in the presence of alkali, R in its Chinese style (XX) ³And R ⁵Preferably and especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed, condition is heterocyclic group R ³A carbon atom by himself is connected on the pyrimidine skeleton of formula (XX) compound,

Wherein

R ⁷Represent C ₁-C ₄Alkyl and R ₅Define as above,

Be applicable to and implement process p of the present invention) thinner be protonic solvent, for example alcohol, particularly ethanol.But aprotic solvent, for example pyridine, N, the mixture of dinethylformamide, N,N-dimethylacetamide or these materials, also be suitable for (referring to US 4,331,590; Org.Prep.and Proced.Int., Vol.10, pp.21-27 Heteroat.Chem., Vol.10, pp.17-23 (1999); Czech.Chem.Commun., Vol.58, pp.2215-2221).

Be applicable to and implement process p of the present invention) acid acceptor be oxyhydroxide, supercarbonate, carbonate and the alkoxide of alkali-metal or alkaline-earth metal, for example KOH, NaOH, NaHCO ₃, Na ₂CO ₃, sodium methylate or sodium ethylate, and nitrogen base, for example pyridine or tri-n-butylamine.

As implementation process p) time, temperature also can change in the scope of relative broad.In general, this process is carried out under 20 ℃ to 250 ℃ temperature, preferably carries out under 70 ℃ to 220 ℃ temperature.

Raw material formula (XVII) compound is known (referring to DE-103575707) and/or can prepare by currently known methods.

When implementing process d of the present invention) time, temperature of reaction can change in the scope of relative broad.In general, this process is carried out under 0 ℃ to 150 ℃ temperature, preferably carries out under 20 ℃ to 100 ℃ temperature.

When implementing process d of the present invention) during with preparation formula (I_) compound, the formula with respect to every mole (I ' a) compound or formula (I " a) compound, generally use 1 to 10 mole, preferably use 1 to 3 mole formula (VII) compound.

Be applicable to and implement process d of the present invention) thinner be used for the solvent of Grignard reaction for all routines.Preferred ether, for example ether or the tetrahydrofuran (THF) of using.

Be applicable to and implement process e of the present invention) catalyzer be used to implement process b of the present invention for what all were mentioned) reaction promotor.

When implementing process e of the present invention) time, temperature of reaction can change in the scope of relative broad.In general, this process is carried out under-20 ℃ to 80 ℃ temperature, preferably carries out under 0 ℃ to 60 ℃ temperature.

When implementing process e of the present invention) during with preparation formula (I_) compound, the formula with respect to every mole (I ' a) compound or formula (I " a) compound, generally use 1 to 10 mole, preferably use 1 to 3 mole formula (VIII) compound.

As implementing process d of the present invention) formula (I ' a) compound and formula (I " a) compound by process b of the present invention) or the process c) acquisition of raw material.Formula (I ' a) and formula (I " a) in R ¹, R ², R ³, R ⁵Preferably and especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed with Hal.

Formula (VII) has defined implements process d of the present invention) other required raw material.In the formula, R ⁴Preferably and especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed.Formula (VII) compound is known or can prepares by currently known methods.

Formula (VIII) has defined implements process e of the present invention) other required raw material.In the formula, R ⁴Preferably and especially have and the implication that the relevant conduct of the description of formula of the present invention (I) compound is preferably proposed.Formula (VIII) compound is known or can prepares by currently known methods.

Process of the present invention is a) to n) under atmospheric pressure carry out usually.But also can under the pressure that improves, carry out.

Compound of the present invention can suppress the growth of Mammals interior tumor cell and the development of relative disease, can be used as drug use.They are particularly useful for making the medicine of antagonism cancer.

The invention still further relates to the method that suppresses interior cancerous swelling tumor cell growth of mammalian body and relative disease development, this Mammals needs this treatment.This method comprises the 5-phenyl pyrimidine of Mammals effective dosage or its pharmaceutically useful salt.The invention still further relates to treatment or suppress growth of tumour cell and the method for relative disease development, described method is by to 5-phenyl pyrimidine or its pharmaceutically useful salt of Mammals effective dosage, thereby interacts with tubulin and microtubule (microtubuli) and promote the polymerization of microtubule.

Compound of the present invention has strong microbiocidal activity, is used in Crop protection and the material protection and prevents and treats unwanted microorganisms, for example fungi and bacterium.

Mycocide can be used to prevent and treat plasmodiophora brassicae (Plasmodiophoromycete), oomycetes (Oomycete), chytrid (Chytridiomycete), zygomycetes (Zygomycete), ascomycetes (Ascomycete), basidiomycetes (Basidiomycete) and imperfect fungi (Deuteromycete) in Crop protection.

Bactericide can be used to prevent and treat pseudomonas (Pseudomonadaceae), root nodule bacterium (Rhizobiaceae), enterobacteria (Enterobacteriaceae), excellent bacillus (Corynebacteriaceae) and streptomycete (Streptomycetaceae) in Crop protection.

Some that are included into above-mentioned generic name below as an example can unrestriced mode proposing cause the pathogenic agent of fungal disease and Micobial Disease:

By the disease that the Powdery Mildew pathogenic agent causes, described pathogenic agent for example

Bu Shi Erysiphe (Blumeria) bacterial classification, for example Gramineae Bu Shi powdery mildew (Blumeriagraminis);

Podosphaera (Podosphaera) bacterial classification, for example white cross hair list softgel shell (Podosphaera leucotricha);

Single softgel shell belongs to (Sphaerotheca) bacterial classification, for example Flower of Garden Balsam list softgel shell (Sphaerothecafuliginea);

Uncinula (Uncinula) bacterial classification, for example grape snag shell (Uncinulanecator);

By the disease that the rust pathogenic agent causes, described pathogenic agent for example

Gymnosporangium bacterial classification, for example Gymnosporangium sabinae;

Hemileia bacterial classification, for example coffee camel spore rest fungus (Hemileia vastatrix);

Phakopsora bacterial classification, for example yam bean layer rest fungus (Phakopsora pachyrhizi) and acutifoliate podocarpium herb layer bacterium (Phakopsora meibomiae);

Handle rest fungus (Puccinia) bacterial classification, for example Puccinia recondita (Puccinia recondita);

Uromyces (Uromyces) bacterial classification, for example wart top uromyce (Uromycesappendiculatus);

By the disease that Oomycete class pathogenic agent causes, described pathogenic agent for example

Dish downy mildew (Bremia) bacterial classification, for example lettuce dish downy mildew (Bremia lactucae);

Downy mildew (Peronospora) bacterial classification, for example pea downy mildew (Peronospora pisi) or Cruciferae downy mildew (P.brassicae);

Epidemic disease mould (Phytophthora) bacterial classification, for example phytophthora infestans (Phytophthorainfestans);

Axle downy mildew (Plasmopara) bacterial classification, for example grape is given birth to axle downy mildew (Plasmoparaviticola);

False downy mildew (Pseudoperonospora) bacterial classification, the false downy mildew (Pseudoperonosporacubensis) of for example careless false downy mildew (Pseudoperonospora humuli) or Cuba;

Rotten mould (Pythium) bacterial classification, for example ultimate corruption mould (Pythium ultimum);

The sick disease of tikka that causes by for example following pathogenic agent and leaf withering,

Alternaria (Alternaria) bacterial classification, for example Alternaria solani;

Cercospora (Cercospora) bacterial classification, Li such as Chard dish are given birth to tail spore (Cercosporabeticola);

Cladiosporum bacterial classification, for example Cladiosporium cucumerinum;

Cochliobolus belongs to (Cochliobolus) bacterial classification, for example standing grain cochliobolus (Cochliobolussativus) (conidial form: Drechslera, syn:Helminthosporium);

Colletotrichum bacterial classification, for example Colletotrichum lindemuthanium;

Cycloconium bacterial classification, for example Cycloconium oleaginum;

Diaporthe bacterial classification, for example seat shell (Diaporthe citri) between citrus;

Elsinoe bacterial classification, for example citrus Elsinochrome (Elsinoe fawcettii);

The Gloeosporium bacterial classification is for example pleased the long spore of colour disk (Gloeosporium laeticolor);

The Glomerella bacterial classification for example encloses small cluster shell (Glomerella cingulata);

Guignardia bacterial classification, for example grape Guignardia (Guignardia bidwelli);

Leptosphaeria (Leptosphaeria) bacterial classification, for example Leptosphaeria maculans;

Magnaporthe bacterial classification, for example Magnaporthe grisea;

Mycosphaerella bacterial classification, for example standing grain green-ball chamber bacterium (Mycosphaerellegraminicola);

Phaeosphaeria bacterial classification, for example Phaeosphaeria nodorum;

Nuclear cavity Pseudomonas (Pyrenophora) bacterial classification, for example round nuclear cavity bacteria (Pyrenophorateres);

Ramularia bacterial classification, for example Ramularia collo-cygni;

Rhynchosporium bacterial classification, for example rye beak spore (Rhynchosporium secalis);

The pin spore belongs to (Septoria) bacterial classification, for example Septoria apii (Septoria apii);

Typhula bacterial classification, for example meat spore nuclear coral bacterium (Typhula incarnata);

Venturia (Venturia) bacterial classification, for example apple black star bacteria (Venturiainaequalis);

It is harmful by root and stem disease that for example following pathogenic agent causes,

Corticium bacterial classification, for example Corticium graminearum;

Fusarium (Fusarium) bacterial classification, for example sharp sickle spore (Fusarium oxysporum);

Gaeumannomyces bacterial classification, for example Gaeumannomyces graminis;

Rhizoctonia (Rhizoctonia) bacterial classification, for example dry thread Pyrenomycetes (Rhizoctoniasolani).

Tapesia bacterial classification, for example Tapesia acuformis;

Thielaviopsis bacterial classification, for example thielaviopsis sp (Thielaviopsis basicola);

By for example following the pathogenic agent spadix that causes and steady inflorescence (the comprising mealie) disease of loosing,

Alternaria (Alternaria) bacterial classification, for example Alternaria spp.;

Aspergillus (Aspergillus) bacterial classification, for example flavus (Aspergillus flavus);

Cladosporium bacterial classification, for example Cladosporium spp.;

Claviceps bacterial classification, for example ergot (Claviceps purpurea);

Fusarium (Fusarium) bacterial classification, for example yellow sickle spore (Fusarium culmorum);

Gibberella bacterial classification, for example Gibberella zeae (Gibberella zeae);

Monographella bacterial classification, for example Monographella nivalis;

By the disease that ustilago causes, ustilago for example

Sphacelotheca bacterial classification, for example Sphacelotheca reiliana;

Tilletia (Tilletia) bacterial classification, for example wheat net fungus tilletia (Tilletiacaries);

The Urocystis bacterial classification, for example latent bar ustilago (Urocystis occulta);

Ustilago (Ustilago) bacterial classification, for example naked smut (Ustilago nuda);

The fruit rot that causes by for example following pathogenic agent,

Staphlosporonites (Botrytis) bacterial classification, for example Botrytis cinerea (Botrytis cinerea);

Penicillium (Penicillium) bacterial classification, for example Penicilllum expansum (Penicilliumexpansum);

Sclerotinia (Sclerotinia) bacterial classification, for example sclerotinite (Sclerotiniasclerotiorum);

Verticilium bacterial classification, for example Verticilium alboatrum;

That the kind that is caused by for example following pathogenic agent passes and soil passes rots and wilt disease and seedling disease,

Epidemic disease mould (Phytophthora) bacterial classification, for example Phytophthora cactorum (Phytophthora cactorum);

Rhizoctonia (Rhizoctonia) bacterial classification, for example dry thread Pyrenomycetes (Rhizoctoniasolani);

Sclerotium bacterial classification, for example Sclerotium rolfsii (Sclerotium rolfsii);

The ulcer, mycoceicidum and the witches' broom disease that cause by for example following pathogenic agent,

Nectria bacterial classification, for example Nectria galligena;

The wilting that causes by for example following pathogenic agent,

Chain sclerotinia sclerotiorum belongs to (Monilinia) bacterial classification, for example drupe chain sclerotinia sclerotiorum (Monilinialaxa);

The deformity of leaf, flower and the fruit that causes by for example following pathogenic agent,

Taphrina bacterial classification, for example peach external capsule bacterium (Taphrina deformans);

The degeneration disease of the woody species that cause by for example following pathogenic agent,

Esca bacterial classification, for example Phaemoniella clamydospora;

The inflorescence and the seed disease that cause by for example following pathogenic agent,

The plant tuber disease that causes by for example following pathogenic agent,

Active compound of the present invention also shows significant strengthening effect in plant materials.Therefore, they are applicable to the resistibility of transferring in the plant materials the invasion and attack of unwanted microorganisms.

In this application, plant strengthen (resistance is brought out) thus compound should be understood that to excite the system of defense of plant make treated plant after quilt can show material when having been inoculated unwanted microorganisms to the remarkable resistance of these microorganisms.

Among the present invention, unwanted microorganisms should be understood that phytopathogenic fungi, bacterium and virus.Therefore compound of the present invention is used in the invasion and attack that protective plant in for some time after the processing is resisted described pathogenic agent.The time that this protection continued can reach usually with active compound handled plant 1 to 10 day afterwards, preferred 1 to 7 day.

Active compound of the present invention has good plant tolerance under the required concentration of controlling plant diseases, this makes and can handle over-ground part, in-vitro propagate strain (propagationstock) and seed and the soil of plant.

Active compound of the present invention can produce good especially effect when the following disease of control: control cereal disease, for example resist the Fusaria bacterial classification; Control rice class disease, for example resist the disease in Magnaporthe grisea (Pyricularia oryzae) and control viticulture and fruit and the vegetable growing, for example resist Staphlosporonites (Botrytis) bacterial classification, Venturia (Venturia) bacterial classification, single softgel shell genus (Sphaerotheca) bacterial classification and Podosphaera (Podosphaera) bacterial classification.

Active compound of the present invention also is applicable to the output that improves crop.In addition, they also show the toxicity of reduction and have good plant tolerance.

If suitable, active compound of the present invention also can be used as weedicide with certain concentration and rate of application, with coordinate plant growth and control animal pest.If suitable, they can also be as the intermediate or the precursor of synthetic other active compounds.

All plants and plant parts all can be handled according to the present invention.The implication of plant is interpreted as all plants and plant population among the present invention, for example need with unwanted wild plant or crop (comprising the crop that nature exists).Crop can be by conventional plant breeding and optimum seeking method or the plant that obtains by biotechnology and gene engineering method or the combination by described method; comprise transgenic plant, also comprise the plant cultivars that is subjected to the protection of plant seedling power or is not subjected to its protection.The implication of plant parts is interpreted as all grounds of plant and underground position and organ, and for example bud, leaf, Hua Hegen, the example that can propose have leaf, needle, stem, do, flower, sporophore (fruit-body), fruit and seed and root, stem tuber and rhizome.Plant parts also comprises harvested material, and asexual and sexual propagation thing, for example rice shoot, stem tuber, rhizome, cutting and seed.

The processing that use active compound of the present invention carries out plant and plant parts, directly carry out or act on its surrounding environment, habitat or storage space by conventional treatment method, described conventional treatment method for example soaks, sprays, evaporates, atomizes, broadcasts sowing, smears (brushing-on), for the breeding thing particularly for seed, but also dressing one or more layers.

In material protection, compound of the present invention can be used for the safeguard industries material and avoids infecting of unwanted microorganisms and destroy.

The implication of the Industrial materials among the present invention is interpreted as to being used for the non-living body material that industry is made.For example, intend by active compound protection of the present invention to avoid microorganism and change or the destructive Industrial materials can be tackiness agent, sizing material, paper and sheet material, fabric, leather, timber, lacquer and plastics, cooling lubricant (cooling lubricant) and other can be subjected to microbial infection or destructive material.The production unit parts that can be damaged by microbial reproduction, chilled(cooling) water return (CWR) for example is also in the scope of material to be protected.The Industrial materials that can mention are preferably tackiness agent, sizing material, paper and sheet material, leather, timber, lacquer, cooling lubricant and heat transfer liquids within the scope of the present invention, preferred especially timber.

The made Industrial materials generation deterioration that can mention or the microorganism of change be, for example bacterium, fungi, yeast, algae and mucus biology (slime organism).Active compound of the present invention preferably acts on fungi, particularly mould, timber fade fungi and wood-rotting fungi (basidiomycetes) and mucus biology and algae.

Can enumerate following each microorganism that belongs to as an example:

Alternaria (Alternaria), chain lattice spore (Alternaria tenuis) for example,

Aspergillus (Aspergillus), aspergillus niger (Aspergillus niger) for example,

Chaetomium (Chaetomium), chaetomium globosum (Chaetomium globosum) for example,

Coniophora, Coniophora puetana for example,

Lentinus (Lentinus), Lentinus tigrinus bacterium (Lentinus tigrinus) for example,

Penicillium (Penicillium), Penicillum glaucum (Penicillium glaucum) for example,

Pore fungus (Polyporus), for example variegated pore fungus (Polyporus versicolor),

Aureobasidium genus (Aureobasidium), Aureobasidium pullulans (Aureobasidiumpullulans) for example,

Nuclear stem point genus (Sclerophoma), Sclerophoma pityophila for example,

Trichoderma (Trichoderma), viride (Trichoderma viride) for example,

Escherichia (Escherichia), colon bacillus (Escherichia coli) for example,

Rhodopseudomonas (Pseudomonas), Pseudomonas aeruginosa (Pseudomonasaeruginosa) for example, and

Staphylococcus (Staphylococcus), for example streptococcus aureus (Staphylococcus aureus).

Active compound of the present invention can be converted into conventional formulation according to its concrete physics and/or chemical property, for example microcapsule in solution, emulsion, suspension agent, pulvis, foaming agent, paste, granule, aerosol and polymkeric substance and dressing (coating) composition and the ULV cooling and atomizing (fogging) preparation of heating.

Described preparation prepares in a known way, for example active compound is mixed with weighting agent, promptly mixes with liquid solvent, pressurized liquefied gas and/or solid carrier, can choose the use tensio-active agent wantonly simultaneously, i.e. emulsifying agent and/or dispersion agent and/or whipping agent.If the weighting agent that uses is water, for example also can use organic solvent as secondary solvent.The liquid solvent that is fit to mainly contains: aromatics, for example dimethylbenzene, toluene or alkylnaphthalene; Chlorination aromatics or chlorination aliphatic hydrocrbon, for example chlorobenzene, vinylchlorid or methylene dichloride; Aliphatic hydrocrbon, for example hexanaphthene or paraffin (as petroleum fractions); Alcohol, for example butanols or ethylene glycol and ether and ester; Ketone, for example acetone, methylethylketone, methyl iso-butyl ketone (MIBK) or pimelinketone; Intensive polar solvent, for example dimethyl formamide or dimethyl sulfoxide (DMSO); Or water.The implication of liquefied gas weighting agent or carrier is interpreted as being gasiform liquid, for example aerosol propellants, for example halohydrocarbon or butane, propane, nitrogen and carbonic acid gas under standard temperature and normal atmosphere.The solid carrier that is fit to is: for example natural mineral of Fen Suiing, for example kaolin, clay, talcum, chalk, quartz, attapulgite, montmorillonite or diatomite; And the synthetic mineral of pulverizing, for example high dispersive silicon-dioxide, aluminum oxide and silicate.The solid carrier that is applicable to granule is: for example pulverize and fractionated natural rock, for example calcite, float stone, marble, sepiolite and rhombspar; Or the inorganic and organic powder particles of synthetic, and organic particle, for example wood sawdust, coconut husk, corn cob and tobacco stem.The emulsifying agent and/or the whipping agent that are fit to are: for example nonionic and anionic emulsifier, for example for example alkylaryl polyglycol ether, alkylsulfonate, alkyl-sulphate, arylsulphonate or protein hydrolyzate of polyoxyethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether.The dispersion agent that is fit to is: for example lignin sulfite waste lye and methylcellulose gum.

Can use tackiness agent in the preparation, for example carboxymethyl cellulose, and the natural and synthetic polymer of powder, particle or emulsion form for example gum arabic, polyvinyl alcohol and polyvinyl acetate, and natural phospholipid for example kephalin and Yelkin TTS, and synthetic phospholipid.Other possible additives are mineral oil and vegetables oil.

Can use tinting material, for example inorganic pigment, for example ferric oxide, titanium oxide and Prussian blue, and organic dye, for example alizarine dyestuff, azoic dyestuff and metallopeptide cyanine dyes also have micro-nutrients, for example molysite, manganese salt, boron salt, mantoquita, cobalt salt, molybdenum salt and zinc salt.

Generally comprise the active compound of 0.1 to 95 weight % in the preparation, preferred 0.5 to 90%.

Active compound of the present invention also can itself or its preparation form mix use with known mycocide, bactericide, miticide, nematocides or insecticide, to widen its activity profile for example or to prevent the generation of resistance.Under many circumstances, obtained synergistic effect, promptly the activity of mixture is greater than the activity of independent component.

The example of suitable blending ingredients is following compound:

Mycocide:

1. nucleic acid synthetic inhibitor

M 9834 (benalaxyl), efficient M 9834 (benalaxyl-M), bupirimate (bupirimate), chiralaxyl, clozylacon, dimethirimol (dimethirimol), the phonetic phenol of second (ethirimol), furalaxyl (furalaxyl), dislike mould spirit (hymexazol), mefenoxam, metaxanin (metalaxyl), efficient metaxanin (metalaxyl-M), ofurace (ofurace), Wakil (oxadixyl), oxolinic acide (oxolinic acid)

2. mitotic division and cell division inhibitor

F-1991 (benomyl), derosal (carbendazim), the mould one-tenth of second (diethofencarb), fuberidazole (fuberidazole), pencycuron (pencycuron), thiabendazole (thiabendazole), thiophanate_methyl (thiophanate-methyl), zoxamide (zoxamide)

3. respiratory chain inhibitor

3.1 complex body I

Fluorine mepanipyrim (diflumetorim)

3.2 complex body II

Boscalid, carboxin (carboxin), fenfuram (fenfuram), fultolanil (flutolanil), furan pyrrole bacterium amine (furametpyr), seed dressing amine (furmecyclox), mebenil (mepronil), oxycarboxin (oxycarboxin), penthiopyrad, thiophene fluorine bacterium amine (thifluzamide)

3.3 complex body III

Amisulbrom, Azoxystrobin (azoxystrobin), cyanogen frost azoles (cyazofamid), ether bacterium amine (dimoxystrobin), enestrobin, Famoxate (famoxadone), fenamidone (fenamidone), fluoxastrobin (fluoxastrobin), kresoxim-methyl (kresoxim-methyl), SSF 126 (metominostrobin), orysastrobin (orysastrobin), ZEN 90160 (picoxystrobin), Strobilurin (pyraclostrobin), oxime bacterium ester (trifloxystrobin)

3.4 uncoupling agents (decoupler)

Dinocap (dinocap), fluazinam (fluazinam), methyldinocap

3.5ATP generation inhibitor

Fentinacetate (fentin acetate), Fentin chloride (fentin chloride), fentin hydroxide (fentin hydroxide), silthiofam

4. amino acid and protein biosynthesis inhibitor

Andoprim, miewensu (blasticidin-S), cyprodinil (cyprodinil), kasugamycin (kasugamycin), kasugamycin hydrochloride hydrate (kasugamycinhydrochloride hydrate), mepanipyrim (mepanipyrim), phonetic mould amine (pyrimethanil)

5. signal transduction inhibitor

Fenpiclonil (fenpiclonil), fludioxonil (fludioxonil), benzene oxygen quinoline (quinoxyfen)

6. lipid and film synthetic inhibitor

Chlozolinate (chlozolinate), RP-26019 (iprodione), procymidone (procymidone), Vinclozoline (vinclozolin)

Pyrazophos (pyrazophos), edifenphos (edifenphos), iprobenfos (iprobenfos) (IBP), isoprothiolane (isoprothiolane)

Tolclofosmethyl (tolclofos-methyl), biphenyl (biphenyl)

Iodocarb, Propamocarb (propamocarb), Propamocarb hydrochloride (propamocarbhydrochloride)

7. ergosterol biosynthesis inhibitor

Fenhexamid (fenhexamid),

Oxygen ring azoles (azaconazole), bitertanol (bitertanol), bromuconazole (bromuconazole), SN-108266 (cyproconazole), diclobutrazol (diclobutrazole), difenoconazole (difenoconazole), alkene azoles alcohol (diniconazole), alkene azoles alcohol-M (diniconazole-M), fluorine ring azoles (epoxiconazole), etaconazole (etaconazole), RH-7592 (fenbuconazole), fluquinconazole (fluquinconazole), flurprimidol (flurprimidol), fluzilazol (flusilazole), flutriafol (flutriafol), furconazole (furconazole), furconazole_cis (furconazole-cis), own azoles alcohol (hexaconazole), imibenconazole (imibenconazole), plant bacterium azoles (ipconazole), metconazole (metconazole), nitrile bacterium azoles (myclobutanil), paclobutrazol (paclobutrazole), Topaze (penconazole), Wocosin 50TK (propiconazole), prothioconazole, pyrifenox (pyrifenox), simeconazoles (simeconazole), tebuconazole (tebuconazole), tertraconazole (tetraconazole), triazolone (triadimefon), triadimenol (triadimenol), triticonazole (triticonazole), uniconazole (uniconazole), voriconazole;

Press down mould azoles (imazalil), Imazalil sulfate (imazalil sulphate), dislike imidazoles (oxpoconazole), fenarimol (fenarimol), flurprimidol (flurprimidol), nuarimol (nuarimol), pyrifenox (pyrifenox), triforine (triforine), pefurazoate (pefurazoate), prochloraz (prochloraz), fluorine bacterium azoles (triflumizole), triforine (triforin), alkene frost benzyl azoles (viniconazole),

Aldimorph, dodemorfe (dodemorph), dodemorfe (dodemorphacetate), fenpropidin (fenpropidin), fenpropimorph (fenpropimorph), tridemorph (tridemorph), volution bacterium amine (spiroxamine), naftifine, pyributicarb (pyributicarb), terbinafine

8. cell walls synthetic inhibitor

Benthiavalicarb, dimethomorph (dimethomorph), flumorph (flumorph), iprovalicarb (iprovalicarb), polyoxin (polyoxins), Polyoxin (polyoxorim), Validacin (Takeda) (validamycin A)

9. melanochrome biosynthesis inhibitor

Ring propionyl bacterium amine (capropamid), two chlorine zarilamid (diclocymet), zarilamid (fenoxanil), phthalide (phthalide), pyroquilon (pyroquilon), tricyclazole (tricyclazole)

10. induction of resistance thing

Acibenzolar-S-methyl (acibenzolar-S-methyl), probenazole (probenazole), tiadinil

Put active compound 11. have multidigit

Bordeaux mixture (Bordeaux mixture), Difolatan (captafo1), Vancide 89 (captan), m-tetrachlorophthalodinitrile (chlorothalonil); Mantoquita, for example copper hydroxide, copper naphthenate, COPPER OXYCHLORIDE 37,5 (copper oxychloride), cupric oxide, copper sulfate, oxinecopper (oxinecopper); Dichlofluanid (dichlofluanid), dithianon (dithianon), dodine (dodine), dodine free base, Karbam Black (ferbam), fluorofolpet, Phaltan (folpet), Guanoctine (guazatine), the hot second salt (guazatineacetate) of biguanides, biguanide spicy acid salt (iminoctadine), two eight guanidinesalts (iminoctadinealbesilate), iminoctadine triacetate (iminoctadine triacetate), mancopper (mancopper), zinc manganese ethylenebisdithiocarbamate (mancozeb), maneb (maneb), Carbatene (metiram), metiram zinc, zinc 1,2-propylene bisdithiocarbamate (propineb), sulphur and sulphur preparation comprise calcium polysulfide, thiram (thiram), Tolylfluanid (tolyfluanid), zineb (zineb), ziram (ziram)

12. it is unknown

Amibromdol, benthiozole (benthiazole), bethoxazin, capsicum mycin (capsimycin), Karvon (carvone), chinomethionate (chinomethionat), trichloronitromethane (chloropicrin), cufraneb (cufraneb), cyflufenamid (cyflufenamid), frost urea cyanogen (cymoxanil), dazomet, debacarb (debacarb), dichlorophen (dichlorophen), diclomezin (diclomezine), dicloran (dic1oran), benzene enemy fast (difenzoquat), benzene enemy fast (difenzoquat methylsulphate), pentanoic (diphenylamine), ferimzone (ferimzone), fluorine acyl bacterium amine (flumetover), fluopicolide, fluorine bacterium peace (fluoroimide), flusulfamide (flusulfamide), three second aluminum phosphates (fosetyl-aluminium), three second calcium phosphate (fosetyl-calcium), three second sodium phosphates (fosetyl-sodium), Perchlorobenzene (hexachlorobenzene), oxine sulfuric ester (8-hydroxyquinoline sulphate), people's metamycin (irumamycin), the sulphur bacterium becomes (methasulfocarb), Trapex, metrafenone, midolthromycin (mildiomycin), myprozine (natamycin), Sankel (nickel dimethyldithiocarbamate), nitrothalisopropyl (nitrothal-isopropyl), octhilinone (octhilinone), oxamocarb, oxyfenthiin, pentachlorophenol and salt thereof, 2-phenylphenol and salt thereof, phosphorous acid and salt thereof, disease is spent spirit (piperalin), propamocarb fosetylate, propanosine-sodium, the third oxygen quinoline (proquinazid), pyrroles's rhzomorph (pyrrolnitrin), quintozene (quintozene), tecloftalam (tecloftalam), tecnazene (tecnazene), triazoxide (triazoxide), poplar bacterium amine (trichlamid), chlorine bacterium amine (zarilamid);

2-amino-4-methyl-N-phenyl-5-thiazole carboxamides,

2-chloro-N-(2,3-dihydro-1,1,3-trimethylammonium-1H-indenes-4-yl)-3-pyridine carboxamide,

3-[5-(4-chloro-phenyl-)-2,3-dimethyl isoxazole alkane-3-yl] pyridine,

Cis-1-(4-chloro-phenyl-)-2-(1H-1,2,4-triazol-1-yl) suberyl alcohol,

2,4-dihydro-5-methoxyl group-2-methyl-4-[[[[1-[3-(trifluoromethyl)-phenyl] ethylidene] amino] the oxygen base] methyl] phenyl]-3H-1,2,3-triazole-3-ketone,

1-(2,3-dihydro-2,2-dimethyl-1-H-indenes-1-yl)-1H-imidazoles-5-methyl-formiate,

2-[[[cyclopropyl [(4-methoxyl group-phenyl) imino-] methyl] sulfenyl] methyl] phenyl-3-methoxy-methyl acrylate,

3-(4-chloro-phenyl-)-3-{[N-(isopropoxy carbonyl) is valyl] amino } methyl propionate,

4-chloro-alpha-propynyl oxygen base-N-[2-[3-methoxyl group-4-(2-propynyl oxygen base)-phenyl] ethyl] phenyl-acetamides,

2-(2-{[6-(3-chloro-2-methylphenoxy) 5-fluorine pyrimidine-4-yl] the oxygen base } phenyl)-the 2-methoxyimino)-the N-methylacetamide,

(2S)-and N-[2-[4-[[3-(4-chloro-phenyl-)-2-propynyl] the oxygen base]-the 3-p-methoxy-phenyl] ethyl]-3-methyl-2-[(methylsulfonyl) amino] butyramide,

5-chloro-7-(4-methyl piperidine-1-yl)-6-(2,4, the 6-trifluorophenyl) [1,2,4] triazolos [1,5-a] pyrimidine,

5-chloro-6-(2,4, the 6-trifluorophenyl)-N-[(1R)-1,2,2-trimethylammonium propyl group]-1,2,4] triazolo [1,5-a] pyrimidine-7-amine,

5-chloro-N-[(1R)-1, the 2-dimethyl propyl]-6-(2,4, the 6-trifluorophenyl) [1,2,4] triazolos [1,5-a] pyrimidine-7-amine,

N-[1-(5-bromo-3-chloropyridine-2-yl) ethyl]-2,4-two chloro-nicotinamides,

N-(5-bromo-3-chloropyridine-2-yl) methyl-2,4-two chloro-nicotinamides,

N-[1-(5-bromo-3-chloropyridine-2-yl) ethyl]-2-fluoro-4-iodine niacinamide,

2-butoxy-6-iodo-3-propyl group benzopyrone-4-ketone,

N-[2-(4-{[3-(4-chloro-phenyl-) third-2-alkynes-1-yl] the oxygen base }-the 3-p-methoxy-phenyl) ethyl]-N-2-(methylsulfonyl) valine amide,

N-{ (z)-[(cyclo propyl methoxy) imino-] [6-(difluoro-methoxy)-2,3-difluorophenyl] methyl }-the 2-phenyl-acetamides,

N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methyl benzenesulfonamide,

N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-formyl radical amino-2-hydroxybenzamide,

2-[[[[1-[3 (1-fluoro-2-phenylethyl) oxygen base] phenyl] ethylidene] amino] the oxygen base] methyl]-α-(methoxyimino)-N-methyl-redusterol,

N-{2-[3-chloro-5-(trifluoromethyl) pyridine-2-yl] ethyl }-2-(trifluoromethyl) benzamide,

N-(3 ', 4 '-two chloro-5-fluorine biphenyl-2-yls)-3-(difluoromethyl)-1-methyl isophthalic acid H-pyrazole-4-carboxamide,

N-(6-methoxyl group-3-pyridyl) cyclopropane carboxamide,

1-[(4-methoxyl group phenoxy group) methyl]-2, the 2-dimethyl propyl]-1H-imidazoles-1-formic acid,

0-[1-[(4-methoxyl group phenoxy group) methyl]-2, the 2-dimethyl propyl]-1H-imidazoles-1-carbothioic acid carbothiolic acid,

2,3,5,6-tetrachloro-4 (methyl sulphonyl) pyridine,

3,4,5-three chloro-2,6-pyridine dimethoxy nitrile,

Bactericide:

Bronopol (bronopol), dichlorophen, nitrapyrin (nitrapyrin), Sankel (nickel dimethyldithiocarbamate), kasugamycin, octhilinone (octhilinone), carboxylic acid furans (furancarboxylic acid), terramycin (oxytetracyclin), probenazole (probenazole), Streptomycin sulphate (streptomycin), tecloftalam (tecloftalam), copper sulfate and other copper agent.

Insecticide/miticide/nematocides:

1. acetylcholinesterase (AChE) inhibitor

1.1 carbamate (alanycarb (alanycarb) for example, aldicarb (aldicarb), aldoxycarb (aldoxycarb), allyxycarb (allyxycarb), aminocarb (aminocarb), azamethiphos (azamethiphos), bendiocarb (bendiocarb), benfuracarb (benfuracarb), bufencarb (bufencarb), butacarb (butacarb), butocarboxim (butocarboxim), butanone sulfone prestige (butoxycarboxim), carbaryl (carbaryl), carbofuran (carbofuran), carbosulfan (carbosulfan), chloethocarb, Coumaphos (coumaphos), S-4087 (cyanofenphos), cynock (cyanophos), dimetilan (dimetilan), ethiofencarb (ethiofencarb), fenobucarb (fenobucarb), fenothiocarb (fenothiocarb), formetanate (formetanate), furathiocarb (furathiocarb), isoprocarb (isoprocarb), metamsodium (metam-sodium), methiocarb (methiocarb), many one-tenth (methomyl) go out, meta-tolyl-N-methylcarbamate (MTMC) (metolcarb), oxamyl (oxamyl), Aphox (pirimicarb), promecarb (promecarb), Propoxur (propoxur), the two prestige (thiodicarb) of sulphur, imitate (thiofanox) for a long time, triaxamate (triazamate), trimethacarb (trimethacarb), XMC, kill (xylylcarb))

1.2 organophosphorus compounds (orthene (acephate) for example; Azamethiphos (azamethiphos); Azinphos-methyl (azinphos-methyl); Azinphos ethyl (azinphos-ethyl); Rilariol (bromophos-ethyl); Bromobenzene alkene phosphorus (methyl) (bromfenvinfos (methyl)); Special Pyrimitate (butathiofos); Cadusafos (cadusafos); Carbophenothion (carbophenothion); Chlorethoxyfos (chlorethoxyfos); Chlorfenviphos (chlorfenvinphos); Chlormephos (chlormephos); Chlopyrifos (methyl/-ethyl) (chlorpyrifos (methyl/-ethyl)); Resistox (coumaphos); Surecide (cyanofenphos); Cynock (cyanophos); Chlorfenviphos (chlorfenvinphos); Demeton-methyl (demeton-S-methyl); Metilomerkaptofosoksid (demeton-S-methylsulfone); Dialifos (dialiphos); Diazinon (diazinon); Dichlofenthion (dichlofenthion); DDVP (dichlorvos)/DDVP; Carbicron (dicrotophos); Rogor (dimethoate); Dimethylvinphos (dimethylvinphos); Salithion (dioxabenzofos); Disulfoton (disulfoton); EPN; Ethodan (ethion); Phonamiphos (ethoprophos); Etrimfos (etrimfos); Famphur (famphur); Fenamiphos (fenamiphos); Fenifrothion (fenitrothion); Fensulfothion (fensulfothion); Entex (fenthion); Pyrrole fluorine sulphur phosphorus (flupyrazofos); Fonofos (fonofos); Formothion (formothion); Fosmethilan (fosmethilan); Lythidathion (fosthiazate); Heptenophos (heptenophos); Iodfenphos (iodofenphos); IBP (iprobenfos); Fluorine azoles phosphorus (isazofos); Isofenphos (isofenphos); Ortho-, meta-or p-isopropyl salicylate (isopropylo-salicylate); Isoxathion (isoxathion); Malathion (malathion); Afos (mecarbam); Methacrifos (methacrifos); Acephatemet (methamidophos); Methidathion (methidathion); Menite (mevinphos); Azodrin (monocrotophos); 2-dichloroethylk dimethyl phosphate (naled); Omethoate (omethoate); Oxydemeton_methyl (oxydemeton-methyl); Parathion (methyl/-ethyl) (parathion (methyl/-ethyl)); Phenthoate dimephenthoate cidial (phenthoate); Thimet (phorate); Phosalone (phosalone); Phosmet (phosmet); Phosphamidon (phosphamidon); Second the third phosphorus prestige (phosphocarb); Phoxim (phoxim); Pirimiphos-methyl/Diothyl (pirimiphos methyl/ethyl); Profenofos (profenofos); Kayaphos (propaphos); Propetamphos (propetamphos); Toyodan (prothiofos); Prothoate (prothoate); Pyraclofos (pyraclofos); Pyridaphethione (pyridaphenthion); Pyridathion; Quinalphos (quinalphos); Cadusafos (sebufos); Sulfotep (sulfotep); Sulprofos (sulprofos); Butyl pyrimidine phosphorus (tebupirimphos); Swebate (temephos); Terbufos (terbufos); Ravap (tetrachlorvinphos); Thiometon (thiometon); Hostathion (triazophos); Metrifonate (triclorfon); Vamidothion (vamidothion)).

2. the blocker of sodium channel modulators/voltage control sodium channel

2.1 pyrethroid (acrinathrin (acrinathrin) for example, d-cis-trans allethrin (allethrind-cis-trans), the trans allethrin of d-(allethrind-trans), betacyfluthrin (beta-cyfluthrin), bifenthrin (bifenthrin), bioallethrin (bioallethrin), bioallethrin-S-cyclopentyl isomer, bioethanomethrin, biopermethrin (biopermethrin), bioresmethrin (bioresmethrin), chlovaporthrin, suitable-Cypermethrin (cis-cypermethrin), suitable-resmethrin (cis-resmethrin), suitable-permethrin (cis-permethrin), cyhalothrin (clocythrin), cycloprothrin (cycloprothrin), cyfloxylate (cyfluthrin), cyhalothrin (cyhalothrin), α-Cypermethrin (alpha-cypermethrin), β-Cypermethrin (beta-cypermethrin), θ-Cypermethrin (theta-cypermethrin), ζ-Cypermethrin (zeta-cypermethrin), phenylate permethrin (cyphenothrin), DDT, Deltamethrin (deltamethrin), empenthrin (1R isomer) (empenthrin (1R isomer)), S-fenvalerate (esfenvalerate), ether chrysanthemum ester (etofenprox), fenfluthrin (fenfluthrin), Fenvalerate (fenpropathrin), fenpyrithrin, fenvalerate (fenvalerate), brofluthrinate (flubrocythrinate), flucythrinate (flucythrinate), trifluoro chrysanthemum ester (flufenprox), flumethrin (flumethrin), taufluvalinate (fluvalinate), fubfenprox, smart lambda-cyhalothrin (gamma-cyhalothrin), miaow alkynes chrysanthemum ester (imiprothrin), kadethrin (kadethrin), lambda-cyhalothrin (lamda-cyhalothrin), methoxy benzyl Flumethrin (metofluthrin), suitable-permethrin (cis-permethrin), instead-permethrin (trans-permethrin), phenothrin (1R trans-isomer(ide)) (phenothrin (1Rtrans isomer), prallethrin (prallethrin), third Flumethrin (profluthrin), protrifenbute, anti-Chryson (pyresmethrin), resmethrin (resmethrin), RU-15525, salifluofen (silafluofen), taufluvalinate (tau-fluvalinate), tefluthrin (tefluthrin), terallethrin (terallethrin), Tetramethrin (1R isomer) (tetramethrin (1R-isomer)), tralomethrin (tralomethrin), transfluthrin (transfluthrin), ZXI-8901, pyrethrin (pyrethrins, pyrethrum))

2.2 oxadiazine class (for example indenes worm prestige (indoxacarb))

3. acetyl choline receptor agonists/antagonist

3.1 chloro nicotinyl (chloronicotinyl)/anabasine (neonicotinoid) (for example acetamiprid (acetamiprid), thiophene worm amine (clothianidin), MTI-446 (dinotefuran), Provado (imidacloprid), Ti304 (nitenpyram), WL 35651 (nithiazine), thiophene worm quinoline (thiacloprid), thiophene worm piperazine (thiamethoxam))

3.2 nicotine, bensultap (bensultap), cartap (cartap)

4. acetylcholine receptor modulators

(4.1spinosyns for example pleocidin (spinosad))

5.GABA-control chloride channel antagonist

5.1 cyclic diolefine organochlorine (for example toxaphene (camphechlor), Niran (chlordane), 5a,6,9,9a-hexahydro-6,9-methano-2,4 (endosulfan), lindane (gamma-HCH), HCH, heptachlor (heptachlor), lindane (lindane), methoxychlor (methoxychlor)

5.2 fiprol class (for example acetoprole, ethiprole (ethiprole), fluorine worm nitrile (fipronil), fluorine pyrazoles worm (vaniliprole))

6. chloride channel activator

6.1mectin class (for example A Wei mite element (abamectin), Avrmectin (avermectin), emamectin, emaricin (emamectin-benzoate), ivermectin (ivermectin), more visit mite element (milbemectin), close) than mycin (milbemycin)

7. neotonin stand-in

(for example difenolan (diofenolan), protect young ether (epofenonane), fenoxycarb (fenoxycarb), hydroprene (hydroprene), kinoprene (kinoprene), methoprene (methoprene), pyrrole propyl ether (pyriproxyfen), sulphur olefin(e) acid ester (triprene))

8. ecdysone agonist/agent interfering (disruptor)

8.1 diacyl hydrazide class (for example encircling worm hydrazides (chromafenozide), fluorine worm hydrazides (halofenozide), methoxyfenozide (methoxyfenozide), worm hydrazides (tebufenozide))

9. chitin biosynthesis inhibitor

9.1 benzoyl area kind (for example two three flufenoxuron (bistrifluron), chlofluazuron, diflubenzuron (diflubenzuron), fluazuron (fluazuron), flucycloxuron (flucycloxuron), flufenoxuron (flufenoxuron), fluorine bell urea (hexaflumuron), Acarus tritici urea (lufenuron), fluorine uride (novaluron), noviflumuron (noviflumuron), flufenoxuron (penfluron), fluorobenzene urea (teflubenzuron), kill bell urea (triflumuron))

9.2 Buprofezin (buprofezin)

9.3 fly eradication amine (cyromazine)

10. oxidative phosphorylation inhibitor, ATP agent interfering

10.1 butyl ether urea (diafenthiuron)

10.2 organic tin (for example azocyclotin (azocyclotin), cyhexatin (cyhexatin), fenbutatin oxide (fenbutatin oxide))

11. by interrupting the oxidative phosphorylation uncoupler of H-proton gradient effect

11.1 pyroles (for example Chlorfenapyr (chlorfenapyr))

11.2 dinitrophenols (for example Niagara 9044 (binapacryl), dinobuton (dinobuton), dinocap (dinocap), DNOC)

12.I site electron transfer inhibitor

12.1METI class (for example fenazaquin (fenazaquin), azoles mite ester (fenpyroximate), pyrimidifen (pyrimidifen), pyridaben (pyridaben), tebufenpyrad (tebufenpyrad), azoles insect amide (tolfenpyrad))

12.2 Hydramethylnon Bait (hydramethylnon)

12.3 kelthane (dicofol)

13.II site electron transfer inhibitor

13.1 tubatoxin (rotenone)

14.III site electron transfer inhibitor

Mite quinone (acequinocyl), phonetic full ester (fluacryPyrim) 14.1 go out

15. the microorganism agent interfering of insect goldbeater's skin

Bacillus thuringiensis (Bacillus thuringiensis) bacterial strain

16. lipogenesis inhibitor

16.1 tetronic acid class (for example spiral shell mite ester (spirodiclofen), Spiromesifen (spiromesifen))

16.2 [for example 3-(2 for the tetramates acids, the 5-3,5-dimethylphenyl)-8-methoxyl group-2-oxo-1-azaspiro [4.5] last of the ten Heavenly stems-3-alkene-4-base ethyl carbonate ester (that is: carbonic acid, 3-(2, the 5-3,5-dimethylphenyl)-8-methoxyl group-2-oxo-1-azaspiro [4.5] last of the ten Heavenly stems-3-alkene-4-base ethyl ester, CAS Reg.No.:382608-10-8) and carbonic acid, suitable-3-(2, the 5-3,5-dimethylphenyl)-8-methoxyl group-2-oxo-1-azaspiro [4.5] last of the ten Heavenly stems-3-alkene-4-base ethyl ester (CAS Reg.No.:203313-25-1)]

17. amides

(for example flonicamid (flonicamid))

18. octopaminergic agonist

(for example amitraz (amitraz))

19. magnesium stimulates atpase inhibitor

(for example alkynes mite spy (propargite))

20. phthalyl amine

(N2-[1 for example, 1-dimethyl-2-(methylsulfonyl) ethyl]-3-iodo-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl) ethyl] phenyl]-1,2-benzenedicarboxamide (CASReg.No.:272451-65-7), flubendiamide)

21. the similar thing of nereistoxin

(for example thiocyclam oxalate (thiocyclam hydrogen oxalate), disosultap (thiosultap-sodium))

22. biotechnological formulation, hormone or pheromone

(for example nimbin (azadirachtin), genus bacillus bacterial classification (Bacillus spec.), muscardine bacterial classification (Beauveria spec.), Pherocon CM (codlemone), green muscardine fungus kind (Metarrhizium spec.), Paecilomyces varioti bacterial classification (Paecilomyces spec.), enemy Bei Te (Thuringiensin), Verticillium bacterial classification (Verticillium spec.)

23. mechanism of action is unknown or uncertain active compound

23.1 fumigant (for example aluminium phosphide, monobromomethane, sulfuryl fluoride)

23.2 selectivity food refusal agent (for example sodium aluminum fluoride (cryolite), flonicamid (flonicamid), pyrrole aphid ketone (pymetrozine))

23.3 mite growth inhibitor (for example four mite piperazines (clofentezine), second mite azoles (etoxazole), hexythiazox (hexythiazox))

23.4amidoflumet, benclothiaz, benzoximate (benzoximate), Bifenazate (bifenazate), bromopropylate (bromopropylate), Buprofezin (buprofezin), chinomethionate (chinomethionat), chlordimeform (chlordimeform), G-23922 (chlorobenzilate), trichloronitromethane (chloropicrin), clothiazoben, cycloprene, cyflumetofen, CGA 183893 (dicyclanil), fenoxacrim, fluorine nitre pentanoic (fentrifanil), thiazole mite (flubenzimine), flufenerim, fluorine mite piperazine (flutenzin), gossyplure (gossyplure), Hydramethylnon Bait (hydramethylnon), japonilure, metoxadiazone (metoxadiazone), oil, Piperonyl Butoxide (piperonyl butoxide), potassium oleate, pyrafluprole, pyridalyl (pyridalyl), pyriprole, sulfluramid (sulfluramid), tetradifon (tetradifon), kill mite thioether (tetrasul), benzene match mite (thiarathene), synergy alkynes ether (verbutin)

And compound propyl carbamic acid-3-aminomethyl phenyl ester (meta-tolyl-N-methylcarbamate (MTMC) Z (tsumacideZ)), compound 3-(5-chloro-3-pyridyl)-8-(2,2, the 2-trifluoroethyl)-8-azabicyclo [3.2.1] octane-3-nitrile (CAS number of registration 185982-80-3) and corresponding 3-endo isomer (CAS number of registration 185984-60-5) (referring to WO 96/37494, WO 98/25923), and the preparation that comprises insecticidal activity plant milk extract, nematode, fungi or virus.

Also can mix, perhaps mix with other known active compounds---for example weedicide---with fertilizer and growth regulator, safener and/or semiochemical.

In addition, formula of the present invention (I) compound also has extraordinary anti-mycotic activity.This compounds has the anti-mycotic activity spectrum of non-constant width, particularly at dermatophytosis (dermatophyte) and yeast, mould and two-phase fungi (diphasic fungi) are (for example at Candida (Candida) bacterial classification, Candida albicans (Candida albicans) for example, Candida glabrata (Candida glabrata)), and cotton-shaped surperficial tinea bacterium (Epidermophytonfloccosum), aspergillus (Aspergillus) bacterial classification, for example aspergillus niger (Aspergillusniger) and Aspergillus fumigatus (Aspergillus fumigatus), trichophyton (Trichophyton) bacterial classification, alpha fungus (Trichophyton mentagrophytes) for example, Microsporon (Microsporon) bacterial classification is microsporum canis (Microsporon canis) and Microsporon audouinii for example.Enumerate these fungies and never represent the fungi spectrum that can contain is limited, and only for the purpose of illustration.

Active compound of the present invention can itself, its dosage form or type of service prepared therefrom use, for example i.e. solution of usefulness, suspension agent, wettable powder, paste, soluble powder, powder agent and granule.Use in a usual manner and carry out, for example water, spray, atomize, broadcast sowing (broadcasting), dust, foam, shed etc.Also can use active compound, perhaps active agent preparations or active compound itself are injected in the soil by ultra-low volume method (ultra-lowvolume method).Also can handle plant seed.

When active compound of the present invention was used as mycocide, rate of application can change in the scope of relative broad according to using type.For the processing of plant parts, the active compound rate of application is generally 0.1 to 10000g/ha (hectare), and preferred 10 to 1000g/ha.For seed dressing, the active compound rate of application is generally 0.001 to 50g every kilogram of seed, preferred 0.01 to 10g every kilogram of seed.For soil treatment, the active compound rate of application is generally 0.1 to 10000g/ha, and preferred 1 to 5000g/ha.

As mentioned above, can handle all plants and its position according to the present invention.---for example merging---plant species and the plant cultivars of acquisition of in preferred embodiments, having handled wild plant kind and plant cultivars, or by the biological breeding method of routine by hybridization or protoplastis, with and the position.---suitable also can combine---and the transgenic plant and plant cultivars (genetically modified organisms) and the position thereof that obtain in more preferred, if handled with ordinary method by genetically engineered.Term " position " or " position of plant " or " plant parts " are explained as above.

Especially preferably the plant of handling according to the present invention is commercially available separately or the plant of the plant cultivars of use.The implication of plant cultivars is interpreted as the plant with new features (" feature ") by conventional breeding, mutagenesis or recombinant DNA technology breeding acquisition.They can be cultivar, mutation, biotype (biotype) or genotype.

According to plant species or plant cultivars, its plantation place and growth conditions (soil, weather, vegetation period, nutrition), processing of the present invention also can produce superadditivity (superadditive) (" collaborative ") effect.Can obtain the following effect that surpasses actual desired thus, for example can reduce the rate of application of spendable material of the present invention and composition and/or widen its action spectrum and/or improve its activity, improve plant-growth, improve high temperature or cold tolerance, raising to arid or to the tolerance of water or soil salt content, improve the quality of blooming, make gather simpler and easy, accelerates maturing, raising output, improve the quality of the product of gathering and/or improve its nutritive value, improve storage character and/or its processing characteristics of the product of gathering.

Preferably transgenic plant or the plant cultivars of being handled by the present invention (promptly obtaining by genetically engineered) is included in all plants of accepting genetic material in the genetic modification, and described genetic material is given described plant with particularly advantageous useful property (" feature ").The example of described characteristic has: improve plant-growth, improve high temperature or cold tolerance, raising to arid or to the tolerance of water or soil salt content, improve the quality of blooming, make gather simpler and easy, accelerates maturing, raising output, improve the quality of the product of gathering and/or improve its nutritive value, improve package stability and/or its processing characteristics of the product of gathering.Need other examples of ben described characteristic to have: to improve the resistibility of plant to animal and microorganism insect, for example to the resistibility of insect, acarid, phytopathogenic fungi, bacterium and/or virus, and improve the tolerance of plant to some weeding active compound.The example of the transgenic plant that can propose is: important crop, such as grain (wheat, rice), corn, soybean, potato, cotton, rape (oilseed rape), and fruit plant (fruit is apple, pears, citrus fruits and grape), lay special stress on corn, soybean, potato, cotton, tobacco and rape.Ben being characterized as by form toxin in plant materials is particularly by genetic material (for example gene C ry I A (a), Cry I A (b), Cry I A (c), Cry II A, Cry III A, Cry III B2, Cry9c, Cry2Ab, Cry3Bb and Cry I F and the combination thereof of Bacillus thuringiensis; Be designated hereinafter simply as " Bt plant ") toxin that forms in plant materials, improve the resistibility of plant to insect, arachnid, nematode and slug type larva and snail.Ben feature also comprises by systemic acquired resistance (SAR), systemin, phytoalexin, releaser and resistant gene and corresponding expressing protein and toxin and improves the resistibility of plant to fungi, bacterium and virus.Ben other characteristics are for improving the tolerance of plant to some weeding active compound, for example imidazolone type, sulfonylurea, glyphosate (glyphosate) or phosphinotricin (for example " PAT " gene).The gene of giving described desired characteristic also can mutually combine in the transgenic plant body.The example of " the Bt plant " that can propose is that commercially available trade(brand)name is corn mutation, cotton mutation, soybean mutation and the potato mutation of YIELD GARD_ (for example corn, cotton, soybean), KnockOut_ (for example corn), StarLink_ (for example corn), Bollgard_ (cotton), Nucoton_ (cotton) and NewLeaf_ (potato).The example of the plant with herbicide tolerant that can propose is that commercially available trade(brand)name is that Roundup Ready_ (has the glyphosate tolerance, for example corn, cotton, soybean), LibertyLink_ (has the phosphinotricin tolerance, rape for example), corn mutation, cotton mutation and the soybean mutation of IMI_ (having imidazolinone-tolerant) and STS_ (having the sulfonylurea tolerance, for example corn).The plant with Herbicid resistant that can propose (the herbicide tolerant plant of breeding in a usual manner) comprises that also trade(brand)name is the commercially available mutation (for example corn) of Clearfield_.Certainly, more than narration also is applicable to the plant cultivars with described gene expression characteristics or gene expression characteristics leaved for development, and described plant cultivars will be developed and/or goes on the market in future.

Cited plant can particularly advantageously be handled with the compound or the active compound combinations of general formula of the present invention (I) according to the present invention.The preferable range of above-mentioned active compound or mixture also is applicable to the processing of described plant.Lay special stress on is handled plant with concrete compound or the mixture that proposes of the present invention.

Describe by the preparation and the purposes of following examples active compound of the present invention.

Preparation embodiment

Embodiment 1[process 1)-k)-j)-f)-a)-b)]

Step 1, process 1):

37.5g (0.694mol) sodium methylate is dissolved in the 330g methyl alcohol.Add 31.7g (0.417mol) thiocarbamide under the room temperature, add 59.5g (0.278mol) 3-thienyl dimethyl malonate (DE3942952) again.Mixture boiled was refluxed 4 hours.With the dilute hydrochloric acid acidifying mixture and stir for some time.Leach product, it is washed with water and drying.Obtain 48g 2-sulfydryl-4,6-dihydroxyl-5-thiene-3-yl-pyrimidine.

HPLC:logp ^a=-0.12* (maximum λ: 302,246).

¹H NMR (DMSO-d6, tetramethylsilane): δ=7.39-7.41 (1H); 7.52-7.53 (1H); 7.70-7.71 (1H) ppm.

Step 2, process k)

11.46g (0.212mol) sodium methylate is dissolved in the 240ml ethanol.Add 48g (0.212mol) 2-sulfydryl-4,6-dihydroxyl-5-thiene-3-yl-pyrimidine down at 0 ℃.Under 0 ℃, dropwise add 30.1g (0.212mol) methyl-iodide then.With reaction mixture refluxed 30 minutes, concentrating under reduced pressure then.The residue water is boiled fast, be cooled to 0 ℃ then.Leach product and dry.

Obtain 37.9g 2-methylthio group-4,6-dihydroxyl-5-thiene-3-yl-pyrimidine.

HPLC:logp ^a=1.10* (maximum λ: 304).

¹H NMR (DMSO-d6, tetramethylsilane): δ=7.39-7.41 (1H); 7.70-7.71 (1H); 7.89-7.90 (1H) ppm

Step 3, process j)

To contain 15g (0.062mol) 2-methylthio group-4,119.64g (0.78mol) the phosphoryl chloride boiling reflux of 6-dihydroxyl-5-thiene-3-yl-pyrimidine 4 hours.Under the pressure of 10torr, distill volatile component, residuum is dissolved in the ethyl acetate, wash with water earlier, and then wash with dilute solution of sodium bicarbonate.Distilling off solvent under the pressure of 10torr.Obtain 11.3g 2-methylthio group-4,6-two chloro-5-thiene-3-yl-pyrimidines.

HPTLC:log p ^a=3.94* (maximum λ: 270).

¹H NMR (DMSO-d6, tetramethylsilane): δ=2.58 (3H); 7.19-7.20 (1H); 7.68-7.70 (1H); 7.72-7.73 (1H) ppm.

Step 4, process f)

At first 6.19g (0.031mol) 4-methyl piperidine is added in the 75ml methylene dichloride.Add 7.5g (0.031mol) 2-methylthio group-4 down at 0 ℃, 6-two chloro-5-thiene-3-yl-pyrimidines at room temperature stir mixture 12 hours then.Concentrated reaction mixture under the pressure of 10torr is dissolved in residuum in the ethyl acetate, successively with dilute hydrochloric acid, water and dilute solution of sodium bicarbonate washing.Drying solution also distills solvent under the pressure of 10torr, obtain 9.1g 2-methylthio group-4-chloro-5-thiene-3-yl--6-(4 '-methyl piperidine-1-yl) pyrimidine.

HPLC:log p ^a=5.47* (maximum λ: 244).

¹H NMR (DMSO-d6, tetramethylsilane): δ=0.83-0.84 (3H); 4.01-4.06 (1H); 7.11-7.12 (1H); 7.51-7.52 (1H); 7.65-7.67 (1H) ppm

Step 5, process a)

6g (0.018mol) 2-methylthio group-4-chloro-5-thiene-3-yl--6-(4 '-methyl piperidine-1-yl) pyrimidine is dissolved in the 120ml methylene dichloride.Under 0 ℃, add 8.67g (0.035mol) 3-chlorine peroxybenzoic acid slightly altogether at every turn.Under 0 ℃, reaction mixture was stirred 1 hour, at room temperature stirred then 14 hours.Distill solvent, residuum is dissolved in the ethyl acetate and washs with 10% sodium bicarbonate aqueous solution.Organic phase is dry and concentrated.Residuum is used hexanaphthene on silica gel: ethyl acetate=3: 1 is carried out chromatographic separation.Obtain 7.8g 2-methylsulfonyl-4-chloro-5-thiene-3-yl--6-(4 '-methyl piperidine-1-yl) pyrimidine.

HPLC:log p ^a=3.53* (maximum λ: 214,278).

¹H NMR (DMSO-d6, tetramethylsilane): δ=0.84-0.85 (3H); 0.97-1.07 (2H); 1.40-1.58 (3H); 2.742.81 (2H); 3.25 (3H); 3.84-3.87 (2H); 7.19-7.21 (1H); 7.65-7.66 (1H); 7.73-7.75 (1H) ppm.GC-MS: retention index=3014 (M=371,336,256,55).

Step 6, process b)

At first 0.108g (0.003mol) sodium hydride is added in the 20ml dimethyl formamide.Under 0 ℃, dropwise add 0.18g (0.003mol) pyrazoles, and mixture was stirred 1 hour.Add 1g (0.003mol) then and be dissolved in 2-methyl sulphonyl-4-chloro-5-thiene-3-yl--6-(4 '-methyl piperidine-1-yl) pyrimidine in the dimethyl formamide.Reaction mixture was at room temperature stirred two hours, pour in the water then and use ethyl acetate extraction.Organic phase is dry and concentrated, the mixture of residuum with ether and sherwood oil ground.Product is leached and drying.Obtain 0.9g2-(pyrazol-1-yl)-4-chloro-5-thiene-3-yl--6-(4 '-methyl piperidine-1-yl) pyrimidine.

HPLC:log p ^a=4.37* (maximum λ: 256).

¹H NMR (DMSO-d6, tetramethylsilane): δ=0.84-0.86 (3H); 1.01-1.24 (2H); 1.48-1.53 (3H); 3.90-3.94 (2H); 6.55-6.56 (1H); 7.17-7.19 (1H); 7.59 (1H); 7.71 (1H); 7.81-7.82 (1H); 8.55-8.56 (1H) ppm.

GC-MS: retention index=2910 (M=359; 344,324,310,296,280,254,227,200,186,159,133,118,98,79,55,41,27).

The formula of listing among the following table B (I) 5-heterocyclyl pyrimidines also obtains by aforesaid method.

Table B

The logP value uses reversed-phase column (C18) to measure by the following method according to EEC Directive 79/831 Annex V.A8 by HPLC (high performance liquid chromatography):

* temperature: 40 ℃; Moving phase: 0.1% aqueous formic acid and acetonitrile; Linear gradient from 10% acetonitrile to 95% acetonitrile.

* temperature: 43 ℃; Moving phase: 0.1% phosphate aqueous solution and acetonitrile; Linear gradient from 10% acetonitrile to 95% acetonitrile.

Each unbranched alkane-2-ketone (3 to 16 carbon atoms) with known logP value that uses is calibrated (by carrying out linear interpolation between the alkane ketone of having measured at two kinds, thereby determining the logP value according to retention time).

Each by using the UV spectrum between the 190nm to 400nm, determine maximum λ value at the chromatographic signal maximum.

Embodiment 196

2-[4-chloro-6-(1,2-dimethyl propyl amino)-5-(3 methyl thiophene-2-yl) pyrimidine-2- Base]-4,5-dimethyl-2,4-pyrazoline-3-ketone

Step 1

The adding of 1.9g (0.0384mol) hydrazine hydrate is contained in the 75ml alcohol suspension of 5.6g (0.0150mol) [6-chloro-2-methylsulfonyl-5-(3 methyl thiophene-2-yl) pyrimidine-4-yl]-(1, the 2-dimethyl propyl) amine.Mixture heating up was refluxed 90 minutes cooling back concentrating under reduced pressure.Residuum is used dissolve with ethanol again, be evaporated to dried then with dried over sodium sulfate.Obtain 6.0g[6-chloro-2-diazanyl-5-(3 methyl thiophene-2-yl) pyrimidine-4-yl]-(1, the 2-dimethyl propyl) amine.

HPLC：log p＝2.26

Step 2

The adding of 6.5ml Glacial acetic acid is contained in the 6.5ml methyl alcohol of 0.65g (2.0mmol) [6-chloro-2-diazanyl-5-(3 methyl thiophene-2-yl) pyrimidine-4-yl]-(1, the 2-dimethyl propyl) amine and 0.29g (2.2mmol) 2-methyl-3-ketobutyric acid mixtures of methyl esters.Mixture heating up was refluxed 3 hours cooling back concentrating under reduced pressure.With residuum on silica gel with 2-methoxyl group-2-methylpropane: sherwood oil=4: 1 carries out chromatographic separation.Obtain 0.1g 2-[4-chloro-6-(1,2-dimethyl propyl amino)-5-(3 methyl thiophene-2-yl) pyrimidine-2-base]-4,5-dimethyl-2,4-pyrazoline-3-ketone.

HPLC：log p＝4.46

Table C

2-(3 methyl thiophene-2-yl) dimethyl malonate

Step 1

At first (163g 1.222mol) adds in the 540ml methylene dichloride, and mixture is cooled to 0 ℃, dropwise adds 112ml (150g, 1.222mol) oxalyl chloride methyl esters under this temperature with aluminum chloride.Under this temperature, mixture was stirred 10 minutes then, under 0 ℃, dropwise adds 3 methyl thiophene equally, temperature is elevated to room temperature after, under this temperature, reaction mixture stirred and spends the night.Mixture poured in 21 frozen water be hydrolyzed; Shift out organic phase,,, after filtering the removal siccative and using Rotary Evaporators to evaporate, obtain 119.5g (3 methyl thiophene-2-yl) oxo methyl acetate the organic phase dried over sodium sulfate with the sodium hydrogen carbonate solution washing.Productive rate: 57%.

¹H NMR(DMSO)：δ＝8.09(d，1H)，7.19(d，1H)，7.67(dd，1H)，3.90(s，3H)，2.49(s，3H).

Step 2

(116g, 2.312mol) hydrazine hydrate was with mixture reflux 30 minutes slowly to add 112.5ml in the 260ml glycol ether that contains 90g (0.489mol) (3 methyl thiophene-2-yl) oxo methyl acetate.After being cooled to 30-40 ℃, add 82g (1.246mol) potassium hydroxide slightly altogether at every turn, meanwhile temperature is elevated to 70-80 ℃ and logical nitrogen.Then mixture slowly is heated to and refluxes and under this temperature, stirred altogether 5 hours.Behind the cool to room temperature, mixture is poured in 21 water, used the hydrochloric acid of 250ml intermediate concentration that the pH value is adjusted to pH=1, use the ethyl acetate extraction mixture.Use the dried over mgso organic phase, obtain 50g (3 methyl thiophene-2-yl) acetate behind filtration and the removal solvent.Productive rate: 66%.

¹H NMR(DMSO)：δ＝7.25(d，1H)，6.84(d，2H)，3.67(s，2H)，2.11(s，3H)

Step 3

The adding of the 5ml vitriol oil is contained in the 500ml methanol solution of 50g (0.32mol) (3 methyl thiophene-2-yl) acetate, mixture heating up was refluxed 8 hours.Use Rotary Evaporators to remove solvent, in residuum, add entry and methylene dichloride.Be separated and water carried out single extraction again, use the dried over sodium sulfate organic phase, filter and, obtain 42.5g (3 methyl thiophene-2-yl) methyl acetate with after the Rotary Evaporators evaporation with methylene dichloride.Productive rate: 70%.

¹H NMR(DMSO)：δ＝7.30(d，1H)，6.87(d，1H)，3.82(s，2H)，3.65(s，3H)，2.13(s，3H).

Step 4

In argon gas atmosphere, 14.7g sodium hydride (in the mineral oil, concentration 60%) is added 311ml, and (332g is 3.685mol) in the methylcarbonate, with mixture heating up to 80 ℃.Under this temperature, dropwise slowly add the 50ml toluene solution that contains 41g (0.217mol) (3 methyl thiophene-2-yl) methyl acetate.Mixture backflow stirring is spent the night.For carrying out aftertreatment,, be poured into then and also use the dilute hydrochloric acid acidifying in the frozen water with about 200ml methyl alcohol diluted mixture thing.Use dichloromethane extraction, use the dried over sodium sulfate organic phase, filter and remove back acquisition 43.6g 2-(3 methyl thiophene-2-yl) dimethyl malonate that desolvates.Productive rate: 88%.

¹H NMR(DMSO)：δ＝7.42(d，1H)，6.89(d，1H)，5.27(s，1H)，3.69(s，6H)，2.15(s，3H).

Spectroscopic data with the intermediate of similar approach preparation

Purposes embodiment

Embodiment A

Single softgel shell test (cucumber)/protectiveness

Solvent: 24.5 weight part acetone

24.5 weight part N,N-DIMETHYLACETAMIDE

Emulsifying agent: 1 weight part alkylaryl polyglycol ether

For preparing suitable active agent preparations,, and dope is diluted with water to desired concn with the active compound of 1 weight part and the solvent and the emulsifier mix of described amount.

Be test protection activity, active agent preparations sprayed to plant seedlings with described rate of application handle.The spraying layer is handled the plant spraying with the aqueous spore suspension of Flower of Garden Balsam list softgel shell (Sphaerothecafuliginea) after drying on the plant.Then plant is placed about 23 ℃, the relative greenhouse of atmospheric moisture about 70%.

Inoculate and evaluate and test after 7 days.The 0% expression drug effect identical with control group, 100% drug effect is represented not observe to infect.

In this test, the The compounds of this invention of following example number shows 70% or higher drug effect under the activity compound concentration of 100ppm:

11、38、70

Embodiment B

Black star bacterium test (apple)/protectiveness

Solvent: 24.5 weight part acetone

24.5 weight part N,N-DIMETHYLACETAMIDE

Emulsifying agent: 1 weight part alkylaryl polyglycol ether

Be test protection activity, active agent preparations sprayed to plant seedlings with described rate of application handle.The spraying layer is after drying on the plant, with the conidium aqeous suspension inoculation plant of apple scab substance apple black star bacteria (Venturia inaequalis).Then with plant about 20 ℃, relatively placed 1 day in the culturing room of atmospheric moisture about 100%.

Then plant is placed about 21 ℃, the relative greenhouse of atmospheric moisture about 90%.

Inoculate and evaluate and test after 10 days.The 0% expression drug effect identical with control group, 100% drug effect is represented not observe to infect.

11、38、70

Embodiment C

Grape spore test (cucumber)/protectiveness

Solvent: 49 weight part dimethyl formamides

Emulsifying agent: 1 weight part alkylaryl polyglycol ether

Active for the test protection, active agent preparations is handled the spraying of cucumber plant seedling with described rate of application.Handle after 1 day, with the spore suspension of Botrytis cinerea (Botrytis cinerea) plant is inoculated, it is following 48 hours to remain on 100% relative humidity, 20 ℃ then.Then plant is retained under 96% relative atmospheric moisture, 13 ℃ the temperature.

Inoculate and evaluate and test after 5-6 days.The 0% expression drug effect identical with control group, 100% drug effect is represented not observe to infect.

In this test, the The compounds of this invention of following example number shows 70% or higher drug effect under the activity compound concentration of 500ppm:

T-1、134、182、214

Claims

1. general formula (I) compound,

Wherein

R ¹Represent hydrogen, C ₁-C ₈Alkyl, C ₂-C ₈Thiazolinyl, C ₃-C ₈Alkynyl or C ₃-C ₈Cycloalkyl, wherein R ¹Can be by one to three identical or different radicals R ^aReplace, and

R ^aRepresent halogen, hydroxyl, cyano group, C ₁-C ₄Alkoxyl group and/or C ₃-C ₆Cycloalkyl,

Perhaps

R ²Represent hydrogen or C ₁-C ₆Alkyl, perhaps

R ¹And R ²The nitrogen-atoms that is connected with them represents ternary to hexavalent saturated, unsaturated or fragrant monocycle or bicyclic heterocycles jointly, and described heterocycle can contain the other heteroatoms that is selected from O, N and S, and described heterocycle can be by one to three identical or different radicals R ^cReplace, and

R ^cRepresent halogen, C ₁-C ₆Alkyl and/or C ₁-C ₆Haloalkyl,

2. general formula (I) compound,

Wherein

Perhaps

R ²Represent hydrogen or C ₁-C ₆Alkyl, perhaps

R ^cRepresent halogen, C ₁-C ₆Alkyl and/or C ₁-C ₆Haloalkyl,

R ³Represent saturated, the monocycle or the bicyclic heterocycles that part is unsaturated or fragrant of ternary to ten yuan, described heterocycle contains one to four heteroatoms that is selected from O, N and S, wherein R ³Can be by one to three identical or different radicals R ^dReplace, and

R ⁴Represent halogen or C ₁-C ₈Alkyl, C ₁-C ₈Alkoxyl group, C1 _-C ₈Haloalkyl, C ₁-C ₈Alkylthio, C ₁-C ₈Alkyl sulphinyl, C ₁-C ₈Alkyl sulphonyl or cyano group,

3. claim 1 or 2 formula (I) compound is characterized in that R ¹Represent following group

Wherein # represents tie point.

4. one or multinomial formula (I) compound in the claim 1 to 3 is characterized in that R ¹Represent following group

5. one or multinomial formula (I) compound in the claim 1 to 4 is characterized in that R ²Represent hydrogen, methyl, ethyl or propyl group.

6. one or multinomial formula (I) compound in the claim 1 to 4 is characterized in that R ¹And R ²The following group of the common representative of the nitrogen-atoms that is connected with them

Wherein

R ⁷Represent hydrogen or methyl,

R ⁸Represent methylidene, ethyl, fluorine, chlorine or trifluoromethyl,

R ⁹Represent methylidene, ethyl, fluorine, chlorine or trifluoromethyl,

And

7. one or multinomial formula (I) compound in the claim 1 to 4 is characterized in that R ¹And R ²The nitrogen-atoms that is connected with them is represented pyrrolidyl, piperidyl, morpholinyl, thio-morpholinyl, piperazinyl, 3 jointly, 6-dihydro-1 (2H)-piperidyl or tetrahydrochysene-1 (2H)-pyridazinyl, wherein above-mentioned group can be replaced by 1 to 3 fluorine atom, 1 to 3 methyl and/or trifluoromethyl.

8. one or multinomial formula (I) compound in the claim 1 to 7 is characterized in that R ³Be ternary, five yuan or hexa-member heterocycle, particularly five-membered ring.

9. one or multinomial formula (I) compound in the claim 1 to 8 is characterized in that R ³Be the heterocycle that is connected with pyrimidine ring by nitrogen.

10. one or multinomial formula (I) compound in the claim 1 to 9 is characterized in that R ³Represent following group: pyrazoles, pyrroles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazoles, tetrazolium, 2-pyridine, 2-pyrimidine, pyrazine or 3-pyridazine, each above-mentioned group is optional by maximum four radicals R ^dReplace.

11. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 9 ³Represent following group: pyrazoles, pyrroles, imidazoles, 1,2,3-triazoles, 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazoles, tetrazolium, 2-pyridine, 2-pyrimidine, pyrazine or 3-pyridazine, each above-mentioned group is optional by maximum three radicals R ^dReplace.

12. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 11 ³Represent pyrazoles, 1,2,3-triazoles, 1,2,4-triazole or pyridazine wherein encircle R ³By one to four identical or different following radicals R ^dReplace:

Halogen, hydroxyl, cyano group, nitro, amino, sulfydryl, C ₁-C ₆Alkyl, C ₁-C ₆Haloalkyl, C ₂-C ₆Thiazolinyl, C ₂-C ₆Alkynyl, C ₃-C ₆Cycloalkyl, C ₁-C ₆Alkoxyl group, C ₁-C ₆Halogenated alkoxy, carboxyl, C ₁-C ₇Alkoxy carbonyl, formamyl, C ₁-C ₇Alkyl amino-carbonyl, C ₁-C ₆Alkyl-C ₁-C ₆Alkyl amino-carbonyl, morpholino carbonyl, pyrrolidyl carbonyl, C ₁-C ₇Alkyl-carbonyl-amino, C ₁-C ₆Alkylamino, two-(C ₁-C ₆Alkyl) amino, C ₁-C ₆Alkylthio, C ₁-C ₆Alkyl sulphinyl, C ₁-C ₆Alkyl sulphonyl, hydroxyl alkylsulfonyl, amino-sulfonyl, C ₁-C ₆Alkyl amino sulfonyl or two-(C ₁-C ₆Alkyl) amino-sulfonyl or oxo.

13. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 11 ³Represent pyrazoles, 1,2,3-triazoles, 1,2,4-triazole or pyridazine wherein encircle R ³By one to three identical or different following radicals R ^dReplace:

14. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 13 ⁴Represent halogen, C ₁-C ₆Alkyl, C ₁-C ₆Haloalkyl or C ₁-C ₆Alkoxyl group.

15. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 13 ⁴Represent chlorine.

16. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 15 ⁵The pyridyl that representative connects on its 2-position or 4-position, described pyridyl can be by identical or different substituent R ^eThe single replacement to four replacements, R ^eRepresent fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

17. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 15 ⁵The pyrimidyl that representative connects on its 2-position or 4-position, described pyrimidyl can be by identical or different substituent R ^eThe single replacement to three replacements, R ^eRepresent fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

18. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 15 ⁵The thienyl that representative connects on its 2-position or 3-position, described thienyl can be by identical or different substituent R ^eThe single replacement to three replacements, R ^eRepresent fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

19. one or multinomial formula (I) compound is characterized in that R in the claim 1 to 15 ⁵The thiazolyl that representative connects on its 2-position, 4-position or 5-position, described thiazolyl can be by identical or different substituent R ^eSingle replacement or two replacement, R ^eRepresent fluorine, chlorine, bromine, cyano group, nitro, methyl, ethyl, methoxyl group, methylthio group, oximido methyl, oximido ethyl, methoxyimino methyl, methoxyimino ethyl and/or trifluoromethyl.

20. general formula (II) compound

Wherein

R ¹, R ², R ⁴And R ⁵Define as claim 1 R ⁶Represent C ₁-C ₆Alkyl.

21. general formula (III) compound

Wherein

R ¹, R ², R ⁴And R ⁵Define as claim 1 n=1 or 2, R ⁶Represent C ₁-C ₆Alkyl.

22. logical formula V compound

Wherein

R ³, R ⁴And R ⁵Definition is as claim 1, and Hal represents halogen.

23. general formula (IX) compound

Wherein

R ⁴And R ⁵Define as claim 1 R ⁶Represent C ₁-C ₆Alkyl, Hal represents halogen.

24. general formula (X) compound

Wherein

R ⁴And R ⁵Define as claim 1 R ⁶Represent C ₁-C ₆Alkyl.

25. general formula (XI) compound

Wherein

R ⁴And R ⁵Definition is as claim 1.

26. general formula (XVIII) compound

Wherein

R ³, R ⁴And R ⁵Definition is as claim 1.

27. general formula (XX) compound

Wherein

R ³And R ⁵Definition is as claim 1.

28. prepare the method for general formula (I ') compound,

R wherein ¹, R ²And R ⁵Define as claim 1 R ³The heterocycle that representative connects by nitrogen, R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

It is characterized in that process a) uses oxygenant oxidation formula (II) if compound--this reaction is suitably in thinner and carries out under existing, with process b) formula (III) compound that will obtain like this and formula (IV) be if the compound reaction--and if this reaction is suitably in thinner and exists and carries out down and be suitably under the acid acceptor existence carrying out

R wherein ¹, R ²And R ⁵Define as claim 1 R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl, and

R ⁶Represent C ₁-C ₆Alkyl,

R ³-H(IV)

29. prepare the method for general formula (I ") compound,

R wherein ¹, R ²And R ⁵Define as claim 1 R ³The heterocycle that representative connects by carbon, R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

It is characterized in that process c) make the reaction of formula V compound and formula (VI) compound, exist down and carry out if this reaction is suitably in thinner, carry out under existing if be suitably in catalyzer, and if be suitably under the acid acceptor existence and carry out,

R wherein ³, R ⁵Define as above, condition is R ³Be the heterocycle that is connected with the pyrimidine ring of (V) type compound by carbon atom, and

R ⁴Represent halogen, C ₁-C ₄Alkyl or C ₁-C ₄Haloalkyl,

HNR ¹R ² (VI)

R wherein ¹And R ²Definition as above.

30. the method for preparation formula (I_) compound,

Wherein

R ¹, R ²And R ⁵Define as claim 1 R ³The heterocycle that representative connects by nitrogen or carbon, R ⁴Represent C ₁-C ₈Alkyl, C ₁-C ₈Alkoxyl group, C ₁-C ₈Alkylthio, C ₁-C ₈Alkyl sulphonyl or cyano group,

It is characterized in that formula (I ' and a) or in the formula (I " a) compound is at process d) with formula (VII) if the compound reaction--this reaction is suitably in the presence of the thinner to be carried out; perhaps at process e) in the presence of thinner with formula (VIII) if Grignard compound reacts--this reaction is suitably in the presence of the catalyzer to be carried out

R wherein ¹, R ², R ³And R ⁵Define as above, Hal represents halogen,

R ⁴-M ¹ (VII)

M ¹Represent sodium or potassium,

R ⁴-MgHal (VIII)

R wherein ⁴Represent C ₁-C ₈Alkyl, and

Hal represents chlorine or bromine.

If 31. that be used to prevent and treat harmful organism and include weighting agent and/or carrier and the suitable composition that also comprises tensio-active agent, it is characterized in that said composition comprises any defined compound at least a claim 1 to 19.

32. the method for control harmful organism is characterized in that any defined compound or the defined composition of claim 31 in the claim 1 to 19 are acted on harmful organism and/or its habitat.

33. any defined formula (I) compound or the defined composition of claim 31 are used to prevent and treat the purposes of unwanted microorganisms in the claim 1 to 19.