CN108822045A - A kind of 1,4- pentadiene -3- ketoxime ether derivative, Preparation method and use containing quinazoline - Google Patents

A kind of 1,4- pentadiene -3- ketoxime ether derivative, Preparation method and use containing quinazoline Download PDF

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CN108822045A
CN108822045A CN201811016574.2A CN201811016574A CN108822045A CN 108822045 A CN108822045 A CN 108822045A CN 201811016574 A CN201811016574 A CN 201811016574A CN 108822045 A CN108822045 A CN 108822045A
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isosorbide
nitrae
pentadiene
phenyl
ketone
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CN108822045B (en
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薛伟
李琴
王会
王一会
张橙
李普
张菊平
阮祥辉
吴小琼
王俊
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Guizhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • 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

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  • Agronomy & Crop Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention discloses a kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative, it is characterised in that：Its general formula is as follows：Wherein, R1For phenyl, substituted-phenyl or replace aromatic heterocyclic；R2For phenyl, substituted-phenyl or replace aromatic heterocyclic；R3For more than one hydrogen atom, the methoxyl group contained on the 5 of quinazoline, 6,7 or 8, nitro, methyl, trifluoromethyl or halogen atom.The compounds of this invention has higher therapeutic and protective effects to Cucumber Mosaic Virus (CMV) and tobacco mosaic virus disease (TMV), shows higher anti-phytoviral activity, can be used for preparing Antiphytoviral pesticide.

Description

A kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative, preparation method and Purposes
Technical field
The present invention relates to chemical technology fields, relate in particular to a kind of pentadienone oxime ether derivative containing quinazoline Preparation method and its application in terms of Antiphytoviral.
Background technique
Every year, economic loss caused by crops are due to infection plant's virus is up to 600,000,000,000 dollars, therefore, effectively controls There is very important meaning to the development of entire agricultural with the treatment viroses of plant.In numerous plant viruses, tobacco Leaf disease has the characteristics that disease incidence height and prevention and treatment are difficult, is listed in one of most destructive plant virus.However, so far All plant antiviral agents being commercialized are only 30~50% to the therapeutic activity of plant virus under 500 μ g/mL concentration, Its suppression result is obviously unsatisfactory.Therefore, novel, efficient and environment amenable plant antiviral agent how is developed to remain unchanged It is the significant challenge put in face of drug initiative worker.
Natural products and its bionic pesticide have environmentally friendly, action site uniqueness and highly selective feature, anti- Increasingly important role is played in terms of controlling plant disease.Curcumin as a kind of polyphenol compound in turmeric, It is widely used as fragrance, food preservative, monosodium glutamate and dyestuff.Isosorbide-5-Nitrae-pentadiene ketone compounds, as a kind of important ginger Flavin derivatives, because its have desinsection, antibacterial, Antiphytoviral, anticancer, anti-inflammatory and the more wide spectrum such as anti-oxidant biology Activity has been increasingly becoming one of the hot spot in medicament initiative field.In particular, relevant report in recent years shows Isosorbide-5-Nitrae-pentadiene- 3- ketone compounds possess extremely good anti-phytoviral activity.Therefore, based on such compound, its structure is carried out Transformation, it is most likely that obtain the organic active molecule with excellent anti-phytoviral activity.
(the conjunction of Chou Qiujuan, Xue Wei, Lu Ping, Wang Zhenchao, Wei Xue the curcumin derivate of esters containing oxime such as Juan of enemy autumn in 2011 At and its antiviral activity [J] synthesis chemistry, 2011,19 (1)：Method 36-40.) is spliced for oxime ester knot using bioactie agent Structure is introduced into single carbonyl curcumin derivative 1, in the skeleton of 5- substituted-phenyl-Isosorbide-5-Nitrae-pentadiene -3- ketone, synthesized it is a series of not Symmetrical 1,5- disubstituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime class ester curcumin derivate, and anti-cucumber mosaic virus has been carried out to it The active testing of poison.Test result shows：In the drug concentration of 500 μ g/mL, synthesized target compound is to cucumber mosaic Virus has certain inhibiting effect, but is below its comparison medicament Ningnanmycin.
(Luo, the H. such as Luo in 2013；Liu, J.；Jin, L.；Hu, D.；Chen, Z.；Yang, S.；Wu, J.；Song, B.Synthesis and antiviral bioactivity of novel- (1E, 4E) -1-aryl-5- (2- (quinazolin-4-yloxy) phenyl)-Isosorbide-5-Nitrae-pentadien-3-one derivatives [J] .Eur.J.Med.Chem., 2013,63：Quinazoline structure 662-669.) is introduced into 1,5- diaryl-Isosorbide-5-Nitrae-pentadiene -3- In the skeleton of ketone, a series of (1E, 4E) -1- aryl -5- (2- (4- oxoquinazolin) phenyl)-Isosorbide-5-Nitrae-pentadiene -3- has been synthesized Ketone compounds, and the active testing of resisting tobacco mosaic virus and anti cucumber mosaic virus has been carried out to it.Test result shows： The series compound has significantly protective effect to tobacco mosaic virus (TMV), wherein there is part of compounds right in terms of protective effect The EC of tobacco mosaic virus (TMV)50Value is better than its comparison medicament Ningnanmycin.
(Ma, the J. such as Ma in 2014；Li, P.；Li, X.；Shi, Q.；Wan, Z.；Hu, D.；Jin, L.；Song, B.Synthesis and Antiviral Bioactivity ofNovel 3- ((2- ((1E, 4E) -3-oxo-5- Arylpenta-1,4-dien-1-yl) phenoxy) methyl) -4 (3H)-quinazolinone Derivatives [J] .J.Agric.Food Chem., 2014,62,8928-8934.) 4 (3H)-quinazolinone structures are introduced into 1,5- diaryl- In Isosorbide-5-Nitrae-pentadiene -3- ketone skeleton, a series of pentadiene ketone compounds of Quinazolinone-containings are synthesized, and carry out to it The active testing of anti-TMV.Test result shows：When drug concentration is 500 μ g/mL, compound synthesized by major part is to TMV There are certain living body inhibition and healing effect.Wherein there is effect of the part of compounds in terms of living body treatment fabulous, inhibits Rate is better than its comparison medicament Ningnanmycin.
(Chen, the M. such as Chen in 2015；Hu, D.；Li, X.；Yang, S.；Zhang, W.；Li, P.；Song, B.Antiviral activity and interaction mechanisms study of novel Glucopyranoside derivatives [J] .Bioorg.Med.Chem.Lett., 2015,25：3840-3844.) in order to New and effective and less toxic anti-plant virus agent is formulated, based on curcumin, principle is spliced using active group, will naturally be lived Property ingredient pyranoside is introduced into pentadienone structure, has synthesized a series of pentadiene ketone compounds containing pyranoside, and Using half leaf withered spot method, using virazole as comparison medicament, the passivation activity of the anti-TMV of target compound is tested.Test result Show：Synthesized compound has certain passivation activity to TMV, wherein have the passivation effect of part of compounds preferable, EC50Value is superior to its comparison medicament virazole.Preliminary mechanism study shows：Such compound mainly by with TMV shell egg White independence in conjunction with and make its passivation inactivation.
(Han, the Y. such as Han in 2015；Ding, Y.；Xie, D.；Hu, D.；Li, P.；Li, X.；Xue, W.；Jin, L.； Song, B.Design, synthesis and antiviral activity of novel rutin derivatives Containing Isosorbide-5-Nitrae-pentadien-3-one moiety [J] .Eur.J.Med.Chem., 2015,92：732-737.) will Isolated rutin is introduced into the skeleton of 1,5- diaryl-Isosorbide-5-Nitrae-pentadiene -3- ketone in stalwart wormwood artemisia, has synthesized a series of molecules In containing Isosorbide-5-Nitrae-pentadiene -3- ketone structure novel rutin class compound, and it has been carried out anti-TMV and anti-CMV activity survey Examination.Test result shows：When drug concentration is 500 μ g/mL, the compound largely synthesized has certain anti-TMV and resists The activity of CMV.Wherein there is the therapeutic activity of the anti-CMV of part of compounds best, EC50Value is mould better than its comparison medicament Ningnan Element.
(Long, the C. such as Long in 2015；Li, P.；Chen, M.；Dong, L.；Hu, D.；Song, B.Synthesis, Anti-tobacco mosaic virus and curcumber mosaic virus activity, and3D-QSAR Study of novel Isosorbide-5-Nitrae-pentadien-3-one derivatives containing4-thioquinazoline Moiety [J] .Eur.J.Med.Chem., 2015,102：Thio quinazoline 639-647.) is introduced into 1,5- diaryl-Isosorbide-5-Nitrae- In the skeleton of pentadiene -3- ketone, a series of pentadiene ketone compounds replaced in molecules containing quinazoline thioether have been synthesized, and The active testing of anti-TMV and anti-CMV have been carried out to it.Test result shows：When drug concentration is 500 μ g/mL, the change of synthesis Close the activity that object has certain anti-TMV and anti-CMV.Part of compound is to TMV and CMV in terms of therapeutic and protective effects With excellent inhibitory activity, EC50Value is better than comparison medicament Ningnanmycin.
(Gan, the X. such as Gan in 2016；Hu, D.；Li, P.；Wu, J.；Chen, X.；Xue, W.；Song, B.Design, Synthesis, antiviral activity and three-dimentional quantitative structure- Activity relationship study of novel Isosorbide-5-Nitrae-pentadien-3-one derivatives Containing 1,3,4-oxadiazole moiety [J] .Pest Manag.Sci., 2016,72：534-543.) by 1,3, 4- oxadiazole structure is introduced into the skeleton of 1,5- diaryl-Isosorbide-5-Nitrae-pentadiene -3- ketone, has been synthesized in a series of molecules and has been contained 1, The pentadiene ketone compounds of 3,4- oxadiazole thio ethoxies, and anti-TMV active testing has been carried out to it.Test result table It is bright：When drug concentration is 500 μ g/mL, the compound of synthesis has the activity of preferable anti-TMV.Part of compound exists There is excellent activity, EC in terms of anti-TMV protection activity50Value is much better than its comparison medicament virazole.
Quianzolinones, as a kind of important heterocycle compound, because it in variability and has in structure More the bioactivity of broad-spectrum high efficacy and become medicament initiative field in hot spot.Recent studies indicate that：Such compound There is relatively broad prospect in terms of Antiphytoviral.
(Gao, the X. such as Gao in 2007；Cai, X.；Yah, K.；Song, B.；Gao, L.；Chen, Z.Synthesis and antiviral bioactivities of 2-phenyl-3-(substituted-benzalamino)-4(3H)- Quinazolinone derivatives [J] .Molecules, 2007,12：2621-2642.) design synthesized and a series of contained 4 The Schiff class compound of (3H)-quinazolinone structure, and the active testing of anti-TMV has been carried out to it.Test result shows： When drug concentration is 500 μ g/mL, compound synthesized by major part has certain living body inhibiting effect to TMV.
(Ma, the J. such as Ma in 2014；Li, P.；Li, X.；Shi, Q.；Wan, Z.；Hu, D.；Jin, L.；Song, B.Synthesis and Antiviral Bioactivity of Novel 3- ((2- ((1E, 4E) -3-oxo-5- Arylpenta-1,4-dien-1-yl) phenoxy) methyl) -4 (3H)-quinazolinone Derivatives [J] .J.Agric.Food Chem., 2014,62,8928-8934.) 4 (3H)-quinazolinone structures are introduced into 1,5- diaryl- In Isosorbide-5-Nitrae-pentadiene -3- ketone skeleton, a series of pentadiene ketone compounds of Quinazolinone-containings are synthesized, and carry out to it The active testing of anti-TMV.Test result shows：When drug concentration is 500 μ g/mL, compound synthesized by major part is to TMV There are certain living body inhibition and healing effect.Effect of part of compound in terms of living body treatment is fabulous, inhibiting rate Better than its comparison medicament Ningnanmycin.
(Chen, the M. such as Chen in 2016；Li, P.；Hu, D.；Zeng, S.；Li, T.；Jin, L.；Xue, W.；Song, B.Synthesis, antiviral activity, 3D-QSAR, and interaction mechanisms study of novel malonate derivatives containing quinazolin-4(3H)-4-one moitey[J] .Bioorg.Med.Chem.Lett., 2016,26：168-173.) 4 (3H)-quinazolinone structures are effectively tied with malonate It closes, design has synthesized a series of quianzolinones in molecules containing malonate, and the activity of anti-CMV has been carried out to it Test.Test result shows：When drug concentration is 500 μ g/mL, compound synthesized by major part has CMV certain Living body inhibiting effect.Effect of part of compound in terms of living body treatment is fabulous, and inhibiting rate is peaceful better than its comparison medicament Southern mycin.
In conclusion Isosorbide-5-Nitrae-pentadiene -3- ketone compounds and quianzolinones have in terms of Antiphytoviral The compound with antiviral activity for having certain researching value, but currently formulating out is not yet in protection and therapeutic activity Two aspects are more than simultaneously Ningnanmycin, while also be there are no about the Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether Report in terms of the synthesis of conjunction object and anti-phytoviral activity and bacteriostatic activity.
Summary of the invention
The technical problem to be solved by the present invention is to：Pentadienone oximido ether compound containing quinazoline in a kind of structure is provided And preparation method thereof, such compound has preferable control efficiency to plant virus and suppression phytopathogen, can be used as antivirotic And disinfectant use in agriculture.
The technical scheme is that：A kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative, general formula is such as Shown in lower：
Wherein, R1For phenyl, substituted-phenyl or replace aromatic heterocyclic；R2For phenyl, substituted-phenyl or replace aromatic heterocyclic； R3For contain on the 5 of quinazoline, 6,7 or 8 more than one hydrogen atom, methoxyl group, nitro, methyl, trifluoromethyl or Halogen atom.
The substituted-phenyl be on phenyl ring it is o-, m-, pair or aforementioned two upper contain more than one methoxyl group, nitro, first Base, trifluoromethyl or halogen atom.
The substitution aromatic heterocyclic is furyl, pyridyl group, thienyl, pyrrole radicals, thiazolyl, 2- chloropyridine base or 2- Diuril oxazolyl.
A kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative preparation method, to contain substituent group 4- chloro-quinazoline and 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime or 1- (2- (replaces Benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime be raw material prepare the Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketone Oxime ether derivative：
(2- (replaces by 1- (4- (substituted benzyloxy) the phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime or 1- Benzyloxy) phenyl) preparation method of -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime is：(1) with acetone, salicylide or 4- hydroxyl Benzaldehyde is raw material, prepares 2- (hydroxy phenyl)-3- butene-2 -one or 4- (hydroxy phenyl)-3- butylene-under alkaline condition 2- ketone：(2) with substituted aroma aldehyde, 2- (hydroxy phenyl) -3- fourth Alkene-2- ketone or 4- (hydroxy phenyl)-3- butene-2 -one are raw material, prepare 1- substituted aryl-5- (4- hydroxyl under alkaline condition Phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- substituted aryl -5- (2- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone：(3) to replace benzyl chloride, 1- substituted aryl -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- substituted aryl -5- (2- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene - 3- ketone is that raw material prepares 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone：(4) with hydroxylamine hydrochloride, 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- (2- (substituted benzyloxy) phenyl) -5- take It is that raw material prepares 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene-for aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone 3- ketoxime or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
The preparation method of the 4- chloro-quinazoline containing substituent group is：With quinazolinone and thionyl chloride containing substituent group The 4- chloro-quinazoline containing substituent group is prepared for raw material：
A kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative is used to prepare Cucumber Mosaic Virus (CMV) With the Antiphytoviral pesticide of tobacco mosaic virus disease (TMV).
Pentadiene -3- ketoxime ether derivative is used to prepare citrus processing and rice is white for a kind of Isosorbide-5-Nitrae containing quinazoline - The disinfectant use in agriculture of leaf spoting bacteria.
Beneficial effects of the present invention：Quinazoline structure with excellent activity is introduced the knot of pentadiene ketoxime ether by the present invention In structure, design has synthesized a series of pentadienone oximido ether compound in structures containing quinazoline, and synthesized is contained quinoline The Isosorbide-5-Nitrae of oxazoline-pentadiene -3- ketoxime ether compound is applied to the research in terms of Antiphytoviral, finds such compound ratio Currently existing compound (cucumber mosaic virus and tobacco mosaic virus (TMV)) in terms of Antiphytoviral possesses work more outstanding Property, part of compound is more than its comparison medicament to the inhibitory activity of tobacco mosaic virus (TMV) in terms for the treatment of with protection activity Ningnanmycin has certain application value.
Specific embodiment
Total embodiment：
(1) using acetone, salicylide or 4- hydroxy benzaldehyde as raw material, 2- (hydroxy phenyl) -3- is prepared under alkaline condition Butene-2 -one or 4- (hydroxy phenyl)-3- butene-2 -one：
(2) it is with substituted aroma aldehyde, 2- (hydroxy phenyl)-3- butene-2 -one or 4- (hydroxy phenyl)-3- butene-2 -one Raw material prepares 1- substituted aryl -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- substituted aryl -5- under alkaline condition (2- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
(3) to replace benzyl chloride, 1- substituted aryl -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- substituted aryl - 5- (2- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene-3- ketone is that raw material prepares 1- (4- (substituted benzyloxy) phenyl) substituted aryl-1-5-, 4- pentadiene -3- ketone or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone：
(4) with hydroxylamine hydrochloride, 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone is that raw material prepares 1- (4- (substituted benzyloxy) benzene Base) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-penta two Alkene -3- ketoxime：
(5) using containing substituent group quinazolinone and thionyl chloride as raw material prepare the 4- chloro-quinazoline containing substituent group：
(6) with 4- chloro-quinazoline and 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-penta two containing substituent group Alkene -3- ketoxime or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime are that raw material preparation contains quinoline The Isosorbide-5-Nitrae of oxazoline-pentadiene -3- ketoxime ether derivative：
Specific embodiment is listed in a manner of list below, see the table below：
Embodiment 1
(4- quinazolyl) -1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime Synthesis (the compound number I of ether1), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
4- hydroxy benzaldehyde (50mmol) is added in the acetone of 60mL, after stir about 15min, the ice bath reaction system After about 30min, 5% NaOH solution of about 100mL is added into system, after being added dropwise, removes ice bath room, stirring at normal temperature About for 24 hours.To after reaction, system is transferred in the beaker of 500mL and appropriate ice water is added, then with 5% dilute hydrochloric acid After solution regulation system pH is about 5~6, there are a large amount of yellow solids to be precipitated, solid is extracted out, is finally tied again with ethanol/water system Crystalline substance is to get yellow solid, yield 68%.
(2) synthesis of 1- (2- pyridyl group) -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
By 4- (hydroxy phenyl)-3- butene-2 -one (24.7mmol), pyridine-2-formaldehyde (29.6mmol) and 50mL ethyl alcohol It is added in the three-necked flask of 250mL, after stir about 30min, 5% NaOH solution of 60mL into system, wait be added dropwise Afterwards, ice bath room is removed, stirring at normal temperature is about for 24 hours.It is appropriate to which after reaction, system is transferred in the beaker of 500mL and is added Ice water after being about then 5~6 with 5% dilute hydrochloric acid solution regulation system pH, has a large amount of yellow solids to be precipitated, solid is extracted out, Up to yellow solid, yield 82%.
(3) synthesis of 1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
1- (2- pyridyl group) -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- is sequentially added in the three-necked flask of 100mL Ketone (9.95mmol), methyl benzyl chloride (11.94mmol), potassium carbonate (14.92mmol), potassium iodide (4.97mmol) and acetone (60mL), it is to be mixed uniformly after be heated to reflux, after about 3~4h reaction terminate, go it is molten, column chromatography, obtain yellow solid, yield 39%.
(4) synthesis of 1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta is sequentially added in the there-necked flask of 100mL Diene -3- ketone (8.44mmol), hydroxylamine hydrochloride (25.32mmol), pyridine (25mL) and ethyl alcohol (50mL), stirring at normal temperature is about for 24 hours Afterwards, there is white solid precipitation in system, this solid is extracted out, ethanol rinse is to get white solid, yield 60%.
(5) synthesis of 4- chloro-quinazoline：
Quinazolinone (20.53mmol), 5 drop DMF, 1,2- dichloroethanes are sequentially added in the there-necked flask of 100mL (15mL) and thionyl chloride (30mL), it is to be mixed uniformly after, being heated to reflux after 1~2h to react terminates.Recycling design, vacuum distillation Obtain yellow solid.After being dissolved with methylene chloride, adjusting pH with saturated sodium carbonate solution is alkalinity.Liquid separation, three times, collection has for washing Machine phase, dry, concentration obtain faint yellow solid, petroleum ether recrystallization.Obtain white crystal.Yield 81%.
(6) (4- quinazolyl) -1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone The synthesis of oxime ether：
1- (4- (3- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two is sequentially added in the there-necked flask of 50mL Alkene -3- ketoxime (1.28mmol), 4- chloro-quinazoline (1.54mmo1), potassium carbonate (2.56mmol) and acetonitrile (35mL), it is to be mixed After uniformly, being heated to reflux after 3~4h to react terminates.System filters while hot, and filtrate is gone molten, is then tied again with acetonitrile (35mL × 3) Crystalline substance is to get white needle-like crystals, yield 72%.
Embodiment 2
(4- chloro-quinazoline base) -1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime Synthesis (the compound number I of ether2), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment.
(2) synthesis of 1- (2- pyridyl group) -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment.
(3) synthesis of 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- pyridyl group) -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and o-chloro benzyl chloride are raw material.
(4) synthesis of 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of 4- chloro-quinazoline：
Such as 1 (5) step of embodiment.
(6) (4- chloro-quinazoline base) -1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone The synthesis of oxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime is raw material.
Embodiment 3
(4- chloro-quinazoline base) -1- (4- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime Synthesis (the compound number I of ether3), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment.
(2) synthesis of 1- (2- pyridyl group) -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment.
(3) synthesis of 1- (4- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- pyridyl group) -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and to benzyl chloride chlorine be raw material.
(4) synthesis of 1- (4- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (4- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of 4- chloro-quinazoline：
Such as 1 (5) step of embodiment.
(6) (4- chloro-quinazoline base) -1- (4- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone The synthesis of oxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (4- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime is raw material.
Embodiment 4
(4- chloro-quinazoline base) -1- (4- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Synthesis (the compound number I of ketoxime ether4), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment.
(2) synthesis of 1- (2- pyridyl group) -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment.
(3) synthesis of 1- (4- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 2,4- dichloro benzyl chloride and 1- (2- pyridyl group) -5- (4- hydroxy phenyl) - Isosorbide-5-Nitrae-pentadiene -3- ketone is raw material.
(4) synthesis of 1- (4- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (4- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketone is raw material.
(5) synthesis of 4- chloro-quinazoline：
Such as 1 (5) step of embodiment.
(6) (4- chloro-quinazoline base) -1- (4- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene - The synthesis of 3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (4- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketoxime is raw material.
Embodiment 5
(8- methyl -4- chloro-quinazoline base) -1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two Synthesis (the compound number I of alkene -3- ketoxime ether5), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment.
(3) synthesis of 1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment.
(5) synthesis of 8- methyl -4- chloro-quinazoline：
Such as 1 (5) step of embodiment, difference is using 8- methylquinazolin ketone as raw material.
(6) (8- methyl -4- chloro-quinazoline base) -1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta The synthesis of diene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae - Pentadiene -3- ketoxime and 8- methyl -4- chloro-quinazoline are raw material.
Embodiment 6
(8- methyl -4- chloro-quinazoline base) -1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene - Synthesis (the compound number I of 3- ketoxime ether6), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment.
(3) synthesis of 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (4- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and o-chloro benzyl chloride are raw material.
(4) synthesis of 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of 8- methyl -4- chloro-quinazoline：
Such as 1 (5) step of embodiment, difference is using 8- methylquinazolin ketone as raw material.
(6) (8- methyl -4- chloro-quinazoline base) -1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime and 8- methyl -4- chloro-quinazoline are raw material.
Embodiment 7
(the chloro- 4- chloro-quinazoline base of 6-) -1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene - Synthesis (the compound number I of 3- ketoxime ether7), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment.
(3) synthesis of 1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment.
(4) synthesis of 1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment.
(5) synthesis of the chloro- 4- chloro-quinazoline of 6-：
Such as 1 (5) step of embodiment, difference is using 6- chloro-quinazoline ketone as raw material.
(6) (the chloro- 4- chloro-quinazoline base of 6-) -1- (4- (3- methylbenzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is using the chloro- 4- chloro-quinazoline of 6- as raw material.
Embodiment 8
(the chloro- 4- chloro-quinazoline base of 6-) -1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Synthesis (the compound number I of ketoxime ether8), include the following steps：
(1) synthesis of 4- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment.
(2) synthesis of 1- (4- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment.
(3) synthesis of 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is using o-chloro benzyl chloride as raw material.
(4) synthesis of 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of the chloro- 4- chloro-quinazoline of 6-：
Such as 1 (5) step of embodiment, difference is using 6- chloro-quinazoline ketone as raw material.
(6) (the chloro- 4- chloro-quinazoline base of 6-) -1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (4- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime and the chloro- 4- chloro-quinazoline of 6- are raw material.
Embodiment 9
(4- chloro-quinazoline base) -1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime Synthesis (the compound number I of ether9), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and adjacent chlorine Bian chlorine are raw material.
(4) synthesis of 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of 4- chloro-quinazoline：
Such as 1 (5) step of embodiment.
(6) (4- chloro-quinazoline base) -1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone The synthesis of oxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime is raw material.
Embodiment 10
(4- chloro-quinazoline base) -1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Synthesis (the compound number I of ketoxime ether10), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and 2,4- dichloro Bian chlorine are raw material.
(4) synthesis of 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketone is raw material.
(5) synthesis of 4- chloro-quinazoline：
Such as 1 (5) step of embodiment.
(6) (4- chloro-quinazoline base) -1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene - The synthesis of 3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketoxime is raw material.
Embodiment 11
(8- methyl -4- chloro-quinazoline base) -1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene - Synthesis (the compound number I of 3- ketoxime ether11), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and adjacent chlorine Bian chlorine are raw material.
(4) synthesis of 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of 8- methyl -4- chloro-quinazoline：
Such as 1 (5) step of embodiment, difference is using 8- methyl -4- chloro-quinazoline ketone as raw material.
(6) (8- methyl -4- chloro-quinazoline base) -1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime and 8- methyl -4- chloro-quinazoline are raw material.
Embodiment 12
(8- methyl -4- chloro-quinazoline base) -1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Synthesis (the compound number I of diene -3- ketoxime ether12), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and 2,4- dichloro Bian chlorine are raw material.
(4) synthesis of 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketone is raw material.
(5) synthesis of 8- methyl -4- chloro-quinazoline：
Such as 1 (5) step of embodiment, difference is using 8- methyl -4- chloro-quinazoline ketone as raw material.
(6) (8- methyl -4- chloro-quinazoline base) -1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae - The synthesis of pentadiene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketoxime and 8- methyl -4- chloro-quinazoline are raw material.
Embodiment 13
(4- chloro-quinazoline base) -1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime Synthesis (the compound number I of ether13), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and to chlorine Bian chlorine be raw material.
(4) synthesis of 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of 4- chloro-quinazoline：
Such as 1 (5) step of embodiment.
(6) (4- chloro-quinazoline base) -1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone The synthesis of oxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime is raw material.
Embodiment 14
(8- methyl -4- chloro-quinazoline base) -1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene - Synthesis (the compound number I of 3- ketoxime ether14), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and to chlorine Bian chlorine be raw material.
(4) synthesis of 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of 8- methyl -4- chloro-quinazoline：
Such as 1 (5) step of embodiment, difference is using 8- methyl -4- chloro-quinazoline ketone as raw material.
(6) (8- methyl -4- chloro-quinazoline base) -1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime and 8- methyl -4- chloro-quinazoline are raw material.
Embodiment 15
(the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Synthesis (the compound number I of ketoxime ether15), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and adjacent chlorine Bian chlorine are raw material.
(4) synthesis of 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of the chloro- 4- chloro-quinazoline of 6-：
Such as 1 (5) step of embodiment, difference is using the chloro- 4- chloro-quinazoline ketone of 6- as raw material.
(6) (the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (2- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime and the chloro- 4- chloro-quinazoline of 6- are raw material.
Embodiment 16
(the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two Synthesis (the compound number I of alkene -3- ketoxime ether16), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and 2,4- dichloro Bian chlorine are raw material.
(4) synthesis of 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketone is raw material.
(5) synthesis of the chloro- 4- chloro-quinazoline of 6-：
Such as 1 (5) step of embodiment, difference is using the chloro- 4- chloro-quinazoline ketone of 6- as raw material.
(6) (the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta The synthesis of diene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (2,4- dichloro-benzyloxy) phenyl) -5- (2- pyridyl group) -1, 4- pentadiene -3- ketoxime and the chloro- 4- chloro-quinazoline of 6- are raw material.
Embodiment 17
(the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Synthesis (the compound number I of ketoxime ether17), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and to chlorine Bian chlorine be raw material.
(4) synthesis of 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
(5) synthesis of the chloro- 4- chloro-quinazoline of 6-：
Such as 1 (5) step of embodiment, difference is using the chloro- 4- chloro-quinazoline ketone of 6- as raw material.
(6) (the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (4- benzyl chloride oxygroup) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime and the chloro- 4- chloro-quinazoline of 6- are raw material.
Embodiment 18
(the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (2- fluorine benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Synthesis (the compound number I of ketoxime ether18), include the following steps：
(1) synthesis of 2- (hydroxy phenyl)-3- butene-2 -one：
Such as 1 (1) step of embodiment, difference is using salicylide as raw material.
(2) synthesis of 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (2) step of embodiment, difference is using 2- (hydroxy phenyl)-3- butene-2 -one as raw material.
(3) synthesis of 1- (2- (2- fluorine benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketone：
Such as 1 (3) step of embodiment, difference is with 1- (2- hydroxy phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- Ketone and adjacent fluorine Bian chlorine are raw material.
(4) synthesis of 1- (2- (2- fluorine benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
Such as 1 (4) step of embodiment, difference is with 1- (2- (2- fluorine benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketone is raw material.
The synthesis of (5) 6 one chloro- 4- chloro-quinazolines：
Such as 1 (5) step of embodiment, difference is using the chloro- 4- chloro-quinazoline ketone of 6- as raw material.
(6) (the chloro- 4- chloro-quinazoline base of 6-) -1- (2- (2- fluorine benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta two The synthesis of alkene -3- ketoxime ether：
Such as 1 (6) step of embodiment, difference is with 1- (2- (2- fluorine benzyloxy) phenyl) -5- (2- pyridyl group)-Isosorbide-5-Nitrae-penta Diene -3- ketoxime and the chloro- 4- chloro-quinazoline of 6- are raw material.
The Isosorbide-5-Nitrae containing the quinazoline-pentadiene -3- ketoxime ether derivative physicochemical property and mass spectrometric data of synthesis are shown in Table 1, Nuclear magnetic resonance spectroscopy (1H NMR) and carbon spectrum (13C NMR) data are shown in Table 2 and table 3.
1 target compound physicochemical property of table
Compound Yield (%) Character Fusing point (DEG C)
I1 72 White solid 144-146
I2 75 White solid 170-172
I3 60 White solid 188-189
I4 86 White solid 140-142
I5 76 White solid 143-144
I6 66 White solid 145-147
I7 70 White solid 176-177
I8 79 White solid 161-162
I9 76 White solid 164-165
I10 67 White solid 201-202
I11 86 White solid 174-176
I12 87 White solid 135-135
I13 45 White solid 161-162
I14 64 White solid 159-161
I15 78 White solid 181-182
I16 72 White solid 184-186
I17 71 White solid 174-175
I18 86 White solid 160-160
2 target compound hydrogen nuclear magnetic resonance modal data of table
3 target compound carbon-13 nmr spectra data of table
The activity of resisting tobacco mosaic virus of above-mentioned target compound：
(1) test method
A. Virus purification
Quadratic method (Zhou, X.P. are avenged using week；Xu, Z.X.；Xu, J.；Li, D.B.J.South Chin.Agric.Univ.1995,16,74-79.), inoculation 3 weeks or more are chosen, TMV systemic infection host Nicotiana Tabacum.L plant upper blade, is homogenized in phosphate buffer, double gauze filtering, 8000g centrifugation, through 2 polyethylene glycol Processing, then be centrifuged, precipitating phosphate buffer suspends to get the refining liquid body of TMV is arrived.Entire experiment carries out at 4 DEG C.With purple The absorbance value of outer spectrophotometric determination 260nm wavelength calculates virus concentration according to formula.
Virus concentration (mg/mL)=(A260× extension rate)/E0.1% 1cm 260nm
Wherein E indicates extinction coefficient, i.e. when wavelength 260nm, concentration is the suspension of 0.1% (1mg/mL), is in light path Absorbance value when 1cm.The E of TMV0.1% 1cm 260nmIt is 5.0.
B. the living body therapeutic effect that medicament infects TMV
Living body therapeutic effect of the medicament to infecting：It selects the Nicotiana glutinosa of growing way consistent 5-6 leaf phase to pinch, sprinkles evenly gold to full leaf Emery dips viral juice (6 × 10 with spread pen-3Mg/mL) full leaf virus inoculation is rinsed with clear water after natural drying.To blade After dry, medicament is gently spread in left half leaf with writing brush, the solvent for the concentration that right half leaf spreads corresponding solvent compares, 6-7d postscript Withered spot number is recorded, inhibiting rate is calculated according to the following formula.
C. the living body protective effect that medicament infects TMV
The living body protective effect that medicament infects TMV：It selects the Nicotiana glutinosa of growing way consistent 5-6 leaf phase to pinch, is existed with writing brush Zuo Banye gently spreads medicament, and the solvent for the concentration that right half leaf spreads corresponding solvent compares.After for 24 hours, Buddha's warrior attendant is sprinkled evenly to full leaf Sand dips viral juice (6 × 10 with spread pen-3Mg/mL) full leaf virus inoculation is rinsed with clear water, and withered spot number is recorded after 6-7d, is pressed Following equation calculates inhibiting rate.
Wherein, the average withered spot number for being not coated with application half leaf of agent and the half leaf withered spot number for spreading medicament all use each group to weigh three times Multiple average.
(2) biological activity test result
Protection and therapeutic activity of 4 target compound of table to tobacco mosaic virus (TMV)
It is control with commodity medicament Ningnanmycin using half leaf withered spot method, when test concentrations are 500 μ g/mL, tests Treatment and protection activity (be shown in Table 4) of the target compound I1~I18 to tobacco mosaic virus (TMV) (TMV).The test result shows：Greatly Partial target compound has preferable treatment and protection activity to TMV.Wherein, target compound I3And I10To TMV possess compared with Good therapeutic effect, inhibiting rate is respectively 55.5% and 62.5%, is slightly better than Ningnanmycin (52.9%).Target compound I1 Preferable protective effect is possessed to TMV, inhibiting rate is respectively 70.6%, is slightly better than Ningnanmycin (64.8%).I3、I11And I17 Inhibiting rate is 63.8,61.0 and 60.1%.Close to Ningnanmycin (64.8%).
The antibacterial activity of above-mentioned target compound
(1) test method
Using nephelometry, target compound is tested to rice leaf spot bacteria (X.oryzae) and citrus processing (X.citri) inhibitory activity, concrete operation step are as follows：
A. in 2000mL beaker be added 1000mL sterile purified water, sequentially added under electromagnetic agitation peptone 5.0g, Yeast powder 1.0g, glucose 10.0g, beef extract 3.0g, it is to be mixed uniformly after pH adjusted to neutrality with sodium hydrate aqueous solution (7.2±0.2)；
B. test tube is cleaned sterilizing to be placed on rack for test tube, is pipetted into every test tube in the first step (1) using liquid-transfering gun After solution 4.0mL plus rubber stopper, every 6 test tubes packaging are once, stand-by after 121 DEG C of sterilizing 20min using autoclave；
C. 0.00375-0.0042g test compound sample is weighed in centrifuge tube, to distinguish after 150 μ L DMSO dissolution Pipette after 80 μ L and 40 μ L to sterilizing in numbered centrifuge tube, separately add 40 μ L DMSO to equipped with 40 μ L sample solution from 4mL Tween-20 is respectively added into above-mentioned centrifuge tube for heart pipe, while setting Thiodiazole-copper or Yekuzuo compares medicament, and DMSO makees empty White control；
D. solution pipettes in 1mL to 3 dress second step (2) and (operates before alcolhol burner in test tube, prevent it in every centrifuge tube Its germ contamination)；
E. 96 orifice plate of blank is taken, blank OD value is surveyed and excludes the hole that OD value is greater than 0.05, to be added 200 in backward each available hole Solution is surveyed OD value and is recorded in test tube in μ L (4), the citrus processing after 40 μ L activation is finally accessed into every test tube (X.citri) or tobacco ralstonia solanacearum (R.solanacearum) or rice leaf spot bacteria (X.oryzae) strain, newspaper is used 24~48h of shaken cultivation in 30 DEG C, 180rpm constant-temperature table is wrapped, during which solution O D value is raw to track bacterium in test tube Long status takes 200 μ L solution to survey OD value in test tube and records after culture；
F. compound is as follows to Bacteria suppression rate calculation formula,
Correct OD value=value of OD containing bacterium culture medium-aseptic culture medium OD value
(2) biological activity test result
5 target compound of table is set under concentration respectively to the inhibiting rate of two kinds of bacteriums
Using nephelometry, using commodity medicament thiophene bacterium ketone and Yekuzuo as positive control, test concentrations be 100 μ g/mL and When 50 μ g/mL, target compound is tested to the inhibitory activity (being shown in Table 5) of hundred leaf spoting bacteria of citrus processing and rice.It should Test result shows：Most of target compound is presented with good inhibition to citrus processing and hundred leaf spoting bacteria of rice and lives Property.Most of target compound is superior to comparison medicament thiophene bacterium ketone to the inhibiting rate of hundred leaf spoting bacteria of citrus processing and rice (66.67%) and Yekuzuo (70.53%).The compound I when drug concentration is 100 μ g/mL1、I3And I12To citrus bacterial canker disease Bacterium inhibiting rate is 94.87,77.03 and 78.77% better than Yekuzuo (70.53%), is 50 μ g/mL compounds in drug concentration I1、I2、I3、I5、I9、I11And I12Comparison medicament is higher than to the inhibiting rate of citrus processing and is better than Yekuzuo (48.97%), Inhibiting rate is respectively 70.45,52.03,63.13,60.54,63.89 and 69.51%.The chemical combination when drug concentration is 100 μ g/mL Object is higher to hundred leaf spoting bacteria inhibiting rate of rice, wherein compound I2、I9And I16Inhibiting rate be more than 80%.It is much better than Yekuzuo (54.38%).
This also indicate that such compound to TMV and phytopathogen (hundred leaf spoting bacteria of citrus processing and rice) possess compared with Good inhibiting effect, the part of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative is to plant virus and phytopathy Bacterium is presented with excellent inhibitory activity, can be used as potential Antiphytoviral drug, has the prospect preferably applied.
The above described is only a preferred embodiment of the present invention, being not intended to limit the present invention in any form, appoint What is to the above embodiments according to the technical essence of the invention any simply to repair without departing from technical solution of the present invention content Change, equivalent variations and modification, all of which are still within the scope of the technical scheme of the invention.

Claims (8)

1. a kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative, it is characterised in that：Its general formula is as follows：
Wherein, R1Including phenyl, substituted-phenyl or replace aromatic heterocyclic；R2Including phenyl, substituted-phenyl or replace aromatic heterocyclic； R3Including more than one hydrogen atom, methoxyl group, nitro, methyl, the trifluoromethyl contained on 5,6,7 or 8 of quinazoline Or halogen atom.
2. a kind of Isosorbide-5-Nitrae containing quinazoline according to claim 1-pentadiene-3- ketoxime ether derivative, feature exist In：The substituted-phenyl be on phenyl ring it is o-, m-, pair or aforementioned two upper contain more than one methoxyl group, nitro, methyl, three Methyl fluoride or halogen atom.
3. a kind of Isosorbide-5-Nitrae containing quinazoline according to claim 1-pentadiene-3- ketoxime ether derivative, feature exist In：The substitution aromatic heterocyclic includes furyl, pyridyl group, thienyl, pyrrole radicals, thiazolyl, 2- chloropyridine base or 2- chlorine Thiazolyl.
4. a kind of preparation method of the Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative as described in claim 1, It is characterized in that：With 4- chloro-quinazoline and 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-penta two containing substituent group Alkene -3- ketoxime or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime are that raw material preparation contains quinoline The Isosorbide-5-Nitrae of oxazoline-pentadiene -3- ketoxime ether derivative：
5. a kind of Isosorbide-5-Nitrae containing quinazoline according to claim 4-pentadiene-3- ketoxime ether derivative preparation method, It is characterized in that：1- (4- (substituted benzyloxy) the phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime or 1- (2- (substituted benzyloxy) phenyl) preparation method of -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime is：(1) with acetone, salicylide or 4- hydroxy benzaldehyde is raw material, prepares 2- (hydroxy phenyl)-3- butene-2 -one or 4- (hydroxy phenyl)-3- under alkaline condition Butene-2 -one：(2) with substituted aroma aldehyde, 2- (hydroxy phenyl)- 3- butene-2 -one or 4- (hydroxy phenyl)-3- butene-2 -one are raw material, prepare 1- substituted aryl-5- (4- under alkaline condition Hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- substituted aryl -5- (2- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone：(3) to replace benzyl chloride, 1- substituted aryl -5- (4- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- substituted aryl -5- (2- hydroxy phenyl)-Isosorbide-5-Nitrae-pentadiene -3- Ketone is that raw material prepares 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone：(4) with hydroxylamine hydrochloride, 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone or 1- (2- (substituted benzyloxy) phenyl) -5- take It is that raw material prepares 1- (4- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene-for aryl-Isosorbide-5-Nitrae-pentadiene -3- ketone 3- ketoxime or 1- (2- (substituted benzyloxy) phenyl) -5- substituted aryl-Isosorbide-5-Nitrae-pentadiene -3- ketoxime：
6. a kind of Isosorbide-5-Nitrae containing quinazoline according to claim 4-pentadiene-3- ketoxime ether derivative preparation method, It is characterized in that：The preparation method of the 4- chloro-quinazoline containing substituent group is：With quinazolinone and dichloro containing substituent group Sulfoxide is that raw material prepares the 4- chloro-quinazoline containing substituent group：
7. a kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative as described in claim 1 is used to prepare cucumber The Antiphytoviral pesticide of mosaic virus (CMV) and tobacco mosaic virus disease (TMV).
8. a kind of Isosorbide-5-Nitrae containing quinazoline-pentadiene -3- ketoxime ether derivative as described in claim 1 is used to prepare citrus The disinfectant use in agriculture of ulcer bacteria and rice leaf spot bacteria.
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