CN105524047A - Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base - Google Patents

Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base Download PDF

Info

Publication number
CN105524047A
CN105524047A CN201510987905.7A CN201510987905A CN105524047A CN 105524047 A CN105524047 A CN 105524047A CN 201510987905 A CN201510987905 A CN 201510987905A CN 105524047 A CN105524047 A CN 105524047A
Authority
CN
China
Prior art keywords
methyl
quinazoline
triazole
dihydro
thioketones
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201510987905.7A
Other languages
Chinese (zh)
Inventor
鲍小平
闫柏任
杨岚
范治江
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guizhou University
Original Assignee
Guizhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guizhou University filed Critical Guizhou University
Priority to CN201510987905.7A priority Critical patent/CN105524047A/en
Publication of CN105524047A publication Critical patent/CN105524047A/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • C07D403/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • C07D403/14—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 three or more hetero rings

Abstract

The invention discloses a preparation method and a bacteriostatic activity of plant pathogen prevention and treatment compounds quinazolinone compounds containing a 1,2,4-triazolethione Schiff base, and concretely relates to compounds represented by general formula (I), and a preparation method thereof. The quinazolinone target compounds containing the 1,2,4-triazolethione Schiff base are synthesized from methyl ortho-aminobenzoate, methanamide, ethyl bromoacetate, hydrazine hydrate, carbon disulfide, potassium hydroxide and aromatic aldehyde through the steps of ring closure, alkylation, hydrazinolysis, salt formation, ring closure and a Schiff base reaction. Compounds F11 and F19 have better Xanthomonas oryzae and Xanthomonas axonopodis pv. citri inhibition activity than a contrast medicate bismerthiazol under 200mg/mL or 100mg/mL; and the synthesized compounds have medium to excellent Sclerotinia scleotiorum inhibition activity, and compounds F4, F5, F6, F8, F9, F17 and F25 have broad-spectrum inhibition activity on six test fungi.

Description

A kind of synthetic method of the quianzolinones containing 1,2,4-triazolinthione schiff bases and application
Technical field
The present invention relates to technical field of chemistry, relate in particular to a kind of containing 1,2, the preparation method of the quianzolinones of 4-triazolinthione schiff bases and to the bacterium such as rice leaf spot bacteria and citrus processing, the purposes that the fungies such as fusarium graminearum, capsicum wilt bacterium, Valsa mali, botrytis cinerea pers, Sclerotinia sclerotiorum and botrytis cinerea are inhibited.
Background technology
Plant diseases is a large factor of restriction agricultural sustainable development, and wherein occur at most with bacterial diseases of plants and plant fungal disease, be difficult to control again, serious threat is to the grain security of the mankind.Nineteen forty-two occurs in bengalee Hemintho-sporum leaf spot of rice plants, result in 2,000,000 people and is died of hunger; The popular of the late blight of potato that 1844-1846 Ireland occurs causes national famine; 1950, the stripe rust of wheat occurring in China for 1964,1990,2002 causes huge financial loss.Conventional sterilants is owing to existing that toxicity is large, drug effect is low and the problem such as resistance; Thus developing green, novel agricultural sterilant that is efficient, highly selective seem particularly urgent.
Quinazolinone analog derivative is that a class has extensive bioactive compound, obtains research and apply widely at medicine and pesticide field, as antitumor, antibacterium, antimycotic and antiviral etc.; 1,2,4-triazole is the important nitrogen heterocyclic ring of a class, and this compounds has excellent biological activity and pharmacological activity, is the focus that Pharmaceutical Chemists are studied to the modification transformation of its structure and bioactivity research always.The molecule fragment of different activities is integrated in the biological activity obviously improving target compound in same a part, if sterilant fluquinconazole is exactly that quinazolinone and 1,2,4-triazole ring are constructed the compound with broad spectrum antibacterial activity obtained in same a part; In addition, schiff base compounds also has good biological activity.
In sum, for finding, there is high reactivity, hypotoxicity, low residue and eco-friendly new type bactericide, the present invention is based on active group splicing principle, by quinazoline-4-one and 1,2,4-triazole schiff bases unit is constructed in same small molecules, one class is novel contains 1 for design and synthesis, 2, the quinazolinone analog derivative of 4-triazolinthione schiff bases, and anti-microbial activity test has been carried out to this compounds, to filtering out the compound had compared with high antibacterial activity, the initiative for new type bactericide is provided certain theoretical reference by this.
Summary of the invention
The object of the invention is to filter out the good compound of anti-microbial activity, is specially the quianzolinones containing 1,2,4-triazolinthione schiff bases providing and have excellent fungicidal activity.
The present invention is a kind of quianzolinones containing 1,2,4-triazolinthione schiff bases, its general structure following ( i):
Wherein: R be phenyl, 2-pyridyl, 3-indyl, 2-naphthyl, 3-methoxyl group-4-hydroxy phenyl, o-methoxyphenyl, to tert-butyl-phenyl, p-methylphenyl, 3-hydroxyl-4-p-methoxy-phenyl, neighbour/rubigan, 2,3-dichlorophenyl, 3,4-dichlorophenyl, neighbour// to fluorophenyl, neighbour// to bromophenyl, neighbour// p-nitrophenyl, 2,3,4-trimethoxyphenyl, 3,4,5-trimethoxyphenyls, 2,4,6-trimethoxyphenyl.
Above-mentioned formula provided by the present invention ( i) in compound to the bacterium such as rice leaf spot bacteria and citrus processing, the fungies such as fusarium graminearum, capsicum wilt bacterium, Valsa mali, botrytis cinerea pers, Sclerotinia sclerotiorum and botrytis cinerea have certain inhibit activities, part of compounds shows excellent inhibit activities, thus can be used as the effective constituent of sterilant.
One of the present invention is containing 1,2, the synthetic method of the quianzolinones of 4-triazolinthione schiff bases, is characterized in that with methyl o-aminobenzoate, methane amide, ethyl bromoacetate, hydrazine hydrate, dithiocarbonic anhydride, potassium hydroxide and aromatic aldehyde for raw material, obtains through following six step synthesis:
The first step: the preparation of quinazoline-4-one
In there-necked flask, add methyl o-aminobenzoate, formic acid and methane amide successively, be warming up to 130-140 DEG C of back flow reaction; Stopped reaction after 6-8h, after being cooled to room temperature, pours into reaction solution in appropriate cold water, has a large amount of white solid to separate out, and continues to stir 0.5h, and suction filtration, washing, oven dry, dehydrated alcohol recrystallization obtains white fluffy solid.
Mol ratio: methyl o-aminobenzoate: methane amide: formic acid=1:5.5:1.3
Temperature of reaction: 130-140 DEG C
Reaction times: 6-8h
Second step: 2-(4-oxoquinazolin-3-(4 h)-Ji) preparation of ethyl acetate
Quinazoline-4-one and salt of wormwood is added in single port bottle, then adding proper amount of acetone stirring makes it be uniformly dispersed, then under room temperature, slowly drip the acetone soln of ethyl bromoacetate, dropwise rear temperature rising reflux reaction 3-4h after stopped reaction, after being cooled to room temperature, reaction solution is poured in frozen water, separate out a large amount of white solid, suction filtration, washing, dries to obtain product.
Mol ratio: quinazoline-4-one: salt of wormwood: ethyl bromoacetate=1:1.5:1.5
Temperature of reaction: 70-90 DEG C
Reaction times: 3-4h
3rd step: 2-(4-oxoquinazolin-3-(4 h)-Ji) preparation of acethydrazide
2-(4-oxoquinazolin-3-(4 is added in single port bottle h)-Ji) ethyl acetate, dehydrated alcohol and hydrazine hydrate, temperature rising reflux reacts, and stopped reaction after 2-3h, is chilled to room temperature, suction filtration, and dehydrated alcohol recrystallization obtains white solid.
Mol ratio: 2-(4-oxoquinazolin-3-(4 h)-Ji) ethyl acetate: hydrazine hydrate=1:5.2
Temperature of reaction: 80-100 DEG C
Reaction times: 2-3h
4th step: 2-(2-(4-oxoquinazolin-3 (4 h)-Ji) ethanoyl) preparation of diazanyl dithiocarbonic acid sylvite
In single port bottle, add potassium hydroxide and dehydrated alcohol, stir after it dissolves completely, slowly add 2-(4-oxoquinazolin-3-(4 h)-Ji) acethydrazide, now system is white opacity liquid; Under room temperature under nitrogen protection, continue reaction after adding dithiocarbonic anhydride, about 0.5h system produces a large amount of white precipitate, stopped reaction after 6h, suction filtration, and absolute ethanol washing for several times, dries to obtain faint yellow solid, directly carries out next step reaction.
Mol ratio: 2-(4-oxoquinazolin-3-(4 h)-Ji) acethydrazide: potassium hydroxide=1:1.7
Temperature of reaction: 20-25 DEG C
Reaction times: 6-8h
5th step: 3-((4-amino-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) preparation of-one
2-(2-(4-oxoquinazolin-3 (4 is added in single port bottle h)-Ji) ethanoyl) diazanyl dithiocarbonic acid sylvite and dehydrated alcohol; hydrazine hydrate is added after stirring; temperature rising reflux reacts; system becomes light green solution from white opacity, stopped reaction when system becomes blackish green clear liquor, adds suitable quantity of water after being cooled to room temperature; about pH to 5.0 is adjusted with 10% hydrochloric acid; now separate out a large amount of white solid, suction filtration, after filter cake recrystallization, obtain product.
Temperature of reaction: 80-100 DEG C
Reaction times: 5-7h
6th step: 3-((4-(replacing benzyl enamino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) preparation of-one
3-((4-amino-5-thioketones-4,5-dihydro-1 is added successively in single port bottle h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one and acetic acid, add aromatic aldehyde after stirring and temperature rising reflux reaction, TLC follows the tracks of reaction stopped reaction after aminotriazole transforms completely, separates out solid, suction filtration, filter cake absolute ethanol washing after being cooled to room temperature.
Mol ratio: 3-((4-amino-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one: aromatic aldehyde=1:1.3
Temperature of reaction: 100-120 DEG C
Reaction times: 3-7h
Above-mentioned steps be applicable to general formula ( i) in the synthesis of all compounds.
Embodiment
Embodiment one: compound 3-((4-(benzyl enamino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis of-one:
(1) preparation of quinazoline-4-one
9.0g (59.54mmol) methyl o-aminobenzoate and 3mL (79.52mmol) formic acid is added successively in 100mL there-necked flask, 13mL (327.3mmol) methane amide is added after stirring, be warming up to 130-140 DEG C of back flow reaction, stopped reaction after 6h, question response liquid cooling is but poured in appropriate cold water afterwards, a large amount of white solid is had to separate out, continue to stir 0.5h, suction filtration, washing, oven dry, dehydrated alcohol recrystallization obtains White Flocculus 4.10g, yield 47.1%.
(2) 2-(4-oxoquinazolin-3-(4 h)-Ji) preparation of ethyl acetate
3.00g (20.53mmol) quinazoline-4-one, 60mL acetone and 3.00g salt of wormwood is added successively at 100mL single port flask, evenly rear acetone (5mL) solution slowly dripped containing 3.85g (22.58mmol) ethyl bromoacetate to be mixed, stopped reaction after temperature rising reflux 3.5h, be poured into after being cooled to room temperature in appropriate frozen water, leave standstill, separate out a large amount of white solid, suction filtration, oven dry, obtain White Flocculus 3.10g, yield 65.0%.
(3) 2-(4-oxoquinazolin-3-(4 h)-Ji) preparation of acethydrazide
2.50g (10.76mmol) 2-(4-oxoquinazolin-3-(4 is added in 100mL there-necked flask h)-Ji) ethyl acetate and 65mL dehydrated alcohol, stir the hydrazine hydrate adding 5mL (80%) after making it dissolve completely, stop after heating reflux reaction 2.5h, be cooled to room temperature, suction filtration, washing with alcohol for several times, dry, obtain white solid 2.16g, yield: 92.0%.
(4) 2-(2-(4-oxoquinazolin-3 (4 h)-Ji) ethanoyl) preparation of diazanyl dithiocarbonic acid sylvite
In 100mL single port flask, add 0.9g (16.04mmol) potassium hydroxide and 60mL dehydrated alcohol, stir after making it dissolve completely and slowly add 2.00g (9.17mmol) 2-(4-oxoquinazolin-3-(4 h)-Ji) acethydrazide; 1.40mL (23.17mmol) dithiocarbonic anhydride is added again after stirring; after room temperature under nitrogen protection lower continuation reaction 0.5h, system produces white solid; react stopped reaction after 6h again; suction filtration; absolute ethanol washing for several times, is dried and is obtained micro-yellow solid 2.0g, yield 65.6%.
(5) 3-((4-amino-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) preparation of-one
1.50g (4.51mmol) 2-(2-(4-oxoquinazolin-3 (4 is added in 100mL single port flask h)-Ji) ethanoyl) diazanyl dithiocarbonic acid sylvite and 50mL dehydrated alcohol; 8mL80% hydrazine hydrate is added after stirring; after temperature rising reflux reaction 1h, solution becomes light green from white opacity; after continuing reaction 6h, system becomes blackish green; be cooled to room temperature after stopped reaction and add suitable quantity of water dilution, adjust about pH to 5.0 with 10% hydrochloric acid, now separate out a large amount of white solid; suction filtration, filter cake DMF/H 2o (1:5, v/v) recrystallization obtains white solid 0.65g, yield 52.5%.
(6) target product 3-((4-(benzyl enamino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) preparation (compound number of-one f1):
150mg (0.55mmol) 3-((4-amino-5-thioketones-4,5-dihydro-1 is added in 25mL single port flask h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one and 10mL acetic acid, 70mg (0.66mmol) phenyl aldehyde is added after stirring, temperature rising reflux reacts, TLC follows the tracks of and reacts stopped reaction to the conversion of raw material aminotriazole, be cooled to room temperature and separate out solid, suction filtration, filter cake absolute ethanol washing several, purify to obtain white solid 65mg, yield 32.6%.m.p.248-249℃; 1HNMR(DMSO- d 6,500MHz) δ:5.43(s,2H),7.55-7.60(m,3H),7.64(t, J=7.45Hz,1H),7.71(d, J=7.50Hz,1H),7.86(t, J=7.45Hz,1H),7.97(d, J=7.00Hz,2H),8.16(d, J=7.00Hz,1H),8.49(s,1H),10.11(s,1H),14.04(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.18,121.90,126.64,127.86,127.92,129.22,129.71,132.48,133.36,135.28,147.50,148.35,148.52,160.51,162.53,163.56.IR(KBr,cm -1) v:3453,3064,2924,1681,1617;Anal.CalcdforC 18H 14N 6OS:C,59.65;H,3.89;N,23.19.Found:C,60.03;H,4.26;N,23.46.MS(ESI)m/z:363.1([M+H] +),385.1([M+Na] +).
Embodiment two: compound 3-((4-((pyridine-2-methene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f2):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with pyridine-2-formaldehyde to be raw material, dark green solid of purifying after reaction to obtain, yield 54.5%m.p.238-240 DEG C. 1HNMR(DMSO- d 6,500MHz) δ:5.47(s,2H),7.57-7.62(m,2H),7.71(d, J=8.00Hz,1H),7.87(t, J=8.00Hz,1H),8.02(t, J=7.60Hz,1H),8.16(t, J=7.60Hz,2H),8.50(s,1H),8.76(d, J=5.00Hz,1H),10.47(s,1H),14.12(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.03,121.91,122.12,126.66,127.06,127.86,127.94,135.30,137.90,147.88,148.34,148.52,150.73,151.77,160.51,160.71,162.60.IR(KBr,cm -1) v:3443,3031,1696,1617;Anal.CalcdforC 17H 13N 7OS:C,56.19;H,3.61;N,26.98.Found:C,56.58;H,4.03;N,27.08.MS(ESI)m/z:364.1([M+H] +),386.1([M+Na] +).
Embodiment three: compound 3-((4-(((1 h-indoles-3-methene) amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f3):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is to take indole-3-formaldehyde as raw material, and purifying after reaction obtains yellow solid, yield 56.4%.m.p.>250℃。 1HNMR(DMSO- d 6,500MHz) δ:5.42(s,2H),7.17(t, J=7.45Hz,1H),7.28(t, J=7.45Hz,1H),7.53(d, J=8.00Hz,1H),7.58(t, J=8.00Hz,1H),7.70(d, J=8.00Hz,1H),7.87(t, J=7.50Hz,1H),8.11-8.17(m,3H),8.47(s,1H),9.79(s,1H),12.07(s,1H),13.82(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.30,110.30,112.90,121.92,122.14,122.64,123.86,124.65,126.65,127.86,127.89,135.25,136.37,137.93,147.25,148.40,148.47,160.52,161.87,162.53.IR(KBr,cm -1) v:3258,3064,2930,1695,1616;Anal.CalcdforC 20H 15N 7OS:C,59.84;H,3.77;N,24.42.Found:C,60.14;H,4.10;N,24.69.MS(ESI)m/z:402.1([M+H] +),424.1([M+Na] +).
Embodiment four: compound 3-((4-((3-methoxyl group-4-hydroxyl benzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f4):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with Vanillin to be raw material, white solid of purifying after reaction to obtain, yield 40.7%.m.p.>250℃。 1HNMR(DMSO- d 6,500MHz) δ:3.87(s,3H),5.39(s,2H),6.91(d, J=8.00Hz,1H),7.28(dd, J 1 =7.45Hz, J 2 =7.45Hz,1H),7.46(d, J=2.50Hz,1H),7.57(t, J=8.00Hz,1H),7.69(d, J=8.00Hz,1H),7.86(t, J=7.00Hz,1H),8.14(d, J=7.00Hz,1H),8.49(s,1H),9.70(s,1H),10.07(s,1H),13.95(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.47,56.16,110.39,116.05,121.91,123.56,125.57,126.62,127.80,127.90,135.27,147.05,148.33,148.72,148.76,152.12,160.52,162.46,164.69.IR(KBr,cm -1) v:3444,3067,2922,1684,1617;Anal.CalcdforC 19H 16N 6O 3S:C,55.87;H,3.95;N,20.58.Found:C,55.98;H,4.31;N,20.77.MS(ESI)m/z:409.1([M+H] +),431.1([M+Na] +).
Embodiment five: compound 3-((4-((naphthalene-2-methene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f5):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with naphthalene-2-formaldehyde for raw material, and purifying after reaction obtains white solid, yield 36.2%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.48(s,2H),7.58(t, J=7.45Hz,1H),7.63-7.72(m,3H),7.86(t, J=7.00Hz,1H),8.03(d, J=7.50Hz,1H),8.07-8.10(m,3H),8.17(d, J=7.50Hz,1H),8.41(s,1H),8.52(s,1H),10.34(s,1H),14.06(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.25,121.92,122.90,126.66,127.73,127.87,127.94,128.47,129.02,129.47,129.52,130.15,133.00,133.09,135.29,135.42,147.59,148.37,148.57,160.54,162.56,162.89.IR(KBr,cm -1) v:3461,3059,2955,1691,1617;Anal.CalcdforC 22H 16N 6OS:C,64.06;H,3.91;N,20.38.Found:C,64.23;H,4.35;N,20.65.MS(ESI)m/z:413.1([M+H] +),435.1([M+Na] +).
Embodiment six: compound 3-((4-((2-methoxybenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f6):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with o-methoxybenzaldehyde to be raw material, has reacted rear purification and has obtained white solid, yield 55.9%.m.p.228-229℃; 1HNMR(DMSO- d 6,500MHz) δ:3.89(s,3H),5.41(s,2H),7.09(t, J=7.45Hz,1H),7.20(d, J=8.00Hz,1H),7.56-7.63(m,2H),7.70(d, J=8.00Hz,1H),7.86(t, J=8.00Hz,1H),7.97(d, J=7.45Hz,1H),8.15(d, J=8.00Hz,1H),8.46(s,1H),10.42(s,1H),13.99(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.19,56.58,112.86,120.53,121.42,121.89,126.64,127.01,127.84,127.92,135.20,135.27,147.60,148.35,148.52,158.49,159.81,160.50,162.38.IR(KBr,cm -1) v:3443,3052,2901,1684,1616;Anal.CalcdforC 19H 16N 6O 2S:C,58.15;H,4.11;N,21.42.Found:C,58.46;H,4.52;N,21.76.MS(ESI)m/z:393.2([M+H] +),415.1([M+Na] +).
Embodiment seven: compound 3-((4-((4-tertiary butyl benzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f7):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with p-t-Butylbenzaldehyde to be raw material, obtains white solid, yield: 52.4% after having reacted.m.p.245-247℃; 1HNMR(DMSO- d 6,500MHz) δ:1.33(s,9H),5.40(s,2H),7.56-7.59(m,3H),7.71(d, J=8.00Hz,1H),7.82-7.88(m,3H),8.15(d, J=7.45Hz,1H),8.48(s,1H),10.00(s,1H),14.01(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:31.37,35.46,41.16,121.89,126.56,126.64,127.85,127.92,129.15,129.77,135.28,147.38,148.35,148.54,156.54,160.51,162.51,163.82.IR(KBr,cm -1) v:3461,3065,2958,1681,1617;Anal.CalcdforC 22H 22N 6OS:C,63.14;H,5.30;N,20.08.Found:C,63.52;H,5.65;N,20.19.MS(ESI)m/z:419.2([M+H] +),441.2([M+Na] +).
Embodiment eight: compound 3-((4-((4-methyl benzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f8):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as the method for embodiment one step (6) and condition synthesis, and difference is with p-tolyl aldehyde to be raw material, obtains white solid, yield 49.5% after having reacted.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:2.34(s,3H),5.34(s,2H),7.31(d, J=7.45Hz,2H),7.51(t, J=7.45Hz,1H),7.64(d, J=8.00Hz,1H),7.72(d, J=8.00Hz,2H),7.80(t, J=7.45Hz,1H),8.08(d, J=7.45Hz,1H),8.40(s,1H),9.94(s,1H),13.94(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:21.82,41.20,121.89,126.64,127.85,127.94,129.25,129.76,130.31,135.29,143.77,147.43,148.34,148.53,160.50,162.50,163.70.IR(KBr,cm -1) v:3461,3067,2920,1684,1617;Anal.CalcdforC 19H 16N 6OS:C,60.62;H,4.28;N,22.33.Found:C,60.88;H,4.59;N,22.56.MS(ESI)m/z:377.1([M+H] +),399.1([M+Na] +).
Embodiment nine: compound 3-((4-((3-hydroxyl-4-methoxybenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f9):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as the method for embodiment one step (6) and condition synthesis, and difference is with 3-hydroxyl-4-methoxybenzaldehyde for raw material, obtains white solid, yield 46.2% after having reacted.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:3.87(s,3H),5.37(s,2H),7.08(d, J=8.00Hz,1H),7.30(dd, J 1 =2.50Hz, J 2 =2.50Hz,1H),7.40(d, J=2.50Hz,1H),7.58(d, J=8.00Hz,1H),7.71(d, J=8.00Hz,1H),7.87(t, J=8.00Hz,1H),8.15(d, J=8.00Hz,1H),8.47(s,1H),9.52(s,1H),9.75(s,1H),13.95(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.10,56.28,112.39,113.84,121.89,123.59,124.99,126.64,127.86,127.92,135.28,147.38,147.56,148.39,148.51,152.63,160.47,162.56,164.54.IR(KBr,cm -1) v:3397,3068,2931,1683,1608;Anal.CalcdforC 19H 16N 6O 3S:C,55.87;H,3.95;N,20.58.Found:C,60.13;H,4.32;N,20.71.MS(ESI)m/z:409.1([M+H] +),431.1([M+Na] +).
Embodiment ten: compound 3-((4-((2-benzyl chloride thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f10):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as the method for embodiment one step (6) and condition synthesis, and difference is with o-chlorobenzaldehyde to be raw material, white solid of purifying after having reacted to obtain, yield 58.9%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.47(s,2H),7.50-7.54(m,1H),7.58(t, J=8.00Hz,1H),7.63-7.66(m,2H),7.71(d, J=8.00Hz,1H),7.86(t, J=8.00Hz,1H),8.16-8.18(m,2H),8.48(s,1H),10.92(s,1H),14.08(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.04,121.90,126.66,127.86,127.96,128.20,128.46,130.29,130.87,134.68,135.30,135.74,147.92,148.34,148.49,156.88,160.51,162.44.IR(KBr,cm -1) v:3443,3064,2908,1683,1613;Anal.CalcdforC 18H 13ClN 6OS:C,54.48;H,3.30;N,21.18.Found:C,54.82;H,3.69;N,21.50.MS(ESI)m/z:397.2([M+H] +),419.0([M+Na] +).
Embodiment 11: compound 3-((4-((4-benzyl chloride thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f11):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as the method for embodiment one step (6) and condition synthesis, and difference is with 4-chloro-benzaldehyde to be raw material, has reacted rear purification and has obtained white solid, yield 54.5%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.42(s,2H),7.58(t, J=7.45Hz,1H),7.64(d, J=8.00Hz,2H),7.71(d, J=8.00Hz,1H),7.86(t, J=7.45Hz,1H),7.93(d, J=8.00Hz,2H),8.15(d, J=7.00Hz,1H),8.47(s,1H),10.15(s,1H),14.06(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.12,121.88,126.65,127.86,127.94,129.88,130.86,131.44,135.29,137.98,147.55,148.34,148.49,160.49,161.95,162.54.IR(KBr,cm -1) v:3441,3065,2861,1683,1617;Anal.CalcdforC 18H 13ClN 6OS:C,54.48;H,3.30;N,21.18.Found:C,54.90;H,3.85;N,21.47.MS(ESI)m/z:397.2([M+H] +),419.0([M+Na] +).
Embodiment 12: compound 3-((4-((2,3-benzyl dichloride thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f12):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with 2,3 dichloro benzaldehyde to be raw material, yellow fluffy solid of purifying after having reacted to obtain, yield 63.6%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.48(s,2H),7.51-7.60(m,2H),7.71(d, J=8.00Hz,1H),7.85(t, J=7.00Hz,1H),7.91(d, J=7.00Hz,1H),8.16(d, J=8.00Hz,2H),8.48(s,1H),11.06(s,1H),14.14(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:40.98,121.89,126.66,126.84,127.86,127.96,129.36,132.86,133.34,133.48,134.57,135.32,148.00,148.32,148.47,155.93,160.51,162.46.IR(KBr,cm -1) v:3451,3057,2986,1677,1617;Anal.CalcdforC 18H 12Cl 2N 6OS:C,50.13;H,2.80;N,19.49.Found:C,50.35;H,3.13;N,19.68.MS(ESI)m/z:431.1([M+H] +),453.1([M+Na] +).
Embodiment 13: compound 3-((4-((3,4-benzyl dichloride thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f13):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with 3,4-dichlorobenzaldehyde for raw material, white solid of purifying after having reacted to obtain, yield 37.7%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.46(s,2H),7.58(t, J=7.50Hz,1H),7.71(d, J=7.45Hz,1H),7.90-7.82(m,3H),8.16(d, J=7.00Hz,1H),8.18(d, J=7.00Hz,1H),8.47(s,1H),10.26(s,1H),14.09(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.11,121.87,126.64,127.87,127.96,129.27,130.30,131.99,132.76,133.27,135.29,135.69,147.63,148.31,148.46,159.95,160.50,162.56.IR(KBr,cm -1) v:3421,3061,1689,1614;Anal.CalcdforC 18H 12Cl 2N 6OS:C,50.13;H,2.80;N,19.49.Found:C,50.45;H,3.09;N,19.76.MS(ESI)m/z:431.1([M+H] +),453.1([M+Na] +).
Embodiment 14: compound 3-((4-((2-fluorine benzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f14):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with o fluorobenzaldehyde to be raw material, has reacted rear purification and has obtained white solid, yield 54.4%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.44(s,2H),7.38-7.44(m,2H),7.58(t, J=8.00Hz,1H),7.67-7.72(m,2H),7.86(t, J=8.00Hz,1H),8.08(t, J=7.00Hz,1H),8.16(d, J=7.00Hz,1H),8.48(s,1H),10.61(s,1H),14.06(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.05,116.95,117.10,120.27,120.34,121.90,125.84,126.65,127.80,127.86,127.94,135.30,135.60,135.64,147.77,148.34,148.51,154.92,160.51,161.32,162.44,163.30.IR(KBr,cm -1) v:3420,3065,2914,1681,1613;Anal.CalcdforC 18H 13FN 6OS:C,56.83;H,3.44;N,22.09.Found:C,57.20;H,3.91;N,22.46.MS(ESI)m/z:381.1([M+H] +),403.1([M+Na] +).
Embodiment 15: compound 3-((4-((3-fluorine benzyl thiazolinyl) is amino)-5-sulphur subunit-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f15):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with a fluorobenzaldehyde for raw material, white solid of purifying after having reacted to obtain, yield 39.7%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.45(s,2H),7.49(t, J=7.45Hz,1H),7.56-7.62(m,2H),7.70-7.78(m,3H),7.86(t, J=7.00Hz,1H),8.15(d, J=7.00Hz,1H),8.48(s,1H),10.23(s,1H),14.07(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.14,114.62,114.80,120.08,120.24,121.88,126.08,126.63,127.86,127.94,131.86,131.93,134.94,134.99,135.30,147.59,148.33,148.50,160.51,161.41,161.92,162.54,163.88.IR(KBr,cm -1) v:3447,3064,2986,1684,1613;Anal.CalcdforC 18H 13FN 6OS:C,56.83;H,3.44;N,22.09.Found:C,57.15;H,3.57;N,22.43.MS(ESI)m/z:381.1([M+H] +),403.1([M+Na] +).
Embodiment 16: compound 3-((4-((4-fluorine benzyl thiazolinyl) is amino)-5-sulphur subunit-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f16):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with p-Fluorobenzenecarboxaldehyde to be raw material, white solid of purifying after having reacted to obtain, yield 68.7%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.42(s,2H),7.41(t, J=8.00Hz,2H),7.57(t, J=8.00Hz,1H),7.70(d, J=7.00Hz,1H),7.86(t, J=7.00Hz,1H),7.98(t, J=8.00Hz,2H),8.14(d, J=8.00Hz,1H),8.47(s,1H),10.82(s,1H),14.00(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.15,116.87,117.04,121.88,126.64,127.86,127.94,129.12,131.79,131.86,135.30,147.47,148.34,148.51,160.49,162.51,162.56,164.28,166.28.IR(KBr,cm -1) v:3446,3068,2913,1689,1617;Anal.CalcdforC 18H 13FN 6OS:C,56.83;H,3.44;N,22.09.Found:C,57.01;H,3.68;N,22.33.MS(ESI)m/z:381.1([M+H] +),403.1([M+Na] +).
Embodiment 17: compound 3-((4-((2-bromobenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f17):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with o-bromobenzaldehye to be raw material, white solid of purifying after having reacted to obtain, yield 30.7%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.47(s,2H),7.54-7.60(m,3H),7.71(d, J=8.00Hz,1H),7.80-7.82(m,1H),7.86(t, J=8.00Hz,1H),8.15-8.17(m,2H),8.48(s,1H),10.91(s,1H),14.08(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.04,121.92,126.04,126.66,127.86,127.94,128.58,128.89,131.94,134.14,134.78,135.27,147.93,148.36,148.46,159.03,160.51,162.49.IR(KBr,cm -1) v:3454,3062,2906,1682,1612;Anal.CalcdforC 18H 13BrN 6OS:C,48.99;H,2.97;N,19.04.Found:C,49.16;H,2.51;N,19.37.MS(ESI)m/z:441.1([M+H] +),463.1([M+Na] +).
Embodiment 18: compound 3-((4-((3-bromobenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f18):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with 3-bromobenzaldehyde to be raw material, white solid of purifying after having reacted to obtain, yield 56.6%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.45(s,2H),7.52(t, J=8.00Hz,1H),7.58(t, J=8.00Hz,1H),7.71(d, J=8.00Hz,1H),7.81-7.89(m,3H),8.12(s,1H),8.16(d, J=8.00Hz,1H),8.47(s,1H),10.19(s,1H),14.07(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.14,121.88,123.01,126.65,127.88,127.94,128.65,130.92,131.84,134.87,135.29,135.81,147.58,148.92,148.47,160.50,161.33,162.56.IR(KBr,cm -1) v:3447,3057,2918,1684,1612;Anal.CalcdforC 18H 13BrN 6OS:C,48.99;H,2.97;N,19.04.Found:C,49.26;H,3.36;N,19.29.MS(ESI)m/z:441.1([M+H] +),463.1([M+Na] +).
Embodiment 19: compound 3-((4-((4-bromobenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f19):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with p-bromobenzaldehyde to be raw material, white solid of purifying after having reacted to obtain, yield 51.1%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.43(s,2H),7.58(t, J=8.00Hz,1H),7.71(d, J=8.00Hz,1H),7.78(d, J=8.00Hz,2H),7.85-7.88(m,3H),8.16(d, J=8.00Hz,1H),8.48(s,1H),10.17(s,1H),14.06(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.12,121.88,126.65,127.03,127.86,127.94,130.98,131.76,132.81,135.29,147.56,148.33,148.48,160.49,161.99,162.54.IR(KBr,cm -1) v:3431,3067,2856,1684,1617;Anal.CalcdforC 18H 13BrN 6OS:C,48.99;H,2.97;N,19.04.Found:C,49.36;H,3.43;N,19.44.MS(ESI)m/z:441.1([M+H] +),463.1([M+Na] +).
Embodiment 20: compound 3-((4-((2-nitrobenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f20):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with Ortho Nitro Benzaldehyde to be raw material, light yellow solid of purifying after having reacted to obtain, yield 50.5%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.46(s,2H),7.58(t, J=7.45Hz,1H),7.71(d, J=8.00Hz,1H),7.85-7.88(m,2H),7.92(t, J=7.40Hz,1H),8.16(d, J=7.00Hz,1H),8.20(d, J=7.00Hz,2H),8.48(s,1H),11.09(s,1H),14.12(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.03,121.87,125.50,126.65,127.43,127.86,127.96,129.54,133.54,134.66,135.30,148.12,148.34,148.47,149.22,155.99,160.51,162.66.IR(KBr,cm -1) v:3442,3062,2860,1679,1613;Anal.CalcdforC 18H 13N 7O 3S:C,53.07;H,3.22;N,24.07.Found:C,53.43;H,3.60;N,24.35.MS(ESI)m/z:408.1([M+H] +),430.1([M+Na] +).
Embodiment 21: compound 3-((4-((3-nitrobenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f21):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with m-nitrobenzaldehyde to be raw material, white solid of purifying after having reacted to obtain, yield 56.3%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.47(s,2H),7.57(t, J=8.00Hz,1H),7.70(d, J=8.00Hz,1H),7.86(t, J=8.00Hz,2H),8.15(d, J=7.00Hz,1H),8.35(d, J=8.00Hz,1H),8.45(d, J=8.00Hz,1H),8.48(s,1H),8.72(s,1H),10.37(s,1H),14.12(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.13,121.87,123.30,126.63,127.42,127.87,127.94,131.41,134.25,135.22,135.29,147.65,148.33,148.47,148.88,160.50,160.94,162.64.IR(KBr,cm -1) v:3417,3065,2978,1684,1612;Anal.CalcdforC 18H 13N 7O 3S:C,53.07;H,3.22;N,24.07.Found:C,53.52;H,3.45;N,24.48.MS(ESI)m/z:408.1([M+H] +),430.1([M+Na] +).
Embodiment 22: compound 3-((4-((4-nitrobenzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f22):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with paranitrobenzaldehyde to be raw material, yellow solid of purifying after having reacted to obtain, yield 73.4%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:5.47(s,2H),7.58(t, J=7.50Hz,1H),7.71(d, J=8.00Hz,1H),7.87(t, J=7.45Hz,1H),8.15-8.20(m,3H),8.38(d, J=8.00Hz,2H),8.49(s,1H),10.49(s,1H),14.13(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.07,121.87,124.75,126.66,127.87,127.97,130.28,135.33,138.52,147.81,148.33,148.47,150.09,159.76,160.50,162.61.IR(KBr,cm -1) v:3442,3063,2925,1688,1616;Anal.CalcdforC 18H 13N 7O 3S:C,53.07;H,3.22;N,24.07.Found:C,53.45;H,3.63;N,24.40.MS(ESI)m/z:408.1([M+H] +),430.1([M+Na] +).
Embodiment 23: compound 3-((4-((2,3,4-trimethoxy benzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f23):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with 2,3,4-TMB for raw material, light yellow solid of purifying after having reacted to obtain, yield 47.6%.m.p.240-242℃; 1HNMR(DMSO- d 6,500MHz) δ:3.80(s,3H),3.88(s,3H),3.92(s,3H),5.40(s,2H),7.02(d, J=8.00Hz,1H),7.58(t, J=8.00Hz,1H),7.71(d, J=8.00Hz,1H),7.77(d, J=8.00Hz,1H),7.86(t, J=7.50Hz,1H),8.15(d, J=8.00Hz,1H),8.47(s,1H),10.18(s,1H),14.00(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.18,56.79,61.13,62.88,109.53,118.51,121.90,122.38,126.64,127.84,127.91,135.26,142.09,147.42,148.35,148.53,154.88,158.08,159.16,160.50,162.40.IR(KBr,cm -1) v:3447,3062,2942,1658,1612;Anal.CalcdforC 21H 20N 6O 4S:C,55.74;H,4.46;N,18.57.Found:C,60.03;H,4.81;N,18.96.MS(ESI)m/z:453.1([M+H] +),475.2([M+Na] +).
Embodiment 24: compound 3-((4-((3,4,5-trimethoxy benzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f24):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with 3,4,5-Trimethoxybenzaldehyde to be raw material, white solid of purifying after having reacted to obtain, yield 33.7%.m.p.>250℃; 1HNMR(DMSO- d 6,500MHz) δ:3.76(s,3H),3.87(s,6H),5.42(s,2H),7.22(s,2H),7.57(t, J=8.00Hz,1H),7.68(d, J=8.00Hz,1H),7.85(t, J=8.00Hz,1H),8.14(d, J=7.00Hz,1H),8.50(s,1H),9.91(s,1H),14.02(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.53,56.64,60.78,106.54,121.90,126.61,127.73,127.79,127.91,135.30,141.85,147.12,148.31,148.74,153.80,160.54,162.44,163.65.IR(KBr,cm -1) v:3440,3064,2939,1686,1611;Anal.CalcdforC 21H 20N 6O 4S:C,55.74;H,4.46;N,18.57.Found:C,55.88;H,4.74;N,18.66.MS(ESI)m/z:453.1([M+H] +),475.2([M+Na] +).
Embodiment 25: compound 3-((4-((2,4,6-trimethoxy benzyl thiazolinyl) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) synthesis (compound number of-one f25):
Step (1)-(5) are with embodiment one step (1)-(5);
Step (6) is as embodiment one step (6) method and condition synthesis, and difference is with 2,4,6-TMB for raw material, White Flocculus of purifying after completion of the reaction to obtain, yield 49.3%.m.p.221-224℃; 1HNMR(DMSO- d 6,500MHz) δ:3.85(s,3H),3.90(s,6H),5.29(s,2H),6.34(s,2H),7.57(t, J=8.00Hz,1H),7.69(d, J=8.00Hz,1H),7.85(t, J=7.50Hz,1H),8.14(d, J=7.50Hz,1H),8.50(s,1H),9.88(s,1H),13.84(s,1H); 13CNMR(DMSO- d 6,125MHz) δ:41.18,56.29,56.80,91.67,102.22,121.92,126.61,127.79,135.18,147.08,148.36,148.73,160.49,160.58,162.13,162.42,165.60.IR(KBr,cm -1) v:3441,3044,2930,1688,1611;Anal.CalcdforC 21H 20N 6O 4S:C,55.74;H,4.46;N,18.57.Found:C,55.92;H,4.93;N,18.86.MS(ESI)m/z:453.1([M+H] +),475.2([M+Na] +).
As can be seen from bacteriostatic activity test experiments below, with sterilant epoxiconazole and bismerthiazol for positive control medicament, formula of the present invention ( i) represented by compound to the bacterium such as rice leaf spot bacteria and citrus processing, the fungies such as fusarium graminearum, capsicum wilt bacterium, Valsa mali, botrytis cinerea pers, Sclerotinia sclerotiorum and botrytis cinerea all show certain or excellent inhibit activities, as compound f11with f19200 and 100 μunder g/mL concentration, all 100% is reached to the inhibiting rate of rice leaf spot bacteria and citrus processing; On the other hand, in six kinds of test fungal, this compounds shows the most excellent inhibit activities to Sclerotinia sclerotiorum.
Embodiment 26: anti-fungal activity of plant pathogenic experiment (suppressing mycelial growth rate method)
Adopt and suppress mycelial growth rate method, with formula ( i) compound carried out anti-mycotic activity test to fusarium graminearum, capsicum wilt bacterium, Valsa mali, botrytis cinerea pers, Sclerotinia sclerotiorum and botrytis cinerea, with sterilant epoxiconazole for positive control medicament, sample concentration is 50 μg/mL.
With the tested medicament of electronic balance precise 5mg, dissolve with 1mLDMSO, add 9mL0.1% tween 20 solution and be settled to 10mL, joined by the medicament prepared in 90mLPDA substratum (40-50 DEG C), fully shake up, being namely made into concentration is 50 μg/mL sample, is poured in the culture dish after sterilizing, arranges three repetitions, arranges blank simultaneously.With tested bacterial classification for screening object, with 4mm punch tool, some bacterium cakes are made in normal for growth bacterium colony punching for subsequent use, with inoculating needle bacterium cake moved and receive dull and stereotyped central authorities, every ware connects a bacterium cake, be placed in 27 DEG C of constant incubators and cultivate 24-72 hour, measure bacterial plaque diameter, each bacterium colony measures 2 times by right-angled intersection method.Represent the size of bacterium colony with its mean number, bacteriostasis rate calculation formula is as follows:
Bacteriostasis rate=(contrast bacterial plaque diameter-sample bacterial plaque diameter)/(contrast bacterial plaque diameter-0.4) × 100%
Table 1 be formula ( i) in compound to the Antibacterial Activity result of subject plant fungi.
Embodiment 27: anti-plant pathogenetic bacteria activity experiment (opacity method)
Adopting opacity method, with rice leaf spot bacteria and citrus processing for tested object, with commercialization sterilant bismerthiazol for positive control medicament, is 200 and 100 at sample concentration μunder g/mL concentration, to formula ( i) compound carried out in vitro Antibacterial activity screening.
It is 200 and 100 that medicament and contrast medicament are configured to concentration respectively μg/mL, and it is joined respectively in the test tube of NB liquid nutrient medium, measure OD value, this value is aseptic culture medium OD value.Then access tested bacterial classification, at 28 DEG C, 180rpm constant-temperature table shaking culture 24-48h, the bacterium liquid of each concentration is being divided
Light photometer measures OD value, this value is the OD value containing bacterium culture medium.
Correction OD value=containing bacterium culture medium OD value-aseptic culture medium OD value
Bacteriostasis rate=(after correcting the rear sample cultivation base OD value of control medium OD value-correction)/correct rear control medium OD value × 100%
Table 2 be formula ( i) in compound to tested vegetative bacteria inhibit activities measurement result.
When compound of the present invention uses as sterilant, can by carrier that compound of the present invention and other plant protection allow and mixing diluents, be modulated into normally used various formulation whereby, as mixture, granule, aqueous emulsion etc. use, also can be as used in combination in sterilant, Insecticides (tech) & Herbicides (tech), plant-growth regulator etc. or simultaneously and use with other agricultural chemicals.

Claims (9)

1. the quianzolinones containing 1,2,4-triazolinthione schiff bases, is characterized in that: its general formula be following formula ( i):
Wherein: R be phenyl, 2-pyridyl, 3-indyl, 3-methoxyl group-4-hydroxy phenyl, 2-naphthyl, o-methoxyphenyl, to tert-butyl-phenyl, p-methylphenyl, 3-hydroxyl-4-p-methoxy-phenyl, neighbour/rubigan, 2,3-dichlorophenyl, 3,4-dichlorophenyl, neighbour// to fluorophenyl, neighbour// to bromophenyl, neighbour// p-nitrophenyl, 2,3,4-trimethoxyphenyl, 3,4,5-trimethoxyphenyls, 2,4,6-trimethoxyphenyl.
2. compound according to claim 1, is characterized in that: the compound of partial synthesis is as follows:
f1: 3-((4-(benzyl enamino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f2: 3-((4-((pyridine-2-methylene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f3: 3-((4-(((1 h-indoles-3-methylene) amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f4: 3-((4-((3-methoxyl group-4-hydroxyl benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f5: 3-((4-((naphthalene-2-methylene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f6: 3-((4-((2-methoxybenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f7: 3-((4-((4-tertiary butyl benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f8: 3-((4-((4-methyl benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f9: 3-((4-((3-hydroxyl-4-methoxybenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f10: 3-((4-((2-benzyl chloride alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f11: 3-((4-((4-benzyl chloride alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f12: 3-((4-((2,3-benzyl dichloride alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f13: 3-((4-((3,4-benzyl dichloride alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f14: 3-((4-((2-fluorine benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f15: 3-((4-((3-fluorine benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f16: 3-((4-((4-fluorine benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f17: 3-((4-((2-bromobenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f18: 3-((4-((3-bromobenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f19: 3-((4-((4-bromobenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f20: 3-((4-((2-nitrobenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f21: 3-((4-((3-nitrobenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f22: 3-((4-((4-nitrobenzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f23: 3-((4-((2,3,4-trimethoxy benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f24: 3-((4-((3,4,5-trimethoxy benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one;
f25: 3-((4-((2,4,6-trimethoxy benzyl alkene) is amino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one.
3. according to described in claim 1 or 2 containing 1,2, the synthetic method of the quianzolinones of 4-triazolinthione schiff bases, it is characterized in that: with methyl o-aminobenzoate, methane amide, ethyl bromoacetate, hydrazine hydrate, dithiocarbonic anhydride, potassium hydroxide and aromatic aldehyde for raw material, obtain through following six step synthesis:
。
4. the synthetic method of the quianzolinones containing 1,2,4-triazolinthione schiff bases as claimed in claim 1 or 2, is characterized in that: synthesis step and processing condition are:
The first step: the preparation of quinazoline-4-one
Add methyl o-aminobenzoate, formic acid and methane amide successively in there-necked flask, be warming up to 130-140 DEG C of back flow reaction; Stopped reaction after 6-8h, after being cooled to room temperature, pours into reaction solution in appropriate cold water, has a large amount of white solid to separate out, and continues to stir 0.5h, suction filtration, washing, oven dry, and dehydrated alcohol recrystallization obtains white fluffy solid;
Mol ratio: methyl o-aminobenzoate: methane amide: formic acid=1:5.5:1.3
Temperature of reaction: 130-140 DEG C
Reaction times: 6-8h
Second step: 2-(4-oxoquinazolin-3-(4 h)-Ji) preparation of ethyl acetate
Quinazoline-4-one and salt of wormwood is added in single port bottle, then adding proper amount of acetone stirring makes it be uniformly dispersed, the acetone soln of ethyl bromoacetate is slowly dripped under room temperature, dropwise rear temperature rising reflux reaction 3-4h after stopped reaction, after being cooled to room temperature, reaction solution is poured in frozen water, separate out a large amount of white solid, suction filtration, washing, dries to obtain product;
Mol ratio: quinazoline-4-one: salt of wormwood: ethyl bromoacetate=1:1.5:1.5
Temperature of reaction: 70-90 DEG C
Reaction times: 3-4h
3rd step: 2-(4-oxoquinazolin-3-(4 h)-Ji) preparation of acethydrazide
2-(4-oxoquinazolin-3-(4 is added in single port bottle h)-Ji) ethyl acetate, dehydrated alcohol and hydrazine hydrate, temperature rising reflux reacts, and stopped reaction after 2-3h, is chilled to room temperature, suction filtration, and dehydrated alcohol recrystallization obtains white solid;
Mol ratio: 2-(4-oxoquinazolin-3-(4 h)-Ji) ethyl acetate: hydrazine hydrate=1:5.2
Temperature of reaction: 80-100 DEG C
Reaction times: 2-3h
4th step: 2-(2-(4-oxoquinazolin-3 (4 h)-Ji) ethanoyl) preparation of diazanyl dithiocarbonic acid sylvite
Add potassium hydroxide and dehydrated alcohol in single port bottle, stir after it dissolves completely, slowly add 2-(4-oxoquinazolin-3-(4 h)-Ji) acethydrazide, now system is white opacity liquid; Under room temperature under nitrogen protection, continue reaction after adding dithiocarbonic anhydride, about 0.5h system produces a large amount of white precipitate, stopped reaction after 6h, suction filtration, and absolute ethanol washing for several times, dries to obtain faint yellow solid, directly carries out next step reaction;
Mol ratio: 2-(4-oxoquinazolin-3-(4 h)-Ji) acethydrazide: potassium hydroxide=1:1.7
Temperature of reaction: 20-25 DEG C
Reaction times: 6-8h
5th step: 3-((4-amino-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) preparation of-one
2-(2-(4-oxoquinazolin-3 (4 is added in single port bottle h)-Ji) ethanoyl) diazanyl dithiocarbonic acid sylvite and dehydrated alcohol, hydrazine hydrate is added and temperature rising reflux reaction after stirring, system becomes light green solution from white opacity, stopped reaction when system becomes blackish green clear liquor again, add suitable quantity of water after being cooled to room temperature, adjust about pH to 5.0 with 10% hydrochloric acid, now separate out a large amount of white solid, suction filtration, obtains product after filter cake recrystallization;
Temperature of reaction: 80-100 DEG C
Reaction times: 5-7h
6th step: 3-((4-(replacing benzyl enamino)-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h) preparation of-one
3-((4-amino-5-thioketones-4,5-dihydro-1 is added successively in single port bottle h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3 h)-one and acetic acid, add aromatic aldehyde after stirring and temperature rising reflux reaction, TLC follows the tracks of reaction stopped reaction after aminotriazole transforms completely; Solid is separated out, suction filtration, filter cake absolute ethanol washing after being cooled to room temperature;
Mol ratio: 3-((4-amino-5-thioketones-4,5-dihydro-1 h-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one: aromatic aldehyde=1:1.3
Temperature of reaction: 100-120 DEG C
Reaction times: 3-7h
Above-mentioned steps be applicable to general formula ( i) in the synthesis of all compounds.
5. the application of a kind of quianzolinones containing 1,2,4-triazolinthione schiff bases as claimed in claim 1 or 2, is characterized in that: the medicine and the medicament that are used as preparation control phytopathogen.
6. as claimed in claim 1 or 2 a kind of containing 1,2, the application of the quianzolinones of 4-triazolinthione schiff bases, it is characterized in that: as preparing water prevention rice bacterial leaf spot pathogenic bacteria and citrus processing bacterium, the medicine of fusarium graminearum, capsicum wilt bacterium, Valsa mali, botrytis cinerea pers, Sclerotinia sclerotiorum and botrytis cinerea fungi and medicament.
7. the application of a kind of quianzolinones containing 1,2,4-triazolinthione schiff bases as claimed in claim 2, is characterized in that: compound f11with f19rice leaf spot bacteria and citrus processing are all shown and comparatively contrasts the more excellent inhibit activities of medicament bismerthiazol.
8. the application of a kind of quianzolinones containing 1,2,4-triazolinthione schiff bases as claimed in claim 2, is characterized in that: inhibit activities by the time excellent during this synthesized compounds shows sclerotinia rot of colza fungal pathogens.
9. the application of a kind of quianzolinones containing 1,2,4-triazolinthione schiff bases as claimed in claim 2, is characterized in that: compound f4, f5, f6, f8, f9, f17with f25show the anti-mycotic activity compared with wide spectrum.
CN201510987905.7A 2015-12-27 2015-12-27 Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base Pending CN105524047A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510987905.7A CN105524047A (en) 2015-12-27 2015-12-27 Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510987905.7A CN105524047A (en) 2015-12-27 2015-12-27 Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base

Publications (1)

Publication Number Publication Date
CN105524047A true CN105524047A (en) 2016-04-27

Family

ID=55766618

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510987905.7A Pending CN105524047A (en) 2015-12-27 2015-12-27 Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base

Country Status (1)

Country Link
CN (1) CN105524047A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108358896A (en) * 2018-04-18 2018-08-03 贵州大学 A kind of compound and preparation method being used to prepare prevention crop pathogenic bacteria drug
CN109265448A (en) * 2018-11-15 2019-01-25 三峡大学 TMSIM N imidazole acetyldihydro quinoxaline derivatives of the one kind containing tert-butyl, synthetic method and its as the application on fungicide
CN110447651A (en) * 2019-09-18 2019-11-15 兰州大学 A kind of quianzolinones and the application in preparation or prevention and treatment agricultural plant disease

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104829598A (en) * 2015-05-27 2015-08-12 贵州大学 Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104829598A (en) * 2015-05-27 2015-08-12 贵州大学 Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
EL-SAMII等: "Design, synthesis and molecular modeling study of quinazolinones with potential anti-inflammatory activity", 《BIOSCIENCES, BIOTECHNOLOGY RESEARCH ASIA》 *
闫柏任，吕新阳，杜欢，鲍小平: "新型含4-苯基-5-硫亚基-1,2,4-三唑曼尼希碱的喹唑啉酮类衍生物的设计合成及其生物活性研究", 《有机化学》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108358896A (en) * 2018-04-18 2018-08-03 贵州大学 A kind of compound and preparation method being used to prepare prevention crop pathogenic bacteria drug
CN109265448A (en) * 2018-11-15 2019-01-25 三峡大学 TMSIM N imidazole acetyldihydro quinoxaline derivatives of the one kind containing tert-butyl, synthetic method and its as the application on fungicide
CN109265448B (en) * 2018-11-15 2020-09-15 三峡大学 Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide
CN110447651A (en) * 2019-09-18 2019-11-15 兰州大学 A kind of quianzolinones and the application in preparation or prevention and treatment agricultural plant disease

Similar Documents

Publication Publication Date Title
CN104829598A (en) Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound
Sridhar et al. Synthesis and antibacterial screening of hydrazones, Schiff and Mannich bases of isatin derivatives
CN113336720B (en) Guanidyl thiazole compound and preparation method and application thereof
He et al. Synthesis, characterization and crystal structures of vanadium (V) complexes derived from halido-substituted tridentate hydrazone compounds with antimicrobial activity
CN105524047A (en) Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base
CN104829608B (en) A kind of cumarin thiazole indolone type compound and its preparation method and purposes
CN112645897A (en) Thiazole derivative and preparation method and application thereof
CN102070556B (en) 5-benzyl-4-alkyl-2-aminothiazole as well as preparation and application of 5-benzyl-4-alkyl-2-aminothiazole
AU2018384770B2 (en) Pyrazole amide compound and application thereof, and fungicide
CN108358896A (en) A kind of compound and preparation method being used to prepare prevention crop pathogenic bacteria drug
CN108605949A (en) A kind of application of the class diphenyl ethene compounds as fungicide containing thiazole ring
CN115322147A (en) Benzene sulfonamide derivative, preparation method and application
CN103880836A (en) 1-substituted-5-amino-4-pyrazol di-1,3,4-diazole sulfur ether or 1,3,4-diazole sulfone derivatives and application thereof
CN106317025B (en) A kind of triazole class compounds containing trifluoromethyl pyrazol and preparation method thereof and its application
EP3253750B1 (en) Novel flavone based egfr inhibitors and process for preparation thereof
Cicekli et al. Schiff bases of 3-[(4-amino-5-thioxo-1, 2, 4-triazole-3-yl) methyl]-2 (3H)-benzoxazolone derivatives: Synthesis and biological activity
CN115521267B (en) Benzenesulfonamide compound containing N-5-chloroisoxazole malonate structure, preparation method and application
CN103224470A (en) Preparation method and application of quinoxaline-6-phenylhydrazone derivants
CN104817552A (en) Preparing method of (E)-N'-arylmethylene-4-(coumarin-3-yl)thiazole-2-hydrazide compound and its application
CN106117180B (en) A kind of substituted pyridine connection pyrazoles bishydrazide compounds and its preparation method and application
CN103980209B (en) A kind of 4-N-replaces-5-chloro-quinazoline compounds and preparation method and application
Sethi et al. Synthesis., Characterization and Antibacterial Activity of Cobalt Complex of 2-Pyrazoline with Pyridinyl Moiety
WO2009005381A1 (en) The novel chiral triazole derivatives, synthesis and application thereof
Kumar et al. Synthesis of benzo [g] quinoxaline-5, 10-dione based pyridine derivatives and their antimycobacterial activity
CN103554026A (en) 3-trifluoromethyl-4-formyl pyrazole compounds

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20160427