CN102285971B - Pyrazolyl quinazolinone compound and application thereof - Google Patents
Pyrazolyl quinazolinone compound and application thereof Download PDFInfo
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- CN102285971B CN102285971B CN 201010212405 CN201010212405A CN102285971B CN 102285971 B CN102285971 B CN 102285971B CN 201010212405 CN201010212405 CN 201010212405 CN 201010212405 A CN201010212405 A CN 201010212405A CN 102285971 B CN102285971 B CN 102285971B
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention discloses a pyrazolyl quinazolinone compound with a novel structure, and as shown in a general formula I: each substituent group in the formula is defined in a specification. The compound shown in the general formula I has excellent insecticidal and bactericidal activity and can be used for preventing and curing insect pests and diseases.
Description
Technical field
The invention belongs to agricultural insecticidal, sterilant field.Be specifically related to a kind of Pyrazolyl quinazolinone compound and application thereof.
Background technology
Due to sterilant, sterilant in use for some time, insect, germ can produce resistance to it, therefore, need constantly invention novel with compound and composition improved tool desinsection, fungicidal activity.Simultaneously, along with people's needs growing to agricultural and animal products etc. with to the pay attention to day by day of environment protection, also need lower, the environment amenable new desinsection of use cost, sterilant.
US20090163545 has reported quianzolinones as follows, in medical field for changing the most eukaryotes life cycle:
WO2002048115A2 has reported quinazolone class general formula compound as follows, under 250ppm dosage, small cabbage moth is had to very high preventive effect:
In formula: B is selected from O or S; J is selected from phenyl ring, naphthalene nucleus, 5-or 6-unit's heterocycle or aromaticity 8-, 9-or 10-unit heterocycle etc.; K forms phenyl ring or pyridine ring with the carbon atom be connected; R
3be selected from C
1-C
6alkyl, C
3-C
6cycloalkyl, C
2-C
6thiazolinyl or C
2-C
6alkynyl; R
4be selected from H, halogen, CN, C
1-C
6alkyl, C
3-C
6cycloalkyl, C
2-C
6thiazolinyl or C
2-C
6alkynyl etc.
In prior art, as the preparation of Pyrazolyl quinazolinone compound shown in the present and desinsection thereof, fungicidal activity have no open.
Summary of the invention
The object of the present invention is to provide a kind of Pyrazolyl quinazolinone compound of novel structure, it can be applicable to the control of insect pest on agricultural, forestry or health, disease.
Technical scheme of the present invention is as follows:
A kind of Pyrazolyl quinazolinone compound, as shown in general formula I:
In formula:
R
1be selected from C
1-C
6alkyl, phenyl or heteroaryl; Hydrogen on described alkyl group can also further be replaced by 1-3 following substituting group: halogen, CN, NO
2, C
1-C
3alkyl, C
3-C
6cycloalkyl, C
2-C
5thiazolinyl, C
2-C
5alkynyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group or C
1-C
3halogenated alkoxy; Described phenyl or heteroaryl ring hydrogen can also further be replaced by 1-3 following radicals: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group, C
1-C
3haloalkyl, C
1-C
3halogenated alkoxy, C
1-C
2alkoxy carbonyl or C
1-C
3alkyl sulphonyl;
R
2be selected from halogen, C
1-C
6alkyl, C
1-C
6haloalkyl, C
3-C
6cycloalkyl, C
1-C
6alkoxyl group, C
1-C
6halogenated alkoxy, C
2-C
6cyanogen is for alkoxyl group, C
3-C
6alkene oxygen base or C
3-C
6alkynyloxy group;
R
3be selected from H, halogen, CN, NO
2, C
1-C
6alkyl or C
1-C
6haloalkyl;
R
4be selected from H, C
1-C
6alkyl, C
1-C
6haloalkyl, C
2-C
6thiazolinyl or C
2-C
6alkynyl;
R
5be selected from H; C
1-C
6alkyl, C
3-C
6cycloalkyl, C
2-C
5thiazolinyl or C
2-C
5alkynyl, any one hydrogen on described group can also further be replaced by following group: halogen, CN, NO
2, OH, C
1-C
3alkoxyl group, C
1-C
3alkylthio, C
1-C
3alkyl sulphinyl or C
1-C
3alkyl sulphonyl;
R
6, R
7, R
8, R
9respectively independently selected from H, halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group, C
1-C
3alkylthio or C
1-C
3alkyl sulphonyl.
The further preferred compound of the present invention is, in general formula I:
R
1be selected from C
1-C
6alkyl, phenyl or pyridyl; Hydrogen on described alkyl group can also further be replaced by 1-3 following substituting group: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group or C
1-C
3halogenated alkoxy; Described phenyl or pyridyl ring hydrogen can also further be replaced by 1-3 following radicals: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group, C
1-C
3haloalkyl, C
1-C
3halogenated alkoxy, C
1-C
2alkoxy carbonyl or C
1-C
3alkyl sulphonyl;
R
2be selected from halogen, C
1-C
3alkyl, C
1-C
3haloalkyl, C
3-C
6cycloalkyl, C
1-C
3alkoxyl group, C
1-C
3halogenated alkoxy, C
2-C
4cyanogen is for alkoxyl group, C
3-C
6alkene oxygen base or C
3-C
6alkynyloxy group;
R
3be selected from H, halogen, CN, NO
2or C
1-C
3alkyl;
R
4be selected from H, C
1-C
3alkyl, C
1-C
3haloalkyl, C
2-C
4thiazolinyl or C
2-C
4alkynyl;
R
5be selected from H; C
1-C
6alkyl or C
3-C
6cycloalkyl, any one hydrogen on described group can also further be replaced by following group: halogen, CN, NO
2, OH, C
1-C
3alkoxyl group, C
1-C
3alkylthio, C
1-C
3alkyl sulphinyl or C
1-C
3alkyl sulphonyl;
R
6, R
7, R
8, R
9respectively independently selected from H, halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group, C
1-C
3alkylthio or C
1-C
3alkyl sulphonyl.
The present invention further preferred compound is, in general formula I:
R
1be selected from C
1-C
6alkyl, phenyl or 2-pyridyl; Any one hydrogen on described alkyl group can also further be replaced by following substituting group: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group or C
1-C
3halogenated alkoxy; Described phenyl or 2-pyridyl ring hydrogen can also further be replaced by 1-3 following radicals: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group, C
1-C
3haloalkyl or C
1-C
3halogenated alkoxy;
R
2be selected from halogen, C
1-C
3alkyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group, C
1-C
3halogenated alkoxy, C
2-C
4cyanogen is for alkoxyl group, C
3-C
6alkene oxygen base or C
3-C
6alkynyloxy group;
R
3be selected from H, halogen, CN, NO
2or C
1-C
3alkyl;
R
4be selected from H;
R
5be selected from H; C
1-C
6alkyl or C
3-C
6cycloalkyl, any one hydrogen on described group can also further be replaced by following group: halogen, CN, NO
2, OH, C
1-C
3alkoxyl group, C
1-C
3alkylthio, C
1-C
3alkyl sulphinyl or C
1-C
3alkyl sulphonyl;
R
6, R
7, R
8, R
9respectively independently selected from H, halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group, C
1-C
3alkylthio or C
1-C
3alkyl sulphonyl.
In the definition of the compound of Formula I that the above provides, collect term General Definition used as follows:
Alkyl refers to the straight or branched form, such as methyl, ethyl, n-propyl, sec.-propyl etc.Cycloalkyl comprises cyclopropyl, cyclobutyl, cyclopropyl methyl, methyl cyclopropyl etc.Haloalkyl refers to the group that alkyl is replaced by one or more halogen atoms, as chloroethyl, trifluoromethyl etc.Thiazolinyl refers to the straight or branched thiazolinyl, as 1-propenyl, 2-propenyl etc.Alkynyl refers to the straight or branched alkynyl, as 1-proyl, 2-propynyl etc.Alkoxyl group refers to that the alkyl end is connected with the group of Sauerstoffatom, such as methoxyl group, oxyethyl group, positive propoxy, isopropoxy etc.Halogenated alkoxy refers to that alkyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Cyanogen refers to that for alkoxyl group alkyl is replaced by one or more cyano group, and end is connected with the group of Sauerstoffatom.Alkene oxygen base refers to that the thiazolinyl end is connected with the group of Sauerstoffatom.Alkynyloxy group refers to that the alkynyl end is connected with the group of Sauerstoffatom.Alkylthio refers to that the alkyl end is connected with the group of sulphur atom, such as methylthio group, ethylmercapto group etc.Alkoxy carbonyl refers to that the oxygen of alkoxyl group end is connected with carbonyl, for example methoxycarbonyl.Alkyl sulphinyl refers to the group that the alkyl end is (SO-), as methylsulfinyl.Alkyl sulphonyl refers to the group that the alkyl end is (SO2-), as methyl sulphonyl.Heteroaryl is containing 1-3 N, O or the heteroatomic five-ring of S, six-ring, eight yuan, nine yuan or ten yuan of condensed ring.Such as pyrroles, furans, thiophene, pyrazoles, oxazole, thiazole, triazole, thiadiazoles, pyridine, pyrimidine, pyrazine, pyridazine, triazine, cumarone, benzoxazoles, benzothiazole or quinoline etc.Halogen refers to fluorine, chlorine, bromine, iodine.
Can prepare by compound of Formula I of the present invention, in reaction formula, each group definition is the same by the following method.
General formula I I compound with compound of formula III in suitable solvent, temperature makes target compound I for-10 ℃ in 0.5-48 hour to reacting under boiling point.
Suitable solvent is selected from 1,2-ethylene dichloride, methylene dichloride, chloroform, tetracol phenixin, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran (THF), dioxane, DMF or dimethyl sulfoxide (DMSO) etc.
Add suitable acid or alkaloids all to reacting favourable.Suitable acid can be selected from organic acid as methylsulfonic acid, tosic acid or acetic acid etc., or mineral acid is as hydrogenchloride or sulfuric acid etc.; Suitable alkali is selected from organic bases as triethylamine, sodium methylate, sodium tert-butoxide, potassium tert.-butoxide, DMA or pyridine etc., or mineral alkali is as sodium hydroxide or potassium hydroxide etc.Add suitable water-retaining agent class material to reacting favourable.Suitable water-retaining agent class material is selected from Vanadium Pentoxide in FLAKES, calcium oxide, calcium chloride or anhydrous magnesium sulfate etc.
Can prepare with reference to the method in WO2005118552A2, WO2004067528A1, WO2006062978A1 or US2006/079561A1 by general formula I I compound.
Compound of formula III can be by following two kinds of methods preparation.
Method one:
Acylimidazole compound (IV) with Lithium Aluminium Hydride in solvent, temperature for react under-20 to-15 ℃ the pyrazoles formolation compound that makes general formula (III) representative in 5-30 minute (referring to Staab H A., Angew.Chem.Int.ed.1962,1; 351-367; Staab HA.Ann.Chem., the method in 1962,654,119-130.).
The preparation of acylimidazole compound (IV): at first by carboxylic acid cpd (being general formula VI compound) with chloride reagent in solvent, temperature leads to the acid chloride compounds shown in formula V for-10 ℃ to react under reflux temperature to make in 0.5-48 hour; Suitable chloride reagent is selected from oxalyl chloride, sulfur oxychloride, phosphorus trichloride or phosphorus pentachloride; Suitable solvent is selected from methylene dichloride, hexane, benzene, toluene, acetonitrile, dioxane or liquid chloride reagent.Again by acid chloride compounds (V) with imidazoles in solvent, temperature for-10 ℃ to react under room temperature within 0.5-48 hour, make general formula (IV) representative acylimidazole compound (referring to Barbara M.T.Wolf, Gernor A.Eller and Wolfgang Holzer, J.Org.Chem.1988,53,4901-4908; Staab H A., Angew.Chem.Int.ed.1962,1; 351-367; StaabHA.Ann.Chem., the method in 1962,654,119-130.).
The carbonate of general formula (VII) representative can be obtained to the carboxylic acid cpd of representative in general formula (VI) (referring to T.W.Greene and P.G.M.Wuts by alkaline hydrolysis; protecting group in organic synthesis; 2nd ed., John wiley& Sons, Inc., New York.1991, the method summary of pp.224-269), suitable alkali comprises the oxyhydroxide of basic metal as sodium, potassium or lithium.
Can prepare with reference to the method in WO2008134969A1, WO2010003350A1 or CN1626520A by general formula compound VII.
Method two:
In general formula (III), the pyrazoles formolation compound of representative can make by the pyrazoles benzylalcohol compound that adopts suitable oxygenant oxidation general formula (VIII) representative.The complexing salt of pyridine and chromic oxide), potassium permanganate or ozone etc. suitable oxygenant comprises PCC (Sha Ruite reagent:.
(R is C to general formula VII
1-C
4alkyl) carbonate of representative can be reduced to by suitable reductive agent the pyrazoles benzylalcohol compound of representative in general formula (VIII), and suitable reductive agent comprises sodium borohydride, Lithium Aluminium Hydride or POTASSIUM BOROHYDRIDE etc.
Table 1 has been listed structure and the physical properties of part compound of Formula I.
Table 1
Pyrazolyl quinazolinone compound of the present invention has high desinsection, fungicidal activity.Therefore, the present invention also comprises that compound of Formula I is for controlling the purposes of insect pest, disease.
The present invention also comprises take the insect-killing composition that compound of Formula I is active ingredient.In this insect-killing composition, the weight percentage of active ingredient is between 1-99%.Also comprise acceptable carrier on agricultural, forestry, health in this insect-killing composition.
The present invention also comprises take the fungicidal composition that compound of Formula I is active ingredient.In this fungicidal composition, the weight percentage of active ingredient is between 1-99%.Also comprise acceptable carrier on agricultural, forestry, health in this fungicidal composition.
Composition of the present invention can preparation form use.Compound of Formula I is as solubilization of active ingredient or be scattered in carrier or be mixed with preparation in order to be easier to disperse while using as desinsection or sterilant.For example: these chemicals can be made into wettable powder or missible oil.In these compositions, at least add a kind of liquid or solid carrier, and can add suitable tensio-active agent when needed.
Technical scheme of the present invention also comprises the method for pest control: insect-killing composition of the present invention is imposed on described insect or its growth medium.Usually the comparatively suitable significant quantity of selecting be per hectare 10 grams to 1000 grams, preferably significant quantity is that per hectare 20 grams are to 500 grams.
Technical scheme of the present invention also comprises the method for preventing and treating disease: fungicidal composition of the present invention is imposed on described disease or its growth medium.Usually the comparatively suitable significant quantity of selecting be per hectare 10 grams to 1000 grams, preferably significant quantity is that per hectare 20 grams are to 500 grams.
For some application, such as can in desinsection of the present invention, fungicidal composition, add one or more other sterilant, Insecticides (tech) & Herbicides (tech), plant-growth regulator or fertilizer etc. on agricultural, can produce additional advantage and effect thus.
Should be clear and definite, in claim limited range of the present invention, can carry out various conversion and change.
Embodiment
Following synthetic example, living test are tested result and be can be used to further illustrate the present invention, but do not mean that restriction the present invention.
Synthetic example
The preparation of example 1, compound 4
(1), the bromo-1H-pyrazoles of 1-(3-chloro-2-pyridyl)-3--5-formyl imidazoles is synthetic
Add successively the bromo-1H-pyrazoles of 1-(3-chloro-2-pyridyl)-3--5-formic acid (0.9 gram in 100 milliliters of there-necked flasks, 3.0 mmole, its preparation is with reference to example in WO2008134969A1 2), the methylene dichloride of 20 milliliters of dryings, stirring at room 5 minutes, add oxalyl chloride (1.1 grams, 9.0 mmole), there is gas to generate, when emitting minimizing, gas adds 1 DMF, there is again a large amount of gas to generate, stirring at room reduces pressure after 4 hours and steams solvent to the greatest extent, then add a small amount of toluene again concentrating under reduced pressure obtain 0.96 gram oily matter, yield: 100%.
Add successively imidazoles (0.4 gram in 100 milliliters of there-necked flasks, 6.0 mmole), the methylene dichloride of 5 milliliters of dryings, under room temperature, stir 30 minutes, treat that imidazoles is entirely molten, step product (0.96 gram in dropping, 3.0 methylene dichloride mmole) (10 milliliters) solution, within 20 minutes, dropwise, TLC monitoring reaction process, continue stir about 5 hours, remove by filter imidazole hydrochloride, methylene dichloride for filter cake (3 * 10 milliliters) washing, filtrate decompression is steamed methylene dichloride to the greatest extent and is obtained 1.06 gram yellow solids, yield: 100%.
(2), the bromo-1H-pyrazoles of 1-(3-chloro-2-pyridyl)-3--5-formaldehyde is synthetic
Add successively the bromo-1H-pyrazoles of 1-(3-chloro-2-pyridyl)-3--5-formyl imidazoles (0.9 gram in 100 milliliters of there-necked flasks; 3.0 mmole), the tetrahydrofuran (THF) of 10 milliliters of dryings; cryosel is bathed and is cooled to-20～-15 ℃; add Lithium Aluminium Hydride (0.03 gram in batches; 1.0 mmole); maintaining temperature of reaction is-20～-15 ℃; within 5 minutes, add; TLC monitoring reaction process; splash into ethanol (10 milliliters) quencher reaction after 30 minutes, then with 10% dilute sulphuric acid, be acidified to the reaction solution clarification.By in reaction solution impouring 100 ml waters, by ethyl acetate (2 * 100 milliliters), extract, saturated sodium carbonate solution, saturated common salt water washing for organic layer, concentrated after anhydrous magnesium sulfate drying, resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 2) obtain 0.33 gram light yellow solid, yield: 38%, fusing point: 100-102 ℃.
1H?NMR(300MHz，CDCl
3)：9.79(s，1H)，8.52(dd，1H)，7.97(dd，1H)，7.48(dd，1H)，7.11(s，1H)。
(3), compound 4 is synthetic
Add successively the bromo-1H-pyrazoles of 1-(3-chloro-2-pyridyl)-3--5-formaldehyde (0.3 gram in 100 milliliters of there-necked flasks, 1.0 mmole), 3, the chloro-2-amido of 5-bis-benzoyl methylamine (0.2 gram, 1.0 mmole), anhydrous magnesium sulfate (0.4 gram, 3.3 mmole), 25 milliliter 1, the 2-ethylene dichloride, heating reflux reaction 16 hours, react completely, be down to room temperature, by in reaction solution impouring 60 ml waters, by ethyl acetate (2 * 100 milliliters), extract, the organic layer saturated sodium carbonate solution, the saturated common salt water washing, concentrated after anhydrous magnesium sulfate drying, resistates column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 5), obtain 0.32 gram yellow solid, yield: 61%, fusing point: 145-146 ℃.
1H?NMR(300MHz，CDCl
3)：8.52(dd，1H)，8.04(dd，1H)，7.88(d，1H)，7.46(dd，1H)，7.36(d，1H)，6.41(d，1H)，6.27(s，1H)，5.73(d，1H)，3.09(s，3H)。
The preparation of example 2, compound 13
Add successively the bromo-1H-pyrazoles of 1-(3-chloro-2-pyridyl)-3--5-formaldehyde (0.3 gram in 100 milliliters of reaction flasks, 1.1 mmole, example 1 step 2 product), 3-methyl-2-amino-5-cyano group benzoyl methylamine (0.2 gram, 1.1 mmole), anhydrous magnesium sulfate (0.4 gram, 3.3 mmole), 25 milliliter 1, the 2-ethylene dichloride, heating reflux reaction 16 hours, react completely, be down to room temperature, by in reaction solution impouring 60 ml waters, by ethyl acetate (2 * 100 milliliters), extract, the organic layer saturated sodium bicarbonate solution, the saturated common salt water washing, concentrated after anhydrous magnesium sulfate drying, resistates column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 5), obtain 0.23 gram white solid, yield: 54%, fusing point: 140-142 ℃.
1H?NMR(300MHz，CDCl
3)：8.50(dd，1H)，8.16(s，1H)，8.08(dd，1H)，7.50(dd，1H)，7.38(s，1H)，6.76(s，1H)，6.28(s，1H)，5.78(s，1H)，3.08(s，3H)，2.16(s，3H)。
The preparation of example 3, compound 46
(1), (1-(2-chloro-phenyl-)-3-methyl isophthalic acid H-pyrazoles-5-yl)-methyl alcohol is synthetic
Add successively 1-(2-chloro-phenyl-)-3-methyl isophthalic acid H-pyrazoles-5-methyl-formiate (5.0 grams in 150 milliliters of there-necked flasks, 20 mmoles, its the preparation referring to CN101298451 example 2), 50 milliliters of ethanol, add sodium borohydride (2.3 grams, 60 mmoles) under room temperature in batches.Within 30 minutes, finish, stirring at normal temperature is after 20 minutes, heating reflux reaction 13 hours.After pressure reducing and steaming ethanol, add ethyl acetate (200 milliliters), the extraction of water (100 milliliters) separatory, the organic layer anhydrous magnesium sulfate drying, solvent is to the greatest extent steamed in decompression.Resistates column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 1), obtain 0.8 gram yellow oil, yield 18%.
1H?NMR(300MHz，CDCl
3)：7.48-7.31(m，4H)，6.12(s，1H)，4.30(s，2H)，2.26(s，3H)。
(2), 1-(2-chloro-phenyl-)-3-methyl isophthalic acid H-pyrazoles-5-base-formaldehyde is synthetic
Add successively PCC (Sha Ruite reagent: the complexing salt of pyridine and chromic oxide) (1.0 grams in 100 milliliters of there-necked flasks, 4.7 mmole), 30 milliliters of methylene dichloride, to dripping the dichloromethane solution of (1-(2-chloro-phenyl-)-3-methyl isophthalic acid H-pyrazoles-5-yl)-methyl alcohol (0.7 gram, 3.1 mmoles) of 15 milliliters in reaction system.Within 10 minutes, finish, within 5 hours, react completely, solvent is to the greatest extent steamed in decompression, and resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 3), obtain 0.65 gram yellow oil, yield: 94%.
1H?NMR(300MHz，CDCl
3)：9.65(s，1H)，7.52-7.42(m，4H)，6.87(s，1H)，2.40(s，3H)。
(3), compound 46 is synthetic
In 100 milliliters of there-necked flasks, add successively 1-(2-chloro-phenyl-)-3-methyl isophthalic acid H-pyrazoles-5-base-formaldehyde (0.3 gram, 1.4 mmole), 3, the chloro-2-amido of 5-bis-benzoyl methylamine (0.3 gram, 1.36 mmole), anhydrous magnesium sulfate (0.5 gram, 4.1 mmole), 25 milliliter 1,2-ethylene dichloride, heating reflux reaction 10 hours.React completely, be down to room temperature, by reaction solution impouring 60 ml waters, with ethyl acetate (2 * 100 milliliters) extraction.Organic phase is successively with the saturated sodium-chloride water solution washing, and anhydrous magnesium sulfate drying, reduce pressure and steam ethyl acetate to the greatest extent, resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 5), obtain 0.31 gram yellow solid, yield: 52%, fusing point:>250 ℃.
1H?NMR(300MHz，DMSO-d
6)：7.52-7.45(m，6H)，7.06(d，1H)，6.31(s，1H)，6.18(d，1H)，3.00(s，3H)，2.16(s，3H)。
The preparation of example 4, compound 74
(1), (1-(3,5-dichloro-2-pyridyl the base)-chloro-1H-pyrazoles of 3--5-yl)-methyl alcohol is synthetic
Add successively 1-(3 in 250 milliliters of there-necked flasks, 5-dichloro-2-pyridyl base) chloro-1H-pyrazole-5-ethyl formate (6.4 grams of-3-, 20 mmoles, its the preparation with reference to WO2010003350A1 example 4), 70 milliliters of ethanol, add sodium borohydride (2.3 grams, 60 mmoles) under room temperature in batches.Within 30 minutes, finish, stirring at normal temperature is after 20 minutes, heating reflux reaction 13 hours.React completely, after pressure reducing and steaming ethanol, add ethyl acetate (200 milliliters), the extraction of water (100 milliliters) separatory, the organic layer anhydrous magnesium sulfate drying, solvent is to the greatest extent steamed in decompression.Resistates column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 1), obtain 1.0 gram yellow oil, yield 17%.
1H?NMR(300MHz，CDCl
3)：8.38(dd，1H)，7.99(dd，1H)，6.39(s，1H)，4.53(s，2H)。
(2), 1-(3,5-dichloro-2-pyridyl the base)-chloro-1H-pyrazoles of 3--5-formaldehyde is synthetic
Add successively PCC (Sha Ruite reagent: the complexing salt of pyridine and chromic oxide) (1.2 grams in 100 milliliters of there-necked flasks, 5.4 mmole), 30 milliliters of methylene dichloride, to drip in reaction system 15 milliliters (1-(3, the dichloromethane solution of the chloro-1H-pyrazoles of 5-dichloro-2-pyridyl base)-3--5-yl)-methyl alcohol (1.0 grams, 3.6 mmoles).Solution colour becomes black by yellow, and bubble formation is arranged.Within 10 minutes, finish, within 5 hours, react completely, solvent is to the greatest extent steamed in decompression, and resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 2), obtain 0.4 gram yellow solid, yield: 40%.
1H?NMR(300MHz，CDCl
3)：9.78(s，1H)，8.45(dd，1H)，7.96(dd，1H)，7.01(s，1H)。
(3), compound 74 is synthetic
In 100 milliliters of there-necked flasks, add successively 1-(3, 5-dichloro-2-pyridyl base) the chloro-1H-pyrazoles of-3--5-formaldehyde (0.3 gram, 1.1 mmole), 3, the chloro-2-amido of 5-bis-benzoyl methylamine (0.2 gram, 1.1 mmole), anhydrous magnesium sulfate (0.4 gram, 3.3 mmole), 25 milliliter 1, the 2-ethylene dichloride, heating reflux reaction 10 hours, react completely, be down to room temperature, by in reaction solution impouring 60 ml waters, by ethyl acetate (2 * 100 milliliters), extract, organic phase is washed with saturated sodium-chloride water solution successively, anhydrous magnesium sulfate drying, ethyl acetate is to the greatest extent steamed in decompression, resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 5), obtain 0.22 gram white solid, yield: 51%.
1H?NMR(300MHz，DMSO-d
6)：8.59(d，1H)，8.50(d，1H)，8.35(d，1H)，7.58-7.53(m，1H)，7.26-7.216(m，1H)，7.02(d，1H)，6.73-6.68(m，1H)，6.65(d，1H)，6.32(s，1H)，5.93(t，1H)。
The preparation of example 5, compound 82
(1), 1-(3-chloro-2-pyridyl)-3-hydroxyl-1H-pyrazole-5-ethyl formate is synthetic
Add 1-(3-chloro-2-pyridyl)-3-pyrazolidone-5-carboxylic acid, ethyl ester (5.0 grams in 250 milliliters of reaction flasks, 18.5 mmole, its preparation is with reference to 1 step 7 of example in WO2008134969A1), 50 milliliters of acetonitriles and 98% sulfuric acid (3.7 grams, 37 mmoles).Stir after 10 minutes, add Potassium Persulphate (8.0 grams, 29.6 mmoles), reflux 5 hours.Reacting liquor while hot (50-65 ℃) is filtered, and filter cake washs with 10 milliliters of acetonitriles.Filtrate is concentrated into about 10 milliliters on Rotary Evaporators, adds 50 ml waters, the solid collected by filtration product, and product washs with the acetonitrile solution of 3 * 15 milliliter 25%, obtains orange solids 3.8 grams after drying, yield 76%, fusing point: 158-160 ℃.
1H?NMR(300MHz，CDCl
3)：8.44(dd，1H)，7.91(dd，1H)，7.41(dd，1H)，6.54(s，1H)，4.26(q，2H)，1.23(t，3H)。
(2), 1-(3-chloro-2-pyridyl)-3-methoxyl group-1H-pyrazole-5-ethyl formate is synthetic
Add successively 1-(3-chloro-2-pyridyl)-3-hydroxyl-1H-pyrazole-5-ethyl formate (1.0 grams in 250 milliliters of reaction flasks, 3.7 mmole), 10 milliliters of acetonitriles, salt of wormwood (0.5 gram, 3.7 mmole) and methyl iodide (0.5 gram, 3.7 mmole), be heated to 50 ℃, react 2 hours.After reacting completely, by in reaction solution impouring 100 ml waters, by ethyl acetate (2 * 100 milliliters), extract, saturated sodium bicarbonate solution, saturated common salt water washing for organic layer, concentrated after anhydrous magnesium sulfate drying, resistates column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 3), obtain 0.51 gram yellow oil, yield 48.6%.
1H?NMR(300MHz，CDCl
3)：8.51(dd，1H)，7.89(dd，1H)，7.39(dd，1H)，6.45(s，1H)，4.21(q，2H)，3.97(s，3H)，1.20(t，3H)。
(3), (1-(3-chloro-2-pyridyl)-3-methoxyl group-1H-pyrazoles-5-yl)-methyl alcohol is synthetic
Add successively 1-(3-chloro-2-pyridyl)-3-methoxyl group-1H-pyrazole-5-ethyl formate (2.6 grams, 9.2 mmoles), 30 milliliters of ethanol in 100 milliliters of there-necked flasks, add sodium borohydride (1.1 grams, 30 mmoles) under room temperature in batches.Within 30 minutes, finish, stirring at normal temperature is after 20 minutes, heating reflux reaction 13 hours.After pressure reducing and steaming ethanol, add ethyl acetate (200 milliliters), the extraction of water (100 milliliters) separatory, the organic layer anhydrous magnesium sulfate drying, solvent is to the greatest extent steamed in decompression.Resistates column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 1), obtain 1.5 gram yellow oil, yield 34%.
1H?NMR(300MHz，CDCl
3)：8.53(dd，1H)，7.85(dd，1H)，7.36(dd，1H)，6.44(s，1H)，4.51(s，2H)，3.87(s，3H)。
(4), 1-(3-chloro-2-pyridyl)-3-methoxyl group-1H-pyrazoles-5-formaldehyde is synthetic
Add successively PCC (Sha Ruite reagent: the complexing salt of pyridine and chromic oxide) (2.1 grams in 100 milliliters of there-necked flasks, 9.4 mmole), 30 milliliters of methylene dichloride, to dripping the dichloromethane solution of (1-(3-chloro-2-pyridyl)-3-methoxyl group-1H-pyrazoles-5-yl)-methyl alcohol (1.5 grams, 6.2 mmoles) of 15 milliliters in reaction system.Within 10 minutes, finish, within 5 hours, react completely, solvent is to the greatest extent steamed in decompression, and resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 2), obtain 1.1 gram yellow solids, yield: 59%.
1H?NMR(300MHz，CDCl
3)：9.76(s，1H)，8.49(dd，1H)，7.93(dd，1H)，7.40(dd，1H)，6.46(s，1H)，3.97(s，3H)。
(5), compound 82 is synthetic
In 100 milliliters of there-necked flasks, add successively 1-(3-chloro-2-pyridyl)-3-methoxyl group-1H-pyrazoles-5-formaldehyde (0.5 gram, 2 mmoles), 3, the chloro-2-amido of 5-bis-benzoyl methylamine (0.4 gram, 2 mmoles), anhydrous magnesium sulfate (0.7 gram, 6 mmoles), 25 milliliter 1, the 2-ethylene dichloride, heating reflux reaction 10 hours, react completely, be down to room temperature, by in reaction solution impouring 60 ml waters, by ethyl acetate (2 * 100 milliliters), extract, organic phase is washed with saturated sodium-chloride water solution successively, anhydrous magnesium sulfate drying, ethyl acetate is to the greatest extent steamed in decompression, resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 5), obtain 0.15 gram white solid, yield: 17%.
1H?NMR(300MHz，CDCl
3)：8.46(dd，1H)，7.98(dd，1H)，7.85(d，1H)，7.35(dd，1H)，7.33(d，1H)，6.90(s，1H)，5.79(d，1H)，5.71(d，1H)，3.88(s，3H)，3.08(s，3H)。
The preparation of example 6, compound 87
(1), 1, the chloro-1H-pyrazoles of 3-dimethyl-4--5-methyl alcohol synthetic
Add successively 1 to 100 milliliters of reaction flasks, the chloro-1H-pyrazole-5-ethyl formate of 3-dimethyl-4-(it prepares referring to CN1626520A for 6.1 grams, 30 mmoles), 30 milliliters of ethanolic solns, add sodium borohydride (3.4 grams, 90 mmoles) under room temperature in batches.Within 20 minutes, finish, stirring at normal temperature is after 20 minutes, and heating reflux reaction 13 hours, react completely, and solvent is to the greatest extent steamed in decompression, adds ethyl acetate (200 milliliters), the extraction of water (100 milliliters) separatory, and the organic layer anhydrous magnesium sulfate drying, solvent is to the greatest extent steamed in decompression.Resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 1), obtain white solid 4.2 grams, yield 87%.
1H?NMR(300MHz，CDCl
3)：4.65(s，2H)，3.85(s，3H)，2.20(s，3H)。
(2), 1, the chloro-1H-pyrazoles of 3-dimethyl-4--5-formaldehyde synthetic
Add successively PCC (Sha Ruite reagent: the complexing salt of pyridine and chromic oxide) (8.3 grams in 100 milliliters of reaction flasks, 38.3 mmole), 30 milliliters of methylene dichloride, to drip in reaction system 15 milliliters 1, the dichloromethane solution of the chloro-1H-pyrazoles of 3-dimethyl-4--5-methyl alcohol (4.1 grams, 25.5 mmoles).Within 20 minutes, finish, within 5 hours, react completely, solvent is to the greatest extent steamed in decompression, and resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 2), obtain 3.2 gram yellow solids, yield: 79%.
1H?NMR(300MHz，CDCl
3)：9.80(s，1H)，4.02(s，3H)，2.19(s，3H)。
(3), compound 87 is synthetic
Add successively 4-chloro-1 in 50 milliliters of reaction flasks, 3-dimethyl-1H-pyrazoles-5-formaldehyde (0.3 gram, 2.0 mmole), 3-methyl-2-amino-5-chlorobenzoyl methylamine (0.4 gram, 2.0 mmole), 25 milliliter 1,2-ethylene dichloride, anhydrous magnesium sulfate (0.7 gram, 6 mmoles), heating reflux reaction 20 hours, react completely, be down to room temperature, by reaction solution impouring 60 ml waters, with ethyl acetate (2 * 100 milliliters) extraction, the organic layer anhydrous magnesium sulfate drying, solvent is to the greatest extent steamed in decompression.Resistates is through column chromatography purification (leacheate: ethyl acetate: sherwood oil=1: 5), obtain 0.35 gram yellow oil, yield: 51%.
1H?NMR(300MHz，CDCl
3)：8.16(d，1H)，7.59(d，1H)，6.90(s，1H)，6.83(s，1H)，3.88(s，3H)，3.55(s，3H)，2.59(s，3H)，2.57(s，3H)。
Can prepare other compounds in general formula I of the present invention according to above method.
Part of compounds
1h NMR (300MHz, CDCl
3) δ (ppm) data are as follows:
Compound 1 (400MHz): 8.39 (dd, 1H), 7.95 (dd, 1H), (7.68 d, 1H), 7.37 (dd, 1H), (7.11 d, 1H), 6.92 (s, 1H), 6.47 (s, 1H), (5.81 t, 1H), 5.64 (s, 1H), 2.08 (s, 3H).
Compound 2 (DMSO-d
6): 8.54 (d, 1H), 8.19 (d, 1H), 8.15 (s, 1H), 7.61-7.58 (d, 2H), 7.22 (t, 1H), 6.89 (s, 1H), 6.70 (s, 1H), (6.66 s, 1H), 6.35 (s, 1H), 5.89 (s, 1H).
Compound 5:8.50 (d, 1H), 8.06 (dd, 1H), 7.82 (d, 1H), 7.47 (dd, 1H), 7.14 (d, 1H), 6.26 (s, 1H), 6.10 (s, 1H), (5.71 s, 1H), 3.08 (s, 3H), 2.10 (s, 3H).
Compound 6:8.52 (dd, 1H), 8.04 (dd, 1H), 7.88 (d, 1H), 7.46 (dd, 1H), 7.36 (d, 1H), 6.41 (d, 1H), 6.27 (s, 1H), 5.73 (d, 1H), 3.09 (s, 3H).
Compound 7 (DMSO-d
6): 8.55 (dd, 1H), 8.18 (dd, 1H), 7.68-7.59 (m, 2H), 7.25 (s, 1H), 6.63 (d, 1H), 6.27 (s, 1H), 6.11 (d, 1H), 3.02 (s, 3H), 1.89 (s, 3H).
Compound 8 (DMSO-d
6): 8.51 (d, 1H), 8.12 (d, 1H), 7.66-7.61 (m, 2H), 7.34 (s, 1H), 6.56 (d, 1H), 6.20 (s, 1H), 6.07 (d, 1H), 3.01 (s, 3H), 1.90 (s, 3H).
Compound 9 (DMSO-d
6): 8.49 (d, 1H), 8.15 (d, 1H), 7.60 (dd, 1H), 7.43 (d, 1H), 7.11 (d, 1H), 7.01 (d, 1H), 6.70 (d, 1H), (6.30 s, 1H), 6.12 (d, 1H), 2.98 (s, 3H).
Compound 10 (DMSO-d
6): 8.47 (d, 1H), 8.11 (d, 1H), 7.58 (dd, 1H), 7.53 (s, 1H), 7.29 (s, 1H), 7.20 (d, 1H), 6.31 (d, 1H), 6.14 (s, 1H), 3.00 (s, 3H).
Compound 11:8.49 (dd, 1H), 8.03 (dd, 1H), 7.83 (d, 1H), 7.46-7.42 (m, 2H), 6.92 (s, 1H), 6.51 (s, 1H), 6.38 (s, 1H), 5.95 (t, 1H).
Compound 12:8.52 (dd, 1H), 8.00 (dd, 1H), 7.89 (dd, 1H), (7.42-7.34 m, 2H), 6.81 (m, 1H), 6.56 (d, 1H), (6.28 s, 1H), 5.82 (d, 1H), 3.08 (s, 3H).
Compound 14:3.04 (s, 3H), 5.64 (d, 1H), 5.90 (d, 1H), (6.26 s, 1H), 6.59 (d, 1H), 7.46-7.22 (m, 2H), (7.93 d, 1H), 8.03 (d, 1H), 8.50 (dd, 1H).
Compound 15:8.52 (d, 1H), 8.04-8.02 (m, 2H), 7.49 (d, 1H), 7.46 (dd, 1H), 6.65 (d, 1H), 6.27 (s, 1H), 5.80 (d, 1H), 3.08 (s, 3H).
Compound 16:8.52 (d, 1H), 8.06 (d, 1H), 8.04 (d, 1H), 7.50 (s, 1H), 7.44 (dd, 1H), 6.65 (s, 1H), 6.27 (s, 1H), 5.82 (s, 1H), 3.09 (s, 3H).
Compound 17:8.53 (d, 1H), 8.06 (d, 1H), 8.04 (d, 1H), 7.64 (d, 1H), 7.46 (dd, 1H), 6.72 (s, 1H), 6.27 (s, 1H), 5.81 (s, 1H), 3.09 (s, 3H).
Compound 18:8.52 (d, 1H), 8.20 (d, 1H), 8.07 (d, 1H), 7.61 (d, 1H), 7.48 (dd, 1H), 7.39 (s, 1H), 6.30 (s, 1H), 5.88 (s, 1H), 3.09 (s, 3H).
Compound 21:8.54 (dd, 1H), 8.04 (dd, 1H), (7.90 d, 1H), 7.47 (dd, 1H), (7.38 d, 1H), 6.54 (d, 1H), (6.28 s, 1H), 5.76 (d, 1H), (5.76-5.73 m, 1H), 4.91-4.84 (m, 2H), (4.07 q, 1H), 3.43 (q, 1H).
Compound 23:8.54 (dd, 1H), 8.03 (dd, 1H), (7.88 d, 1H), 7.46 (dd, 1H), (7.39 d, 1H), 6.63 (d, 1H), (6.27 s, 1H), 6.16 (d, 1H), (4.89 dd, 1H), 3.93 (dd, 1H), 2.19 (t, 1H).
Compound 24:8.54 (dd, 1H), 8.06 (dd, 1H), 7.86 (d, 1H), 7.47 (dd, 1H), 7.34 (d, 1H), 6.59 (d, 1H), 6.27 (s, 1H), (5.82 d, 1H), 4.07 (q, 2H), 1.25 (t, 3H).
Compound 25:8.54 (dd, 1H), 8.04 (dd, 1H), 7.87 (d, 1H), 7.47 (dd, 1H), 7.35 (d, 1H), 6.58 (d, 1H), 6.27 (s, 1H), (5.82 d, 1H), 4.07 (t, 2H), 1.21 (t, 2H).
Compound 26 (DMSO-d
6): 8.58 (dd, 1H), 8.16 (dd, 1H), 7.76 (d, 1H), 7.66 (dd, 1H), 7.41 (d, 1H), 6.50 (d, 1H), 6.43 (d, 1H), 6.35 (s, 1H), 1.80 (s, 6H).
Compound 27:8.53 (dd, 1H), 8.07 (dd, 1H), (7.85 d, 1H), 7.51 (dd, 1H), (7.18 d, 1H), 6.41 (s, 1H), (6.08 s, 1H), 5.88 (s, 1H), (2.06 s, 3H), 1.85 (s, 3H), 1.76 (s, 3H).
Compound 32:8.57 (dd, 1H), 8.07 (dd, 1H), (7.90 d, 1H), 7.50 (dd, 1H), (7.36 d, 1H), 6.47 (d, 1H), (6.28 s, 1H), 5.77 (d, 1H), (4.94 m, 1H), 1.19 (d, 3H), 1.02 (d, 3H).
Compound 33:8.56 (d, 1H), 8.07 (d, 1H), (7.84 d, 1H), 7.51 (dd, 1H), (7.13 d, 1H), 6.27 (d, 1H), (5.92 s, 1H), 5.68 (d, 1H), (4.97 m, 1H), 2.09 (s, 3H), (1.18 d, 3H), 1.01 (d, 3H).
Compound 34:8.52 (d, 1H), 8.07 (d, 1H), 7.81 (d, 1H), 7.48 (dd, 1H), 7.12 (d, 1H), (6.25 s, 1H), 5.99 (s, 1H), 5.71 (s, 1H), 4.10 (m, 1H), 2.82 (m, 1H), (2.07 s, 3H), 1.56-1.51 (m, 2H), (1.37-1.29 m, 2H), 0.88 (t, 3H).
Compound 35 (400MHz): 8.45 (dd, 1H), 7.99 (dd, 1H), (7.71 d, 1H), 7.41 (dd, 1H), (7.07 d, 1H), 6.24 (s, 1H), (5.89 d, 1H), 5.64 (d, 1H), (2.60 m, 1H), 2.01 (s, 3H), 0.56-0.59 (m, 4H).
Compound 36 (400MHz): 8.57 (d, 1H), 8.20 (d, 1H), (7.85 s, 1H), 7.66 (dd, 1H), (7.47 s, 1H), 7.45 (d, 1H), (6.36 s, 1H), 6.09 (d, 1H), (2.59 m, 1H), 1.94 (s, 3H), 0.61-0.99 (m, 4H).
Compound 37:8.54 (dd, 1H), 8.07 (dd, 1H), 7.89 (d, 1H), 7.47 (dd, 1H), 7.36 (d, 1H), 6.58 (d, 1H), 6.33 (s, 1H), (5.80 d, 1H), 2.67 (m, 1H), 1.00-0.51 (m, 4H).
Compound 45 (DMSO-d
6): 8.08 (s, 1H), 7.58-7.44 (m, 5H), 7.18-7.16 (m, 1H), 6.69-6.67 (m, 2H), 6.64 (s, 1H), 6.28 (s, 1H), 5.45 (s, 1H), 2.22 (s, 3H).
Compound 47 (DMSO-d
6): 8.60 (s, 1H), 8.26 (s, 1H), (8.09 s, 1H), 7.88 (d, 1H), (7.63 d, 1H), 7.23 (s, 1H), (7.00 s, 1H), 6.75 (t, 1H), (6.70 s, 1H), 6.53 (s, 1H), 6.25 (s, 1H).
Compound 49 (400MHz): 8.38 (dd, 1H), 7.94 (dd, 1H), (7.66 s, 1H), 7.36 (dd, 1H), (7.27 s, 1H), 7.10 (d, 1H), 6.38 (s, 1H), (5.80 s, 1H), 5.70 (s, 1H), 2.07 (s, 3H).
Compound 50:8.49 (dd, 1H), 8.01 (dd, 1H), 7.80 (d, 1H), 7.45-7.41 (m, 2H), 7.19 (s, 1H), 6.57 (s, 1H), 6.39 (s, 1H), 5.96 (s, 1H).
Compound 51:8.47 (dd, 1H), 7.98 (dd, 1H), 7.90 (dd, 1H), 7.42-7.04 (m, 4H), 6.98 (dd, 1H), 6.68 (d, 1H), 6.47 (s, 1H), 5.83 (d, 1H).
Compound 52 (400MHz): 8.45 (dd, 1H), 7.97 (dd, 1H), 7.80 (d, 1H), (7.38 dd, 1H), 7.29 (d, 1H), 6.53 (d, 1H), (6.12 s, 1H), 5.73 (d, 1H), 3.02 (s, 3H).
Compound 53 (400MHz): 8.42 (d, 1H), 7.96 (d, 1H), (7.73 s, 1H), 7.38 (d, 1H), (7.06 s, 1H), 6.10 (d, 1H), 5.91 (s, 1H), (5.64 d, 1H), 2.99 (s, 3H), 2.00 (s, 3H).
Compound 54 (DMSO-d
6): 8.43 (d, 1H), 8.07 (d, 1H), 7.74 (s, 1H), 7.55 (dd, 1H), 7.38 (s, 1H), 7.37 (d, 1H), 6.32 (s, 1H), (6.19 d, 1H), 2.99 (s, 3H), 1.98 (s, 3H).
Compound 55 (DMSO-d
6): 8.54 (d, 1H), 8.16 (dd, 1H), 7.69-7.60 (m, 2H), 7.22 (s, 1H), 6.59 (d, 1H), 6.18 (s, 1H), 6.09 (d, 1H), 3.03 (s, 3H), 1.90 (s, 3H).
Compound 56:8.52 (d, 1H), 8.16 (dd, 1H), 7.74-7.60 (m, 2H), (7.38 s, 1H), 6.63 (d, 1H), 6.20 (s, 1H), (6.08 d, 1H), 3.00 (s, 3H), 1.86 (s, 3H).
Compound 57 (DMSO-d
6): 8.47 (dd, 1H), 8.14 (dd, 1H), 7.60 (dd, 1H), 7.48 (s, 1H), 7.39 (dd, 1H), 7.29 (d, 1H), 6.35 (s, 1H), 6.16 (d, 1H), 2.99 (s, 3H).
Compound 58:8.52 (d, 1H), 8.04 (d, 1H), 7.91 (s, 1H), 7.49 (s, 1H), 7.44 (dd, 1H), 6.66 (s, 1H), 6.18 (s, 1H), 5.82 (s, 1H), 3.08 (s, 3H).
Compound 59 (DMSO-d
6): 8.51 (d, 1H), 8.14 (d, 1H), 7.69 (s, 1H), 7.61 (dd, 1H), 7.50 (s, 1H), 7.12 (d, 1H), 6.24 (s, 1H), 6.17 (d, 1H), 3.02 (s, 3H).
Compound 60 (DMSO-d
6): 8.52 (d, 1H), 8.17 (d, 1H), 7.71 (d, 1H), 7.69 (d, 1H), 7.62 (dd, 1H), 7.06 (s, 1H), 6.06 (s, 1H), 5.81 (s, 1H), 3.00 (s, 3H).
Compound 61 (DMSO-d
6): 8.60 (d, 1H), 8.23 (d, 1H), (7.69 dd, 1H), 7.62 (s, 1H), (7.18 s, 1H), 6.47 (d, 1H), (6.37 d, 1H), 6.25 (s, 1H), (1.98 s, 3H3), 1.82 (s, 3H), 1.80 (s, 3H).
Compound 62 (DMSO-d
6): 8.62 (dd, 1H), 8.26 (dd, 1H), (7.72-7.67 m, 2H), 7.17 (dd, 1H), (6.81 t, 1H), 6.38 (d, 1H), (6.32 d, 1H), 6.26 (s, 1H), (1.98 s, 3H), 1.81 (s, 3H), 1.79 (s, 3H).
Compound 63 (DMSO-d
6): 8.60 (d, 1H), 8.24 (d, 1H), 7.74 (d, 1H), 7.70 (dd, 1H), 7.54 (d, 1H), 6.92 (d, 1H), 6.41 (d, 1H), 6.32 (s, 1H), 1.79 (s, 6H).
Compound 68:0.96 (d, 3H), 8.50 (dd, 1H), (7.99 dd, 1H), 7.83 (d, 1H), (7.42 dd, 1H), 7.28 (d, 1H), (6.38 d, 1H), 6.14 (s, 1H), (5.70 d, 1H), 4.86 (m, 1H), 1.12 (d, 3H).
Compound 69 (400MHz): 8.45 (d, 1H), 7.99 (d, 1H), (7.77 s, 1H), 7.41 (dd, 1H), (7.06 s, 1H), 6.16 (s, 1H), (5.91 s, 1H), 5.63 (s, 1H), (2.60 m, 1H), 2.00 (s, 3H), 0.60-0.56 (m, 4H).
Compound 70 (400MHz): 8.56 (d, 1H), 8.16 (d, 1H), (7.86 s, 1H), 7.64 (dd, 1H), (7.42 s, 1H), 7.41 (s, 1H), (6.24 s, 1H), 6.07 (d, 1H), (2.58 d, 1H), 1.95 (s, 3H), 0.98-0.65 (m, 4H).
Compound 78:8.46 (dd, 1H), 7.98 (dd, 1H), (7.85 d, 1H), 7.36 (dd, 1H), (7.33 d, 1H), 6.88 (s, 1H), (5.78 d, 1H), 5.76 (d, 1H), (4.82 dd, 2H), 3.08 (s, 3H), 2.50 (t, 1H).
Compound 80:8.46 (dd, 1H), 7.98 (dd, 1H), 7.85 (d, 1H), 7.35 (dd, 1H), 7.33 (d, 1H), (6.90 s, 1H), 6.08 (m, 1H), (5.78 d, 1H), 5.73 (d, 1H), (5.38 dd, 1H), 5.25 (dd, 1H), (4.67 dd, 2H), 3.09 (s, 3H).
Compound 88 (DMSO-d
6): 7.61 (s, 1H), 7.39 (s, 1H), 7.10 (d, 1H), 6.22 (d, 1H), 3.83 (s, 3H), 2.79 (s, 3H), 2.10 (s, 3H).
Compound 89 (DMSO-d
6): 7.52 (s, 1H), 7.10 (s, 1H), 6.84 (d, 1H), 5.97 (d, 1H), 5.63 (s, 1H), 3.81 (s, 3H), 2.92 (s, 3H), 2.09 (s, 3H), 2.03 (s, 3H).
Compound 90 (DMSO-d
6): 7.63 (s, 1H), 7.42 (s, 1H), 7.30 (d, 1H), 6.04 (d, 1H), 5.62 (s, 1H), 3.81 (s, 3H), 2.94 (s, 3H), 2.03 (s, 3H).
Compound 91:8.10 (d, 1H), 7.40 (d, 1H), 6.26 (s, 1H), 5.15 (s, 1H), 3.92 (s, 3H), 2.80 (s, 3H), 2.21 (s, 3H), 2.04 (s, 3H).
Compound 92 (DMSO-d
6): 8.21 (s, 1H), 7.62 (d, 1H), 7.22 (t, 1H), 6.97 (s, 1H), 6.74-6.69 (m, 2H), 5.93 (s, 1H), 5.88 (s, 1H), 3.81 (s, 3H), 2.09 (s, 3H).
Compound 93 (DMSO-d
6): 8.21 (s, 1H), 7.62 (d, 1H), 7.22 (t, 1H), 6.75-6.69 (m, 2H), 6.66 (s, 1H), 5.93 (s, 1H), 5.89 (s, 1H), (4.17 q, 2H), 2.11 (s, 3H), 1.38 (t, 3H).
Compound 94 (DMSO-d
6): 7.97 (s, 1H), 7.65 (dd, 1H), 7.22 (t, 1H), 6.81 (s, 1H), 6.74-6.70 (m, 2H), 6.00 (s, 1H), 3.88 (s, 3H), (2.47 q, 2H), 1.98 (s, 3H), 1.16 (t, 3H).
Compound 95 (DMSO-d
6): 8.22 (s, 1H), 7.67 (m, 1H), 7.24 (t, 1H), 6.97 (s, 1H), 6.75 (m, 2H), 6.04 (s, 1H), 3.95 (s, 3H), 1.988 (s, 3H).
Compound 96 (DMSO-d
6): 7.51 (d, 1H), 7.11 (t, 1H), 6.44 (s, 1H), 6.03 (d, 1H), 3.81 (s, 3H), 2.64 (s, 3H), 2.49 (q, 2H), (2.11 s, 3H), 1.95 (s, 3H), 1.17 (t, 3H).
Biological activity determination
The mensuration of example 7 insecticidal activities
According to the solvability of testing compound, former medicinal acetone or methyl-sulphoxide dissolve, and then with 1 ‰ tween 80 solution preparation, become 50 milliliters of the liquid to be measured of desired concn, and acetone or the methyl-sulphoxide content in total solution is no more than 10%.
Kill the mensuration of small cabbage moth activity
Cabbage leaves is broken into to the leaf dish of 1 centimetre of diameter with punch tool, with the Airbrush spraying, process, certain density test compounds is sprayed at every leaf dish pros and cons, and spouting liquid is 0.5 milliliter, 8 of the rear every processing accesses of drying in the shade try worms (3 age), and every processing repeats for 3 times.Put into 24 ℃, the indoor cultivation of relative humidity 60%～70%, unglazed photograph after processing, 72 hours " Invest, Then Investigate " survival borer populations, calculate mortality ratio.
In the compound of part for examination, following compounds prevention effect to small cabbage moth when concentration is 10ppm is better, and mortality ratio is more than 80%: 4,5,6,7,10,13,15,16,17,23,24,25,32,51,52,55,57,58,59,60,68,70.
In the compound of part for examination, following compounds prevention effect to small cabbage moth when concentration is 1ppm is better, and mortality ratio is more than 80%: 4,52.
The mensuration of example 8, fungicidal activity
According to the solvability of testing compound, former medicinal acetone or methyl-sulphoxide dissolve, and then with 1 ‰ tween 80 solution preparation, become 50 milliliters of the liquid to be measured of desired concn, and acetone or the methyl-sulphoxide content in total solution is no more than 10%.
The two leaf phase stem and leaf of Wheat that greenhouse dixie cup Nutrition Soil is cultivated are as the test host plant of wheat powdery mildew.Spraying is processed, and then natural air drying, inoculate pathogenic bacteria after 24h.The Powdery Mildew spore is shaken off on wheat leaf blade, and continued to cultivate the fungicidal activity of 7 days " Invest, Then Investigate " compounds in greenhouse.
In the compound of part for examination, following compounds when concentration is 400ppm to the prevention effect of wheat powdery mildew more than 90%: 51,87,88,89,90.
Claims (7)
1. a Pyrazolyl quinazolinone compound, as shown in general formula I:
In formula:
R
1be selected from C
1-C
6alkyl, phenyl or pyridyl; Hydrogen on described alkyl group can also further be replaced by 1-3 following substituting group: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group or C
1-C
3halogenated alkoxy; Described phenyl or pyridyl ring hydrogen can also further be replaced by 1-3 following radicals: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group, C
1-C
3haloalkyl, C
1-C
3halogenated alkoxy, C
1-C
2alkoxy carbonyl or C
1-C
3alkyl sulphonyl;
R
2be selected from halogen, C
1-C
3alkyl, C
1-C
3haloalkyl, C
3-C
6cycloalkyl, C
1-C
3alkoxyl group, C
1-C
3halogenated alkoxy, C
2-C
4cyanogen is for alkoxyl group, C
3-C
6alkene oxygen base or C
3-C
6alkynyloxy group;
R
3be selected from H, halogen, CN, NO
2or C
1-C
3alkyl;
R
4be selected from H, C
1-C
3alkyl, C
1-C
3haloalkyl, C
2-C
4thiazolinyl or C
2-C
4alkynyl;
R
5be selected from H; C
1-C
6alkyl or C
3-C
6cycloalkyl, any one hydrogen on described group can also further be replaced by following group: halogen, CN, NO
2, OH, C
1-C
3alkoxyl group, C
1-C
3alkylthio, C
1-C
3alkyl sulphinyl or C
1-C
3alkyl sulphonyl;
R
6, R
7, R
8, R
9respectively independently selected from H, halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group, C
1-C
3alkylthio or C
1-C
3alkyl sulphonyl.
2. according to compound claimed in claim 1, it is characterized in that, in general formula I:
R
1be selected from C
1-C
6alkyl, phenyl or 2-pyridyl; Any one hydrogen on described alkyl group can also further be replaced by following substituting group: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group or C
1-C
3halogenated alkoxy; Described phenyl or 2-pyridyl ring hydrogen can also further be replaced by 1-3 following radicals: halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3alkoxyl group, C
1-C
3haloalkyl or C
1-C
3halogenated alkoxy;
R
2be selected from halogen, C
1-C
3alkyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group, C
1-C
3halogenated alkoxy, C
2-C
4cyanogen is for alkoxyl group, C
3-C
6alkene oxygen base or C
3-C
6alkynyloxy group;
R
3be selected from H, halogen, CN, NO
2or C
1-C
3alkyl;
R
4be selected from H:
R
5be selected from H; C
1-C
6alkyl or C
3-C
6cycloalkyl, any one hydrogen on described group can also further be replaced by following group: halogen, CN, NO
2, OH, C
1-C
3alkoxyl group, C
1-C
3alkylthio, C
1-C
3alkyl sulphinyl or C
1-C
3alkyl sulphonyl;
R
6, R
7, R
8, R
9respectively independently selected from H, halogen, CN, NO
2, C
1-C
3alkyl, C
1-C
3haloalkyl, C
1-C
3alkoxyl group, C
1-C
3alkylthio or C
1-C
3alkyl sulphonyl.
3. a purposes of controlling agricultural or forestry insect pest according to compound of Formula I claimed in claim 1.
4. a purposes of controlling agricultural or forestry disease according to compound of Formula I claimed in claim 1.
5. a desinsection, fungicidal composition, containing compound shown in general formula I as claimed in claim 1 is active ingredient and agricultural or forestry acceptable carrier, in composition, the weight percentage of active ingredient is 1-99%.
6. a method of controlling agricultural or forestry insect pest is characterized in that: composition claimed in claim 5 is imposed on the medium of insect that needs control or its growth to the effective dose of 1000 grams with per hectare 10 grams.
7. a method of controlling agricultural or forestry disease is characterized in that: composition claimed in claim 5 is imposed on the medium of disease that needs control or its growth to the effective dose of 1000 grams with per hectare 10 grams.
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|---|---|---|---|
| CN 201010212405 CN102285971B (en) | 2010-06-21 | 2010-06-21 | Pyrazolyl quinazolinone compound and application thereof |
| PCT/CN2011/075938 WO2011160569A1 (en) | 2010-06-21 | 2011-06-20 | Pyrazolyl quinazolone compounds and uses thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010212405 CN102285971B (en) | 2010-06-21 | 2010-06-21 | Pyrazolyl quinazolinone compound and application thereof |
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ID=45332747
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002048115A2 (en) * | 2000-12-11 | 2002-06-20 | E. I. Du Pont De Nemours And Company | Quinazolinones and pyridinopyrimidinones for controlling invertebrate pests |
| WO2004011447A2 (en) * | 2002-07-31 | 2004-02-05 | E.I. Du Pont De Nemours And Company | Method for preparing fused oxazinones from ortho-amino aromatic carboxylic acid and a carboxylic acid in the presence of a sulfonyl chloride and pyridine |
| CN1620450A (en) * | 2002-01-22 | 2005-05-25 | 纳幕尔杜邦公司 | Quinazoline(di) ones for invertebrate pest control |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3412080A1 (en) * | 1984-03-31 | 1985-10-03 | Bayer Ag, 5090 Leverkusen | MICROBICIDES CONTAINING 2- (1H-PYRAZOL-1-YL) -4- (3H) -QUINAZOLINONE |
| GB9719411D0 (en) * | 1997-09-12 | 1997-11-12 | Ciba Geigy Ag | New Pesticides |
-
2010
- 2010-06-21 CN CN 201010212405 patent/CN102285971B/en active Active
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2011
- 2011-06-20 WO PCT/CN2011/075938 patent/WO2011160569A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002048115A2 (en) * | 2000-12-11 | 2002-06-20 | E. I. Du Pont De Nemours And Company | Quinazolinones and pyridinopyrimidinones for controlling invertebrate pests |
| CN1620450A (en) * | 2002-01-22 | 2005-05-25 | 纳幕尔杜邦公司 | Quinazoline(di) ones for invertebrate pest control |
| WO2004011447A2 (en) * | 2002-07-31 | 2004-02-05 | E.I. Du Pont De Nemours And Company | Method for preparing fused oxazinones from ortho-amino aromatic carboxylic acid and a carboxylic acid in the presence of a sulfonyl chloride and pyridine |
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|---|---|
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| CN102285971A (en) | 2011-12-21 |
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Effective date of registration: 20160122 Address after: 110021 Liaodong Road, Tiexi District, Liaoning, No. 8-1, No. Patentee after: SHENYANG SINOCHEM PESTICIDE CHEMICAL RESEARCH AND DEVELOPMENT CO., LTD. Address before: 100031 Beijing, Xicheng District, the door of the revitalization of the main street, No. 28 Patentee before: Sinochem Corporation Patentee before: Shenyang Research Institute of Chemical Industry |