WO2022262821A1 - Diclazuril derivative and application thereof, and fungicide for combating plant diseases - Google Patents

Diclazuril derivative and application thereof, and fungicide for combating plant diseases Download PDF

Info

Publication number
WO2022262821A1
WO2022262821A1 PCT/CN2022/099231 CN2022099231W WO2022262821A1 WO 2022262821 A1 WO2022262821 A1 WO 2022262821A1 CN 2022099231 W CN2022099231 W CN 2022099231W WO 2022262821 A1 WO2022262821 A1 WO 2022262821A1
Authority
WO
WIPO (PCT)
Prior art keywords
halogen
alkyl
substituted
group
diclazuril
Prior art date
Application number
PCT/CN2022/099231
Other languages
French (fr)
Chinese (zh)
Inventor
杨光富
曾令强
陈涛
朱晓磊
张璞
吴耀军
姚凯诚
Original Assignee
江苏中旗科技股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 江苏中旗科技股份有限公司 filed Critical 江苏中旗科技股份有限公司
Publication of WO2022262821A1 publication Critical patent/WO2022262821A1/en

Links

Classifications

    • 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
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/707—1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/553—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C07D239/96—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D253/075—Two hetero atoms, in positions 3 and 5
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D403/12—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 linked by a chain containing hetero atoms as chain links

Definitions

  • the invention relates to the field of pesticide fungicides, in particular to a diclazuril derivative and its application and a fungicide for resisting plant diseases.
  • Diclazuril is an anticoccidial drug reported by Belgian Janssen Company in 1986, which belongs to triazine benzyl cyanide compound in structure, and is used for poultry coccidiosis, mainly for preventing and treating chicken coccidiosis, and concurrently It has the advantages of high efficiency, broad spectrum, low toxicity, low drug resistance and small dosage.
  • CN107459493A the following general formula of diclazuril derivatives with diphenyl ether fragments used as fungicides is disclosed, which shows better control effect on cucumber downy mildew at a concentration of 200 mg/L. Specifically, it is disclosed that the compounds shown below exhibit 100% control effect on cucumber downy mildew at a concentration of 200 mg/L, but the activity significantly decreases or disappears when the concentration is lowered.
  • the object of the present invention is to provide a new diclazuril derivative, in the hope that the diclazuril derivative can achieve significantly higher anti-plant disease control effect.
  • the first aspect of the present invention provides a diclazuril derivative, which has the formula (I):
  • R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 are each independently selected from H, C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano.
  • the second aspect of the present invention provides a kind of diclazuril derivative, and this derivative has the structural formula shown in formula (II):
  • Q is N or C (R 28 );
  • R is selected from a C 6-18 aryl group, a C 6-18 aryl group substituted by at least one group in combination A, a 4-8 membered heterocyclic group containing at least one N atom, a combination A A 4-8-membered heterocyclic group containing at least one N atom substituted by at least one group; the combination A is composed of C 1-8 alkyl, halogen, C 1-8 alkyl substituted by at least one halogen , C 1-8 alkoxy, benzyl, phenoxy substituted by at least one halogen;
  • R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-8 alkyl, C 1-8 alkoxy;
  • R 25 is selected from H, C 1-8 alkyl
  • R 26 and R 27 are each independently selected from H, halogen, C 1-8 alkyl, C 1-8 alkoxy, cyano, nitro, C 1-8 alkane substituted by at least one halogen Base, benzyl, CH 3 -C(O)-;
  • R 28 is selected from H, halogen, C 1-8 alkyl, CH 3 -OC(O)-, C 1-8 alkoxy, C 1-8 alkyl substituted by at least one halogen;
  • Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-10 membered carbocycle.
  • the third aspect of the present invention provides the use of the diclazuril derivatives described in any one of the first aspect and the second aspect as mitochondrial succinate dehydrogenase inhibitors in pesticides.
  • the fourth aspect of the present invention provides the application of the diclazuril derivatives described in any one of the aforementioned first aspect and second aspect in resisting plant diseases.
  • the fifth aspect of the present invention provides a fungicide for resisting plant diseases, the active ingredient of the fungicide is at least one of the diclazuril derivatives described in the first aspect or the second aspect, and Based on the total weight of the bactericide, the content of the active ingredient is 0.1-100% by weight.
  • the compounds provided by the present invention are superior to plant diseases such as cucumber downy mildew, soybean rust, corn rust, rice sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean gray mold, and rice blast.
  • the control effect of the reference compound is obviously better than that of the prior art (such as penthiopyrad, cyanazazole, indazole sulfamethoxazole, etc.), and has potential commercial value.
  • the compound provided by the invention has better control effect on cucumber downy mildew at a relatively low concentration.
  • Halogen means at least one element among fluorine, chlorine, bromine and iodine.
  • C 1-8 alkyl means an alkyl group with a total of 1-8 carbon atoms, including straight-chain alkyl and branched-chain alkyl, such as methyl, ethyl, n-propyl, isopropyl, n- Butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, etc.
  • the definition of "C 1-6 alkyl”, “C 1-4 alkyl”, “C 1-3 alkyl” is similar to the definition of "C 1-8 alkyl", the difference is that the carbon The total number of atoms is different.
  • C 1-8 alkoxy is similar to the definition of "C 1-8 alkyl", the difference is that "C 1-8 alkoxy” is directly connected to the parent core structure through an oxygen atom, And the total number of carbon atoms of the C 1-8 alkoxy group is 1-8, the C 1-8 alkoxy group can be expressed as -OR 1 , wherein, R 1 is the C 1-8 alkoxy group
  • the alkyl group in the group can be, for example, methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, tert-butyloxy radical, n-pentyloxy, isopentyloxy, n-hexyloxy.
  • C 1-6 alkoxy and “C 1-4 alkoxy” are similar to the definitions of "C 1-8 alkoxy", except that the total number of carbon atoms is different.
  • C 1-8 alkyl substituted by at least one halogen is similar to the definition of “C 1-8 alkyl", except that "C 1-8 alkyl substituted by at least one halogen”
  • At least one H on is replaced by a halogen atom, for example, 1, 2, 3, 4, 5, 6, 7 or 8 H may be replaced by at least one halogen atom selected from fluorine, chlorine, bromine, iodine, and the
  • the C 1-8 alkyl group substituted by at least one halogen has a total of 1-6 carbon atoms, for example, trifluoromethyl, difluoromethyl, monofluoromethyl, monofluoroethyl, difluoromethyl, Fluoroethyl, trifluoroethyl, etc.
  • C 1-6 alkyl substituted by at least one halogen "C 1-4 alkyl substituted by at least one halogen”, “C 1-3 alkyl substituted by at least one halogen”
  • the definition of is similar to the definition of "C 1-8 alkyl substituted by at least one halogen", except that the total number of carbon atoms and/or the number of halogen substituents are different.
  • C 3-20 cycloalkyl means a cycloalkyl group with a total of 3-20 carbon atoms, such as 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, including monocyclic, bicyclic, tricyclic, etc., for example, the bicyclic also includes bicyclic, spiro bicyclic, bridge bicyclic, condensed bicyclic, etc.
  • each ring is independently selected from three-membered rings, four-membered rings, five-membered rings, six-membered rings, seven-membered rings, eight-membered rings, nine-membered rings, ten-membered rings, eleven-membered rings or twelve-membered rings etc.
  • the H in the cycloalkyl group can be arbitrarily substituted or unsubstituted; when the "C 3-20 cycloalkyl" is a substituted C 3-20 cycloalkyl, the substituent is included
  • the total number of carbon atoms in the whole group is 3-20, and the definition for the remaining cycloalkyl groups is similar, only the total number of carbon atoms is different.
  • C 2-10 alkenyl means straight-chain alkenyl and branched alkenyl with a total of 2-10 carbon atoms.
  • the C 2-10 alkenyl can be vinyl, propenyl, butyl alkenyl etc.
  • the definitions for the remaining alkenyl groups are similar, differing only in the total number of carbon atoms.
  • C 6-18 aryl means an aryl group with a total of 6-18 carbon atoms, which contains at least one unsaturated aromatic ring, and may also contain at least two unsaturated aromatic rings, if it contains more than two unsaturated aromatic rings
  • the H in the aryl group can be arbitrarily substituted or unsubstituted by at least one group in the combination A
  • the preferred group in the combination A is: C 1-8 alkyl, halogen, C 1-8 alkyl substituted by at least one halogen, C 1-8 alkoxy, benzyl, phenoxy substituted by at least one halogen, when the "C 6 When -18 aryl" is a substituted C 6-18 aryl, it means "C 6-18 aryl substituted by at least one group in combination A", and the number of carbon atoms of the substituent Not included in the total number of carbon atoms 6-18.
  • a 4-8-membered heterocyclic group containing at least one N atom means a heterocyclic group with a total of 4-8 ring atoms, and contains at least one N ring heteroatom, and the remaining ring atoms are C, including saturated or unsaturated heterocyclic groups.
  • Cyclic group which contains at least one saturated or unsaturated heterocyclic ring, and may also contain at least two saturated or unsaturated heterocyclic rings.
  • each ring contains more than two saturated or unsaturated heterocyclic rings, there is no special limitation on the connection method of each ring , for example, can be pyrrolyl, pyridyl, pyrimidyl, piperidyl, pyrazolyl, etc., and any position that can be substituted in the heterocyclic group can be arbitrarily substituted by at least one group in combination A Or unsubstituted, when the "4-8 membered heterocyclic group containing at least one N atom" is substituted, it means "a 4-8 membered heterocyclic group containing at least one N atom substituted by at least one group in combination A membered heterocyclic group", and the number of atoms of the substituent is not included in the total number of 4-8 ring atoms.
  • 5-7 membered heterocyclic group containing 1-3 N atoms and "5-7-membered heterocyclic group containing 1-3 N atoms substituted by at least one group in combination A” and "containing A 4-8 membered heterocyclic group with at least one N atom” is defined similarly, except that the total number of ring atoms and/or the number of N atoms is different.
  • the first aspect of the present invention provides a diclazuril derivative, which has a structural formula shown in formula (I):
  • R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 are each independently selected from H, C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano.
  • R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 are each independently selected from H, C 1-4 alkyl ,halogen.
  • R 11 , R 12 , R 13 , R 14 , R 15 , and R 19 are each independently selected from H and halogen;
  • R 16 , R 17 , and R 18 are each independently selected from H, halogen, C 1-3 alkyl;
  • R 11 and R 14 are all Cl; R 12 , R 13 , R 15 and R 19 are all H; R 16 , R 17 and R 18 are each independently selected from H, F, Cl, Br and methyl.
  • the diclazuril derivative is any one of the following compounds:
  • the second aspect of the present invention provides a diclazuril derivative, which has a structural formula shown in formula (II):
  • Q is N or C (R 28 );
  • R is selected from a C 6-18 aryl group, a C 6-18 aryl group substituted by at least one group in combination A, a 4-8 membered heterocyclic group containing at least one N atom, a combination A A 4-8-membered heterocyclic group containing at least one N atom substituted by at least one group; the combination A is composed of C 1-8 alkyl, halogen, C 1-8 alkyl substituted by at least one halogen , C 1-8 alkoxy, benzyl, phenoxy substituted by at least one halogen;
  • R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-8 alkyl, C 1-8 alkoxy;
  • R 25 is selected from H,
  • C 1-8 R 26 and R 27 are each independently selected from H, halogen, C 1-8 alkyl, C 1-8 alkoxy, cyano, nitro, C 1 substituted by at least one halogen -8 alkyl, benzyl, CH 3 -C(O)-;
  • R 28 is selected from H, halogen, C 1-8 alkyl, CH 3 -OC(O)-, C 1-8 alkoxy A group, a C 1-8 alkyl group substituted by at least one halogen;
  • Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-10 membered carbocycle.
  • Q is N or C (R 28 );
  • R is selected from C 6-12 aryl group, C 6-12 aryl group substituted by at least one group in combination A, 5-7 membered heterocyclic group containing 1-3 N atoms, combination A A 5-7-membered heterocyclic group containing 1-3 N atoms substituted by at least one group in the group; said combination A is composed of C 1-6 alkyl, halogen, C 1- substituted by at least one halogen 6 alkyl, C 1-6 alkoxy, benzyl, phenoxy substituted by at least one halogen;
  • R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy;
  • R 25 is selected from H, C 1-6 the alkyl group;
  • R 26 and R 27 are each independently selected from H, halogen, C 1-6 alkyl, C 1-6 alkoxy, cyano, nitro, C 1-6 alkane substituted by at least one halogen Base, benzyl, CH 3 -C(O)-;
  • R 28 is selected from H, halogen, C 1-6 alkyl, CH 3 -OC(O)-, C 1-6 alkoxy, consisting of at least A halogen substituted C 1-6 alkyl group;
  • Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered carbocycle.
  • Q is N or C (R 28 );
  • R is selected from phenyl, phenyl substituted by at least one group in combination A, naphthyl, pyrimidinyl, biphenyl, biphenyl substituted by at least one group in combination A, pyrazolyl , pyrazolyl, pyridyl substituted by at least one group in combination A, pyridyl substituted by at least one group in combination A; said combination A is composed of C 1-4 alkyl, halogen, Composed of at least one halogen-substituted C 1-4 alkyl, C 1-4 alkoxy, benzyl, 4-Cl-phenoxy;
  • R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-3 alkyl;
  • R 25 is selected from H, methyl;
  • R 26 and R 27 are each independently selected from H, halogen, C 1-3 alkyl, C 1-3 alkoxy, cyano, nitro, C 1-3 alkyl substituted by at least one halogen, benzyl, CH 3 -C( O)-;
  • R 28 is selected from H, halogen, C 1-3 alkyl, CH 3 -OC(O)-, C 1-3 alkoxy, C 1-3 substituted by at least one halogen alkyl;
  • Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered unsaturated carbocycle.
  • Q is N or C (R 28 );
  • R is selected from phenyl, phenyl substituted by at least one group in combination A, naphthyl, pyrimidinyl, biphenyl, biphenyl substituted by at least one group in combination A, pyrazolyl , pyrazolyl, pyridyl substituted by at least one group in combination A, pyridyl substituted by at least one group in combination A; said combination A is composed of C 1-4 alkyl, halogen, Composed of at least one F-substituted C 1-3 alkyl, methoxy, benzyl, 4-Cl-phenoxy;
  • R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-3 alkyl;
  • R 25 is selected from H, methyl;
  • R 26 and R 27 are each independently selected from H, Cl, Br, C 1-3 alkyl, methoxy, cyano, nitro, C 1-3 alkyl substituted by at least one F, benzyl, CH 3 -C(O)-;
  • R 28 is selected from H, Cl, methyl, CH 3 -OC(O)-, methoxy, C 1-3 alkyl substituted by at least one F;
  • Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered unsaturated carbocycle, and the carbon atom on the bridging atom in the unsaturated carbocycle is an unsaturated carbon atom.
  • the diclazuril derivative is any one of the following compounds:
  • the method for preparing the diclazuril derivatives is not particularly limited in the present invention, and those skilled in the art can prepare them through the characteristics of the structural formula in combination with common knowledge in the field of organic synthesis.
  • the examples of the present invention provide an exemplary Those skilled in the art should not understand the method for preparing the aforementioned diclazuril derivatives as a limitation of the present invention.
  • the fourth aspect of the present invention provides the application of the diclazuril derivative described in any one of the first aspect and the second aspect as a mitochondrial succinate dehydrogenase inhibitor in pesticides.
  • the fifth aspect of the present invention provides the use of the diclazuril derivatives described in any one of the aforementioned first aspect and second aspect in resisting plant diseases.
  • the plant is selected from at least one of cucumber, soybean, wheat, corn, rice, pepper, and potato.
  • the plant diseases mentioned in the present invention include but not limited to plant fungal diseases and plant oomycosis.
  • Plant diseases described in the present invention include but are not limited to at least one of cucumber downy mildew, soybean rust, corn rust and rice sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean gray mold, rice blast A sort of.
  • the plant disease is at least one of cucumber downy mildew, soybean rust, corn rust, cucumber gray mold, cucumber powdery mildew and rice sheath blight.
  • the fifth aspect of the present invention provides a fungicide for resisting plant diseases
  • the active ingredient of the fungicide is the diclazuril derivative described in the first aspect or the second aspect
  • At least one, based on the total weight of the fungicide, the content of the active ingredient is 0.1-100% by weight.
  • the content of the active ingredient is 1-98% by weight. More preferably, the content of the active ingredient is 5-90% by weight.
  • the formulation of the fungicide is at least one selected from the group consisting of hydrated formulations, powders, emulsions, suspensions, emulsifiable concentrates and granules.
  • the reference compound A15 involved below is a compound with excellent activity in CN107459493A, and its structural formula is It is obtained by the method disclosed in CN107459493A, and the purity used for testing is higher than 98wt%.
  • Indazole sulfame purchased from DR, the product number is DRE-C10229000, the purity is 99%.
  • the room temperature described below is 25 ⁇ 1°C.
  • Step b Add the compound (50mmol) shown in formula 1-4, anhydrous methanol (80mL) and concentrated sulfuric acid (98wt%, 2mL) in the 200mL round bottom flask, heat to reflux, stop the reaction after TLC monitoring raw material reaction After most of the solvent was distilled off under reduced pressure, 50 mL of ethyl acetate was added for extraction. The organic phase was washed with saturated sodium bicarbonate solution and saturated brine successively, dried over anhydrous sodium sulfate, filtered with suction, and the solvent was removed to obtain the compound shown in formula 1-5. compound.
  • Step c In a 200mL round bottom flask, add the compound (20mmol) shown in formula 1-5, DMSO (20mL), potassium tert-butoxide (40mmol) and the compound shown in formula 1-6 (3,5-dichloro -4-fluoronitrobenzene, 30mmol), reacted at room temperature for 30 minutes, after the completion of the TLC monitoring reaction, quenched the reaction with water, and extracted three times with ethyl acetate (50mL each time), the organic phases were combined, washed with water and saturated brine successively , dried over anhydrous sodium sulfate, the solvent was removed, and the compound represented by formula 1-7 was obtained by column chromatography.
  • Step d Add the compound (10mmol) shown in formula 1-7, sodium hydroxide solution (20wt%, 20mL) and 1,4-dioxane (20mL) in a 100mL round bottom flask, and react at 65°C , stop reaction after TLC monitors raw material reaction, add ethyl acetate and extract 3 times (every 50mL), organic phase merges, washes with water, saturated saline successively, anhydrous sodium sulfate is dried, removes solvent, and column chromatography obtains formula 1 The compound shown in -8.
  • Step e add compound (20mmol), ammonium chloride (24mmol) and ethanol (90wt%, 100mL) shown in formula 1-8 in 200mL round bottom flask, add reduced iron powder (80mmol) after being heated to reflux, TLC Stop the reaction after monitoring the completion of the raw material reaction, remove the iron filings by suction filtration and wash the filter cake with ethyl acetate, extract the filtrate with ethyl acetate, and obtain the compound shown in formula 1-9 by column chromatography.
  • Step f In a 200mL round bottom flask, add the compound (5mmol), glacial acetic acid (10mL) and concentrated hydrochloric acid (37wt%, 1mL) shown in formula 1-9, control the temperature at 0-5°C, and add sodium nitrite dropwise Aqueous solution (5.5mmol, 1mL water), continue to insulate and stir for 30min after the dropwise addition, add NaOAc (12.5mmol) and the compound (6mmol) shown in formula 1-3, then move the reaction system to room temperature.
  • Step g Add 3 mmol of the compound shown in formula 1-10 and 5 mL of mercaptoacetic acid in a 50 mL round bottom flask, heat to 180 ° C, stop the reaction after TLC monitors the complete conversion of raw materials, cool to room temperature, add saturated NaHCO 3 aqueous solution to neutralize Excessive thioglycolic acid precipitated a large amount of solids, and the crude product of the target compound was obtained by suction filtration. After drying, the compound I-1 was obtained by column chromatography.
  • Compound I-2, Compound I-3, and Compound I-4 can be prepared according to a method similar to Preparation Example 1, and adaptively adjust raw materials according to the structural formula provided by the present invention.
  • Step a Add the compound represented by formula 2-11 (20mmol), anhydrous methanol (80mL) and concentrated sulfuric acid (98wt%, 1mL) into a 200mL round bottom flask, and heat to reflux. The reaction was stopped after the complete reaction of the raw materials was monitored by TLC. Most of the solvent was distilled off under reduced pressure and then extracted with 50 mL of ethyl acetate. The solvent is removed to obtain the compound shown in formula 2-12.
  • Step b Add the compound (9.6mmol), potassium carbonate (16mmol) and DMF (10mL) shown in the formula 2-13 in the 100mL eggplant-shaped bottle, add the compound (8mmol) shown in the formula 2-12 after stirring at room temperature for 30 minutes ), the temperature was raised to 100° C., and the reaction was stopped after TLC monitored the completion of the reaction of the raw materials. After cooling to room temperature, water was added under vigorous stirring, and a large amount of solid was precipitated by suction filtration, and the compound shown in formula 2-14 was obtained.
  • Step c Under nitrogen protection, in a 100mL three-necked flask, add the compound (5mmol) shown in formula 2-14 and anhydrous tetrahydrofuran (20mL), add DIBAL solution (1M in THF, 15mL) dropwise at 0°C, and react at room temperature , TLC monitors that after the reaction of raw materials is completed, quench the reaction with saturated ammonium chloride solution, add 50 mL of ethyl acetate for extraction, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, remove the solvent, and obtain formula 2-15 by column chromatography Compounds shown.
  • Step d Under nitrogen protection, add the compound (4mol), triphenylphosphine (4.8mol) and carbon tetrachloride (20mL) shown in the formula 2-15 into a 50mL two-necked bottle, heat to reflux, and monitor the reaction of raw materials by TLC Stop the reaction after completion, remove the solvent, and obtain the compound shown in formula 2-16 by column chromatography.
  • Step e In a 200mL round bottom flask, add the compound shown in formula 2-17 (6-azauracil, 3mmol), N, O-bistrimethylsilylacetamide (3.6mmol)) and anhydrous acetonitrile (20mL ), after heating to reflux reaction for 3 hours, add compound (3.6mmol) and sodium iodide (0.6mmol) shown in formula 2-16, continue reflux reaction, after TLC monitors that the reaction is complete, cool to room temperature, add 50mL ethyl acetate Extract the ester, combine the organic phases, wash with saturated brine, dry over anhydrous sodium sulfate, and perform column chromatography to obtain compound II-1.
  • Preparation Example 2 is the preparation method of the general formula compound formula (II) of the present invention.
  • the specific target compound of the present invention can be prepared according to a method similar to Preparation Example 2, and adaptively adjust the raw materials according to the structural formula provided by the present invention.
  • This test example is used to illustrate the inhibitory activity test of some specific compounds provided by the present invention on succinate dehydrogenase (SDH).
  • SDH succinate dehydrogenase
  • the enzyme used in the test is succinate dehydrogenase derived from pig heart mitochondria isolated from pig hearts, and the reaction substrates are succinic acid and 2,6-dichloroindophenol sodium (2,6-dichlorophenolindophenol, DCIP).
  • the target compound was dissolved in DMSO and prepared as a 50 mM stock solution, which was diluted with water to a concentration of 10 ⁇ M when used.
  • the test results of this test case are shown in Table 1.
  • Table 1 shows that the compounds of the present invention have good inhibitory activity on SDH derived from porcine heart, which is obviously better than that of the reference compound A15.
  • This test example is used to illustrate the use of some specific compounds provided by the invention to test the fungicidal activity of corn rust and cucumber downy mildew at the living level.
  • the specific test method is:
  • Test of fungicidal activity against cucumber downy mildew the test adopts the seedling pot method.
  • Bactericidal activity test of corn rust the test adopts the seedling pot method.
  • Grade 0 No disease
  • Grade 1 Lesion area accounts for less than 5% of the entire leaf area
  • Grade 3 Lesion area accounts for 6% to 10% of the entire leaf area
  • Grade 5 Lesion area accounts for the entire leaf area 11% to 25% of the area
  • Grade 7 the lesion area accounts for 26% to 50% of the entire leaf area
  • Grade 9 the lesion area accounts for more than 50% of the entire leaf area.
  • disease index before application in CK 0 blank control area disease index after application in CK 1 blank control area
  • disease index before application in PT 0 drug treatment area disease index after application in PT 1 drug treatment area.
  • compound 1-1 of the present invention compound 1-2, compound 1-3, compound 1-4 have all shown relatively to corn rust, cucumber downy mildew at the concentration of 100mg/L. Good control effect.
  • compound I-1, compound I-2, compound I-3, and compound I-4 were all significantly better than the control compound A15 at, for example, 25 mg/L.
  • the compound of the present invention all has good control effect to corn rust and cucumber downy mildew, especially to cucumber downy mildew, most of the compounds are still under the concentration of 6.25mg/L Maintain a control effect of more than 75%.
  • This test example is used to illustrate the use of some compounds with relatively better activity in Table 4 to test the fungicidal activity of cucumber downy mildew at the in vivo level.
  • test method and evaluation method are the same as in Test Example 2.
  • the control ratings are listed in Table 5.
  • the compounds provided by the present invention are effective against plant diseases such as cucumber downy mildew, soybean rust, corn rust, rice sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean gray mold, and rice blast.
  • plant diseases such as cucumber downy mildew, soybean rust, corn rust, rice sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean gray mold, and rice blast.
  • the compound provided by the present invention has better control effect on cucumber downy mildew than the prior art (such as indazole sulfasulfame) at a relatively low concentration.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Environmental Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Plant Pathology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • General Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Health & Medical Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

A diclazuril derivative and an application thereof, as well as a fungicide for combating plant diseases, are disclosed, relating to the field of pesticides and fungicides. The derivative has a structural formula represented by formula (I) or formula (II). The provided compound has significantly better control effects than existing technologies for plant diseases such as cucumber downy mildew, soybean rust, corn rust and rice-sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean botrytis, and rice blast.

Description

地克珠利衍生物及其应用和一种用于抗植物病的杀菌剂Diclazuril derivatives and their application and a fungicide for resisting plant diseases
相关申请的交叉引用Cross References to Related Applications
本申请要求2021年06月16日提交的中国专利申请202110665569.X的权益，该申请的内容通过引用被合并于本文。This application claims the benefit of Chinese patent application 202110665569.X filed on June 16, 2021, the contents of which are incorporated herein by reference.
技术领域technical field
本发明涉及农药杀菌剂领域，具体涉及一种地克珠利衍生物及其应用和一种用于抗植物病的杀菌剂。The invention relates to the field of pesticide fungicides, in particular to a diclazuril derivative and its application and a fungicide for resisting plant diseases.
背景技术Background technique
地克珠利(Diclazuril)是比利时杨森公司于1986年报道的抗球虫药，其结构上属于三嗪苯乙腈类化合物，用于禽类的球虫病，主要用于防治鸡球虫病，兼具高效、广谱、低毒、耐药性低和用量小的优点。Diclazuril (Diclazuril) is an anticoccidial drug reported by Belgian Janssen Company in 1986, which belongs to triazine benzyl cyanide compound in structure, and is used for poultry coccidiosis, mainly for preventing and treating chicken coccidiosis, and concurrently It has the advantages of high efficiency, broad spectrum, low toxicity, low drug resistance and small dosage.
临床试验表明，地克珠利对耐药性的球虫也有非常好的防效。Clinical trials have shown that diclazuril also has a very good control effect on drug-resistant coccidia.
目前，地克珠利的作用机制尚不明确，对其作用机理的研究也只是基于细胞和亚细胞水平。At present, the mechanism of action of diclazuril is not yet clear, and the research on its mechanism of action is only based on the cellular and subcellular levels.
Taylor等报道了地克珠利对感染羔羊的艾美耳球虫的第一代和第二代分裂体和配子体阶段有效，它还能影响球虫核酸的合成。Taylor et al. reported that diclazuril was effective against the first and second generation cleavage and gametophyte stages of Eimeria infecting lambs, and it could also affect the synthesis of coccidia nucleic acid.
在CN107459493A中公开了以下作为杀菌剂使用的具有二苯醚片段的地克珠利衍生物的通式，其对黄瓜霜霉病在200mg/L浓度下表现出较好的防效。具体地，公开了如下所示的化合物在200mg/L浓度下对黄瓜霜霉病表现出100％的防效，但降低浓度后活性显著降低或消失。In CN107459493A, the following general formula of diclazuril derivatives with diphenyl ether fragments used as fungicides is disclosed, which shows better control effect on cucumber downy mildew at a concentration of 200 mg/L. Specifically, it is disclosed that the compounds shown below exhibit 100% control effect on cucumber downy mildew at a concentration of 200 mg/L, but the activity significantly decreases or disappears when the concentration is lowered.
Figure PCTCN2022099231-appb-000001
Figure PCTCN2022099231-appb-000001
发明内容Contents of the invention
本发明的目的是为了提供一种新的地克珠利衍生物，以期该类地克珠利衍生物能够实现明显更高的抗植物病防效。The object of the present invention is to provide a new diclazuril derivative, in the hope that the diclazuril derivative can achieve significantly higher anti-plant disease control effect.
为了实现上述目的，本发明的第一方面提供一种地克珠利衍生物，该衍生物具有式(I)：In order to achieve the above object, the first aspect of the present invention provides a diclazuril derivative, which has the formula (I):
Figure PCTCN2022099231-appb-000002
Figure PCTCN2022099231-appb-000002
其中，在式(I)中，R 11、R 12、R 13、R 14、R 15、R 16、R 17、R 18、R 19各自独立地选自H、C 1-6的烷基、C 1-6的烷氧基、卤素、氰基。 Wherein, in formula (I), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 are each independently selected from H, C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano.
本发明的第二方面提供一种地克珠利衍生物，该衍生物具有式(II)所示的结构式：The second aspect of the present invention provides a kind of diclazuril derivative, and this derivative has the structural formula shown in formula (II):
Figure PCTCN2022099231-appb-000003
Figure PCTCN2022099231-appb-000003
其中，在式(II)中，Wherein, in formula (II),
Q为N或C(R 28)； Q is N or C (R 28 );
R选自C 6-18的芳基、由组合A中的至少一种基团取代的C 6-18的芳基、含至少一个N原子的4-8元杂环基、由组合A中的至少一种基团取代的含至少一个N原子的4-8元杂环基；所述组合A由C 1-8的烷基、卤素、由至少一种卤素取代的C 1-8的烷基、C 1-8的烷氧基、苄基、由至少一种卤素取代的苯氧基组成； R is selected from a C 6-18 aryl group, a C 6-18 aryl group substituted by at least one group in combination A, a 4-8 membered heterocyclic group containing at least one N atom, a combination A A 4-8-membered heterocyclic group containing at least one N atom substituted by at least one group; the combination A is composed of C 1-8 alkyl, halogen, C 1-8 alkyl substituted by at least one halogen , C 1-8 alkoxy, benzyl, phenoxy substituted by at least one halogen;
R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-8的烷基、C 1-8的烷氧基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-8 alkyl, C 1-8 alkoxy;
R 25选自H、C 1-8的烷基； R 25 is selected from H, C 1-8 alkyl;
R 26和R 27各自独立地选自H、卤素、C 1-8的烷基、C 1-8的烷氧基、氰基、硝基、由至少一种卤素取代的C 1-8的烷基、苄基、CH 3-C(O)-； R 26 and R 27 are each independently selected from H, halogen, C 1-8 alkyl, C 1-8 alkoxy, cyano, nitro, C 1-8 alkane substituted by at least one halogen Base, benzyl, CH 3 -C(O)-;
R 28选自H、卤素、C 1-8的烷基、CH 3-O-C(O)-、C 1-8的烷氧基、由至少一种卤素取代的C 1-8的烷基； R 28 is selected from H, halogen, C 1-8 alkyl, CH 3 -OC(O)-, C 1-8 alkoxy, C 1-8 alkyl substituted by at least one halogen;
或者Q为C(R 28)，R 27与R 28一起环合形成5-10元碳环。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-10 membered carbocycle.
本发明的第三方面提供前述第一方面、第二方面的任意一方面中所述的地克珠利衍生物作为线粒体琥珀酸脱氢酶抑制剂在农药中的应用。The third aspect of the present invention provides the use of the diclazuril derivatives described in any one of the first aspect and the second aspect as mitochondrial succinate dehydrogenase inhibitors in pesticides.
本发明的第四方面提供前述第一方面、第二方面的任意一方面中所述的地克珠利衍生物在抗植物病中的应用。The fourth aspect of the present invention provides the application of the diclazuril derivatives described in any one of the aforementioned first aspect and second aspect in resisting plant diseases.
本发明的第五方面提供一种用于抗植物病的杀菌剂，该杀菌剂的活性成分为前述第一方面或第二方面中所述的地克珠利衍生物中的至少一种，以所述杀菌剂的总重量计，所述活性成分的含量为0.1-100重量％。The fifth aspect of the present invention provides a fungicide for resisting plant diseases, the active ingredient of the fungicide is at least one of the diclazuril derivatives described in the first aspect or the second aspect, and Based on the total weight of the bactericide, the content of the active ingredient is 0.1-100% by weight.
本发明提供的化合物针对黄瓜霜霉病、大豆锈病、玉米锈病、水稻纹枯病、小麦白粉病、黄瓜炭疽病、黄瓜白粉病、大豆灰霉病、水稻稻瘟病等植物病均表现出优于对照化合物的防效，具有明显比现有技术(如吡噻菌胺、氰霜唑、吲唑磺菌胺等)更好的防效，具有潜在的商业化价值。The compounds provided by the present invention are superior to plant diseases such as cucumber downy mildew, soybean rust, corn rust, rice sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean gray mold, and rice blast. The control effect of the reference compound is obviously better than that of the prior art (such as penthiopyrad, cyanazazole, indazole sulfamethoxazole, etc.), and has potential commercial value.
特别地，本发明提供的化合物在相对较低浓度下，对黄瓜霜霉病具有更优异的防效。In particular, the compound provided by the invention has better control effect on cucumber downy mildew at a relatively low concentration.
具体实施方式detailed description
在本文中所披露的范围的端点和任何值都不限于该精确的范围或值，这些范围或值应当理解为包含接近这些范围或值的值。对于数值范围来说，各个范围的端点值之间、各个范围的端点值和单独的点值之间，以及单独的点值之间可以彼此组合而得到一个或多个新的数值范围，这些数值范围应被视为在本文中具体公开。Neither the endpoints nor any values of the ranges disclosed herein are limited to such precise ranges or values, and these ranges or values are understood to include values approaching these ranges or values. For numerical ranges, between the endpoints of each range, between the endpoints of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, these values Ranges should be considered as specifically disclosed herein.
“卤素”表示氟元素、氯元素、溴元素和碘元素中的至少一种元素。"Halogen" means at least one element among fluorine, chlorine, bromine and iodine.
“C 1-8的烷基”表示碳原子总数为1-8的烷基，包括直链烷基、支链烷基，例如可以为甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基等。“C 1-6的烷基”、“C 1-4的烷基”、“C 1-3的烷基”的定义与“C 1-8的烷基”的定义相似，不同的是，碳原子总数不同。“C 1-8的烷氧基”的定义与“C 1-8的烷基”的定义相似，不同的是，“C 1-8的烷氧基”通过氧原子与母核结构直接连接，且该C 1-8的烷氧基的碳原子总数为1-8，该C 1-8的烷氧基例如可以表示为-O-R 1，其中，R 1即为该C 1-8的烷氧基中的烷基，示例性地，可以为甲基氧基、乙基氧基、正丙基氧基、异丙基氧基、正丁基氧基、异丁基氧基、叔丁基氧基、正戊基氧基、异戊基氧基、正己基氧基。“C 1-6的烷氧基”、“C 1-4的烷氧基”的定义与“C 1-8的烷氧基”的定义相似，不同的是，碳原子总数不同。“由至少一种卤素取代的C 1-8的烷基”与“C 1-8的烷基”的定义相似，不同的是，“由至少一种卤素取代的C 1-8的烷基”上的至少一个H被卤素原子取代，例如可以有1、2、3、4、5、6、7或8个H由选自氟、氯、溴、碘的至少一种卤素原子取代，且该由至少一种卤素取代的C 1-8的烷基的碳原子总数为1-6，示例性地，可以为三氟甲基、二氟甲基、一氟甲基、一氟乙基、二氟乙基、三氟乙基等。“由至少一种卤素取代的C 1-6的烷基”、“由至少一种卤素取代的C 1-4的烷基”、“由至少一种卤素取代的C 1-3的烷基”的定义与“由至少一种卤素取代的C 1-8的烷基”的定义相似，不同的是，碳原子总数和/或卤素取代基的个数不同。 "C 1-8 alkyl" means an alkyl group with a total of 1-8 carbon atoms, including straight-chain alkyl and branched-chain alkyl, such as methyl, ethyl, n-propyl, isopropyl, n- Butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, etc. The definition of "C 1-6 alkyl", "C 1-4 alkyl", "C 1-3 alkyl" is similar to the definition of "C 1-8 alkyl", the difference is that the carbon The total number of atoms is different. The definition of "C 1-8 alkoxy" is similar to the definition of "C 1-8 alkyl", the difference is that "C 1-8 alkoxy" is directly connected to the parent core structure through an oxygen atom, And the total number of carbon atoms of the C 1-8 alkoxy group is 1-8, the C 1-8 alkoxy group can be expressed as -OR 1 , wherein, R 1 is the C 1-8 alkoxy group The alkyl group in the group can be, for example, methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, tert-butyloxy radical, n-pentyloxy, isopentyloxy, n-hexyloxy. The definitions of "C 1-6 alkoxy" and "C 1-4 alkoxy" are similar to the definitions of "C 1-8 alkoxy", except that the total number of carbon atoms is different. "C 1-8 alkyl substituted by at least one halogen" is similar to the definition of "C 1-8 alkyl", except that "C 1-8 alkyl substituted by at least one halogen" At least one H on is replaced by a halogen atom, for example, 1, 2, 3, 4, 5, 6, 7 or 8 H may be replaced by at least one halogen atom selected from fluorine, chlorine, bromine, iodine, and the The C 1-8 alkyl group substituted by at least one halogen has a total of 1-6 carbon atoms, for example, trifluoromethyl, difluoromethyl, monofluoromethyl, monofluoroethyl, difluoromethyl, Fluoroethyl, trifluoroethyl, etc. "C 1-6 alkyl substituted by at least one halogen", "C 1-4 alkyl substituted by at least one halogen", "C 1-3 alkyl substituted by at least one halogen" The definition of is similar to the definition of "C 1-8 alkyl substituted by at least one halogen", except that the total number of carbon atoms and/or the number of halogen substituents are different.
“C 3-20的环烷基”表示碳原子总数为3-20的环烷基，例如可以为碳原子总数为3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20，包括单环、二环、三环等，例如所述二环还包括联二环、螺二环、桥二环、稠二环等，且各个环各自独立地选自三元环、四元环、五元环、六元环、七元环、八元环、九元环、十元环、十一元环或十二元环等，并且，环烷基中的H可以任意地被取代基取代或者未取代；当所述“C 3-20环烷基”为取代的C 3-20环烷基时，包括取代基在内的整个基团的碳原子总数为3-20，针对其余环烷基的定义与此类似，仅是碳原子总数不同。 "C 3-20 cycloalkyl" means a cycloalkyl group with a total of 3-20 carbon atoms, such as 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, including monocyclic, bicyclic, tricyclic, etc., for example, the bicyclic also includes bicyclic, spiro bicyclic, bridge bicyclic, condensed bicyclic, etc. , and each ring is independently selected from three-membered rings, four-membered rings, five-membered rings, six-membered rings, seven-membered rings, eight-membered rings, nine-membered rings, ten-membered rings, eleven-membered rings or twelve-membered rings etc., and the H in the cycloalkyl group can be arbitrarily substituted or unsubstituted; when the "C 3-20 cycloalkyl" is a substituted C 3-20 cycloalkyl, the substituent is included The total number of carbon atoms in the whole group is 3-20, and the definition for the remaining cycloalkyl groups is similar, only the total number of carbon atoms is different.
“C 2-10的烯基”表示碳原子总数为2-10的直链烯基、支链烯基，示例性地，所述C 2-10的烯基可以为乙烯基、 丙烯基、丁烯基等。针对其余烯基的定义与此类似，仅是碳原子总数不同。 "C 2-10 alkenyl" means straight-chain alkenyl and branched alkenyl with a total of 2-10 carbon atoms. Exemplarily, the C 2-10 alkenyl can be vinyl, propenyl, butyl alkenyl etc. The definitions for the remaining alkenyl groups are similar, differing only in the total number of carbon atoms.
“C 6-18的芳基”表示碳原子总数为6-18的芳基，其中至少含有一个不饱和芳香环，也可以含有至少两个不饱和芳香环，若含有两个以上不饱和芳香环时，对各个环的连接方式没有特别的限定，并且芳基中的H可以任意地被组合A中的至少一种基团取代或者未取代，组合A中优选的基团为：C 1-8的烷基、卤素、由至少一种卤素取代的C 1-8的烷基、C 1-8的烷氧基、苄基、由至少一种卤素取代的苯氧基，当所述“C 6-18的芳基”为取代的C 6-18芳基时，即为“由组合A中的至少一种基团取代的C 6-18的芳基”，且所述取代基的碳原子数不计入碳原子总数6-18中。“C 6-12的芳基”和“由组合A中的至少一种基团取代的C 6-12的芳基”与“C 6-18的芳基”的定义相似，不同的是，碳原子总数不同。 "C 6-18 aryl" means an aryl group with a total of 6-18 carbon atoms, which contains at least one unsaturated aromatic ring, and may also contain at least two unsaturated aromatic rings, if it contains more than two unsaturated aromatic rings When , there is no special limitation on the connection mode of each ring, and the H in the aryl group can be arbitrarily substituted or unsubstituted by at least one group in the combination A, and the preferred group in the combination A is: C 1-8 alkyl, halogen, C 1-8 alkyl substituted by at least one halogen, C 1-8 alkoxy, benzyl, phenoxy substituted by at least one halogen, when the "C 6 When -18 aryl" is a substituted C 6-18 aryl, it means "C 6-18 aryl substituted by at least one group in combination A", and the number of carbon atoms of the substituent Not included in the total number of carbon atoms 6-18. "C 6-12 aryl" and "C 6-12 aryl substituted by at least one group in combination A" have similar definitions to "C 6-18 aryl", except that the carbon The total number of atoms is different.
“含至少一个N原子的4-8元杂环基”表示环原子总数为4-8个的杂环基，且含有至少一个N环杂原子，其余环原子是C，包括饱和或不饱和杂环基，其中至少含有一个饱和或不饱和杂环，也可以含有至少两个饱和或不饱和杂环，若含有两个以上饱和或不饱和杂环时，对各个环的连接方式没有特别的限定，示例性地，可以为吡咯基、吡啶基、嘧啶基、哌啶基、吡唑基等，并且杂环基中任意能够被取代的位置可以任意地被组合A中的至少一种基团取代或者未取代，当所述“含至少一个N原子的4-8元杂环基”被取代时，即为“由组合A中的至少一种基团取代的含至少一个N原子的4-8元杂环基”，且所述取代基的原子数不计入环原子总数4-8中。“含1-3个N原子的5-7元杂环基”和“由组合A中的至少一种基团取代的含1-3个N原子的5-7元杂环基”与“含至少一个N原子的4-8元杂环基”的定义相似，不同的是，环原子总数和/或N原子数不同。"A 4-8-membered heterocyclic group containing at least one N atom" means a heterocyclic group with a total of 4-8 ring atoms, and contains at least one N ring heteroatom, and the remaining ring atoms are C, including saturated or unsaturated heterocyclic groups. Cyclic group, which contains at least one saturated or unsaturated heterocyclic ring, and may also contain at least two saturated or unsaturated heterocyclic rings. If it contains more than two saturated or unsaturated heterocyclic rings, there is no special limitation on the connection method of each ring , for example, can be pyrrolyl, pyridyl, pyrimidyl, piperidyl, pyrazolyl, etc., and any position that can be substituted in the heterocyclic group can be arbitrarily substituted by at least one group in combination A Or unsubstituted, when the "4-8 membered heterocyclic group containing at least one N atom" is substituted, it means "a 4-8 membered heterocyclic group containing at least one N atom substituted by at least one group in combination A membered heterocyclic group", and the number of atoms of the substituent is not included in the total number of 4-8 ring atoms. "5-7 membered heterocyclic group containing 1-3 N atoms" and "5-7-membered heterocyclic group containing 1-3 N atoms substituted by at least one group in combination A" and "containing A 4-8 membered heterocyclic group with at least one N atom" is defined similarly, except that the total number of ring atoms and/or the number of N atoms is different.
第一方面first
如前所述，本发明的第一方面提供了一种地克珠利衍生物，该衍生物具有式(I)所示的结构式：As mentioned above, the first aspect of the present invention provides a diclazuril derivative, which has a structural formula shown in formula (I):
Figure PCTCN2022099231-appb-000004
Figure PCTCN2022099231-appb-000004
其中，在式(I)中，R 11、R 12、R 13、R 14、R 15、R 16、R 17、R 18、R 19各自独立地选自H、C 1-6的烷基、C 1-6的烷氧基、卤素、氰基。 Wherein, in formula (I), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 are each independently selected from H, C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano.
优选地，在式(I)中，R 11、R 12、R 13、R 14、R 15、R 16、R 17、R 18、R 19各自独立地选自H、C 1-4的烷基、卤素。 Preferably, in formula (I), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 are each independently selected from H, C 1-4 alkyl ,halogen.
优选情况下，在式(I)中，R 11、R 12、R 13、R 14、R 15、R 19各自独立地选自H、卤素；R 16、R 17、R 18各自独立地选自H、卤素、C 1-3的烷基； Preferably, in formula (I), R 11 , R 12 , R 13 , R 14 , R 15 , and R 19 are each independently selected from H and halogen; R 16 , R 17 , and R 18 are each independently selected from H, halogen, C 1-3 alkyl;
根据一种特别优选的具体实施方式，在式(I)中，According to a particularly preferred embodiment, in formula (I),
R 11和R 14均为Cl；R 12、R 13、R 15和R 19均为H；R 16、R 17和R 18各自独立地选自H、F、Cl、Br、甲基。 R 11 and R 14 are all Cl; R 12 , R 13 , R 15 and R 19 are all H; R 16 , R 17 and R 18 are each independently selected from H, F, Cl, Br and methyl.
根据另一种特别优选的具体实施方式，所述地克珠利衍生物为以下化合物中的任意一种：According to another particularly preferred embodiment, the diclazuril derivative is any one of the following compounds:
Figure PCTCN2022099231-appb-000005
Figure PCTCN2022099231-appb-000005
第二方面second aspect
如前所述，本发明的第二方面提供了一种地克珠利衍生物，该衍生物具有式(II)所示的结构式：As mentioned above, the second aspect of the present invention provides a diclazuril derivative, which has a structural formula shown in formula (II):
Figure PCTCN2022099231-appb-000006
Figure PCTCN2022099231-appb-000006
其中，在式(II)中，Wherein, in formula (II),
Q为N或C(R 28)； Q is N or C (R 28 );
R选自C 6-18的芳基、由组合A中的至少一种基团取代的C 6-18的芳基、含至少一个N原子的4-8元杂环基、由组合A中的至少一种基团取代的含至少一个N原子的4-8元杂环基；所述组合A由C 1-8的烷基、卤素、由至少一种卤素取代的C 1-8的烷基、C 1-8的烷氧基、苄基、由至少一种卤素取代的苯氧基组成； R is selected from a C 6-18 aryl group, a C 6-18 aryl group substituted by at least one group in combination A, a 4-8 membered heterocyclic group containing at least one N atom, a combination A A 4-8-membered heterocyclic group containing at least one N atom substituted by at least one group; the combination A is composed of C 1-8 alkyl, halogen, C 1-8 alkyl substituted by at least one halogen , C 1-8 alkoxy, benzyl, phenoxy substituted by at least one halogen;
R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-8的烷基、C 1-8的烷氧基；R 25选自H、C 1-8的烷基；R 26和R 27各自独立地选自H、卤素、C 1-8的烷基、C 1-8的烷氧基、氰基、硝基、由至少一种卤素取代的C 1-8的烷基、苄基、CH 3-C(O)-；R 28选自H、卤素、C 1-8的烷基、CH 3-O-C(O)-、C 1-8的烷氧基、由至少一种卤素取代的C 1-8的烷基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-8 alkyl, C 1-8 alkoxy; R 25 is selected from H, C 1-8 R 26 and R 27 are each independently selected from H, halogen, C 1-8 alkyl, C 1-8 alkoxy, cyano, nitro, C 1 substituted by at least one halogen -8 alkyl, benzyl, CH 3 -C(O)-; R 28 is selected from H, halogen, C 1-8 alkyl, CH 3 -OC(O)-, C 1-8 alkoxy A group, a C 1-8 alkyl group substituted by at least one halogen;
或者Q为C(R 28)，且R 27与R 28一起环合形成5-10元碳环。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-10 membered carbocycle.
优选情况下，在式(II)中，Preferably, in formula (II),
Q为N或C(R 28)； Q is N or C (R 28 );
R选自C 6-12的芳基、由组合A中的至少一种基团取代的C 6-12的芳基、含1-3个N原子的5-7元杂环基、由组合A中的至少一种基团取代的含1-3个N原子的5-7元杂环基；所述组合A由C 1-6的烷基、卤素、由至少一种卤素取代的C 1-6的烷基、C 1-6的烷氧基、苄基、由至少一种卤素取代的苯氧基组成； R is selected from C 6-12 aryl group, C 6-12 aryl group substituted by at least one group in combination A, 5-7 membered heterocyclic group containing 1-3 N atoms, combination A A 5-7-membered heterocyclic group containing 1-3 N atoms substituted by at least one group in the group; said combination A is composed of C 1-6 alkyl, halogen, C 1- substituted by at least one halogen 6 alkyl, C 1-6 alkoxy, benzyl, phenoxy substituted by at least one halogen;
R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-6的烷基、C 1-6的烷氧基；R 25选自H、C 1-6的烷基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy; R 25 is selected from H, C 1-6 the alkyl group;
R 26和R 27各自独立地选自H、卤素、C 1-6的烷基、C 1-6的烷氧基、氰基、硝基、由至少一种卤素取代的C 1-6的烷基、苄基、CH 3-C(O)-；R 28选自H、卤素、C 1-6的烷基、CH 3-O-C(O)-、C 1-6的烷氧基、由至少一种卤素取代的C 1-6的烷基； R 26 and R 27 are each independently selected from H, halogen, C 1-6 alkyl, C 1-6 alkoxy, cyano, nitro, C 1-6 alkane substituted by at least one halogen Base, benzyl, CH 3 -C(O)-; R 28 is selected from H, halogen, C 1-6 alkyl, CH 3 -OC(O)-, C 1-6 alkoxy, consisting of at least A halogen substituted C 1-6 alkyl group;
或者Q为C(R 28)，且R 27与R 28一起环合形成5-7元碳环。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered carbocycle.
根据一种特别优选的具体实施方式，在式(II)中，According to a particularly preferred embodiment, in formula (II),
Q为N或C(R 28)； Q is N or C (R 28 );
R选自苯基、由组合A中的至少一种基团取代的苯基、萘基、嘧啶基、联苯基、由组合A中的至少一种基团取代的联苯基、吡唑基、由组合A中的至少一种基团取代的吡唑基、吡啶基、由组合A中的至少一种基团取代的吡啶基；所述组合A由C 1-4的烷基、卤素、由至少一种卤素取代的C 1-4的烷基、C 1-4的烷氧基、苄基、4-Cl-苯氧基组成； R is selected from phenyl, phenyl substituted by at least one group in combination A, naphthyl, pyrimidinyl, biphenyl, biphenyl substituted by at least one group in combination A, pyrazolyl , pyrazolyl, pyridyl substituted by at least one group in combination A, pyridyl substituted by at least one group in combination A; said combination A is composed of C 1-4 alkyl, halogen, Composed of at least one halogen-substituted C 1-4 alkyl, C 1-4 alkoxy, benzyl, 4-Cl-phenoxy;
R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-3的烷基；R 25选自H、甲基；R 26和R 27各自独立地选自H、卤素、C 1-3的烷基、C 1-3的烷氧基、氰基、硝基、由至少一种卤素取代的C 1-3的烷基、苄基、CH 3-C(O)-；R 28选自H、卤素、C 1-3的烷基、CH 3-O-C(O)-、C 1-3的烷氧基、由至少一种卤素取代的C 1-3的烷基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-3 alkyl; R 25 is selected from H, methyl; R 26 and R 27 are each independently selected from H, halogen, C 1-3 alkyl, C 1-3 alkoxy, cyano, nitro, C 1-3 alkyl substituted by at least one halogen, benzyl, CH 3 -C( O)-; R 28 is selected from H, halogen, C 1-3 alkyl, CH 3 -OC(O)-, C 1-3 alkoxy, C 1-3 substituted by at least one halogen alkyl;
或者Q为C(R 28)，且R 27与R 28一起环合形成5-7元不饱和碳环。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered unsaturated carbocycle.
根据另一种特别优选的具体实施方式，在式(II)中，According to another particularly preferred embodiment, in formula (II),
Q为N或C(R 28)； Q is N or C (R 28 );
R选自苯基、由组合A中的至少一种基团取代的苯基、萘基、嘧啶基、联苯基、由组合A中的至少一种基团取代的联苯基、吡唑基、由组合A中的至少一种基团取代的吡唑基、吡啶基、由组合A中的至少一种基团取代的吡啶基；所述组合A由C 1-4的烷基、卤素、由至少一个F取代的C 1-3的烷基、甲氧基、苄基、4-Cl-苯氧基组成； R is selected from phenyl, phenyl substituted by at least one group in combination A, naphthyl, pyrimidinyl, biphenyl, biphenyl substituted by at least one group in combination A, pyrazolyl , pyrazolyl, pyridyl substituted by at least one group in combination A, pyridyl substituted by at least one group in combination A; said combination A is composed of C 1-4 alkyl, halogen, Composed of at least one F-substituted C 1-3 alkyl, methoxy, benzyl, 4-Cl-phenoxy;
R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-3的烷基；R 25选自H、甲基；R 26和R 27各自独立地选自H、Cl、Br、C 1-3的烷基、甲氧基、氰基、硝基、由至少一个F取代的C 1-3的烷基、苄基、CH 3-C(O)-；R 28选自H、Cl、甲基、CH 3-O-C(O)-、甲氧基、由至少一个F取代的C 1-3的烷基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-3 alkyl; R 25 is selected from H, methyl; R 26 and R 27 are each independently selected from H, Cl, Br, C 1-3 alkyl, methoxy, cyano, nitro, C 1-3 alkyl substituted by at least one F, benzyl, CH 3 -C(O)-; R 28 is selected from H, Cl, methyl, CH 3 -OC(O)-, methoxy, C 1-3 alkyl substituted by at least one F;
或者Q为C(R 28)，且R 27与R 28一起环合形成5-7元不饱和碳环，所述不饱和碳环中桥原子上的碳原子为不 饱和碳原子。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered unsaturated carbocycle, and the carbon atom on the bridging atom in the unsaturated carbocycle is an unsaturated carbon atom.
特别优选地，所述地克珠利衍生物为以下化合物中的任意一种：Particularly preferably, the diclazuril derivative is any one of the following compounds:
Figure PCTCN2022099231-appb-000007
Figure PCTCN2022099231-appb-000007
Figure PCTCN2022099231-appb-000008
Figure PCTCN2022099231-appb-000008
Figure PCTCN2022099231-appb-000009
Figure PCTCN2022099231-appb-000009
Figure PCTCN2022099231-appb-000010
Figure PCTCN2022099231-appb-000010
本发明对制备所述地克珠利衍生物的方法没有特别的限制，本领域技术人员可以通过结构式的特征，结合有机合成领域内的公知常识制备获得，本发明的实例部分示例性地提供了制备前述地克珠利衍生物的方法，本领域技术人员不应理解为对本发明的限制。The method for preparing the diclazuril derivatives is not particularly limited in the present invention, and those skilled in the art can prepare them through the characteristics of the structural formula in combination with common knowledge in the field of organic synthesis. The examples of the present invention provide an exemplary Those skilled in the art should not understand the method for preparing the aforementioned diclazuril derivatives as a limitation of the present invention.
第三方面third aspect
如前所述，本发明的第四方面提供了前述第一方面、第二方面的任意一方面中所述的地克珠利衍生物作为线粒体琥珀酸脱氢酶抑制剂在农药中的应用。As mentioned above, the fourth aspect of the present invention provides the application of the diclazuril derivative described in any one of the first aspect and the second aspect as a mitochondrial succinate dehydrogenase inhibitor in pesticides.
第四方面fourth aspect
如前所述，本发明的第五方面提供了前述第一方面、第二方面的任意一方面中所述的地克珠利衍生物在抗植物病中的应用。As mentioned above, the fifth aspect of the present invention provides the use of the diclazuril derivatives described in any one of the aforementioned first aspect and second aspect in resisting plant diseases.
优选地，所述植物选自黄瓜、大豆、小麦、玉米、水稻、辣椒、马铃薯中的至少一种。Preferably, the plant is selected from at least one of cucumber, soybean, wheat, corn, rice, pepper, and potato.
本发明中所述植物病包括但不限于植物真菌病和植物卵菌病。The plant diseases mentioned in the present invention include but not limited to plant fungal diseases and plant oomycosis.
本发明中所述植物病包括但不限于黄瓜霜霉病、大豆锈病、玉米锈病和水稻纹枯病、小麦白粉病、黄瓜炭疽病、黄瓜白粉病、大豆灰霉病、水稻稻瘟病中的至少一种。Plant diseases described in the present invention include but are not limited to at least one of cucumber downy mildew, soybean rust, corn rust and rice sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean gray mold, rice blast A sort of.
优选地，所述植物病为黄瓜霜霉病、大豆锈病、玉米锈病、黄瓜灰霉病、黄瓜白粉病和水稻纹枯病中的至少一种。Preferably, the plant disease is at least one of cucumber downy mildew, soybean rust, corn rust, cucumber gray mold, cucumber powdery mildew and rice sheath blight.
第五方面fifth aspect
如前所述，本发明的第五方面提供了一种用于抗植物病的杀菌剂，该杀菌剂的活性成分为第一方面或第二方面中所述的地克珠利衍生物中的至少一种，以所述杀菌剂的总重量计，所述活性成分的含量为0.1-100重量％。As mentioned above, the fifth aspect of the present invention provides a fungicide for resisting plant diseases, the active ingredient of the fungicide is the diclazuril derivative described in the first aspect or the second aspect At least one, based on the total weight of the fungicide, the content of the active ingredient is 0.1-100% by weight.
优选地，所述活性成分的含量为1-98重量％。更优选地，所述活性成分的含量为5-90重量％。Preferably, the content of the active ingredient is 1-98% by weight. More preferably, the content of the active ingredient is 5-90% by weight.
特别优选地，所述杀菌剂的剂型选自水合剂、粉剂、乳剂、悬浮剂、乳油剂和粒剂中的至少一种。Particularly preferably, the formulation of the fungicide is at least one selected from the group consisting of hydrated formulations, powders, emulsions, suspensions, emulsifiable concentrates and granules.
以下将通过实例对本发明进行详细描述。以下实例中，在没有特别说明的情况下，使用的各种原料均为市售 分析纯。The present invention will be described in detail below by way of examples. In the following examples, unless otherwise specified, all raw materials used are commercially available analytically pure.
以下涉及的对照化合物A15为CN107459493A中活性优异的化合物，其结构式为
Figure PCTCN2022099231-appb-000011
采用CN107459493A中公开的方法获得，并且用于测试的纯度高于98wt％。 The reference compound A15 involved below is a compound with excellent activity in CN107459493A, and its structural formula is
Figure PCTCN2022099231-appb-000011
It is obtained by the method disclosed in CN107459493A, and the purity used for testing is higher than 98wt%.
吲唑磺菌胺：购自DR，货号为DRE-C10229000，纯度为99％。Indazole sulfame: purchased from DR, the product number is DRE-C10229000, the purity is 99%.
在没有特别说明的情况下，以下所述的室温均表示25±1℃。Unless otherwise specified, the room temperature described below is 25±1°C.
制备例1Preparation Example 1
该制备例用来说明化合物I-1的合成：This preparation example is used to illustrate the synthesis of compound I-1:
化合物I-1：
Figure PCTCN2022099231-appb-000012
Compound I-1:
Figure PCTCN2022099231-appb-000012
Figure PCTCN2022099231-appb-000013
Figure PCTCN2022099231-appb-000013
步骤a：在200mL圆底烧瓶中加入式1-1所示的化合物(0.5mol)、式1-2所示的化合物(1mol)和乙酸酐(100mL)，升温至100℃。TLC监测原料反应完全后停止反应，冷至室温，搅拌下倒入异丙醚和石油醚的混合溶液中(v/v＝10:1)，有固体沉淀析出，抽滤并用异丙醚洗涤滤饼，干燥后即得到式1-3所示的化合物。Step a: Add the compound represented by formula 1-1 (0.5 mol), the compound represented by formula 1-2 (1 mol) and acetic anhydride (100 mL) into a 200 mL round bottom flask, and heat up to 100°C. Stop the reaction after TLC monitors that the reaction of the raw materials is complete, cool to room temperature, pour into the mixed solution of isopropyl ether and petroleum ether (v/v=10:1) under stirring, a solid precipitates out, filter with suction and wash the filter with isopropyl ether After drying, the compound shown in formula 1-3 is obtained.
步骤b：在200mL圆底烧瓶中加入式1-4所示的化合物(50mmol)、无水甲醇(80mL)和浓硫酸(98wt％，2mL)，加热至回流，TLC监测原料反应完毕后停止反应，减压蒸馏除去大部分溶剂后加入50mL乙酸乙酯萃取，有机相依次用饱和碳酸氢钠溶液、饱和食盐水洗涤，无水硫酸钠干燥，抽滤，除去溶剂得到式1-5所示的化合物。Step b: Add the compound (50mmol) shown in formula 1-4, anhydrous methanol (80mL) and concentrated sulfuric acid (98wt%, 2mL) in the 200mL round bottom flask, heat to reflux, stop the reaction after TLC monitoring raw material reaction After most of the solvent was distilled off under reduced pressure, 50 mL of ethyl acetate was added for extraction. The organic phase was washed with saturated sodium bicarbonate solution and saturated brine successively, dried over anhydrous sodium sulfate, filtered with suction, and the solvent was removed to obtain the compound shown in formula 1-5. compound.
步骤c：在200mL圆底烧瓶中加入式1-5所示的化合物(20mmol)、DMSO(20mL)、叔丁醇钾(40mmol)和式1-6所示的化合物(3,5-二氯-4-氟硝基苯，30mmol)，室温反应30分钟，TLC监测反应完成后，加水淬灭反应，并用乙酸乙酯萃取三次(每次50mL)，有机相合并，依次用水、饱和食盐水洗涤，无水硫酸钠干燥，除去溶剂，柱层析得到式1-7所示的化合物。Step c: In a 200mL round bottom flask, add the compound (20mmol) shown in formula 1-5, DMSO (20mL), potassium tert-butoxide (40mmol) and the compound shown in formula 1-6 (3,5-dichloro -4-fluoronitrobenzene, 30mmol), reacted at room temperature for 30 minutes, after the completion of the TLC monitoring reaction, quenched the reaction with water, and extracted three times with ethyl acetate (50mL each time), the organic phases were combined, washed with water and saturated brine successively , dried over anhydrous sodium sulfate, the solvent was removed, and the compound represented by formula 1-7 was obtained by column chromatography.
步骤d：在100mL圆底烧瓶中加入式1-7所示的化合物(10mmol)、氢氧化钠溶液(20wt％，20mL)和1,4-二氧六环(20mL)，在65℃下反应，TLC监测原料反应完毕后停止反应，加入乙酸乙酯萃取3次(每次50mL)，有机相合并，依次用水、饱和食盐水洗涤，无水硫酸钠干燥，除去溶剂，柱层析得到式1-8所示的化合物。Step d: Add the compound (10mmol) shown in formula 1-7, sodium hydroxide solution (20wt%, 20mL) and 1,4-dioxane (20mL) in a 100mL round bottom flask, and react at 65°C , stop reaction after TLC monitors raw material reaction, add ethyl acetate and extract 3 times (every 50mL), organic phase merges, washes with water, saturated saline successively, anhydrous sodium sulfate is dried, removes solvent, and column chromatography obtains formula 1 The compound shown in -8.
步骤e：在200mL圆底烧瓶中加入式1-8所示的化合物(20mmol)、氯化铵(24mmmol)和乙醇(90wt％，100mL)，加热至回流后加入还原铁粉(80mmol)，TLC监测原料反应完毕后停止反应，抽滤除去铁屑并用乙 酸乙酯洗涤滤饼，滤液用乙酸乙酯萃取，柱层析得到式1-9所示的化合物。Step e: add compound (20mmol), ammonium chloride (24mmol) and ethanol (90wt%, 100mL) shown in formula 1-8 in 200mL round bottom flask, add reduced iron powder (80mmol) after being heated to reflux, TLC Stop the reaction after monitoring the completion of the raw material reaction, remove the iron filings by suction filtration and wash the filter cake with ethyl acetate, extract the filtrate with ethyl acetate, and obtain the compound shown in formula 1-9 by column chromatography.
步骤f：在200mL圆底烧瓶中加入式1-9所示的化合物(5mmol)、冰醋酸(10mL)和浓盐酸(37wt％，1mL)，控制温度在0-5℃，滴加亚硝酸钠的水溶液(5.5mmol，1mL水)，滴加完毕后继续保温搅拌30min，加入NaOAc(12.5mmol)和式1-3所示的化合物(6mmol)，随后将反应体系移至室温。反应30min后再加入NaOAc(4mmol)，升温至回流，TLC监测原料完全转化后加入8mL浓盐酸(37wt％)，继续反应，TLC监测水解完毕后停止反应，减压除去大部分溶剂后加入50mL水并剧烈搅拌，有大量固体析出，抽滤并用水洗涤滤饼，干燥得到式1-10所示的化合物，不提纯直接进行下一步反应。Step f: In a 200mL round bottom flask, add the compound (5mmol), glacial acetic acid (10mL) and concentrated hydrochloric acid (37wt%, 1mL) shown in formula 1-9, control the temperature at 0-5°C, and add sodium nitrite dropwise Aqueous solution (5.5mmol, 1mL water), continue to insulate and stir for 30min after the dropwise addition, add NaOAc (12.5mmol) and the compound (6mmol) shown in formula 1-3, then move the reaction system to room temperature. After reacting for 30min, add NaOAc (4mmol), heat up to reflux, add 8mL concentrated hydrochloric acid (37wt%) after TLC monitors that the raw material is completely converted, continue the reaction, stop the reaction after TLC monitors that the hydrolysis is complete, remove most of the solvent under reduced pressure and add 50mL of water And vigorously stirred, a large amount of solids precipitated, suction filtered and washed the filter cake with water, and dried to obtain the compound represented by formula 1-10, which was directly carried out to the next reaction without purification.
步骤g：在50mL圆底烧瓶中加入3mmol的式1-10所示的化合物，5mL巯基乙酸，加热至180℃，TLC监测原料完全转化后停止反应，冷却至室温，加入饱和NaHCO 3水溶液中和过量的巯基乙酸，析出大量固体，抽滤得目标化合物粗产品，干燥后柱层析即得化合物I-1。 Step g: Add 3 mmol of the compound shown in formula 1-10 and 5 mL of mercaptoacetic acid in a 50 mL round bottom flask, heat to 180 ° C, stop the reaction after TLC monitors the complete conversion of raw materials, cool to room temperature, add saturated NaHCO 3 aqueous solution to neutralize Excessive thioglycolic acid precipitated a large amount of solids, and the crude product of the target compound was obtained by suction filtration. After drying, the compound I-1 was obtained by column chromatography.
化合物I-2、化合物I-3、化合物I-4可按照制备例1相似的方法进行，并根据本发明提供的结构式进行适应性的调整原料制备得到。Compound I-2, Compound I-3, and Compound I-4 can be prepared according to a method similar to Preparation Example 1, and adaptively adjust raw materials according to the structural formula provided by the present invention.
以下列举前述获得的化合物I-1、化合物I-2、化合物I-3、化合物I-4的核磁数据：The nuclear magnetic data of Compound I-1, Compound I-2, Compound I-3, and Compound I-4 obtained above are listed below:
化合物I-1：m.p.,165.5-167.1℃； 1H NMR(400MHz,DMSO-d 6)δ12.47(s,1H),7.72(s,2H),7.70(s,1H),7.30(t,J＝6.4Hz,2H),7.21(t,J＝6.8Hz,1H),7.15(d,J＝7.6Hz,2H),4.30(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.05,147.73,139.77,137.48,136.95,135.48,134.79,128.72,128.04,126.60,125.38,35.89.HRMS(ESI)理论值C 16H 11Cl 2N 3O 2[M-H] -:346.0150,实测值:346.0134. Compound I-1: mp, 165.5-167.1°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.47(s, 1H), 7.72(s, 2H), 7.70(s, 1H), 7.30(t, J＝6.4Hz, 2H), 7.21(t, J＝6.8Hz, 1H), 7.15(d, J＝7.6Hz, 2H), 4.30(s, 2H). 13 C NMR (100MHz, DMSO-d 6 ) δ157.05, 147.73, 139.77, 137.48, 136.95, 135.48, 134.79, 128.72, 128.04, 126.60, 125.38, 35.89. HRMS (ESI) theoretical value C 16 H 11 Cl 2 N 3 O 2 [MH] - :346.0150, 346.0134.
化合物I-2：m.p.,176.4-177.5℃； 1H NMR(400MHz,DMSO-d 6)δ12.48(s,1H),7.74(s,2H),7.71(s,1H),7.48(d,J＝6.0Hz,1H),7.32(t,J＝8.8Hz,1H),7.14(s,1H),4.30(s,2H). 13C NMR(100MHz,DMSO-d 6)δ158.21,156.84,155.79,147.55,139.92,136.86,135.60,135.57,134.58,134.44,132.62,129.05,128.98,125.19,116.94,116.72,108.08,107.87,34.59.HRMS(ESI)理论值C 16H 9BrCl 2FN 3O 2[M-H] -:441.9161,实测值:441.9142. Compound I-2: mp, 176.4-177.5°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.48(s, 1H), 7.74(s, 2H), 7.71(s, 1H), 7.48(d, J＝6.0Hz, 1H), 7.32(t, J＝8.8Hz, 1H), 7.14(s, 1H), 4.30(s, 2H). 13 C NMR(100MHz, DMSO-d 6 )δ158.21, 156.84, 155.79 , 147.55, 139.92, 136.86, 135.60, 135.57, 134.58, 134.44, 132.62 , 129.05 , 128.98, 125.19, 116.94, 116.72 , 108.08 , 107.87 , 34.59. MH] - :441.9161, measured value: 441.9142.
化合物I-3：m.p.,174.1-175.4℃； 1H NMR(400MHz,DMSO-d 6)δ12.48(s,1H),7.73(s,2H),7.70(s,1H),7.05(t,J＝8.0Hz,2H),4.28(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.01,151.65,151.61,151.55,151.51,149.19,149.15,149.09,149.05,147.70,140.22,139.00,138.85,138.70,137.04,136.54,136.39,136.23,135.13,135.09,135.06,135.01,134.98,134.94,134.83,133.84,125.30,112.64,112.59,112.48,112.43,35.04.HRMS(ESI)理论值C 16H 8Cl 2F 3N 3O 2[M-H] -:399.9868,实测值:399.9851. Compound I-3: mp, 174.1-175.4°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.48(s, 1H), 7.73(s, 2H), 7.70(s, 1H), 7.05(t, J＝8.0Hz, 2H), 4.28(s, 2H). 13 C NMR (100MHz, DMSO-d 6 ) δ157.01, 151.65, 151.61, 151.55, 151.51, 149.19, 149.15, 149.09, 149.05, 147.70, 140.22, 139.00, 138.85,138.70,137.04,136.54,136.39,136.23,135.13,135.09,135.06,135.01,134.98,134.94,134.83,133.84,125.30,112.64,112.59,112.48,112.43,35.04.HRMS(ESI)理论值C 16 H 8 Cl 2 F 3 N 3 O 2 [MH] - : 399.9868, found value: 399.9851.
化合物I-4：m.p.,165.5-167.1℃； 1H NMR(400MHz,DMSO-d 6)δ12.48(s,1H),7.70(s,3H),7.04(d,J＝7.6Hz,1H),6.93(s,1H),6.81(d,J＝7.2Hz,1H),4.21(s,2H),2.16(s,6H). 13C NMR(100MHz,DMSO-d 6)δ156.92,147.61,139.54,136.82,136.23,135.55,134.61,134.23,129.60,129.06,129.01,125.23,125.17,35.39,19.52,18.97.HRMS(ESI)理论值C 18H 15Cl 2N 3O 2[M+H] +:376.0620,实测值:376.0623. Compound I-4: mp, 165.5-167.1°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.48(s, 1H), 7.70(s, 3H), 7.04(d, J=7.6Hz, 1H) ,6.93(s,1H),6.81(d,J＝7.2Hz,1H),4.21(s,2H),2.16(s,6H). 13 C NMR(100MHz,DMSO-d 6 )δ156.92,147.61,139.54 ,136.82,136.23,135.55,134.61,134.23,129.60,129.06,129.01,125.23,125.17,35.39,19.52,18.97. HRMS (ESI) theoretical value C 18 H 15 Cl 2 N 3 O 2 [M+H] + : 376.0620, measured value: 376.0623.
制备例2：Preparation example 2:
该制备例用来说明化合物II-1的合成：This preparation example is used to illustrate the synthesis of compound II-1:
化合物II-1：
Figure PCTCN2022099231-appb-000014
Compound II-1:
Figure PCTCN2022099231-appb-000014
Figure PCTCN2022099231-appb-000015
Figure PCTCN2022099231-appb-000015
步骤a：在200mL圆底烧瓶中加入式2-11所示的化合物(20mmol)，无水甲醇(80mL)和浓硫酸(98wt％，1mL)，加热至回流。TLC监测原料反应完全后停止反应，减压蒸馏除去大部分溶剂后加入50mL乙酸乙酯萃取，有机相依次用饱和碳酸氢钠溶液、饱和食盐水洗涤，无水硫酸钠干燥，抽滤，有机相除去溶剂，即得式2-12所示的化合物。Step a: Add the compound represented by formula 2-11 (20mmol), anhydrous methanol (80mL) and concentrated sulfuric acid (98wt%, 1mL) into a 200mL round bottom flask, and heat to reflux. The reaction was stopped after the complete reaction of the raw materials was monitored by TLC. Most of the solvent was distilled off under reduced pressure and then extracted with 50 mL of ethyl acetate. The solvent is removed to obtain the compound shown in formula 2-12.
步骤b：在100mL茄形瓶中加入式2-13所示的化合物(9.6mmol)、碳酸钾(16mmol)和DMF(10mL)，室温搅拌30分钟后加入式2-12所示的化合物(8mmol)，升温至100℃，TLC监测原料反应完毕后停止反应，冷却至室温，剧烈搅拌下加水，抽滤析出大量固体，即得到式2-14所示的化合物。Step b: Add the compound (9.6mmol), potassium carbonate (16mmol) and DMF (10mL) shown in the formula 2-13 in the 100mL eggplant-shaped bottle, add the compound (8mmol) shown in the formula 2-12 after stirring at room temperature for 30 minutes ), the temperature was raised to 100° C., and the reaction was stopped after TLC monitored the completion of the reaction of the raw materials. After cooling to room temperature, water was added under vigorous stirring, and a large amount of solid was precipitated by suction filtration, and the compound shown in formula 2-14 was obtained.
步骤c：氮气保护下，在100mL三口瓶中，加入式2-14所示的化合物(5mmol)、无水四氢呋喃(20mL)，0℃下滴加DIBAL溶液(1M in THF,15mL)，室温反应，TLC监测原料反应完毕后，用饱和氯化铵溶液淬灭反应，加入50mL乙酸乙酯萃取，有机相用饱和食盐水洗涤，无水硫酸钠干燥，除去溶剂，柱层析得到式2-15所示的化合物。Step c: Under nitrogen protection, in a 100mL three-necked flask, add the compound (5mmol) shown in formula 2-14 and anhydrous tetrahydrofuran (20mL), add DIBAL solution (1M in THF, 15mL) dropwise at 0°C, and react at room temperature , TLC monitors that after the reaction of raw materials is completed, quench the reaction with saturated ammonium chloride solution, add 50 mL of ethyl acetate for extraction, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, remove the solvent, and obtain formula 2-15 by column chromatography Compounds shown.
步骤d：氮气保护下，在50mL两口瓶中加入式2-15所示的化合物(4mol)、三苯基膦(4.8mol)和四氯化碳(20mL)，加热至回流，TLC监测原料反应完毕后停止反应，除去溶剂，柱层析得到式2-16所示的化合物。Step d: Under nitrogen protection, add the compound (4mol), triphenylphosphine (4.8mol) and carbon tetrachloride (20mL) shown in the formula 2-15 into a 50mL two-necked bottle, heat to reflux, and monitor the reaction of raw materials by TLC Stop the reaction after completion, remove the solvent, and obtain the compound shown in formula 2-16 by column chromatography.
步骤e：在200mL圆底烧瓶中加入式2-17所示的化合物(6-氮杂尿嘧啶，3mmol)、N,O-双三甲硅基乙酰胺(3.6mmol))和无水乙腈(20mL)，加热至回流反应3小时后，加入式2-16所示的化合物(3.6mmol)和碘化钠(0.6mmol)，继续回流反应，TLC监测反应完成后，冷却至室温，加入50mL乙酸乙酯萃取，有机相合并，用饱和食盐水洗涤，无水硫酸钠干燥，柱层析即得到化合物II-1。Step e: In a 200mL round bottom flask, add the compound shown in formula 2-17 (6-azauracil, 3mmol), N, O-bistrimethylsilylacetamide (3.6mmol)) and anhydrous acetonitrile (20mL ), after heating to reflux reaction for 3 hours, add compound (3.6mmol) and sodium iodide (0.6mmol) shown in formula 2-16, continue reflux reaction, after TLC monitors that the reaction is complete, cool to room temperature, add 50mL ethyl acetate Extract the ester, combine the organic phases, wash with saturated brine, dry over anhydrous sodium sulfate, and perform column chromatography to obtain compound II-1.
制备例2为本发明通式化合物式(II)的制备方法，本发明的具体目标化合物可按照制备例2相似的方法进行，并根据本发明提供的结构式进行适应性的调整原料制备得到。Preparation Example 2 is the preparation method of the general formula compound formula (II) of the present invention. The specific target compound of the present invention can be prepared according to a method similar to Preparation Example 2, and adaptively adjust the raw materials according to the structural formula provided by the present invention.
以下列举前述获得的化合物II-1至化合物II-75的核磁数据：The nuclear magnetic data of compound II-1 to compound II-75 obtained above are listed below:
化合物II-1：m.p.,140.7-141.0℃； 1H NMR(400MHz,DMSO-d 6)δ12.22(s,1H),7.58(s,2H),7.52(s,1H),7.05(d,J＝8.0Hz,1H),6.64(d,J＝2.4Hz,1H),6.43(dd,J＝8.8,2.8Hz,1H),5.07(s,2H),2.16(s,3H),2.14(s,3H). 13C NMR(100MHz,DMSO-d 6)δ157.47,154.51,148.68,145.61,138.26,136.65,136.35,130.69,130.66,128.93,128.79,115.80,111.47,52.00,19.69,18.61.HRMS(ESI)理论值C 18H 15Cl 2N 3O 3[M-H] -:390.0412,实测值:390.0435. Compound II-1: mp, 140.7-141.0°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.22(s, 1H), 7.58(s, 2H), 7.52(s, 1H), 7.05(d, J＝8.0Hz, 1H), 6.64(d, J＝2.4Hz, 1H), 6.43(dd, J＝8.8, 2.8Hz, 1H), 5.07(s, 2H), 2.16(s, 3H), 2.14( s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ157.47,154.51,148.68,145.61,138.26,136.65,136.35,130.69,130.66,128.93,128.79,115.80,1161.47,52.090,19(MS ESI) theoretical value C 18 H 15 Cl 2 N 3 O 3 [MH] - : 390.0412, measured value: 390.0435.
化合物II-2：m.p.,106.8-108.2℃； 1H NMR(400MHz,DMSO-d 6)δ12.21(s,1H),7.53(d,J＝1.6Hz,1H),7.50(d,J＝1.6Hz,1H),7.26(dd,J＝8.4,2.0Hz,1H),7.12(d,J＝8.0Hz,1H),6.95(d,J＝8.4Hz,1H),6.80(d,J＝2.4Hz,1H),6.67(dd,J＝8.4,2.4Hz,1H),5.01(s,2H),2.18(s,6H). 13C NMR(100MHz,DMSO-d 6)δ157.14,154.09,151.74,148.36,138.32,136.16,133.15,131.71,130.77,129.99,128.18,124.00,120.13,119.14,115.19,52.17,19.51,18.64.HRMS(ESI)理论值C 18H 16ClN 3O 3[M-H] -:356.0802,实测值:356.0830. Compound II-2: mp, 106.8-108.2°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.21(s, 1H), 7.53(d, J=1.6Hz, 1H), 7.50(d, J= 1.6Hz, 1H), 7.26(dd, J=8.4, 2.0Hz, 1H), 7.12(d, J=8.0Hz, 1H), 6.95(d, J=8.4Hz, 1H), 6.80(d, J= 2.4Hz, 1H), 6.67(dd, J＝8.4, 2.4Hz, 1H), 5.01(s, 2H), 2.18(s, 6H). 13 C NMR(100MHz, DMSO-d 6 ) δ157.14, 154.09, 151.74 , 148.36, 138.32 , 136.16 , 133.15 , 131.71 , 130.77, 129.99, 128.18, 124.00, 120.13 , 119.14, 115.19, 52.17, 19.51, 18.64. 356.0802, measured value: 356.0830.
化合物II-3：m.p.,134.3-135.8℃； 1H NMR(400MHz,DMSO-d 6)δ12.21(s,1H),7.59(s,2H),7.52(s,1H),7.08(s,1H),6.84(d,J＝8.4Hz,1H),6.14(d,J＝8.0Hz,1H),5.07(s,2H),2.32(s,3H),2.21(s,3H). 13C NMR(100MHz,DMSO-d 6)δ157.28,152.39,148.51,146.12,136.53,136.10,131.95,131.41,128.66,128.64,127.23,125.46,111.87, 51.85,20.11,15.83.HRMS(ESI)理论值C 18H 15Cl 2N 3O 3[M-H] -:390.0412,实测值:390.0425. Compound II-3: mp, 134.3-135.8°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.21(s, 1H), 7.59(s, 2H), 7.52(s, 1H), 7.08(s, 1H), 6.84(d, J=8.4Hz, 1H), 6.14(d, J=8.0Hz, 1H), 5.07(s, 2H), 2.32(s, 3H), 2.21(s, 3H). 13 C NMR(100MHz,DMSO-d 6 )δ157.28,152.39,148.51,146.12,136.53,136.10,131.95,131.41,128.66,128.64,127.23,125.46,111.87, 51.85,20.11,15.88 H I MS (ESI) 15 Cl 2 N 3 O 3 [MH] - : 390.0412, found value: 390.0425.
化合物II-4：m.p.,152.4-153.7℃； 1H NMR(400MHz,DMSO-d 6)δ12.20(s,1H),7.61(s,2H),7.53(s,1H),7.33(t,J＝8.0Hz,2H),7.07(t,J＝7.2Hz,1H),6.80(d,J＝8.0Hz,2H),5.08(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.25,156.23,148.48,145.23,136.53,136.45,130.00,128.72,128.69,122.75,114.54,51.80.HRMS(ESI)理论值C 16H 11Cl 2N 3O 3[M-H] -:362.0099,实测值:362.0112. Compound II-4: mp, 152.4-153.7°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.20(s, 1H), 7.61(s, 2H), 7.53(s, 1H), 7.33(t, J＝8.0Hz, 2H), 7.07(t, J＝7.2Hz, 1H), 6.80(d, J＝8.0Hz, 2H), 5.08(s, 2H). 13 C NMR (100MHz, DMSO-d 6 ) δ157.25, 156.23, 148.48, 145.23, 136.53, 136.45, 130.00, 128.72, 128.69, 122.75, 114.54, 51.80. HRMS (ESI) theoretical value C 16 H 11 Cl 2 N 3 O 3 [MH] - :362.0099, 362.0112.
化合物II-5：m.p.,141.6-142.9℃； 1H NMR(400MHz,DMSO-d 6)δ12.20(s,1H),7.63(s,2H),7.52(d,J＝2.0Hz,1H),7.37(t,J＝8.0Hz,1H),7.16(dd,J＝7.2,0.8Hz,1H),6.93(t,J＝2.0Hz,1H),6.79–6.74(m,1H),5.09(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.40,157.04,148.63,144.82,137.01,136.66,134.29,131.70,128.94,128.62,123.15,115.02,113.52,51.99,40.15,39.94,39.73,39.52,39.31,39.10,38.89.HRMS(ESI)理论值C 16H 10Cl 3N 3O 3[M-H] -:395.9709,实测值:395.9728. Compound II-5: mp, 141.6-142.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.20(s, 1H), 7.63(s, 2H), 7.52(d, J=2.0Hz, 1H) ,7.37(t,J=8.0Hz,1H),7.16(dd,J=7.2,0.8Hz,1H),6.93(t,J=2.0Hz,1H),6.79–6.74(m,1H),5.09( s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ157.40,157.04,148.63,144.82,137.01,136.66,134.29,131.70,128.94,128.62,123.15,115.02,113.52,51.97359,39,49 39.52, 39.31, 39.10, 38.89. HRMS (ESI) theoretical value C 16 H 10 Cl 3 N 3 O 3 [MH] - : 395.9709, found value: 395.9728.
化合物II-6：m.p.,178.6-179.8℃； 1H NMR(400MHz,DMSO-d 6)δ12.21(s,1H),7.60(s,2H),7.53(s,1H),7.15(d,J＝7.6Hz,1H),6.78(d,J＝7.6Hz,1H),6.08(s,1H),5.08(s,2H),2.31(s,3H),2.13(s,3H). 13C NMR(100MHz,DMSO-d 6)δ157.28,154.27,148.52,145.92,136.55,136.48,136.15,131.13,128.63,128.59,123.26,122.70,112.47,51.84,20.74,15.52.HRMS(ESI)理论值C 18H 15Cl 2N 3O 3[M-H] -:390.0412,实测值:390.0428. Compound II-6: mp, 178.6-179.8°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.21(s, 1H), 7.60(s, 2H), 7.53(s, 1H), 7.15(d, J＝7.6Hz, 1H), 6.78(d, J＝7.6Hz, 1H), 6.08(s, 1H), 5.08(s, 2H), 2.31(s, 3H), 2.13(s, 3H). 13 C NMR(100MHz,DMSO-d 6 ) δ157.28,154.27,148.52,145.92,136.55,136.48,136.15,131.13,128.63,128.59,123.26,122.70,112.47,51.84,20.74,15.58 HRC theoretical value. 15 Cl 2 N 3 O 3 [MH] - : 390.0412, found value: 390.0428.
化合物II-7：m.p.,149.8-151.3℃； 1H NMR(400MHz,DMSO-d 6)δ12.22(s,1H),7.51(s,1H),7.29(d,J＝8.8Hz,2H),7.07(d,J＝8.4Hz,1H),6.76(d,J＝2.4Hz,1H),6.61(dd,J＝8.0,2.4Hz,1H),5.05(s,2H),2.17(s,3H),2.15(s,3H). 13C NMR(100MHz,DMSO-d 6)δ157.32,156.63,156.58,155.42,154.16,154.11,148.54,138.19,136.59,135.48,135.40,135.32,130.99,130.61,129.83,129.68,129.53,115.97,112.14,112.08,111.97,111.91,111.82,52.16,19.55,18.54.HRMS(ESI)理论值C 18H 15F 2N 3O 3[M+Na] +:382.0979,实测值:382.0980. Compound II-7: mp, 149.8-151.3°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.22(s, 1H), 7.51(s, 1H), 7.29(d, J=8.8Hz, 2H) ,7.07(d,J=8.4Hz,1H),6.76(d,J=2.4Hz,1H),6.61(dd,J=8.0,2.4Hz,1H),5.05(s,2H),2.17(s, 3H),2.15(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ157.32,156.63,156.58,155.42,154.16,154.11,148.54,138.19,136.59,135.48,135.40,135.31,310.96 , 129.68, 129.53, 115.97, 112.14, 112.08, 111.97, 111.91, 111.82, 52.16, 19.55, 18.54. HRMS (ESI) theoretical value C 18 H 15 F 2 N 3 O 3 [M+Na] + : 382.0979, measured value :382.0980.
化合物II-8：m.p.,154.5-155.6℃； 1H NMR(400MHz,DMSO-d 6)δ12.22(s,1H),7.60(s,2H),7.53(s,1H),7.34(d,J＝8.8Hz,2H),6.71(d,J＝8.8Hz,2H),5.08(s,2H),1.25(s,9H). 13C NMR(100MHz,DMSO-d 6)δ157.29,154.08,148.52,145.51,144.99,136.55,136.37,128.82,128.71,126.68,114.03,51.87,33.98,31.30.HRMS(ESI)理论值C 20H 19Cl 2N 3O 3[M+H] +:420.0882,实测值:420.0898. Compound II-8: mp, 154.5-155.6°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.22(s, 1H), 7.60(s, 2H), 7.53(s, 1H), 7.34(d, J＝8.8Hz, 2H), 6.71(d, J＝8.8Hz, 2H), 5.08(s, 2H), 1.25(s, 9H). 13 C NMR (100MHz, DMSO-d 6 ) δ157.29, 154.08, 148.52 , 145.51, 144.99, 136.55, 136.37, 128.82, 128.71, 126.68, 114.03, 51.87, 33.98, 31.30. HRMS (ESI) theoretical value C 20 H 19 Cl 2 N 3 O 3 [M+H] + : 420.0882, measured value :420.0898.
化合物II-9：m.p.,209.8-211.0℃； 1H NMR(400MHz,DMSO-d 6)δ12.22(s,1H),7.65(s,2H),7.58(dd,J＝8.0,1.6Hz,1H),7.53(s,1H),7.23(td,J＝8.4,1.6Hz,1H),7.11(td,J＝7.6,1.2Hz,1H),6.50(dd,J＝8.4,1.2Hz,1H),5.09(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.31,151.52,148.54,145.03,136.95,136.59,130.82,128.81,128.58,128.35,124.07,121.19,114.28,51.85.HRMS(ESI)理论值C 16H 10Cl 3N 3O 3[M-H] -:395.9709,实测值:395.9731. Compound II-9: mp, 209.8-211.0°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.22(s, 1H), 7.65(s, 2H), 7.58(dd, J=8.0, 1.6Hz, 1H),7.53(s,1H),7.23(td,J=8.4,1.6Hz,1H),7.11(td,J=7.6,1.2Hz,1H),6.50(dd,J=8.4,1.2Hz,1H ),5.09(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ157.31,151.52,148.54,145.03,136.95,136.59,130.82,128.81,128.58,128.35,124.07,121.19,114.85.5MS(HR ESI) theoretical value C 16 H 10 Cl 3 N 3 O 3 [MH] - : 395.9709, measured value: 395.9731.
化合物II-10：m.p.,164.5-166.4℃； 1H NMR(400MHz,DMSO-d 6)δ12.21(s,1H),7.63(s,2H),7.53(d,J＝2.0Hz,1H),7.39(d,J＝8.8Hz,2H),6.85(d,J＝8.8Hz,2H),5.08(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.26,155.03,148.49,144.97,136.78,136.55,129.86,128.76,128.53,126.64,116.43,51.80.HRMS(ESI)理论值C 16H 10Cl 3N 3O 3[M-H] -:395.9709,实测值:395.9719. Compound II-10: mp, 164.5-166.4°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.21(s, 1H), 7.63(s, 2H), 7.53(d, J=2.0Hz, 1H) ,7.39(d,J=8.8Hz,2H),6.85(d,J=8.8Hz,2H),5.08(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ157.26,155.03,148.49,144.97 ,136.78,136.55,129.86,128.76,128.53,126.64,116.43,51.80. HRMS (ESI) theoretical value C 16 H 10 Cl 3 N 3 O 3 [MH] - : 395.9709, measured value: 395.9719.
化合物II-11：m.p.,180.4-181.3℃； 1H NMR(400MHz,DMSO-d 6)δ12.21(s,1H),7.63(s,2H),7.53(d,J＝2.0Hz,1H),7.35(t,J＝8.8Hz,1H),7.23(dd,J＝5.6,3.2Hz,1H),6.85(dt,J＝8.8,3.6Hz,1H),5.08(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.29,155.41,153.03,152.75,152.72,148.52,144.87,136.99,136.57,128.87,128.46,119.32,117.75,117.50,115.52,115.44,108.92,108.69,51.84.HRMS(ESI)理论值C 16H 9BrCl 2N 3O 3[M+H] +:459.9267,实测值:459.9288. Compound II-11: mp, 180.4-181.3°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.21(s, 1H), 7.63(s, 2H), 7.53(d, J=2.0Hz, 1H) ,7.35(t,J=8.8Hz,1H),7.23(dd,J= 5.6,3.2Hz ,1H),6.85(dt,J=8.8,3.6Hz,1H),5.08(s,2H). NMR(100MHz,DMSO-d 6 )δ157.29,155.41,153.03,152.75,152.72,148.52,144.87,136.99,136.57,128.87,128.46,119.32,117.75,117.50,115.52,115.44,108.92,108.69,51.84.HRMS(ESI ) theoretical value C 16 H 9 BrCl 2 N 3 O 3 [M+H] + : 459.9267, measured value: 459.9288.
化合物II-12：m.p.,156.9-158.0℃； 1H NMR(400MHz,DMSO-d 6)δ12.22(s,1H),7.64(s,2H),7.53(d,J＝2.4Hz,1H),6.97(dd,J＝8.8,5.6Hz,2H),5.08(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.25,152.11,152.06,152.01,151.95,151.90,151.87,151.78,151.75,151.66,151.64,149.65,149.60,149.55,149.49,148.49,144.32,137.25,136.54,136.34,136.18,134.07,133.91,133.76,128.93,128.32,100.65,100.58,100.47,100.41,51.76.HRMS(ESI)理论值C 16H 8Cl 2F 3N 3O 3[M] +:416.9895,实测值:416.9893. Compound II-12: mp, 156.9-158.0°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.22(s, 1H), 7.64(s, 2H), 7.53(d, J=2.4Hz, 1H) ,6.97(dd,J＝8.8,5.6Hz,2H),5.08(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ157.25,152.11,152.06,152.01,151.95,151.90,151.87,151.78,151.75 ,151.66,151.64,149.65,149.60,149.55,149.49,148.49,144.32,137.25,136.54,136.34,136.18,134.07,133.91,133.76,128.93,128.32,100.65,100.58,100.47,100.41,51.76.HRMS(ESI)理论Value C 16 H 8 Cl 2 F 3 N 3 O 3 [M] + : 416.9895, found value: 416.9893.
化合物II-13：m.p.,149.5-150.6℃； 1H NMR(400MHz,DMSO-d 6)δ12.23(s,1H),8.07(d,J＝1.6Hz,1H),7.69(s,2H),7.63(dd,J＝8.4,1.6Hz,1H),7.54(d,J＝2.0Hz,1H),6.74(d,J＝8.8Hz,1H),5.11(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.28,154.22,148.50,144.29,137.59,136.61,128.82,128.13,128.09,128.06,126.13,126.09,125.11,124.78,124.67,124.45,124.12,122.09,121.96,114.84,51.77.HRMS(ESI)理论值C 17H 9Cl 3F 3N 3O 3[M] +:464.9662,实测值:464.9657. Compound II-13: mp, 149.5-150.6°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.23(s, 1H), 8.07(d, J=1.6Hz, 1H), 7.69(s, 2H) , 7.63(dd, J=8.4, 1.6Hz, 1H), 7.54(d, J=2.0Hz, 1H), 6.74(d, J=8.8Hz, 1H), 5.11(s, 2H). 13 C NMR( 100MHz,DMSO-d 6 )δ157.28,154.22,148.50,144.29,137.59,136.61,128.82,128.13,128.09,128.06,126.13,126.09,125.11,124.78,124.67,124.45,124.12,122.09,121.96,114.84,51.77.HRMS (ESI) theoretical value C 17 H 9 Cl 3 F 3 N 3 O 3 [M] + : 464.9662, found value: 464.9657.
化合物II-14：m.p.,178.9-181.2℃； 1H NMR(400MHz,DMSO-d 6)δ12.23(s,1H),7.73(d,J＝8.8Hz,2H),7.66(s,2H),7.53(s,1H),7.03(d,J＝8.4Hz,2H),5.10(s,2H). 13C NMR(100MHz,DMSO-d 6)δ158.84,157.28,148.51,144.52,137.12,136.58,128.78,128.44,127.66,127.63,125.53,124.04,123.72,123.40,123.08,122.83,120.13,115.32,51.80.HRMS(ESI)理论值C 17H 10Cl 2F 3N 3O 3[M] +:431.0051,实测值:431.0048. Compound II-14: mp, 178.9-181.2°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.23(s, 1H), 7.73(d, J=8.8Hz, 2H), 7.66(s, 2H) ,7.53(s,1H),7.03(d,J=8.4Hz,2H),5.10(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ158.84,157.28,148.51,144.52,137.12,136.58, 128.78, 128.44, 127.66, 127.63, 125.53, 124.04, 123.72, 123.40, 123.08, 122.83, 120.13, 115.32, 51.80. HRMS (ESI) theoretical value C 17 H 10 Cl 2 F 3 N 3 O 3 [M] + 0 5 : , measured value: 431.0048.
化合物II-15：m.p.,194.2-195.4℃； 1H NMR(600MHz,DMSO-d 6)δ12.24(s,1H),7.96(d,J＝9.0Hz,1H),7.89(d,J＝8.4Hz,1H),7.79(d,J＝7.8Hz,1H),7.67(s,2H),7.55(s,1H),7.46(t,J＝7.8Hz,1H),7.41(t,J＝7.2Hz,1H),7.30(d,J＝8.4Hz,1H),7.01(s,1H),5.12(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.30,154.15,148.56,145.31,136.59,133.76,130.34,129.50,128.80,128.73,127.67,126.97,126.88,124.67,117.07,108.58,51.85.HRMS(ESI)理论值C 20H 13Cl 2F 3N 3O 3[M] +:412.0256,实测值:412.0280. Compound II-15: mp, 194.2-195.4°C; 1 H NMR (600MHz, DMSO-d 6 ) δ12.24(s, 1H), 7.96(d, J=9.0Hz, 1H), 7.89(d, J= 8.4Hz, 1H), 7.79(d, J=7.8Hz, 1H), 7.67(s, 2H), 7.55(s, 1H), 7.46(t, J=7.8Hz, 1H), 7.41(t, J= 7.2Hz, 1H), 7.30(d, J＝8.4Hz, 1H), 7.01(s, 1H), 5.12(s, 2H). 13 C NMR(100MHz, DMSO-d 6 ) δ157.30, 154.15, 148.56, 145.31 ,136.59,133.76,130.34,129.50,128.80,128.73,127.67,126.97,126.88,124.67,117.07,108.58,51.85. HRMS (ESI) theoretical value C 20 H 13 Cl 2 F 3 N 3 O 3 [M] + 412.0256, measured value: 412.0280.
化合物II-16：m.p.,134.1-135.2℃； 1H NMR(600MHz,DMSO-d 6)δ12.22(s,1H),7.61(s,2H),7.53(s,1H),7.21(t,J＝8.4Hz,1H),6.66(d,J＝8.4Hz,1H),6.44(s,1H),6.25(d,J＝7.8Hz,1H),5.08(s,2H),3.73(s,3H). 13C NMR(100MHz,DMSO-d 6)δ160.78,157.40,157.29,148.53,145.22,136.55,136.52,130.54,128.75,128.72,108.28,106.32,101.38,55.35,51.87.HRMS(ESI)理论值C 17H 13Cl 2N 3O 4[M+H] +:394.0361,实测值:394.0388. Compound II-16: mp, 134.1-135.2°C; 1 H NMR (600MHz, DMSO-d 6 ) δ12.22(s, 1H), 7.61(s, 2H), 7.53(s, 1H), 7.21(t, J＝8.4Hz, 1H), 6.66(d, J＝8.4Hz, 1H), 6.44(s, 1H), 6.25(d, J＝7.8Hz, 1H), 5.08(s, 2H), 3.73(s, 3H). 13 C NMR (100MHz, DMSO-d 6 ) δ160.78, 157.40, 157.29, 148.53, 145.22, 136.55, 136.52, 130.54, 128.75, 128.72, 108.28, 106.32, 101.38, 55.37. C 17 H 13 Cl 2 N 3 O 4 [M+H] + : 394.0361, Found: 394.0388.
化合物II-17：m.p.,141.2-142.3℃； 1H NMR(400MHz,DMSO-d 6)δ12.24(s,1H),7.74(d,J＝7.6Hz,2H),7.54(s,1H),7.36(d,J＝9.2Hz,2H),7.16(d,J＝7.6Hz,2H),5.09(s,2H). 13C NMR(100MHz,DMSO-d 6)δ159.67,157.28,156.20,156.16,153.73,153.68,148.50,136.60,136.49,136.41,128.60,128.45,128.29,128.18,127.67,127.63,125.48,124.36,124.04,123.72,123.40,122.78,115.50,112.25,112.20,112.08,112.03,52.07.HRMS(ESI)理论值C 17H 10F 5N 3O 3[M+H] +:400.2850,实测值:400.2868. Compound II-17: mp, 141.2-142.3°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.24(s, 1H), 7.74(d, J=7.6Hz, 2H), 7.54(s, 1H) ,7.36(d,J=9.2Hz,2H),7.16(d,J=7.6Hz,2H),5.09(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ159.67,157.28,156.20,156.16 ,153.73,153.68,148.50,136.60,136.49,136.41,128.60,128.45,128.29,128.18,127.67,127.63,125.48,124.36,124.04,123.72,123.40,122.78,115.50,112.25,112.20,112.08,112.03,52.07.HRMS (ESI) Theoretical value C 17 H 10 F 5 N 3 O 3 [M+H] + : 400.2850, found value: 400.2868.
化合物II-18：m.p.,141.6-142.7℃； 1H NMR(400MHz,DMSO-d 6O)δ12.25(s,1H),7.75(d,J＝9.2Hz,2H),7.72(s,1H),7.53(s,1H),7.42(d,J＝8.4Hz,1H),7.26(d,J＝8.4Hz,1H),7.06(d,J＝8.4Hz,2H),5.07(s,2H). 13C NMR(100MHz,DMSO-d 6)δ159.81,157.15,150.57,148.39,136.26,135.66,133.13,129.18,128.28,127.59,127.56,127.52,127.48,125.58,123.95,123.63,123.31,122.99,122.89,122.70,116.94,115.10,52.03.HRMS(ESI)理论值C 17H 11BrF 3N 3O 3[M+Na] +:463.9834,实测值:463.9858. Compound II-18: mp, 141.6-142.7°C; 1 H NMR (400MHz, DMSO-d 6 O) δ12.25(s, 1H), 7.75(d, J=9.2Hz, 2H), 7.72(s, 1H ),7.53(s,1H),7.42(d,J=8.4Hz,1H),7.26(d,J=8.4Hz,1H),7.06(d,J=8.4Hz,2H),5.07(s,2H ). 13 C NMR(100MHz,DMSO-d 6 )δ159.81,157.15,150.57,148.39,136.26,135.66,133.13,129.18,128.28,127.59,127.56,127.52,127.48,125.58,123.95,123.63,123.31,122.99,122.89 , 122.70, 116.94, 115.10, 52.03. HRMS (ESI) theoretical value C 17 H 11 BrF 3 N 3 O 3 [M+Na] + : 463.9834, measured value: 463.9858.
化合物II-19：m.p.,146.8-148.1℃； 1H NMR(400MHz,DMSO-d 6)δ12.24(s,1H),7.73(d,J＝8.4Hz,2H),7.53(s,1H),7.42(d,J＝11.2Hz,1H),7.32(t,J＝8.4Hz,1H),7.23(d,J＝8.4Hz,1H),7.12(d,J＝8.4Hz,2H),5.07(s,2H). 13C NMR(100MHz,DMSO-d 6)δ160.15,157.26,154.87,152.41,148.47,140.61,140.49,136.36,135.76,135.70,127.66,127.62,127.58,127.55,125.63,124.92,124.89,123.74,123.42,123.32,122.94,116.81,116.62,52.28.HRMS(ESI)理论值C 17H 11F 4N 3O 3[M+H] +:382.0815,实测值:382.0841. Compound II-19: mp, 146.8-148.1°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.24(s, 1H), 7.73(d, J=8.4Hz, 2H), 7.53(s, 1H) ,7.42(d,J=11.2Hz,1H),7.32(t,J=8.4Hz,1H),7.23(d,J=8.4Hz,1H),7.12(d,J=8.4Hz,2H),5.07 (s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ160.15,157.26,154.87,152.41,148.47,140.61,140.49,136.36,135.76,135.70,127.66,127.62,127.58,1127.549,2 , 123.74, 123.42, 123.32, 122.94, 116.81, 116.62, 52.28. HRMS (ESI) theoretical value C 17 H 11 F 4 N 3 O 3 [M+H] + : 382.0815, measured value: 382.0841.
化合物II-20：m.p.,124.8-125.4℃； 1H NMR(400MHz,DMSO-d 6)δ12.24(s,1H),7.73(d,J＝8.4Hz,2H),7.63(d,J＝1.6Hz,1H),7.53(s,1H),7.38(dd,J＝8.4,1.6Hz,1H),7.29(d,J＝8.4Hz,1H),7.07(d,J＝8.4Hz,2H),5.07(s,2H). 13C NMR(100MHz,DMSO-d 6)δ159.85,157.21,149.26,148.43,136.34,135.52,130.11,128.52,127.67,127.64,127.60,127.56,125.53,123.65,123.33,122.91,116.87,52.11.HRMS(ESI)理论值C 17H 11ClF 3N 3O 3[M+H] +:398.0519,实测值:398.0533. Compound II-20: mp, 124.8-125.4°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.24(s, 1H), 7.73(d, J=8.4Hz, 2H), 7.63(d, J= 1.6Hz, 1H), 7.53(s, 1H), 7.38(dd, J=8.4, 1.6Hz, 1H), 7.29(d, J=8.4Hz, 1H), 7.07(d, J=8.4Hz, 2H) ,5.07(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ159.85,157.21,149.26,148.43,136.34,135.52,130.11,128.52,127.67,127.64,127.60,127.56,123.535,312 , 116.87, 52.11. HRMS (ESI) theoretical value C 17 H 11 ClF 3 N 3 O 3 [M+H] + : 398.0519, measured value: 398.0533.
化合物II-21：m.p.,149.4-150.5℃； 1H NMR(400MHz,DMSO-d 6)δ12.25(s,1H),7.72(d,J＝8.8Hz,2H),7.52(s,1H),7.40(d,J＝8.4Hz,2H),7.12(t,J＝8.4Hz,4H),5.04(s,2H). 13C NMR(100MHz,DMSO-d 6)δ160.31,157.11,154.55,148.33,135.99,132.94,129.92,128.35,127.54,127.51,127.47,127.43,125.65,123.91,123.59,123.28,122.96,120.01,118.01,52.61.HRMS(ESI)理论值C 17H 12F 3N 2O 3[M] +:363.0831,实测值:363.0852. Compound II-21: mp, 149.4-150.5°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.25(s, 1H), 7.72(d, J=8.8Hz, 2H), 7.52(s, 1H) ,7.40(d,J=8.4Hz,2H),7.12(t,J=8.4Hz,4H),5.04(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ160.31,157.11,154.55,148.33 H _ _ _ _ M] + : 363.0831, measured value: 363.0852.
化合物II-22：m.p.,160.8-162.2℃； 1H NMR(400MHz,DMSO-d 6)δ12.23(s,1H),7.93(s,1H),7.81(d,J＝8.4Hz,2H),7.68(d,J＝8.8Hz,1H),7.52(s,1H),7.30(d,J＝8.4Hz,2H),7.20(d,J＝8.4Hz,1H),5.08(s,2H). 13C NMR(100MHz,DMSO-d 6)δ158.72,158.71,157.49,157.33,156.52,149.21,148.53,136.49,135.59,134.94,133.75,133.31,127.93,127.90,127.86,127.83,125.51,125.20,124.88,122.81,119.74,119.11,115.48,104.15,51.98.HRMS(ESI)理论值C 18H 11F 3N 4O 3[M+H] +:389.0861,实测值:389.0887. Compound II-22: mp, 160.8-162.2°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.23(s, 1H), 7.93(s, 1H), 7.81(d, J=8.4Hz, 2H) ,7.68(d,J=8.8Hz,1H),7.52(s,1H),7.30(d,J=8.4Hz,2H),7.20(d,J=8.4Hz,1H),5.08(s,2H) . 13 C NMR(100MHz,DMSO-d 6 )δ158.72,158.71,157.49,157.33,156.52,149.21,148.53,136.49,135.59,134.94,133.75,133.31,127.93,127.90,127.86,127.83,125.51,125.20,124.88, 122.81, 119.74, 119.11, 115.48, 104.15, 51.98. HRMS (ESI) theoretical value C 18 H 11 F 3 N 4 O 3 [M+H] + : 389.0861, measured value: 389.0887.
化合物II-23：m.p.,161.8-162.5℃； 1H NMR(400MHz,DMSO-d 6)δ7.80(s,1H),7.67–7.64(m,2H),7.25–7.21(m,2H),7.15–7.11(m,2H),6.90–6.86(m,2H),5.20(q,J＝6.8Hz,1H),1.60(d,J＝6.8Hz,3H). 13C NMR(100MHz,DMSO-d 6)δ158.65,157.94,156.39,149.42,135.41,135.14,128.09,127.40,124.98,122.83,119.54,118.96,57.19,21.20.HRMS(ESI)理论值C 18H 14F 3N 3O 3[M+H] +:378.1066,实测值:378.1167. Compound II-23: mp, 161.8-162.5°C; 1 H NMR (400MHz, DMSO-d 6 ) δ7.80(s,1H),7.67–7.64(m,2H),7.25–7.21(m,2H), 7.15–7.11(m,2H),6.90–6.86(m,2H),5.20(q,J=6.8Hz,1H),1.60(d,J=6.8Hz,3H). 13 C NMR(100MHz,DMSO- d 6 )δ158.65, 157.94, 156.39, 149.42, 135.41, 135.14, 128.09, 127.40, 124.98, 122.83, 119.54, 118.96, 57.19, 21.20. HRMS (ESI) theoretical value C 18 H 14 F 3 N 3 O 3 H] + : 378.1066, measured value: 378.1167.
化合物II-24：m.p.,190.8-191.9℃； 1H NMR(400MHz,DMSO-d 6)δ9.88(s,1H),7.93(s,1H),7.09–7.04(m,2H), 6.92(s,2H),5.26(s,2H). 13C NMR(100MHz,DMSO-d 6)δ158.45,154.06,153.37,152.81,149.76,135.77,134.37,133.30,128.00,118.95,104.55,50.86.HRMS(ESI)理论值C 16H 8Cl 2F 3N 3O 3[M+H] +:417.9973,实测值:417.9957. Compound II-24: mp, 190.8-191.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ9.88(s, 1H), 7.93(s, 1H), 7.09–7.04(m, 2H), 6.92( s,2H),5.26(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ158.45,154.06,153.37,152.81,149.76,135.77,134.37,133.30,128.00,118.95,104.55,50.86.HRMS(ESI ) theoretical value C 16 H 8 Cl 2 F 3 N 3 O 3 [M+H] + : 417.9973, measured value: 417.9957.
化合物II-25：m.p.,162.3-163.9℃； 1H NMR(400MHz,DMSO-d 6)δ11.34(s,1H),7.63(s,1H),7.56(d,J＝2.0Hz,1H),7.22(dd,J＝8.5,2.1Hz,1H),7.10(t,J＝7.8Hz,1H),7.03(d,J＝7.5Hz,1H),6.74(d,J＝8.4Hz,1H),6.67(d,J＝8.0Hz,1H),4.81(s,2H),2.28(s,3H),2.20(q,J＝7.5Hz,2H),2.08(s,3H),1.03(t,J＝7.4Hz,3H). 13C NMR(100MHz,DMSO-d 6)δ164.47,154.89,151.59,150.89,140.73,138.47,131.97,129.73,127.70,126.73,126.68,125.14,122.73,117.43,114.27,112.70,50.93,19.89,19.83,12.69,11.67.HRMS(ESI)理论值C 18H 15Cl 2N 3O 3[M+H] +:392.0569,实测值:392.0564. Compound II-25: mp, 162.3-163.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.34(s, 1H), 7.63(s, 1H), 7.56(d, J=2.0Hz, 1H) ,7.22(dd,J=8.5,2.1Hz,1H),7.10(t,J=7.8Hz,1H),7.03(d,J=7.5Hz,1H),6.74(d,J=8.4Hz,1H) ,6.67(d,J=8.0Hz,1H),4.81(s,2H),2.28(s,3H),2.20(q,J=7.5Hz,2H),2.08(s,3H),1.03(t, J＝7.4Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ164.47,154.89,151.59,150.89,140.73,138.47,131.97,129.73,127.70,126.73,126.68,125.17,121.723,114.7 , 50.93, 19.89, 19.83, 12.69, 11.67. HRMS (ESI) theoretical value C 18 H 15 Cl 2 N 3 O 3 [M+H] + : 392.0569, measured value: 392.0564.
化合物II-26：m.p.,165.8-167.4℃； 1H NMR(400MHz,Chloroform-d)δ7.48(s,2H),7.46(s,1H),6.46(dd,J＝8.5,5.5Hz,2H),5.08(s,2H),3.37(s,3H). 13C NMR(100MHz,Chloroform-d)δ158.83,153.56,152.83,151.87,148.71,134.82,133.75,132.51,128.22,127.30,104.11,51.10,27.98.HRMS(ESI)理论值C 17H 10Cl 2F 3N 3O 3[M+H] +:432.0130,实测值:432.0122. Compound II-26: mp, 165.8-167.4°C; 1 H NMR (400MHz, Chloroform-d) δ7.48(s, 2H), 7.46(s, 1H), 6.46(dd, J=8.5, 5.5Hz, 2H ),5.08(s,2H),3.37(s,3H) .13 C NMR(100MHz,Chloroform-d)δ158.83,153.56,152.83,151.87,148.71,134.82,133.75,132.51,128.22,127.30,104.101,51.1 27.98. HRMS (ESI) theoretical value C 17 H 10 Cl 2 F 3 N 3 O 3 [M+H] + : 432.0130, found value: 432.0122.
化合物II-28：m.p.,165.8-167.4℃； 1H NMR(400MHz,DMSO-d 6)δ12.15(s,1H),7.58(s,2H),7.05(d,J＝8.4Hz,1H),6.65(d,J＝2.8Hz,1H),6.44(dd,J＝8.3,2.8Hz,1H),5.04(s,2H),2.16(d,J＝8.5Hz,6H),2.08(s,3H). 13C NMR(100MHz,DMSO-d 6)δ157.87,154.84,149.53,145.81,144.59,138.50,137.03,130.97,130.89,129.21,128.81,116.13,111.81,52.14,19.99,18.91,16.60.HRMS(ESI)理论值C 19H 17Cl 2N 3O 3[M+H] +:406.0725,实测值:406.0726. Compound II-28: mp, 165.8-167.4°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.15(s, 1H), 7.58(s, 2H), 7.05(d, J=8.4Hz, 1H) ,6.65(d,J=2.8Hz,1H),6.44(dd,J=8.3,2.8Hz,1H),5.04(s,2H),2.16(d,J=8.5Hz,6H),2.08(s, 3H). 13 C NMR (100MHz, DMSO-d 6 ) δ157.87, 154.84, 149.53, 145.81, 144.59, 138.50, 137.03, 130.97, 130.89, 129.21, 128.81, 116.13, 111.81, 52.19, 18.9 ESI) theoretical value C 19 H 17 Cl 2 N 3 O 3 [M+H] + : 406.0725, measured value: 406.0726.
化合物II-29：m.p.,193.5-195.1℃； 1H NMR(400MHz,DMSO-d 6)δ12.66(s,1H),7.61(s,2H),7.57(s,1H),7.41(d,J＝8.9Hz,2H),7.04(d,J＝9.0Hz,2H),6.98(d,J＝8.9Hz,2H),6.85(d,J＝9.0Hz,2H),4.94(s,2H). 13C NMR(100MHz,DMSO-d 6)δ156.85,156.72,153.03,151.45,149.71,145.89,136.39,135.49,130.29,129.48,128.95,127.28,121.22,119.94,116.64,41.70.HRMS(ESI)理论值C 22H 14Cl 3N 3O 4[M+H] +:490.0128,实测值:490.0116. Compound II-29: mp, 193.5-195.1°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.66(s, 1H), 7.61(s, 2H), 7.57(s, 1H), 7.41(d, J=8.9Hz, 2H), 7.04(d, J=9.0Hz, 2H), 6.98(d, J=8.9Hz, 2H), 6.85(d, J=9.0Hz, 2H), 4.94(s, 2H) . 13 C NMR (100MHz, DMSO-d 6 ) δ156.85, 156.72, 153.03, 151.45, 149.71, 145.89, 136.39, 135.49, 130.29, 129.48, 128.95, 127.28, 121.22, 119.94, 1416.6 C 22 H 14 Cl 3 N 3 O 4 [M+H] + : 490.0128, Found: 490.0116.
化合物II-32：m.p.,198.2-198.7℃； 1H NMR(400MHz,Chloroform-d)δ7.49(d,J＝7.4Hz,2H),7.45(d,J＝1.5Hz,1H),7.36–7.27(m,5H),7.07(t,J＝6.8Hz,3H),6.93(d,J＝8.0Hz,2H),5.09(s,2H),5.05(s,2H). 13C NMR(100MHz,DMSO-d 6)δ157.61,156.96,156.91,156.48,154.49,154.44,149.25,136.31,136.04,135.95,135.87,135.79,130.48,129.93,129.78,129.63,128.84,128.38,127.92,123.62,115.23,112.66,112.43,53.78,43.80.HRMS(ESI)理论值C 23H 17F 2N 3O 3[M+H] +:422.1316,实测值:422.1322. Compound II-32: mp, 198.2-198.7°C; 1 H NMR (400MHz, Chloroform-d) δ7.49 (d, J=7.4Hz, 2H), 7.45 (d, J=1.5Hz, 1H), 7.36– 7.27(m, 5H), 7.07(t, J=6.8Hz, 3H), 6.93(d, J=8.0Hz, 2H), 5.09(s, 2H), 5.05(s, 2H). 13 C NMR (100MHz ,DMSO-d 6 )δ157.61,156.96,156.91,156.48,154.49,154.44,149.25,136.31,136.04,135.95,135.87,135.79,130.48,129.93,129.78,129.63,128.84,128.38,127.92,123.62,115.23,112.66, 112.43, 53.78, 43.80. HRMS (ESI) theoretical value C 23 H 17 F 2 N 3 O 3 [M+H] + : 422.1316, found value: 422.1322.
化合物II-37：m.p.,165.1-166.9℃； 1H NMR(400MHz,DMSO-d 6)δ12.18(s,1H),7.51(s,1H),7.48(s,2H),7.05(d,J＝7.4Hz,2H),6.97(dd,J＝8.4,6.4Hz,1H),5.02(s,2H),2.03(s,6H). 13C NMR(100MHz,DMSO-d 6)δ157.65,153.25,148.87,148.41,136.84,134.00,129.80,129.43,128.19,125.70,124.58,52.11,17.08,2.26.HRMS(ESI)理论值C 18H 15Cl 2N 3O 3[M+H] +:392.0569,实测值:392.0556. Compound II-37: mp, 165.1-166.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.18(s, 1H), 7.51(s, 1H), 7.48(s, 2H), 7.05(d, J＝7.4Hz, 2H), 6.97(dd, J＝8.4, 6.4Hz, 1H), 5.02(s, 2H), 2.03(s, 6H). 13 C NMR (100MHz, DMSO-d 6 ) δ157.65, 153.25 ,148.87,148.41,136.84,134.00,129.80,129.43,128.19,125.70,124.58,52.11,17.08,2.26. HRMS (ESI) theoretical value C 18 H 15 Cl 2 N 3 O 3 [M+H] + :392.0569, Measured value: 392.0556.
化合物II-38：m.p.,152.7-153.9℃； 1H NMR(400MHz,DMSO-d 6)δ11.33(s,1H),7.79(d,J＝8.0Hz,1H),7.54(d,J＝2.0Hz,1H),7.25(dd,J＝8.4,2.0Hz,1H),7.13(d,J＝8.0Hz,1H),6.97(d,J＝8.4Hz,1H),6.80(d,J＝2.0Hz,1H),6.68(dd,J＝8.4,2.4Hz,1H),5.61(dd,J＝8.0,2.0Hz,1H),4.84(s,2H),2.19(s,6H). 13C NMR(100MHz,DMSO-d 6)δ163.82,154.07,151.90,151.13,145.59,138.39,133.53,131.82,130.83,129.99,128.13,124.07,120.26,119.23,115.27,101.65,49.52,19.54,18.68.HRMS(ESI)理论值C 19H 17ClN 2O 3[M-H] -:355.0849,实测值:355.0861. Compound II-38: mp, 152.7-153.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.33(s, 1H), 7.79(d, J=8.0Hz, 1H), 7.54(d, J= 2.0Hz, 1H), 7.25(dd, J=8.4, 2.0Hz, 1H), 7.13(d, J=8.0Hz, 1H), 6.97(d, J=8.4Hz, 1H), 6.80(d, J= 13C NMR(100MHz,DMSO-d 6 )δ163.82,154.07,151.90,151.13,145.59,138.39,133.53,131.82,130.83,129.99,128.13,124.07,120.26,119.23,115.27,101.65,49.52,19.54,18.68.HRMS(ESI ) theoretical value C 19 H 17 ClN 2 O 3 [MH] - : 355.0849, measured value: 355.0861.
化合物II-39：m.p.,143.7-144.3℃； 1H NMR(400MHz,DMSO-d 6)δ12.53(s,1H),7.53(s,2H),7.33(d,J＝8.4Hz,2H),6.71(d,J＝8.4Hz,2H),5.99(s,1H),4.93(s,2H),1.25(s,9H). 13C NMR(100MHz,DMSO-d 6)δ161.22,154.05,150.72,146.36,145.43,144.99,136.31,128.98,127.84,126.67,114.01,102.90,47.16,33.96,31.27.HRMS(ESI)理论值C 21H 19Cl 3N 2O 3[M-H] -:451.0383,实测值:451.0404. Compound II-39: mp, 143.7-144.3°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.53(s, 1H), 7.53(s, 2H), 7.33(d, J=8.4Hz, 2H) ,6.71(d,J＝8.4Hz,2H),5.99(s,1H),4.93(s,2H),1.25(s,9H). 13 C NMR(100MHz,DMSO-d 6 )δ161.22,154.05,150.72 , 146.36, 145.43, 144.99, 136.31, 128.98, 127.84, 126.67, 114.01, 102.90, 47.16, 33.96, 31.27. HRMS (ESI) theoretical value C 21 H 19 Cl 3 N 2 O 3 [MH] - : 451.0383, measured value :451.0404.
化合物II-40：m.p.,145.4-147.1℃； 1H NMR(400MHz,DMSO-d 6)δ11.36–11.33(m,1H),7.79(d,J＝7.9Hz,1H),7.54(d,J＝2.2Hz,1H),7.21(dd,J＝8.5,2.1Hz,1H),7.14(s,1H),7.01(d,J＝8.1Hz,1H),6.74(d,J＝8.3Hz,2H),5.61(dd,J＝7.9,2.3Hz,1H),4.82(s,2H),2.27(s,3H),2.11(s,3H). 13C NMR(100MHz,DMSO-d 6)δ164.25,156.36,151.30,150.52,145.11,139.79,132.85,129.71,127.72,126.42,123.59,117.60,115.99,102.35,50.94,21.31.HRMS(ESI)理论值C 19H 17ClN 2O 3[M-H] -:357.1006,实测值:357.1024. Compound II-40: mp, 145.4-147.1°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.36–11.33 (m, 1H), 7.79 (d, J=7.9Hz, 1H), 7.54 (d, J＝2.2Hz, 1H), 7.21(dd, J＝8.5, 2.1Hz, 1H), 7.14(s, 1H), 7.01(d, J＝8.1Hz, 1H), 6.74(d, J＝8.3Hz, 2H), 5.61(dd, J＝7.9, 2.3Hz, 1H), 4.82(s, 2H), 2.27(s, 3H), 2.11(s, 3H). 13 C NMR (100MHz, DMSO-d 6 ) δ164 .25, 156.36, 151.30, 150.52, 145.11, 139.79 , 132.85, 129.71 , 127.72 , 126.42 , 123.59, 117.60, 115.99, 102.35 , 50.94, 21.31. 357.1006, measured value: 357.1024.
化合物II-41：m.p.,204.3-205.4℃； 1H NMR(600MHz,DMSO-d 6)δ11.39(s,1H),7.83(d,J＝7.8Hz,1H),7.58(s,2H),7.05(d,J＝8.4Hz,1H),6.66(s,1H),6.44(dd,J＝8.4,1.8Hz,1H),5.64(d,J＝7.8Hz,1H),4.88(s,2H),2.16 (s,3H),2.14(s,3H). 13C NMR(100MHz,DMSO-d 6)δ163.75,154.36,151.14,145.67,145.47,138.10,136.48,130.54,130.51,128.88,115.74,111.36,101.81,49.29,19.56,18.49.HRMS(ESI)理论值C 19H 16Cl 2N 2O 3[M-H] -:389.0460,实测值:389.0484. Compound II-41: mp, 204.3-205.4°C; 1 H NMR (600MHz, DMSO-d 6 ) δ11.39(s, 1H), 7.83(d, J=7.8Hz, 1H), 7.58(s, 2H) ,7.05(d,J=8.4Hz,1H),6.66(s,1H),6.44(dd,J=8.4,1.8Hz,1H),5.64(d,J=7.8Hz,1H),4.88(s, 2H), 2.16 (s, 3H), 2.14 (s, 3H). 13 C NMR (100MHz, DMSO-d 6 ) δ163.75, 154.36, 151.14, 145.67, 145.47, 138.10, 136.48, 130.54, 130.51, 128.88, 115.74, 111.36, 101.81, 49.29, 19.56, 18.49. HRMS (ESI) theoretical value C 19 H 16 Cl 2 N 2 O 3 [MH] - : 389.0460, found value: 389.0484.
化合物II-42：m.p.,159.7-161.2℃； 1H NMR(400MHz,DMSO-d 6)δ11.38(s,1H),7.79(d,J＝8.0Hz,1H),7.25(d,J＝8.8Hz,2H),7.07(d,J＝8.4Hz,1H),6.76(s,1H),6.61(dd,J＝8.0,2.0Hz,1H),5.63(dd,J＝8.0,1.6Hz,1H),4.88(s,2H),2.17(s,3H),2.08(s,3H). 13C NMR(100MHz,DMSO-d 6)δ163.72,156.55,156.50,155.32,154.08,154.03,151.09,145.42,138.11,135.58,135.50,135.42,130.94,130.52,130.00,129.85,129.70,115.96,112.30,112.25,112.13,112.08,111.79,101.77,49.50,19.48,18.48.HRMS(ESI)理论值C 19H 16F 2N 2O 3[M+H] +:359.1207,实测值:359.1230. Compound II-42: mp, 159.7-161.2°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.38(s, 1H), 7.79(d, J=8.0Hz, 1H), 7.25(d, J= 8.8Hz, 2H), 7.07(d, J=8.4Hz, 1H), 6.76(s, 1H), 6.61(dd, J=8.0, 2.0Hz, 1H), 5.63(dd, J=8.0, 1.6Hz, 1H),4.88(s,2H),2.17(s,3H),2.08(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ163.72,156.55,156.50,155.32,154.08,154.03,151.09,145.42 , 138.11,135.5.5.50, 135.42,130.94,130.52,130.00, 129.85,129.70, 115.96 , 112.30.25,112.13.08.79.77,49.48.48.48.hrms 2 N 2 O 3 [M+H] + : 359.1207, measured value: 359.1230.
化合物II-43：m.p.,152.6-153.5℃； 1H NMR(400MHz,DMSO-d 6)δ11.35(s,1H),7.80(d,J＝8.0Hz,1H),7.69(s,1H),7.29(d,J＝8.4Hz,1H),7.12(d,J＝8.0Hz,1H),6.93(d,J＝8.4Hz,1H),6.80(s,1H),6.67(d,J＝8.4Hz,1H),5.61(d,J＝8.0Hz,1H),4.84(s,2H),2.18(s,6H). 13C NMR(100MHz,DMSO-d 6)δ163.67,154.01,153.00,151.03,145.46,138.28,133.76,132.90,131.71,130.73,128.73,119.96,119.26,115.29,113.48,101.56,49.30,19.47,18.61.HRMS(ESI)理论值C 19H 17BrN 2O 3[M-H] -:399.0344,实测值:399.0365. Compound II-43: mp, 152.6-153.5°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.35(s, 1H), 7.80(d, J=8.0Hz, 1H), 7.69(s, 1H) ,7.29(d,J=8.4Hz,1H),7.12(d,J=8.0Hz,1H),6.93(d,J=8.4Hz,1H),6.80(s,1H),6.67(d,J= 8.4Hz,1H),5.61(d,J＝8.0Hz,1H),4.84(s,2H),2.18(s,6H). 13 C NMR(100MHz,DMSO-d 6 )δ163.67,154.01,153.00,151.03 , 145.46,138.28,133.76,132.90,131.71,130.73,128.73,119.96,119.26,115.29,113.48,101.56,49.30,19.47,18.61 . _ _ 399.0344, measured value: 399.0365.
化合物II-44：m.p.,160.2-161.3℃； 1H NMR(600MHz,Chloroform-d)δ8.52(s,1H),7.35(s,1H),7.06(t,J＝7.7Hz,1H),7.02(d,J＝8.4Hz,1H),7.00(d,J＝7.5Hz,1H),6.71(d,J＝8.0Hz,1H),6.66(d,J＝8.4Hz,1H),4.90(s,2H),2.81(t,J＝7.2Hz,2H),2.73(t,J＝7.1Hz,2H),2.32(s,3H),2.14(s,3H),2.12–2.05(m,2H). 13C NMR(101MHz,Chloroform-d)δ161.42,157.12,153.63,153.53,152.67,139.19,131.05,129.48,128.36,126.74,126.42,126.19,124.45,118.12,117.06,113.33,47.70,32.47,27.33,21.43,20.19,12.18.HRMS(ESI)理论值C 22H 21ClN 2O 3[M-H] -:397.1319,实测值:397.1297. Compound II-44: mp, 160.2-161.3°C; 1 H NMR (600MHz, Chloroform-d) δ8.52(s, 1H), 7.35(s, 1H), 7.06(t, J=7.7Hz, 1H), 7.02(d, J=8.4Hz, 1H), 7.00(d, J=7.5Hz, 1H), 6.71(d, J=8.0Hz, 1H), 6.66(d, J=8.4Hz, 1H), 4.90( s,2H),2.81(t,J=7.2Hz,2H),2.73(t,J=7.1Hz,2H),2.32(s,3H),2.14(s,3H),2.12–2.05(m,2H ). 13 C NMR(101MHz,Chloroform-d)δ161.42,157.12,153.63,153.53,152.67,139.19,131.05,129.48,128.36,126.74,126.42,126.19,124.45,118.12,117.06,113.33,47.70,32.47,27.33, 21.43, 20.19, 12.18. HRMS (ESI) theoretical value C 22 H 21 ClN 2 O 3 [MH] - : 397.1319, measured value: 397.1297.
化合物II-45：m.p.,145.5-146.7℃； 1H NMR(400MHz,DMSO-d 6)δ11.35(s,1H),7.79(d,J＝7.6Hz,1H),7.34(d,J＝11.6Hz,1H),7.11(d,J＝7.6Hz,2H),7.06(t,J＝8.4Hz,1H),6.81(s,1H),6.69(d,J＝7.6Hz,1H),5.61(d,J＝7.6Hz,1H),4.85(s,2H),2.18(s,6H). 13C NMR(100MHz,DMSO-d 6)δ163.76,154.51,154.35,151.90,151.10,145.53,143.17,143.06,138.21,133.80,133.74,131.48,130.70,124.49,124.46,121.39,118.58,116.59,116.40,114.59,101.60,49.58,19.50,18.59.HRMS(ESI)理论值C 19H 17FN 2O 3[M+H] +:341.1301,实测值:341.1325. Compound II-45: mp, 145.5-146.7°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.35(s, 1H), 7.79(d, J=7.6Hz, 1H), 7.34(d, J= 11.6Hz, 1H), 7.11(d, J=7.6Hz, 2H), 7.06(t, J=8.4Hz, 1H), 6.81(s, 1H), 6.69(d, J=7.6Hz, 1H), 5.61 (d, J=7.6Hz, 1H), 4.85(s, 2H), 2.18(s, 6H). 13 C NMR (100MHz, DMSO-d 6 ) δ163.76, 154.51, 154.35, 151.90, 151.10, 145.53, 143.17, 143.06, 138.21, 133.80, 133.74, 131.48, 130.70 , 124.49, 124.46, 121.39 , 118.58, 116.59 , 116.40 , 114.59, 101.60, 49.58, 19.50, 18.59. +H] + :341.1301, measured value: 341.1325.
化合物II-46：m.p.,195.6-197.1℃； 1H NMR(600MHz,DMSO-d 6)δ11.85(s,1H),8.40(s,1H),7.61(s,1H),7.25(d,J＝7.8Hz,1H),7.09(t,J＝7.5Hz,1H),7.03(d,J＝7.2Hz,1H),6.73(d,J＝8.4Hz,1H),6.67(d,J＝7.8Hz,1H),4.82(s,2H),2.28(s,3H),2.08(s,3H). 13C NMR(101MHz,DMSO-d 6)δ159.64,153.24,152.34,150.41,145.03,138.89,132.30,130.11,128.17,127.33,126.59,125.94,122.80,118.18,116.42,95.34,49.87,19.67,11.77.HRMS(ESI)理论值C 19H 16BrClN 2O 3[M+H] +:435.0111,实测值:435.0134. Compound II-46: mp, 195.6-197.1°C; 1 H NMR (600MHz, DMSO-d 6 ) δ11.85(s, 1H), 8.40(s, 1H), 7.61(s, 1H), 7.25(d, J=7.8Hz, 1H), 7.09(t, J=7.5Hz, 1H), 7.03(d, J=7.2Hz, 1H), 6.73(d, J=8.4Hz, 1H), 6.67(d, J= 7.8Hz,1H),4.82(s,2H),2.28(s,3H),2.08(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ159.64,153.24,152.34,150.41,145.03,138.89, 132.30, 130.11, 128.17, 127.33, 126.59, 125.94, 122.80, 118.18, 116.42, 95.34, 49.87, 19.67, 11.77. HRMS (ESI) theoretical value C 19 H 16 BrClN 2 O 3 [M+H] + 1 measured: 1135.0 Value: 435.0134.
化合物II-47：m.p.,172.8-175.1℃； 1H NMR(600MHz,Chloroform-d)δ8.82(s,1H),7.40(d,J＝2.4Hz,1H),7.09–7.04(m,2H),7.02–6.96(m,2H),6.72(d,J＝8.0Hz,1H),6.69–6.63(m,1H),4.81(s,2H),2.32(s,3H),2.13(s,3H),1.91(s,3H). 13C NMR(101MHz,Chloroform-d)δ164.52,153.89,153.54,151.35,139.70,139.23,130.60,130.31,128.42,127.64,126.46,126.28,124.42,118.06,117.19,111.62,50.21,20.19,12.52,12.19.HRMS(ESI)理论值C 20H 19ClN 2O 3[M+H] +:371.1162,实测值:371.1149. Compound II-47: mp, 172.8-175.1°C; 1 H NMR (600MHz, Chloroform-d) δ8.82 (s, 1H), 7.40 (d, J=2.4Hz, 1H), 7.09-7.04 (m, 2H ),7.02–6.96(m,2H),6.72(d,J＝8.0Hz,1H),6.69–6.63(m,1H),4.81(s,2H),2.32(s,3H),2.13(s, 3H),1.91(s,3H) .13C NMR(101MHz,Chloroform-d)δ164.52,153.89,153.54,151.35,139.70,139.23,130.60,130.31,128.42,127.64,126.46,126.28,1118.46,1 111.62, 50.21, 20.19, 12.52, 12.19. HRMS (ESI) theoretical value C 20 H 19 ClN 2 O 3 [M+H] + : 371.1162, measured value: 371.1149.
化合物II-48：m.p.,166.2-166.8℃； 1H NMR(600MHz,DMSO-d 6)δ11.51(s,1H),7.57(s,1H),7.50(s,1H),7.28(d,J＝8.0Hz,1H),7.13(d,J＝8.3Hz,1H),6.97(d,J＝8.3Hz,1H),6.80(s,1H),6.68(d,J＝8.3Hz,1H),4.80(s,2H),3.61(s,3H),2.19(s,6H). 13C NMR(101MHz,DMSO-d 6)δ159.62,154.09,151.71,149.62,138.32,135.90,133.71,131.71,130.77,129.87,128.02,125.33,123.99,120.23,119.13,115.18,57.25,49.66,19.51,18.63.HRMS(ESI)理论值C 20H 19ClN 2O 4[M+H] +:387.1112,实测值:387.1140. Compound II-48: mp, 166.2-166.8°C; 1 H NMR (600MHz, DMSO-d 6 ) δ11.51(s, 1H), 7.57(s, 1H), 7.50(s, 1H), 7.28(d, J=8.0Hz, 1H), 7.13(d, J=8.3Hz, 1H), 6.97(d, J=8.3Hz, 1H), 6.80(s, 1H), 6.68(d, J=8.3Hz, 1H) ,4.80(s,2H),3.61(s,3H),2.19(s,6H). 13 C NMR(101MHz,DMSO-d 6 )δ159.62,154.09,151.71,149.62,138.32,135.90,133.71,131.71,130.77 , 129.87, 128.02, 125.33, 123.99, 120.23, 119.13, 115.18, 57.25, 49.66, 19.51, 18.63. HRMS (ESI) theoretical value C 20 H 19 ClN 2 O 4 [M+H] + : 387.1112, measured value: 387.11 .
化合物II-49：m.p.,145.6-147.2℃； 1H NMR(400MHz,Chloroform-d)δ8.70(s,1H),7.39(d,J＝1.6Hz,1H),7.14–7.10(m,1H),7.09(d,J＝8.2Hz,1H),6.94(s,1H),6.88(d,J＝8.4Hz,1H),6.80(d,J＝1.4Hz,1H),6.72(dd,J＝8.1,2.1Hz,1H),4.84(s,2H),2.35(q,J＝7.2Hz,2H),2.24(s,6H),1.12(t,J＝7.4Hz,3H). 13C NMR(100MHz,DMSO-d 6)δ163.83,154.02,151.70,150.90,140.71,138.29,133.73,131.70,130.74,129.86,127.99,123.92,120.20,119.13,115.19,114.98,49.33,19.54,19.50,18.63,13.06.HRMS(ESI)理论值C 21H 21ClN 2O 3[M+H] +:385.1319,实测值:385.1322. Compound II-49: mp, 145.6-147.2°C; 1 H NMR (400MHz, Chloroform-d) δ8.70 (s, 1H), 7.39 (d, J=1.6Hz, 1H), 7.14-7.10 (m, 1H ), 7.09(d, J=8.2Hz, 1H), 6.94(s, 1H), 6.88(d, J=8.4Hz, 1H), 6.80(d, J=1.4Hz, 1H), 6.72(dd,J =8.1, 2.1Hz, 1H), 4.84(s, 2H), 2.35(q, J=7.2Hz, 2H), 2.24(s, 6H), 1.12(t, J=7.4Hz, 3H). 13 C NMR (100MHz,DMSO-d 6 )δ163.83,154.02,151.70,150.90,140.71,138.29,133.73,131.70,130.74,129.86,127.99,123.92,120.20,119.13,115.19,114.98,49.33,19.54,19.50,18.63,13.06. HRMS (ESI) theoretical value C 21 H 21 ClN 2 O 3 [M+H] + : 385.1319, found value: 385.1322.
化合物II-50：m.p.,209.2-210.4℃； 1H NMR(400MHz,DMSO-d 6)δ11.33(s,1H),7.85(d,J＝1.6Hz,1H),7.78 (d,J＝8.0Hz,1H),7.56(dd,J＝8.8,1.6Hz,1H),7.21(d,J＝8.4Hz,1H),6.97(d,J＝2.0Hz,1H),6.90–6.84(m,2H),5.60(dd,J＝8.0,2.0Hz,1H),4.84(s,2H),2.22(s,6H). 13C NMR(100MHz,DMSO-d 6)δ163.73,158.96,152.47,151.05,145.42,138.76,134.78,133.34,131.97,131.89,131.05,120.78,117.07,117.00,115.86,102.23,101.64,49.28,19.44,18.73.HRMS(ESI)理论值C 20H 17N 3O 3[M+H] +:348.1348,实测值:348.1364. Compound II-50: mp, 209.2-210.4°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.33 (s, 1H), 7.85 (d, J=1.6Hz, 1H), 7.78 (d, J= 8.0Hz, 1H), 7.56(dd, J＝8.8, 1.6Hz, 1H), 7.21(d, J＝8.4Hz, 1H), 6.97(d, J＝2.0Hz, 1H), 6.90–6.84(m, 2H), 5.60 (dd, J=8.0, 2.0Hz, 1H), 4.84 (s, 2H), 2.22 (s, 6H). 13 C NMR (100MHz, DMSO-d 6 ) δ163.73, 158.96, 152.47, 151.05, 145.42, 138.76 , 134.78, 133.34 , 131.97 , 131.89, 131.05, 120.78, 117.07, 117.00, 115.86 , 102.23, 101.64, 49.28, 19.44, 18.73. ] + :348.1348, measured value: 348.1364.
化合物II-51：m.p.,152.6-154.2℃； 1H NMR(400MHz,DMSO-d 6)δ11.33(s,1H),7.76(d,J＝8.0Hz,1H),7.30(d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,1H),6.93(d,J＝8.4Hz,2H),6.83(d,J＝2.0Hz,1H),6.73(dd,J＝8.0,2.4Hz,1H),5.59(d,J＝7.6Hz,1H),4.82(s,2H),2.18(s,6H). 13C NMR(150MHz,Chloroform-d)δ163.79,158.38,154.08,151.18,143.77,138.36,132.19,130.68,129.70,128.94,120.77,118.39,116.78,102.66,50.74,19.93,19.06.HRMS(ESI)理论值C19H18N2O3[M-H] -:321.1239,实测值:321.1254. Compound II-51: mp, 152.6-154.2°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.33(s, 1H), 7.76(d, J=8.0Hz, 1H), 7.30(d, J= 8.0Hz, 2H), 7.13(d, J=8.0Hz, 1H), 6.93(d, J=8.4Hz, 2H), 6.83(d, J=2.0Hz, 1H), 6.73(dd, J=8.0, 2.4Hz, 1H), 5.59(d, J=7.6Hz, 1H), 4.82(s, 2H), 2.18(s, 6H). 13 C NMR(150MHz, Chloroform-d) δ163.79, 158.38, 154.08, 151.18, 143.77, 138.36, 132.19, 130.68, 129.70, 128.94, 120.77, 118.39, 116.78, 102.66, 50.74, 19.93, 19.06. HRMS (ESI) theoretical value C19H18N2O3[MH] - : 521.12339.1: measured value 2
化合物II-52：m.p.,152.1-154.0℃； 1H NMR(400MHz,DMSO-d 6)δ11.32(s,1H),7.76(d,J＝8.0Hz,1H),7.24(s,1H),7.12–7.07(m,2H),6.78(d,J＝8.4Hz,1H),6.73(d,J＝2.0Hz,1H),6.60(dd,J＝8.0,2.4Hz,1H),5.60(d,J＝7.6Hz,1H),4.81(s,2H),2.16(s,9H). 13C NMR(100MHz,DMSO-d 6)δ159.85,157.21,149.26,148.43,136.34,135.52,130.11,128.52,127.67,127.64,127.60,127.56,125.53,123.65,123.33,122.91,116.87,52.11.HRMS(ESI)理论值C 20H 20N 2O 3[M-H] -:335.1396,实测值:335.1420. Compound II-52: mp, 152.1-154.0℃; 1 H NMR (400MHz, DMSO-d 6 ) δ11.32(s, 1H), 7.76(d, J=8.0Hz, 1H), 7.24(s, 1H) ,7.12–7.07(m,2H),6.78(d,J=8.4Hz,1H),6.73(d,J=2.0Hz,1H),6.60(dd,J=8.0,2.4Hz,1H),5.60( d, J＝7.6Hz, 1H), 4.81(s, 2H), 2.16(s, 9H). 13 C NMR (100MHz, DMSO-d 6 ) δ159.85, 157.21, 149.26, 148.43, 136.34, 135.52, 130.11, 128.52 , 127.67, 127.64, 127.60, 127.56, 125.53, 123.65, 123.33, 122.91, 116.87, 52.11. HRMS (ESI) theoretical value C 20 H 20 N 2 O 3 [MH] - : 335.1396, measured value: 335.1420.
化合物II-54：m.p.,142.1-144.0℃； 1H NMR(400MHz,DMSO-d 6)δ11.89(s,1H),8.34(s,1H),7.60(d,J＝1.5Hz,1H),7.29(dd,J＝8.4,1.6Hz,1H),7.13(d,J＝8.2Hz,1H),6.96(d,J＝8.4Hz,1H),6.80(d,J＝2.0Hz,1H),6.68(dd,J＝8.2,2.3Hz,1H),4.83(s,2H),2.18(s,6H). 13C NMR(101MHz,DMSO-d 6)δ159.49,154.00,151.88,150.21,142.70,138.28,133.01,131.71,130.73,130.08,128.21,123.95,120.11,119.15,115.20,106.84,49.93,19.46,18.60.HRMS(ESI)理论值C 20H 20N 2O 3[M-H] -:390.0538,实测值:390.0527. Compound II-54: mp, 142.1-144.0°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.89(s, 1H), 8.34(s, 1H), 7.60(d, J=1.5Hz, 1H) ,7.29(dd,J=8.4,1.6Hz,1H),7.13(d,J=8.2Hz,1H),6.96(d,J=8.4Hz,1H),6.80(d,J=2.0Hz,1H) ,6.68(dd,J＝8.2,2.3Hz,1H),4.83(s,2H),2.18(s,6H). 13 C NMR(101MHz,DMSO-d 6 )δ159.49,154.00,151.88,150.21,142.70, 138.28, 133.01, 131.71, 130.73, 130.08, 128.21, 123.95, 120.11, 119.15, 115.20, 106.84, 49.93, 19.46, 18.60. HRMS (ESI) theoretical value C 20 H 20 N 2 O 3 [MH,0.08] measured - :39 Value: 390.0527.
化合物II-55：m.p.,183.4-184.1℃； 1H NMR(400MHz,DMSO-d 6)δ11.91(s,1H),8.61(s,1H),7.63(s,1H),7.32(d,J＝8.4Hz,1H),7.13(d,J＝8.2Hz,1H),6.97(d,J＝8.4Hz,1H),6.81(d,J＝2.0Hz,1H),6.68(dd,J＝8.1,2.3Hz,1H),4.92(s,2H),2.19(s,6H). 13C NMR(125MHz,DMSO-d 6)δ160.99,160.96,155.01,151.26,150.79,146.16,146.13,138.38,133.95,131.98,130.24,129.71,127.72,123.59,119.39,117.58,116.12,104.08,103.82,103.57,103.31,50.83,19.80,19.13.HRMS(ESI)理论值C 20H 16ClF 3N 2O 3[M-H] -:425.0880,实测值:425.0905. Compound II-55: mp, 183.4-184.1°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.91(s, 1H), 8.61(s, 1H), 7.63(s, 1H), 7.32(d, J＝8.4Hz, 1H), 7.13(d, J＝8.2Hz, 1H), 6.97(d, J＝8.4Hz, 1H), 6.81(d, J＝2.0Hz, 1H), 6.68(dd, J＝ 8.1,2.3Hz,1H),4.92(s,2H),2.19(s,6H). 13 C NMR(125MHz,DMSO-d 6 )δ160.99,160.96,155.01,151.26,150.79,146.16,146.13,138.38,133.95 , 131.98, 130.24 , 129.71 , 127.72 , 123.59 , 119.39 , 117.58, 116.12, 104.08, 103.82, 103.57, 103.31, 50.83, 19.80, 19.13. - :425.0880, measured value: 425.0905.
化合物II-57：m.p.,157.5-159.2℃； 1H NMR(600MHz,Chloroform-d)δ8.16(s,1H),7.42(s,1H),7.22(d,J＝8.9Hz,1H),7.12(d,J＝9.3Hz,1H),7.00(d,J＝9.0Hz,1H),6.81(s,1H),6.77(d,J＝8.4Hz,1H),5.02(s,2H),2.25(s,6H). 13C NMR(125MHz,Chloroform-d)δ160.80,155.01,151.80,151.26,150.39,138.38,133.95,132.02,130.24,129.71,127.72,123.59,119.39,117.60,117.57,116.12,85.80,50.87,19.80,19.13.HRMS(ESI)理论值C 20H 16ClN 3O 3[M-H] -:382.0958,实测值:382.0940. Compound II-57: mp, 157.5-159.2°C; 1 H NMR (600MHz, Chloroform-d) δ8.16(s, 1H), 7.42(s, 1H), 7.22(d, J=8.9Hz, 1H), 7.12(d, J=9.3Hz, 1H), 7.00(d, J=9.0Hz, 1H), 6.81(s, 1H), 6.77(d, J=8.4Hz, 1H), 5.02(s, 2H), 2.25(s,6H). 13 C NMR(125MHz,Chloroform-d)δ160.80,155.01,151.80,151.26,150.39,138.38,133.95,132.02,130.24,129.71,127.72,123.59,119.39,117.60,117.57,116.12,85.80 , 50.87, 19.80, 19.13. HRMS (ESI) theoretical value C 20 H 16 ClN 3 O 3 [MH] - : 382.0958, measured value: 382.0940.
化合物II-58：m.p.,166.7-168.2℃； 1H NMR(400MHz,DMSO-d 6)δ12.08(s,1H),9.49(s,1H),7.68(s,1H),7.36(dd,J＝8.4,1.7Hz,1H),7.13(d,J＝8.2Hz,1H),6.96(d,J＝8.4Hz,1H),6.80(d,J＝2.2Hz,1H),6.68(dd,J＝8.2,2.4Hz,1H),5.02(s,2H),2.18(s,6H). 13C NMR(151MHz,DMSO-d 6)δ155.10,153.99,152.00,150.71,149.44,138.34,132.16,131.79,130.78,130.33,128.58,125.50,123.94,119.99,119.19,115.24,51.18,19.52,18.65.HRMS(ESI)理论值C 19H 16ClN 3O 5[M-H] -:402.0857,实测值:402.0852. Compound II-58: mp, 166.7-168.2°C; 1 H NMR (400MHz, DMSO-d 6 ) δ12.08(s, 1H), 9.49(s, 1H), 7.68(s, 1H), 7.36(dd, J=8.4,1.7Hz,1H),7.13(d,J=8.2Hz,1H),6.96(d,J=8.4Hz,1H),6.80(d,J=2.2Hz,1H),6.68(dd, J＝8.2,2.4Hz,1H),5.02(s,2H),2.18(s,6H). 13 C NMR(151MHz,DMSO-d 6 )δ155.10,153.99,152.00,150.71,149.44,138.34,132.16,131.79 , 130.78, 130.33, 128.58, 125.50, 123.94, 119.99, 119.19, 115.24, 51.18, 19.52, 18.65. HRMS (ESI) theoretical value C 19 H 16 ClN 3 O 5 [MH] - : 402.0857, measured value: 402.085
化合物II-60：m.p.,188.0-188.9℃； 1H NMR(400MHz,DMSO-d 6)δ11.72(s,1H),8.61(s,1H),7.61(d,J＝1.9Hz,1H),7.30(dd,J＝8.3,1.7Hz,1H),7.13(d,J＝8.3Hz,1H),6.96(d,J＝8.4Hz,1H),6.81(d,J＝2.3Hz,1H),6.68(dd,J＝8.1,2.5Hz,1H),5.00(s,2H),2.45(s,3H),2.19(s,6H). 13C NMR(150MHz,DMSO-d 6)δ193.60,161.71,153.94,151.96,151.47,150.36,138.32,132.78,131.78,130.76,130.25,128.40,123.89,120.05,119.22,115.28,112.04,50.30,30.37,19.50,18.65.HRMS(ESI)理论值C 21H 19ClN 2O 4[M-H] -:399.1112,实测值:399.1103. Compound II-60: mp, 188.0-188.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.72(s, 1H), 8.61(s, 1H), 7.61(d, J=1.9Hz, 1H) ,7.30(dd,J=8.3,1.7Hz,1H),7.13(d,J=8.3Hz,1H),6.96(d,J=8.4Hz,1H),6.81(d,J=2.3Hz,1H) ,6.68(dd,J＝8.1,2.5Hz,1H),5.00(s,2H),2.45(s,3H),2.19(s,6H). 13 C NMR(150MHz,DMSO-d 6 )δ193.60,161.71 , 153.94,151.96151.47,150.36,138.32,132.78,131.78,130.76,130.25,128.40,12.05 , 119.228,112.04,50.30.50,18.65.HRMSSSS 2 O 4 [MH] - : 399.1112, measured value: 399.1103.
化合物II-62：m.p.,145.5-146.9℃； 1H NMR(400MHz,DMSO-d 6)δ11.36(s,1H),7.43(s,1H),7.14(s,1H),7.12(s,1H),6.98(d,J＝8.5Hz,1H),6.80(s,1H),6.68(d,J＝8.1Hz,1H),5.57(s,1H),5.02(s,2H),2.19(s,6H),2.16(s,3H). 13C NMR(100MHz,DMSO-d 6)δ165.18,155.01,152.75,151.29,148.82,138.38,133.95,133.41,130.24,129.21,127.39,123.60,119.39,117.59,116.12,104.02,46.56,19.80,19.13,18.77.HRMS(ESI)理论值C 20H 19ClN 2O 3[M-H] -:371.1162,实测值:371.1144. Compound II-62: mp, 145.5-146.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.36(s, 1H), 7.43(s, 1H), 7.14(s, 1H), 7.12(s, 1H), 6.98(d, J=8.5Hz, 1H), 6.80(s, 1H), 6.68(d, J=8.1Hz, 1H), 5.57(s, 1H), 5.02(s, 2H), 2.19( s,6H),2.16(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ165.18,155.01,152.75,151.29,148.82,138.38,133.95,133.41,130.24,129.21,127.359,123.639,1117. , 116.12, 104.02, 46.56, 19.80, 19.13, 18.77. HRMS (ESI) theoretical value C 20 H 19 ClN 2 O 3 [MH] - : 371.1162, measured value: 371.1144.
化合物II-64：m.p.,172.4-173.9℃； 1H NMR(400MHz,Chloroform-d)δ7.33(s,2H),7.20(d,J＝7.9Hz,1H),7.02(d,J＝8.3Hz,1H),6.65(s,1H),6.49(d,J＝8.2Hz,1H),5.84(d,J＝7.9Hz,1H),4.89(s,2H),3.39(s,3H),2.22(s,3H),2.20(s,3H). 13C NMR(100MHz,DMSO-d 6)δ162.92,153.57,152.03,149.30,146.73,138.43,135.43,133.96, 130.24,128.37,127.20,118.62,114.60,99.15,51.84,27.89,19.80,19.13.HRMS(ESI)理论值C 20H 18Cl 2N 2O 3[M-H] -:405.0773,实测值:405.0754. Compound II-64: mp, 172.4-173.9°C; 1 H NMR (400MHz, Chloroform-d) δ7.33(s, 2H), 7.20(d, J=7.9Hz, 1H), 7.02(d, J=8.3 Hz,1H),6.65(s,1H),6.49(d,J=8.2Hz,1H),5.84(d,J=7.9Hz,1H),4.89(s,2H),3.39(s,3H), 2.22(s,3H),2.20(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ162.92,153.57,152.03,149.30,146.73,138.43,135.43,133.96, 130.24,128.36,127.20,114. , 99.15, 51.84, 27.89, 19.80, 19.13. HRMS (ESI) theoretical value C 20 H 18 Cl 2 N 2 O 3 [MH] - : 405.0773, measured value: 405.0754.
化合物II-66：m.p.,178.9-180.5℃； 1H NMR(400MHz,DMSO-d 6)δ11.34(s,1H),7.79(d,J＝7.8Hz,1H),7.55(d,J＝2.2Hz,1H),7.19(d,J＝7.4Hz,2H),7.15(s,1H),7.13(t,J＝2.3Hz,1H),6.36(d,J＝8.5Hz,1H),5.60(dd,J＝7.9,2.2Hz,1H),4.80(s,2H),2.04(s,6H). 13C NMR(100MHz,DMSO-d 6)δ164.25,153.84,150.73,150.52,145.11,132.76,129.73,129.63,129.13,127.69,125.55,122.08,116.11,102.35,50.94,16.38.HRMS(ESI)理论值C 19H 17ClN 2O 3[M-H] -:357.1006,实测值:357.1012. Compound II-66: mp, 178.9-180.5°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.34(s, 1H), 7.79(d, J=7.8Hz, 1H), 7.55(d, J= 2.2Hz, 1H), 7.19(d, J=7.4Hz, 2H), 7.15(s, 1H), 7.13(t, J=2.3Hz, 1H), 6.36(d, J=8.5Hz, 1H), 5.60 (dd, J=7.9, 2.2Hz, 1H), 4.80(s, 2H), 2.04(s, 6H). 13 C NMR (100MHz, DMSO-d 6 ) δ164.25, 153.84, 150.73, 150.52, 145.11, 132.76, 129.73, 129.63, 129.13, 127.69, 125.55, 122.08, 116.11, 102.35, 50.94, 16.38. HRMS (ESI) theoretical value C 19 H 17 ClN 2 O 3 [MH] - : 357.1006, measured value: 357.1012.
化合物II-67：m.p.,202.3-203.9℃； 1H NMR(400MHz,DMSO-d 6)δ11.38(d,J＝2.3Hz,1H),7.81(d,J＝7.9Hz,1H),7.48(s,2H),7.05(d,J＝7.3Hz,2H),6.98(dd,J＝8.4,6.4Hz,1H),5.63(dd,J＝7.8,2.2Hz,1H),4.83(s,2H),2.03(s,6H). 13C NMR(100MHz,DMSO-d 6)δ164.25,153.84,150.73,150.52,145.11,132.76,129.73,129.63,129.13,127.69,125.55,122.08,116.11,102.35,50.94,16.38.HRMS(ESI)理论值C 19H 16Cl 2N 2O 3[M-H] -:391.0616,实测值:391.0601. Compound II-67: mp, 202.3-203.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.38 (d, J=2.3Hz, 1H), 7.81 (d, J=7.9Hz, 1H), 7.48 (s,2H),7.05(d,J=7.3Hz,2H),6.98(dd,J=8.4,6.4Hz,1H),5.63(dd,J=7.8,2.2Hz,1H),4.83(s, 2H),2.03(s,6H). 13 C NMR(100MHz,DMSO-d 6 )δ164.25,153.84,150.73,150.52,145.11,132.76,129.73,129.63,129.13,127.69,125.55,122.08,1102.19 , 16.38. HRMS (ESI) theoretical value C 19 H 16 Cl 2 N 2 O 3 [MH] - : 391.0616, measured value: 391.0601.
化合物II-68：m.p.,148.3-149.9℃； 1H NMR(400MHz,DMSO-d 6)δ11.40(s,1H),7.43(s,1H),7.13(s,1H),7.11(s,1H),6.98(d,J＝8.4Hz,1H),6.80(s,1H),6.67(d,J＝8.1Hz,1H),5.07(s,2H),2.18(s,6H),2.14(s,3H),1.82(s,3H). 13C NMR(125MHz,DMSO-d 6)δ164.74,155.01,153.12,151.29,147.62,138.38,133.95,132.24,130.24,129.21,127.39,123.60,119.39,117.59,116.12,110.69,46.04,19.80,19.13,16.64,10.15.HRMS(ESI)理论值C 21H 21ClN 2O 3[M-H] -:385.1319,实测值:385.1340. Compound II-68: mp, 148.3-149.9°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.40(s, 1H), 7.43(s, 1H), 7.13(s, 1H), 7.11(s, 1H), 6.98(d, J=8.4Hz, 1H), 6.80(s, 1H), 6.67(d, J=8.1Hz, 1H), 5.07(s, 2H), 2.18(s, 6H), 2.14( s,3H),1.82(s,3H). 13 C NMR(125MHz,DMSO-d 6 )δ164.74,155.01,153.12,151.29,147.62,138.38,133.95,132.24,130.24,129.21,127.359,123.639,1117. , 116.12, 110.69, 46.04, 19.80, 19.13, 16.64, 10.15. HRMS (ESI) theoretical value C 21 H 21 ClN 2 O 3 [MH] - : 385.1319, measured value: 385.1340.
化合物II-69：m.p.,194.7-196.4℃； 1H NMR(400MHz,DMSO-d 6)δ11.36(s,1H),7.68(s,1H),7.55(s,1H),7.25(s,1H),7.12(s,1H),6.97(d,J＝7.2Hz,1H),6.80(s,1H),6.67(s,1H),4.81(s,2H),2.18(s,6H),1.76(s,3H). 13C NMR(150MHz,DMSO-d 6)δ164.65,154.41,152.11,151.42,141.57,138.69,134.08,132.09,131.14,130.27,128.43,124.34,120.61,119.51,115.57,109.60,49.57,19.88,19.02,12.41.HRMS(ESI)理论值C 20H 19ClN 2O 3[M-H] -:371.1162,实测值:371.1155. Compound II-69: mp, 194.7-196.4°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.36(s, 1H), 7.68(s, 1H), 7.55(s, 1H), 7.25(s, 1H),7.12(s,1H),6.97(d,J=7.2Hz,1H),6.80(s,1H),6.67(s,1H),4.81(s,2H),2.18(s,6H), 1.76(s,3H) .13C NMR(150MHz,DMSO-d 6 )δ164.65,154.41,152.11,151.42,141.57,138.69,134.08,132.09,131.14,130.27,128.43,124.354,120.691,119 49.57, 19.88, 19.02, 12.41. HRMS (ESI) theoretical value C 20 H 19 ClN 2 O 3 [MH] - : 371.1162, measured value: 371.1155.
化合物II-70：m.p.,163.4-164.4℃； 1H NMR(400MHz,Chloroform-d)δ8.70(s,1H),7.39(d,J＝1.6Hz,1H),7.14–7.10(m,1H),7.09(d,J＝8.2Hz,1H),6.94(s,1H),6.88(d,J＝8.4Hz,1H),6.80(d,J＝1.4Hz,1H),6.72(dd,J＝8.1,2.1Hz,1H),4.84(s,2H),2.35(q,J＝7.2Hz,2H),2.24(s,6H),1.12(t,J＝7.4Hz,3H). 13C NMR(151MHz,DMSO-d 6)δ163.83,154.02,151.70,150.90,140.71,138.29,133.73,131.70,130.74,129.86,127.99,123.92,120.20,119.13,115.19,114.98,49.33,19.54,19.50,18.63,13.06.HRMS(ESI)理论值C 21H 21ClN 2O 3[M-H] -:385.1319,实测值:385.1306. Compound II-70: mp, 163.4-164.4°C; 1 H NMR (400MHz, Chloroform-d) δ8.70(s, 1H), 7.39(d, J=1.6Hz, 1H), 7.14-7.10(m, 1H ), 7.09(d, J=8.2Hz, 1H), 6.94(s, 1H), 6.88(d, J=8.4Hz, 1H), 6.80(d, J=1.4Hz, 1H), 6.72(dd,J =8.1, 2.1Hz, 1H), 4.84(s, 2H), 2.35(q, J=7.2Hz, 2H), 2.24(s, 6H), 1.12(t, J=7.4Hz, 3H). 13 C NMR (151MHz,DMSO-d 6 )δ163.83,154.02,151.70,150.90,140.71,138.29,133.73,131.70,130.74,129.86,127.99,123.92,120.20,119.13,115.19,114.98,49.33,19.54,19.50,18.63,13.06. HRMS (ESI) theoretical value C 21 H 21 ClN 2 O 3 [MH] - : 385.1319, measured value: 385.1306.
化合物II-71：m.p.,177.8-178.7℃； 1H NMR(600MHz,Chloroform-d)δ8.83(s,1H),7.40(s,1H),7.07(dd,J＝10.0,3.9Hz,2H),7.02–6.96(m,2H),6.72(d,J＝7.9Hz,1H),6.67(d,J＝8.4Hz,1H),4.81(s,2H),2.32(s,3H),2.14(s,3H),1.91(s,3H). 13C NMR(100MHz,Chloroform-d)δ153.73,153.29,151.76,148.87,139.19,131.46,128.65,128.31,126.41,126.14,125.86,124.67,118.35,116.95,108.94,46.69,20.19,16.69,12.18,11.28,1.15.HRMS(ESI)理论值C 21H 21ClN 2O 3[M-H] -:385.1319,实测值:385.1313. Compound II-71: mp, 177.8-178.7°C; 1 H NMR (600MHz, Chloroform-d) δ8.83(s, 1H), 7.40(s, 1H), 7.07(dd, J=10.0, 3.9Hz, 2H ),7.02–6.96(m,2H),6.72(d,J＝7.9Hz,1H),6.67(d,J＝8.4Hz,1H),4.81(s,2H),2.32(s,3H),2.14 (s,3H),1.91(s,3H). 13 C NMR (100MHz,Chloroform-d)δ153.73,153.29,151.76,148.87,139.19,131.46,128.65,128.31,126.41,126.14,125.86,124.69,116.3 , 108.94, 46.69, 20.19, 16.69, 12.18, 11.28, 1.15. HRMS (ESI) theoretical value C 21 H 21 ClN 2 O 3 [MH] - : 385.1319, measured value: 385.1313.
合物II-72：m.p.,161.3-162.7℃； 1H NMR(400MHz,DMSO-d 6)δ11.87(s,1H),8.42(s,1H),7.61(d,J＝1.6Hz,1H),7.30(dd,J＝8.4,1.6Hz,1H),7.13(d,J＝8.2Hz,1H),6.97(d,J＝8.4Hz,1H),6.81(d,J＝2.1Hz,1H),6.68(dd,J＝8.1,2.3Hz,1H),4.84(s,2H),2.19(s,6H). 13C NMR(150MHz,Chloroform-d)δ160.87,155.18,153.05,151.63,146.31,146.25,139.51,134.27,132.93,131.95,131.30,129.43,125.11,121.31,120.37,116.42,96.57,51.09,20.70,19.84.HRMS(ESI)理论值C 17H 16BrClN 2O 3[M-H] -:435.0111,实测值:435.0099. Compound II-72: mp, 161.3-162.7°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.87(s, 1H), 8.42(s, 1H), 7.61(d, J=1.6Hz, 1H ), 7.30(dd, J＝8.4, 1.6Hz, 1H), 7.13(d, J＝8.2Hz, 1H), 6.97(d, J＝8.4Hz, 1H), 6.81(d, J＝2.1Hz, 1H ),6.68(dd,J＝8.1,2.3Hz,1H),4.84(s,2H),2.19(s,6H). 13 C NMR(150MHz,Chloroform-d)δ160.87,155.18,153.05,151.63,146.31, 146.25, 139.51, 134.27, 132.93, 131.95, 131.30, 129.43, 125.11, 121.31, 120.37, 116.42, 96.57, 51.09, 20.70, 19.84. HRMS (ESI) Theoretical C 17 H 11 [ M14H 5 ] 0 : BrClN 2 O 3 , measured value: 435.0099.
合物II-73：m.p.,204.3-205.7℃； 1H NMR(400MHz,DMSO-d 6)δ11.77(s,1H),7.44(s,1H),7.21(d,J＝8.1Hz,1H),7.12(d,J＝8.1Hz,1H),6.94(d,J＝8.3Hz,1H),6.78(s,1H),6.66(d,J＝8.2Hz,1H),5.17(s,1H),4.87(s,2H),3.81(s,3H),2.18(s,6H). 13C NMR(100MHz,DMSO-d 6)δ165.73,162.90,155.01,153.74,151.29,138.38,133.95,132.94,130.24,129.22,127.48,123.59,119.39,117.58,116.12,85.87,56.20,46.44,19.80,19.13.HRMS(ESI)理论值C 20H 19ClN 2O 4[M-H] -:387.1112,实测值:387.1103. Compound II-73: mp, 204.3-205.7°C; 1 H NMR (400MHz, DMSO-d 6 ) δ11.77(s, 1H), 7.44(s, 1H), 7.21(d, J=8.1Hz, 1H ), 7.12(d, J=8.1Hz, 1H), 6.94(d, J=8.3Hz, 1H), 6.78(s, 1H), 6.66(d, J=8.2Hz, 1H), 5.17(s, 1H ),4.87(s,2H),3.81(s,3H),2.18(s,6H). 13 C NMR(100MHz,DMSO-d 6 )δ165.73,162.90,155.01,153.74,151.29,138.38,133.95,132.94, 130.24, 129.22, 127.48, 123.59, 119.39, 117.58, 116.12, 85.87, 56.20, 46.44, 19.80, 19.13. HRMS (ESI) theoretical value C 20 H 19 ClN 2 O 4 [MH] - :387.1112, found value: 387.110387
化合物II-74：m.p.,155.8-156.9℃； 1H NMR(400MHz,Chloroform-d)δ8.91(s,1H),7.33(s,2H),7.03(s,1H),7.01(s,1H),6.65(d,J＝2.2Hz,1H),6.49(dd,J＝8.2,2.4Hz,1H),4.85(s,2H),2.22(s,3H),2.20(s,3H),1.96(s,3H). 13C NMR(100MHz,Chloroform-d)δ165.16,153.57,150.91,149.30,141.19,138.43,133.96,133.51,130.24,128.37,127.20,118.62,114.60,108.94,50.31,19.80,19.13,12.43.HRMS(ESI)理论值C 20H 18Cl 2N 2O 3[M-H] -: 405.0773,实测值:405.0798. Compound II-74: mp, 155.8-156.9°C; 1 H NMR (400MHz, Chloroform-d) δ8.91(s,1H),7.33(s,2H),7.03(s,1H),7.01(s,1H ),6.65(d,J=2.2Hz,1H),6.49(dd,J=8.2,2.4Hz,1H),4.85(s,2H),2.22(s,3H),2.20(s,3H),1.96 (s,3H). 13 C NMR (100MHz, Chloroform-d) δ165.16, 153.57, 150.91, 149.30, 141.19, 138.43, 133.96, 133.51, 130.24, 128.37, 127.20, 118.62, 114.60, 108.380, 19, 5 12.43. HRMS (ESI) theoretical value C 20 H 18 Cl 2 N 2 O 3 [MH] - : 405.0773, found value: 405.0798.
化合物II-75：m.p.,177.4-179.0℃； 1H NMR(400MHz,Chloroform-d)δ9.00(s,1H),7.23(s,2H),7.02(d,J＝8.3Hz,1H),6.65(d,J＝2.1Hz,1H),6.49(dd,J＝8.2,2.4Hz,1H),5.66(s,1H),5.07(s,2H),2.25(s,3H),2.22(s,3H),2.20(s,3H). 13C NMR(100MHz,Chloroform-d)δ165.18,153.57,152.75,149.31,148.82,138.43,134.55,133.96,130.24,127.85,127.27,118.62,114.60,104.02,46.13,19.80,19.13,18.77.HRMS(ESI)理论值C 20H 18Cl 2N 2O 3[M-H] -:405.0773,实测值:405.0791. Compound II-75: mp, 177.4-179.0°C; 1 H NMR (400MHz, Chloroform-d) δ9.00(s, 1H), 7.23(s, 2H), 7.02(d, J=8.3Hz, 1H), 6.65(d,J=2.1Hz,1H),6.49(dd,J=8.2,2.4Hz,1H),5.66(s,1H),5.07(s,2H),2.25(s,3H),2.22(s ,3H),2.20(s,3H). 13 C NMR(100MHz,Chloroform-d)δ165.18,153.57,152.75,149.31,148.82,138.43,134.55,133.96,130.24,127.85,127.27,118.62,1140.60 , 19.80, 19.13, 18.77. HRMS (ESI) theoretical value C 20 H 18 Cl 2 N 2 O 3 [MH] - : 405.0773, measured value: 405.0791.
测试例1test case 1
本测试例用来说明本发明提供的部分具体化合物对琥珀酸脱氢酶(SDH)的抑制活性测试。This test example is used to illustrate the inhibitory activity test of some specific compounds provided by the present invention on succinate dehydrogenase (SDH).
测试所用的酶为从猪心中分离获得的猪心线粒体来源的琥珀酸脱氢酶，反应底物为琥珀酸和2,6-二氯靛酚钠(2,6-dichlorophenolindophenol，DCIP)。测试时目标化合物用DMSO溶解，并配成50mM的储液，使用时用水稀释至浓度10μM。本测试例的测试结果见表1。The enzyme used in the test is succinate dehydrogenase derived from pig heart mitochondria isolated from pig hearts, and the reaction substrates are succinic acid and 2,6-dichloroindophenol sodium (2,6-dichlorophenolindophenol, DCIP). During the test, the target compound was dissolved in DMSO and prepared as a 50 mM stock solution, which was diluted with water to a concentration of 10 μM when used. The test results of this test case are shown in Table 1.
表1Table 1
编号serial number I％I%
I-2I-2 44.64％44.64%
I-3I-3 34.09％34.09%
I-4I-4 46.32％46.32%
II-1II-1 34.44％34.44%
II-3II-3 33.56％33.56%
II-4II-4 31.53％31.53%
II-5II-5 47.97％47.97%
II-6II-6 45.60％45.60%
II-8II-8 48.25％48.25%
II-9II-9 33.68％33.68%
II-10II-10 44.55％44.55%
II-11II-11 49.56％49.56%
II-12II-12 43.90％43.90%
II-13II-13 48.40％48.40%
II-14II-14 47.23％47.23%
II-15II-15 49.04％49.04%
II-16II-16 34.06％34.06%
II-18II-18 30.10％30.10%
II-29II-29 30.26％30.26%
II-50II-50 45.13％45.13%
A15A15 27.12％27.12%
表1中显示本发明的化合物对猪心来源的SDH具有较好的抑制活性，并且明显优于对照化合物A15的抑制活性。Table 1 shows that the compounds of the present invention have good inhibitory activity on SDH derived from porcine heart, which is obviously better than that of the reference compound A15.
测试例2test case 2
本测试例用来说明使用发明提供的部分具体化合物进行活体水平的玉米锈病和黄瓜霜霉病杀菌活性测试。This test example is used to illustrate the use of some specific compounds provided by the invention to test the fungicidal activity of corn rust and cucumber downy mildew at the living level.
具体测试方法为：The specific test method is:
黄瓜霜霉病杀菌活性测试：试验采取幼苗盆栽法。Test of fungicidal activity against cucumber downy mildew: the test adopts the seedling pot method.
幼苗盆栽试验的处理，实验化合物剂量见表2、表4。另设不施药剂的空白对照。每个处理重复3次。选用2片真叶平展的黄瓜盆栽幼苗，剪去生长点，用喉头喷雾器进行人工手动喷雾。处理后的试验材料均在药液晾干，24h后接种黄瓜霜霉病孢子悬浮液，然后放置人工气候室中培养。培养温度：昼25℃。夜间20℃；相对湿度：90％～100％。保湿培养7天后调查防治效果。调查方法按农业部药检所《农药室内生物测定试验准则》-杀菌剂防 治黄瓜霜霉病试验盆栽法(NY/T 1156.7-2006)的分级标准分级记载，以病情指数计算防治效果。See Table 2 and Table 4 for the treatment of the seedling pot test, and the dosage of the experimental compound. A blank control without drug application was also set up. Each treatment was repeated 3 times. Select 2 cucumber potted seedlings with flat true leaves, cut off the growth point, and spray manually with a throat sprayer. The treated test materials were all dried in the liquid medicine, inoculated with cucumber downy mildew spore suspension 24 hours later, and then placed in an artificial climate chamber for cultivation. Cultivation temperature: daytime 25°C. 20°C at night; relative humidity: 90% to 100%. After 7 days of moisturizing culture, the control effect was investigated. The investigation method was recorded in accordance with the grading standards of the "Pesticide Indoor Bioassay Test Guidelines" - Fungicide Control of Cucumber Downy Mildew Test Pot Planting Method (NY/T 1156.7-2006) by the Institute of Drug Control of the Ministry of Agriculture, and the control effect was calculated by the disease index.
玉米锈病杀菌活性测试：试验采取幼苗盆栽法。Bactericidal activity test of corn rust: the test adopts the seedling pot method.
幼苗盆栽试验的处理，实验化合物剂量见表3。另设不施药剂的空白对照。每个处理重复3次。选择两叶期长势一致的盆栽玉米苗。采用茎叶喷雾，喷雾处理后将试材在通风橱或室温中处阴干24h。药剂处理后24小时，接种玉米锈病孢子悬浮液。接种后的盆栽玉米苗置于保湿箱(室)或人工气候室内(温度为25℃，相对湿度>80％)培养，24h后置于光照强度大于2000lx的培养箱(室)或温度高湿培养，7d后根据空白对照发病情况进行分级调查。See Table 3 for the treatment of seedling pot experiments, and the doses of the experimental compounds. A blank control without drug application was also set up. Each treatment was repeated 3 times. Choose potted corn seedlings with consistent growth in the two-leaf stage. Spray the stems and leaves, and dry the test materials in a fume hood or at room temperature for 24 hours after spraying. 24 hours after the chemical treatment, the corn rust spore suspension was inoculated. After inoculation, the potted corn seedlings are cultivated in a humidity chamber (room) or in an artificial climate room (temperature is 25°C, relative humidity > 80%), and after 24 hours, they are placed in an incubator (room) with a light intensity greater than 2000 lx or with a high temperature and high humidity. After 7 days, a graded investigation was carried out according to the incidence of the blank control group.
采用以下分级方法：The following grading methods are used:
0级：无病；1级：病斑面积占整片叶面积的5％以下；3级：病斑面积占整片叶面积的6％～10％；5级：病斑面积占整片叶面积的11％～25％；7级：病斑面积占整片叶面积的26％～50％；9级：病斑面积占整片叶面积的50％以上。Grade 0: No disease; Grade 1: Lesion area accounts for less than 5% of the entire leaf area; Grade 3: Lesion area accounts for 6% to 10% of the entire leaf area; Grade 5: Lesion area accounts for the entire leaf area 11% to 25% of the area; Grade 7: the lesion area accounts for 26% to 50% of the entire leaf area; Grade 9: the lesion area accounts for more than 50% of the entire leaf area.
病情指数及防治效果计算方法如下：The calculation method of disease index and control effect is as follows:
Figure PCTCN2022099231-appb-000016
Figure PCTCN2022099231-appb-000016
式中：CK 0空白对照区施药前病情指数，CK 1空白对照区施药后病情指数，PT 0药剂处理区施药前病情指数，PT 1药剂处理区施药后病情指数。 In the formula: disease index before application in CK 0 blank control area, disease index after application in CK 1 blank control area, disease index before application in PT 0 drug treatment area, disease index after application in PT 1 drug treatment area.
防效评级结果分别列于表2、表3和表4中。The control effect rating results are listed in Table 2, Table 3 and Table 4 respectively.
表2Table 2
Figure PCTCN2022099231-appb-000017
Figure PCTCN2022099231-appb-000017
90％≦A≦100％，75％≦B<90％，60％≦C<75％，45％≦D<60％，0％≦E<45％90%≦A≦100%, 75%≦B<90%, 60%≦C<75%, 45%≦D<60%, 0%≦E<45%
表3table 3
编号serial number 玉米锈病防效等级，浓度(100mg/L)/防效评级Corn rust control effect level, concentration (100mg/L) / control effect rating
II-1II-1 BB
II-2II-2 AA
II-3II-3 AA
II-4II-4 AA
II-5II-5 AA
II-9II-9 BB
II-10II-10 AA
II-11II-11 BB
II-13II-13 AA
II-14II-14 BB
A15A15 EE.
90％≦A≦100％，75％≦B<90％，60％≦C<75％，45％≦D<60％，0％≦E<45％90%≦A≦100%, 75%≦B<90%, 60%≦C<75%, 45%≦D<60%, 0%≦E<45%
表4Table 4
Figure PCTCN2022099231-appb-000018
Figure PCTCN2022099231-appb-000018
Figure PCTCN2022099231-appb-000019
Figure PCTCN2022099231-appb-000019
90％≦A≦100％，75％≦B<90％，60％≦C<75％，45％≦D<60％，0％≦E<45％90%≦A≦100%, 75%≦B<90%, 60%≦C<75%, 45%≦D<60%, 0%≦E<45%
从表2中可以看出，本发明的化合物I-1、化合物I-2、化合物I-3、化合物I-4在100mg/L的浓度下对玉米锈病、黄瓜霜霉病均表现出了较好的防治效果。特别地，针对黄瓜霜霉病，化合物I-1、化合物I-2、化合物I-3、化合物I-4在例如25mg/L时均明显优于对照化合物A15。As can be seen from Table 2, compound 1-1 of the present invention, compound 1-2, compound 1-3, compound 1-4 have all shown relatively to corn rust, cucumber downy mildew at the concentration of 100mg/L. Good control effect. In particular, for cucumber downy mildew, compound I-1, compound I-2, compound I-3, and compound I-4 were all significantly better than the control compound A15 at, for example, 25 mg/L.
由表3和表4的结果可知，本发明的化合物对玉米锈病和黄瓜霜霉病均具有良好的防治效果，尤其是对黄瓜霜霉病，绝大多数化合物在6.25mg/L的浓度下仍然维持有75％以上的防效。As can be seen from the results of table 3 and table 4, the compound of the present invention all has good control effect to corn rust and cucumber downy mildew, especially to cucumber downy mildew, most of the compounds are still under the concentration of 6.25mg/L Maintain a control effect of more than 75%.
测试例3：Test case 3:
本测试例用来说明使用表4中活性相对更好的部分化合物进行活体水平的黄瓜霜霉病杀菌活性测试。This test example is used to illustrate the use of some compounds with relatively better activity in Table 4 to test the fungicidal activity of cucumber downy mildew at the in vivo level.
测试方法和评价方法与测试例2相同。防效评级列于表5中。The test method and evaluation method are the same as in Test Example 2. The control ratings are listed in Table 5.
表5table 5
Figure PCTCN2022099231-appb-000020
Figure PCTCN2022099231-appb-000020
90％≦A≦100％，75％≦B<90％，60％≦C<75％，45％≦D<60％，0％≦E<45％90%≦A≦100%, 75%≦B<90%, 60%≦C<75%, 45%≦D<60%, 0%≦E<45%
由上述结果可知，本发明提供的化合物针对黄瓜霜霉病、大豆锈病、玉米锈病、水稻纹枯病、小麦白粉病、黄瓜炭疽病、黄瓜白粉病、大豆灰霉病、水稻稻瘟病等植物病具有良好的防效。特别地，本发明提供的化合物在相对较低浓度下，对黄瓜霜霉病具有比现有技术(如吲唑磺菌胺)更好的防效。From the above results, it can be seen that the compounds provided by the present invention are effective against plant diseases such as cucumber downy mildew, soybean rust, corn rust, rice sheath blight, wheat powdery mildew, cucumber anthracnose, cucumber powdery mildew, soybean gray mold, and rice blast. Has good control effect. In particular, the compound provided by the present invention has better control effect on cucumber downy mildew than the prior art (such as indazole sulfasulfame) at a relatively low concentration.
以上详细描述了本发明的优选实施方式，但是，本发明并不限于此。在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，包括各个技术特征以任何其它的合适方式进行组合，这些简单变型和组合同样应当视为本发明所公开的内容，均属于本发明的保护范围。The preferred embodiments of the present invention have been described in detail above, however, the present invention is not limited thereto. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the disclosed content of the present invention. All belong to the protection scope of the present invention.

Claims (15)

  1. 一种地克珠利衍生物，其特征在于，该衍生物具有式(I)所示的结构式：A kind of diclazuril derivative, it is characterized in that, this derivative has the structural formula shown in formula (I):
    Figure PCTCN2022099231-appb-100001
    Figure PCTCN2022099231-appb-100001
    其中，在式(I)中，R 11、R 12、R 13、R 14、R 15、R 16、R 17、R 18、R 19各自独立地选自H、C 1-6的烷基、C 1-6的烷氧基、卤素、氰基。 Wherein, in formula (I), R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 are each independently selected from H, C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano.
  2. 根据权利要求1所述的地克珠利衍生物，其中，在式(I)中，R 11、R 12、R 13、R 14、R 15、R 16、R 17、R 18、R 19各自独立地选自H、C 1-4的烷基、卤素。 The diclazuril derivative according to claim 1, wherein, in formula (I), each of R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , and R 19 independently selected from H, C 1-4 alkyl, halogen.
  3. 根据权利要求1或2所述的地克珠利衍生物，其中，在式(I)中，R 11、R 12、R 13、R 14、R 15、R 19各自独立地选自H、卤素； The diclazuril derivative according to claim 1 or 2, wherein, in formula (I), R 11 , R 12 , R 13 , R 14 , R 15 , and R 19 are each independently selected from H, halogen ;
    R 16、R 17、R 18各自独立地选自H、卤素、C 1-3的烷基； R 16 , R 17 , and R 18 are each independently selected from H, halogen, and C 1-3 alkyl;
    优选地，在式(I)中，Preferably, in formula (I),
    R 11和R 14均为Cl； R 11 and R 14 are both Cl;
    R 12、R 13、R 15和R 19均为H； R 12 , R 13 , R 15 and R 19 are all H;
    R 16、R 17和R 18各自独立地选自H、F、Cl、Br、甲基。 R 16 , R 17 and R 18 are each independently selected from H, F, Cl, Br, methyl.
  4. 根据权利要求1-3中任意一项所述的地克珠利衍生物，其中，所述地克珠利衍生物为以下化合物中的任意一种：The diclazuril derivative according to any one of claims 1-3, wherein the diclazuril derivative is any one of the following compounds:
    Figure PCTCN2022099231-appb-100002
    Figure PCTCN2022099231-appb-100002
  5. 一种地克珠利衍生物，其特征在于，该衍生物具有式(II)所示的结构式：A diclazuril derivative, characterized in that the derivative has a structural formula shown in formula (II):
    Figure PCTCN2022099231-appb-100003
    Figure PCTCN2022099231-appb-100003
    其中，在式(II)中，Among them, in formula (II),
    Q为N或C(R 28)； Q is N or C (R 28 );
    R选自C 6-18的芳基、由组合A中的至少一种基团取代的C 6-18的芳基、含至少一个N原子的4-8元杂环基、由组合A中的至少一种基团取代的含至少一个N原子的4-8元杂环基；所述组合A由C 1-8的烷基、卤素、由至少一种卤素取代的C 1-8的烷基、C 1-8的烷氧基、苄基、由至少一种卤素取代的苯氧基组成； R is selected from a C 6-18 aryl group, a C 6-18 aryl group substituted by at least one group in combination A, a 4-8 membered heterocyclic group containing at least one N atom, a combination A A 4-8-membered heterocyclic group containing at least one N atom substituted by at least one group; the combination A is composed of C 1-8 alkyl, halogen, C 1-8 alkyl substituted by at least one halogen , C 1-8 alkoxy, benzyl, phenoxy substituted by at least one halogen;
    R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-8的烷基、C 1-8的烷氧基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-8 alkyl, C 1-8 alkoxy;
    R 25选自H、C 1-8的烷基； R 25 is selected from H, C 1-8 alkyl;
    R 26和R 27各自独立地选自H、卤素、C 1-8的烷基、C 1-8的烷氧基、氰基、硝基、由至少一种卤素取代的C 1-8的烷基、苄基、CH 3-C(O)-； R 26 and R 27 are each independently selected from H, halogen, C 1-8 alkyl, C 1-8 alkoxy, cyano, nitro, C 1-8 alkane substituted by at least one halogen Base, benzyl, CH 3 -C(O)-;
    R 28选自H、卤素、C 1-8的烷基、CH 3-O-C(O)-、C 1-8的烷氧基、由至少一种卤素取代的C 1-8的烷基； R 28 is selected from H, halogen, C 1-8 alkyl, CH 3 -OC(O)-, C 1-8 alkoxy, C 1-8 alkyl substituted by at least one halogen;
    或者Q为C(R 28)，且R 27与R 28一起环合形成5-10元碳环。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-10 membered carbocycle.
  6. 根据权利要求5所述的地克珠利衍生物，其中，在式(II)中，The diclazuril derivative according to claim 5, wherein, in formula (II),
    Q为N或C(R 28)； Q is N or C (R 28 );
    R选自C 6-12的芳基、由组合A中的至少一种基团取代的C 6-12的芳基、含1-3个N原子的5-7元杂环基、由组合A中的至少一种基团取代的含1-3个N原子的5-7元杂环基；所述组合A由C 1-6的烷基、卤素、由至少一种卤素取代的C 1-6的烷基、C 1-6的烷氧基、苄基、由至少一种卤素取代的苯氧基组成； R is selected from C 6-12 aryl group, C 6-12 aryl group substituted by at least one group in combination A, 5-7 membered heterocyclic group containing 1-3 N atoms, combination A A 5-7-membered heterocyclic group containing 1-3 N atoms substituted by at least one group in the group; said combination A is composed of C 1-6 alkyl, halogen, C 1- substituted by at least one halogen 6 alkyl, C 1-6 alkoxy, benzyl, phenoxy substituted by at least one halogen;
    R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-6的烷基、C 1-6的烷氧基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy;
    R 25选自H、C 1-6的烷基； R 25 is selected from H, C 1-6 alkyl;
    R 26和R 27各自独立地选自H、卤素、C 1-6的烷基、C 1-6的烷氧基、氰基、硝基、由至少一种卤素取代的C 1-6的烷基、苄基、CH 3-C(O)-； R 26 and R 27 are each independently selected from H, halogen, C 1-6 alkyl, C 1-6 alkoxy, cyano, nitro, C 1-6 alkane substituted by at least one halogen Base, benzyl, CH 3 -C(O)-;
    R 28选自H、卤素、C 1-6的烷基、CH 3-O-C(O)-、C 1-6的烷氧基、由至少一种卤素取代的C 1-6的烷基； R 28 is selected from H, halogen, C 1-6 alkyl, CH 3 -OC(O)-, C 1-6 alkoxy, C 1-6 alkyl substituted by at least one halogen;
    或者Q为C(R 28)，且R 27与R 28一起环合形成5-7元碳环。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered carbocycle.
  7. 根据权利要求5或6所述的地克珠利衍生物，其中，在式(II)中，The diclazuril derivative according to claim 5 or 6, wherein, in formula (II),
    Q为N或C(R 28)； Q is N or C (R 28 );
    R选自苯基、由组合A中的至少一种基团取代的苯基、萘基、嘧啶基、联苯基、由组合A中的至少一种基团取代的联苯基、吡唑基、由组合A中的至少一种基团取代的吡唑基、吡啶基、由组合A中的至少一种基团取代的吡啶基；所述组合A由C 1-4的烷基、卤素、由至少一种卤素取代的C 1-4的烷基、C 1-4的烷氧基、苄基、4-Cl-苯氧基组成； R is selected from phenyl, phenyl substituted by at least one group in combination A, naphthyl, pyrimidinyl, biphenyl, biphenyl substituted by at least one group in combination A, pyrazolyl , pyrazolyl, pyridyl substituted by at least one group in combination A, pyridyl substituted by at least one group in combination A; said combination A is composed of C 1-4 alkyl, halogen, Composed of at least one halogen-substituted C 1-4 alkyl, C 1-4 alkoxy, benzyl, 4-Cl-phenoxy;
    R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-3的烷基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-3 alkyl;
    R 25选自H、甲基； R 25 is selected from H, methyl;
    R 26和R 27各自独立地选自H、卤素、C 1-3的烷基、C 1-3的烷氧基、氰基、硝基、由至少一种卤素取代的C 1-3的烷基、苄基、CH 3-C(O)-； R 26 and R 27 are each independently selected from H, halogen, C 1-3 alkyl, C 1-3 alkoxy, cyano, nitro, C 1-3 alkane substituted by at least one halogen Base, benzyl, CH 3 -C(O)-;
    R 28选自H、卤素、C 1-3的烷基、CH 3-O-C(O)-、C 1-3的烷氧基、由至少一种卤素取代的C 1-3的烷基； R 28 is selected from H, halogen, C 1-3 alkyl, CH 3 -OC(O)-, C 1-3 alkoxy, C 1-3 alkyl substituted by at least one halogen;
    或者Q为C(R 28)，且R 27与R 28一起环合形成5-7元不饱和碳环； Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered unsaturated carbocycle;
    优选地，在式(II)中，Preferably, in formula (II),
    Q为N或C(R 28)； Q is N or C (R 28 );
    R选自苯基、由组合A中的至少一种基团取代的苯基、萘基、嘧啶基、联苯基、由组合A中的至少一种基团取代的联苯基、吡唑基、由组合A中的至少一种基团取代的吡唑基、吡啶基、由组合A中的至少一种基团取代的吡啶基；所述组合A由C 1-4的烷基、卤素、由至少一个F取代的C 1-3的烷基、甲氧基、苄基、4-Cl-苯氧基组成； R is selected from phenyl, phenyl substituted by at least one group in combination A, naphthyl, pyrimidinyl, biphenyl, biphenyl substituted by at least one group in combination A, pyrazolyl , pyrazolyl, pyridyl substituted by at least one group in combination A, pyridyl substituted by at least one group in combination A; said combination A is composed of C 1-4 alkyl, halogen, Composed of at least one F-substituted C 1-3 alkyl, methoxy, benzyl, 4-Cl-phenoxy;
    R 21、R 22、R 23和R 24各自独立地选自H、卤素、氰基、C 1-3的烷基； R 21 , R 22 , R 23 and R 24 are each independently selected from H, halogen, cyano, C 1-3 alkyl;
    R 25选自H、甲基； R 25 is selected from H, methyl;
    R 26和R 27各自独立地选自H、Cl、Br、C 1-3的烷基、甲氧基、氰基、硝基、由至少一个F取代的C 1-3的烷基、苄基、CH 3-C(O)-； R 26 and R 27 are each independently selected from H, Cl, Br, C 1-3 alkyl, methoxy, cyano, nitro, C 1-3 alkyl substituted by at least one F, benzyl , CH 3 -C(O)-;
    R 28选自H、Cl、甲基、CH 3-O-C(O)-、甲氧基、由至少一个F取代的C 1-3的烷基； R 28 is selected from H, Cl, methyl, CH 3 -OC(O)-, methoxy, C 1-3 alkyl substituted by at least one F;
    或者Q为C(R 28)，且R 27与R 28一起环合形成5-7元不饱和碳环，所述不饱和碳环中桥原子上的碳原子为不饱和碳原子。 Or Q is C(R 28 ), and R 27 and R 28 are cyclized together to form a 5-7 membered unsaturated carbocycle, and the carbon atom on the bridging atom in the unsaturated carbocycle is an unsaturated carbon atom.
  8. 根据权利要求5-7中任意一项所述的地克珠利衍生物，其中，所述地克珠利衍生物为以下化合物中的任意一种：The diclazuril derivative according to any one of claims 5-7, wherein the diclazuril derivative is any one of the following compounds:
    Figure PCTCN2022099231-appb-100004
    Figure PCTCN2022099231-appb-100004
    Figure PCTCN2022099231-appb-100005
    Figure PCTCN2022099231-appb-100005
    Figure PCTCN2022099231-appb-100006
    Figure PCTCN2022099231-appb-100006
    Figure PCTCN2022099231-appb-100007
    Figure PCTCN2022099231-appb-100007
  9. 权利要求1-8中任意一项所述的地克珠利衍生物作为线粒体琥珀酸脱氢酶抑制剂在农药中的应用。Use of the diclazuril derivative described in any one of claims 1-8 as an inhibitor of mitochondrial succinate dehydrogenase in pesticides.
  10. 权利要求1-8中任意一项所述的地克珠利衍生物在抗植物病中的应用。The application of the diclazuril derivative described in any one of claims 1-8 in resisting plant diseases.
  11. 根据权利要求10所述的应用，其中，所述植物病为植物真菌病、植物卵菌病中的至少一种；The application according to claim 10, wherein the plant disease is at least one of plant mycoses and plant oomycosis;
    优选地，所述植物病为黄瓜霜霉病、大豆锈病、玉米锈病、黄瓜灰霉病、黄瓜白粉病和水稻纹枯病中的至少一种。Preferably, the plant disease is at least one of cucumber downy mildew, soybean rust, corn rust, cucumber gray mold, cucumber powdery mildew and rice sheath blight.
  12. 一种用于抗植物病的杀菌剂，其特征在于，该杀菌剂的活性成分为权利要求1-8中任意一项所述的地克珠利衍生物中的至少一种，以所述杀菌剂的总重量计，所述活性成分的含量为0.1-100重量％。A bactericide for resisting plant diseases, characterized in that, the active ingredient of the bactericide is at least one of the diclazuril derivatives described in any one of claims 1-8, with the bactericidal Based on the total weight of the agent, the content of the active ingredient is 0.1-100% by weight.
  13. 根据权利要求12所述的杀菌剂，其中，所述活性成分的含量为1-98重量％。The fungicide according to claim 12, wherein the content of the active ingredient is 1-98% by weight.
  14. 根据权利要求12或13所述的杀菌剂，其中，所述活性成分的含量为5-90重量％。The fungicide according to claim 12 or 13, wherein the content of the active ingredient is 5-90% by weight.
  15. 根据权利要求12-14中任意一项所述的杀菌剂，其中，所述杀菌剂的剂型选自水合剂、粉剂、乳剂、悬浮剂、乳油剂和粒剂中的至少一种。The fungicide according to any one of claims 12-14, wherein the dosage form of the fungicide is selected from at least one of hydration, powder, emulsion, suspension, emulsifiable concentrate and granule.
PCT/CN2022/099231 2021-06-16 2022-06-16 Diclazuril derivative and application thereof, and fungicide for combating plant diseases WO2022262821A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110665569.X 2021-06-16
CN202110665569 2021-06-16

Publications (1)

Publication Number Publication Date
WO2022262821A1 true WO2022262821A1 (en) 2022-12-22

Family

ID=84421828

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/099231 WO2022262821A1 (en) 2021-06-16 2022-06-16 Diclazuril derivative and application thereof, and fungicide for combating plant diseases

Country Status (2)

Country Link
CN (2) CN115477622B (en)
WO (1) WO2022262821A1 (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1175577A (en) * 1996-08-30 1998-03-11 武田药品工业株式会社 1, 2, 4 -triazine -3, 5 -dione derivatives, their production and use thereof
US5994355A (en) * 1993-10-15 1999-11-30 Takeda Chemical Industries, Ltd. 1, 2, 4-Triazin-3-one derivatives, production and use thereof
CN107459493A (en) * 2016-06-02 2017-12-12 华中师范大学 Diclazuril derivative and its application and the bactericide containing the derivative

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014025993A1 (en) * 2012-08-08 2014-02-13 The Johns Hopkins University Inhibitors of d-amino acid oxidase
WO2014179144A1 (en) * 2013-04-29 2014-11-06 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
RU2628456C1 (en) * 2016-06-29 2017-08-17 Федеральное Государственное Бюджетное Учреждение Науки Институт Молекулярной Биологии Им. В.А. Энгельгардта Российской Академии Наук (Имб Ран) New pyrimidine inhibitors of human adenovirus replication
CN113527221B (en) * 2020-04-20 2023-06-23 江苏中旗科技股份有限公司 Dekkolii derivative, application thereof and bactericide for resisting plant mycosis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5994355A (en) * 1993-10-15 1999-11-30 Takeda Chemical Industries, Ltd. 1, 2, 4-Triazin-3-one derivatives, production and use thereof
CN1175577A (en) * 1996-08-30 1998-03-11 武田药品工业株式会社 1, 2, 4 -triazine -3, 5 -dione derivatives, their production and use thereof
CN107459493A (en) * 2016-06-02 2017-12-12 华中师范大学 Diclazuril derivative and its application and the bactericide containing the derivative

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE REGISTRY 4 November 2015 (2015-11-04), ANONYMOUS : "-2,4(1H,3H)-Pyrimidinedione, 1-[[4-(4-bromophenoxy)phenyl]methyl]- (CA INDEX NAME) ", XP093014682, retrieved from STN Database accession no. 1817862-61-5 *

Also Published As

Publication number Publication date
CN115477622B (en) 2023-09-22
CN115477623A (en) 2022-12-16
CN115477623B (en) 2023-09-26
CN115477622A (en) 2022-12-16

Similar Documents

Publication Publication Date Title
CN103649049B (en) For 3-(biphenyl-3-base)-8,8-two fluoro-hydroxyl-1-azaspiro [4.5]-3-in the last of the ten Heavenly stems alkene-2-ketone being replaced treated and the spirocyclic ketoenols being optionally substituted by halogen
TW201702229A (en) Novel 5-substituted imidazole derivatives
JPH05310748A (en) Thienopyrimidine derivative
JPS59225150A (en) Pesticidal fragrant compound, synthesis and intermediate therefor, drug containing same and use as medicine
TW200906807A (en) Piperazine compounds having herbicidal action
JPS61277652A (en) Acrylic acid ester and fungicide
TWI647216B (en) Substituted pyrazolylpyrazole derivative and use of same as herbicide
JPS59205368A (en) Microbicidal
Zhang et al. Discovery of novel bis-sulfoxide derivatives bearing acylhydrazone and benzothiazole moieties as potential antibacterial agents
US3397273A (en) Controlling phytopathogenic fungi on plants with 3-pyridyl methane derivatives
KR860001001B1 (en) Process for the preparation of majusculamide c
WO2022127564A1 (en) Isoxazoline-containing pyridine biphenyl compounds, preparation method therefor and use thereof
CN113278020B (en) Pityriacitrin alkaloid derivative containing acylthiourea structure and preparation method and application thereof
FR2606971A1 (en) Carboxylic acid amide(s) used as herbicide antidotes
KR100191182B1 (en) Pyrazole derivatives having herbicidal activity, their preparation and their use
JPH05310743A (en) Furopyrimidine derivative
WO2022262821A1 (en) Diclazuril derivative and application thereof, and fungicide for combating plant diseases
JPS60185783A (en) (2-imidazoline-2-yl)thieno- and furo(2,3-b) and (3,2-b) pyridines
CN105960401B (en) Pyridyl group or pyrimidyl compounds
AU2017353352B2 (en) Antimicrobial compounds
CN106749288B (en) N- (substituted-phenyl) Bi Zuo Bing fraxinellones analog derivative, preparation method and application
CN113620894A (en) Oxadiazole thioether compounds containing amide substructure as well as preparation method and application thereof
US5494888A (en) 6-chloro-2-(4,6-dimethoxypyrimidin-2-yl)oxybenzoic acid imino ester derivatives, processes for their production and a method for their application as herbicides
WO2011063615A1 (en) Macrocyclic amides, pharmaceutical compositions, preparation methods and uses thereof
JPH11292720A (en) Herbicide containing condensed imidazolinone derivative

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22824294

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22824294

Country of ref document: EP

Kind code of ref document: A1