CN105418516B - A kind of quinazoline compounds and preparation method thereof - Google Patents
A kind of quinazoline compounds and preparation method thereof Download PDFInfo
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- CN105418516B CN105418516B CN201510957056.0A CN201510957056A CN105418516B CN 105418516 B CN105418516 B CN 105418516B CN 201510957056 A CN201510957056 A CN 201510957056A CN 105418516 B CN105418516 B CN 105418516B
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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
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
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Abstract
The invention discloses a kind of quinazoline compounds, concrete structure formula is：Wherein, R1For aryl, substituted aryl or alkyl；R2For fluorine, chlorine or methyl；R3For aryl, substituted aryl or alkyl.Using amino acid and o-nitroacetophenone compound as the raw material reacted, in recyclable palladium carbon（Pd/C）Under catalytic action, by agitating and heating in a solvent, there can be compatibility well to water and air, you can obtain quinazoline compounds.This method need not add any oxidant, reducing agent, part and alkalinity additive, and reaction condition is gentle, it is easy to accomplish large-scale production.Test result indicates that the yield of the quinazoline compounds of acquisition may be up to 92%.
Description
Technical field
The present invention relates to the field of chemical synthesis, specially a kind of quinazoline compounds and preparation method thereof.
Background technology
Quinazoline compounds are largely present in nature, including large biological molecule, drug molecule and natural products
In, it is a kind of most important organic compound type.Quinazoline compounds are widely used, can be used as agricultural chemicals, spices, with
And the bioactive molecule such as intermediate, synthetic protein of medicine and the monomer of functional material（J. Med. Chem.,
2004, 47, 871; J. Med. Chem., 2006, 49, 6015）.
Due to the importance of quinazoline compound, therefore by region of chemistry and living nature and the widely pass of medical field
Note.But regrettably, traditional method is exactly to pass through oxygen in the presence of strong oxidizer by o-aminoacetophenone and benzylamine etc.
Change condensation can with a step formed quinoline compound (Chem. Commun., 2010, 46, 5244; Chem. Commun.,
2011, 47, 7818–7820;Angew. Chem. Int. Ed. 2012, 51, 8077–8081).These methods will be used
To some excess of oxidant, such as TBHP, these oxidants easily explode, to being brought in actual production process
Some unsafe factors.The problem of simultaneously maximum is that the prepared product out of these methods is often confined to 2- aryl quinoline azoles
Quinoline, just it cannot get for the quinazoline of 2 fat substitutions.Therefore the prospect of its application is leveraged.
Therefore, existing quinazoline compounds and preparation method thereof are improved, greatly improve its application field, have been one
Individual urgent problem.
The content of the invention
In order to overcome above-mentioned deficiency of the prior art, the invention provides one kind with amino acid and ortho-nitroacetophenone class
Initiation material of the compound as reaction, it is easy to accomplish quinazoline compounds of large-scale production and preparation method thereof.Reaction
Mild condition, can be compatible with water and air, it is not necessary to adds any oxidant, reducing agent, part and alkalescence and adds
Add agent, it is only necessary in a solvent agitating and heating can high productivity obtain various substituted quinazoline compounds.
The object of the present invention is achieved like this：
A kind of quinazoline compounds, its concrete structure formula are：
Wherein, R1For aryl, substituted aryl, alkyl；R2For fluorine, chlorine, methyl；R3For aryl, substituted aryl, alkyl.
The preparation method of described quinazoline compounds is：
a）There to be structure（I）Amino acid and structure（II）O-nitroacetophenone compound and palladium carbon catalysis
Agent, disperse in a solvent；
b）To step a）Obtained mixture is 90-140o8-24h is reacted at a temperature of C, is obtained containing structure（III）'s
Quinazoline compounds；
。
The R1For aryl when, described aryl is phenyl or naphthyl；
The R1For substituted aryl when, described substituted aryl be rubigan, p-methylphenyl, 3,4- dimethoxy benzenes
Base, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, p-trifluoromethyl phenyl, to tert-butyl-phenyl, to fluorobenzene
Base, to Ethyl formate phenyl or p-bromophenyl；
The R1For alkyl when, described R1For methyl, n-propyl, the tert-butyl group or cyclohexyl；
The R2For fluorine, chlorine or methyl；
The R3For aryl when, phenyl can be divided.
The R3For substituted aryl when, described substituted aryl be p-fluorophenyl, p-bromophenyl, rubigan, to methyl
Phenyl；
The R3For alkyl when, described alkyl is the tert-butyl group, cyclopenta or n-hexadecyl；
The catalyst is commercially available various palladium carbons（Pd/C）；
The mol ratio of the o-nitroacetophenone compound and amino acid is 1:1—1:3；
The mol ratio of the o-nitroacetophenone compound and palladium carbon is 20:1—200:1；
The solvent of the reaction is acetonitrile, toluene, N,N-dimethylformamide, dimethyl sulfoxide, dioxane or water；
Described reaction temperature is 90-140oC；
The described reaction time is 8-24h.
Positive beneficial effect：Compared with existing the field of chemical synthesis correlation technique, the present invention is realized with adjacent nitre for the first time
Benzoylformaldoxime class compound and Amino acid synthesis quinazoline compounds and preparation method thereof, in the method, it is not necessary to add and appoint
What oxidant, reducing agent, part and alkalinity additive, and reaction condition is gentle, can have to water and air fine
Compatibility, it is easy to accomplish large-scale production.Test result indicates that the yield of the quinazoline compounds of acquisition may be up to 92%.
Brief description of the drawings
Fig. 1 a are the nuclear magnetic resonance of the 4- methyl -2- phenylquinazolines prepared according to the embodiment of the present invention 1,2,3,4,5,6
Hydrogen is composed；
Fig. 1 b are the nuclear magnetic resonance of the 4- methyl -2- phenylquinazolines prepared according to the embodiment of the present invention 1,2,3,4,5,6
Carbon is composed；
Fig. 2 a are the 4- methyl -2- prepared according to the embodiment of the present invention 7（4- chlorphenyls）The hydrogen nuclear magnetic resonance of-quinazoline
Spectrum.
Fig. 2 b are the 4- methyl -2- prepared according to the embodiment of the present invention 7（4- chlorphenyls）The nuclear magnetic resonance carbon of-quinazoline
Spectrum；
Fig. 3 a are the proton nmr spectra of the 2- phenylquinazolines prepared according to the embodiment of the present invention 8；
The carbon-13 nmr spectra of 2- phenylquinazolines prepared by Fig. 3 b according to embodiments of the present invention 8；
Fig. 4 a are the 4- methyl -2- prepared according to the embodiment of the present invention 9（4- fluorophenyls）The hydrogen nuclear magnetic resonance of-quinazoline
Spectrum；
Fig. 4 b are the 4- methyl -2- prepared according to the embodiment of the present invention 9（4- fluorophenyls）The nuclear magnetic resonance carbon of-quinazoline
Spectrum；
Fig. 5 a are the proton nmr spectra of the 2,4- dimethyl quinazolines prepared according to the embodiment of the present invention 10；
Fig. 5 b are the carbon-13 nmr spectra of the 2,4- dimethyl quinazolines prepared according to the embodiment of the present invention 10；
Fig. 6 a are the proton nmr spectra of the 2,4- diphenyl quinazolines prepared according to the embodiment of the present invention 11；
Fig. 6 b are the carbon-13 nmr spectra of the 2,4- diphenyl quinazolines prepared according to the embodiment of the present invention 11；
Fig. 7 a are the proton nmr spectra of the 4,6- dimethyl -2- phenylquinazolines prepared according to the embodiment of the present invention 12；
Fig. 7 b are the carbon-13 nmr spectra of the 4,6- dimethyl -2- phenylquinazolines prepared according to the embodiment of the present invention 12.
Embodiment
Below in conjunction with the accompanying drawings and embodiment, the present invention is described further：
A kind of quinazoline compounds, its concrete structure formula are：
Wherein, R1For aryl, substituted aryl or alkyl；R2For fluorine, chlorine or methyl；R3For aryl, substituted aryl or alkyl.
A kind of preparation method of described quinazoline compounds, comprises the following steps：
a）There to be structure（I）Amino acid and structure（II）Catalytic action of the o-nitroacetophenone compound in palladium carbon
Under, pass through agitating and heating in a solvent, you can obtain with structure（III）Quinazoline compounds of the invention：
Wherein, R1For aryl, substituted aryl or alkyl；R2For fluorine, chlorine or methyl；R3For aryl, substituted aryl or alkyl.
R1For aryl, described aryl is phenyl or naphthyl；Described R1For substituted aryl, described substituted aryl is pair
It is chlorphenyl, p-methylphenyl, 3,4- Dimethoxyphenyls, p-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, right
Trifluoromethyl, to tert-butyl-phenyl, p-fluorophenyl, to Ethyl formate phenyl or p-bromophenyl；Described R1For alkyl, institute
The alkyl stated is methyl, n-propyl, the tert-butyl group or cyclohexyl.
Described R2For fluorine, chlorine or methyl.
Described R3For aryl when, described aryl includes phenyl；Described R3For substituted aryl, described substituted aryl
For p-fluorophenyl, p-bromophenyl, rubigan or p-methylphenyl；Described R3For alkyl, described alkyl include the tert-butyl group,
Cyclopenta or n-hexadecyl.
The mol ratio of the o-nitroacetophenone compound and amino acid is 1:1—1:3.
The o-nitroacetophenone compound is 20 with palladium carbon mol ratio:1—200:1；The solvent of the reaction is second
Nitrile, toluene, N,N-dimethylformamide, dimethyl sulfoxide, dioxane or water.
Described reaction temperature is 90oC—140oC。
The described reaction time is 8-24h.
Embodiment 1
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C to sequentially add mass fraction
4.09 milligrams, 113 milligrams, 1 milliliter 40 milligrams of ortho-nitroacetophenone, phenylglycine toluene make solvent, load onto condensing reflux pipe,
130 under nitrogen protectionoC reacts 24 hours.After reaction terminates, by filtering, the catalyst of recovery, which can be circulated directly next time, to be made
With a small amount of petroleum ether and ethyl acetate after being directly spin-dried for, filtrate（Volume ratio is 30：1）Dissolving, post is crossed by short silicagel column
Separation, obtains 49.5 milligrams of white solids, yield 90%.
As shown in Figure 1a, carbon-13 nmr spectra is as shown in Figure 1 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- phenylquinazolines in collection of illustrative plates.
Embodiment 2
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C to sequentially add mass fraction
13.25 milligrams, 110 milligrams, 1 milliliter 40 milligrams of ortho-nitroacetophenone, phenylglycine toluene make solvent, load onto condensing reflux pipe,
120 under nitrogen protectionoC reacts 24 hours.After reaction terminates, by filtering, the catalyst of recovery, which can be circulated directly next time, to be made
With a small amount of petroleum ether and ethyl acetate after being directly spin-dried for, filtrate（Volume ratio is 30：1）Dissolving, post is crossed by short silicagel column
Separation, obtains 47 milligrams of white solids, yield 85%.
As shown in Figure 1a, carbon-13 nmr spectra is as shown in Figure 1 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- phenylquinazolines in collection of illustrative plates.
Embodiment 3
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C to sequentially add mass fraction
10.25 milligrams, 40 milligrams of ortho-nitroacetophenone, 113 milligrams, 1 milliliter water as solvent of phenylglycine, load onto condensing reflux pipe, nitrogen
100 under gas shieldedoC reacts 24 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time,
Filtrate be directly spin-dried for after with a small amount of petroleum ether and ethyl acetate（Volume ratio is 30：1）Dissolving, post point is crossed by short silicagel column
From obtaining 33 milligrams of white solids, yield 60%.
As shown in Figure 1a, carbon-13 nmr spectra is as shown in Figure 1 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- phenylquinazolines in collection of illustrative plates.
Embodiment 4
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C to sequentially add mass fraction
10.25 milligrams, 40 milligrams of ortho-nitroacetophenone, 98 milligrams, 1 milliliter water as solvent of phenylglycine, load onto condensing reflux pipe, nitrogen
140 under gas shieldedoC reacts 18 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time,
Filtrate be directly spin-dried for after with a small amount of petroleum ether and ethyl acetate（Volume ratio is 30：1）Dissolving, post point is crossed by short silicagel column
From obtaining 51 milligrams of white solids, yield 92%.
As shown in Figure 1a, carbon-13 nmr spectra is as shown in Figure 1 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- phenylquinazolines in collection of illustrative plates.
Embodiment 5
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C 5.5 to sequentially add mass fraction
120 milligrams, 1 milliliter milligram, 40 milligrams of ortho-nitroacetophenone, phenylglycine DMF make solvent, load onto condensing reflux pipe, and nitrogen is protected
120 under shieldoC reacts 24 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time, filtrate
With a small amount of petroleum ether and ethyl acetate after being directly spin-dried for（Volume ratio is 30：1）Dissolving, crosses post separation by short silicagel column, obtains
To 48 milligrams of white solids, yield 88%.
As shown in Figure 1a, carbon-13 nmr spectra is as shown in Figure 1 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- phenylquinazolines in collection of illustrative plates.
Embodiment 6
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C 6.0 to sequentially add mass fraction
110 milligrams, 1 milliliter milligram, 40 milligrams of ortho-nitroacetophenone, phenylglycine dioxane make solvent, load onto condensing reflux pipe, nitrogen
130 under gas shieldedoC reacts 10 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time,
Filtrate be directly spin-dried for after with a small amount of petroleum ether and ethyl acetate（Volume ratio is 30：1）Dissolving, post point is crossed by short silicagel column
From obtaining 46 milligrams of white solids, yield 84%.
As shown in Figure 1a, carbon-13 nmr spectra is as shown in Figure 1 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- phenylquinazolines in collection of illustrative plates.
Embodiment 7
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C to sequentially add mass fraction
4.05 milligrams, 140 milligrams, 1 milliliter 40 milligrams of ortho-nitroacetophenone, p-chlorophenylglycine dioxane make solvent, load onto condensation
Return duct, 130 under nitrogen protectionoC reacts 10 hours.After reaction terminates, by filtering, the catalyst of recovery can be directly next
Recycle, filtrate be directly spin-dried for after with a small amount of petroleum ether and ethyl acetate（Volume ratio is 30：1）Dissolving, passes through short silica gel
Post crosses post separation, obtains 57 milligrams of white solids, yield 89%.
As shown in Figure 2 a, carbon-13 nmr spectra is as shown in Figure 2 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- in collection of illustrative plates（4- chlorphenyls）- quinazoline.
Embodiment 8
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C to sequentially add mass fraction
4.05 milligrams, 38 milligrams of o-nitrobenzaldehyde, 113 milligrams, 1 milliliter water as solvent of phenylglycine, load onto condensing reflux pipe, nitrogen
130 under gas shieldedoC reacts 18 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time,
Filtrate be directly spin-dried for after with a small amount of petroleum ether and ethyl acetate（Volume ratio is 10：1）Dissolving, post point is crossed by short silicagel column
From obtaining 31 milligrams of white solids, yield 60%.
As shown in Figure 3 a, carbon-13 nmr spectra is as shown in Figure 3 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is to 2- phenylquinazolines in collection of illustrative plates.
Embodiment 9
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C 4.5 to sequentially add mass fraction
Milligram, 40 milligrams of ortho-nitroacetophenone, to 113 milligrams, 1 milliliter water as solvent of fluorophenyl glycine, load onto condensing reflux pipe, nitrogen
130 under protectionoC reacts 12 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time, filter
Liquid be directly spin-dried for after with a small amount of petroleum ether and ethyl acetate（Volume ratio is 25：1）Dissolving, post separation is crossed by short silicagel column,
Obtain 53 milligrams of white solids, yield 89%.
As shown in fig. 4 a, carbon-13 nmr spectra is as shown in Figure 4 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4- methyl -2- in collection of illustrative plates（4- fluorophenyls）- quinazoline.
Embodiment 10
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C 4.5 to sequentially add mass fraction
67 milligrams, 1 milliliter milligram, 40 milligrams of ortho-nitroacetophenone, the third glycine toluene make solvent, load onto condensing reflux pipe, and nitrogen is protected
140 under shieldoC reacts 24 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time, filtrate
With a small amount of petroleum ether and ethyl acetate after being directly spin-dried for（Volume ratio is 3：1）Dissolving, crosses post separation by short silicagel column, obtains
24 milligrams of white solids, yield 62%.
As shown in Figure 5 a, carbon-13 nmr spectra is as shown in Figure 5 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 2,4- dimethyl quinazolines in collection of illustrative plates.
Embodiment 11
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C 4.5 to sequentially add mass fraction
113 milligrams, 1 milliliter milligram, 57 milligrams of adjacent nitro benzophenone, phenylglycine toluene make solvent, load onto condensing reflux pipe, nitrogen
140 under protectionoC reacts 18 hours.After reaction terminates, by filtering, the catalyst of recovery can be recycled directly next time, filter
Liquid be directly spin-dried for after with a small amount of petroleum ether and ethyl acetate（Volume ratio is 40：1）Dissolving, post separation is crossed by short silicagel column,
Obtain 55 milligrams of white solids, yield 78%.
As shown in Figure 6 a, carbon-13 nmr spectra is as shown in Figure 6 b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 2,4- diphenyl quinazolines in collection of illustrative plates.
Embodiment 12
In 10 milliliters of Schlenk reaction tubes of a clean dried, it is 10% Pd/C 4.5 to sequentially add mass fraction
113 milligrams, 1 milliliter milligram, 45 milligrams of 5- methyl -2- nitro-acetophenones, phenylglycine water as solvent, load onto condensing reflux pipe,
130 under nitrogen protectionoC reacts 20 hours.After reaction terminates, by filtering, the catalyst of recovery, which can be circulated directly next time, to be made
With a small amount of petroleum ether and ethyl acetate after being directly spin-dried for, filtrate（Volume ratio is 40：1）Dissolving, post is crossed by short silicagel column
Separation, obtains 54 milligrams of white solids, yield 90%.
As shown in Figure 7a, carbon-13 nmr spectra is as shown in Figure 7b for the proton nmr spectra of product manufactured in the present embodiment.From
It has been confirmed that the product obtained is 4,6- dimethyl -2- phenylquinazolines in collection of illustrative plates.
In one embodiment, the preparation method of a kind of quinazoline compounds provided by the invention, wherein by adjacent nitre
Benzoylformaldoxime class compound and amino acid, and catalyst palladium carbon, disperse in a solvent；By obtained reactant mixture by stirring
Heating is mixed, obtains corresponding quinazoline compounds.
In the present invention, described amino acid is under the catalytic action of palladium carbon, can easily occur a depickling and
Dehydrogenation reaction, generation reactive intermediate PdH2, the intermediate can be easy to ortho-nitroacetophenone being reduced into adjacent aminobenzene second
Ketone, twice dehydration condensation reaction then occurs with the imines of generation again, generation intermediate product dihydroquinazoline, the intermediate product can
Again under the catalytic action of palladium carbon through dehydrogenation oxidation, to generate last product quinazoline.It is adjacent in whole catalytic cycle
Nitro-acetophenone is the acceptor of hydrogen, and amino acid is then hydrogen and the donor of carbon dioxide.The advantage of this method clearly, is not required to
Want any oxidant, reducing agent, part and alkalinity additive, you can be smoothed out the reaction.
Above-mentioned is the explanation to the preferred embodiment of the invention, so that those skilled in the art can realize or use this hair
Bright, some modifications to these embodiments are it will be apparent that as defined herein general for those skilled in the art
Principle can be realized in other embodiments without departing from the scope or spirit of the present invention.Therefore, the scope of the invention is not
Limited by above-mentioned specific embodiment.
Claims (6)
1. a kind of preparation method of quinazoline compounds, it is characterised in that its concrete structure formula is：
Wherein, R1For aryl, substituted aryl or alkyl；R2For fluorine, chlorine or methyl；R3For aryl, substituted aryl or alkyl；
The preparation method of described quinazoline compounds, comprises the following steps：
a）There to be structure（I）Amino acid and structure（II）O-nitroacetophenone compound under the catalytic action of palladium carbon,
Pass through agitating and heating in a solvent, you can obtain with structure（III）Quinazoline compounds of the invention：
Wherein, R1For aryl, substituted aryl or alkyl；R2For fluorine, chlorine or methyl；R3For aryl, substituted aryl or alkyl；
Described R1For aryl when, described aryl is phenyl or naphthyl；
Described R1For substituted aryl when, described substituted aryl be rubigan, p-methylphenyl, 3,4- Dimethoxyphenyls,
P-methoxyphenyl, m-methoxyphenyl, o-methoxyphenyl, p-trifluoromethyl phenyl, to tert-butyl-phenyl, p-fluorophenyl,
To Ethyl formate phenyl or p-bromophenyl；Described R1For alkyl when, described alkyl is methyl, n-propyl, the tert-butyl group or ring
Hexyl；
Described R3For aryl when, described aryl is phenyl；Described R3For substituted aryl when, described substituted aryl for pair
Fluorophenyl, p-bromophenyl, rubigan or p-methylphenyl；Described R3For alkyl when, described alkyl be the tert-butyl group, ring penta
Base or n-hexadecyl.
A kind of 2. preparation method of quinazoline compounds according to claim 1, it is characterised in that：The ortho-nitrophenyl
The mol ratio of second ketone compounds and amino acid is 1:1—1:3.
A kind of 3. preparation method of quinazoline compounds according to claim 1, it is characterised in that：The ortho-nitrophenyl
Second ketone compounds are 20 with palladium carbon mol ratio:1—200:1.
A kind of 4. preparation method of quinazoline compounds according to claim 1, it is characterised in that：The reaction it is molten
Agent is acetonitrile, toluene, N,N-dimethylformamide, dimethyl sulfoxide, dioxane or water.
A kind of 5. preparation method of quinazoline compounds according to claim 1, it is characterised in that：Described reaction temperature
Spend for 90oC—140oC。
A kind of 6. preparation method of quinazoline compounds according to claim 1, it is characterised in that：During described reaction
Between be 8-24h.
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| CN111620824B (en) * | 2020-06-24 | 2023-08-22 | 武汉理工大学 | Method for synthesizing quinazoline compound by taking aromatic aldehyde as substrate |
| CN112125900B (en) * | 2020-09-29 | 2022-11-18 | 常州工程职业技术学院 | Synthetic method of isoquinolino-quinazolinone compound |
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