WO2019056247A1 - Triazinone derivative containing acylhydrazone structure and preparation method therefor, and insecticidal and bactericidal uses thereof - Google Patents

Triazinone derivative containing acylhydrazone structure and preparation method therefor, and insecticidal and bactericidal uses thereof Download PDF

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WO2019056247A1
WO2019056247A1 PCT/CN2017/102601 CN2017102601W WO2019056247A1 WO 2019056247 A1 WO2019056247 A1 WO 2019056247A1 CN 2017102601 W CN2017102601 W CN 2017102601W WO 2019056247 A1 WO2019056247 A1 WO 2019056247A1
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group
substituted
formula
nmr
dmso
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PCT/CN2017/102601
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French (fr)
Chinese (zh)
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汪清民
宋红健
杨岩
刘玉秀
王兹稳
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南开大学
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/36—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< directly attached to at least one heterocyclic ring; Thio analogues thereof
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the invention belongs to the technical field of pesticides, and particularly relates to a hydrazide-containing triazinone derivative, a preparation method thereof and application thereof in insecticide and sterilization.
  • pymetrozine which belongs to triazinone compounds and has a new mode of action, which has excellent control effects on a variety of sucking mouthparts.
  • pymetrozine has no cross-resistance with traditional organochlorine, organochlorine, carbamate, pyrethroid, 1-phenylpyrazole, and neonicotinoid insecticides. Therefore, pymetrozine can be applied.
  • Pyridoxone has unique toxicological properties, is compatible with the environment, has interactive selectivity for insects, and is beneficial to the implementation of integrated control measures and comprehensive treatment of resistance in agricultural production.
  • pymetrozine can also reduce the occurrence of crop virus damage.
  • the above advantages determine the broad application prospect of pymetrozine in agricultural production. Summarizing the structure-activity relationship that has been reported, it is found that the previous research work on pymetrozine insecticides mainly focused on modifying and modifying the triazinone ring and the pyridine ring moiety, while the modification of the intermediate linker was less reported.
  • Beriger reported the structure of compounds in which an imine was converted to an amide, but no activity data was reported (Beriger, E.; Kristinsson, H. US 5324842. 1994-06-28.).
  • the hydrazide-containing triazinone derivative of the present invention exhibits excellent insecticidal activity and also has bactericidal activity.
  • a hydrazide-containing triazinone derivative wherein the triazinone derivative is a compound represented by the following formula (I):
  • the compound represented by the formula (I) is selected from one of the compounds shown in the I a series, the I b series, and the I c series:
  • R 2 is hydrogen
  • R 1 is a C2-C10 hydrocarbon group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group.
  • substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C6 hydrocarbon group, and a C1-C6 alkoxy group;
  • R 1 and R 2 are each independently selected from a C1-C10 hydrocarbon group, a substituted or unsubstituted phenyl group and a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, wherein The substituents of the substituted phenyl are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl and One or more of C1-C6 alkoxy groups; or, R 1 and R 2 are cyclized to form a C3-C10 carbon ring;
  • R 2 is a methyl group
  • R 1 is R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C10 hydrocarbyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or phenyl substituted C1-C10 Alkoxy, C1-C10 alkylamino, substituted carbonyl and substituted carbonyloxy, substituted carbonyl and substituted carbonyloxy are each independently selected from phenyl, benzyl, C1-C10 alkane One or more of a C1-C10 alkoxy group and a C1-C10 alkylamine group.
  • a process for the preparation of the above triazinone derivative which comprises: reacting a semicarbazide triazolone of the formula (IV) with a formula (V) in a first organic solvent in the presence of a catalyst The compound shown is subjected to a dehydration condensation reaction to give a compound of the formula (I);
  • a third aspect of the invention provides the use of the above triazinone derivative for insecticidal purposes.
  • the fourth aspect of the invention provides the use of the above triazinone derivative for sterilization.
  • the triazinone derivatives provided by the present invention exhibit very excellent insecticidal activity and bactericidal activity.
  • a hydrazide-containing triazinone derivative wherein the triazinone derivative is a compound represented by the following formula (I):
  • the compound represented by the formula (I) is selected from one of the compounds shown in the I a series, the I b series, and the I c series:
  • R 2 is hydrogen
  • R 1 is a C2-C10 hydrocarbon group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group.
  • substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C6 hydrocarbon group, and a C1-C6 alkoxy group;
  • R 1 and R 2 are each independently selected from a C1-C10 hydrocarbon group, a substituted or unsubstituted phenyl group and a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, wherein The substituents of the substituted phenyl are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl and One or more of C1-C6 alkoxy groups; or, R 1 and R 2 are cyclized to form a C3-C10 carbon ring;
  • R 2 is a methyl group
  • R 1 is R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C10 hydrocarbyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or phenyl substituted C1-C10 Alkoxy, C1-C10 alkylamino, substituted carbonyl and substituted carbonyloxy, substituted carbonyl and substituted carbonyloxy are each independently selected from phenyl, benzyl, C1-C10 alkane One or more of a C1-C10 alkoxy group and a C1-C10 alkylamine group.
  • the substituted phenyl group, the substituted naphthyl group or the substituted benzyl group may be a single point substitution or a multiple point substitution.
  • R may represent two groups of R 1 and R 2 and may also represent a group which is cyclized.
  • R 1 and R 2 may also represent a group which is cyclized.
  • the hydrocarbon group of C1-C10 may be a C1-C10 alkyl group, or may be a C1-C10 hydrocarbon group having an unsaturated bond, and a specific example of the C1-C10 alkyl group may be, for example, a methyl group. ,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-decyl, n-decyl Wait.
  • the hydrocarbon group having an unsaturated bond for C1 to C10 may be a C2-C10 alkenyl group, and specific examples of the C2-C10 alkenyl group may be, for example, a vinyl group, an allyl group, or a 1-n-butene-4- Base, 1-n-penten-5-yl, 1-n-hexen-6-yl, 1-n-hepten-7-yl, 1-n-octene-8-yl, 1-n-decene-9-yl , 1-n-decene-10-yl group, and the like.
  • the alkyl group of C1-C8, the alkenyl group of C2-C8, the C2-C6 alkyl group, and the C1-C5 alkyl group may be selected from the above specific examples of the alkyl group or the alkenyl group and may be appropriately defined.
  • the alkoxy group of C1-C6 may be an alkoxy group formed by the above specific examples satisfying the alkyl group defined by 1 to 6 carbon atoms, and is, for example, a methoxy group, an ethoxy group, a n-propoxy group or the like.
  • cycloalkyl group of C3-C8 may be, for example: Wait.
  • the nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated nitrogen heterocyclic ring or a saturated nitrogen heterocyclic ring as long as the ring structure of the heterocyclic ring has a nitrogen atom as a structural atom and the heterocyclic ring has a carbon atom Numbers from 1 to 10, such as unsubstituted or C1-C6 alkyl-substituted pyrrole, unsubstituted or C1-C6 alkyl-substituted hydropyrrole, unsubstituted or C1-C7 alkyl substituted Imidazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated imidazole, unsubstituted or C1-C5 alkyl-substituted pyridine, unsubstituted or C1-C5 alkyl-substituted hydrogenated pyridine, unsubstituted Or a C1-C7
  • the oxygen-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated oxygen heterocyclic ring or a saturated oxygen heterocyclic ring as long as the heterocyclic ring structure has oxygen as a structural atom and the heterocyclic ring has a carbon atom.
  • Numbers from 1 to 10 such as unsubstituted or C1-C6 alkyl-substituted furan, unsubstituted or C1-C6 alkyl-substituted hydrofuran, unsubstituted or C1-C7 alkyl substituted Oxazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated oxazole, unsubstituted or C1-C3 alkyl-substituted 1,3-benzodioxan, unsubstituted or C1-C2 Alkyl-substituted 1,4-benzodioxins and the like.
  • the sulfur-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated sulfur heterocyclic ring or a saturated sulfur heterocyclic ring as long as the ring structure of the heterocyclic ring has sulfur as a structural atom and the heterocyclic ring has carbon atoms.
  • Numbers from 1 to 10 such as unsubstituted or C1-C6 alkyl-substituted thiophenes, unsubstituted or C1-C6 alkyl-substituted thiophenes, unsubstituted or C1-C7 alkyl substitutions Thiazole, unsubstituted or C1-C7 alkyl substituted thiazole or the like.
  • the halogen may be F, Cl, Br, I or the like.
  • the I a series of compounds: in the formula (I), R 2 is hydrogen, R 1 is a C2-C6 alkyl group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or not Substituted naphthyl, substituted or unsubstituted benzyl, nitrogen-containing heterocyclic ring having 2-8 carbon atoms, oxygen-containing heterocyclic ring having 2-8 carbon atoms, sulfur containing 2-8 carbon atoms Heterocyclic.
  • substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C5 alkyl group, and a C1-C5 alkoxy group.
  • R 1 and R 2 are each independently selected from a C1-C8 alkyl group, a C2-C8 alkenyl group, a substituted or unsubstituted phenyl group, and a 2- a nitrogen-containing heterocyclic ring of 8 carbon atoms, wherein the substituents of the substituted phenyl group are each independently selected from the group consisting of a hydroxyl group, a halogen, a cyano group, a nitro group, an ester group, a dimethylamino group, a trifluoromethyl group, and a trisium group.
  • the I c series compound in the formula (I), R 2 is a methyl group, and R 1 is R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C8 alkyl, C2-C8 alkenyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or a phenyl-substituted C1-C8 alkoxy group, a C1-C8 alkylamino group, a substituted carbonyl group and a substituted carbonyloxy group, and the substituents of the substituted carbonyl group and the substituted carbonyloxy group are each independently selected from a phenyl group, One or more of a benzyl group, a C1-C8 alkyl group, a C1-C8 alkoxy group, and a C1-C8 alkylamine group.
  • the I a series of compounds: in the formula (I), R 2 is hydrogen, and R 1 is ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, Phenyl, benzyl, methyl substituted phenyl, methoxy substituted phenyl, trifluoromethyl substituted phenyl, trifluoromethoxy substituted phenyl, fluoro substituted phenyl, chloro substituted benzene a phenyl group, a bromine-substituted phenyl group, an iodine-substituted phenyl group, a cyano-substituted phenyl group, a nitro-substituted phenyl group, a hydroxy-substituted phenyl group, a t-butyl-substituted phenyl group, a dimethyla
  • hydroxy substituted naphthyl methoxy substituted naphthyl, 1,3-benzodioxan, 1,4-benzodioxin, fluorenyl, pyridyl, furyl, thienyl and imidazolyl .
  • I b series of compounds in formula (I), R 2 is methyl, ethyl, n-propyl or n-butyl, R 1 is phenyl, methoxy substituted phenyl, chloro substituted benzene a fluoro-substituted phenyl group, a bromine-substituted phenyl group, an iodine-substituted phenyl group, a methyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a trifluoromethoxy-substituted phenyl group, or a hydroxy-substituted benzene group.
  • R 2 and R 1 are ring-bonded to a 5-membered saturated ring, a 6-membered saturated ring or a 7-membered saturated ring.
  • R 3 is ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, methoxy, ethoxy, positive One or more of a propoxy group, a nitro group, an amine group, F, Cl, Br, I, a benzyloxy group, a phenylcarbonyl group, and an allyl group.
  • the I a series of compounds can also be represented by the compounds of the formula:
  • R 1 may represent a 2-10 carbon hydrocarbon group, a 3-6 carbon cycloalkyl group, a benzyl group, a naphthyl group, a substituted phenyl group (wherein the substituent may be hydrogen, a hydroxyl group, a halogen atom) , cyano, nitro, ester, dimethylamino, trifluoromethyl, trifluoromethoxy, 1-5 carbon, 1-6 alkoxy, and 2-3 of the above substituents) , 1-10 carbon nitrogen-containing heterocycle, 1-10 carbon oxygen-containing heterocycle, 1-10 carbon sulfur-containing heterocycle.
  • the I b series of compounds can also be represented by the compounds of the formula:
  • R 2 may represent a 1-10 carbon hydrocarbon group, a phenyl group, a substituted phenyl group (wherein the substituent may be hydrogen, a hydroxyl group, a halogen atom, a cyano group, a nitro group, an ester group, a fluorine group, a trifluoromethyl group, a trifluoromethoxy group, a 1-5 carbon hydrocarbon group, a 1-6 carbon alkoxy group, and a 2-3 of the above substituents, and a 3-6 carbon composed of R 2 and R 3 together Cycloalkyl;
  • R 1 may represent substituted phenyl (wherein the substituent may be hydrogen, hydroxy, halogen, cyano, nitro, ester, fluoro, trifluoromethyl, trifluoromethoxy, 1-5 A hydrocarbon group, a 1-6 carbon alkoxy group, and at the same time, 2-3 of the above substituents).
  • the I c series of compounds can also be represented by the compounds of the formula:
  • R 3 may represent hydrogen, a hydroxyl group, a 1-6 carboxy alkoxy 1-10 carbamoylamino group, a halogen atom, a cyano group, an aldehyde group, a 1-6 carbon alkyl group, 1 a -10 carboalkoxycarbonyl group, a 1-10 carboalkylamine carbonyl group, a 1-6 carboalkoxycarbonyloxy group, a 1-6 carboalkylamine carbonyloxy group; and a substituent represented by 2-3 R 3 groups.
  • the I a series of compounds is one of the compounds represented by the formula:
  • the I b series compound is one of the compounds represented by the following formula:
  • the I c series compound is one of the compounds represented by the following formula:
  • the hydrazide triazinone derivative of the present invention preferably has the following compounds in view of insecticidal activity and bactericidal activity:
  • a process for the preparation of the above triazinone derivative which comprises: reacting a semicarbazide triazolone of the formula (IV) with a formula (V) in a first organic solvent in the presence of a catalyst The compound shown is subjected to a dehydration condensation reaction to give a compound of the formula (I);
  • the compound represented by the above formula (V) can be specifically selected depending on the triazinone derivative to be prepared, and the present invention will not be repeated herein.
  • the molar ratio of the semicarbazolone of the formula (IV) to the compound of the formula (V) is from 1:0.8 to 2, preferably from 1:1 to 1.5.
  • the first organic solvent is one or more of methanol, ethanol, acetonitrile and N,N-dimethylformamide.
  • the first organic solvent is used in an amount such that the concentration of the semicarbazolone of the formula (IV) is from 0.01 to 0.05 mmol/mL.
  • the catalyst is one or more of trifluoroacetic acid, p-toluenesulfonic acid and glacial acetic acid.
  • the molar ratio of the semicarbazinone of the formula (IV) to the catalyst is from 1:0.1 to 0.5.
  • the conditions of the dehydration condensation reaction include a temperature of 70 to 120 ° C (preferably 70 to 100 ° C or 80 to 120 ° C) for 4 to 10 hours.
  • the preparation of the semicarbazide triazinone of the formula (IV) is preferably carried out by the following method, that is, the preparation method of the semicarbazolizinone of the formula (IV) comprises:
  • the molar ratio of the aminotriazinone represented by the formula (II) to the phenyl chloroformate is 1:0.8-2, preferably 1:1-1.5.
  • the acid binding agent is one or more of pyridine, sodium carbonate, triethylamine, potassium carbonate and cesium carbonate.
  • the molar ratio of the aminotriazinone and the acid binding agent represented by the formula (II) is from 1:0.8 to 1.5.
  • the second organic solvent is one or more of methanol, dichloromethane, chloroform, 1,2-dichloroethane and acetonitrile.
  • the second organic solvent is used in an amount such that the concentration of the aminotriazinone represented by the formula (II) is from 0.1 to 0.5 mmol/mL.
  • the conditions of the substitution reaction include a temperature of 60-80 ° C and a time of 5-8 h.
  • the molar ratio of the compound represented by the formula (III) to the hydrazine hydrate is 1:0.8-2, preferably 1:0.8-1.5.
  • the third organic solvent is one or more of methanol, dichloromethane, ethanol, 1,2-dichloroethane and acetonitrile.
  • the third organic solvent is used in an amount such that the concentration of the compound represented by the formula (III) is from 0.01 to 0.2 mmol/mL.
  • the conditions of the amination reaction include a temperature of 80 to 100 ° C and a time of 6 to 10 h.
  • the preparation process of the semicarbazolone can be obtained from the aminotriazinone represented by the formula (II), which can be represented by the following route:
  • a third aspect of the invention provides the use of the above triazinone derivative for insecticidal purposes.
  • the triazinone derivative provided by the invention has high insecticidal activity, and particularly has higher killing activity against one or more of aphids, mosquito larvae, cotton bollworm, corn borer and armyworm.
  • the hydrazide-containing triazinone derivative of the present invention exhibits good acaricidal activity, wherein the compounds I a -13, I a -14, I a -15, I a -16, I a - 44, I a -50, I a -51, I a -52, I a -54, I a -55, I b -13, I c -2, I c -5, I c -6, I c - 7. I c -8, I c -9, and I c -12 exhibited activity comparable to that of pymetrozine at a concentration of 5 mg/kg.
  • compound I a -47 showed 40% insecticidal activity against mosquito larvae at a concentration of 0.01 mg/kg.
  • all compounds showed insecticidal activity against cotton bollworm, corn borer and armyworm.
  • the compound I b -44 exhibited 30%, 20% and 60% insecticidal activity against cotton bollworm, corn borer and armyworm at 100 mg/kg, respectively.
  • the present invention also provides a method for insecticidal action using the above triazinone derivative as an insecticide.
  • the fourth aspect of the invention provides the use of the above triazinone derivative for sterilization.
  • the triazinone derivative provided by the invention has high insecticidal activity, especially for causing tomato early blight, wheat gibberella, potato late blight, Phytophthora capsici, rape sclerotia, cucumber gray mold, rice stalk, cucumber One or more of pathogens of withered, peanut brown spots, apple rings, wheat stalks, corn plaques, watermelon anthrax and rice seedlings.
  • the compounds I a -18, I a -26, I a -38, I a -53, I b -4, I b -6, I b -11, I c -2, I c -7, I c -9, I c -14 and I c -14 showed good bacteriostatic activity against various pathogenic bacteria at a concentration of 50 mg/kg.
  • the present invention also provides a method of sterilizing using the above triazinone derivative as a bactericide.
  • Example 4 Determination of acaricidal, the measurement procedure is as follows:
  • the aphid activity was determined as follows: the test insect was Aphis laburni Kaltenbach, a normal population fed by laboratory broad bean leaves. Weigh the drug, add 1mL DMF to dissolve, add two drops of Tween-20 emulsifier, add a certain amount of distilled water, stir evenly, and prepare the liquid with the required concentration (specific concentration is shown in the table). Immerse the leaves of the broad bean with aphids (about 60) into the medicine for 5 seconds, take them out and dry them, use the filter paper to blot the excess medicine, then insert the broad bean branches into the absorbent sponge, cover the branches with a glass cover, and seal with gauze. The results were checked 96 hours and each compound was repeated 3 times. The control only added emulsifier and solvent to the distilled water and stirred well.
  • Example 5 Determination of the activity of the mosquito larvae, the measurement procedure is as follows:
  • the experimental method for killing mosquito larvae the subspecies of Culex pipiens pallens, the normal population raised indoors. About 5 mg of the test compound was weighed into a penicillin vial, and 5 mL of acetone (or a suitable solvent) was added thereto, and dissolved by shaking to obtain a 1000 ppm mother liquor. Pipette 1 mL of mother liquor into a 100 mL beaker containing 89 mL of water, and select 10 4-year-old larvae of the first mosquito, and pour them into a beaker together with 10 mL of the stock solution. The concentration of the liquid solution is 10 ppm (the preparation of other chemical concentrations) Obtained by diluting the corresponding multiples). Place in a standard processing room and check the results 24h. An aqueous solution containing 0.5 mL of the test solvent was used as a blank control.
  • Example 6 Determination of the activity of cotton bollworm, corn borer, and armyworm, and the measurement procedure is as follows:
  • the experimental method of cotton bollworm feed mixed method, 3mL was taken from the configured solution and added to about 27g of the newly configured feed, thereby obtaining the required concentration diluted ten times. After mixing the chemicals, evenly pour them into a clean 24-well plate. After cooling, connect to 24 third-instar cotton bollworms and observe the results after 3-4 days.
  • Test method for corn mash Dip leaf method, after the required concentration after the configuration, the leaves with a diameter of about 5-6 cm are immersed in the liquid for 5-6 seconds, taken out, placed on absorbent paper to dry, placed in the designated In the culture dish, 10 3rd instar larvae were inserted and placed in a broiler room at 27 ⁇ 1 °C for 3-4 days to check the results.
  • Example 7 Determination of fungicidal activity, the measurement procedure is as follows:
  • In vitro test method The tomato Phytophthora infestans was cultured on PDA medium for 7 days, and inoculated with a 4 cm diameter dish at the edge of the colony to inoculate a PDA medium containing 50 mg/kg and no drug. The colony diameter was measured for 4 days, and the percentage inhibition of the drug was calculated in comparison with the control.

Abstract

The present invention belongs to the technical field of pesticides, and in particular relates to a triazinone derivative containing an acylhydrazone structure and a preparation method therefor, and insecticidal and bactericidal uses thereof. The triazinone derivative is the compound as shown in formula (I) below. The triazinone derivative provided by the present invention exhibits an excellent insecticidal activity and bactericidal activity.

Description

含有酰腙结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用Triazide derivative containing hydrazide structure, preparation method thereof and application in insecticide and sterilization 技术领域Technical field
本发明属于农药技术领域，具体涉及含有酰腙结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用。The invention belongs to the technical field of pesticides, and particularly relates to a hydrazide-containing triazinone derivative, a preparation method thereof and application thereof in insecticide and sterilization.
背景技术Background technique
瑞士诺华公司1988发现了一种非杀伤性杀虫剂吡蚜酮，它属于三嗪酮类化合物，具有全新的作用方式，对多种刺吸式口器害虫具有优异的防治效果。此外，吡蚜酮与传统的有机氯、有机氯、氨基甲酸酯、拟除虫菊酯、1-苯基吡唑类、新烟碱类杀虫剂无交互抗性，因此，吡蚜酮能应用于多种抗性品系害虫的防治。吡蚜酮的毒理学特性独特，与环境兼容，对昆虫具有交互的选择性，在农业生产中有利于综合防治措施和抗性综合治理的实施，同时吡蚜酮还能减轻农作物病毒危害的发生，以上优点决定了吡蚜酮在农业生产中具有广阔应用前景。总结已经报道的构效关系，发现前人对吡蚜酮类杀虫剂的研究工作主要集中修饰和改造三嗪酮环和吡啶环部分，而对中间连接臂的改造报道较少。1994年Beriger报道了亚胺改造为酰胺的化合物结构，但是没有报道其活性数据(Beriger,E.；Kristinsson,H.US 5324842.1994-06-28.)。1996年Uehara报道了亚胺还原之后N原子含有取代基的化合物结构，并报道了部分化合物在500ppm浓度下，对桃蚜和稻褐粉虱表现出100％的杀虫活性(Uehara,M.；Shimizu.T.；Fujioka.S.et al.EP 0987255A2.1996-03-28.)。2013年欧阳贵平组报道了由酰胺替换亚胺的化合物结构，同时研究了该类化合物对小麦赤霉病菌、辣椒枯萎病菌、苹果腐烂病菌的抑菌活性(张永露,欧阳贵平,贺宝安.现代农药.2013.12(2).10-13.)。随着吡蚜酮的应用广泛，吡蚜酮的抗性问题同样会越来越突出，因此，开发出具有和吡蚜酮类似作用方式的杀虫剂是科研工作者面临的一项重要课题。Swiss Novartis 1988 discovered a non-killing insecticide, pymetrozine, which belongs to triazinone compounds and has a new mode of action, which has excellent control effects on a variety of sucking mouthparts. In addition, pymetrozine has no cross-resistance with traditional organochlorine, organochlorine, carbamate, pyrethroid, 1-phenylpyrazole, and neonicotinoid insecticides. Therefore, pymetrozine can be applied. Prevention and treatment of pests of various resistant strains. Pyridoxone has unique toxicological properties, is compatible with the environment, has interactive selectivity for insects, and is beneficial to the implementation of integrated control measures and comprehensive treatment of resistance in agricultural production. Meanwhile, pymetrozine can also reduce the occurrence of crop virus damage. The above advantages determine the broad application prospect of pymetrozine in agricultural production. Summarizing the structure-activity relationship that has been reported, it is found that the previous research work on pymetrozine insecticides mainly focused on modifying and modifying the triazinone ring and the pyridine ring moiety, while the modification of the intermediate linker was less reported. In 1994, Beriger reported the structure of compounds in which an imine was converted to an amide, but no activity data was reported (Beriger, E.; Kristinsson, H. US 5324842. 1994-06-28.). In 1996, Uehara reported the structure of compounds containing substituents after reduction of imine, and reported that some compounds exhibited 100% insecticidal activity against peach aphid and rice brown meal at 500 ppm (Uehara, M.; Shimizu.T.; Fujioka.S. et al. EP 0987255A2.1996-03-28.). In 2013, Ouyang Guiping Group reported the structure of compounds substituted by amides, and studied the antibacterial activity of these compounds against Fusarium graminearum, Fusarium oxysporum f. sp., and apple rot pathogens (Zhang Yonglu, Ouyang Guiping, He Baoan. Modern pesticides. 2013.12(2).10-13.). With the widespread use of pymetrozine, the problem of resistance to pymetrozine is also becoming more and more prominent. Therefore, the development of insecticides with a similar mode of action to pymetrozine is an important issue for researchers.
Figure PCTCN2017102601-appb-000001
Figure PCTCN2017102601-appb-000001
发明内容Summary of the invention
本发明的目的是提供含有酰腙结构三嗪酮衍生物及其制备方法和在杀虫、杀菌方面的应用。本专利的含有酰腙结构三嗪酮衍生物表现出很好的杀虫活性，还具有杀菌活性。It is an object of the present invention to provide a hydrazide-containing triazinone derivative, a process for the preparation thereof, and use in insecticidal and bactericidal applications. The hydrazide-containing triazinone derivative of the present invention exhibits excellent insecticidal activity and also has bactericidal activity.
本发明第一方面提供了一种含有酰腙结构三嗪酮衍生物，其中，该三嗪酮衍生物为下式(I)所示的化合物：According to a first aspect of the present invention, there is provided a hydrazide-containing triazinone derivative, wherein the triazinone derivative is a compound represented by the following formula (I):
式(I)
Figure PCTCN2017102601-appb-000002
Formula (I)
Figure PCTCN2017102601-appb-000002
所述式(I)所示的化合物选自Ia系列、Ib系列和Ic系列所示化合物中的一种：The compound represented by the formula (I) is selected from one of the compounds shown in the I a series, the I b series, and the I c series:
Ia系列化合物：式(I)中，R2为氢，R1为C2-C10的烃基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环。其中，所述取代的苯基、取代的萘基和取代的苄基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C6的烃基和C1-C6的烷氧基中的一种或多种；I a series of compounds: in the formula (I), R 2 is hydrogen, R 1 is a C2-C10 hydrocarbon group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group. A substituted or unsubstituted benzyl group, a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, an oxygen-containing heterocyclic ring having 1 to 10 carbon atoms, and a sulfur-containing heterocyclic ring having 1 to 10 carbon atoms. Wherein the substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C6 hydrocarbon group, and a C1-C6 alkoxy group;
Ib系列化合物：式(I)中，R1和R2各自独立地选自C1-C10的烃基、取代的或未取代的苯基 和含有1-10个碳原子的含氮杂环，其中，所述取代的苯基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C6的烃基和C1-C6的烷氧基中的一种或多种；或者，R1和R2环合形成C3-C10的碳环；I b series of compounds: In the formula (I), R 1 and R 2 are each independently selected from a C1-C10 hydrocarbon group, a substituted or unsubstituted phenyl group and a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, wherein The substituents of the substituted phenyl are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl and One or more of C1-C6 alkoxy groups; or, R 1 and R 2 are cyclized to form a C3-C10 carbon ring;
Ic系列化合物：式(I)中，R2为甲基，R1为
Figure PCTCN2017102601-appb-000003
R3为单点或多点取代的取代基，选自氢、C1-C10的烃基、羟基、硝基、氨基、氰基、醛基、卤素、未取代的或苯基取代的C1-C10的烷氧基、C1-C10的烷胺基、取代的羰基和取代的羰氧基，取代的羰基和取代的羰氧基的取代基各自独立地选自苯基、苄基、C1-C10的烷基、C1-C10的烷氧基和C1-C10的烷胺基中的一种或多种。I c series compound: In the formula (I), R 2 is a methyl group, and R 1 is
Figure PCTCN2017102601-appb-000003
R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C10 hydrocarbyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or phenyl substituted C1-C10 Alkoxy, C1-C10 alkylamino, substituted carbonyl and substituted carbonyloxy, substituted carbonyl and substituted carbonyloxy are each independently selected from phenyl, benzyl, C1-C10 alkane One or more of a C1-C10 alkoxy group and a C1-C10 alkylamine group.
本发明第二方面提供了上述三嗪酮衍生物的制备方法，该方法包括：在第一有机溶剂中，在催化剂存在下，将式(IV)所示的氨基脲三嗪酮与式(V)所示的化合物进行脱水缩合反应，得到式(I)所示的化合物；According to a second aspect of the present invention, there is provided a process for the preparation of the above triazinone derivative, which comprises: reacting a semicarbazide triazolone of the formula (IV) with a formula (V) in a first organic solvent in the presence of a catalyst The compound shown is subjected to a dehydration condensation reaction to give a compound of the formula (I);
式(IV)
Figure PCTCN2017102601-appb-000004
Formula (IV)
Figure PCTCN2017102601-appb-000004
式(V)
Figure PCTCN2017102601-appb-000005
Formula (V)
Figure PCTCN2017102601-appb-000005
本发明第三方面提供了上述三嗪酮衍生物在杀虫方面的应用。A third aspect of the invention provides the use of the above triazinone derivative for insecticidal purposes.
本发明第四方面供了上述三嗪酮衍生物在杀菌方面的应用。The fourth aspect of the invention provides the use of the above triazinone derivative for sterilization.
本发明提供的三嗪酮衍生物表现出非常优良的杀虫活性和杀菌活性。The triazinone derivatives provided by the present invention exhibit very excellent insecticidal activity and bactericidal activity.
具体实施方式Detailed ways
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。The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to include values that are close to the ranges or values. For numerical ranges, the endpoint values of the various ranges, the endpoint values of the various ranges and the individual point values, and the individual point values can be combined with one another to yield one or more new ranges of values. The scope should be considered as specifically disclosed herein.
本发明第一方面提供了一种含有酰腙结构三嗪酮衍生物，其中，该三嗪酮衍生物为下式(I)所示的化合物：According to a first aspect of the present invention, there is provided a hydrazide-containing triazinone derivative, wherein the triazinone derivative is a compound represented by the following formula (I):
式(I)
Figure PCTCN2017102601-appb-000006
Formula (I)
Figure PCTCN2017102601-appb-000006
所述式(I)所示的化合物选自Ia系列、Ib系列和Ic系列所示化合物中的一种：The compound represented by the formula (I) is selected from one of the compounds shown in the I a series, the I b series, and the I c series:
Ia系列化合物：式(I)中，R2为氢，R1为C2-C10的烃基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环。其中，所述取代的苯基、取代的萘基和取代的苄基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C6的烃基和C1-C6的烷氧基中的一种或多种；I a series of compounds: in the formula (I), R 2 is hydrogen, R 1 is a C2-C10 hydrocarbon group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group. A substituted or unsubstituted benzyl group, a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, an oxygen-containing heterocyclic ring having 1 to 10 carbon atoms, and a sulfur-containing heterocyclic ring having 1 to 10 carbon atoms. Wherein the substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C6 hydrocarbon group, and a C1-C6 alkoxy group;
Ib系列化合物：式(I)中，R1和R2各自独立地选自C1-C10的烃基、取代的或未取代的苯基和含有1-10个碳原子的含氮杂环，其中，所述取代的苯基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C6的烃基和C1-C6的烷氧基中的一种或多种；或者，R1和R2环合形成C3-C10的碳环； I b series of compounds: In the formula (I), R 1 and R 2 are each independently selected from a C1-C10 hydrocarbon group, a substituted or unsubstituted phenyl group and a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, wherein The substituents of the substituted phenyl are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl and One or more of C1-C6 alkoxy groups; or, R 1 and R 2 are cyclized to form a C3-C10 carbon ring;
Ic系列化合物：式(I)中，R2为甲基，R1为
Figure PCTCN2017102601-appb-000007
R3为单点或多点取代的取代基，选自氢、C1-C10的烃基、羟基、硝基、氨基、氰基、醛基、卤素、未取代的或苯基取代的C1-C10的烷氧基、C1-C10的烷胺基、取代的羰基和取代的羰氧基，取代的羰基和取代的羰氧基的取代基各自独立地选自苯基、苄基、C1-C10的烷基、C1-C10的烷氧基和C1-C10的烷胺基中的一种或多种。I c series compound: In the formula (I), R 2 is a methyl group, and R 1 is
Figure PCTCN2017102601-appb-000007
R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C10 hydrocarbyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or phenyl substituted C1-C10 Alkoxy, C1-C10 alkylamino, substituted carbonyl and substituted carbonyloxy, substituted carbonyl and substituted carbonyloxy are each independently selected from phenyl, benzyl, C1-C10 alkane One or more of a C1-C10 alkoxy group and a C1-C10 alkylamine group.
其中，取代的苯基、取代的萘基、取代的苄基可以是单点取代，也可以为多点取代。Wherein, the substituted phenyl group, the substituted naphthyl group or the substituted benzyl group may be a single point substitution or a multiple point substitution.
本发明的上述式(I)所示的化合物可以由下式表示：The compound represented by the above formula (I) of the present invention can be represented by the following formula:
式(I’)
Figure PCTCN2017102601-appb-000008
该R可以表示R1和R2两个基团，也可以表示环合的一个基团，具体参见上述有关式(I)所示的化合物的描述。Formula (I')
Figure PCTCN2017102601-appb-000008
The R may represent two groups of R 1 and R 2 and may also represent a group which is cyclized. For details, refer to the description of the compound represented by the above formula (I).
在本发明中，C1-C10的烃基可以是C1-C10的烷基，也可以是C1-C10的含有不饱和键的烃基，其中，C1-C10的烷基的具体实例例如可以为：甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、正己基、正庚基、正辛基、正壬基、正癸基等。对于C1-C10的含有不饱和键的烃基可以是C2-C10的烯基，其中，C2-C10的烯基的具体实例例如可以为：乙烯基、烯丙基、1-正丁烯-4-基、1-正戊烯-5-基、1-正己烯-6-基、1-正庚烯-7-基、1-正辛烯-8-基、1-正壬烯-9-基、1-正癸烯-10-基等。In the present invention, the hydrocarbon group of C1-C10 may be a C1-C10 alkyl group, or may be a C1-C10 hydrocarbon group having an unsaturated bond, and a specific example of the C1-C10 alkyl group may be, for example, a methyl group. ,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-decyl, n-decyl Wait. The hydrocarbon group having an unsaturated bond for C1 to C10 may be a C2-C10 alkenyl group, and specific examples of the C2-C10 alkenyl group may be, for example, a vinyl group, an allyl group, or a 1-n-butene-4- Base, 1-n-penten-5-yl, 1-n-hexen-6-yl, 1-n-hepten-7-yl, 1-n-octene-8-yl, 1-n-decene-9-yl , 1-n-decene-10-yl group, and the like.
C1-C8的烷基、C2-C8的烯基、C2-C6的烷基、C1-C5的烷基可以从上述的烷基或烯基的具体实例进行选择并进行满足相应限定即可。The alkyl group of C1-C8, the alkenyl group of C2-C8, the C2-C6 alkyl group, and the C1-C5 alkyl group may be selected from the above specific examples of the alkyl group or the alkenyl group and may be appropriately defined.
C1-C6的烷氧基可以是上述的满足1-6个碳原子限定的烷基的具体实例形成的烷氧基，例如为甲氧基、乙氧基、正丙氧基等。The alkoxy group of C1-C6 may be an alkoxy group formed by the above specific examples satisfying the alkyl group defined by 1 to 6 carbon atoms, and is, for example, a methoxy group, an ethoxy group, a n-propoxy group or the like.
C3-C8的环烷基的具体实例例如可以为：
Figure PCTCN2017102601-appb-000009
等。Specific examples of the cycloalkyl group of C3-C8 may be, for example:
Figure PCTCN2017102601-appb-000009
Wait.
含有1-10个碳原子的含氮杂环可以是不饱和氮杂环，也可以是饱和氮杂环，只要其杂环的环结构中以氮为结构原子且该杂环具有的碳原子个数为1-10个，例如可以是未取代的或者C1-C6的烷基取代的吡咯、未取代的或者C1-C6的烷基取代的氢化吡咯、未取代的或者C1-C7的烷基取代的咪唑、未取代的或者C1-C7的烷基取代的氢化咪唑、未取代的或者C1-C5的烷基取代的吡啶、未取代的或者C1-C5的烷基取代的氢化吡啶、未取代的或者C1-C7的烷基取代的吡唑、未取代的或者C1-C7的烷基取代的氢化吡唑、未取代的或者C1-C7的烷基取代的噻唑、未取代的或者C1-C7的烷基取代的氢化噻唑、未取代的或者C1-C7的烷基取代的噁唑、未取代的或者C1-C7的烷基取代的氢化噁唑、未取代的或者C1-C5的烷基取代的吲哚、未取代的或者C1-C5的烷基取代的氢化吲哚、等。其中，作为取代基的烷基可以从上文中所描述的烷基具体实例中进行相应的选择，这些烷基的取代可以是单点的，也可以是多点的取代，本发明对此并无特别的限定。The nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated nitrogen heterocyclic ring or a saturated nitrogen heterocyclic ring as long as the ring structure of the heterocyclic ring has a nitrogen atom as a structural atom and the heterocyclic ring has a carbon atom Numbers from 1 to 10, such as unsubstituted or C1-C6 alkyl-substituted pyrrole, unsubstituted or C1-C6 alkyl-substituted hydropyrrole, unsubstituted or C1-C7 alkyl substituted Imidazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated imidazole, unsubstituted or C1-C5 alkyl-substituted pyridine, unsubstituted or C1-C5 alkyl-substituted hydrogenated pyridine, unsubstituted Or a C1-C7 alkyl-substituted pyrazole, an unsubstituted or a C1-C7 alkyl-substituted hydrogenated pyrazole, an unsubstituted or a C1-C7 alkyl-substituted thiazole, an unsubstituted or a C1-C7 Alkyl-substituted thiazole, unsubstituted or C1-C7 alkyl-substituted oxazole, unsubstituted or C1-C7 alkyl-substituted oxazole, unsubstituted or C1-C5 alkyl substituted Anthracene, unsubstituted or C1-C5 alkyl-substituted hydrazine hydride, and the like. Wherein, the alkyl group as a substituent may be selected from the specific examples of the alkyl group described above, and the substitution of these alkyl groups may be a single point or a multiple point substitution, and the present invention does not Special restrictions.
含有1-10个碳原子的含氧杂环可以是不饱和氧杂环，也可以是饱和氧杂环，只要其杂环的环结构中以氧为结构原子且该杂环具有的碳原子个数为1-10个，例如可以是未取代的或者C1-C6的烷基取代的呋喃、未取代的或者C1-C6的烷基取代的氢化呋喃、未取代的或者C1-C7的烷基取代的噁唑、未取代的或者C1-C7的烷基取代的氢化噁唑、未取代的或者C1-C3的烷基取代的1,3-苯并二噁茂、未取代的或者C1-C2的烷基取代的1,4-苯并二噁等。The oxygen-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated oxygen heterocyclic ring or a saturated oxygen heterocyclic ring as long as the heterocyclic ring structure has oxygen as a structural atom and the heterocyclic ring has a carbon atom. Numbers from 1 to 10, such as unsubstituted or C1-C6 alkyl-substituted furan, unsubstituted or C1-C6 alkyl-substituted hydrofuran, unsubstituted or C1-C7 alkyl substituted Oxazole, unsubstituted or C1-C7 alkyl-substituted hydrogenated oxazole, unsubstituted or C1-C3 alkyl-substituted 1,3-benzodioxan, unsubstituted or C1-C2 Alkyl-substituted 1,4-benzodioxins and the like.
含有1-10个碳原子的含硫杂环可以是不饱和硫杂环，也可以是饱和硫杂环，只要其杂环的环结构中以硫为结构原子且该杂环具有的碳原子个数为1-10个，例如可以是未取代的或者C1-C6的烷基取代的噻吩、未取代的或者C1-C6的烷基取代的氢化噻吩、未取代的或者C1-C7的烷基取代的噻唑、未取代的或者C1-C7的烷基取代的氢化噻唑等。The sulfur-containing heterocyclic ring having 1 to 10 carbon atoms may be an unsaturated sulfur heterocyclic ring or a saturated sulfur heterocyclic ring as long as the ring structure of the heterocyclic ring has sulfur as a structural atom and the heterocyclic ring has carbon atoms. Numbers from 1 to 10, such as unsubstituted or C1-C6 alkyl-substituted thiophenes, unsubstituted or C1-C6 alkyl-substituted thiophenes, unsubstituted or C1-C7 alkyl substitutions Thiazole, unsubstituted or C1-C7 alkyl substituted thiazole or the like.
卤素可以为F、Cl、Br、I等。The halogen may be F, Cl, Br, I or the like.
优选地，Ia系列化合物：式(I)中，R2为氢，R1为C2-C6的烷基、C3-C6的环烷基、取代的 或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、含有2-8个碳原子的含氮杂环、含有2-8个碳原子的含氧杂环、含有2-8个碳原子的含硫杂环。其中，所述取代的苯基、取代的萘基和取代的苄基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C5的烷基和C1-C5的烷氧基中的一种或多种。Preferably, the I a series of compounds: in the formula (I), R 2 is hydrogen, R 1 is a C2-C6 alkyl group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or not Substituted naphthyl, substituted or unsubstituted benzyl, nitrogen-containing heterocyclic ring having 2-8 carbon atoms, oxygen-containing heterocyclic ring having 2-8 carbon atoms, sulfur containing 2-8 carbon atoms Heterocyclic. Wherein the substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C5 alkyl group, and a C1-C5 alkoxy group.
优选地，Ib系列化合物：式(I)中，R1和R2各自独立地选自C1-C8的烷基、C2-C8的烯基、取代的或未取代的苯基和含有2-8个碳原子的含氮杂环，其中，所述取代的苯基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C5的烷基和C1-C5的烷氧基中的一种或多种；或者，R1和R2环合形成C3-C8的碳环。Preferably, the I b series of compounds: in the formula (I), R 1 and R 2 are each independently selected from a C1-C8 alkyl group, a C2-C8 alkenyl group, a substituted or unsubstituted phenyl group, and a 2- a nitrogen-containing heterocyclic ring of 8 carbon atoms, wherein the substituents of the substituted phenyl group are each independently selected from the group consisting of a hydroxyl group, a halogen, a cyano group, a nitro group, an ester group, a dimethylamino group, a trifluoromethyl group, and a trisium group. One or more of a fluoromethoxy group, a C1-C5 alkyl group, and a C1-C5 alkoxy group; or, R 1 and R 2 are cyclized to form a C3-C8 carbocyclic ring.
优选地，Ic系列化合物：式(I)中，R2为甲基，R1为
Figure PCTCN2017102601-appb-000010
R3为单点或多点取代的取代基，选自氢、C1-C8的烷基、C2-C8的烯基、羟基、硝基、氨基、氰基、醛基、卤素、未取代的或苯基取代的C1-C8的烷氧基、C1-C8的烷胺基、取代的羰基和取代的羰氧基，取代的羰基和取代的羰氧基的取代基各自独立地选自苯基、苄基、C1-C8的烷基、C1-C8的烷氧基和C1-C8的烷胺基中的一种或多种。Preferably, the I c series compound: in the formula (I), R 2 is a methyl group, and R 1 is
Figure PCTCN2017102601-appb-000010
R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C8 alkyl, C2-C8 alkenyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or a phenyl-substituted C1-C8 alkoxy group, a C1-C8 alkylamino group, a substituted carbonyl group and a substituted carbonyloxy group, and the substituents of the substituted carbonyl group and the substituted carbonyloxy group are each independently selected from a phenyl group, One or more of a benzyl group, a C1-C8 alkyl group, a C1-C8 alkoxy group, and a C1-C8 alkylamine group.
更优选地，Ia系列化合物：式(I)中，R2为氢，R1为乙基、正丙基、异丙基、正丁基、仲丁基、叔丁基、
Figure PCTCN2017102601-appb-000011
苯基、苄基、甲基取代的苯基、甲氧基取代的苯基、三氟甲基取代的苯基、三氟甲氧基取代的苯基、氟取代的苯基、氯取代的苯基、溴取代的苯基、碘取代的苯基、氰基取代的苯基、硝基取代的苯基、羟基取代的苯基、叔丁基取代的苯基、二甲胺基取代的苯基、羟基取代的萘基、甲氧基取代的萘基、1,3-苯并二噁茂基、1,4-苯并二噁基、吲哚基、吡啶基、呋喃基、噻吩基和咪唑基。More preferably, the I a series of compounds: in the formula (I), R 2 is hydrogen, and R 1 is ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl,
Figure PCTCN2017102601-appb-000011
Phenyl, benzyl, methyl substituted phenyl, methoxy substituted phenyl, trifluoromethyl substituted phenyl, trifluoromethoxy substituted phenyl, fluoro substituted phenyl, chloro substituted benzene a phenyl group, a bromine-substituted phenyl group, an iodine-substituted phenyl group, a cyano-substituted phenyl group, a nitro-substituted phenyl group, a hydroxy-substituted phenyl group, a t-butyl-substituted phenyl group, a dimethylamino group-substituted phenyl group. , hydroxy substituted naphthyl, methoxy substituted naphthyl, 1,3-benzodioxan, 1,4-benzodioxin, fluorenyl, pyridyl, furyl, thienyl and imidazolyl .
更优选地，Ib系列化合物：式(I)中，R2为甲基、乙基、正丙基或正丁基，R1为苯基、甲氧基取代的苯基、氯取代的苯基、氟取代的苯基、溴取代的苯基、碘取代的苯基、甲基取代的苯基、三氟甲基取代的苯基、三氟甲氧基取代的苯基、羟基取代的苯基、硝基取代的苯基、氨基取代的苯基或吡啶基；或者R2和R1环合为5元饱和环、6元饱和环或者7元饱和环。More preferably, I b series of compounds: in formula (I), R 2 is methyl, ethyl, n-propyl or n-butyl, R 1 is phenyl, methoxy substituted phenyl, chloro substituted benzene a fluoro-substituted phenyl group, a bromine-substituted phenyl group, an iodine-substituted phenyl group, a methyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a trifluoromethoxy-substituted phenyl group, or a hydroxy-substituted benzene group. a nitro-substituted phenyl group, an amino-substituted phenyl group or a pyridyl group; or R 2 and R 1 are ring-bonded to a 5-membered saturated ring, a 6-membered saturated ring or a 7-membered saturated ring.
更优选地，Ic系列化合物：式(I)中，R3为乙基、正丙基、异丙基、正丁基、仲丁基、叔丁基、甲氧基、乙氧基、正丙氧基、硝基、胺基、F、Cl、Br、I、苄氧基、苯基羰基和烯丙基中的一种或多种。More preferably, I c series of compounds: in formula (I), R 3 is ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, methoxy, ethoxy, positive One or more of a propoxy group, a nitro group, an amine group, F, Cl, Br, I, a benzyloxy group, a phenylcarbonyl group, and an allyl group.
根据本发明，Ia系列化合物还可以由下式所示化合物表示：According to the invention, the I a series of compounds can also be represented by the compounds of the formula:
式(Ia)
Figure PCTCN2017102601-appb-000012
Formula (I a )
Figure PCTCN2017102601-appb-000012
为此，式(Ia)中，R1可以代表2－10碳烃基、3－6碳环烷基、苄基、萘基、取代的苯基(其中取代基可以是氢、羟基、卤素原子、氰基、硝基、酯基、二甲氨基、三氟甲基、三氟甲氧基、1－5碳烃基、1－6碳烷氧基、以及同时含有2－3个上述取代基)、1－10碳含氮杂环、1－10碳含氧杂环、1－10碳含硫杂环。To this end, in the formula (I a ), R 1 may represent a 2-10 carbon hydrocarbon group, a 3-6 carbon cycloalkyl group, a benzyl group, a naphthyl group, a substituted phenyl group (wherein the substituent may be hydrogen, a hydroxyl group, a halogen atom) , cyano, nitro, ester, dimethylamino, trifluoromethyl, trifluoromethoxy, 1-5 carbon, 1-6 alkoxy, and 2-3 of the above substituents) , 1-10 carbon nitrogen-containing heterocycle, 1-10 carbon oxygen-containing heterocycle, 1-10 carbon sulfur-containing heterocycle.
根据本发明，Ib系列化合物还可以由下式所示化合物表示：According to the invention, the I b series of compounds can also be represented by the compounds of the formula:
式(Ib)
Figure PCTCN2017102601-appb-000013
Formula (I b )
Figure PCTCN2017102601-appb-000013
为此，式(Ib)中，R2可以代表1－10碳烃基、苯基、取代苯基(其中取代基可以是氢、羟基、卤素原子、氰基、硝基、酯基、氟、三氟甲基、三氟甲氧基、1－5碳烃基、1－6碳烷氧基、以及同时含有2－3个上述取代基)，以及R2和R3共同组成的3－6碳环烷基；R1可以代表取代的苯基(其中取代基可以是氢、羟基、卤素原子、氰基、硝基、酯基、氟、三氟甲基、三氟甲氧基、 1－5碳烃基、1－6碳烷氧基、以及同时含有2－3个上述取代基)。To this end, in the formula (I b ), R 2 may represent a 1-10 carbon hydrocarbon group, a phenyl group, a substituted phenyl group (wherein the substituent may be hydrogen, a hydroxyl group, a halogen atom, a cyano group, a nitro group, an ester group, a fluorine group, a trifluoromethyl group, a trifluoromethoxy group, a 1-5 carbon hydrocarbon group, a 1-6 carbon alkoxy group, and a 2-3 of the above substituents, and a 3-6 carbon composed of R 2 and R 3 together Cycloalkyl; R 1 may represent substituted phenyl (wherein the substituent may be hydrogen, hydroxy, halogen, cyano, nitro, ester, fluoro, trifluoromethyl, trifluoromethoxy, 1-5 A hydrocarbon group, a 1-6 carbon alkoxy group, and at the same time, 2-3 of the above substituents).
根据本发明，Ic系列化合物还可以由下式所示化合物表示：According to the invention, the I c series of compounds can also be represented by the compounds of the formula:
式(Ic)
Figure PCTCN2017102601-appb-000014
Formula (I c )
Figure PCTCN2017102601-appb-000014
为此，式(Ic)中，R3可以代表氢、羟基、1－6碳烷氧基1－10碳烷胺基、卤素原子、氰基、醛基、1－6碳烷羰基、1－10碳烷氧羰基、1－10碳烷胺羰基、1－6碳烷氧羰氧基、1－6碳烷胺羰氧基；以及同时含有2－3个R3所代表的取代基。To this end, in the formula (I c ), R 3 may represent hydrogen, a hydroxyl group, a 1-6 carboxy alkoxy 1-10 carbamoylamino group, a halogen atom, a cyano group, an aldehyde group, a 1-6 carbon alkyl group, 1 a -10 carboalkoxycarbonyl group, a 1-10 carboalkylamine carbonyl group, a 1-6 carboalkoxycarbonyloxy group, a 1-6 carboalkylamine carbonyloxy group; and a substituent represented by 2-3 R 3 groups.
在本发明的一种优选的实施方式中，所述Ia系列化合物为下式所示化合物中的一种：In a preferred embodiment of the present invention, the I a series of compounds is one of the compounds represented by the formula:
Figure PCTCN2017102601-appb-000015
Figure PCTCN2017102601-appb-000015
Figure PCTCN2017102601-appb-000016
Figure PCTCN2017102601-appb-000016
Figure PCTCN2017102601-appb-000017
Figure PCTCN2017102601-appb-000017
Figure PCTCN2017102601-appb-000018
Figure PCTCN2017102601-appb-000018
在本发明的一种优选的实施方式中，所述Ib系列化合物为下式所示化合物中的一种：In a preferred embodiment of the present invention, the I b series compound is one of the compounds represented by the following formula:
Figure PCTCN2017102601-appb-000019
Figure PCTCN2017102601-appb-000019
Figure PCTCN2017102601-appb-000020
Figure PCTCN2017102601-appb-000020
Figure PCTCN2017102601-appb-000021
Figure PCTCN2017102601-appb-000021
在本发明的一种优选的实施方式中，所述Ic系列化合物为下式所示化合物中的一种：In a preferred embodiment of the present invention, the I c series compound is one of the compounds represented by the following formula:
Figure PCTCN2017102601-appb-000022
Figure PCTCN2017102601-appb-000022
从杀虫活性和杀菌活性上考虑，本发明所述的含有酰腙三嗪酮衍生物优选如下化合物：The hydrazide triazinone derivative of the present invention preferably has the following compounds in view of insecticidal activity and bactericidal activity:
(E)-2-(2,2-二甲基亚丙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-3)；(E)-2-(2,2-dimethylpropylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I a -3);
(E)-2-(环己基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-4)；(E)-2-(cyclohexylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)amino Formyl hydrazide (I a -4);
(E)-2-(2,3-二甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-13)；(E)-2-(2,3-dimethoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -13);
(E)-2-(2,4-二甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-14)；(E)-2-(2,4-dimethoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -14);
(E)-2-(3,5-二甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-15)；(E)-2-(3,5-dimethoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -15);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(2,3,4-三甲氧基苯基亚甲基)氨基甲酰肼 (Ia-16)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(2,3,4-trimethyl) Oxyphenylmethylene)carbamoyl hydrazide (I a -16);
(E)-2-(3-氰基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-35)；(E)-2-(3-cyanophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H) -yl)carbamoyl hydrazide (I a -35);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(3-硝基苯基亚甲基)氨基甲酰肼(Ia-38)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(3-nitrophenyl Methyl)carbamoyl hydrazide (I a -38);
(E)-2-(4-(二甲氨基)苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-44)；(E)-2-(4-(Dimethylamino)phenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I a -44);
(E)-2-((6-甲氧基萘-2-基)苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-47)；(E)-2-((6-Methoxynaphthalen-2-yl)phenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4 Triazine-4(5H)-yl)carbamoyl hydrazide (I a -47);
(E)-2-((1H-吲哚-3-基)苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-50)；(E)-2-((1H-indol-3-yl)phenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-tri Pyrazin-4(5H)-yl)carbamoyl hydrazide (I a -50);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(吡啶-2-基苯基亚甲基)氨基甲酰肼(Ia-51)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(pyridin-2-ylphenyl) Methylene)carbamoyl hydrazide (I a -51);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(吡啶-3-基苯基亚甲基)氨基甲酰肼(Ia-52)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(pyridin-3-ylphenyl) Methylene)carbamoyl hydrazide (I a -52);
(E)-2-(呋喃-2-基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-54)；(E)-2-(furan-2-ylphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I a -54);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(噻吩-2-基苯基亚甲基)氨基甲酰肼(Ia-55)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(thiophen-2-ylphenyl) Methylene)carbamoyl hydrazide (I a -55);
2-亚环戊基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-3)；2-cyclopentylene-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I b - 3);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ib-6)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene) Carbamoyl hydrazide (I b -6);
(E)-2-(1-(4-甲氧基苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ib-11)；(E)-2-(1-(4-methoxyphenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine -4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I b -11);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(3,4,5-三甲氧基苯基)亚乙基)氨基甲酰肼(Ib-13)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(3,4, 5-trimethoxyphenyl)ethylidene hydrazide (I b -13);
(E)-2-(1-(4-氯苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ib-16)；(E)-2-(1-(4-chlorophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I b -16);
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-对甲基苯基亚乙基)氨基甲酰肼(Ib-22)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-p-methylphenyl) Ethylene)carbamoyl hydrazide (I b -22);
(E)-2-(1-(4-羟基苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ib-25)；(E)-2-(1-(4-hydroxyphenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I b -25);
(E)-2-(1-(6-(2-乙氧基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ic-2)；(E)-2-(1-(6-(2-ethoxyphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-di Hydrogen-1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I c -2);
(E)-2-(1-(6-(4-乙基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ic-5)；(E)-2-(1-(6-(4-ethylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro -1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I c -5);
(E)-2-(1-(6-(4-异丙基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ic-6)；(E)-2-(1-(6-(4-isopropylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-di Hydrogen-1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I c -6);
(E)-2-(1-(6-(4-叔丁基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ic-7)；(E)-2-(1-(6-(4-tert-Butylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-di Hydrogen-1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I c -7);
(E)-2-(1-(6-(4-溴苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ic-8)；(E)-2-(1-(6-(4-Bromophenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro- 1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I c -8);
(E)-2-(1-(6-(4-碘苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ic-9)；(E)-2-(1-(6-(4-iodophenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro- 1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I c -9);
(E)-2-(1-(6-(4-异丙基-3-甲基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯亚乙基)氨基甲酰肼(Ic-12)。(E)-2-(1-(6-(4-isopropyl-3-methylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-one- 2,3-Dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-phenylethylidene)carbamoyl hydrazide (I c -12).
本发明第二方面提供了上述三嗪酮衍生物的制备方法，该方法包括：在第一有机溶剂中，在催化剂存在下，将式(IV)所示的氨基脲三嗪酮与式(V)所示的化合物进行脱水缩合反应，得到式(I)所示的化合物； According to a second aspect of the present invention, there is provided a process for the preparation of the above triazinone derivative, which comprises: reacting a semicarbazide triazolone of the formula (IV) with a formula (V) in a first organic solvent in the presence of a catalyst The compound shown is subjected to a dehydration condensation reaction to give a compound of the formula (I);
式(IV)
Figure PCTCN2017102601-appb-000023
Formula (IV)
Figure PCTCN2017102601-appb-000023
式(V)
Figure PCTCN2017102601-appb-000024
Formula (V)
Figure PCTCN2017102601-appb-000024
根据本发明，上述式(V)所示化合物可以根据所需制备的三嗪酮衍生物进行具体的选择，本发明在此不再赘述。According to the present invention, the compound represented by the above formula (V) can be specifically selected depending on the triazinone derivative to be prepared, and the present invention will not be repeated herein.
根据本发明，优选地，式(IV)所示的氨基脲三嗪酮与式(V)所示的化合物的用量的摩尔比为1：0.8-2，优选为1：1-1.5。According to the present invention, preferably, the molar ratio of the semicarbazolone of the formula (IV) to the compound of the formula (V) is from 1:0.8 to 2, preferably from 1:1 to 1.5.
优选地，所述第一有机溶剂为甲醇、乙醇、乙腈和N,N-二甲基甲酰胺中的一种或多种。Preferably, the first organic solvent is one or more of methanol, ethanol, acetonitrile and N,N-dimethylformamide.
优选地，所述第一有机溶剂的用量使得式(IV)所示的氨基脲三嗪酮的浓度为0.01-0.05mmol/mL。Preferably, the first organic solvent is used in an amount such that the concentration of the semicarbazolone of the formula (IV) is from 0.01 to 0.05 mmol/mL.
优选地，所述催化剂为三氟乙酸、对甲基苯磺酸和冰乙酸中的一种或多种。Preferably, the catalyst is one or more of trifluoroacetic acid, p-toluenesulfonic acid and glacial acetic acid.
优选地，式(IV)所示的氨基脲三嗪酮和所述催化剂的用量的摩尔比为1：0.1-0.5。Preferably, the molar ratio of the semicarbazinone of the formula (IV) to the catalyst is from 1:0.1 to 0.5.
优选地，所述脱水缩合反应的条件包括：温度为70-120℃(优选为70-100℃或80-120℃)，时间为4-10h。Preferably, the conditions of the dehydration condensation reaction include a temperature of 70 to 120 ° C (preferably 70 to 100 ° C or 80 to 120 ° C) for 4 to 10 hours.
根据本发明，式(IV)所示的氨基脲三嗪酮的制备优选采用以下方法制得，即式(IV)所示的氨基脲三嗪酮的制备方法包括：According to the present invention, the preparation of the semicarbazide triazinone of the formula (IV) is preferably carried out by the following method, that is, the preparation method of the semicarbazolizinone of the formula (IV) comprises:
(1)在缚酸剂存在下，在第二有机溶剂中，将式(II)所示的氨基三嗪酮与氯甲酸苯酯进行取代反应，制得式(III)所示的化合物；(1) subjecting an aminotriazinone of the formula (II) to a phenyl chloroformate in a second organic solvent in the presence of an acid-binding agent, to obtain a compound of the formula (III);
(2)在第三有机溶剂中，将式(III)所示的化合物与水合肼进行氨基化反应，从而制得式(IV)所示的氨基脲三嗪酮；(2) subjecting a compound represented by the formula (III) to hydrazine hydrate in a third organic solvent to obtain a semicarbazolone of the formula (IV);
式(II)
Figure PCTCN2017102601-appb-000025
Formula (II)
Figure PCTCN2017102601-appb-000025
式(III)
Figure PCTCN2017102601-appb-000026
Formula (III)
Figure PCTCN2017102601-appb-000026
优选地，步骤(1)中，式(II)所示的氨基三嗪酮与氯甲酸苯酯用量的摩尔比为1：0.8-2，优选为1：1-1.5。Preferably, in the step (1), the molar ratio of the aminotriazinone represented by the formula (II) to the phenyl chloroformate is 1:0.8-2, preferably 1:1-1.5.
优选地，所述缚酸剂为吡啶、碳酸钠、三乙胺、碳酸钾和碳酸铯中的一种或多种。Preferably, the acid binding agent is one or more of pyridine, sodium carbonate, triethylamine, potassium carbonate and cesium carbonate.
优选地，式(II)所示的氨基三嗪酮和缚酸剂的用量的摩尔比为1：0.8-1.5。Preferably, the molar ratio of the aminotriazinone and the acid binding agent represented by the formula (II) is from 1:0.8 to 1.5.
优选地，所述第二有机溶剂为甲醇、二氯甲烷、氯仿、1,2-二氯乙烷和乙腈中的一种或多种。Preferably, the second organic solvent is one or more of methanol, dichloromethane, chloroform, 1,2-dichloroethane and acetonitrile.
优选地，所述第二有机溶剂的用量使得式(II)所示的氨基三嗪酮的浓度为0.1-0.5mmol/mL。Preferably, the second organic solvent is used in an amount such that the concentration of the aminotriazinone represented by the formula (II) is from 0.1 to 0.5 mmol/mL.
优选地，所述取代反应的条件包括：温度为60-80℃，时间为5-8h。Preferably, the conditions of the substitution reaction include a temperature of 60-80 ° C and a time of 5-8 h.
优选地，步骤(2)中，式(III)所示的化合物与水合肼用量的摩尔比为1：0.8-2，优选为1：0.8-1.5。Preferably, in the step (2), the molar ratio of the compound represented by the formula (III) to the hydrazine hydrate is 1:0.8-2, preferably 1:0.8-1.5.
优选地，所述第三有机溶剂为甲醇、二氯甲烷、乙醇、1,2-二氯乙烷和乙腈中的一种或多种。Preferably, the third organic solvent is one or more of methanol, dichloromethane, ethanol, 1,2-dichloroethane and acetonitrile.
优选地，所述第三有机溶剂的用量使得式(III)所示的化合物的浓度为0.01-0.2mmol/mL。Preferably, the third organic solvent is used in an amount such that the concentration of the compound represented by the formula (III) is from 0.01 to 0.2 mmol/mL.
优选地，所述氨基化反应的条件包括：温度为80-100℃，时间为6-10h。Preferably, the conditions of the amination reaction include a temperature of 80 to 100 ° C and a time of 6 to 10 h.
根据本发明，由式(II)所示的氨基三嗪酮制得式(IV)所示的氨基脲三嗪酮的制备过程可以由以下路线所表示：According to the present invention, the preparation process of the semicarbazolone can be obtained from the aminotriazinone represented by the formula (II), which can be represented by the following route:
路线一： Route 1:
Figure PCTCN2017102601-appb-000027
Figure PCTCN2017102601-appb-000027
针对Ia系列化合物的制备过程可以由以下路线所表示：The preparation process for the I a series of compounds can be represented by the following route:
路线二：Route 2:
Figure PCTCN2017102601-appb-000028
Figure PCTCN2017102601-appb-000028
针对Ib系列化合物的制备过程可以由以下路线所表示：The preparation process for the I b series of compounds can be represented by the following route:
路线三：Route 3:
Figure PCTCN2017102601-appb-000029
Figure PCTCN2017102601-appb-000029
针对Ic系列化合物的制备过程可以由以下路线所表示：The preparation process for the I c series of compounds can be represented by the following route:
路线四：Route 4:
Figure PCTCN2017102601-appb-000030
Figure PCTCN2017102601-appb-000030
本发明第三方面提供了上述三嗪酮衍生物在杀虫方面的应用。A third aspect of the invention provides the use of the above triazinone derivative for insecticidal purposes.
本发明提供的三嗪酮衍生物具有较高的杀虫活性，特别是对蚜虫、蚊幼虫、棉铃虫、玉米螟和粘虫中的一种或多种具有更高的杀灭活性。The triazinone derivative provided by the invention has high insecticidal activity, and particularly has higher killing activity against one or more of aphids, mosquito larvae, cotton bollworm, corn borer and armyworm.
特别地，本发明的含有酰腙结构三嗪酮衍生物表现出很好的杀蚜虫活性，其中，化合物Ia-13、Ia-14、Ia-15、Ia-16、Ia-44、Ia-50、Ia-51、Ia-52、Ia-54、Ia-55、Ib-13、Ic-2、Ic-5、Ic-6、Ic-7、Ic-8、Ic-9、Ic-12在5mg/kg浓度下表现出和吡蚜酮相当的活性。同时部分化合物对蚊幼虫表现出很好的活性，尤其是化合物Ia-47在0.01mg/kg浓度下对蚊幼虫表现出40％的杀虫活性。此外，所有化合物对棉铃虫、玉米螟及粘虫均表现出杀虫活性。其中化合物Ib-44在100mg/kg时，对棉铃虫、玉米螟和粘虫分别表现出30％、20％和60％的杀虫活性。In particular, the hydrazide-containing triazinone derivative of the present invention exhibits good acaricidal activity, wherein the compounds I a -13, I a -14, I a -15, I a -16, I a - 44, I a -50, I a -51, I a -52, I a -54, I a -55, I b -13, I c -2, I c -5, I c -6, I c - 7. I c -8, I c -9, and I c -12 exhibited activity comparable to that of pymetrozine at a concentration of 5 mg/kg. At the same time, some compounds showed good activity against mosquito larvae, especially compound I a -47 showed 40% insecticidal activity against mosquito larvae at a concentration of 0.01 mg/kg. In addition, all compounds showed insecticidal activity against cotton bollworm, corn borer and armyworm. Among them, the compound I b -44 exhibited 30%, 20% and 60% insecticidal activity against cotton bollworm, corn borer and armyworm at 100 mg/kg, respectively.
本发明还提供了一种采用上述三嗪酮衍生物作为杀虫剂进行杀虫的方法。The present invention also provides a method for insecticidal action using the above triazinone derivative as an insecticide.
本发明第四方面供了上述三嗪酮衍生物在杀菌方面的应用。The fourth aspect of the invention provides the use of the above triazinone derivative for sterilization.
本发明提供的三嗪酮衍生物具有较高的杀虫活性，特别是针对引起番茄早疫、小麦赤霉、马铃薯晚疫、辣椒疫霉、油菜菌核、黄瓜灰霉、水稻纹枯、黄瓜枯萎、花生褐斑、苹果轮纹、小麦纹枯、玉米小斑、西瓜炭疽和水稻恶苗的病原菌中的一种或多种。The triazinone derivative provided by the invention has high insecticidal activity, especially for causing tomato early blight, wheat gibberella, potato late blight, Phytophthora capsici, rape sclerotia, cucumber gray mold, rice stalk, cucumber One or more of pathogens of withered, peanut brown spots, apple rings, wheat stalks, corn plaques, watermelon anthrax and rice seedlings.
特别地，化合物Ia-18、Ia-26、Ia-38、Ia-53、Ib-4、Ib-6、Ib-11、Ic-2、Ic-7、Ic-9、Ic-14和Ic-14在50mg/kg浓度下对多种病原菌均表现出良好的抑菌活性。In particular, the compounds I a -18, I a -26, I a -38, I a -53, I b -4, I b -6, I b -11, I c -2, I c -7, I c -9, I c -14 and I c -14 showed good bacteriostatic activity against various pathogenic bacteria at a concentration of 50 mg/kg.
本发明还提供了一种采用上述三嗪酮衍生物作为杀菌剂进行杀菌的方法。The present invention also provides a method of sterilizing using the above triazinone derivative as a bactericide.
下述的实施例和生测试验结果可用来进一步说明本发明，但不意味着限制本发明。The following examples and bioassay results can be used to further illustrate the invention, but are not meant to limit the invention.
制备例1：Preparation Example 1:
N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼的合成 Synthesis of N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoylhydrazide
Figure PCTCN2017102601-appb-000031
Figure PCTCN2017102601-appb-000031
(1)苯基(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酸酯(III)的合成(1) Synthesis of phenyl (6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamate (III)
在100mL单口瓶中，加入二氯甲烷(50mL)、氨基三嗪酮(II)(2.56g,20mmol)、碳酸钾(2.76g,20mmol)，充分搅拌，室温下慢慢滴加氯甲酸苯酯(3.13g,20mmol)，大约1h滴加完毕，之后加热回流6h，TLC监测反应完毕。降温至室温，过滤，溶液减压脱溶，用石油醚/乙酸乙酯(1:1)进行常压柱层析得化合物III4.5g，白色固体，产率91％,熔点181-182℃。1H NMR(300MHz,DMSO-d6)δ10.08(s,1H,NH),9.92(s,1H,NH),7.42(t,J＝14.7,7.8Hz,2H,Ph-H),7.25(t,J＝14.7,7.2Hz,1H,Ph-H),7.14(d,J＝7.8Hz,2H,Ph-H),4.15(s,2H,CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.0,151.2,150.5,145.2,129.5,125.6,121.5,51.5,19.9；ESI-HRMS(m/z):Calcd.for C11H13N4O3[M+H]+249.0982,found 249.0988In a 100 mL single-mouth bottle, add dichloromethane (50 mL), aminotriazinone (II) (2.56 g, 20 mmol), potassium carbonate (2.76 g, 20 mmol), stir well, and slowly add phenyl chloroformate dropwise at room temperature. (3.13 g, 20 mmol), the addition was completed in about 1 h, then heated to reflux for 6 h, and the reaction was completed by TLC. The mixture was cooled to room temperature, filtered, and the solution was evaporated to dryness. mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj 1 H NMR (300MHz, DMSO- d 6) δ10.08 (s, 1H, NH), 9.92 (s, 1H, NH), 7.42 (t, J = 14.7,7.8Hz, 2H, Ph-H), 7.25 (t, J = 14.7, 7.2 Hz, 1H, Ph-H), 7.14 (d, J = 7.8 Hz, 2H, Ph-H), 4.15 (s, 2H, CH2), 1.88 (s, 3H, CH3) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.0, 151.2, 150.5, 145.2, 129.5, 125.6, 121.5, 51.5, 19.9; ESI-HRMS (m/z): Calcd. for C 11 H 13 N 4 O 3 [M+H] + 249.0982,found 249.0988
(2)N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(IV)的合成(2) Synthesis of N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (IV)
在250mL单口瓶中，加入甲醇(120mL)，化合物III(2.7g,11mmol)、水合肼(10mL)，充分搅拌，之后加热回流8h，TLC监测反应完毕。降温至室温，过滤得到IV1.56g，白色固体，收率77％，熔点229–231℃。1H NMR(300MHz,DMSO-d6)δ9.65(s,1H,NH),8.25(s,1H,NH),7.60(s,1H,NH),4.11(s,2H,NH2),4.02(s,2H,CH2),1.83(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ159.1,151.7,144.7,52.4,19.9.ESI-HRMS(m/z):Calcd.for C5H11N6O2[M+H]+187.0938；found 187.0939.Methanol (120 mL), Compound III (2.7 g, 11 mmol) and hydrazine hydrate (10 mL) were added to a 250 mL one-necked flask, and the mixture was stirred well, and then heated to reflux for 8 h. The mixture was cooled to room temperature and filtered to give EtOAc (m.). 1 H NMR (300MHz, DMSO- d 6) δ9.65 (s, 1H, NH), 8.25 (s, 1H, NH), 7.60 (s, 1H, NH), 4.11 (s, 2H, NH 2), 4.02 (s, 2H, CH 2 ), 1.83 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 159.1, 151.7, 144.7, 52.4, 19.9. ESI-HRMS (m/z): Calcd.for C 5 H 11 N 6 O 2 [M+H] + 187.0938; found 187.0939.
实施例1：Example 1:
(1)(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-亚丙基氨基甲酰肼(Ia-1)的合成(1) (E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-propyleneaminomethyl Synthesis of hydrazide (I a -1)
Figure PCTCN2017102601-appb-000032
Figure PCTCN2017102601-appb-000032
在250mL单口瓶中，加入氨基脲三嗪酮(0.74g,4mmol)、对甲基苯磺酸(0.14g,8mmol)、正丙醛(0.23g,4mmol，购自百灵威科技有限公司)、甲醇(120mL)搅拌溶解，然后加热回流6h，TLC监测反应完毕。将反应液减压脱除溶剂后析出固体，常压抽滤，用甲醇洗涤得到目标化合物0.48g，白色固体，产率53％，熔点148℃。1H NMR(400MHz,CDCl3)δ9.10(s,1H,NH),7.99(s,2H,NH),7.14(t,J＝4.0Hz,1H,＝CH),4.23(s,2H,CH2),2.24(q,2H,CH2CH3),1.94(s,3H,CH3),1.07(t,J＝6.8Hz,3H,CH2CH3)；13C NMR(100MHz,CDCl3)δ155.6,152.2,148.6,145.7,53.0,25.7,20.4,10.6.ESI-HRMS(m/z):Calcd.for C8H14N6O2[M+H]+227.1251；found 227.1253.In a 250 mL single-mouth bottle, a semicarbazolone (0.74 g, 4 mmol), p-toluenesulfonic acid (0.14 g, 8 mmol), n-propanal (0.23 g, 4 mmol, purchased from Belling Technology Co., Ltd.), methanol (120 mL) was stirred and dissolved, then heated to reflux for 6 h, and the reaction was completed by TLC. The solvent was evaporated under reduced pressure to give crystals crystals crystals crystals crystals crystals crystals crystals 1 H NMR (400MHz, CDCl 3 ) δ9.10 (s, 1H, NH), 7.99 (s, 2H, NH), 7.14 (t, J = 4.0Hz, 1H, = CH), 4.23 (s, 2H, CH 2 ), 2.24 (q, 2H, CH 2 CH 3 ), 1.94 (s, 3H, CH 3 ), 1.07 (t, J = 6.8 Hz, 3H, CH 2 CH 3 ); 13 C NMR (100 MHz, CDCl) 3 ) δ 155.6, 152.2, 148.6, 145.7, 53.0, 25.7, 20.4, 10.6. ESI-HRMS (m/z): Calcd. for C 8 H 14 N 6 O 2 [M+H] + 227.1251; found 227.1253.
(2)化合物Ia-2至Ia-57通过重复Ia-1的制备步骤完成。(2) The compounds I a -2 to I a -57 are completed by repeating the preparation steps of I a -1.
但不同的是：But the difference is:
制备化合物Ia-2时，采用等摩尔量的正丁醛(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -2, an equivalent molar amount of n-butyraldehyde (purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) was used instead of n-propanal;
制备化合物Ia-3时，采用等摩尔量的
Figure PCTCN2017102601-appb-000033
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -3, an equimolar amount is used.
Figure PCTCN2017102601-appb-000033
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-4时，采用等摩尔量的
Figure PCTCN2017102601-appb-000034
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -4, an equimolar amount is used.
Figure PCTCN2017102601-appb-000034
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-5时，采用等摩尔量的
Figure PCTCN2017102601-appb-000035
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -5, an equimolar amount is used.
Figure PCTCN2017102601-appb-000035
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-6时，采用等摩尔量的
Figure PCTCN2017102601-appb-000036
(购自天津试剂公司)代替正丙醛； When preparing compound I a -6, an equimolar amount is used.
Figure PCTCN2017102601-appb-000036
(purchased from Tianjin Reagent Company) instead of n-propionaldehyde;
制备化合物Ia-7时，采用等摩尔量的
Figure PCTCN2017102601-appb-000037
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -7, an equimolar amount is used.
Figure PCTCN2017102601-appb-000037
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-8时，采用等摩尔量的
Figure PCTCN2017102601-appb-000038
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -8, an equimolar amount is used.
Figure PCTCN2017102601-appb-000038
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-9时，采用等摩尔量的
Figure PCTCN2017102601-appb-000039
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -9, an equimolar amount is used.
Figure PCTCN2017102601-appb-000039
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-10时，采用等摩尔量的
Figure PCTCN2017102601-appb-000040
(购自天津希恩思生化科技有限公司公司)代替正丙醛；When preparing compound I a -10, an equimolar amount is used.
Figure PCTCN2017102601-appb-000040
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-11时，采用等摩尔量的
Figure PCTCN2017102601-appb-000041
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -11, an equimolar amount is used.
Figure PCTCN2017102601-appb-000041
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-12时，采用等摩尔量的
Figure PCTCN2017102601-appb-000042
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -12, an equimolar amount is used.
Figure PCTCN2017102601-appb-000042
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-13时，采用等摩尔量的
Figure PCTCN2017102601-appb-000043
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -13, an equimolar amount is used.
Figure PCTCN2017102601-appb-000043
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-14时，采用等摩尔量的
Figure PCTCN2017102601-appb-000044
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -14, an equimolar amount is used.
Figure PCTCN2017102601-appb-000044
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-15时，采用等摩尔量的
Figure PCTCN2017102601-appb-000045
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -15, an equimolar amount is used.
Figure PCTCN2017102601-appb-000045
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-16时，采用等摩尔量的
Figure PCTCN2017102601-appb-000046
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -16, an equimolar amount is used.
Figure PCTCN2017102601-appb-000046
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-17时，采用等摩尔量的
Figure PCTCN2017102601-appb-000047
(购自天津希恩思生化科技有限公司)代替正丙醛； When preparing compound I a -17, an equimolar amount is used.
Figure PCTCN2017102601-appb-000047
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-18时，采用等摩尔量的
Figure PCTCN2017102601-appb-000048
(购自上海毕得医药科技有限公司)代替正丙醛；When preparing compound I a -18, an equimolar amount is used.
Figure PCTCN2017102601-appb-000048
(purchased from Shanghai Bi De Pharmaceutical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-19时，采用等摩尔量的
Figure PCTCN2017102601-appb-000049
(购自上海毕得医药科技有限公司)代替正丙醛；When preparing compound I a -19, an equimolar amount is used.
Figure PCTCN2017102601-appb-000049
(purchased from Shanghai Bi De Pharmaceutical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-20时，采用等摩尔量的
Figure PCTCN2017102601-appb-000050
(购自上海毕得医药科技有限公司)代替正丙醛；When preparing compound I a -20, an equimolar amount is used.
Figure PCTCN2017102601-appb-000050
(purchased from Shanghai Bi De Pharmaceutical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-21时，采用等摩尔量的
Figure PCTCN2017102601-appb-000051
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -21, an equimolar amount is used.
Figure PCTCN2017102601-appb-000051
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-22时，采用等摩尔量的
Figure PCTCN2017102601-appb-000052
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -22, an equimolar amount is used.
Figure PCTCN2017102601-appb-000052
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-23时，采用等摩尔量的
Figure PCTCN2017102601-appb-000053
(购自上海阿拉丁生化科技股份有限公司)代替正丙醛；When preparing compound I a -23, an equimolar amount is used.
Figure PCTCN2017102601-appb-000053
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-24时，采用等摩尔量的
Figure PCTCN2017102601-appb-000054
(购自上海阿拉丁生化科技股份有限)代替正丙醛；When preparing compound I a -24, an equimolar amount is used.
Figure PCTCN2017102601-appb-000054
(purchased from Shanghai Aladdin Biotechnology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-25时，采用等摩尔量的
Figure PCTCN2017102601-appb-000055
(购自上海阿拉丁生化科技股份有限公司)代替正丙醛；When preparing compound I a -25, an equimolar amount is used.
Figure PCTCN2017102601-appb-000055
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-26时，采用等摩尔量的
Figure PCTCN2017102601-appb-000056
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -26, an equimolar amount is used.
Figure PCTCN2017102601-appb-000056
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-27时，采用等摩尔量的
Figure PCTCN2017102601-appb-000057
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -27, an equimolar amount is used.
Figure PCTCN2017102601-appb-000057
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-28时，采用等摩尔量的
Figure PCTCN2017102601-appb-000058
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -28, an equimolar amount is used.
Figure PCTCN2017102601-appb-000058
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-29时，采用等摩尔量的
Figure PCTCN2017102601-appb-000059
(购自天津希恩思生化科技有限公司)代替正丙醛； When preparing compound I a -29, an equimolar amount is used.
Figure PCTCN2017102601-appb-000059
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-30时，采用等摩尔量的
Figure PCTCN2017102601-appb-000060
(购自上海毕得医药科技有限公司)代替正丙醛；When preparing compound I a -30, an equimolar amount is used.
Figure PCTCN2017102601-appb-000060
(purchased from Shanghai Bi De Pharmaceutical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-31时，采用等摩尔量的
Figure PCTCN2017102601-appb-000061
(购自上海毕得医药科技有限公司公司)代替正丙醛；When preparing compound I a -31, an equimolar amount is used.
Figure PCTCN2017102601-appb-000061
(purchased from Shanghai Bi De Pharmaceutical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-32时，采用等摩尔量的
Figure PCTCN2017102601-appb-000062
(购自天津希恩思生化科技有限公司)代替正丙醛；When preparing compound I a -32, an equimolar amount is used.
Figure PCTCN2017102601-appb-000062
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-33时，采用等摩尔量的
Figure PCTCN2017102601-appb-000063
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -33, an equimolar amount is used.
Figure PCTCN2017102601-appb-000063
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-34时，采用等摩尔量的
Figure PCTCN2017102601-appb-000064
(购自天津希恩思生化科技有限公司公司)代替正丙醛；When preparing compound I a -34, an equimolar amount is used.
Figure PCTCN2017102601-appb-000064
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-35时，采用等摩尔量的
Figure PCTCN2017102601-appb-000065
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -35, an equimolar amount is used.
Figure PCTCN2017102601-appb-000065
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-36时，采用等摩尔量的
Figure PCTCN2017102601-appb-000066
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -36, an equimolar amount is used.
Figure PCTCN2017102601-appb-000066
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-37时，采用等摩尔量的
Figure PCTCN2017102601-appb-000067
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -37, an equimolar amount is used.
Figure PCTCN2017102601-appb-000067
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-38时，采用等摩尔量的
Figure PCTCN2017102601-appb-000068
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -38, an equimolar amount is used.
Figure PCTCN2017102601-appb-000068
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-39时，采用等摩尔量的
Figure PCTCN2017102601-appb-000069
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -39, an equimolar amount is used.
Figure PCTCN2017102601-appb-000069
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-40时，采用等摩尔量的
Figure PCTCN2017102601-appb-000070
(购自南京多点化学公司)代替正丙醛；When preparing compound I a -40, an equimolar amount is used.
Figure PCTCN2017102601-appb-000070
(purchased from Nanjing Multi-Point Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-41时，采用等摩尔量的
Figure PCTCN2017102601-appb-000071
(购自上海阿拉丁生化科技股份有限公司)代替正丙醛；When preparing compound I a -41, an equimolar amount is used.
Figure PCTCN2017102601-appb-000071
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-42时，采用等摩尔量的
Figure PCTCN2017102601-appb-000072
(购自上海阿拉丁生化科技股份有限公司)代替正丙醛； When preparing compound I a -42, an equimolar amount is used.
Figure PCTCN2017102601-appb-000072
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-43时，采用等摩尔量的
Figure PCTCN2017102601-appb-000073
(购自上海迈瑞尔化学技术有限公司)代替正丙醛；When preparing compound I a -43, an equimolar amount is used.
Figure PCTCN2017102601-appb-000073
(purchased from Shanghai Miner Chemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-44时，采用等摩尔量的
Figure PCTCN2017102601-appb-000074
(购自上海阿拉丁生化科技股份有限公司)代替正丙醛；When preparing compound I a -44, an equimolar amount is used.
Figure PCTCN2017102601-appb-000074
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-45时，采用等摩尔量的
Figure PCTCN2017102601-appb-000075
(购自天津希恩思生化科技有限公司公司)代替正丙醛；When preparing compound I a -45, an equimolar amount is used.
Figure PCTCN2017102601-appb-000075
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-46时，采用等摩尔量的
Figure PCTCN2017102601-appb-000076
(购自百灵威科技有限公司)代替正丙醛；When preparing compound I a -46, an equimolar amount is used.
Figure PCTCN2017102601-appb-000076
(purchased from Bailingwei Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-47时，采用等摩尔量的
Figure PCTCN2017102601-appb-000077
(购自百灵威科技有限公司)代替正丙醛；When preparing compound I a -47, an equimolar amount is used.
Figure PCTCN2017102601-appb-000077
(purchased from Bailingwei Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-48时，采用等摩尔量的
Figure PCTCN2017102601-appb-000078
(购自北京伊诺凯科技有限公司)代替正丙醛；When preparing compound I a -48, an equimolar amount is used.
Figure PCTCN2017102601-appb-000078
(purchased from Beijing Yinuokai Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-49时，采用等摩尔量的
Figure PCTCN2017102601-appb-000079
(购自北京伊诺凯科技有限公司)代替正丙醛；When preparing compound I a -49, an equimolar amount is used.
Figure PCTCN2017102601-appb-000079
(purchased from Beijing Yinuokai Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-50时，采用等摩尔量的
Figure PCTCN2017102601-appb-000080
(购自北京伊诺凯科技有限公司)代替正丙醛；When preparing compound I a -50, an equimolar amount is used.
Figure PCTCN2017102601-appb-000080
(purchased from Beijing Yinuokai Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-51时，采用等摩尔量的
Figure PCTCN2017102601-appb-000081
(购自上海阿拉丁生化科技股份有限公司)代替正丙醛；When preparing compound I a -51, an equimolar amount is used.
Figure PCTCN2017102601-appb-000081
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of n-propionaldehyde;
制备化合物Ia-52时，采用等摩尔量的
Figure PCTCN2017102601-appb-000082
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -52, an equimolar amount is used.
Figure PCTCN2017102601-appb-000082
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-53时，采用等摩尔量的
Figure PCTCN2017102601-appb-000083
(购自南京多点化学公司)代替正丙醛；When preparing compound I a -53, an equimolar amount is used.
Figure PCTCN2017102601-appb-000083
(purchased from Nanjing Multi-Point Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-54时，采用等摩尔量的
Figure PCTCN2017102601-appb-000084
(购自安耐吉化学公司)代替正丙醛； When preparing compound I a -54, an equimolar amount is used.
Figure PCTCN2017102601-appb-000084
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-55时，采用等摩尔量的
Figure PCTCN2017102601-appb-000085
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -55, an equimolar amount is used.
Figure PCTCN2017102601-appb-000085
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-56时，采用等摩尔量的
Figure PCTCN2017102601-appb-000086
(购自安耐吉化学公司)代替正丙醛；When preparing compound I a -56, an equimolar amount is used.
Figure PCTCN2017102601-appb-000086
(purchased from Anheji Chemical Company) instead of n-propionaldehyde;
制备化合物Ia-57时，采用等摩尔量的
Figure PCTCN2017102601-appb-000087
(购自上海毕得医药科技有限公司)代替正丙醛。When preparing compound I a -57, an equimolar amount is used.
Figure PCTCN2017102601-appb-000087
(purchased from Shanghai Bi De Pharmaceutical Technology Co., Ltd.) instead of n-propionaldehyde.
所得化合物的表征结果如下所示：The characterization results of the obtained compounds are as follows:
(E)-2-亚丁基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-2)(E)-2-butylene-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I) a -2)
白色固体，产率57％，熔点173-175℃。1H NMR(400MHz,CDCl3)δ8.63(s,1H,NH),7.90(s,1H,NH),7.66(s,1H,NH),7.08(t,J＝5.2Hz,1H,＝CH),4.25(s,2H,CH2),2.21(m,2H,CH2CH2CH3),1.95(s,3H,CH3),1.54(m,2H,CH2CH2CH3),0.95(t,J＝7.6Hz,3H,CH2CH2CH3)；13C NMR(100MHz,CDCl3)δ155.4,152.0,147.3,145.6,53.0,34.3,20.4,19.8,13.9.ESI-HRMS(m/z):Calcd.for C9H16N6O2[M+H]+241.1408；found 241.1407.White solid, 57% yield, mp 173 - 175. 1 H NMR (400 MHz, CDCl 3 ) δ 8.63 (s, 1H, NH), 7.90 (s, 1H, NH), 7.66 (s, 1H, NH), 7.08 (t, J = 5.2 Hz, 1H, = CH), 4.25 (s, 2H, CH 2 ), 2.21 (m, 2H, CH 2 CH 2 CH 3 ), 1.95 (s, 3H, CH 3 ), 1.54 (m, 2H, CH 2 CH 2 CH 3 ) , 0.95 (t, J = 7.6 Hz, 3H, CH 2 CH 2 CH 3 ); 13 C NMR (100 MHz, CDCl 3 ) δ 155.4, 152.0, 147.3, 145.6, 53.0, 34.3, 20.4, 19.8, 13.9. ESI-HRMS (m/z): Calcd.for C 9 H 16 N 6 O 2 [M+H] + 241.1408; found 241.1407.
(E)-2-(2,2-二甲基亚丙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-3)(E)-2-(2,2-dimethylpropylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I a -3)
白色固体，产率67％，熔点230–231℃。1H NMR(400MHz,DMSO-d6)δ10.25(s,1H,NH),9.73(s,1H,NH),8.60(s,1H,NH),7.12(s,1H,＝CH),4.06(s,2H,CH2),1.84(s,3H,CH3),1.05(s,9H,C(CH3)3)；13C NMR(100MHz,DMSO-d6)δ154.6,152.5,151.7,144.8,52.2,34.2,27.4,19.8.ESI-HRMS(m/z):Calcd.for C10H19N6O2[M+H]+255.1564；found 255.1567.White solid, yield 67%, m.p. 230 - 231. 1 H NMR (400MHz, DMSO- d 6) δ10.25 (s, 1H, NH), 9.73 (s, 1H, NH), 8.60 (s, 1H, NH), 7.12 (s, 1H, = CH), 4.06 (s, 2H, CH 2 ), 1.84 (s, 3H, CH 3 ), 1.05 (s, 9H, C (CH 3 ) 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 152.5, 151.7 , 144.8, 52.2, 34.2, 27.4, 19.8. ESI-HRMS (m/z): Calcd. for C 10 H 19 N 6 O 2 [M+H] + 255.1564; found 255.1567.
(E)-2-(环己基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-4)；(E)-2-(cyclohexylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)amino Formyl hydrazide (I a -4);
白色固体，产率75％，熔点213–214℃。1H NMR(400MHz,DMSO-d6)δ10.26(s,1H,NH),9.72(s,1H,NH),8.64(s,1H,NH),7.09(d,J＝5.2Hz,1H,＝CH),4.05(s,2H,CH2),1.84(s,3H,CH3),1.68–76(m,CH2),1.61–1.64(m,1H),1.14–1.27(m,6H,CH2)；13C NMR(100MHz,DMSO-d6)δ154.6,151.6,149.0,144.8,52.2,29.8,25.6,25.1,19.9.ESI-HRMS(m/z):Calcd.for C12H21N6O2[M+H]+281.1721；found 281.1725.White solid, 75% yield, mp 213 - 214. 1 H NMR (400MHz, DMSO- d 6) δ10.26 (s, 1H, NH), 9.72 (s, 1H, NH), 8.64 (s, 1H, NH), 7.09 (d, J = 5.2Hz, 1H , =CH), 4.05 (s, 2H, CH 2 ), 1.84 (s, 3H, CH 3 ), 1.68–76 (m, CH 2 ), 1.61–1.64 (m, 1H), 1.14–1.27 (m, 6H,CH 2 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 154.6, 151.6, 149.0, 144.8, 52.2, 29.8, 25.6, 25.1,19.9. ESI-HRMS (m/z): Calcd.for C 12 H 21 N 6 O 2 [M+H] + 281.1721; found 281.1725.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(2-苯基亚乙基)氨基甲酰肼(Ia-5)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(2-phenylethylidene) )carbamoyl hydrazide (I a -5)
白色固体，产率48％，熔点125-126℃。1H NMR(400MHz,CDCl3)δ9.10(s,1H,NH),8.03(s,1H,NH),7.81(s,1H,NH),7.33(d,J＝7.2Hz,2H,Ar-H),7.28(t,J＝6.0Hz,1H,＝CH),7.22(d,J＝7.2Hz,2H,Ar-H),7.19(t,J＝5.6Hz,1H,Ar-H),4.24(s,2H,CH2),3.46(d,J＝5.6Hz,2H,＝CHCH2),1.95(s,3H,CH3)；13C NMR(100MHz,CDCl3)δ155.3,152.0,148.5,145.7,130.4,129.1,129.0,127.3,53.0,38.9,20.4.ESI-HRMS(m/z):Calcd.for C13H16N6O2[M+H]+289.1408；found 289.1404.White solid, yield 48%, mp. 125-126. 1 H NMR (400 MHz, CDCl 3 ) δ 9.10 (s, 1H, NH), 8.03 (s, 1H, NH), 7.81 (s, 1H, NH), 7.33 (d, J = 7.2 Hz, 2H, Ar -H), 7.28 (t, J = 6.0 Hz, 1H, = CH), 7.22 (d, J = 7.2 Hz, 2H, Ar-H), 7.19 (t, J = 5.6 Hz, 1H, Ar-H) , 4.24 (s, 2H, CH 2 ), 3.46 (d, J = 5.6 Hz, 2H, =CHCH 2 ), 1.95 (s, 3H, CH 3 ); 13 C NMR (100 MHz, CDCl 3 ) δ 155.3, 152.0, 148.5, 145.7, 130.4, 129.1, 129.0, 127.3, 53.0, 38.9, 20.4. ESI-HRMS (m/z): Calcd. for C 13 H 16 N 6 O 2 [M+H] + 289.1408; found 289.1404.
(E)-2-苯基亚甲基-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-6)；(E)-2-phenylmethylene-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl肼(I a -6);
白色固体，产率69％，熔点219–220℃。1H NMR(400MHz,DMSO-d6)δ10.77(s,1H,NH),9.78(s,1H,NH),9.25(s,1H,NH),7.87(s,1H,＝CH),7.78(d,J＝6.8Hz,2H,Ar-H),7.37–7.43(m,3H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.7,144.9,141.1,134.4,129.5,128.6,126.9,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H15N6O2[M+H]+275.1251；found 275.1246.White solid, yield 69%, mp 219 - 220. 1 H NMR (400MHz, DMSO- d 6) δ10.77 (s, 1H, NH), 9.78 (s, 1H, NH), 9.25 (s, 1H, NH), 7.87 (s, 1H, = CH), 7.78 (d, J = 6.8Hz, 2H, Ar-H), 7.37-7.43 (m, 3H, Ar-H), 4.12 (s, 2H, CH 2), 1.87 (s, 3H, CH 3); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.7, 144.9, 141.1, 134.4, 129.5, 128.6, 126.9, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 15 N 6 O 2 [M+H] + 275.1251; found 275.1246.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(2-甲基苯基亚甲基)氨基甲酰肼(Ia-7)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(2-methylphenyl Methyl)carbamoyl hydrazide (I a -7);
白色固体，产率72％，熔点229–230℃。1H NMR(400MHz,DMSO-d6)δ10.69(s,1H,NH),9.77(s,1H,NH),9.16(s,1H,NH),8.18(s,1H,＝CH),8.04(d,J＝6.4Hz,1H,Ar-H),7.22–7.26(m,3H,Ar-H),4.11(s,2H,CH2),2.38(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,151.7,144.8,139.6,136.2,132.3,130.7,129.2,126.0,125.7,52.2,19.9,18.8.ESI-HRMS(m/z):Calcd.for C13H17N6O2[M+H]+289.1408；found 289.1412.White solid, yield 72%, mp 229 - 230. 1 H NMR (400MHz, DMSO- d 6) δ10.69 (s, 1H, NH), 9.77 (s, 1H, NH), 9.16 (s, 1H, NH), 8.18 (s, 1H, = CH), 8.04 (d, J = 6.4 Hz, 1H, Ar-H), 7.22 - 7.26 (m, 3H, Ar-H), 4.11 (s, 2H, CH 2 ), 2.38 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 154.6, 151.7, 144.8, 139.6, 136.2, 132.3, 130.7, 129.2, 126.0, 125.7, 52.2, 19.9, 18.8. ESI-HRMS ( m/z): Calcd.for C 13 H 17 N 6 O 2 [M+H] + 289.1408; found 289.1412.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(3-甲基苯基亚甲基)氨基甲酰肼(Ia-8)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(3-methylphenyl Methyl)carbamoyl hydrazide (I a -8);
白色固体，产率62％，熔点215–216℃。1H NMR(400MHz,DMSO-d6)δ10.73(s,1H,NH),9.77(s,1H,NH),9.22(s,1H,NH),7.83(s,1H,＝CH),7.65(s,1H,Ar-H),7.52(d,J＝7.6Hz,1H,Ar-H),7.29(t,J＝7.6Hz,1H,Ar-H),7.19(d,J＝7.6Hz,1H,Ar-H),4.12(s,2H,CH2),2.33(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.8,151.8,145.0,141.3,137.9,134.4,130.2,128.6,127.2,124.5,52.3,21.0,19.9.ESI-HRMS(m/z):Calcd.for C13H17N6O2[M+H]+289.1408；found 289.1410.White solid, yield 62%, mp 215 - 216. 1 H NMR (400MHz, DMSO- d 6) δ10.73 (s, 1H, NH), 9.77 (s, 1H, NH), 9.22 (s, 1H, NH), 7.83 (s, 1H, = CH), 7.65 (s, 1H, Ar-H), 7.52 (d, J = 7.6 Hz, 1H, Ar-H), 7.29 (t, J = 7.6 Hz, 1H, Ar-H), 7.19 (d, J = 7.6) Hz, 1H, Ar-H), 4.12 (s, 2H, CH 2 ), 2.33 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.8, 151.8, 145.0, 141.3, 137.9, 134.4, 130.2, 128.6, 127.2, 124.5, 52.3, 21.0, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 17 N 6 O 2 [M+H ] + 289.1408; found 289.1410.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(4-甲基苯基亚甲基)氨基甲酰肼(Ia-9)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(4-methylphenyl Methyl)carbamoyl hydrazide (I a -9);
白色固体，产率78％，熔点264–265℃。1H NMR(400MHz,DMSO-d6):δ10.69(s,1H,NH),9.76(s,1H,NH),9.20(s,1H,NH),7.83(s,1H,＝CH),7.67(d,J＝7.2Hz,2H,Ar-H),7.22(d,J＝7.2Hz,2H,Ar-H),4.11(s,2H,CH2),2.32(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.8,144.9,141.2,139.2,131.8,129.3,126.9,52.2,21.0,19.9.ESI-HRMS(m/z):Calcd.for C13H17N6O2[M+H]+289.1408；found 289.1413.White solid, 78% yield, mp 264 - 265. 1 H NMR (400MHz, DMSO- d 6): δ10.69 (s, 1H, NH), 9.76 (s, 1H, NH), 9.20 (s, 1H, NH), 7.83 (s, 1H, = CH) , 7.67 (d, J = 7.2 Hz, 2H, Ar-H), 7.22 (d, J = 7.2 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 2.32 (s, 3H, CH) 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.8, 144.9, 141.2, 139.2, 131.8, 129.3, 126.9, 52.2, 21.0, 19.9. ESI-HRMS ( m/z): Calcd.for C 13 H 17 N 6 O 2 [M+H] + 289.1408; found 289.1413.
(E)-2-(2-甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-10)；(E)-2-(2-methoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I a -10);
黄色固体，产率67％，熔点232–233℃。1H NMR(400MHz,DMSO-d6)δ10.73(s,1H,NH),9.76(s,1H,NH), 9.21(s,1H,NH),8.22(s,1H,＝CH),8.08(d,J＝7.6Hz,1H,Ar-H),7.36(t,J＝8.0Hz,1H,Ar-H),7.07(d,J＝8.0Hz,1H,Ar-H),6.97(t,J＝7.6Hz,1H,Ar-H),4.11(s,2H,CH2),3.83(s,3H,OCH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ157.3,154.6,151.7,144.8,136.4,130.9,125.8,122.3,120.5,111.6,55.6,52.2,19.9.ESI-HRMS(m/z):Calcd.for C13H17N6O3[M+H]+305.1357；found 305.1359.Yellow solid, yield 67%, mp 232 - 233. 1 H NMR (400MHz, DMSO- d 6) δ10.73 (s, 1H, NH), 9.76 (s, 1H, NH), 9.21 (s, 1H, NH), 8.22 (s, 1H, = CH), 8.08 (d, J = 7.6 Hz, 1H, Ar-H), 7.36 (t, J = 8.0 Hz, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 6.97 ( t, J = 7.6 Hz, 1H, Ar-H), 4.11 (s, 2H, CH 2 ), 3.83 (s, 3H, OCH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 157.3, 154.6, 151.7, 144.8, 136.4, 130.9, 125.8, 122.3, 120.5, 111.6, 55.6, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 17 N 6 O 3 [M+H] + 305.1357; found 305.1359.
(E)-2-(3-甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-11)；(E)-2-(3-methoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I a -11);
白色固体，产率67％，熔点226–227℃。1H NMR(400MHz,DMSO-d6)δ10.78(s,1H,NH),9.78(s,1H,NH),9.29(s,1H,NH),7.83(s,1H,＝CH),7.43(s,1H,Ar-H),7.31(t,J＝7.6Hz,1H,Ar-H),7.25(d,J＝7.2Hz,1H,Ar-H),6.94(d,J＝7.2Hz,1H,Ar-H),4.12(s,2H,CH2),3.80(s,3H,OCH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ159.6,154.6,151.8,144.9,141.0,135.8,129.7,120.2,115.8,110.8,55.3,52.2,19.9.ESI-HRMS(m/z):Calcd.for C13H17N6O3[M+H]+305.1357；found 305.1359.White solid, yield 67%, mp 226 - 227. 1 H NMR (400MHz, DMSO- d 6) δ10.78 (s, 1H, NH), 9.78 (s, 1H, NH), 9.29 (s, 1H, NH), 7.83 (s, 1H, = CH), 7.43 (s, 1H, Ar-H), 7.31 (t, J = 7.6 Hz, 1H, Ar-H), 7.25 (d, J = 7.2 Hz, 1H, Ar-H), 6.94 (d, J = 7.2) Hz, 1H, Ar-H), 4.12 (s, 2H, CH 2 ), 3.80 (s, 3H, OCH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 159.6, 154.6, 151.8, 144.9, 141.0, 135.8, 129.7, 120.2, 115.8, 110.8, 55.3, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 17 N 6 O 3 [M+H ] + 305.1357; found 305.1359.
(E)-2-(4-甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-12)；(E)-2-(4-methoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I a -12);
白色固体，产率82％，熔点230–231℃。1H NMR(400MHz,DMSO-d6)δ10.62(s,1H,NH),9.76(s,1H,NH),9.17(s,1H,NH),7.80(s,1H,＝CH),7.72(d,J＝8.0Hz,2H,Ar-H),6.96(d,J＝8.0Hz,2H,Ar-H),4.11(s,2H,CH2),3.79(s,3H,OCH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ160.4,154.7,151.7,144.8,141.0,128.5,127.1,114.1,55.3,52.2,19.9.ESI-HRMS(m/z):Calcd.for C13H17N6O3[M+H]+305.1357；found 305.1359.White solid, yield 82%, m.p. 230 - 231. 1 H NMR (400MHz, DMSO- d 6) δ10.62 (s, 1H, NH), 9.76 (s, 1H, NH), 9.17 (s, 1H, NH), 7.80 (s, 1H, = CH), 7.72 (d, J = 8.0 Hz, 2H, Ar-H), 6.96 (d, J = 8.0 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 3.79 (s, 3H, OCH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 160.4, 154.7, 151.7, 144.8, 141.0, 128.5, 127.1, 114.1, 55.3, 52.2, 19.9. ESI-HRMS (m) /z): Calcd.for C 13 H 17 N 6 O 3 [M+H] + 305.1357; found 305.1359.
(E)-2-(2,3-二甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-13)；(E)-2-(2,3-dimethoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -13);
白色固体，产率80％，熔点226–227℃。1H NMR(400MHz,DMSO-d6)δ10.75(s,1H,NH),9.77(s,1H,NH),9.21(s,1H,NH),8.16(s,1H,＝CH),7.68(d,J＝6.8Hz,2H,Ar-H),7.04–7.10(m,2H,Ar-H),4.10(s,2H,CH2),3.82(s,3H,OCH3),3.74(s,3H,OCH3),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,152.6,151.7,147.5,144.8,136.7,127.8,124.1,117.4,113.6,61.2,55.7,52.2,19.9.ESI-HRMS(m/z):Calcd.for C14H19N6O4[M+H]+335.1462；found 335.1469.White solid, yield 80%, mp 226 - 227. 1 H NMR (400MHz, DMSO- d 6) δ10.75 (s, 1H, NH), 9.77 (s, 1H, NH), 9.21 (s, 1H, NH), 8.16 (s, 1H, = CH), 7.68 (d, J = 6.8 Hz, 2H, Ar-H), 7.04 - 7.10 (m, 2H, Ar-H), 4.10 (s, 2H, CH 2 ), 3.82 (s, 3H, OCH 3 ), 3.74 (s, 3H, OCH 3 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 152.6, 151.7, 147.5, 144.8, 136.7, 127.8, 124.1, 117.4, 113.6, 61.2, 55.7, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 14 H 19 N 6 O 4 [M+H] + 335.1462; found 335.1469.
(E)-2-(2,4-二甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-14)；(E)-2-(2,4-dimethoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -14);
白色固体，产率76％，熔点210–211℃。1H NMR(400MHz,DMSO-d6)δ10.57(s,1H,NH),9.75(s,1H,NH),9.13(s,1H,NH),8.11(s,1H,＝CH),7.99(d,J＝8.4Hz,1H,Ar-H),6.59(s,1H,Ar-H),6.56(d,J＝8.4Hz,1H,Ar-H),4.10(s,2H,CH2),3.82(s,3H,OCH3),3.80(s,3H,OCH3),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ161.9,158.6,154.7,151.7,144.8,136.6,127.0,115.2,106.2,98.0,55.7,55.4,52.2,19.9.ESI-HRMS(m/z):Calcd.for C14H19N6O4[M+H]+335.1462；found 335.1463.White solid, 76% yield, m.p. 210 - 211. 1 H NMR (400MHz, DMSO- d 6) δ10.57 (s, 1H, NH), 9.75 (s, 1H, NH), 9.13 (s, 1H, NH), 8.11 (s, 1H, = CH), 7.99 (d, J = 8.4 Hz, 1H, Ar-H), 6.59 (s, 1H, Ar-H), 6.56 (d, J = 8.4 Hz, 1H, Ar-H), 4.10 (s, 2H, CH) 2 ), 3.82 (s, 3H, OCH 3 ), 3.80 (s, 3H, OCH 3 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 161.9, 158.6, 154.7, 151.7, 144.8, 136.6, 127.0, 115.2, 106.2, 98.0, 55.7, 55.4, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 14 H 19 N 6 O 4 [M+H] + 335.1462; Found 335.1463.
(E)-2-(3,5-二甲氧基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-15)；(E)-2-(3,5-dimethoxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -15);
白色固体，产率87％，熔点245℃。1H NMR(400MHz,DMSO-d6)δ10.81(s,1H,NH),9.80(s,1H,NH),9.33(s,1H,NH),7.77(s,1H,＝CH),6.95(brs,2H,Ar-H),6.49(s,1H,Ar-H),4.13(s,2H,CH2),3.77(s,6H,OCH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ160.6,154.6,151.8,144.9,141.0,136.4,104.7,101.8,55.4,52.2,19.9.ESI-HRMS(m/z):Calcd.for C14H19N6O4[M+H]+335.1462；found 335.1460.White solid, yield 87%, mp 245. 1 H NMR (400MHz, DMSO- d 6) δ10.81 (s, 1H, NH), 9.80 (s, 1H, NH), 9.33 (s, 1H, NH), 7.77 (s, 1H, = CH), 6.95 (brs, 2H, Ar-H), 6.49 (s, 1H, Ar-H), 4.13 (s, 2H, CH 2 ), 3.77 (s, 6H, OCH 3 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 160.6, 154.6, 151.8, 144.9, 141.0, 136.4, 104.7, 101.8, 55.4, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 14 H 19 N 6 O 4 [M+H] + 335.1462; found 335.1460.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(2,3,4-三甲氧基苯基亚甲基)氨基甲酰肼(Ia-16)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(2,3,4-trimethyl) Oxyphenylmethylene)carbamoyl hydrazide (I a -16);
白色固体，产率78％，熔点244–245℃。1H NMR(400MHz,DMSO-d6)δ10.64(s,1H,NH),9.77(s,1H,NH),9.17(s,1H,NH),8.06(s,1H,＝CH),7.81(d,J＝8.4Hz,1H,Ar-H),6.87(d,J＝8.4Hz,1H,Ar-H),4.10(s,2H,CH2),3.84(s,3H,OCH3),3.79(s,3H,OCH3),3.75(s,3H,OCH3),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,152.2,151.8,144.8,141.5,136.7,120.8,120.5,108.5,61.8,60.5,56.0,52.2,19.9.ESI-HRMS(m/z):Calcd.for C15H21N6O5[M+H]+365.1568；found 365.1569.White solid, yield 78%, mp 244 - 245. 1 H NMR (400MHz, DMSO- d 6) δ10.64 (s, 1H, NH), 9.77 (s, 1H, NH), 9.17 (s, 1H, NH), 8.06 (s, 1H, = CH), 7.81 (d, J = 8.4 Hz, 1H, Ar-H), 6.87 (d, J = 8.4 Hz, 1H, Ar-H), 4.10 (s, 2H, CH 2 ), 3.84 (s, 3H, OCH 3 ), 3.79 (s, 3H, OCH 3 ), 3.75 (s, 3H, OCH 3 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 152.2, 151.8, 144.8 , 141.5, 136.7, 120.8, 120.5, 108.5, 61.8, 60.5, 56.0, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 15 H 21 N 6 O 5 [M+H] + 365.1568; 365.1569.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(3,4,5-三甲氧基苯基亚甲基)氨基甲酰肼(Ia-17)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(3,4,5-trimethyl Oxyphenylmethylene)carbamoyl hydrazide (I a -17);
白色固体，产率71％，熔点233–234℃。1H NMR(400MHz,DMSO-d6)δ10.80(s,1H,NH),9.81(s,1H,NH),9.32(s,1H,NH),7.78(s,1H,＝CH),7.09(s,2H,Ar-H),4.16(s,2H,CH2),3.84(s,6H,OCH3),3.69(s,3H,OCH3),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,153.2,151.9,145.0,141.1,138.6,129.9,104.2,60.1,56.1,52.2,19.9.ESI-HRMS(m/z):Calcd.for C15H21N6O5[M+H]+365.1568；found 365.1569.White solid, 71% yield, mp 233 - 234. 1 H NMR (400MHz, DMSO- d 6) δ10.80 (s, 1H, NH), 9.81 (s, 1H, NH), 9.32 (s, 1H, NH), 7.78 (s, 1H, = CH), 7.09 (s, 2H, Ar-H), 4.16 (s, 2H, CH 2 ), 3.84 (s, 6H, OCH 3 ), 3.69 (s, 3H, OCH 3 ), 1.88 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 153.2, 151.9, 145.0, 141.1, 138.6, 129.9, 104.2, 60.1, 56.1, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 15 H 21 N 6 O 5 [M+H] + 365.1568; found 365.1569.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(2-(三氟甲基)苯基亚甲基)氨基甲酰肼(Ia-18)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(2-(trifluoromethyl) Phenylmethylene)carbamoyl hydrazide (I a -18);
白色固体，产率79％，熔点262–263℃。1H NMR(400MHz,DMSO-d6)δ11.07(s,1H,NH),9.80(s,1H,NH),9.41(s,1H,NH),8.48(d,J＝7.2Hz,1H,Ar-H),8.23(s,1H,＝CH),7.70–7.77(m,2H,Ar-H),7.58(t,J＝7.2Hz,1H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.4,151.7,144.9,136.2,132.5,132.2,129.5,127.1,126.3(q,J＝268.5Hz),125.7(q,J＝8.4Hz),122.9,52.1,19.9.ESI-HRMS(m/z):Calcd.for C13H14F3N6O2[M+H]+343.1125；found 343.1130. White solid, yield 79%, m.p. 262 - 263. 1 H NMR (400MHz, DMSO- d 6) δ11.07 (s, 1H, NH), 9.80 (s, 1H, NH), 9.41 (s, 1H, NH), 8.48 (d, J = 7.2Hz, 1H , Ar-H), 8.23 (s, 1H, =CH), 7.70 - 7.77 (m, 2H, Ar-H), 7.58 (t, J = 7.2 Hz, 1H, Ar-H), 4.12 (s, 2H) , CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.4, 151.7, 144.9, 136.2, 132.5, 132.2, 129.5, 127.1, 126.3 (q, J = 268.5 Hz ), 125.7 (q, J = 8.4 Hz), 122.9, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 14 F 3 N 6 O 2 [M+H] + 343.1125; found 343.1130 .
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(3-(三氟甲基)苯基亚甲基)氨基甲酰肼(Ia-19)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(3-(trifluoromethyl) Phenylmethylene)carbamoyl hydrazide (I a -19);
白色固体，产率86％，熔点278–279℃。1H NMR(300MHz,DMSO-d6)δ10.95(s,1H,NH),9.79(s,1H,NH),9.46(s,1H,NH),8.28(s,1H,＝CH),8.00(d,J＝7.5Hz,1H,Ar-H),7.95(s,1H,Ar-H),7.71(d,J＝6.0Hz,1H,Ar-H),7.63(t,J＝7.5Hz,1H,Ar-H),4.14(s,2H,CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,151.8,144.9,139.5,135.6,131.3,129.7,129.7(q,J＝253.2Hz),129.6(q,J＝31.8Hz)，125.6,122.8,52.2,19.9.ESI-HRMS(m/z):Calcd.for C13H14F3N6O2[M+H]+343.1125；found 343.1128.White solid, yield 86%, mp 278 - 279. 1 H NMR (300MHz, DMSO- d 6) δ10.95 (s, 1H, NH), 9.79 (s, 1H, NH), 9.46 (s, 1H, NH), 8.28 (s, 1H, = CH), 8.00 (d, J = 7.5 Hz, 1H, Ar-H), 7.95 (s, 1H, Ar-H), 7.71 (d, J = 6.0 Hz, 1H, Ar-H), 7.63 (t, J = 7.5) Hz, 1H, Ar-H), 4.14 (s, 2H, CH 2 ), 1.88 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 151.8, 144.9, 139.5, 135.6, 131.3, 129.7, 129.7 (q, J = 253.2 Hz), 129.6 (q, J = 31.8 Hz), 125.6, 122.8, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 14 F 3 N 6 O 2 [M+H] + 343.1125; found 343.1128.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(4-(三氟甲基)苯基亚甲基)氨基甲酰肼(Ia-20)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(4-(trifluoromethyl) Phenylmethylene)carbamoyl hydrazide (I a -20);
白色固体，产率76％，熔点239–241℃。1H NMR(400MHz,DMSO-d6)δ10.99(s,1H,NH),9.79(s,1H,NH),9.40(s,1H,NH),8.02(d,J＝8.0Hz,2H,Ar-H),7.94(s,1H,＝CH),7.76(d,J＝8.0Hz,2H,Ar-H),4.13(s,2H,CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.7,144.9,139.4,138.4,129.1(q,J＝254.4Hz),127.4,125.4(q,J＝10.0Hz),122.9,52.2,19.9.ESI-HRMS(m/z):Calcd.for C13H14F3N6O2[M+H]+343.1125；found343.1130.White solid, 76% yield, mp 239 - 241. 1 H NMR (400MHz, DMSO- d 6) δ10.99 (s, 1H, NH), 9.79 (s, 1H, NH), 9.40 (s, 1H, NH), 8.02 (d, J = 8.0Hz, 2H , Ar-H), 7.94 (s, 1H, =CH), 7.76 (d, J = 8.0 Hz, 2H, Ar-H), 4.13 (s, 2H, CH 2 ), 1.88 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.7, 144.9, 139.4, 138.4, 129.1 (q, J = 254.4 Hz), 127.4, 125.4 (q, J = 10.0 Hz), 122.9, 52.2, 19.9 .ESI-HRMS (m/z): Calcd. for C 13 H 14 F 3 N 6 O 2 [M+H] + 343.1125; found 343.1130.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(3-(三氟甲氧基)苯基亚甲基)氨基甲酰肼(Ia-21)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(3-(trifluoromethoxy) Phenylmethylene)carbamoyl hydrazide (I a -21);
白色固体，产率78％，熔点264–265℃。1H NMR(300MHz,DMSO-d6)δ10.94(s,1H,NH),9.80(s,1H,NH),9.44(s,1H,NH),7.97(s,1H,＝CH),7.89(s,1H,Ar-H),7.71(d,J＝8.0Hz,1H,Ar-H),7.53(t,J＝8.0Hz,1H,Ar-H),7.36(d,J＝8.0Hz,1H,Ar-H),4.13(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,151.8,148.9,144.9,139.4,137.0,130.6,126.7,121.6,120.1(q,J＝254.5Hz),118.6,52.2,19.8.ESI-HRMS(m/z):Calcd.for C13H14F3N6O3[M+H]+359.1074；found 359.1077.White solid, 78% yield, mp 264 - 265. 1 H NMR (300MHz, DMSO- d 6) δ10.94 (s, 1H, NH), 9.80 (s, 1H, NH), 9.44 (s, 1H, NH), 7.97 (s, 1H, = CH), 7.89 (s, 1H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.53 (t, J = 8.0 Hz, 1H, Ar-H), 7.36 (d, J = 8.0) Hz, 1H, Ar-H), 4.13 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 151.8, 148.9, 144.9, 139.4, 137.0, 130.6, 126.7, 121.6, 120.1 (q, J = 254.5 Hz), 118.6, 52.2, 19.8. ESI-HRMS (m/z): Calcd. for C 13 H 14 F 3 N 6 O 3 [M+H ] + 359.1074; found 359.1077.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(4-(三氟甲氧基)苯基亚甲基)氨基甲酰肼(Ia-22)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(4-(trifluoromethoxy) Phenylmethylene)carbamoyl hydrazide (I a -22);
白色固体，产率87％，熔点266–267℃。1H NMR(400MHz,DMSO-d6)δ10.86(s,1H,NH),9.78(s,1H,NH),9.32(s,1H,NH),7.93(d,J＝8.4Hz,2H,Ar-H),7.89(s,1H,＝CH),7.40(d,J＝8.4Hz,2H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.8,148.9,144.9,139.5,133.9,128.8,121.2,120.1(q,J＝254.8Hz),52.2,19.9.ESI-HRMS(m/z):Calcd.for C13H14F3N6O3[M+H]+359.1074；found 359.1081.White solid, yield 87%, mp 266 - 267. 1 H NMR (400MHz, DMSO- d 6) δ10.86 (s, 1H, NH), 9.78 (s, 1H, NH), 9.32 (s, 1H, NH), 7.93 (d, J = 8.4Hz, 2H , Ar-H), 7.89 (s, 1H, =CH), 7.40 (d, J = 8.4 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.8, 148.9, 144.9, 139.5, 133.9, 128.8, 121.2, 120.1 (q, J = 254.8 Hz), 52.2, 19.9. ESI-HRMS (m/z ): Calcd.for C 13 H 14 F 3 N 6 O 3 [M+H] + 359.1074; found 359.1081.
(E)-2-(2-氟苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-23)；(E)-2-(2-fluorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H)- Carbamoyl hydrazide (I a -23);
白色固体，产率78％，熔点233–234℃。1H NMR(400MHz,DMSO-d6)δ10.92(s,1H,NH),9.79(s,1H,NH),9.33(s,1H,NH),8.17–7.22(m,1H,Ar-H),8.09(s,1H,＝CH),7.41–7.46(m,1H,Ar-H),7.23–7.28(m,2H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ160.5(d,J＝248.1Hz),154.5,151.7,144.9,133.5,131.3(d,J＝6.8Hz),126.6,124.6,121.9(d,J＝9.3Hz),115.8(d,J＝20.5Hz),52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14FN6O2[M+H]+293.1157；found 293.1157.White solid, 78% yield, mp 233 - 234. 1 H NMR (400MHz, DMSO- d 6) δ10.92 (s, 1H, NH), 9.79 (s, 1H, NH), 9.33 (s, 1H, NH), 8.17-7.22 (m, 1H, Ar- H), 8.09 (s, 1H, =CH), 7.41 - 7.46 (m, 1H, Ar-H), 7.23 - 7.28 (m, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 160.5 (d, J = 248.1 Hz), 154.5, 151.7, 144.9, 133.5, 131.3 (d, J = 6.8 Hz), 126.6, 124.6, 121.9 (d, J = 9.3 Hz), 115.8 (d, J = 20.5 Hz), 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 FN 6 O 2 [M +H] + 293.1157;found 293.1157.
(E)-2-(3-氟苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-24)；(E)-2-(3-fluorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)- Carbamoyl hydrazide (I a -24);
白色固体，产率87％，熔点213–215℃。1H NMR(400MHz,DMSO-d6)δ10.88(s,1H,NH),9.78(s,1H,NH),9.38(s,1H,NH),7.86(s,1H,＝CH),7.82(d,J＝10.4Hz,1H,Ar-H),7.51(d,J＝7.6Hz,1H,Ar-H),7.41–7.47(m,2H,Ar-H),7.20(t,J＝8.0Hz,1H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ162.6(d,J＝241.4Hz),154.6,151.7,144.9,139.6,137.1(d,J＝8.1Hz),130.6(d,J＝8.3Hz),123.9,116.2(d,J＝21.1Hz),112.4(d,J＝22.7Hz),52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14FN6O2[M+H]+293.1157；found 293.1160.White solid, yield 87%, mp 213 - 215. 1 H NMR (400MHz, DMSO- d 6) δ10.88 (s, 1H, NH), 9.78 (s, 1H, NH), 9.38 (s, 1H, NH), 7.86 (s, 1H, = CH), 7.82 (d, J = 10.4 Hz, 1H, Ar-H), 7.51 (d, J = 7.6 Hz, 1H, Ar-H), 7.41 - 7.47 (m, 2H, Ar-H), 7.20 (t, J) = 8.0 Hz, 1H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 162.6 (d, J = 241.4 Hz), 154.6, 151.7, 144.9, 139.6, 137.1 (d, J = 8.1 Hz), 130.6 (d, J = 8.3 Hz), 123.9, 116.2 (d, J = 21.1 Hz), 112.4 (d, J = 22.7 Hz), 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 FN 6 O 2 [M+H] + 293.1157; found 293.1160.
(E)-2-(4-氟苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-25)；(E)-2-(4-fluorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H)- Carbamoyl hydrazide (I a -25);
白色固体，产率75％，熔点240℃。1H NMR(400MHz,DMSO-d6)δ10.77(s,1H,NH),9.77(s,1H,NH),9.27(s,1H,NH),7.87(s,1H,＝CH),7.85(d,J＝8.0Hz,2H,Ar-H),7.25(t,J＝8.0Hz,2H,Ar-H),4.11(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ162.8(d,J＝245.4Hz),154.7,151.7,144.8,139.9,131.7(d,J＝2.4Hz),129.0(d,J＝8.2Hz),115.6(d,J＝21.6Hz),52.2,19.8.ESI-HRMS(m/z):Calcd.for C12H14FN6O2[M+H]+293.1157；found 293.1159.White solid, 75% yield, mp. 1 H NMR (400MHz, DMSO- d 6) δ10.77 (s, 1H, NH), 9.77 (s, 1H, NH), 9.27 (s, 1H, NH), 7.87 (s, 1H, = CH), 7.85 (d, J = 8.0 Hz, 2H, Ar-H), 7.25 (t, J = 8.0 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 162.8 (d, J = 245.4 Hz), 154.7, 151.7, 144.8, 139.9, 131.7 (d, J = 2.4 Hz), 129.0 (d, J = 8.2) Hz), 115.6 (d, J = 21.6 Hz), 52.2, 19.8. ESI-HRMS (m/z): Calcd. for C 12 H 14 FN 6 O 2 [M+H] + 293.1157; found 293.1159.
(E)-2-(2-氯苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-26)；(E)-2-(2-chlorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H)- Carbamoyl hydrazide (I a -26);
白色固体，产率89％，熔点248–249℃。1H NMR(400MHz,DMSO-d6)δ10.99(s,1H,NH),9.78(s,1H,NH),9.35(s,1H,NH),8.28(brs,2H,＝CH,Ar-H),7.47–7.50(m,1H,Ar-H),7.36–7.42(m,2H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.7,144.9,137.0,132.6,131.6,130.9,129.9,127.3,129.2,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14ClN6O2[M+H]+309.0861；found 309.0865.White solid, yield 89%, mp 248 - 249. 1 H NMR (400MHz, DMSO- d 6) δ10.99 (s, 1H, NH), 9.78 (s, 1H, NH), 9.35 (s, 1H, NH), 8.28 (brs, 2H, = CH, Ar -H), 7.47-7.50 (m, 1H , Ar-H), 7.36-7.42 (m, 2H, Ar-H), 4.12 (s, 2H, CH 2), 1.87 (s, 3H, CH 3); 13 C NMR (100MHz, DMSO- d 6) δ154.5,151.7,144.9,137.0,132.6,131.6,130.9,129.9,127.3,129.2,52.2,19.9.ESI-HRMS (m / z): Calcd.for C 12 H 14 ClN 6 O 2 [M+H] + 309.0861; found 309.0865.
(E)-2-(3-氯苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-27)；(E)-2-(3-chlorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H)- Carbamoyl hydrazide (I a -27);
白色固体，产率88％，熔点242–243℃。1H NMR(400MHz,DMSO-d6)δ10.89(s,1H,NH),9.79(s,1H,NH),9.41(s,1H,NH),8.05(s,1H,Ar-H),7.84(s,1H,＝CH),7.61(d,J＝3.2Hz,1H,Ar-H),7.41–7.44(m,2H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,151.8,144.9,139.5,136.7,133.8,130.5,129.1,126.3,125.6,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14ClN6O2[M+H]+309.0861；found 309.0867.White solid, yield 88%, m.p. 242 - 243. 1 H NMR (400MHz, DMSO- d 6) δ10.89 (s, 1H, NH), 9.79 (s, 1H, NH), 9.41 (s, 1H, NH), 8.05 (s, 1H, Ar-H) , 7.84 (s, 1H, =CH), 7.61 (d, J = 3.2 Hz, 1H, Ar-H), 7.41 - 7.44 (m, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87(s,3H,CH 3 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 154.6, 151.8, 144.9, 139.5, 136.7, 133.8, 130.5, 129.1, 126.3, 125.6, 52.2, 19.9. ESI-HRMS (m) /z): Calcd.for C 12 H 14 ClN 6 O 2 [M+H] + 309.0861; found 309.0867.
(E)-2-(4-氯苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-28)；(E)-2-(4-chlorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)- Carbamoyl hydrazide (I a -28);
白色固体，产率85％，熔点275–276℃。1H NMR(400MHz,DMSO-d6)δ10.86(s,1H,NH),9.79(s,1H,NH), 9.33(s,1H,NH),7.85(s,1H,＝CH),7.83(d,J＝8.0Hz,2H,Ar-H),7.47(d,J＝8.0Hz,2H,Ar-H),4.11(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,151.7,144.9,139.7,133.8,133.4,128.9,128.6,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14ClN6O2[M+H]+309.0861；found 309.0861.White solid, 85% yield, mp 275 - 276. 1 H NMR (400MHz, DMSO- d 6) δ10.86 (s, 1H, NH), 9.79 (s, 1H, NH), 9.33 (s, 1H, NH), 7.85 (s, 1H, = CH), 7.83 (d, J = 8.0 Hz, 2H, Ar-H), 7.47 (d, J = 8.0 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 151.7, 144.9, 139.7, 133.8, 133.4, 128.9, 128.6, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 ClN 6 O 2 [M+H] + 309.0861; found 309.0861.
(E)-2-(2,4-二氯苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-29)；(E)-2-(2,4-dichlorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 ( 5H)-yl)carbamoyl hydrazide (I a -29);
白色固体，产率93％，熔点285–286℃。1H NMR(400MHz,DMSO-d6)δ11.05(s,1H,NH),9.80(s,1H,NH),9.43(s,1H,NH),8.31(d,J＝8.8Hz,1H,Ar-H),8.21(s,1H,＝CH),7.68(s,1H,Ar-H),7.49(d,J＝8.8Hz,1H,Ar-H),4.11(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.4,151.7,144.9,135.8,134.4,133.2,130.7,129.2,128.4,127.7,52.1,19.9.ESI-HRMS(m/z):Calcd.for C12H13Cl2N6O2[M+H]+343.0472；found 343.0470.White solid, 93% yield, mp 285 - 286. 1 H NMR (400MHz, DMSO- d 6) δ11.05 (s, 1H, NH), 9.80 (s, 1H, NH), 9.43 (s, 1H, NH), 8.31 (d, J = 8.8Hz, 1H , Ar-H), 8.21 (s, 1H, =CH), 7.68 (s, 1H, Ar-H), 7.49 (d, J = 8.8 Hz, 1H, Ar-H), 4.11 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.4, 151.7, 144.9, 135.8, 134.4, 133.2, 130.7, 129.2, 128.4, 127.7, 52.1, 19.9. HRMS (m/z): Calcd. for C 12 H 13 Cl 2 N 6 O 2 [M+H] + 343.0472; found 343.0470.
(E)-2-(3,4-二氯苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-30)；(E)-2-(3,4-Dichlorophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 ( 5H)-yl)carbamoyl hydrazide (I a -30);
白色固体，产率88％，熔点265–266℃。1H NMR(400MHz,DMSO-d6)δ10.97(s,1H,NH),9.80(s,1H,NH),9.47(s,1H,NH),8.24(s,1H,Ar-H),7.83(s,1H,＝CH),7.71(d,J＝8.0Hz,1H,Ar-H),7.67(d,J＝8.0Hz,1H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.7,144.8,138.4,135.3,131.7,131.5,130.8,127.8,127.5,52.1,19.9.ESI-HRMS(m/z):Calcd.for C12H13Cl2N6O2[M+H]+343.0472；found 343.0466.White solid, yield 88%, mp 265 - 266. 1 H NMR (400MHz, DMSO- d 6) δ10.97 (s, 1H, NH), 9.80 (s, 1H, NH), 9.47 (s, 1H, NH), 8.24 (s, 1H, Ar-H) , 7.83 (s, 1H, =CH), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.7, 144.8, 138.4, 135.3, 131.7, 131.5, 130.8, 127.8, 127.5, 52.1, 19.9. HRMS (m/z): Calcd. for C 12 H 13 Cl 2 N 6 O 2 [M+H] + 343.0472; found 343.0466.
(E)-2-(2-溴苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-31)；(E)-2-(2-bromophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)- Carbamoyl hydrazide (I a -31);
白色固体，产率89％，熔点265℃。1H NMR(400MHz,DMSO-d6)δ11.00(s,1H,NH),9.78(s,1H,NH),9.34(s,1H,NH),8.24(s,2H,＝CH,Ar-H),7.65(d,J＝7.6Hz,1H,Ar-H),7.41(t,J＝7.6Hz,1H,Ar-H),7.31(t,J＝7.6Hz,1H,Ar-H),4.11(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.7,144.9,139.4,133.0,131.2,127.8,127.6,123.0,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14BrN6O2[M+H]+353.0356；found 353.0356.White solid, yield 89%, mp 265. 1 H NMR (400MHz, DMSO- d 6) δ11.00 (s, 1H, NH), 9.78 (s, 1H, NH), 9.34 (s, 1H, NH), 8.24 (s, 2H, = CH, Ar -H), 7.65 (d, J = 7.6 Hz, 1H, Ar-H), 7.41 (t, J = 7.6 Hz, 1H, Ar-H), 7.31 (t, J = 7.6 Hz, 1H, Ar-H) ), 4.11 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.7, 144.9, 139.4, 133.0, 131.2, 127.8, 127.6, 123.0 , 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 BrN 6 O 2 [M+H] + 353.0356; found 353.0356.
(E)-2-(3-溴苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-32)；(E)-2-(3-bromophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)- Carbamoyl hydrazide (I a -32);
白色固体，产率85％，熔点253–254℃。1H NMR(400MHz,DMSO-d6)δ10.87(s,1H,NH),9.78(s,1H,NH),9.40(s,1H,NH),8.18(s,1H,Ar-H),7.83(s,1H,＝CH),7.66(d,J＝8.0Hz,1H,Ar-H),7.54(d,J＝8.0Hz,1H,Ar-H),7.35(t,J＝8.0Hz,1H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,151.8,144.9,139.4,136.9,132.0,130.8,128.5,126.8,122.4,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14BrN6O2[M+H]+353.0356；found 353.0355.White solid, 85% yield, mp 253 - 254. 1 H NMR (400MHz, DMSO- d 6) δ10.87 (s, 1H, NH), 9.78 (s, 1H, NH), 9.40 (s, 1H, NH), 8.18 (s, 1H, Ar-H) , 7.83 (s, 1H, =CH), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.54 (d, J = 8.0 Hz, 1H, Ar-H), 7.35 (t, J = 8.0) Hz, 1H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 151.8, 144.9, 139.4, 136.9, 132.0, 130.8, 128.5, 126.8, 122.4, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 BrN 6 O 2 [M+H] + 353.0356; found 353.0355.
(E)-2-(4-溴苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-33)；(E)-2-(4-bromophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)- Carbamoyl hydrazide (I a -33);
白色固体，产率82％，熔点271–272℃。1H NMR(400MHz,DMSO-d6)δ10.86(s,1H,NH),9.79(s,1H,NH),9.33(s,1H,NH),7.84(s,1H,＝CH),7.76(d,J＝8.0Hz,2H,Ar-H),7.61(d,J＝8.0Hz,2H,Ar-H),4.11(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.6,151.7,144.9,139.8,133.8,131.6,128.9,122.6,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14BrN6O2[M+H]+353.0356；found 353.0354.White solid, yield 82%, mp 271 - 272. 1 H NMR (400MHz, DMSO- d 6) δ10.86 (s, 1H, NH), 9.79 (s, 1H, NH), 9.33 (s, 1H, NH), 7.84 (s, 1H, = CH), 7.76 (d, J = 8.0 Hz, 2H, Ar-H), 7.61 (d, J = 8.0 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.6, 151.7, 144.9, 139.8, 133.8, 131.6, 128.9, 122.6, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 BrN 6 O 2 [M+H] + 353.0356; found 353.0354.
(E)-2-(2-氰基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-34)；(E)-2-(2-cyanophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H) -yl)carbamoyl hydrazide (I a -34);
白色固体，产率84％，熔点274–275℃。1H NMR(400MHz,DMSO-d6)δ11.15(s,1H,NH),9.81(s,1H,NH),9.33(s,1H,NH),8.36(d,J＝6.8Hz,1H,Ar-H),8.22(s,1H,＝CH),7.87(d,J＝7.6Hz,1H,Ar-H),7.74(t,J＝7.6Hz,1H,Ar-H),7.56(t,J＝7.6Hz,1H,Ar-H),4.13(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.3,151.6,144.9,137.0,136.5,133.2,129.8,126.2,117.4,110.0,52.1,19.9.ESI-HRMS(m/z):Calcd.for C13H14N7O2[M+H]+300.1203；found 300.1202.White solid, yield 84%, mp 274 - 275. 1 H NMR (400MHz, DMSO- d 6) δ11.15 (s, 1H, NH), 9.81 (s, 1H, NH), 9.33 (s, 1H, NH), 8.36 (d, J = 6.8Hz, 1H , Ar-H), 8.22 (s, 1H, =CH), 7.87 (d, J = 7.6 Hz, 1H, Ar-H), 7.74 (t, J = 7.6 Hz, 1H, Ar-H), 7.56 ( t, J = 7.6 Hz, 1H, Ar-H), 4.13 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.3, 151.6, 144.9 , 137.0, 136.5, 133.2, 129.8, 126.2, 117.4, 110.0, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 14 N 7 O 2 [M+H] + 300.1203; found 300.1202.
(E)-2-(3-氰基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-35)；(E)-2-(3-cyanophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H) -yl)carbamoyl hydrazide (I a -35);
白色固体，产率65％，熔点249–250℃。1H NMR(300MHz,DMSO-d6)δ10.99(s,1H,NH),9.79(s,1H,NH),9.46(s,1H,NH),8.46(s,1H,Ar-H),8.02(d,J＝7.8Hz,1H,Ar-H),7.88(s,1H,＝CH),7.81(d,J＝7.8Hz,1H,Ar-H),7.61(t,J＝7.8Hz,1H,Ar-H),4.13(s,2H,CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.7,144.9,138.6,135.8,132.3,131.9,129.8,129.7,118.7,111.9,52.1,19.9.ESI-HRMS(m/z):Calcd.for C13H14N7O2[M+H]+300.1203；found 300.1210.White solid, yield 65%, mp 249 - 250. 1 H NMR (300MHz, DMSO- d 6) δ10.99 (s, 1H, NH), 9.79 (s, 1H, NH), 9.46 (s, 1H, NH), 8.46 (s, 1H, Ar-H) , 8.02 (d, J = 7.8 Hz, 1H, Ar-H), 7.88 (s, 1H, =CH), 7.81 (d, J = 7.8 Hz, 1H, Ar-H), 7.61 (t, J = 7.8) Hz, 1H, Ar-H), 4.13 (s, 2H, CH 2 ), 1.88 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.7, 144.9, 138.6, 135.8, 132.3, 131.9, 129.8, 129.7, 118.7, 111.9, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 14 N 7 O 2 [M+H] + 300.1203; found 300.1210.
(E)-2-(4-氰基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-36)；(E)-2-(4-cyanophenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H) -yl)carbamoyl hydrazide (I a -36);
白色固体，产率78％，熔点293–294℃。1H NMR(400MHz,DMSO-d6)δ11.06(s,1H,NH),9.80(s,1H,NH),9.44(s,1H,NH),8.00(d,J＝7.2Hz,2H,Ar-H),7.90(s,1H,＝CH),7.88(d,J＝7.2Hz,2H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.6,144.8,139.1,139.0,132.5,127.5,118.8,111.2,52.1,19.9.ESI-HRMS(m/z):Calcd.for C13H14N7O2[M+H]+300.1203；found 300.1206.White solid, 78% yield, mp 293 - 294. 1 H NMR (400MHz, DMSO- d 6) δ11.06 (s, 1H, NH), 9.80 (s, 1H, NH), 9.44 (s, 1H, NH), 8.00 (d, J = 7.2Hz, 2H , Ar-H), 7.90 (s, 1H, =CH), 7.88 (d, J = 7.2 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.6, 144.8, 139.1, 139.0, 132.5, 127.5, 118.8, 111.2, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 14 N 7 O 2 [M+H] + 300.1203; found 300.1206.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(2-硝基苯基亚甲基)氨基甲酰肼(Ia-37)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(2-nitrophenyl Methyl)carbamoyl hydrazide (I a -37);
黄色固体，产率89％，熔点232–233℃。1H NMR(300MHz,DMSO-d6)δ11.11(s,1H,NH),9.80(s,1H,NH),9.38(s,1H,NH),8.43(d,J＝7.5Hz,1H,Ar-H),8.31(s,1H,＝CH),8.03(d,J＝7.5Hz,1H,Ar-H),7.76(t,J＝7.5Hz,1H,Ar-H),7.62(t,J＝7.5Hz,1H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.4,151.7,148.0,144.9,136.2,133.3,130.1,128.6,128.0,124.6,52.1,19.9.ESI-HRMS(m/z):Calcd.for C12H14N7O4[M+H]+320.1102；found 320.1103.Yellow solid, yield 89%, mp 232 - 233. 1 H NMR (300MHz, DMSO- d 6) δ11.11 (s, 1H, NH), 9.80 (s, 1H, NH), 9.38 (s, 1H, NH), 8.43 (d, J = 7.5Hz, 1H , Ar-H), 8.31 (s, 1H, =CH), 8.03 (d, J = 7.5 Hz, 1H, Ar-H), 7.76 (t, J = 7.5 Hz, 1H, Ar-H), 7.62 ( t, J = 7.5 Hz, 1H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.4, 151.7, 148.0 , 144.9, 136.2, 133.3, 130.1, 128.6, 128.0, 124.6, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 N 7 O 4 [M+H] + 320.1102; found 320.1103.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(3-硝基苯基亚甲基)氨基甲酰肼(Ia-38)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(3-nitrophenyl Methyl)carbamoyl hydrazide (I a -38);
白色固体，产率79％，熔点277–278℃。1H NMR(300MHz,DMSO-d6)δ11.02(s,1H,NH),9.80(s,1H,NH),9.53(s,1H,NH),8.69(s,1H,Ar-H),8.20(d,J＝7.2Hz,2H,Ar-H),7.99(s,1H,＝CH),7.69(t,J＝8.0Hz,1H,Ar-H), 4.13(s,2H,CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.7,148.4,144.9,139.0,136.4,133.4,130.1,123.6,120.8,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H14N7O4[M+H]+320.1102；found 320.1102.White solid, yield 79%, mp 277 - 278. 1 H NMR (300MHz, DMSO- d 6) δ11.02 (s, 1H, NH), 9.80 (s, 1H, NH), 9.53 (s, 1H, NH), 8.69 (s, 1H, Ar-H) , 8.20 (d, J = 7.2 Hz, 2H, Ar-H), 7.99 (s, 1H, =CH), 7.69 (t, J = 8.0 Hz, 1H, Ar-H), 4.13 (s, 2H, CH 2 ), 1.88 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.7, 148.4, 144.9, 139.0, 136.4, 133.4, 130.1, 123.6, 120.8, 52.2, 19.9. HRMS (m/z): Calcd. for C 12 H 14 N 7 O 4 [M+H] + 320.1102; found 320.1102.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(4-硝基苯基亚甲基)氨基甲酰肼(Ia-39)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(4-nitrophenyl Methyl)carbamoyl hydrazide (I a -39);
白色固体，产率82％，熔点294–295℃。1H NMR(400MHz,DMSO-d6)δ11.13(s,1H,NH),9.81(s,1H,NH),9.49(s,1H,NH),8.24(d,J＝7.2Hz,2H,Ar-H),8.08(d,J＝7.2Hz,2H,Ar-H),7.97(s,1H,＝CH),4.13(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.7,147.4,144.9,140.9,138.7,127.8,123.9,52.1,19.9.ESI-HRMS(m/z):Calcd.for C12H14N7O4[M+H]+320.1102；found 320.1103.White solid, yield 82%, mp 294 - 295. 1 H NMR (400MHz, DMSO- d 6) δ11.13 (s, 1H, NH), 9.81 (s, 1H, NH), 9.49 (s, 1H, NH), 8.24 (d, J = 7.2Hz, 2H , Ar-H), 8.08 (d, J = 7.2 Hz, 2H, Ar-H), 7.97 (s, 1H, =CH), 4.13 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.7, 147.4, 144.9, 140.9, 138.7, 127.8, 123.9, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 14 N 7 O 4 [M+H] + 320.1102; found 320.1103.
(E)-2-(3-羟基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-40)；(E)-2-(3-hydroxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)- Carbamoyl hydrazide (I a -40);
白色固体，产率95％，熔点264–265℃。1H NMR(300MHz,DMSO-d6)δ10.69(s,1H,NH),9.76(s,1H,NH),9.52(s,1H,NH),9.17(s,1H,OH),7.78(s,1H,＝CH),7.16–7.23(m,3H,Ar-H),6.80(s,1H,Ar-H),4.10(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ157.6,154.7,151.7,144.9,141.4,135.8,129.6,118.1,116.6,113.3,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H15N6O3[M+H]+291.1200；found 291.1205.White solid, 95% yield, mp 264 - 265. 1 H NMR (300MHz, DMSO- d 6) δ10.69 (s, 1H, NH), 9.76 (s, 1H, NH), 9.52 (s, 1H, NH), 9.17 (s, 1H, OH), 7.78 (s, 1H, =CH), 7.16–7.23 (m, 3H, Ar-H), 6.80 (s, 1H, Ar-H), 4.10 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 157.6, 154.7, 151.7, 144.9, 141.4, 135.8, 129.6, 118.1, 116.6, 113.3, 52.2, 19.9. ESI-HRMS (m/z): Calcd.for C 12 H 15 N 6 O 3 [M+H] + 291.1200; found 291.1205.
(E)-2-(4-羟基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-41)；(E)-2-(4-hydroxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)- Carbamoyl hydrazide (I a -41);
白色固体，产率74％，熔点237–238℃。1H NMR(400MHz,DMSO-d6)δ10.54(s,1H,NH),9.81(s,1H,NH),9.75(s,1H,NH),9.10(s,1H,OH),7.76(s,1H,＝CH),7.59(d,J＝8.0Hz,2H,Ar-H),6.77(d,J＝8.0Hz,2H,Ar-H),4.10(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ158.9,154.8,151.8,144.8,141.4,128.6,125.5,115.5,52.2,19.9.ESI-HRMS(m/z):Calcd.for C12H15N6O3[M+H]+291.1200；found 291.1200.White solid, yield 74%, mp 237 - 238. 1 H NMR (400MHz, DMSO- d 6) δ10.54 (s, 1H, NH), 9.81 (s, 1H, NH), 9.75 (s, 1H, NH), 9.10 (s, 1H, OH), 7.76 (s, 1H, =CH), 7.59 (d, J = 8.0 Hz, 2H, Ar-H), 6.77 (d, J = 8.0 Hz, 2H, Ar-H), 4.10 (s, 2H, CH 2 ) , 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 158.9, 154.8, 151.8, 144.8, 141.4, 128.6, 125.5, 115.5, 52.2, 19.9. ESI-HRMS (m/z) :Calcd.for C 12 H 15 N 6 O 3 [M+H] + 291.1200;found 291.1200.
(E)-2-(2,4-二羟基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-42)；(E)-2-(2,4-dihydroxyphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 ( 5H)-yl)carbamoyl hydrazide (I a -42);
白色固体，产率68％，熔点251–252℃。1H NMR(300MHz,DMSO-d6)δ10.48(s,1H,NH),9.74(s,1H,NH),9.42(s,1H,NH),9.02(s,1H,OH),8.94(s,1H,OH),7.69(s,1H,＝CH),7.19(s,1H,Ar-H),6.98(d,J＝7.8Hz,1H,Ar-H),6.74(d,J＝7.8Hz,1H,Ar-H),4.10(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.8,151.8,147.3,145.6,144.9,141.9,126.0,119.7,115.4,113.6,52.3,19.9.ESI-HRMS(m/z):Calcd.for C12H15N6O4[M+H]+307.1149；found 307.1153.White solid, yield 68%, mp 251 - 252. 1 H NMR (300MHz, DMSO- d 6) δ10.48 (s, 1H, NH), 9.74 (s, 1H, NH), 9.42 (s, 1H, NH), 9.02 (s, 1H, OH), 8.94 (s, 1H, OH), 7.69 (s, 1H, =CH), 7.19 (s, 1H, Ar-H), 6.98 (d, J = 7.8 Hz, 1H, Ar-H), 6.74 (d, J) = 7.8 Hz, 1H, Ar-H), 4.10 (s, 2H, CH 2 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.8, 151.8, 147.3, 145.6, 144.9, 141.9, 126.0, 119.7, 115.4, 113.6, 52.3, 19.9. ESI-HRMS (m/z): Calcd. for C 12 H 15 N 6 O 4 [M+H] + 307.1149; found 307.1153.
(E)-2-(4-叔丁基苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-43)；(E)-2-(4-tert-Butylphenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I a -43);
白色固体，产率69％，熔点211–212℃。1H NMR(400MHz,DMSO-d6)δ10.71(s,1H,NH),9.77(s,1H,NH),9.19(s,1H,NH),7.84(s,1H,＝CH),7.69(d,J＝7.2Hz,2H,Ar-H),7.42(d,J＝7.2Hz,2H,Ar-H),4.12(s,2H,CH2),1.87(s,3H,CH3),1.29(s,9H,C(CH3)3)；13C NMR(100MHz,DMSO-d6)δ154.7,152.2,151.7,144.8,141.1,131.7,126.7,125.4,52.2,34.6,31.0,19.9.ESI-HRMS(m/z):Calcd.for C16H23N6O2[M+H]+331.1877；found 331.1882.White solid, yield 69%, mp 211 - 212. 1 H NMR (400MHz, DMSO- d 6) δ10.71 (s, 1H, NH), 9.77 (s, 1H, NH), 9.19 (s, 1H, NH), 7.84 (s, 1H, = CH), 7.69 (d, J = 7.2 Hz, 2H, Ar-H), 7.42 (d, J = 7.2 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ) ), 1.29 (s, 9H, C(CH 3 ) 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 152.2, 151.7, 144.8, 141.1, 131.7, 126.7, 125.4, 52.2, 34.6, 31.0, 19.9 .ESI-HRMS (m/z): Calcd. for C 16 H 23 N 6 O 2 [M+H] + 331.1877; found 331.1882.
(E)-2-(4-(二甲氨基)苯基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-44)；(E)-2-(4-(Dimethylamino)phenylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I a -44);
粉红色固体，产率69％，熔点229–230℃。1H NMR(400MHz,DMSO-d6)δ10.46(s,1H,NH),9.75(s,1H,NH),9.06(s,1H,NH),7.73(s,1H,＝CH),7.57(d,J＝8.4Hz,2H,Ar-H),6.70(d,J＝8.4Hz,2H,Ar-H),4.11(s,2H,CH2),2.95(s,6H,N(CH3)2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.7,151.1,144.8,141.9,128.1,121.9,111.7,52.2,39.8,19.8.ESI-HRMS(m/z):Calcd.for C14H20N7O2[M+H]+318.1673；found 318.1677.Pink solid, yield 69%, m.p. 229 - 230. 1 H NMR (400MHz, DMSO- d 6) δ10.46 (s, 1H, NH), 9.75 (s, 1H, NH), 9.06 (s, 1H, NH), 7.73 (s, 1H, = CH), 7.57 (d, J = 8.4 Hz, 2H, Ar-H), 6.70 (d, J = 8.4 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 2.95 (s, 6H, N ( CH 3 ) 2 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.7, 151.1, 144.8, 141.9, 128.1, 121.9, 111.7, 52.2, 39.8, 19.8. -HRMS (m/z): Calcd. for C 14 H 20 N 7 O 2 [M+H] + 318.1673; found 318.1677.
(E)-2-((2-羟基萘-1-基)亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-45)；(E)-2-((2-hydroxynaphthalen-1-yl)methylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -45);
黄色固体，产率98％，熔点258℃。1H NMR(400MHz,DMSO-d6)δ10.77(s,1H,NH),9.85(s,1H,NH),9.00(s,2H,NH,OH),8.37(s,1H,＝CH),7.87(d,J＝4.4Hz,1H,Ar-H),7.85(d,J＝3.6Hz,1H,Ar-H),7.56(t,J＝7.2Hz,1H,Ar-H),7.38(t,J＝7.2Hz,1H,Ar-H),7.20(d,J＝8.8Hz,1H,Ar-H),4.13(s,2H,CH2),1.89(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ156.6,154.2,151.8,145.0,142.4,132.0,131.4,128.8,128.0,127.7,123.5,122.1,118.6,109.5,52.3,19.9.ESI-HRMS(m/z):Calcd.for C16H17N6O3[M+H]+341.1357；found 341.1360.Yellow solid, 98% yield, 258 ° C. 1 H NMR (400MHz, DMSO- d 6) δ10.77 (s, 1H, NH), 9.85 (s, 1H, NH), 9.00 (s, 2H, NH, OH), 8.37 (s, 1H, = CH ), 7.87 (d, J = 4.4 Hz, 1H, Ar-H), 7.85 (d, J = 3.6 Hz, 1H, Ar-H), 7.56 (t, J = 7.2 Hz, 1H, Ar-H), 7.38 (t, J = 7.2 Hz, 1H, Ar-H), 7.20 (d, J = 8.8 Hz, 1H, Ar-H), 4.13 (s, 2H, CH 2 ), 1.89 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 156.6, 154.2, 151.8, 145.0, 142.4, 132.0, 131.4, 128.8, 128.0, 127.7, 123.5, 122.1, 118.6, 109.5, 52.3, 19.9. ESI-HRMS (m) /z): Calcd.for C 16 H 17 N 6 O 3 [M+H] + 341.1357; found 341.1360.
(E)-2-((6-羟基萘-2-基)亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-46)；(E)-2-((6-Hydroxynaphthalen-2-yl)methylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -46);
黄色固体，产率92％，熔点265–267℃。1H NMR(300MHz,DMSO-d6)δ10.74(s,1H,NH),9.92(s,1H,NH),9.77(s,1H,NH),9.25(s,1H,OH),8.03(d,J＝8.4Hz,1H,Ar-H),7.96(s,1H,＝CH),7.93(s,1H,Ar-H),7.78(d,J＝8.7Hz,1H,Ar-H),7.69(d,J＝8.7Hz,1H,Ar-H),7.09–7.14(m,2H,Ar-H),4.14(s,2H,CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ156.3,154.7,151.8,144.9,141.6,135.3,129.9,129.2,128.1,127.4,126.5,123.3,119.1,109.1,52.2,19.9.ESI-HRMS(m/z):Calcd.for C16H17N6O3[M+H]+341.1357；found 341.1359.Yellow solid, yield 92%, mp 265 - 267. 1 H NMR (300MHz, DMSO- d 6) δ10.74 (s, 1H, NH), 9.92 (s, 1H, NH), 9.77 (s, 1H, NH), 9.25 (s, 1H, OH), 8.03 (d, J = 8.4 Hz, 1H, Ar-H), 7.96 (s, 1H, =CH), 7.93 (s, 1H, Ar-H), 7.78 (d, J = 8.7 Hz, 1H, Ar-H ), 7.69 (d, J = 8.7 Hz, 1H, Ar-H), 7.09 - 7.14 (m, 2H, Ar-H), 4.14 (s, 2H, CH 2 ), 1.88 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 156.3, 154.7, 151.8, 144.9, 141.6, 135.3, 129.9, 129.2, 128.1, 127.4, 126.5, 123.3, 119.1, 109.1, 52.2, 19.9. ESI-HRMS (m/ z): Calcd.for C 16 H 17 N 6 O 3 [M+H] + 341.1357; found 341.1359.
(E)-2-((6-甲氧基萘-2-基)亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-47)；(E)-2-((6-methoxynaphthalen-2-yl)methylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-tri Pyrazin-4(5H)-yl)carbamoyl hydrazide (I a -47);
黄色固体，产率79％，熔点232–233℃。1H NMR(300MHz,DMSO-d6)δ10.79(s,1H,NH),9.79(s,1H,NH),9.29(s,1H,NH),8.11(d,J＝8.4Hz,1H,Ar-H),8.02(s,1H,Ar-H),7.99(s,1H,＝CH),7.84(t,J＝8.0Hz,2H,Ar-H),7.36(s,1H,Ar-H),7.20(d,J＝8.4Hz,1H,Ar-H),4.14(s,2H,CH2),3.89(s,3H,OCH3),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ158.0,154.7,151.7,144.8,141.3,135.0,130.0,129.7,128.2,127.8,127.1,123.6,119.0,106.4,55.3,52.2,19.8.ESI-HRMS(m/z):Calcd.for C17H19N6O3[M+H]+355.1513；found 355.1516. Yellow solid, yield 79%, mp 232 - 233. 1 H NMR (300MHz, DMSO- d 6) δ10.79 (s, 1H, NH), 9.79 (s, 1H, NH), 9.29 (s, 1H, NH), 8.11 (d, J = 8.4Hz, 1H , Ar-H), 8.02 (s, 1H, Ar-H), 7.99 (s, 1H, =CH), 7.84 (t, J = 8.0 Hz, 2H, Ar-H), 7.36 (s, 1H, Ar -H), 7.20 (d, J = 8.4 Hz, 1H, Ar-H), 4.14 (s, 2H, CH 2 ), 3.89 (s, 3H, OCH 3 ), 1.88 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 158.0, 154.7, 151.7, 144.8, 141.3, 135.0, 130.0, 129.7,128.2,127.8,127.1,123.6,119.0,106.4,55.3,52.2,19.8.ESI-HRMS(m) /z): Calcd.for C 17 H 19 N 6 O 3 [M+H] + 355.1513; found 355.1516.
(E)-2-(苯并[d][1,3]二氧-5-亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-48)；(E)-2-(benzo[d][1,3]dioxo-5-methylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2, 4-triazin-4(5H)-yl)carbamoyl hydrazide (I a -48);
白色固体，产率96％，熔点266–267℃。1H NMR(400MHz,DMSO-d6)δ10.64(s,1H,NH),9.76(s,1H,NH),9.27(s,1H,NH),7.76(s,1H,＝CH),7.62(s,1H,Ar-H),7.07(d,J＝8.0Hz,1H,Ar-H),6.93(d,J＝8.0Hz,1H,Ar-H),6.06(s,2H,OCH2),4.11(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.7,148.5,148.0,144.8,140.7,129.1,123.1,108.1,105.1,101.4,52.2,19.9.ESI-HRMS(m/z):Calcd.for C13H15N6O4[M+H]+319.1149；found 319.1155.White solid, 96% yield, mp 266 - 267. 1 H NMR (400MHz, DMSO- d 6) δ10.64 (s, 1H, NH), 9.76 (s, 1H, NH), 9.27 (s, 1H, NH), 7.76 (s, 1H, = CH), 7.62 (s, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 6.93 (d, J = 8.0 Hz, 1H, Ar-H), 6.06 (s, 2H, OCH) 2 ), 4.11 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.7, 148.5, 148.0, 144.8, 140.7, 129.1, 123.1, 108.1, 105.1, 101.4, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 13 H 15 N 6 O 4 [M+H] + 319.1149; found 319.1155.
(E)-2-((2,3-二氢苯并[b][1,4]二氧芑-6-基)亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-49)；(E)-2-((2,3-Dihydrobenzo[b][1,4]dioxo-6-yl)methylene)-N-(6-methyl-3-keto-2 , 3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I a -49);
白色固体，产率86％，熔点264–265℃。1H NMR(400MHz,DMSO-d6)δ10.63(s,1H,NH),9.76(s,1H,NH),9.22(s,1H,NH),7.73(s,1H,＝CH),7.41(s,1H,Ar-H),7.18(d,J＝8.0Hz,1H,Ar-H),6.87(d,J＝8.0Hz,1H,Ar-H),4.26(s,4H,-OCH2),4.10(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.7,144.8,144.7,143.6,140.7,127.9,120.8,117.1,114.9,64.3,64.0,52.2,19.9.ESI-HRMS(m/z):Calcd.for C14H17N6O4[M+H]+333.1306；found 333.1309.White solid, yield 86%, m.p. 264 - 265. 1 H NMR (400MHz, DMSO- d 6) δ10.63 (s, 1H, NH), 9.76 (s, 1H, NH), 9.22 (s, 1H, NH), 7.73 (s, 1H, = CH), 7.41 (s, 1H, Ar-H), 7.18 (d, J = 8.0 Hz, 1H, Ar-H), 6.87 (d, J = 8.0 Hz, 1H, Ar-H), 4.26 (s, 4H, - OCH 2 ), 4.10 (s, 2H, CH 2 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.7, 144.8, 144.7, 143.6, 140.7, 127.9, 120.8 , 117.1, 114.9, 64.3, 64.0, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 14 H 17 N 6 O 4 [M+H] + 333.1306; found 333.1309.
(E)-2-((1H-吲哚-3-基)亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-50)；(E)-2-((1H-indol-3-yl)methylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine- 4(5H)-yl)carbamoyl hydrazide (I a -50);
白色固体，产率97％，熔点255–257℃。1H NMR(400MHz,DMSO-d6)δ11.51(s,1H,NH),10.36(s,1H,NH),9.76(s,1H,NH),8.69(s,1H,NH),8.31(d,J＝8.0Hz,1H,Ar-H),8.08(s,1H,N＝CH),7.74(s,1H,C＝CH),7.40(d,J＝7.6Hz,1H,Ar-H),7.18(t,J＝7.6Hz,1H,Ar-H),7.10(d,J＝7.2Hz,1H,Ar-H),4.15(s,2H,CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.8,144.9,139.4,137.0,129.9,124.0,122.6,122.5,120.3,111.6,111.4,52.3,19.9.ESI-HRMS(m/z):Calcd.for C14H16N7O2[M+H]+314.1360；found 314.1359.White solid, 97% yield, mp 255 - 257. 1 H NMR (400MHz, DMSO- d 6) δ11.51 (s, 1H, NH), 10.36 (s, 1H, NH), 9.76 (s, 1H, NH), 8.69 (s, 1H, NH), 8.31 (d, J = 8.0 Hz, 1H, Ar-H), 8.08 (s, 1H, N = CH), 7.74 (s, 1H, C = CH), 7.40 (d, J = 7.6 Hz, 1H, Ar- H), 7.18 (t, J = 7.6 Hz, 1H, Ar-H), 7.10 (d, J = 7.2 Hz, 1H, Ar-H), 4.15 (s, 2H, CH 2 ), 1.88 (s, 3H) , CH 3 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 154.7, 151.8, 144.9, 139.4, 137.0, 129.9, 124.0, 122.6, 122.5, 120.3, 111.6, 111.4, 52.3, 19.9. ESI-HRMS (m/ z): Calcd.for C 14 H 16 N 7 O 2 [M+H] + 314.1360; found 314.1359.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(吡啶-2-基亚甲基)氨基甲酰肼(Ia-51)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(pyridin-2-yl) Carbamoyl hydrazide (I a -51);
白色固体，产率55％，熔点230–231℃。1H NMR(400MHz,DMSO-d6)δ11.02(s,1H,NH),9.80(s,1H,NH),9.40(s,1H,NH),8.55(d,J＝4.4Hz,1H,Py-H),8.22(d,J＝3.6Hz,1H,Py-H),7.91(s,1H,＝CH),7.84(t,J＝7.6Hz,1H,Py-H),7.36(t,J＝6.8Hz,1H,Py-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,153.4,151.7,149.3,144.9,141.6,136.6,123.9,119.9,52.2,19.9.ESI-HRMS(m/z):Calcd.for C11H14N7O2[M+H]+276.1203；found 276.1206.White solid, yield 55%, m.p. 230 - 231. 1 H NMR (400 MHz, DMSO-d 6 ) δ 11.02 (s, 1H, NH), 9.80 (s, 1H, NH), 9.40 (s, 1H, NH), 8.55 (d, J = 4.4 Hz, 1H) , Py-H), 8.22 (d, J = 3.6 Hz, 1H, Py-H), 7.91 (s, 1H, =CH), 7.84 (t, J = 7.6 Hz, 1H, Py-H), 7.36 ( t, J = 6.8 Hz, 1H, Py-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 153.4, 151.7 , 149.3, 144.9, 141.6, 136.6, 123.9, 119.9, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 11 H 14 N 7 O 2 [M+H] + 276.1203; found 276.1206.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(吡啶-3-基亚甲基)氨基甲酰肼(Ia-52)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(pyridin-3-yl] Carbamoyl hydrazide (I a -52);
白色固体，产率89％，熔点227–228℃。1H NMR(400MHz,DMSO-d6)δ10.96(s,1H,NH),9.73(s,1H,NH),9.37(s,1H,NH),8.93(s,1H,Py-H),8.55(d,J＝4.0Hz,1H,Py-H),8.24(d,J＝4.0Hz,1H,Py-H),7.90(s,1H,＝CH),7.42-7.45(m,1H,Py-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.5,151.8,150.0,148.4,145.0,138.2,133.7,130.4,123.8,52.2,19.9.ESI-HRMS(m/z):Calcd.for C11H14N7O2[M+H]+276.1203；found276.1205.White solid, yield 89%, mp 227 - 228. 1 H NMR (400MHz, DMSO- d 6) δ10.96 (s, 1H, NH), 9.73 (s, 1H, NH), 9.37 (s, 1H, NH), 8.93 (s, 1H, Py-H) , 8.55 (d, J = 4.0 Hz, 1H, Py-H), 8.24 (d, J = 4.0 Hz, 1H, Py-H), 7.90 (s, 1H, =CH), 7.42-7.45 (m, 1H) , Py-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.5, 151.8, 150.0, 148.4, 145.0, 138.2, 133.7 , 130.4, 123.8, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 11 H 14 N 7 O 2 [M+H] + 276.1203; found276.1205.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(吡啶-4-基亚甲基)氨基甲酰肼(Ia-53)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(pyridin-4-yl] Carbamoyl hydrazide (I a -53);
白色固体，产率80％，熔点289–290℃。1H NMR(400MHz,DMSO-d6)δ11.10(s,1H,NH),9.81(s,1H,NH),9.44(s,1H,NH),8.59(brs,2H,Py-H),7.84(s,1H,＝CH),7.76(brs,2H,Py-H),4.12(s,2H,CH2),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.4,151.7,150.0,144.9,141.6,138.5,120.9,52.1,19.9.ESI-HRMS(m/z):Calcd.for C11H14N7O2[M+H]+276.1203；found 276.1205.White solid, yield 80%, m.p. 289 - 290. 1 H NMR (400MHz, DMSO- d 6) δ11.10 (s, 1H, NH), 9.81 (s, 1H, NH), 9.44 (s, 1H, NH), 8.59 (brs, 2H, Py-H) , 7.84 (s, 1H, =CH), 7.76 (brs, 2H, Py-H), 4.12 (s, 2H, CH 2 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO- d 6 ) δ 154.4, 151.7, 150.0, 144.9, 141.6, 138.5, 120.9, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 11 H 14 N 7 O 2 [M+H] + 276.1203; 276.1205.
(E)-2-(呋喃-2-基亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-54)；(E)-2-(furan-2-ylmethylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4(5H)- Carbamoyl hydrazide (I a -54);
棕色固体，产率65％，熔点186–187℃。1H NMR(400MHz,DMSO-d6)δ10.74(s,1H,NH),9.76(s,1H,NH),8.91(s,1H,NH),7.79(brs,2H,＝CH,Het-H),6.88(brs,1H,Het-H),6.62(brs,1H,Het-H),4.09(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.4,151.6,149.6,144.8,144.4,131.7,112.1,111.7,52.1,19.9.ESI-HRMS(m/z):Calcd.for C10H13N6O3[M+H]+265.1044；found 265.1047.Brown solid, yield 65%, mp 186 - 187. 1 H NMR (400MHz, DMSO- d 6) δ10.74 (s, 1H, NH), 9.76 (s, 1H, NH), 8.91 (s, 1H, NH), 7.79 (brs, 2H, = CH, Het -H), 6.88 (brs, 1H, Het-H), 6.62 (brs, 1H, Het-H), 4.09 (s, 2H, CH 2 ), 1.86 (s, 3H, CH 3 ); 13 C NMR ( 100 MHz, DMSO-d 6 ) δ 154.4, 151.6, 149.6, 144.8, 144.4, 131.7, 112.1, 111.7, 52.1, 19.9. ESI-HRMS (m/z): Calcd. for C 10 H 13 N 6 O 3 [M+ H] + 265.1044; found 265.1047.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(噻吩-2-基亚甲基)氨基甲酰肼(Ia-55)；(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(thiophen-2-yl) Carbamoyl hydrazide (I a -55);
黄色固体，产率68％，熔点226–227℃。1H NMR(400MHz,DMSO-d6)δ10.73(s,1H,NH),9.76(s,1H,NH),8.89(s,1H,NH),8.09(s,1H,＝CH),7.62(d,J＝4.8Hz,1H,Het-H),7.39(d,J＝3.2Hz,1H,Het-H),7.10(t,J＝4.8Hz,1H,Het-H),4.10(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.3,151.7,144.9,138.9,136.8,129.7,128.2,127.8,52.1,19.9.ESI-HRMS(m/z):Calcd.for C10H13N6O2S[M+H]+281.0815；found 281.0815.Yellow solid, yield 68%, mp 226 - 227. 1 H NMR (400MHz, DMSO- d 6) δ10.73 (s, 1H, NH), 9.76 (s, 1H, NH), 8.89 (s, 1H, NH), 8.09 (s, 1H, = CH), 7.62 (d, J = 4.8 Hz, 1H, Het-H), 7.39 (d, J = 3.2 Hz, 1H, Het-H), 7.10 (t, J = 4.8 Hz, 1H, Het-H), 4.10 ( s, 2H, CH 2 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.3, 151.7, 144.9, 138.9, 136.8, 129.7, 128.2, 127.8, 52.1, 19.9. -HRMS (m/z): Calcd. for C 10 H 13 N 6 O 2 S [M+H] + 281.0815; found 281.0815.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(噻吩-3-基亚甲基)氨基甲酰肼(Ia-56)；(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(thiophen-3-yl) Carbamoyl hydrazide (I a -56);
黄色固体，产率87％，熔点244–245℃。1H NMR(400MHz,DMSO-d6)δ10.67(s,1H,NH),9.78(s,1H,NH),9.17(s,1H,NH),7.90(s,1H,＝CH),7.83(s,1H,Het-H),7.69(d,J＝4.8Hz,1H,Het-H),7.60(d,J＝4.8Hz,1H,Het-H),4.11(s,2H,CH2),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.8,144.9,137.8,136.8,127.1,126.7,125.3,52.2,19.9.ESI-HRMS(m/z):Calcd.for C10H13N6O2S[M+H]+281.0815；found 281.0819.Yellow solid, yield 87%, mp 244 - 245. 1 H NMR (400MHz, DMSO- d 6) δ10.67 (s, 1H, NH), 9.78 (s, 1H, NH), 9.17 (s, 1H, NH), 7.90 (s, 1H, = CH), 7.83 (s, 1H, Het-H), 7.69 (d, J = 4.8 Hz, 1H, Het-H), 7.60 (d, J = 4.8 Hz, 1H, Het-H), 4.11 (s, 2H, CH) 2 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.8, 144.9, 137.8, 136.8, 127.1, 126.7, 125.3, 52.2, 19.9. ESI-HRMS (m/) z): Calcd.for C 10 H 13 N 6 O 2 S[M+H] + 281.0815; found 281.0819.
(E)-2-((1H-咪唑-2-yl)亚甲基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ia-57)；(E)-2-((1H-imidazol-2-yl)methylene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I a -57);
白色固体，产率59％，熔点215–216℃。1H NMR(400MHz,DMSO-d6)δ12.37(s,1H,Het-H),10.92(s,1H,NH),9.85(s,1H,NH),9.25(s,1H,NH),7.70(s,1H,＝CH),7.32(brs,1H,Het-H),7.01(brs,1H,Het-H),4.16(s,2H, CH2),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.7,151.8,145.1,143.5,131.5,52.2,19.9.ESI-HRMS(m/z):Calcd.for C9H13N8O2[M+H]+265.1156；found 265.1157.White solid, 59% yield, mp 215 - 216. 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.37 (s, 1H, Het-H), 10.92 (s, 1H, NH), 9.85 (s, 1H, NH), 9.25 (s, 1H, NH) , 7.70 (s, 1H, =CH), 7.32 (brs, 1H, Het-H), 7.01 (brs, 1H, Het-H), 4.16 (s, 2H, CH 2 ), 1.88 (s, 3H, CH) 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.7, 151.8, 145.1, 143.5, 131.5, 52.2, 19.9. ESI-HRMS (m/z): Calcd. for C 9 H 13 N 8 O 2 [M +H] + 265.1156;found 265.1157.
实施例2：Example 2:
(1)N-(6-甲基-3-酮-2，3-二氢-1，2，4-三嗪-4(5H)-基)-2-(丙烷-2-酮)氨基甲酰肼(Ib-1)的合成(1) N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(propan-2-one)carbamate Synthesis of hydrazide (I b -1)
Figure PCTCN2017102601-appb-000088
Figure PCTCN2017102601-appb-000088
在250mL单口瓶中，加入氨基脲三嗪酮(IV)(0.93g,4mmol)、对甲基苯磺酸(0.14g,0.8mmol)、丙酮(0.23g,4mmol)、甲醇(120mL)搅拌溶解，然后加热回流5h，TLC监测反应完毕。将反应液减压脱除溶剂后析出固体，常压抽滤，用甲醇洗涤得到化合物Ib-10.79g，白色固体，产率88％，熔点224–226℃。1H NMR(400MHz,DMSO-d6)δ9.70(s,1H,NH),9.42(s,1H,NH),8.69(s,1H,NH),4.07(s,2H,CH2),1.90(s,3H,CH3),1.85(s,3H,CH3),1.80(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.3,151.6,148.6,144.7,52.2,24.9,19.9,16.9.ESI-HRMS(m/z):Calcd.for C8H15N6O2[M+H]+227.1251；found 227.1256.In a 250 mL single-mouth bottle, a semicarbazide (IV) (0.93 g, 4 mmol), p-toluenesulfonic acid (0.14 g, 0.8 mmol), acetone (0.23 g, 4 mmol), and methanol (120 mL) were dissolved and dissolved. Then, it was heated to reflux for 5 h, and the reaction was completed by TLC. After the solvent was removed under reduced pressure and the reaction solution precipitated solid was filtered off with suction pressure, to give the compound I b -10.79g washed with methanol, a white solid, 88% yield, m.p. 224-226 ℃. 1 H NMR (400MHz, DMSO- d 6) δ9.70 (s, 1H, NH), 9.42 (s, 1H, NH), 8.69 (s, 1H, NH), 4.07 (s, 2H, CH 2), 1.90 (s, 3H, CH 3 ), 1.85 (s, 3H, CH 3 ), 1.80 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d6) δ 155.3, 151.6, 148.6, 144.7, 52.2, 24.9, 19.9, 16.9. ESI-HRMS (m/z): Calcd. for C 8 H 15 N 6 O 2 [M+H] + 227.1251; found 227.1256.
(2)化合物Ib-2至Ib-28通过重复上述Ib-1的制备步骤完成。(2) The compounds I b -2 to I b -28 are completed by repeating the preparation steps of the above I b -1.
但是不同的是：But the difference is:
制备化合物Ib-2时，采用等摩尔量的
Figure PCTCN2017102601-appb-000089
(购自北京伊诺凯科技有限公司)代替丙酮；When preparing compound I b -2, an equimolar amount is used.
Figure PCTCN2017102601-appb-000089
(purchased from Beijing Inoke Technology Co., Ltd.) instead of acetone;
制备化合物Ib-3时，采用等摩尔量的
Figure PCTCN2017102601-appb-000090
(购自安耐吉化学公司)代替丙酮；When preparing compound I b -3, an equimolar amount is used.
Figure PCTCN2017102601-appb-000090
(purchased from Anheji Chemical Company) instead of acetone;
制备化合物Ib-4时，采用等摩尔量的
Figure PCTCN2017102601-appb-000091
(购自安耐吉化学公司)代替丙酮；When preparing compound I b -4, an equimolar amount is used.
Figure PCTCN2017102601-appb-000091
(purchased from Anheji Chemical Company) instead of acetone;
制备化合物Ib-5时，采用等摩尔量的
Figure PCTCN2017102601-appb-000092
(购自百灵威科技有限公司)代替丙酮；When preparing compound I b -5, an equimolar amount is used.
Figure PCTCN2017102601-appb-000092
(purchased from Bailingwei Technology Co., Ltd.) instead of acetone;
制备化合物Ib-6时，采用等摩尔量的
Figure PCTCN2017102601-appb-000093
(购自天津试剂公司)代替丙酮；When preparing compound I b -6, an equimolar amount is used.
Figure PCTCN2017102601-appb-000093
(purchased from Tianjin Reagent Company) instead of acetone;
制备化合物Ib-7时，采用等摩尔量的
Figure PCTCN2017102601-appb-000094
(购自安耐吉化学公司)代替丙酮；When preparing compound I b -7, an equimolar amount is used.
Figure PCTCN2017102601-appb-000094
(purchased from Anheji Chemical Company) instead of acetone;
制备化合物Ib-8时，采用等摩尔量的
Figure PCTCN2017102601-appb-000095
(购自天津希恩思生化科技有限公司公司)代替丙酮；When preparing compound I b -8, an equimolar amount is used.
Figure PCTCN2017102601-appb-000095
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-9时，采用等摩尔量的
Figure PCTCN2017102601-appb-000096
(购自安耐吉化学公司)代替丙酮；When preparing compound I b -9, an equimolar amount is used.
Figure PCTCN2017102601-appb-000096
(purchased from Anheji Chemical Company) instead of acetone;
制备化合物Ib-10时，采用等摩尔量的
Figure PCTCN2017102601-appb-000097
(购自天津希恩思生化科技有限公司)代替丙酮； When preparing compound I b -10, an equimolar amount is used.
Figure PCTCN2017102601-appb-000097
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-11时，采用等摩尔量的
Figure PCTCN2017102601-appb-000098
(购自天津希恩思生化科技有限公司)代替丙酮；When preparing compound I b -11, an equimolar amount is used.
Figure PCTCN2017102601-appb-000098
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-12时，采用等摩尔量的
Figure PCTCN2017102601-appb-000099
(购自天津希恩思生化科技有限公司)代替丙酮；When preparing compound I b -12, an equimolar amount is used.
Figure PCTCN2017102601-appb-000099
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-13时，采用等摩尔量的
Figure PCTCN2017102601-appb-000100
(购自安耐吉化学公司)代替丙酮；When preparing compound I b -13, an equimolar amount is used.
Figure PCTCN2017102601-appb-000100
(purchased from Anheji Chemical Company) instead of acetone;
制备化合物Ib-14时，采用等摩尔量的
Figure PCTCN2017102601-appb-000101
(购自上海阿拉丁生化科技股份有限公司)代替丙酮；When preparing compound I b -14, an equimolar amount is used.
Figure PCTCN2017102601-appb-000101
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-15时，采用等摩尔量的
Figure PCTCN2017102601-appb-000102
(购自天津希恩思生化科技有限公司)代替丙酮；When preparing compound I b -15, an equimolar amount is used.
Figure PCTCN2017102601-appb-000102
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-16时，采用等摩尔量的
Figure PCTCN2017102601-appb-000103
(购自南京多点化学公司)代替丙酮；When preparing compound I b -16, an equimolar amount is used.
Figure PCTCN2017102601-appb-000103
(purchased from Nanjing Multi-Point Chemical Company) instead of acetone;
制备化合物Ib-17时，采用等摩尔量的
Figure PCTCN2017102601-appb-000104
(购自天津希恩思生化科技有限公司)代替丙酮；When preparing compound I b -17, an equimolar amount is used.
Figure PCTCN2017102601-appb-000104
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-18时，采用等摩尔量的
Figure PCTCN2017102601-appb-000105
(购自安耐吉化学公司)代替丙酮；When preparing compound I b -18, an equimolar amount is used.
Figure PCTCN2017102601-appb-000105
(purchased from Anheji Chemical Company) instead of acetone;
制备化合物Ib-19时，采用等摩尔量的
Figure PCTCN2017102601-appb-000106
(购自南京多点化学公司)代替丙酮；When preparing compound I b -19, an equimolar amount is used.
Figure PCTCN2017102601-appb-000106
(purchased from Nanjing Multi-Point Chemical Company) instead of acetone;
制备化合物Ib-20时，采用等摩尔量的
Figure PCTCN2017102601-appb-000107
(购自天津希恩思生化科技有限公司)代替丙酮；When preparing compound I b -20, an equimolar amount is used.
Figure PCTCN2017102601-appb-000107
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-21时，采用等摩尔量的
Figure PCTCN2017102601-appb-000108
(购自天津希恩思生化科技有限公司公司)代替丙酮； When preparing compound I b -21, an equimolar amount is used.
Figure PCTCN2017102601-appb-000108
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-22时，采用等摩尔量的
Figure PCTCN2017102601-appb-000109
(购自南京多点化学公司)代替丙酮；When preparing compound I b -22, an equimolar amount is used.
Figure PCTCN2017102601-appb-000109
(purchased from Nanjing Multi-Point Chemical Company) instead of acetone;
制备化合物Ib-23时，采用等摩尔量的
Figure PCTCN2017102601-appb-000110
(购自天津希恩思生化科技有限公司公司)代替丙酮；When preparing compound I b -23, an equimolar amount is used.
Figure PCTCN2017102601-appb-000110
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-24时，采用等摩尔量的
Figure PCTCN2017102601-appb-000111
(购自天津希恩思生化科技有限公司公司)代替丙酮；When preparing compound I b -24, an equimolar amount is used.
Figure PCTCN2017102601-appb-000111
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-25时，采用等摩尔量的
Figure PCTCN2017102601-appb-000112
(购自南京多点化学公司)代替丙酮；When preparing compound I b -25, an equimolar amount is used.
Figure PCTCN2017102601-appb-000112
(purchased from Nanjing Multi-Point Chemical Company) instead of acetone;
制备化合物Ib-26时，采用等摩尔量的
Figure PCTCN2017102601-appb-000113
(购自上海阿拉丁生化科技股份有限公司)代替丙酮；When preparing compound I b -26, an equimolar amount is used.
Figure PCTCN2017102601-appb-000113
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-27时，采用等摩尔量的
Figure PCTCN2017102601-appb-000114
(购自上海阿拉丁生化科技股份有限公司)代替丙酮；When preparing compound I b -27, an equimolar amount is used.
Figure PCTCN2017102601-appb-000114
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of acetone;
制备化合物Ib-28时，采用等摩尔量的
Figure PCTCN2017102601-appb-000115
(购自天津希恩思生化科技有限公司公司)代替丙酮。When preparing compound I b -28, an equimolar amount is used.
Figure PCTCN2017102601-appb-000115
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of acetone.
所得化合物的表征结果如下所示：The characterization results of the obtained compounds are as follows:
(E)-2-(丁烷-2-酮)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-2)(E)-2-(butan-2-one)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl) Carbamoyl hydrazide (I b -2)
白色固体，产率65％，熔点225–226℃。1H NMR(400MHz,DMSO-d6)δ9.70(s,1H,NH),9.41(s,1H,NH),8.62(s,1H,NH),4.07(s,2H,CH2),2.20(q,J＝7.6Hz,2H,CH2CH3),1.85(s,3H,CH3),1.79(s,3H,CH3),1.03(t,J＝7.6Hz,3H,CH2CH3)；13C NMR(100MHz,DMSO-d6)δ155.3,152.5,151.6,144.8,52.2,31.4,19.9,15.5,10.8.ESI-HRMS(m/z):Calcd.for C9H17N6O2[M+H]+241.1408；found 241.1410.White solid, 65% yield, mp 225 - 226. 1 H NMR (400MHz, DMSO- d 6) δ9.70 (s, 1H, NH), 9.41 (s, 1H, NH), 8.62 (s, 1H, NH), 4.07 (s, 2H, CH 2), 2.20 (q, J = 7.6 Hz, 2H, CH 2 CH 3 ), 1.85 (s, 3H, CH 3 ), 1.79 (s, 3H, CH 3 ), 1.03 (t, J = 7.6 Hz, 3H, CH 2 ) CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.3, 152.5, 151.6, 144.8, 52.2, 31.4, 19.9, 15.5, 10.8. ESI-HRMS (m/z): Calcd. for C 9 H 17 N 6 O 2 [M+H] + 241.1408; found 241.1410.
2-环戊基酮-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-3)2-cyclopentyl ketone-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I b - 3)
白色固体，产率68％，熔点227–229℃。1H NMR(400MHz,DMSO-d6)δ9.70(s,1H,NH),9.33(s,1H,NH),8.66(s,1H,NH),4.05(s,2H,CH2),2.29(t,J＝7.2Hz,2H),2.22(t,J＝7.6Hz,2H),1.84(s,3H,CH3),1.72–1.77(m,2H),1.64–1.69(m,2H)；13C NMR(100MHz,DMSO-d6)δ160.7,155.2,151.6,144.7,52.2,32.8,28.0,24.5,19.9.ESI-HRMS(m/z):Calcd.for C10H17N6O2[M+H]+253.1408；found 253.1413.White solid, yield 68%, mp 227 - 229. 1 H NMR (400MHz, DMSO- d 6) δ9.70 (s, 1H, NH), 9.33 (s, 1H, NH), 8.66 (s, 1H, NH), 4.05 (s, 2H, CH 2), 2.29 (t, J = 7.2 Hz, 2H), 2.22 (t, J = 7.6 Hz, 2H), 1.84 (s, 3H, CH 3 ), 1.72 - 1.77 (m, 2H), 1.64 - 1.69 (m, 2H) 13 C NMR (100 MHz, DMSO-d 6 ) δ 160.7, 155.2, 151.6, 144.7, 52.2, 32.8, 28.0, 24.5, 19.9. ESI-HRMS (m/z): Calcd. for C 10 H 17 N 6 O 2 [M+H] + 253.1408; found 253.1413.
2-环己基酮-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-4)2-cyclohexyl ketone-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I b -4 )
白色固体，产率56％，熔点233℃。1H NMR(400MHz,DMSO-d6)δ9.69(s,1H,NH),9.60(s,1H,NH),8.69(s,1H,NH),4.07(s,2H,CH2),2.31(t,J＝6.4Hz,2H),2.21(t,J＝6.4Hz,2H),1.84(s,3H,CH3),1.61(brs,2H),1.54(brs,4H)；13C NMR(100MHz,DMSO-d6)δ155.5,153.8,151.6,144.7,52.2,34.8,26.8,26.3,25.6,25.2,19.9.ESI-HRMS(m/z):Calcd.for C11H19N6O2[M+H]+267.1564；found 267.1567.White solid, yield 56%, mp 233. 1 H NMR (400MHz, DMSO- d 6) δ9.69 (s, 1H, NH), 9.60 (s, 1H, NH), 8.69 (s, 1H, NH), 4.07 (s, 2H, CH 2), 2.31 (t, J = 6.4 Hz, 2H), 2.21 (t, J = 6.4 Hz, 2H), 1.84 (s, 3H, CH 3 ), 1.61 (brs, 2H), 1.54 (brs, 4H); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.5, 153.8, 151.6, 144.7, 52.2, 34.8, 26.8, 26.3, 25.6, 25.2,19.9. ESI-HRMS (m/z): Calcd. for C 11 H 19 N 6 O 2 [M+H] + 267.1564;found 267.1567.
2-环庚基酮-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-5)2-cycloheptyl ketone-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I b - 5)
白色固体，产率55％，熔点224–226℃。1H NMR(400MHz,DMSO-d6)δ9.72(s,1H,NH),9.33(s,1H,NH),8.75(s,1H,NH),4.07(s,2H,CH2),2.39(d,J＝5.6Hz,2H),2.32(t,J＝5.6Hz,2H),1.85(s,3H,CH3),1.62(brs,2H), 1.53(brs,6H)；13C NMR(100MHz,DMSO-d6)δ156.5,155.2,151.6,144.7,52.2,36.4,30.1,29.9,29.8,27.3,24.0,19.8.ESI-HRMS(m/z):Calcd.for C12H21N6O2[M+H]+281.1721；found 281.1723.White solid, 55% yield, mp 224 - 226. 1 H NMR (400MHz, DMSO- d 6) δ9.72 (s, 1H, NH), 9.33 (s, 1H, NH), 8.75 (s, 1H, NH), 4.07 (s, 2H, CH 2), 2.39 (d, J = 5.6 Hz, 2H), 2.32 (t, J = 5.6 Hz, 2H), 1.85 (s, 3H, CH 3 ), 1.62 (brs, 2H), 1.53 (brs, 6H); 13 C NMR (100 MHz, DMSO-d 6 ) δ 156.5, 155.2, 151.6, 144.7, 52.2, 36.4, 30.1, 29.9, 29.8, 27.3, 24.0, 19.8. ESI-HRMS (m/z): Calcd. for C 12 H 21 N 6 O 2 [M+H] + 281.1721; found 281.1723.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯乙基酮)氨基甲酰肼(Ib-6)(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-phenylethyl ketone) Carbamoyl hydrazide (I b -6)
白色固体，产率66％，熔点249–250℃。1H NMR(400MHz,DMSO-d6)δ9.89(s,1H,NH),9.76(s,1H,NH),9.13(s,1H,NH),7.91(d,J＝7.6Hz,2H,Ar-H),7.38(d,J＝5.6Hz,3H,Ar-H),4.13(s,2H,CH2),2.21(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.2,151.7,146.0,144.8,137.8,128.8,128.2,126.3,52.2,19.9,13.3.ESI-HRMS(m/z):Calcd.for C13H17N6O2[M+H]+289.1408；found 289.1407.White solid, 66% yield, mp 249 - 250. 1 H NMR (400MHz, DMSO- d 6) δ9.89 (s, 1H, NH), 9.76 (s, 1H, NH), 9.13 (s, 1H, NH), 7.91 (d, J = 7.6Hz, 2H , Ar-H), 7.38 (d, J = 5.6 Hz, 3H, Ar-H), 4.13 (s, 2H, CH 2 ), 2.21 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.2, 151.7, 146.0, 144.8, 137.8, 128.8, 128.2, 126.3, 52.2, 19.9, 13.3. ESI-HRMS (m/z): Calcd. for C 13 H 17 N 6 O 2 [M+H] + 289.1408; found 289.1407.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯丙基酮)氨基甲酰肼(Ib-7)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-phenylpropyl ketone) Carbamoyl hydrazide (I b -7)
白色固体，产率68％，熔点232–233℃。1H NMR(400MHz,DMSO-d6)δ10.03(s,1H,NH),9.76(s,1H,NH),9.11(s,1H,NH),7.91(d,J＝7.2Hz,2H,Ar-H),7.38(d,J＝6.8Hz,3H,Ar-H),4.13(s,2H,CH2),2.76(q,J＝7.2Hz,2H,CH2CH3),1.87(s,3H,CH3),1.01(t,J＝7.2Hz,3H,CH2CH3)；13C NMR(100MHz,DMSO-d6)δ155.2,151.7,145.0,144.8,136.6,128.8,128.3,126.3,52.2,19.9,18.7,10.7.ESI-HRMS(m/z):Calcd.for C14H19N6O2[M+H]+303.1564；found 303.1565.White solid, yield 68%, mp 232 - 233. 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.03 (s, 1H, NH), 9.76 (s, 1H, NH), 9.11 (s, 1H, NH), 7.91 (d, J = 7.2 Hz, 2H) , Ar-H), 7.38 (d, J = 6.8 Hz, 3H, Ar-H), 4.13 (s, 2H, CH 2 ), 2.76 (q, J = 7.2 Hz, 2H, CH 2 CH 3 ), 1.87 (s, 3H, CH 3 ), 1.01 (t, J = 7.2 Hz, 3H, CH 2 CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.2, 151.7, 145.0, 144.8, 136.6, 128.8, 128.3 , 126.3, 52.2, 19.9, 18.7, 10.7. ESI-HRMS (m/z): Calcd. for C 14 H 19 N 6 O 2 [M+H] + 303.1564; found 303.1565.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-苯丁基酮)氨基甲酰肼(Ib-8)(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-phenylbutyl ketone) Carbamoyl hydrazide (I b -8)
白色固体，产率60％，熔点221–222℃。1H NMR(300MHz,DMSO-d6)δ10.07(s,1H,NH),9.76(s,1H,NH),9.10(s,1H,NH),7.90(d,J＝5.1Hz,2H,Ar-H),7.38(d,J＝5.4Hz,,3H,Ar-H),4.13(s,2H,CH2),2.73(t,J＝7.5Hz,2H,CH2CH2CH3),1.87(s,3H,CH3),1.43(q,J＝7.2Hz,2H,CH2CH2CH3),0.94(t,J＝6.9Hz,3H,CH3CH2CH3)；13C NMR(100MHz,DMSO-d6)δ155.3,151.7,149.9,144.8,136.9,128.8,128.3,126.4,52.2,27.1,19.9,19.4,13.8.ESI-HRMS(m/z):Calcd.for C15H21N6O2[M+H]+317.1721；found 317.1724.White solid, yield 60%, mp 221 - 222. 1 H NMR (300MHz, DMSO- d 6) δ10.07 (s, 1H, NH), 9.76 (s, 1H, NH), 9.10 (s, 1H, NH), 7.90 (d, J = 5.1Hz, 2H , Ar-H), 7.38 (d, J = 5.4 Hz, 3H, Ar-H), 4.13 (s, 2H, CH 2 ), 2.73 (t, J = 7.5 Hz, 2H, CH 2 CH 2 CH 3 ), 1.87 (s, 3H, CH 3 ), 1.43 (q, J = 7.2 Hz, 2H, CH 2 CH 2 CH 3 ), 0.94 (t, J = 6.9 Hz, 3H, CH 3 CH 2 CH 3 ); 13 C NMR (100MHz, DMSO- d 6) δ155.3,151.7,149.9,144.8,136.9,128.8,128.3,126.4,52.2,27.1,19.9,19.4,13.8.ESI-HRMS (m / z): Calcd.for C 15 H 21 N 6 O 2 [M+H] + 317.1721; found 317.1724.
(E)-2-(1-(2-甲氧基苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-9)(E)-2-(1-(2-methoxyphenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine -4(5H)-yl)carbamoyl hydrazide (I b -9)
白色固体，产率66％，熔点188–189℃。1H NMR(400MHz,DMSO-d6)δ9.78(s,1H,NH),9.71(s,1H,NH),8.82(s,1H,NH),7.37(brs,2H,Ar-H),7.05(brs,1H,Ar-H),6.95(brs,1H,Ar-H),4.08(s,2H,CH2),3.80(s,3H,OCH3),2.12(s,3H,CH3),1.85(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ157.2,155.3,151.6,148.5,144.8,130.0,129.6,129.0,120.3,111.6,55.6,52.2,19.9,17.7.ESI-HRMS(m/z):Calcd.for C14H19N6O3[M+H]+319.1513；found 319.1519.White solid, 66% yield, mp 188 - 189. 1 H NMR (400MHz, DMSO- d 6) δ9.78 (s, 1H, NH), 9.71 (s, 1H, NH), 8.82 (s, 1H, NH), 7.37 (brs, 2H, Ar-H) , 7.05 (brs, 1H, Ar-H), 6.95 (brs, 1H, Ar-H), 4.08 (s, 2H, CH 2 ), 3.80 (s, 3H, OCH 3 ), 2.12 (s, 3H, CH) 3 ), 1.85 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 157.2, 155.3, 151.6, 148.5, 144.8, 130.0, 129.6, 129.0, 120.3, 111.6, 55.6, 52.2, 19.9, 17.7. ESI-HRMS (m/z): Calcd. for C 14 H 19 N 6 O 3 [M+H] + 319.1513; found 319.1519.
(E)-2-(1-(3-甲氧基苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-10)(E)-2-(1-(3-methoxyphenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine -4(5H)-yl)carbamoyl hydrazide (I b -10)
白色固体，产率86％，熔点228–229℃。1H NMR(400MHz,DMSO-d6)δ9.85(s,1H,NH),9.75(s,1H,NH),9.13(s,1H,NH),7.43–7.47(m,2H,Ar-H),7.30(t,J＝8.0Hz,1H,Ar-H),6.94(d,J＝8.0Hz,,1H,Ar-H),4.12(s,2H,CH2),3.80(s,3H,OCH3),2.19(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ159.3,155.2,151.7,146.1,144.9,139.4,129.3,118.9,114.3,111.9,55.3,52.2,19.9,13.6.ESI-HRMS(m/z):Calcd.for C14H19N6O3[M+H]+319.1513；found 319.1517.White solid, yield 86%, mp 228 - 229. 1 H NMR (400MHz, DMSO- d 6) δ9.85 (s, 1H, NH), 9.75 (s, 1H, NH), 9.13 (s, 1H, NH), 7.43-7.47 (m, 2H, Ar- H), 7.30 (t, J = 8.0 Hz, 1H, Ar-H), 6.94 (d, J = 8.0 Hz, 1H, Ar-H), 4.12 (s, 2H, CH 2 ), 3.80 (s, 3H, OCH 3 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 159.3, 155.2, 151.7, 146.1, 144.9, 139.4, 129.3 , 118.9, 114.3, 111.9, 55.3, 52.2, 19.9, 13.6. ESI-HRMS (m/z): Calcd. for C 14 H 19 N 6 O 3 [M+H] + 319.1513; found 319.1517.
(E)-2-(1-(4-甲氧基苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-11)(E)-2-(1-(4-methoxyphenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine -4(5H)-yl)carbamoyl hydrazide (I b -11)
白色固体，产率77％，熔点249℃。1H NMR(400MHz,DMSO-d6)δ9.76(s,2H,NH),9.09(s,1H,NH),7.86(d,J＝8.4Hz,2H,Ar-H),6.92(d,J＝8.4Hz,2H,Ar-H),4.12(s,2H,CH2),3.78(s,3H,OCH3),2.17(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ159.9,155.3,151.7,145.9,144.8,130.4,127.8,113.5,55.2,52.2,19.9,13.2.ESI-HRMS(m/z):Calcd.for C14H19N6O3[M+H]+319.1513；found 319.1518.White solid, 77% yield, mp 249. 1 H NMR (400MHz, DMSO- d 6) δ9.76 (s, 2H, NH), 9.09 (s, 1H, NH), 7.86 (d, J = 8.4Hz, 2H, Ar-H), 6.92 (d , J = 8.4 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 3.78 (s, 3H, OCH 3 ), 2.17 (s, 3H, CH 3 ), 1.87 (s, 3H, CH) 3 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 159.9, 155.3, 151.7, 145.9, 144.8, 130.4, 127.8, 113.5, 55.2, 52.2, 19.9, 13.2. ESI-HRMS (m/z): Calcd.for C 14 H 19 N 6 O 3 [M+H] + 319.1513; found 319.1518.
(E)-2-(1-(3,4-二甲氧基苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-12)(E)-2-(1-(3,4-dimethoxyphenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4 -Triazine-4(5H)-yl)carbamoyl hydrazide (I b -12)
白色固体，产率86％，熔点226–227℃。1H NMR(400MHz,DMSO-d6)δ9.76(s,1H,NH),9.73(s,1H,NH),9.12(s,1H,NH),7.51(s,1H,Ar-H),7.33(d,J＝8.0Hz,2H,Ar-H),6.93(d,J＝8.0Hz,2H,Ar-H),4.14(s,2H,CH2),3.83(s,3H,OCH3),3.78(s,3H,OCH3),2.18(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.3,151.8,149.9,148.6,146.3,144.8,130.6,119.6,110.9,109.7,55.9,55.5,52.2,19.9,13.5.ESI-HRMS(m/z):Calcd.for C15H21N6O4[M+H]+349.1619；found 349.1622.White solid, yield 86%, mp 226 - 227. 1 H NMR (400MHz, DMSO- d 6) δ9.76 (s, 1H, NH), 9.73 (s, 1H, NH), 9.12 (s, 1H, NH), 7.51 (s, 1H, Ar-H) , 7.33 (d, J = 8.0 Hz, 2H, Ar-H), 6.93 (d, J = 8.0 Hz, 2H, Ar-H), 4.14 (s, 2H, CH 2 ), 3.83 (s, 3H, OCH) 3 ), 3.78 (s, 3H, OCH 3 ), 2.18 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.3, 151.8, 149.9, 148.6, 146.3, 144.8, 130.6, 119.6, 110.9, 109.7, 55.9, 55.5, 52.2, 19.9, 13.5. ESI-HRMS (m/z): Calcd. for C 15 H 21 N 6 O 4 [M+H] + 349.1619; found 349.1622.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(3,4,5-三甲氧基苯基)亚乙基)氨基甲酰肼(Ib-13)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(3,4, 5-trimethoxyphenyl)ethylidene carbamoyl hydrazide (I b -13)
白色固体，产率85％，熔点260℃。1H NMR(400MHz,DMSO-d6)δ9.79(s,1H,NH),9.77(s,1H,NH),9.15(s,1H,NH),7.10(s,2H,Ar-H),4.14(s,2H,CH2),3.84(s,6H,OCH3),3.67(s,3H,OCH3),2.21(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.2,152.7,151.8,146.4,144.8,138.5,133.6,104.2,60.1,56.2,52.2,19.9,13.8.ESI-HRMS(m/z):Calcd.for C16H23N6O5[M+H]+379.1724；found 379.1724.White solid, yield 85%, mp 260. 1 H NMR (400MHz, DMSO- d 6) δ9.79 (s, 1H, NH), 9.77 (s, 1H, NH), 9.15 (s, 1H, NH), 7.10 (s, 2H, Ar-H) , 4.14 (s, 2H, CH 2 ), 3.84 (s, 6H, OCH 3 ), 3.67 (s, 3H, OCH 3 ), 2.21 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.2, 152.7, 151.8, 146.4, 144.8, 138.5, 133.6, 104.2, 60.1, 56.2, 52.2, 19.9, 13.8. ESI-HRMS (m/z): Calcd.for C 16 H 23 N 6 O 5 [M+H] + 379.1724; found 379.1724.
(E)-2-(1-(2-氯苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-14)(E)-2-(1-(2-chlorophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I b -14)
白色固体，产率50％，熔点218–219℃。1H NMR(400MHz,DMSO-d6)δ9.97(s,1H,NH),9.73(s,1H,NH),8.87(s,1H,NH),7.45–7.50(m,2H,Ar-H),7.36–7.42(m,2H,Ar-H),4.07(s,2H,CH2),2.18(s,3H,CH3),1.84(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.0,151.5,147.2,144.7,138.9,131.2,130.7,130.0,129.6,127.2,52.1,19.8,18.0.ESI-HRMS(m/z):Calcd.for C13H16ClN6O2[M+H]+323.1018；found 323.1022.White solid, yield 50%, m.p. 218 - 219. 1 H NMR (400MHz, DMSO- d 6) δ9.97 (s, 1H, NH), 9.73 (s, 1H, NH), 8.87 (s, 1H, NH), 7.45-7.50 (m, 2H, Ar- H), 7.36 - 7.42 (m, 2H, Ar-H), 4.07 (s, 2H, CH 2 ), 2.18 (s, 3H, CH 3 ), 1.84 (s, 3H, CH 3 ); 13 C NMR ( 100 MHz, DMSO-d 6 ) δ 155.0, 151.5, 147.2, 144.7, 138.9, 131.2, 130.7, 130.0, 129.6, 127.2, 52.1, 19.8, 18.0. ESI-HRMS (m/z): Calcd. for C 13 H 16 ClN 6 O 2 [M+H] + 323.1018; found 323.1022.
(E)-2-(1-(3-氯苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-15) (E)-2-(1-(3-chlorophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I b -15)
白色固体，产率86％，熔点274–275℃。1H NMR(400MHz,DMSO-d6)δ9.96(s,1H,NH),9.76(s,1H,NH),9.29(s,1H,NH),8.07(s,1H,Ar-H),7.76–7.85(m,1H,Ar-H),7.34–7.46(m,2H,Ar-H),4.13(s,2H,CH2),2.20(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.1,151.7,144.8,144.7,139.9,133.5,130.0,128.6,125.8,125.0,52.1,19.9,13.3.ESI-HRMS(m/z):Calcd.for C13H16ClN6O2[M+H]+323.1018；found 323.1020.White solid, yield 86%, m.p. 274 - 275. 1 H NMR (400MHz, DMSO- d 6) δ9.96 (s, 1H, NH), 9.76 (s, 1H, NH), 9.29 (s, 1H, NH), 8.07 (s, 1H, Ar-H) , 7.76–7.85 (m, 1H, Ar-H), 7.34–7.46 (m, 2H, Ar-H), 4.13 (s, 2H, CH 2 ), 2.20 (s, 3H, CH 3 ), 1.87 (s , 3H, CH 3 ); 13 C NMR (100MHz, DMSO-d 6 ) δ 155.1, 151.7, 144.8, 144.7, 139.9, 133.5, 130.0, 128.6, 125.8, 125.0, 52.1, 19.9, 13.3. ESI-HRMS (m/ z): Calcd.for C 13 H 16 ClN 6 O 2 [M+H] + 323.1018; found 323.1020.
(E)-2-(1-(4-氯苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-16)(E)-2-(1-(4-chlorophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I b -16)
白色固体，产率89％，熔点268–269℃。1H NMR(400MHz,DMSO-d6)δ9.96(s,1H,NH),9.77(s,1H,NH),9.21(s,1H,NH),7.96(d,J＝8.0Hz,2H,Ar-H),7.43(d,J＝8.0Hz,2H,Ar-H),4.12(s,2H,CH2),2.19(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.1,151.7,144.8,136.7,133.5,128.1,52.1,19.9,13.2.ESI-HRMS(m/z):Calcd.for C13H16ClN6O2[M+H]+323.1018；found 323.1022.White solid, yield 89%, m.p. 268 - 269. 1 H NMR (400MHz, DMSO- d 6) δ9.96 (s, 1H, NH), 9.77 (s, 1H, NH), 9.21 (s, 1H, NH), 7.96 (d, J = 8.0Hz, 2H , Ar-H), 7.43 (d, J = 8.0 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.1, 151.7, 144.8, 136.7, 133.5, 128.1, 52.1, 19.9, 13.2. ESI-HRMS (m/z): Calcd. for C 13 H 16 ClN 6 O 2 [M+H] + 323.1018; found 323.1022.
(E)-2-(1-(2,4-二氯苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-17)(E)-2-(1-(2,4-dichlorophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-tri Pyrazin-4(5H)-yl)carbamoyl hydrazide (I b -17)
白色固体，产率80％，熔点252–253℃。1H NMR(400MHz,DMSO-d6)δ10.02(s,1H,NH),9.74(s,1H,NH),8.92(s,1H,NH),7.68(s,1H,Ar-H),7.46–7.52(m,2H,Ar-H),4.07(s,2H,CH2),2.17(s,3H,CH3),1.84(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.0,151.5,146.1,144.8,137.8,133.8,132.4,132.1,129.1,127.4,52.1,19.9,17.9.ESI-HRMS(m/z):Calcd.for C13H15Cl2N6O2[M+H]+357.0628；found 357.0630.White solid, yield 80%, mp 252 - 253. 1 H NMR (400MHz, DMSO- d 6) δ10.02 (s, 1H, NH), 9.74 (s, 1H, NH), 8.92 (s, 1H, NH), 7.68 (s, 1H, Ar-H) , 7.46 - 7.52 (m, 2H, Ar-H), 4.07 (s, 2H, CH 2 ), 2.17 (s, 3H, CH 3 ), 1.84 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.0, 151.5, 146.1, 144.8, 137.8, 133.8, 132.4, 132.1, 129.1, 127.4, 52.1, 19.9, 17.9. ESI-HRMS (m/z): Calcd. for C 13 H 15 Cl 2 N 6 O 2 [M+H] + 357.0628; found 357.0630.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(2,3,4-三氯苯基)亚乙基)氨基甲酰肼(Ib-18)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(2,3, 4-trichlorophenyl)ethylidene carbamoyl hydrazide (I b -18)
白色固体，产率97％，熔点258℃。1H NMR(400MHz,DMSO-d6)δ10.05(s,1H,NH),9.71(s,1H,NH),8.90(s,1H,NH),7.70(d,J＝8.4Hz,1H,Ar-H),7.47(d,J＝8.4Hz,1H,Ar-H),4.07(s,2H,CH2),2.18(s,3H,CH3),1.84(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.9,151.5,145.9,144.7,140.0,132.8,131.5,130.5,129.6,128.9,52.1,19.9,17.8.ESI-HRMS(m/z):Calcd.for C13H14Cl3N6O2[M+H]+391.0238；found 391.0236.White solid, 97% yield, 258. 1 H NMR (400MHz, DMSO- d 6) δ10.05 (s, 1H, NH), 9.71 (s, 1H, NH), 8.90 (s, 1H, NH), 7.70 (d, J = 8.4Hz, 1H , Ar-H), 7.47 (d, J = 8.4 Hz, 1H, Ar-H), 4.07 (s, 2H, CH 2 ), 2.18 (s, 3H, CH 3 ), 1.84 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.9, 151.5, 145.9, 144.7, 140.0, 132.8, 131.5, 130.5, 129.6, 128.9, 52.1, 19.9, 17.8. ESI-HRMS (m/z): Calcd. For C 13 H 14 Cl 3 N 6 O 2 [M+H] + 391.0238;found 391.0236.
(E)-2-(1-(4-氟苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-19)(E)-2-(1-(4-fluorophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I b -19)
白色固体，产率88％，熔点272–274℃。1H NMR(400MHz,DMSO-d6)δ9.90(s,1H,NH),9.77(s,1H,NH),9.18(s,1H,NH),7.98(d,J＝8.0Hz,2H,Ar-H),7.20(t,J＝8.0Hz,2H,Ar-H),4.12(s,2H,CH2),2.20(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ162.6(d,J＝244.7Hz),155.2,151.7,145.1,144.8,134.3(d,J＝2.5Hz),128.5(d,J＝8.0Hz),115.0(d,J＝21.2Hz),52.2,19.9,13.3.ESI-HRMS(m/z):Calcd.for C13H16FN6O2[M+H]+307.1313；found 307.1316.White solid, yield 88%, mp 272 - 274. 1 H NMR (400MHz, DMSO- d 6) δ9.90 (s, 1H, NH), 9.77 (s, 1H, NH), 9.18 (s, 1H, NH), 7.98 (d, J = 8.0Hz, 2H , Ar-H), 7.20 (t, J = 8.0 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 2.20 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 162.6 (d, J = 244.7 Hz), 155.2, 151.7, 145.1, 144.8, 134.3 (d, J = 2.5 Hz), 128.5 (d, J = 8.0) Hz), 115.0 (d, J = 21.2 Hz), 52.2, 19.9, 13.3. ESI-HRMS (m/z): Calcd. for C 13 H 16 FN 6 O 2 [M+H] + 307.1313; found 307.1316.
(E)-2-(1-(4-溴苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-20)(E)-2-(1-(4-bromophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I b -20)
白色固体，产率90％，熔点265–266℃。1H NMR(400MHz,DMSO-d6)δ9.96(s,1H,NH),9.77(s,1H,NH),9.21(s,1H,NH),7.89(d,J＝7.2Hz,2H,Ar-H),7.56(d,J＝7.2Hz,2H,Ar-H),4.12(s,2H,CH2),2.19(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.1,151.6,144.9,144.8,137.0,131.0,128.4,122.2,52.1,19.9,13.1.ESI-HRMS(m/z):Calcd.for C13H16BrN6O2[M+H]+367.0513；found 367.0516.White solid, yield 90%, m.p. 265 - 266. 1 H NMR (400MHz, DMSO- d 6) δ9.96 (s, 1H, NH), 9.77 (s, 1H, NH), 9.21 (s, 1H, NH), 7.89 (d, J = 7.2Hz, 2H , Ar-H), 7.56 (d, J = 7.2 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.1, 151.6, 144.9, 144.8, 137.0, 131.0, 128.4, 122.2, 52.1, 19.9, 13.1. ESI-HRMS (m/z): Calcd. for C 13 H 16 BrN 6 O 2 [M+H] + 367.0513; found 367.0516.
(E)-2-(1-(4-碘苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-21)(E)-2-(1-(4-iodophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I b -21)
黄色固体，产率79％，熔点279–280℃。1H NMR(400MHz,DMSO-d6)δ9.93(s,1H,NH),9.76(s,1H,NH),9.17(s,1H,NH),7.73(brs,4H,Ar-H),4.12(s,2H,CH2),2.17(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.1,151.6,144.1,144.8,137.4,136.9,128.4,95.2,52.1,19.9,13.0.ESI-HRMS(m/z):Calcd.for C13H16IN6O2[M+H]+415.0374；found 415.0372.Yellow solid, yield 79%, m.p. 279 - 280. 1 H NMR (400MHz, DMSO- d 6) δ9.93 (s, 1H, NH), 9.76 (s, 1H, NH), 9.17 (s, 1H, NH), 7.73 (brs, 4H, Ar-H) , 4.12 (s, 2H, CH 2 ), 2.17 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.1, 151.6, 144.1, 144.8, 137.4, 136.9, 128.4, 95.2, 52.1, 19.9, 13.0. ESI-HRMS (m/z): Calcd. for C 13 H 16 IN 6 O 2 [M+H] + 415.0374; found 415.0372.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-对甲基苯基亚乙基)氨基甲酰肼(Ib-22)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-p-methylphenyl) Ethylene)carbamoyl hydrazide (I b -22)
白色固体，产率87％，熔点271–273℃。1H NMR(400MHz,DMSO-d6)δ9.83(s,1H,NH),9.76(s,1H,NH),9.10(s,1H,NH),7.81(d,J＝7.6Hz,2H,Ar-H),7.19(d,J＝7.6Hz,2H,Ar-H),4.12(s,2H,CH2),2.32(s,3H,CH3),2.18(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.3,151.7,146.0,144.8,138.3,135.1,128.8,126.2,52.2,20.9,19.9,13.2.ESI-HRMS(m/z):Calcd.for C14H19N6O2[M+H]+303.1564；found 303.1561.White solid, yield 87%, mp 271 - 273. 1 H NMR (400MHz, DMSO- d 6) δ9.83 (s, 1H, NH), 9.76 (s, 1H, NH), 9.10 (s, 1H, NH), 7.81 (d, J = 7.6Hz, 2H , Ar-H), 7.19 (d, J = 7.6 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 2.32 (s, 3H, CH 3 ), 2.18 (s, 3H, CH 3 ) ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.3, 151.7, 146.0, 144.8, 138.3, 135.1, 128.8, 126.2, 52.2, 20.9, 19.9, 13.2. ESI-HRMS (m/z): Calcd.for C 14 H 19 N 6 O 2 [M+H] + 303.1564; found 303.1561.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(4-(三氟甲基)苯基)亚乙基)氨基甲酰肼(Ib-23)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(4-(three) Fluoromethyl)phenyl)ethylidene carbamoyl hydrazide (I b -23)
白色固体，产率89％，熔点280–281℃。1H NMR(400MHz,DMSO-d6)δ10.08(s,1H,NH),9.79(s,1H,NH),9.27(s,1H,NH),8.14(d,J＝7.6Hz,2H,Ar-H),7.72(d,J＝7.6Hz,2H,Ar-H),4.13(s,2H,CH2),2.25(s,3H,CH3),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.1,151.7,144.8,144.5,141.7,128.7(q,J＝31.3Hz),127.0,125.0(d,J＝3.4Hz),124.3(q,J＝270.1Hz),52.1,19.9,13.3.ESI-HRMS(m/z):Calcd.for C14H16F3N6O2[M+H]+357.1281；found 357.1282.White solid, yield 89%, m.p. 280 - 281. 1 H NMR (400MHz, DMSO- d 6) δ10.08 (s, 1H, NH), 9.79 (s, 1H, NH), 9.27 (s, 1H, NH), 8.14 (d, J = 7.6Hz, 2H , Ar-H), 7.72 (d, J = 7.6 Hz, 2H, Ar-H), 4.13 (s, 2H, CH 2 ), 2.25 (s, 3H, CH 3 ), 1.88 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.1, 151.7, 144.8, 144.5, 141.7, 128.7 (q, J = 31.3 Hz), 127.0, 125.0 (d, J = 3.4 Hz), 124.3 (q, J) = 270.1Hz), 52.1,19.9,13.3.ESI-HRMS ( m / z): Calcd.for C 14 H 16 F 3 N 6 O 2 [m + H] + 357.1281; found 357.1282.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(4-(三氟甲氧基)苯基)亚乙基)氨基甲酰肼(Ib-24)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(4-(three) Fluoromethoxy)phenyl)ethylidene)carbazide (I b -24)
白色固体，产率86％，熔点280–281℃。1H NMR(400MHz,DMSO-d6)δ9.99(s,1H,NH),9.78(s,1H,NH),9.22(s,1H,NH),8.04(brs,2H,Ar-H),7.35(brs,2H,Ar-H),4.13(s,2H,CH2),2.22(s,3H,CH3),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.2,151.7,148.6,144.8,144.7,137.1,128.3,120.6,120.1(q,J＝244.8Hz),52.1,19.9,13.3.ESI-HRMS(m/z):Calcd.for C14H16F3N6O3[M+H]+373.1230；found 357.1234.White solid, yield 86%, m.p. 280 - 281. 1 H NMR (400MHz, DMSO- d 6) δ9.99 (s, 1H, NH), 9.78 (s, 1H, NH), 9.22 (s, 1H, NH), 8.04 (brs, 2H, Ar-H) , 7.35 (brs, 2H, Ar-H), 4.13 (s, 2H, CH 2 ), 2.22 (s, 3H, CH 3 ), 1.88 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO- d 6 ) δ 155.2, 151.7, 148.6, 144.8, 144.7, 137.1, 128.3, 120.6, 120.1 (q, J = 244.8 Hz), 52.1, 19.9, 13.3. ESI-HRMS (m/z): Calcd. for C 14 H 16 F 3 N 6 O 3 [M+H] + 373.1230; found 357.1234.
(E)-2-(1-(4-羟基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-25)(E)-2-(1-(4-hydroxy)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H )-yl)carbamoyl hydrazide (I b -25)
白色固体，产率75％，熔点237–238℃。1H NMR(300MHz,DMSO-d6)δ9.74(s,1H,NH),9.70(s,1H,NH), 9.66(s,1H,OH),9.02(s,1H,NH),7.75(d,J＝8.7Hz,2H,Ar-H),6.75(d,J＝8.7Hz,2H,Ar-H),4.12(s,2H,CH2),2.14(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ158.4,155.4,151.8,146.4,144.9,128.9,127.9,115.0,52.3,19.9,13.2.ESI-HRMS(m/z):Calcd.for C13H17N6O3[M+H]+305.1357；found 305.1357.White solid, 75% yield, mp 237 - 238. 1 H NMR (300MHz, DMSO- d 6) δ9.74 (s, 1H, NH), 9.70 (s, 1H, NH), 9.66 (s, 1H, OH), 9.02 (s, 1H, NH), 7.75 (d, J = 8.7 Hz, 2H, Ar-H), 6.75 (d, J = 8.7 Hz, 2H, Ar-H), 4.12 (s, 2H, CH 2 ), 2.14 (s, 3H, CH 3 ) , 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 158.4, 155.4, 151.8, 146.4, 144.9, 128.9, 127.9, 115.0, 52.3, 19.9, 13.2. ESI-HRMS (m/ z): Calcd.for C 13 H 17 N 6 O 3 [M+H] + 305.1357; found 305.1357.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(4-硝基苯基)亚乙基)氨基甲酰肼(Ib-26)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(4-nitro) Phenyl)ethylidene carbamoyl hydrazide (I b -26)
黄色固体，产率89％，熔点229–230℃。1H NMR(300MHz,DMSO-d6)δ10.2(s,1H,NH),9.80(s,1H,NH),9.35(s,1H,NH),8.21(brs,4H,Ar-H),4.14(s,2H,CH2),2.26(s,3H,CH3),1.88(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ154.9,151.6,147.2,144.8,144.0,143.9,127.4,123.3,52.1,19.9,13.2.ESI-HRMS(m/z):Calcd.for C13H16N7O4[M+H]+334.1258；found 334.1258.Yellow solid, yield 89%, mp 229 - 230. 1 H NMR (300MHz, DMSO- d 6) δ10.2 (s, 1H, NH), 9.80 (s, 1H, NH), 9.35 (s, 1H, NH), 8.21 (brs, 4H, Ar-H) , 4.14 (s, 2H, CH 2 ), 2.26 (s, 3H, CH 3 ), 1.88 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 154.9, 151.6, 147.2, 144.8, 144.0, 143.9, 127.4, 123.3, 52.1, 19.9, 13.2. ESI-HRMS (m/z): Calcd. for C 13 H 16 N 7 O 4 [M+H] + 334.1258; found 334.1258.
(E)-2-(1-(4-氨基苯基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ib-27)(E)-2-(1-(4-Aminophenyl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazine-4 (5H)-yl)carbamoyl hydrazide (I b -27)
黄色固体，产率54％，熔点298–300℃。1H NMR(300MHz,DMSO-d6)δ9.73(s,1H,NH),9.58(s,1H,NH),8.95(s,1H,NH),7.61(d,J＝6.3Hz,2H,Ar-H),6.55(d,J＝6.3Hz,2H,Ar-H),5.55(s,2H,NH2),4.11(s,2H,CH2),2.09(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ155.3,151.7,149.7,146.8,144.7,127.4,125.2,113.1,52.2,19.8,12.9.ESI-HRMS(m/z):Calcd.for C13H18N7O2[M+H]+304.1516；found 304.1521.Yellow solid, yield 54%, mp 298 - 300. 1 H NMR (300MHz, DMSO-d 6 ) δ 9.73 (s, 1H, NH), 9.58 (s, 1H, NH), 8.95 (s, 1H, NH), 7.61 (d, J = 6.3 Hz, 2H , Ar-H), 6.55 (d, J = 6.3 Hz, 2H, Ar-H), 5.55 (s, 2H, NH 2 ), 4.11 (s, 2H, CH 2 ), 2.09 (s, 3H, CH 3 ) ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.3, 151.7, 149.7, 146.8, 144.7, 127.4, 125.2, 113.1, 52.2, 19.8, 12.9. ESI-HRMS (m) /z):Calcd.for C 13 H 18 N 7 O 2 [M+H] + 304.1516;found 304.1521.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-2-(1-(吡啶-3-基)亚乙基)氨基甲酰肼(Ib-28)(E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-2-(1-(pyridin-3-yl)) Ethyl)carbamoyl hydrazide (I b -28)
白色固体，产率97.7％，熔点228-229℃。1H NMR(400MHz,CDCl3)δ10.10(s,1H,NH),9.78(s,1H,NH),9.32(s,1H,NH),9.07(s,1H,Py-H),8.61(d,J＝4.4Hz,1H,Py-H),8.43(d,J＝8.0Hz,1H,Py-H),7.53(q,J＝4.8Hz,1H,Py-H),4.12(s,2H,CH2),2.24(s,3H,＝CCH3),1.87(s,3H,CH3)；13C NMR(100MHz,CDCl3)δ155.0,151.6,148.0,146.3,144.8,143.4,135.0,133.9,123.8,52.1,19.9,13.0.ESI-HRMS(m/z):Calcd.for C12H15N7O2[M+H]+290.1360；found 290.1357.White solid, 97.7% yield, mp 228-229. 1 H NMR (400MHz, CDCl 3 ) δ10.10 (s, 1H, NH), 9.78 (s, 1H, NH), 9.32 (s, 1H, NH), 9.07 (s, 1H, Py-H), 8.61 (d, J = 4.4 Hz, 1H, Py-H), 8.43 (d, J = 8.0 Hz, 1H, Py-H), 7.53 (q, J = 4.8 Hz, 1H, Py-H), 4.12 (s , 2H, CH 2 ), 2.24 (s, 3H, = CCH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, CDCl 3 ) δ 155.0, 151.6, 148.0, 146.3, 144.8, 143.4, 135.0 , 133.9, 123.8, 52.1, 19.9, 13.0. ESI-HRMS (m/z): Calcd. for C 12 H 15 N 7 O 2 [M+H] + 290.1360; found 290.1357.
实施例3：Example 3:
(1)(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(6-(邻甲基苯氧基)吡啶-3-基)亚乙基)氨基甲酰肼(Ic-1)的合成(1) (E)-N-(6-Methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(6) Synthesis of (-o-methylphenoxy)pyridin-3-yl)ethylidenecarbonylhydrazide (I c -1)
Figure PCTCN2017102601-appb-000116
Figure PCTCN2017102601-appb-000116
在250mL单口瓶中，加入氨基三嗪酮(0.74g,4mmol)、对甲基苯磺酸(0.14g,0.8mmol)、吡啶酮(0.91g,4mmol，购自南京多点化学公司)、甲醇(120mL)搅拌溶解，然后加热回流6h，TLC监测反应完毕。将反应液减压脱溶后，用石油醚/乙酸乙酯(30:1--10:1)进行硅胶柱层析得到黄色固体0.85g，产率54％，熔点218℃。1H NMR(400MHz,DMSO-d6):δ9.96(s,1H,NH),9.77(s,1H,NH),9.22(s,1H,NH),8.56(s,1H,Py-H),8.45(d,J＝8.0Hz,1H,Py-H),7.31(d,J＝7.2Hz,1H,Ar-H),7.24(t,J＝7.2Hz,1H,Ar-H),7.14(t,J＝7.2Hz,1H,Ar-H),7.06(d,J＝8.0Hz,1H,Py-H),7.02(d,J＝8.8Hz,1H,Ar-H),4.10(s,2H,CH2),2.18(s,3H,CH3),2.08(s,3H,CH3),1.86(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ163.2,155.1,151.9,151.6,145.6,144.7,143.5,137.9,131.2,130.2,128.7,127.2,125.1,122.0,110.0,52.1,19.8,16.0,13.0.ESI-HRMS(m/z):Calcd.for C19H22N7O3[M+H]+396.1779；found 396.1779.In a 250 mL single-mouth bottle, aminotriazinone (0.74 g, 4 mmol), p-toluenesulfonic acid (0.14 g, 0.8 mmol), pyridone (0.91 g, 4 mmol, purchased from Nanjing Multipoint Chemical Co., Ltd.), methanol (120 mL) was stirred and dissolved, then heated to reflux for 6 h, and the reaction was completed by TLC. After the reaction mixture was dissolved in vacuo, EtOAc (EtOAc:EtOAc) 1 H NMR (400MHz, DMSO- d 6): δ9.96 (s, 1H, NH), 9.77 (s, 1H, NH), 9.22 (s, 1H, NH), 8.56 (s, 1H, Py-H ), 8.45 (d, J = 8.0 Hz, 1H, Py-H), 7.31 (d, J = 7.2 Hz, 1H, Ar-H), 7.24 (t, J = 7.2 Hz, 1H, Ar-H), 7.14 (t, J = 7.2 Hz, 1H, Ar-H), 7.06 (d, J = 8.0 Hz, 1H, Py-H), 7.02 (d, J = 8.8 Hz, 1H, Ar-H), 4.10 ( s, 2H, CH 2 ), 2.18 (s, 3H, CH 3 ), 2.08 (s, 3H, CH 3 ), 1.86 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 163 .2,155.1,151.9,151.6,145.6,144.7,143.5,137.9,131.2,130.2,128.7,127.2,125.1,122.0,110.0,52.1,19.8,16.0,13.0.ESI-HRMS(m/z):Calcd.for C 19 H 22 N 7 O 3 [M+H] + 396.1779;found 396.1779.
(2)化合物Ic-2至Ic-15通过重复上述Ic-1的制备步骤完成。(2) The compounds I c -2 to I c -15 are completed by repeating the preparation steps of the above I c -1.
但是不同的是：But the difference is:
制备化合物Ic-2时，采用等摩尔量的
Figure PCTCN2017102601-appb-000117
(购自南京多点化学公司)代替吡啶酮；When preparing compound I c -2, an equimolar amount is used.
Figure PCTCN2017102601-appb-000117
(purchased from Nanjing Multipoint Chemical Company) instead of pyridone;
制备化合物Ic-3时，采用等摩尔量的
Figure PCTCN2017102601-appb-000118
(购自上海阿拉丁生化科技股份有限公司)代替吡啶酮； When preparing compound I c -3, an equimolar amount is used.
Figure PCTCN2017102601-appb-000118
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of pyridone;
制备化合物Ic-4时，采用等摩尔量的
Figure PCTCN2017102601-appb-000119
(购自天津希恩思生化科技有限公司公司)代替吡啶酮；When preparing compound I c -4, an equimolar amount is used.
Figure PCTCN2017102601-appb-000119
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of pyridone;
制备化合物Ic-5时，采用等摩尔量的
Figure PCTCN2017102601-appb-000120
(购自天津希恩思生化科技有限公司公司)代替吡啶酮；When preparing compound I c -5, an equimolar amount is used.
Figure PCTCN2017102601-appb-000120
(purchased from Tianjin Xiens Biochemical Technology Co., Ltd.) instead of pyridone;
制备化合物Ic-6时，采用等摩尔量的
Figure PCTCN2017102601-appb-000121
(购自安耐吉化学公司)代替吡啶酮；When preparing compound I c -6, an equimolar amount is used.
Figure PCTCN2017102601-appb-000121
(purchased from Angie Chemical Company) instead of pyridone;
制备化合物Ic-7时，采用等摩尔量的
Figure PCTCN2017102601-appb-000122
(购自安耐吉化学公司)代替吡啶酮；When preparing compound I c -7, an equimolar amount is used.
Figure PCTCN2017102601-appb-000122
(purchased from Angie Chemical Company) instead of pyridone;
制备化合物Ic-8时，采用等摩尔量的
Figure PCTCN2017102601-appb-000123
(购自北京伊诺凯科技有限公司公司)代替吡啶酮；When preparing compound I c -8, an equimolar amount is used.
Figure PCTCN2017102601-appb-000123
(purchased from Beijing Inokui Technology Co., Ltd.) instead of pyridone;
制备化合物Ic-9时，采用等摩尔量的
Figure PCTCN2017102601-appb-000124
(购自北京伊诺凯科技有限公司公司)代替吡啶酮；When preparing compound I c -9, an equimolar amount is used.
Figure PCTCN2017102601-appb-000124
(purchased from Beijing Inokui Technology Co., Ltd.) instead of pyridone;
制备化合物Ic-10时，采用等摩尔量的
Figure PCTCN2017102601-appb-000125
(购自北京伊诺凯科技有限公司公司)代替吡啶酮；When preparing compound I c -10, an equimolar amount is used.
Figure PCTCN2017102601-appb-000125
(purchased from Beijing Inokui Technology Co., Ltd.) instead of pyridone;
制备化合物Ic-11时，采用等摩尔量的
Figure PCTCN2017102601-appb-000126
(购自北京伊诺凯科技有限公司公司)代替吡啶酮；When preparing compound I c -11, an equimolar amount is used.
Figure PCTCN2017102601-appb-000126
(purchased from Beijing Inokui Technology Co., Ltd.) instead of pyridone;
制备化合物Ic-12时，采用等摩尔量的
Figure PCTCN2017102601-appb-000127
(购自安耐吉化学公司)代替吡啶酮；When preparing compound I c -12, an equimolar amount is used.
Figure PCTCN2017102601-appb-000127
(purchased from Angie Chemical Company) instead of pyridone;
制备化合物Ic-13时，采用等摩尔量的
Figure PCTCN2017102601-appb-000128
(购自安耐吉化学公司)代替吡啶酮； When preparing compound I c -13, an equimolar amount is used.
Figure PCTCN2017102601-appb-000128
(purchased from Angie Chemical Company) instead of pyridone;
制备化合物Ic-14时，采用等摩尔量的
Figure PCTCN2017102601-appb-000129
(购自安耐吉化学公司)代替吡啶酮；When preparing compound I c -14, an equimolar amount is used.
Figure PCTCN2017102601-appb-000129
(purchased from Angie Chemical Company) instead of pyridone;
制备化合物Ic-15时，采用等摩尔量的
Figure PCTCN2017102601-appb-000130
(购自上海阿拉丁生化科技股份有限公司)代替吡啶酮。When preparing compound I c -15, an equimolar amount is used.
Figure PCTCN2017102601-appb-000130
(purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) instead of pyridone.
所得化合物的表征结果如下所示：The characterization results of the obtained compounds are as follows:
(E)-2-(1-(6-(2-乙氧基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-2)(E)-2-(1-(6-(2-ethoxyphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-di Hydrogen-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -2)
白色固体，产率61％，熔点217-218℃。1H NMR(400MHz,DMSO-d6)δ9.94(s,1H,NH),9.77(s,1H,NH),9.22(s,1H,NH),8.54(s,1H,Py-H),8.43(d,J＝8.4Hz,1H,Py-H),7.19(t,J＝8.0Hz,1H,Ar-H),7.12(t,J＝8.0Hz,2H,Ar-H),6.97(t,J＝8.4Hz,2H,Ar-H,Py-H),4.10(s,2H,CH2),3.94(q,J＝6.8Hz,14.0Hz,2H,CH2CH3),2.18(s,3H,CH3),1.87(s,3H,CH3),1.05(t,J＝6.8Hz,3H,CH2CH3)；13C NMR(100MHz,DMSO-d6)δ163.5,155.1,151.7,150.7,145.3,144.8,143.6,142.4,137.5,128.5,126.0,123.0,120.8,114.2,109.7,63.7,52.1,19.9,14.5,13.0.ESI-HRMS(m/z):Calcd.for C20H24N7O4[M+H]+426.1884；found 426.1887.White solid, yield 61%, m.p. 217-218. 1 H NMR (400MHz, DMSO- d 6) δ9.94 (s, 1H, NH), 9.77 (s, 1H, NH), 9.22 (s, 1H, NH), 8.54 (s, 1H, Py-H) , 8.43 (d, J = 8.4 Hz, 1H, Py-H), 7.19 (t, J = 8.0 Hz, 1H, Ar-H), 7.12 (t, J = 8.0 Hz, 2H, Ar-H), 6.97 (t, J = 8.4 Hz, 2H, Ar-H, Py-H), 4.10 (s, 2H, CH 2 ), 3.94 (q, J = 6.8 Hz, 14.0 Hz, 2H, CH 2 CH 3 ), 2.18 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ), 1.05 (t, J = 6.8 Hz, 3H, CH 2 CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 163.5, 155.1 , 151.7, 150.7, 145.3, 144.8, 143.6, 142.4, 137.5, 128.5, 126.0, 123.0, 120.8, 114.2, 109.7, 63.7, 52.1, 19.9, 14.5, 13.0. ESI-HRMS (m/z): Calcd.for C 20 H 24 N 7 O 4 [M+H] + 426.1884; found 426.1887.
(E)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)-2-(1-(6-(2-乙氧基苯氧基)吡啶-3-基)亚乙基)氨基甲酰肼(Ic-3)(E)-N-(6-methyl-3-keto-2,3-dihydro-1,2,4-triazin-4(5H)-yl)-2-(1-(6-(2) -ethoxyphenoxy)pyridin-3-yl)ethylidene carbamoyl hydrazide (I c -3)
黄色固体，产率81％，熔点261-262℃。1H NMR(400MHz,DMSO-d6)δ10.00(s,1H,NH),9.77(s,1H,NH),9.27(s,1H,NH),8.65(s,1H,Py-H),8.54(d,J＝6.8Hz,1H,Py-H),8.10(d,J＝7.2Hz,1H,Ar-H),8.03(s,1H,Ar-H),7.67(m,2H,Ar-H),7.19(d,J＝8.4Hz,1H,Py-H),4.11(s,2H,CH2),2.21(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ162.2,155.0,154.0,151.6,148.4,145.4,144.7,143.2,138.3,130.9,129.8,128.2,119.5,116.2,111.2,52.1,19.8,12.9.ESI-HRMS(m/z):Calcd.for C18H19N8O5[M+H]+427.1473；found 427.1474.Yellow solid, yield 81%, m.p. 261-262. 1 H NMR (400MHz, DMSO- d 6) δ10.00 (s, 1H, NH), 9.77 (s, 1H, NH), 9.27 (s, 1H, NH), 8.65 (s, 1H, Py-H) , 8.54 (d, J = 6.8 Hz, 1H, Py-H), 8.10 (d, J = 7.2 Hz, 1H, Ar-H), 8.03 (s, 1H, Ar-H), 7.67 (m, 2H, Ar-H), 7.19 (d, J = 8.4 Hz, 1H, Py-H), 4.11 (s, 2H, CH 2 ), 2.21 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ) 13 C NMR (100 MHz, DMSO-d 6 ) δ 162.2, 155.0, 154.0, 151.6, 148.4, 145.4, 144.7, 143.2, 138.3, 130.9, 129.8, 128.2, 119.5, 116.2, 111.2, 52.1, 19.8, 12.9. HRMS (m/z): Calcd. for C 18 H 19 N 8 O 5 [M+H] + 427.1473; found 427.1474.
(E)-2-(1-(6-(3-氨基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-4)(E)-2-(1-(6-(3-Aminophenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro- 1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -4)
黄色固体，产率80％，熔点233-234℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.76(s,1H,NH),9.22(s,1H,NH),8.63(s,1H,Py-H),8.42(d,J＝8.4Hz,1H,Py-H),7.02(t,J＝8.0Hz,1H,Ar-H),6.93(d,J＝8.4Hz,1H,Py-H),6.39(d,J＝8.0Hz,1H,Ar-H),6.27(s,1H,Ar-H),6.22(d,J＝8.0Hz,1H,Ar-H),5.24(s,2H,NH2),4.11(s,2H,CH2),2.20(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ163.4,155.1,155.0,151.6,150.3,145.8,144.8,143.5,137.7,129.8,128.9,110.6,110.4,107.8,106.0,52.1,19.9,13.0.ESI-HRMS(m/z):Calcd.for C18H21N8O3[M+H]+397.1731；found 397.1739.Yellow solid, yield 80%, mp 233-234. 1 H NMR (400MHz, DMSO- d 6) δ9.95 (s, 1H, NH), 9.76 (s, 1H, NH), 9.22 (s, 1H, NH), 8.63 (s, 1H, Py-H) , 8.42 (d, J = 8.4 Hz, 1H, Py-H), 7.02 (t, J = 8.0 Hz, 1H, Ar-H), 6.93 (d, J = 8.4 Hz, 1H, Py-H), 6.39 (d, J = 8.0 Hz, 1H, Ar-H), 6.27 (s, 1H, Ar-H), 6.22 (d, J = 8.0 Hz, 1H, Ar-H), 5.24 (s, 2H, NH 2 ) ), 4.11 (s, 2H, CH 2 ), 2.20 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 163.4, 155.1, 155.0, 151.6 , 150.3, 145.8, 144.8, 143.5, 137.7, 129.8, 128.9, 110.6, 110.4, 107.8, 106.0, 52.1, 19.9, 13.0. ESI-HRMS (m/z): Calcd. for C 18 H 21 N 8 O 3 [ M+H] + 397.1731; found 397.1739.
(E)-2-(1-(6-(4-乙基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-5)(E)-2-(1-(6-(4-ethylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro -1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -5)
黄色固体，产率85％，熔点214-216℃。1H NMR(400MHz,DMSO-d6):δ9.95(s,1H,NH),9.76(s,1H,NH),9.22(s,1H,NH),8.59(s,1H,Py-H),8.45(d,J＝8.4Hz,1H,Py-H),7.25(d,J＝8.4Hz,2H,Ar-H),7.05(d,J＝8.4Hz,2H,Ar-H),7.00(d,J＝8.4Hz,1H,Py-H),4.11(s,2H,CH2),2.62(q,J＝7.2,14.8Hz,2H,CH2CH3),2.19(s,3H,CH3),1.87(s,3H,CH3),1.20(t,J＝7.6Hz,3H,CH2CH3)；13C NMR(100MHz,DMSO-d6)δ163.4,155.1,151.2,145.6,144.8,143.5,140.1,137.8,128.9,121.2,110.6,52.1,27.6,19.9,15.8,13.0.ESI-HRMS(m/z):Calcd.for C20H24N7O3[M+H]+410.1935；found 410.1941.Yellow solid, yield 85%, mp 214-216. 1 H NMR (400MHz, DMSO- d 6): δ9.95 (s, 1H, NH), 9.76 (s, 1H, NH), 9.22 (s, 1H, NH), 8.59 (s, 1H, Py-H ), 8.45 (d, J = 8.4 Hz, 1H, Py-H), 7.25 (d, J = 8.4 Hz, 2H, Ar-H), 7.05 (d, J = 8.4 Hz, 2H, Ar-H), 7.00 (d, J = 8.4 Hz, 1H, Py-H), 4.11 (s, 2H, CH 2 ), 2.62 (q, J = 7.2, 14.8 Hz, 2H, CH 2 CH 3 ), 2.19 (s, 3H) , CH 3 ), 1.87 (s, 3H, CH 3 ), 1.20 (t, J = 7.6 Hz, 3H, CH 2 CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 163.4, 155.1, 151.2, 145.6 , 144.8, 143.5, 140.1, 137.8, 128.9, 121.2, 110.6, 52.1, 27.6, 19.9, 15.8, 13.0. ESI-HRMS (m/z): Calcd. for C 20 H 24 N 7 O 3 [M+H] + 410.1935; found 410.1941.
(E)-2-(1-(6-(4-异丙基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-6)(E)-2-(1-(6-(4-isopropylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-di Hydrogen-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -6)
黄色固体，产率87％，熔点222-223℃。1H NMR(400MHz,DMSO-d6)δ9.96(s,1H,NH),9.77(s,1H,NH),9.23(s,1H,NH),8.59(s,1H,Py-H),8.45(d,J＝8.4Hz,1H,Py-H),7.28(d,J＝7.6Hz,2H,Ar-H),7.05(d,J＝8.0Hz,2H,Ar-H),7.01(d,J＝8.4Hz,1H,Py-H),4.11(s,2H,CH2),2.91(m,1H,CH(CH3)2),2.19(s,3H,CH3),1.87(s,3H,CH3),1.22(d,J＝6.4Hz,6H,CH(CH3)2)；13C NMR(100MHz,DMSO-d6)δ155.1,151.6,145.6,144.7,143.4,137.8,128.9,127.4,121.1,110.6,52.1,32.9,24.0,19.9,13.0.ESI-HRMS(m/z):Calcd.for C21H26N7O3[M+H]+424.2092；found424.2096.Yellow solid, yield 87%, m.p. 222 - 223. 1 H NMR (400MHz, DMSO- d 6) δ9.96 (s, 1H, NH), 9.77 (s, 1H, NH), 9.23 (s, 1H, NH), 8.59 (s, 1H, Py-H) , 8.45 (d, J = 8.4 Hz, 1H, Py-H), 7.28 (d, J = 7.6 Hz, 2H, Ar-H), 7.05 (d, J = 8.0 Hz, 2H, Ar-H), 7.01 (d, J = 8.4 Hz, 1H, Py-H), 4.11 (s, 2H, CH 2 ), 2.91 (m, 1H, CH(CH 3 ) 2 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ), 1.22 (d, J = 6.4 Hz, 6H, CH(CH 3 ) 2 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 155.1, 151.6, 145.6, 144.7, 143.4, 137.8 , 128.9, 127.4, 121.1, 110.6, 52.1, 32.9, 24.0, 19.9, 13.0. ESI-HRMS (m/z): Calcd. for C 21 H 26 N 7 O 3 [M+H] + 424.2092; found424.2096 .
(E)-2-(1-(6-(4-叔丁基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基) 氨基甲酰肼(Ic-7)(E)-2-(1-(6-(4-tert-Butylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-di Hydrogen-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -7)
白色固体，产率88％，熔点208℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.76(s,1H,NH),9.22(s,1H,NH),8.59(s,1H,Py-H),8.46(d,J＝8.8Hz,1H,Py-H),7.43(d,J＝8.4Hz,2H,Ar-H),7.06(d,J＝8.4Hz,2H,Ar-H),7.02(d,J＝8.8Hz,1H,Py-H),4.11(s,2H,CH2),2.19(s,3H,CH3),1.87(s,3H,CH3),1.30(s,9H,C(CH3)3)；13C NMR(100MHz,DMSO-d6)δ163.4,155.1,151.6,151.3,147.0,145.6,144.7,143.4,137.8,128.9,126.3,120.8,110.6,52.1,34.2,31.3,19.9,13.0.ESI-HRMS(m/z):Calcd.for C22H28N7O3[M+H]+438.2248；found 438.2253.White solid, yield 88%, m.p. 208. 1 H NMR (400MHz, DMSO- d 6) δ9.95 (s, 1H, NH), 9.76 (s, 1H, NH), 9.22 (s, 1H, NH), 8.59 (s, 1H, Py-H) , 8.46 (d, J = 8.8 Hz, 1H, Py-H), 7.43 (d, J = 8.4 Hz, 2H, Ar-H), 7.06 (d, J = 8.4 Hz, 2H, Ar-H), 7.02 (d, J = 8.8 Hz, 1H, Py-H), 4.11 (s, 2H, CH 2 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ), 1.30 (s, 9H) , C(CH 3 ) 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 163.4, 155.1, 151.6, 151.3, 147.0, 145.6, 144.7, 143.4, 137.8, 128.9, 126.3, 120.8, 110.6, 52.1, 34.2, 31.3, 19.9, 13.0. ESI-HRMS (m/z): Calcd. for C 22 H 28 N 7 O 3 [M+H] + 438.2248; found 438.2253.
(E)-2-(1-(6-(4-溴苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-8)(E)-2-(1-(6-(4-Bromophenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro- 1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -8)
黄色固体，产率75％，熔点238-239℃。1H NMR(400MHz,DMSO-d6)δ9.97(s,1H,NH),9.77(s,1H,NH),9.24(s,1H,NH),8.61(s,1H,Py-H),8.49(d,J＝8.8Hz,1H,Py-H),7.60(d,J＝8.4Hz,2H,Ar-H),7.14(d,J＝8.4Hz,2H,Ar-H),7.08(d,J＝8.8Hz,1H,Py-H),4.11(s,2H,CH2),2.20(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ162.7,155.1,153.0,151.6,145.5,144.7,143.3,138.1,132.4,129.4,123.6,116.6,111.0,52.1,19.8,13.0.ESI-HRMS(m/z):Calcd.for C18H19BrN7O3[M+H]+460.0727；found 460.0722.Yellow solid, 75% yield, mp 238-239. 1 H NMR (400MHz, DMSO- d 6) δ9.97 (s, 1H, NH), 9.77 (s, 1H, NH), 9.24 (s, 1H, NH), 8.61 (s, 1H, Py-H) , 8.49 (d, J = 8.8 Hz, 1H, Py-H), 7.60 (d, J = 8.4 Hz, 2H, Ar-H), 7.14 (d, J = 8.4 Hz, 2H, Ar-H), 7.08 (d, J = 8.8 Hz, 1H, Py-H), 4.11 (s, 2H, CH 2 ), 2.20 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz , DMSO-d 6 ) δ 162.7, 155.1, 153.0, 151.6, 145.5, 144.7, 143.3, 138.1, 132.4, 129.4, 123.6, 116.6, 111.0, 52.1, 19.8, 13.0. ESI-HRMS (m/z): Calcd.for C 18 H 19 BrN 7 O 3 [M+H] + 460.0727; found 460.0722.
(E)-2-(1-(6-(4-碘苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-9)(E)-2-(1-(6-(4-iodophenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-dihydro- 1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -9)
白色固体，产率72％，熔点244-245℃。1H NMR(400MHz,DMSO-d6)δ9.97(s,1H,NH),9.77(s,1H,NH),9.24(s,1H,NH),8.61(s,1H,Py-H),8.48(d,J＝8.8Hz,1H,Py-H),7.75(d,J＝8.4Hz,2H,Ar-H),7.08(d,J＝8.8Hz,1H,Py-H),6.99(d,J＝8.4Hz,2H,Ar-H),4.11(s,2H,CH2),2.19(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ162.7,155.1,153.7,151.6,145.5,144.8,143.3,138.3,138.1,129.4,123.8,111.0,88.8,52.1,19.9,13.0.ESI-HRMS(m/z):Calcd.for C18H19IN7O3[M+H]+508.0589；found 508.0590.White solid, yield 72%, m.p. 244-245. 1 H NMR (400MHz, DMSO- d 6) δ9.97 (s, 1H, NH), 9.77 (s, 1H, NH), 9.24 (s, 1H, NH), 8.61 (s, 1H, Py-H) , 8.48 (d, J = 8.8 Hz, 1H, Py-H), 7.75 (d, J = 8.4 Hz, 2H, Ar-H), 7.08 (d, J = 8.8 Hz, 1H, Py-H), 6.99 (d, J = 8.4 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz , DMSO-d 6 ) δ 162.7, 155.1, 153.7, 151.6, 145.5, 144.8, 143.3, 138.3, 138.1, 129.4, 123.8, 111.0, 88.8, 52.1, 19.9, 13.0. ESI-HRMS (m/z): Calcd.for C 18 H 19 IN 7 O 3 [M+H] + 508.0589; found 508.0590.
(E)-2-(1-(6-(4-(苄氧基)苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-10)(E)-2-(1-(6-(4-(Benzyloxy)phenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3 -dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -10)
黄色固体产率32％，熔点212-213℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.77(s,1H,NH),9.22(s,1H,NH),8.58(s,1H,Py-H),8.44(d,J＝8.4Hz,1H,Py-H),7.47(d,J＝7.2Hz,2H,Ar-H),7.41(t,J＝7.2Hz,2H,Ar-H),7.35(d,J＝6.4Hz,1H,Ar-H),7.06(q,J＝7.2,16.0Hz,4H,Ar-H),6.98(d,J＝8.4Hz,1H,Py-H),5.12(s,2H,OCH2),4.11(s,2H,CH2),2.19(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ163.6,155.3,155.1,151.6,147.1,145.5,144.8,143.5,137.8,137.1,128.8,128.5,127.9,127.7,122.5,115.6,110.3,69.6,52.1,19.9,13.0.ESI-HRMS(m/z):Calcd.for C25H26N7O4[M+H]+488.2041；found 488.2049.The yield of the yellow solid was 32%, m.p.: 212-213. 1 H NMR (400MHz, DMSO- d 6) δ9.95 (s, 1H, NH), 9.77 (s, 1H, NH), 9.22 (s, 1H, NH), 8.58 (s, 1H, Py-H) , 8.44 (d, J = 8.4 Hz, 1H, Py-H), 7.47 (d, J = 7.2 Hz, 2H, Ar-H), 7.41 (t, J = 7.2 Hz, 2H, Ar-H), 7.35 (d, J = 6.4 Hz, 1H, Ar-H), 7.06 (q, J = 7.2, 16.0 Hz, 4H, Ar-H), 6.98 (d, J = 8.4 Hz, 1H, Py-H), 5.12 (s, 2H, OCH 2 ), 4.11 (s, 2H, CH 2 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ163.6,155.3,155.1,151.6,147.1,145.5,144.8,143.5,137.8,137.1,128.8,128.5,127.9,127.7,122.5,115.6,110.3,69.6,52.1,19.9,13.0.ESI-HRMS(m/z) :Calcd.for C 25 H 26 N 7 O 4 [M+H] + 488.2041;found 488.2049.
(E)-2-(1-(6-(4-苯甲酰苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-11)(E)-2-(1-(6-(4-benzoylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-keto-2,3-di Hydrogen-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -11)
白色固体，产率22％，熔点234-235℃。1H NMR(400MHz,DMSO-d6)δ10.00(s,1H,NH),9.77(s,1H,NH),9.27(s,1H,NH),8.69(s,1H,Py-H),8.53(d,J＝8.4Hz,1H,Py-H),7.82(d,J＝8.0Hz,2H,Ar-H),7.75(d,J＝7.2Hz,2H,Ar-H),7.69(t,J＝6.0Hz,1H,Ar-H),7.58(t,J＝7.2Hz,2H,Ar-H),7.32(d,J＝8.4Hz,2H,Ar-H),7.18(d,J＝8.4Hz,1H,Py-H),4.11(s,2H,CH2),2.22(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ194.7,162.3,157.6,155.1,151.6,145.7,144.8,143.3,138.3,137.2,133.0,132.6,131.8,129.9,129.5,128.6,120.7,111.6,52.1,19.9,13.0.ESI-HRMS(m/z):Calcd.for C25H24N7O4[M+H]+486.1884；found 486.1891.White solid, yield 22%, m.p. 234-235. 1 H NMR (400MHz, DMSO- d 6) δ10.00 (s, 1H, NH), 9.77 (s, 1H, NH), 9.27 (s, 1H, NH), 8.69 (s, 1H, Py-H) , 8.53 (d, J = 8.4 Hz, 1H, Py-H), 7.82 (d, J = 8.0 Hz, 2H, Ar-H), 7.75 (d, J = 7.2 Hz, 2H, Ar-H), 7.69 (t, J = 6.0 Hz, 1H, Ar-H), 7.58 (t, J = 7.2 Hz, 2H, Ar-H), 7.32 (d, J = 8.4 Hz, 2H, Ar-H), 7.18 (d , J = 8.4 Hz, 1H, Py-H), 4.11 (s, 2H, CH 2 ), 2.22 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO -d 6 ) δ 194.7, 162.3, 157.6, 155.1, 151.6, 145.7, 144.8, 143.3, 138.3, 137.2, 133.0, 132.6, 131.8, 129.9, 129.5, 128.6, 120.7, 111.6, 52.1, 19.9, 13.0. ESI-HRMS ( m/z): Calcd.for C 25 H 24 N 7 O 4 [M+H] + 486.1884; found 486.1891.
(E)-2-(1-(6-(4-异丙基-3-甲基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-12)(E)-2-(1-(6-(4-isopropyl-3-methylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-one- 2,3-Dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -12)
白色固体，产率78％，熔点224-225℃。1H NMR(400MHz,DMSO-d6)δ9.95(s,1H,NH),9.76(s,1H,NH),9.22(s,1H,NH),8.60(s,1H,Py-H),8.44(d,J＝8.4Hz,1H,Py-H),7.26(d,J＝7.6Hz,1H,Ar-H),6.99(d,J＝8.4Hz,1H,Py-H),6.92(d,J＝7.6Hz,2H,Ar-H),4.11(s,2H,CH2),3.10(m,1H,CH(CH3)2),2.29(s,3H,CH3),2.19(s,3H,CH3),1.87(s,3H,CH3),1.19(d,J＝6.4Hz,6H,CH(CH3)2)；13C NMR(100MHz,DMSO-d6)δ163.5,155.1,151.6,151.2,145.6,144.7,143.5,142.7,137.8,136.2,128.8,125.7,122.6,118.8,110.5,52.1,28.3,23.2,19.8,18.9,13.0.ESI-HRMS(m/z):Calcd.for C22H28N7O3[M+H]+438.2248；found 438.2254.White solid, 78% yield, mp 224 - 225. 1 H NMR (400MHz, DMSO- d 6) δ9.95 (s, 1H, NH), 9.76 (s, 1H, NH), 9.22 (s, 1H, NH), 8.60 (s, 1H, Py-H) , 8.44 (d, J = 8.4 Hz, 1H, Py-H), 7.26 (d, J = 7.6 Hz, 1H, Ar-H), 6.99 (d, J = 8.4 Hz, 1H, Py-H), 6.92 (d, J = 7.6 Hz, 2H, Ar-H), 4.11 (s, 2H, CH 2 ), 3.10 (m, 1H, CH(CH 3 ) 2 ), 2.29 (s, 3H, CH 3 ), 2.19 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ), 1.19 (d, J = 6.4 Hz, 6H, CH(CH 3 ) 2 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 163 .5,155.1,151.6,151.2,145.6,144.7,143.5,142.7,137.8,136.2,128.8,125.7,122.6,118.8,110.5,52.1,28.3,23.2,19.8,18.9,13.0.ESI-HRMS(m/z): Calcd.for C 22 H 28 N 7 O 3 [M+H] + 438.2248;found 438.2254.
(E)-2-(1-(6-(2-异丙基-5-甲基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-13)(E)-2-(1-(6-(2-isopropyl-5-methylphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-one- 2,3-Dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -13)
白色固体，产率25％，熔点236-237℃。1H NMR(400MHz,DMSO-d6)δ9.94(s,1H,NH),9.76(s,1H,NH),9.21(s,1H,NH),8.58(s,1H,Py-H),8.43(d,J＝8.8Hz,1H,Py-H),7.26(d,J＝8.0Hz,1H,Ar-H),7.03(d,J＝8.0Hz,1H,Ar-H),6.99(d,J＝8.8Hz,1H,Py-H),6.83(s,1H,Ar-H),4.11(s,2H,CH2),2.97(m,1H,CH(CH3)2),2.26(s,3H,CH3),2.19(s,3H,CH3),1.87(s,3H,CH3),1.10(d,J＝7.2Hz,6H,CH(CH3)2)；13C NMR(100MHz,DMSO-d6)δ163.8,155.1,151.6,150.6,145.7,144.8,143.5,137.9,137.1,136.3,128.7,126.6,126.1,122.6,110.0,52.1,26.5,23.0,20.4,19.9,13.0.ESI-HRMS(m/z):Calcd.for C22H28N7O3[M+H]+438.2248；found 438.2246.White solid, 25% yield, mp 236-237. 1 H NMR (400MHz, DMSO- d 6) δ9.94 (s, 1H, NH), 9.76 (s, 1H, NH), 9.21 (s, 1H, NH), 8.58 (s, 1H, Py-H) , 8.43 (d, J = 8.8 Hz, 1H, Py-H), 7.26 (d, J = 8.0 Hz, 1H, Ar-H), 7.03 (d, J = 8.0 Hz, 1H, Ar-H), 6.99 (d, J = 8.8 Hz, 1H, Py-H), 6.83 (s, 1H, Ar-H), 4.11 (s, 2H, CH 2 ), 2.97 (m, 1H, CH(CH 3 ) 2 ), 2.26 (s, 3H, CH 3 ), 2.19 (s, 3H, CH 3), 1.87 (s, 3H, CH 3), 1.10 (d, J = 7.2Hz, 6H, CH (CH 3) 2); 13 C NMR (100MHz, DMSO-d 6 ) δ 163.8, 155.1, 151.6, 150.6, 145.7, 144.8, 143.5, 137.9, 137.1, 136.3, 128.7, 126.6, 126.1, 122.6, 110.0, 52.1, 26.5, 23.0, 20.4, 19.9, 13.0. ESI-HRMS (m/z): Calcd. for C 22 H 28 N 7 O 3 [M+H] + 438.2248; found 438.2246.
(E)-2-(1-(6-(4-烯丙基-2-甲氧基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-14)(E)-2-(1-(6-(4-allyl-2-methoxyphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-one -2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -14)
白色固体，产率61％，熔点241-242℃。1H NMR(400MHz,DMSO-d6)δ9.93(s,1H,NH),9.76(s,1H,NH),9.20(s,1H,NH),8.52(s,1H,Py-H),8.40(d,J＝8.8Hz,1H,Py-H),7.05(d,J＝7.6Hz,1H,Ar-H),6.95(d,J＝6.8Hz,2H,Ar-H,Py-H),6.79(d,J＝7.6Hz,1H,Ar-H),6.00(m,1H,＝CH),5.10(m,1H,＝CH2),4.10(s,2H,CH2),3.66(s,3H, CH3),3.39(d,J＝5.6Hz,2H,CH2),2.17(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ163.4,155.1,151.6,151.3,145.4,144.8,143.6,140.0,138.0,137.6,128.5,122.9,120.5,116.0,113.1,109.6,55.5,52.1,19.9,13.0.ESI-HRMS(m/z):Calcd.for C22H26N7O4[M+H]+452.2041；found 452.2044.White solid, yield 61%, m.p. 241 - 242. 1 H NMR (400MHz, DMSO- d 6) δ9.93 (s, 1H, NH), 9.76 (s, 1H, NH), 9.20 (s, 1H, NH), 8.52 (s, 1H, Py-H) , 8.40 (d, J = 8.8 Hz, 1H, Py-H), 7.05 (d, J = 7.6 Hz, 1H, Ar-H), 6.95 (d, J = 6.8 Hz, 2H, Ar-H, Py- H), 6.79 (d, J = 7.6 Hz, 1H, Ar-H), 6.00 (m, 1H, =CH), 5.10 (m, 1H, =CH 2 ), 4.10 (s, 2H, CH 2 ), 3.66 (s, 3H, CH 3 ), 3.39 (d, J = 5.6 Hz, 2H, CH 2 ), 2.17 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz , DMSO-d 6 ) δ 163.4, 155.1, 151.6, 151.3, 145.4, 144.8, 143.6, 140.0, 138.0, 137.6, 128.5, 122.9, 120.5, 116.0, 113.1, 109.6, 55.5, 52.1, 19.9, 13.0. ESI-HRMS ( m/z): Calcd.for C 22 H 26 N 7 O 4 [M+H] + 452.2041; found 452.2044.
(E)-2-(1-(6-(2-苯甲酰-4-甲氧基苯氧基)吡啶-3-基)亚乙基)-N-(6-甲基-3-酮-2,3-二氢-1,2,4-三嗪-4(5H)-基)氨基甲酰肼(Ic-15)(E)-2-(1-(6-(2-benzoyl-4-methoxyphenoxy)pyridin-3-yl)ethylidene)-N-(6-methyl-3-one -2,3-dihydro-1,2,4-triazin-4(5H)-yl)carbamoyl hydrazide (I c -15)
白色固体，产率49％，熔点210-211℃。1H NMR(400MHz,DMSO-d6)δ9.92(s,1H,NH),9.75(s,1H,NH),9.19(s,1H,NH),8.47(s,1H,Py-H),8.29(d,J＝8.4Hz,1H,Py-H),7.55(t,J＝8.8Hz,4H,Ar-H),7.39(t,J＝7.6Hz,2H,Ar-H),6.98(d,J＝8.4Hz,1H,Py-H),6.87(s,1H,Ar-H),6.57(d,J＝8.8Hz,1H,Ar-H),4.10(s,2H,CH2),3.85(s,3H,CH3),2.14(s,3H,CH3),1.87(s,3H,CH3)；13C NMR(100MHz,DMSO-d6)δ193.6,162.8,162.6,155.1,153.0,151.6,145.0,144.8,143.3,137.8,137.7,132.7,132.0,129.0,128.9,128.2,124.2,110.9,110.2,108.6,55.8,52.1,19.9,12.9.ESI-HRMS(m/z):Calcd.for C26H26N7O5[M+H]+516.1990；found 516.1986.White solid, yield 49%, m.p. 210-211. 1 H NMR (400MHz, DMSO- d 6) δ9.92 (s, 1H, NH), 9.75 (s, 1H, NH), 9.19 (s, 1H, NH), 8.47 (s, 1H, Py-H) , 8.29 (d, J = 8.4 Hz, 1H, Py-H), 7.55 (t, J = 8.8 Hz, 4H, Ar-H), 7.39 (t, J = 7.6 Hz, 2H, Ar-H), 6.98 (d, J = 8.4 Hz, 1H, Py-H), 6.87 (s, 1H, Ar-H), 6.57 (d, J = 8.8 Hz, 1H, Ar-H), 4.10 (s, 2H, CH 2 ), 3.85 (s, 3H, CH 3 ), 2.14 (s, 3H, CH 3 ), 1.87 (s, 3H, CH 3 ); 13 C NMR (100 MHz, DMSO-d 6 ) δ 193.6, 162.8, 162.6, 155.1 , 153.0, 151.6, 145.0, 144.8, 143.3, 137.8, 137.7, 132.7, 132.0, 129.0, 128.9, 128.2, 124.2, 110.9, 110.2, 108.6, 55.8, 52.1, 19.9, 12.9. ESI-HRMS (m/z): Calcd.for C 26 H 26 N 7 O 5 [M+H] + 516.1990;found 516.1986.
实施例4：杀蚜虫的测定，测定程序如下：Example 4: Determination of acaricidal, the measurement procedure is as follows:
蚜虫的活性测试Aphid activity test
杀蚜虫活性测定步骤如下：试虫为豆蚜(Aphis laburni Kaltenbach)，实验室蚕豆叶饲养的正常群体。称取药品，加1mL DMF溶解，加两滴吐温－20乳化剂，加入一定量的蒸馏水，搅拌均匀，配成所需浓度(具体浓度见表所示)的药液。将带蚜虫(约60只)蚕豆叶片浸入药剂中5秒钟，拿出轻轻甩干，用滤纸吸干多余药剂，然后将蚕豆枝插入吸水海绵中，并用玻璃罩罩住枝条，用纱布封口，96小时检查结果，每个化合物重复3次。对照只向蒸馏水中加入乳化剂和溶剂，搅拌均匀。The aphid activity was determined as follows: the test insect was Aphis laburni Kaltenbach, a normal population fed by laboratory broad bean leaves. Weigh the drug, add 1mL DMF to dissolve, add two drops of Tween-20 emulsifier, add a certain amount of distilled water, stir evenly, and prepare the liquid with the required concentration (specific concentration is shown in the table). Immerse the leaves of the broad bean with aphids (about 60) into the medicine for 5 seconds, take them out and dry them, use the filter paper to blot the excess medicine, then insert the broad bean branches into the absorbent sponge, cover the branches with a glass cover, and seal with gauze. The results were checked 96 hours and each compound was repeated 3 times. The control only added emulsifier and solvent to the distilled water and stirred well.
表1 含有酰腙结构三嗪酮衍生物(I)的杀蚜虫活性测试结果：Table 1 Test results of acaricidal activity containing a hydrazide structure triazinone derivative (I):
Figure PCTCN2017102601-appb-000131
Figure PCTCN2017102601-appb-000131
Figure PCTCN2017102601-appb-000132
Figure PCTCN2017102601-appb-000132
a–未测. a – not tested.
从表1中可见，在100mg/kg浓度时，大部含有酰腙结构三嗪酮衍生物表现出很好的杀蚜虫活性。在5mg/kg浓度时，Ia-13、Ia-14、Ia-15、Ia-16、Ia-44、Ia-50、Ia-51、Ia-52、Ia-54、Ia-55、Ib-13、Ic-2、Ic-5、Ic-6、Ic-7、Ic-8、Ic-9、Ic-12表现出和吡蚜酮相当的活性。As can be seen from Table 1, most of the hydrazide-containing triazinone derivatives exhibited a good acaricidal activity at a concentration of 100 mg/kg. At a concentration of 5 mg/kg, I a -13, I a -14, I a -15, I a -16, I a -44, I a -50, I a -51, I a -52, I a - 54. I a -55, I b -13, I c -2, I c -5, I c -6, I c -7, I c -8, I c -9, I c -12 exhibit and pyr Anthrone is quite active.
实施例5：杀蚊幼虫活性的测定，测定程序如下： Example 5: Determination of the activity of the mosquito larvae, the measurement procedure is as follows:
蚊幼虫的活性测试Mosquito larva activity test
杀蚊幼虫的实验方法：尖音库蚊淡色亚种，室内饲养的正常群体。称取供试化合物约5mg于盘尼西林药瓶中，加5mL丙酮(或适宜溶剂)，振荡溶解，即为1000ppm母液。移取1mL母液，加入盛有89mL水的100mL烧杯中，选取10头4龄初蚊子幼虫，连同10mL饲养液一并倒入烧杯中，其药液的浓度即为10ppm(其它药液浓度的配制通过稀释相应倍数得到)。放入标准处理室内，24h检查结果。以含有0.5mL试验溶剂的水溶液为空白对照。The experimental method for killing mosquito larvae: the subspecies of Culex pipiens pallens, the normal population raised indoors. About 5 mg of the test compound was weighed into a penicillin vial, and 5 mL of acetone (or a suitable solvent) was added thereto, and dissolved by shaking to obtain a 1000 ppm mother liquor. Pipette 1 mL of mother liquor into a 100 mL beaker containing 89 mL of water, and select 10 4-year-old larvae of the first mosquito, and pour them into a beaker together with 10 mL of the stock solution. The concentration of the liquid solution is 10 ppm (the preparation of other chemical concentrations) Obtained by diluting the corresponding multiples). Place in a standard processing room and check the results 24h. An aqueous solution containing 0.5 mL of the test solvent was used as a blank control.
表2 含有酰腙结构三嗪酮衍生物(I)的杀蚊幼虫活性测试结果：Table 2 Test results of mosquito larva activity containing hydrazide structure triazinone derivative (I):
Figure PCTCN2017102601-appb-000133
Figure PCTCN2017102601-appb-000133
Figure PCTCN2017102601-appb-000134
Figure PCTCN2017102601-appb-000134
a0.25mg/kg下死亡率，b0.1mg/kg下死亡率，c-未测. a mortality rate of 0.25mg/kg, b mortality of 0.1mg/kg, c - not tested.
从表2和表4中可见，大多数含有酰腙结构三嗪酮衍生物对蚊幼虫均表现出良好的活性。尤其是化合物Ia-35、Ia-47、Ia-53、Ib-11、Ib-16、Ib-22和Ib-25。在0.25mg/kg时对蚊幼虫表现出较高的活性，其中化合物Ia-47在0.01mg/kg时表现出40％的杀虫活性。As can be seen from Tables 2 and 4, most of the triazinone derivatives containing a hydrazide structure exhibited good activity against mosquito larvae. In particular, the compounds I a -35, I a -47, I a -53, I b -11, I b -16, I b -22 and I b -25. The mosquito larva showed higher activity at 0.25 mg/kg, wherein the compound I a -47 exhibited 40% insecticidal activity at 0.01 mg/kg.
实施例6：杀棉铃虫、玉米螟、粘虫活性的测定，测定程序如下：Example 6: Determination of the activity of cotton bollworm, corn borer, and armyworm, and the measurement procedure is as follows:
棉铃虫的活性测试Helicoverpa armigera activity test
棉铃虫的实验方法：饲料混药法，从配置好的溶液中移取3mL加入约27g的刚配置好的饲料中，从而得到稀释十倍的所需浓度。药剂混匀后均匀地倒入干净的24孔板中，晾凉后接入24头三龄棉铃虫，观察3-4天后检查结果。The experimental method of cotton bollworm: feed mixed method, 3mL was taken from the configured solution and added to about 27g of the newly configured feed, thereby obtaining the required concentration diluted ten times. After mixing the chemicals, evenly pour them into a clean 24-well plate. After cooling, connect to 24 third-instar cotton bollworms and observe the results after 3-4 days.
玉米螟的活性测试Activity test of corn borer
玉米螟的试验方法：浸叶法，配置后所需浓度后，把直径约为5-6㎝的叶片浸入药液中5-6秒，取出，放在吸水纸上晾干，放在指定的培养皿中，接入10头3龄幼虫，放入27±1℃的养虫室中观察3-4天后检查结果。Test method for corn mash: Dip leaf method, after the required concentration after the configuration, the leaves with a diameter of about 5-6 cm are immersed in the liquid for 5-6 seconds, taken out, placed on absorbent paper to dry, placed in the designated In the culture dish, 10 3rd instar larvae were inserted and placed in a broiler room at 27±1 °C for 3-4 days to check the results.
粘虫的活性测试 Activity test of armyworm
粘虫的实验方法：浸叶法，配置后所需浓度的药液(浓度见下表所示)后，把直径约为5-6cm的叶片浸入药液中5-6秒，取出，放在吸水纸上晾干，放在指定的培养皿中，接入10头3龄幼虫，放入27±1℃的养虫室中观察3-4天后检查结果。Experimental method of armyworm: Dip leaf method, after the required concentration of the drug solution (concentration is shown in the table below), the blade with a diameter of about 5-6 cm is immersed in the liquid for 5-6 seconds, taken out, placed Dry the absorbent paper, place it in the designated Petri dish, and connect 10 3rd instar larvae into the worm room at 27±1°C for 3-4 days and check the results.
表3 含有酰腙结构三嗪酮衍生物(I)的杀棉铃虫、玉米螟、粘虫活性测试结果Table 3 Test results of cotton bollworm, corn borer, and armyworm activity containing hydrazide structure triazinone derivative (I)
Figure PCTCN2017102601-appb-000135
Figure PCTCN2017102601-appb-000135
a200mg/kg下死亡率，b100mg/kg下死亡率 a 200 mg/kg mortality, b 100 mg/kg mortality
从表3中可见，大多数含有酰腙结构三嗪酮衍生物对棉铃虫、玉米螟和粘虫均表现出杀虫活性。尤其是化合物Ia-35和Ia-44在100mg/kg时对棉铃虫、玉米螟和粘虫表现出较高的活性，其中化合物Ib-44在100mg/kg时，对棉铃虫、玉米螟和粘虫分别表现出30％、20％和60％的杀虫活性。 As can be seen from Table 3, most of the triazinone derivatives containing a hydrazide structure exhibited insecticidal activity against cotton bollworm, corn borer, and armyworm. In particular, the compounds I a -35 and I a -44 showed higher activity against cotton bollworm, corn borer and armyworm at 100 mg/kg, wherein the compound I b -44 was at 100 mg/kg against cotton bollworm and corn. Earthworms and armyworms exhibited 30%, 20%, and 60% insecticidal activity, respectively.
实施例7：杀真菌活性的测定，测定程序如下：Example 7: Determination of fungicidal activity, the measurement procedure is as follows:
以番茄早疫病菌为例，可以换成其他菌Take tomato early blight bacteria as an example, you can switch to other bacteria
离体测试方法：将番茄早疫病菌接到PDA培养基上培养7天，用打孔器在菌落边缘制取直径4cm的菌碟接种到含有50mg/kg和不含药剂的PDA培养基上培养4天，量取菌落直径，与对照比较计算出药剂的抑制百分率。In vitro test method: The tomato Phytophthora infestans was cultured on PDA medium for 7 days, and inoculated with a 4 cm diameter dish at the edge of the colony to inoculate a PDA medium containing 50 mg/kg and no drug. The colony diameter was measured for 4 days, and the percentage inhibition of the drug was calculated in comparison with the control.
表4 含有酰腙结构三嗪酮衍衍生物(I)的杀菌活性测试结果：Table 4 Test results of bactericidal activity of hydrazide-containing triazinone derivative (I):
Figure PCTCN2017102601-appb-000136
Figure PCTCN2017102601-appb-000136
Figure PCTCN2017102601-appb-000137
Figure PCTCN2017102601-appb-000137
从表4中可见，大多数含有酰腙结构三嗪酮衍衍生物对14种真菌表现出杀菌活性，尤其是化合物Ia-18、Ia-26、Ia-38、Ia-53、Ib-4、Ib-6、Ib-11、Ic-2、Ic-7、Ic-9、Ic-14和Ic-14在50mg/kg浓度下对多种病原菌均表现出良好的抑菌活性。 As can be seen from Table 4, most of the triazinone derivatives containing a hydrazide structure exhibited bactericidal activity against 14 fungi, especially compounds I a -18, I a -26, I a -38, I a -53, I b -4, I b -6, I b -11, I c -2, I c -7, I c -9, I c -14 and I c -14 at various concentrations of 50 mg/kg against various pathogenic bacteria Shows good antibacterial activity.

Claims (15)

  1. 一种含有酰腙结构三嗪酮衍生物，其中，该三嗪酮衍生物为下式(I)所示的化合物：A triazinone derivative containing a hydrazide structure, wherein the triazinone derivative is a compound represented by the following formula (I):
    Figure PCTCN2017102601-appb-100001
    Figure PCTCN2017102601-appb-100001
    所述式(I)所示的化合物选自Ia系列、Ib系列和Ic系列所示化合物中的一种：The compound represented by the formula (I) is selected from one of the compounds shown in the I a series, the I b series, and the I c series:
    Ia系列化合物：式(I)中，R2为氢，R1为C2-C10的烃基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、含有1-10个碳原子的含氮杂环、含有1-10个碳原子的含氧杂环、含有1-10个碳原子的含硫杂环。其中，所述取代的苯基、取代的萘基和取代的苄基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C6的烃基和C1-C6的烷氧基中的一种或多种；I a series of compounds: in the formula (I), R 2 is hydrogen, R 1 is a C2-C10 hydrocarbon group, a C3-C6 cycloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted naphthyl group. A substituted or unsubstituted benzyl group, a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, an oxygen-containing heterocyclic ring having 1 to 10 carbon atoms, and a sulfur-containing heterocyclic ring having 1 to 10 carbon atoms. Wherein the substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C6 hydrocarbon group, and a C1-C6 alkoxy group;
    Ib系列化合物：式(I)中，R1和R2各自独立地选自C1-C10的烃基、取代的或未取代的苯基和含有1-10个碳原子的含氮杂环，其中，所述取代的苯基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C6的烃基和C1-C6的烷氧基中的一种或多种；或者，R1和R2环合形成C3-C10的碳环；I b series of compounds: In the formula (I), R 1 and R 2 are each independently selected from a C1-C10 hydrocarbon group, a substituted or unsubstituted phenyl group and a nitrogen-containing heterocyclic ring having 1 to 10 carbon atoms, wherein The substituents of the substituted phenyl are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl and One or more of C1-C6 alkoxy groups; or, R 1 and R 2 are cyclized to form a C3-C10 carbon ring;
    Ic系列化合物：式(I)中，R2为甲基，R1为
    Figure PCTCN2017102601-appb-100002
    R3为单点或多点取代的取代基，选自氢、C1-C10的烃基、羟基、硝基、氨基、氰基、醛基、卤素、未取代的或苯基取代的C1-C10的烷氧基、C1-C10的烷胺基、取代的羰基和取代的羰氧基，取代的羰基和取代的羰氧基的取代基各自独立地选自苯基、苄基、C1-C10的烷基、C1-C10的烷氧基和C1-C10的烷胺基中的一种或多种。    I c series compound: In the formula (I), R 2 is a methyl group, and R 1 is
    Figure PCTCN2017102601-appb-100002
    R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C10 hydrocarbyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or phenyl substituted C1-C10 Alkoxy, C1-C10 alkylamino, substituted carbonyl and substituted carbonyloxy, substituted carbonyl and substituted carbonyloxy are each independently selected from phenyl, benzyl, C1-C10 alkane One or more of a C1-C10 alkoxy group and a C1-C10 alkylamine group.
  2. 根据权利要求1所述的三嗪酮衍生物，其中，Ia系列化合物：式(I)中，R2为氢，R1为C2-C6的烷基、C3-C6的环烷基、取代的或未取代的苯基、取代的或未取代的萘基、取代的或未取代的苄基、含有2-8个碳原子的含氮杂环、含有2-8个碳原子的含氧杂环、含有2-8个碳原子的含硫杂环。其中，所述取代的苯基、取代的萘基和取代的苄基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C5的烷基和C1-C5的烷氧基中的一种或多种；The triazinone derivative according to claim 1, wherein the I a series of compounds: in the formula (I), R 2 is hydrogen, R 1 is a C2-C6 alkyl group, a C3-C6 cycloalkyl group, a substitution. Or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted benzyl, nitrogen-containing heterocyclic ring containing 2-8 carbon atoms, oxygenated heteropoly 2-8 carbon atoms Ring, sulfur-containing heterocycle containing 2-8 carbon atoms. Wherein the substituted phenyl, substituted naphthyl and substituted benzyl substituents are each independently selected from the group consisting of hydroxyl, halogen, cyano, nitro, ester, dimethylamino, trifluoromethyl, tri One or more of a fluoromethoxy group, a C1-C5 alkyl group, and a C1-C5 alkoxy group;
    Ib系列化合物：式(I)中，R1和R2各自独立地选自C1-C8的烷基、C2-C8的烯基、取代的或未取代的苯基和含有2-8个碳原子的含氮杂环，其中，所述取代的苯基的取代基各自独立地选自羟基、卤素、氰基、硝基、酯基、二甲胺基、三氟甲基、三氟甲氧基、C1-C5的烷基和C1-C5的烷氧基中的一种或多种；或者，R1和R2环合形成C3-C8的碳环；I b series of compounds: In the formula (I), R 1 and R 2 are each independently selected from a C1-C8 alkyl group, a C2-C8 alkenyl group, a substituted or unsubstituted phenyl group and a 2-8 carbon group. a nitrogen-containing heterocyclic ring of an atom, wherein the substituents of the substituted phenyl group are each independently selected from the group consisting of a hydroxyl group, a halogen, a cyano group, a nitro group, an ester group, a dimethylamino group, a trifluoromethyl group, and a trifluoromethoxy group. groups, C1-C5 alkyl and C1-C5 alkoxy group of one or more; or, R 1 and R 2 cyclize to form a C3-C8 carbocyclic ring;
    Ic系列化合物：式(I)中，R2为甲基，R1为
    Figure PCTCN2017102601-appb-100003
    R3为单点或多点取代的取代基，选自氢、C1-C8的烷基、C2-C8的烯基、羟基、硝基、氨基、氰基、醛基、卤素、未取代的或苯基取代的C1-C8的烷氧基、C1-C8的烷胺基、取代的羰基和取代的羰氧基，取代的羰基和取代的羰氧基的取代基各自独立地选自苯基、苄基、C1-C8的烷基、C1-C8的烷氧基和C1-C8的烷胺基中的一种或多种。    I c series compound: In the formula (I), R 2 is a methyl group, and R 1 is
    Figure PCTCN2017102601-appb-100003
    R 3 is a single or multiple substituted substituent selected from hydrogen, C1-C8 alkyl, C2-C8 alkenyl, hydroxy, nitro, amino, cyano, aldehyde, halogen, unsubstituted or a phenyl-substituted C1-C8 alkoxy group, a C1-C8 alkylamino group, a substituted carbonyl group and a substituted carbonyloxy group, and the substituents of the substituted carbonyl group and the substituted carbonyloxy group are each independently selected from a phenyl group, One or more of a benzyl group, a C1-C8 alkyl group, a C1-C8 alkoxy group, and a C1-C8 alkylamine group.
  3. 根据权利要求1或2所述的三嗪酮衍生物，其中，所述Ia系列化合物为下式所示化合物中的一种： The triazinone derivative according to claim 1 or 2, wherein the I a series compound is one of the compounds represented by the following formula:
    Figure PCTCN2017102601-appb-100004
    Figure PCTCN2017102601-appb-100004
    Figure PCTCN2017102601-appb-100005
    Figure PCTCN2017102601-appb-100005
    Figure PCTCN2017102601-appb-100006
    Figure PCTCN2017102601-appb-100006
    Figure PCTCN2017102601-appb-100007
    Figure PCTCN2017102601-appb-100007
  4. 根据权利要求1或2所述的三嗪酮衍生物，其中，所述Ib系列化合物为下式所示化合物中的一种：The triazinone derivative according to claim 1 or 2, wherein the I b series compound is one of the compounds represented by the following formula:
    Figure PCTCN2017102601-appb-100008
    Figure PCTCN2017102601-appb-100008
    Figure PCTCN2017102601-appb-100009
    Figure PCTCN2017102601-appb-100009
  5. 根据权利要求1或2所述的三嗪酮衍生物，其中，所述Ic系列化合物为下式所示化合物中的一种：The triazinone derivative according to claim 1 or 2, wherein the I c series compound is one of the compounds represented by the following formula:
    Figure PCTCN2017102601-appb-100010
    Figure PCTCN2017102601-appb-100010
    Figure PCTCN2017102601-appb-100011
    Figure PCTCN2017102601-appb-100011
  6. 权利要求1-5中任意一项所述的三嗪酮衍生物的制备方法，该方法包括：A process for the preparation of a triazinone derivative according to any one of claims 1 to 5, which comprises:
    在第一有机溶剂中，在催化剂存在下，将式(IV)所示的氨基脲三嗪酮与式(V)所示的化合物进行脱水缩合反应，得到式(I)所示的化合物；The compound represented by the formula (I) is subjected to a dehydration condensation reaction with a compound represented by the formula (V) in the presence of a catalyst in a first organic solvent to obtain a compound represented by the formula (I);
    Figure PCTCN2017102601-appb-100012
    Figure PCTCN2017102601-appb-100012
  7. 根据权利要求6所述的方法，其中，式(IV)所示的氨基脲三嗪酮与式(V)所示的化合物的用量的摩尔比为1：0.8-2，优选为1：1-1.5。 The method according to claim 6, wherein the molar ratio of the semicarbazolone of the formula (IV) to the compound of the formula (V) is 1:0.8-2, preferably 1:1- 1.5.
  8. 根据权利要求6或7所述的方法，其中，所述第一有机溶剂为甲醇、乙醇、乙腈和N,N-二甲基甲酰胺中的一种或多种；The method according to claim 6 or 7, wherein the first organic solvent is one or more of methanol, ethanol, acetonitrile and N,N-dimethylformamide;
    优选地，所述第一有机溶剂的用量使得式(IV)所示的氨基脲三嗪酮的浓度为0.01-0.05mmol/mL；Preferably, the first organic solvent is used in an amount such that the concentration of the semicarbazolone of the formula (IV) is 0.01-0.05 mmol/mL;
    优选地，所述催化剂为三氟乙酸、对甲基苯磺酸和冰乙酸中的一种或多种；Preferably, the catalyst is one or more of trifluoroacetic acid, p-toluenesulfonic acid and glacial acetic acid;
    优选地，式(IV)所示的氨基脲三嗪酮和所述催化剂的用量的摩尔比为1：0.1-0.5；Preferably, the molar ratio of the semicarbazolone of the formula (IV) and the catalyst is 1:0.1-0.5;
    优选地，所述脱水缩合反应的条件包括：温度为70-100℃，时间为4-10h。Preferably, the conditions of the dehydration condensation reaction include a temperature of 70-100 ° C and a time of 4-10 h.
  9. 根据权利要求6-8中任意一项所述的方法，其中，式(IV)所示的氨基脲三嗪酮的制备方法包括：The method according to any one of claims 6 to 8, wherein the method for producing the semicarbazolizinone of the formula (IV) comprises:
    (1)在缚酸剂存在下，在第二有机溶剂中，将式(II)所示的氨基三嗪酮与氯甲酸苯酯进行取代反应，制得式(III)所示的化合物；(1) subjecting an aminotriazinone of the formula (II) to a phenyl chloroformate in a second organic solvent in the presence of an acid-binding agent, to obtain a compound of the formula (III);
    (2)在第三有机溶剂中，将式(III)所示的化合物与水合肼进行氨基化反应，从而制得式(IV)所示的氨基脲三嗪酮；(2) subjecting a compound represented by the formula (III) to hydrazine hydrate in a third organic solvent to obtain a semicarbazolone of the formula (IV);
    Figure PCTCN2017102601-appb-100013
    Figure PCTCN2017102601-appb-100013
  10. 根据权利要求9所述的方法，其中，步骤(1)中，式(II)所示的氨基三嗪酮与氯甲酸苯酯用量的摩尔比为1：0.8-2，优选为1：1-1.5；The method according to claim 9, wherein in the step (1), the molar ratio of the aminotriazinone represented by the formula (II) to the phenyl chloroformate is 1:0.8-2, preferably 1:1- 1.5;
    优选地，所述缚酸剂为吡啶、碳酸钠、三乙胺、碳酸钾和碳酸铯中的一种或多种；Preferably, the acid binding agent is one or more of pyridine, sodium carbonate, triethylamine, potassium carbonate and cesium carbonate;
    优选地，式(II)所示的氨基三嗪酮和缚酸剂的用量的摩尔比为1：0.8-1.5；Preferably, the molar ratio of the aminotriazinone and the acid binding agent represented by the formula (II) is 1:0.8-1.5;
    优选地，所述第二有机溶剂为甲醇、二氯甲烷、氯仿、1,2-二氯乙烷和乙腈中的一种或多种；Preferably, the second organic solvent is one or more of methanol, dichloromethane, chloroform, 1,2-dichloroethane and acetonitrile;
    优选地，所述第二有机溶剂的用量使得式(II)所示的氨基三嗪酮的浓度为0.1-0.5mmol/mL；Preferably, the second organic solvent is used in an amount such that the concentration of the aminotriazinone represented by the formula (II) is from 0.1 to 0.5 mmol/mL;
    优选地，所述取代反应的条件包括：温度为60-80℃，时间为5-8h。Preferably, the conditions of the substitution reaction include a temperature of 60-80 ° C and a time of 5-8 h.
  11. 根据权利要求9或10所述的方法，其中，步骤(2)中，式(III)所示的化合物与水合肼用量的摩尔比为1：0.8-2，优选为1：0.8-1.5；The method according to claim 9 or 10, wherein, in the step (2), the molar ratio of the compound represented by the formula (III) to the hydrazine hydrate is 1:0.8-2, preferably 1:0.8-1.5;
    优选地，所述第三有机溶剂为甲醇、二氯甲烷、乙醇、1,2-二氯乙烷和乙腈中的一种或多种；Preferably, the third organic solvent is one or more of methanol, dichloromethane, ethanol, 1,2-dichloroethane and acetonitrile;
    优选地，所述第三有机溶剂的用量使得式(III)所示的化合物的浓度为0.01-0.2mmol/mL；Preferably, the third organic solvent is used in an amount such that the concentration of the compound represented by the formula (III) is from 0.01 to 0.2 mmol/mL;
    优选地，所述氨基化反应的条件包括：温度为80-100℃，时间为6-10h。Preferably, the conditions of the amination reaction include a temperature of 80 to 100 ° C and a time of 6 to 10 h.
  12. 权利要求1-5中任意一项所述的三嗪酮衍生物在杀虫方面的应用。Use of a triazinone derivative according to any one of claims 1 to 5 for insecticidal purposes.
  13. 根据权利要求12所述的应用，其中，该应用针对的害虫是蚜虫、蚊幼虫、棉铃虫、玉米螟和粘虫中的一种或多种。The use according to claim 12, wherein the pest targeted by the application is one or more of aphids, mosquito larvae, cotton bollworm, corn borer and armyworm.
  14. 权利要求1-5中任意一项所述的三嗪酮衍生物在杀菌方面的应用。Use of the triazinone derivative according to any one of claims 1 to 5 for sterilization.
  15. 根据权利要求14所述的应用，其中，该应用针对的是引起番茄早疫、小麦赤霉、马铃薯晚疫、辣椒疫霉、油菜菌核、黄瓜灰霉、水稻纹枯、黄瓜枯萎、花生褐斑、苹果轮纹、小麦纹枯、玉米小斑、西瓜炭疽和水稻恶苗的病原菌中的一种或多种。 The application according to claim 14, wherein the application is directed to causing tomato early blight, wheat gibberella, potato late blight, Phytophthora capsici, rape sclerotia, cucumber gray mold, rice stalk, cucumber withered, peanut brown One or more of the pathogens of plaque, apple ring, wheat stalk, corn plaque, watermelon anthrax and rice seedling.
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US4931439A (en) * 1987-10-16 1990-06-05 Ciba-Geigy Corporation Pesticides
US5324842A (en) * 1989-11-15 1994-06-28 Ciba-Geigy Corporation Process for the preparation of aminotriazine derivatives
CN1134933A (en) * 1995-03-31 1996-11-06 日本农药株式会社 Substituted aminoquinazolinone (thione) derivatives or salts thereof, intermediates thereof, and pest controllers and method for using same
CN107266381A (en) * 2016-04-06 2017-10-20 南开大学 Application containing acylhydrazone structure triazone derivatives and preparation method thereof and in terms of desinsection, sterilization

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4931439A (en) * 1987-10-16 1990-06-05 Ciba-Geigy Corporation Pesticides
US5324842A (en) * 1989-11-15 1994-06-28 Ciba-Geigy Corporation Process for the preparation of aminotriazine derivatives
CN1134933A (en) * 1995-03-31 1996-11-06 日本农药株式会社 Substituted aminoquinazolinone (thione) derivatives or salts thereof, intermediates thereof, and pest controllers and method for using same
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