CN103864702A - Method for preparing quinazolinone in water phase through microwave catalysis - Google Patents
Method for preparing quinazolinone in water phase through microwave catalysis Download PDFInfo
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- CN103864702A CN103864702A CN201410068513.6A CN201410068513A CN103864702A CN 103864702 A CN103864702 A CN 103864702A CN 201410068513 A CN201410068513 A CN 201410068513A CN 103864702 A CN103864702 A CN 103864702A
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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
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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
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
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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
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
Abstract
The invention discloses a method for preparing quinazolinone in water phase through microwave catalysis. The method comprises the step: by utilizing a water-soluble coordination compound (such as 8-hydroxyquinoline) as a catalyst, carrying out high-efficiency microwave catalysis on the reaction of 2-halogenated benzaldehyde and amidine salts in pure water phase. The invention relates to a method for preparing a quinazolinone compound, which is environment-friendly, simple and convenient to operate, safe and low-cost, and high-efficiency. Compared with the prior art, the method not only can be applicable to a great deal of functional groups, high in yield, fewer in side products, but also is simple and safe to operate, low in cost, and environment-friendly.
Description
Technical field
The invention discloses the method for synthetic Quinzolone derivatives.Adopt 2-halogenated benzoic acid and amidine salt be raw material taking inorganic mantoquita as catalyzer, in water, the method for Quinazolinone compounds is prepared in microwave catalysis reaction.
Background technology
Quinazolone is the nitrogen-containing heterocycle compound that a class has good biological medicinal activity, because it has biological and pharmacoligical activities widely, has caused that scientists greatly studies interest.Research in recent years shows, the multi-biological activity of Quinazolinone compounds, be mainly manifested in the inhibition activity to EGF-R ELISA (EGFR) or its TYR kinases (EGFR-TK), vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), trk C (NGFR) and other multiple action target spots, thereby bring into play anticancer, antibacterial, the multiple pharmacologically active such as antiviral.Some important natural alkaloids also contain quinazolone class skeleton, as have the febrifugin(e) of anti-malarial effect.The important intermediate that quinazolone or fine chemistry industry and medicine are produced, if the 4-amido quinazoline being obtained after chlorination, ammonification by quinazolone is that a series of medicines are as the basic framework of Gefitinib (Gefitinib), Tarceva (Erlotinib).Therefore, the novel method of synthetic quinazolone is subject to extensive concern always.
According to raw materials used difference, the synthetic method of current common quinazolone mainly contains: (1) taking anthranilic acid as raw material (referring to (a) M. Endicott, E. Wick; M. L. Mercury, J. Am. Chem. Soc., 1946; 68,1299; (b) G. Liu, D. Y. Hu, L. H. Jin, Bioorg. Med. Chem., 2007,15,6608.); (2) taking anthranilamide as raw material (referring to (a) R. J. abdel-Jalil, W. Volter, M. Saeed, Tetrahed. Lett., 2004,45,3475; (b) M. M. Heravi, S. Sadjadi, N. M. Haj, Tetrahed. Lett., 2009,50,943.); (3) taking ortho-nitrophenyl methane amide as raw material (referring to P. Mangeney, T. Tejere, A. Alexakis, Synthesis, 1988,255).These methods are more or less because raw material obtains difficulty, the murder by poisoning of part reagent is large, reaction conditions is violent and need the problems such as special reaction container, and use is restricted.
It is the new problem growing up for nearly 10 years that microwave technology is applied to organic synthesis, since Gedye in 1986 delivers after the paper that microwave technology is applied to organic synthesis first, the application of microwave technology in organic synthesis is increasingly extensive, compared with prior synthesizing method, microwave assisted synthesizing method has that the reaction times is short, energy-conservation, productive rate is high and advantages of environment protection.In pure water phase system, prepare a method that replaces benzothiazole compound by microwave catalysis inorganic sulphide and rarely have so far report.Water is widely distributed on earth; organic solvent relatively; cheap and easy to get; water react product is simple, productive rate is high, good, the easily separated purifying of selectivity, pollute less and nontoxic; meet the idea of Green Chemistry and Sustainable development; simple to operate, safety; there is no the problem such as inflammable and explosive of organic solvent; aspect organic synthesis; can omit such as the protection of functional group and go the synthesis steps such as protection (referring to (a) U. M. Lindstrom; Chem. Rev. 2002,102,2751; (b) S. Kobayahi, K. Manabe, Acc. Chem. Res. 2002,35,209; (c) M. Poliakoff, J. M. Fitzpatrick, T. R. Farren, P. T. Anastas, Science 2002,297,807; (d) C.-J. Li, Chem. Rev. 2005,105,3095; (i) S. Minakata, M. Komatsu, Chem. Rev. 2009,109,711.).
The invention discloses the method for synthetic Quinzolone derivatives.Adopting 2-halogenated benzoic acid and amidine salt is raw material, and taking inorganic mantoquita as catalyzer, in water, the method for Quinazolinone compounds is prepared in microwave catalysis reaction.Compared with method described in prior art, this system not only can be suitable for a large amount of functional groups, and productive rate is high, and by product is few, and simple to operate, and safety is with low cost, environmental protection.
Summary of the invention
The object of this invention is to provide a kind of in water microwave catalysis prepare the method for Quinazolinone compounds, say in more detail pure water mutually in the method for water-soluble catalyst catalysis 2-halogenated benzoic acid and the synthetic Quinazolinone compounds of amidine salt.
Realize technical scheme of the present invention as follows: of the present invention
a kind of in water microwave catalysis prepare the method for Quinazolinone compoundsas chemical equation (B), its concrete steps are as follows: in reaction vessel, add catalytic amount water-soluble catalyst (B) and 2-halogenated benzoic acid substrate, amidine salt, mineral alkali and water, being placed in microwave reactor reacts, after certain hour, be cooled to room temperature, be extracted with ethyl acetate out product, concentrating under reduced pressure, product is through column chromatography purification; Described technical scheme is that reaction substrate 2-halogenated benzoic acid and amidine salt are raw material, under the effect of catalyzer, reacts and forms, and reaction formula is as follows:
Wherein R
1be selected from halogen atom, hydroxyl, C
1-7low alkyl group, phenyl, aralkyl, C
1-4lower alkoxy, nothing replace or have the phenoxy group of replacement, aralkoxy, pyridyl, Phenoxymethyl, ethanoyl, nitro or the cyano group that nothing replaces or have replacement; R
1substituting group is preferably placed at the ortho position of halogen X, and a position and contraposition, more preferably in contraposition; R
2for F, Cl, Br, I.
Described catalyzer (B) be a kind of water-soluble transition metal title complex (as: copper 8-quinolinolate) (B), be preferably oxine copper complex.Following formula is shown in by catalyzer (B):
(B)
Wherein M can be the transition metal such as iron, cobalt, nickel, manganese, copper, platinum, palladium, preferably palladium, copper, iron, more preferably copper.
According to the present invention, substrate (I) is 2-halogenated benzoic acid, can in this water react system, synthesize Quinzolone derivatives.
(I)。
R in above formula (I)
1for F, Cl, Br, I; Hydroxyl, C
1-7low alkyl group, phenyl, aromatic hydrocarbons, aralkyl, C
1-4lower alkoxy, nothing replace or also can have the phenoxy group of replacement, aralkoxy, pyridyl, Phenoxymethyl, ethanoyl, nitro, the cyano group that nothing replaces or also can have replacement.
X is halogen atom Cl, Br, I.
According to the present invention, be amidine salt as shown in the formula (II):
（II）
Wherein R
2for F, Cl, Br, I, hydroxyl, C
1-7low alkyl group, phenyl, aromatic hydrocarbons, aralkyl, pyridyl, Phenoxymethyl, ethanoyl, nitro, cyano group.
Products therefrom (III), wherein R
1for halogen atom, hydroxyl, C
1-7low alkyl group, phenyl, aralkyl, C
1-4lower alkoxy, nothing replace or also can have the phenoxy group of replacement, aralkoxy, pyridyl, Phenoxymethyl, ethanoyl, nitro, the cyano group that nothing replaces or also can have replacement.
R
2for F, Cl, Br, I, hydroxyl, C
1-7low alkyl group, phenyl, aromatic hydrocarbons, aralkyl, pyridyl, Phenoxymethyl, ethanoyl, nitro, cyano group.
（III）
In preferred version of the present invention, the consumption that it is characterized in that concrete steps amidine salt is 1-30 times of substrate (2-halogenated benzoic acid) molar weight.
Reaction system is implemented under mineral alkali or organic bases existence, preferably mineral alkali.Mineral alkali can be potassium hydroxide, lithium hydroxide, sodium hydroxide, cesium carbonate, Potassium monofluoride, salt of wormwood, sodium carbonate, potassiumphosphate, sodium bicarbonate, dipotassium hydrogen phosphate, saleratus, sodium acetate, potassium acetate, Sodium propanecarboxylate, sodium methylate, sodium ethylate, sodium tert-butoxide, potassium tert.-butoxide, trimethylacetic acid sodium, and organic bases can be triethylamine, tripropyl amine, Tributylamine, diisopropylethylamine.Preferably use sodium hydroxide, cesium carbonate, sodium carbonate, potassium hydroxide, potassiumphosphate.
Be standard based on 1 mole of 2-halogenated benzoic acid (I), the consumption of described alkali is 0.5 to 8 mole, is preferably 0.5 to 6 mole, more preferably 0.5 to 5 mole.
In preferred version of the present invention, be standard based on 1 mole of 2-halogenated benzoic acid (I), the usage quantity of catalyzer is 0.01 mole to 0.5 mole, preferably 0.02 mole to 0.4 mole, more preferably 0.05 to 0.3 mole.
In preferred version of the present invention, metal in catalyzer (M) can be the transition metal such as iron, cobalt, nickel, manganese, copper, platinum, palladium, preferably palladium, copper, iron, more preferably copper.
In preferred version of the present invention, preferred quinolines of organism etc. in catalyzer, more preferably oxine.
Consumption as the water of solvent can change in wide scope.The concentration of reaction substrate (2-halogenated benzoic acid) is preferably 0.1 to 0.9mol/L, and more preferably 0.3 to 0.4mol/L.
Temperature of reaction in microwave reactor is 20 to 160 DEG C, preferably 20 to 150 DEG C, and more preferably under the condition of 20 to 130 DEG C, implement.
Reaction times in microwave reactor is 1-300 minute, preferably 5-160 minute.
Microwave irradiation power in microwave reactor is 20-500 W, preferably 30-300W.
Advantage of the present invention is: the present invention is a kind of environmental friendliness, easy and simple to handle, and safety is cheap, prepares efficiently the method for Quinazolinone compounds.Compared with prior art, this method not only can be suitable for a large amount of functional groups, and productive rate is high, and by product is few, and simple to operate, and safety is with low cost, environmental protection.
Embodiment
embodiment 1:4(3H) quinazolone:in reaction vessel, add 2-iodo-benzoic acid 1 mmol, hydrochloric acid carbonamidine (claims again: amitraz hydrochloride, molecular formula: CH
4n
2hCl) 1 mmol, copper 8-quinolinolate (B) 0.05 mmol, sodium hydroxide 1 mmol, water 3 mL.After putting under microwave reactor, put in microwave reactor and heat 100 DEG C to 30 minutes under 150 W power, be cooled to room temperature.Be extracted with ethyl acetate out product, concentrating under reduced pressure, product, through column chromatography purification, obtains white solid, productive rate 94%.
embodiment 2:6-methyl-4(3H) quinazolone:in reaction vessel, add iodo-5-tolyl acid 1 mmol of 2-, hydrochloric acid carbonamidine 1 mmol, copper 8-quinolinolate (B) 0.05 mmol, sodium hydroxide 1 mmol, water 3 mL.After putting under microwave reactor, put in microwave reactor and heat 100 DEG C to 30 minutes under 150 W power, be cooled to room temperature.Be extracted with ethyl acetate out product, concentrating under reduced pressure, product, through column chromatography purification, obtains white solid, productive rate 92%.
embodiment 3:6-methoxyl group-4(3H) quinazolone:preparation method, with embodiment 2, adds iodo-5-methoxybenzoic acid 1 mmol of 2-, obtains colorless solid, productive rate 93%.
embodiment 4:6-nitro-4(3H) quinazolone:preparation method, with embodiment 2, adds iodo-5-nitrobenzoic acid 1 mmol of 2-, obtains yellow solid, productive rate 92%.
the bromo-4(3H of embodiment 5:6-) quinazolone:preparation method, with embodiment 2, adds iodo-5-bromo-benzoic acid 1 mmol of 2-, obtains yellow solid, productive rate 84%.
the chloro-4(3H of embodiment 6:6-) quinazolone:preparation method, with embodiment 2, adds the iodo-5-chloro-benzoic acid of 2-1mmol, obtains white solid, productive rate 81%.
the fluoro-4(3H of embodiment 7:6-) quinazolone:preparation method, with embodiment 2, adds iodo-5-fluorobenzoic acid 1 mmol of 2-, obtains white liquid, productive rate 55%.
embodiment 8:6-ethanoyl-4(3H) quinazolone:preparation method, with embodiment 2, adds iodo-5-acetylbenzoic acid 1 mmol of 2-, obtains white liquid, productive rate 75%.
embodiment 9:6-carboxyl-4(3H) quinazolone:preparation method, with embodiment 2, adds 4-iodine m-phthalic acid 1 mmol, obtains white solid, productive rate 63%.
embodiment 10:4(3H) quinazolone:in reaction vessel, add 2-bromo-benzoic acid 1 mmol, hydrochloric acid carbonamidine 1 mmol, copper 8-quinolinolate (B) 0.05 mmol, sodium hydroxide 1 mmol, water 3 mL.After putting under microwave reactor, put in microwave reactor and heat 100 DEG C to 30 minutes under 150 W power, be cooled to room temperature.Be extracted with ethyl acetate out product, concentrating under reduced pressure, product, through column chromatography purification, obtains white solid, productive rate 84%.
embodiment 11:6-methyl-4(3H) quinazolone:in reaction vessel, add bromo-5-tolyl acid 1 mmol of 2-, hydrochloric acid carbonamidine 1 mmol, copper 8-quinolinolate (B) 0.05 mmol, sodium hydroxide 1 mmol, water 3 mL.After putting under microwave reactor, put in microwave reactor and heat 100 DEG C to 30 minutes under 150 W power, be cooled to room temperature.Be extracted with ethyl acetate out product, concentrating under reduced pressure, product, through column chromatography purification, obtains white solid, productive rate 82%.
embodiment 12:6-methoxyl group-4(3H) quinazolone:preparation method, with embodiment 2, adds bromo-5-methoxybenzoic acid 1 mmol of 2-, obtains colorless solid, productive rate 83%.
embodiment 13:6-nitro-4(3H) quinazolone:preparation method, with embodiment 2, adds bromo-5-nitrobenzoic acid 1 mmol of 2-, obtains yellow solid, productive rate 82%.
the bromo-4(3H of embodiment 14:6-) quinazolone:preparation method, with embodiment 2, adds 2,5-dibromobenzoic acid, 1 mmol, obtains yellow solid, productive rate 74%.
the chloro-4(3H of embodiment 15:6-) quinazolone:preparation method, with embodiment 2, adds the bromo-5-chloro-benzoic acid of 2-1mmol, obtains white solid, productive rate 72%.
the fluoro-4(3H of embodiment 16:6-) quinazolone:preparation method, with embodiment 2, adds bromo-5-fluorobenzoic acid 1 mmol of 2-, obtains white solid, productive rate 45%.
embodiment 17:6-ethanoyl-4(3H) quinazolone:preparation method, with embodiment 2, adds bromo-5-acetylbenzoic acid 1 mmol of 2-, obtains white liquid, productive rate 65%.
embodiment 18:6-carboxyl-4(3H) quinazolone:preparation method, with embodiment 2, adds 4-bromine m-phthalic acid 1 mmol, obtains white solid, productive rate 59%.
embodiment 19:7-methyl-4(3H) quinazolone:in reaction vessel, add iodo-4-tolyl acid 1 mmol of 2-, hydrochloric acid carbonamidine 1 mmol, copper 8-quinolinolate (B) 0.05 mmol, sodium hydroxide 1 mmol, water 3 mL.After putting under microwave reactor, put in microwave reactor and heat 100 DEG C to 30 minutes under 150 W power, be cooled to room temperature.Be extracted with ethyl acetate out product, concentrating under reduced pressure, product, through column chromatography purification, obtains white solid, productive rate 82%.
embodiment 20:7-methoxyl group-4(3H) quinazolone:preparation method, with embodiment 2, adds bromo-4-methoxybenzoic acid 1 mmol of 2-, obtains colorless solid, productive rate 83%.
embodiment 21:7-nitro-4(3H) quinazolone:preparation method, with embodiment 2, adds bromo-4-nitrobenzoic acid 1 mmol of 2-, obtains yellow solid, productive rate 82%.
the bromo-4(3H of embodiment 22:7-) quinazolone:preparation method, with embodiment 2, adds 2,4-dibromobenzoic acid, 1 mmol, obtains yellow solid, productive rate 74%.
the chloro-4(3H of embodiment 23:7-) quinazolone:preparation method, with embodiment 2, adds the bromo-4-chloro-benzoic acid of 2-1mmol, obtains white solid, productive rate 72%.
the fluoro-4(3H of embodiment 24:7-) quinazolone:preparation method, with embodiment 2, adds bromo-4-fluorobenzoic acid 1 mmol of 2-, obtains white solid, productive rate 45%.
embodiment 25:7-ethanoyl-4(3H) quinazolone:preparation method, with embodiment 2, adds bromo-4-acetylbenzoic acid 1 mmol of 2-, obtains white solid, productive rate 65%.
embodiment 26:2-methyl-4(3H) quinazolone:in reaction vessel, add 2-iodo-benzoic acid 1 mmol, acetamidine hydrochloride 1 mmol, copper 8-quinolinolate (B) 0.05 mmol, sodium hydroxide 1 mmol, water 3 mL.After putting under microwave reactor, put in microwave reactor and heat 100 DEG C to 30 minutes under 150 W power, be cooled to room temperature.Be extracted with ethyl acetate out product, concentrating under reduced pressure, product, through column chromatography purification, obtains white solid, productive rate 82%
embodiment 27:2-phenyl-4(3H) quinazolone:preparation method, with embodiment 26, adds benzamidine hydrochloride 1 mmol, obtains colorless solid, productive rate 93%.
embodiment 28:2-(4-methyl) phenyl-4(3H) quinazolone:preparation method, with embodiment 26, adds 4-aminomethyl phenyl amidine 1 mmol, obtains yellow solid, productive rate 93%.
embodiment 29:2-(4-nitro) phenyl-4(3H) quinazolone:preparation method, with embodiment 26, adds 4-nitro base benzene carbon amidine 1 mmol, obtains yellow solid, productive rate 87%.
embodiment 30:2-(4-methoxyl group) phenyl-4(3H) quinazolone:preparation method, with embodiment 26, adds 4-p-methoxy-phenyl amidine 1 mmol, obtains white solid, productive rate 85%.
embodiment 31:2-ethyl-4(3H) quinazolone:preparation method, with embodiment 26, adds hydrochloric acid the third amidine 1 mmol, obtains colorless solid, productive rate 93%.
embodiment 32:2-(4-fluorine) phenyl-4(3H) quinazolone:preparation method, with embodiment 26, adds 4-fluorophenyl amidine 1 mmol, obtains yellow solid, productive rate 93%.
embodiment 33:2-(4-chlorine) phenyl-4(3H) quinazolone:preparation method, with embodiment 26, adds 4-chloro-phenyl-amidine 1 mmol, obtains yellow solid, productive rate 86%.
embodiment 34:2-(4-bromine) phenyl-4(3H) quinazolone:preparation method, with embodiment 26, adds 4-bromophenyl amidine 1 mmol, obtains white solid, productive rate 80%.
embodiment 35:2-propyl group-4(3H) quinazolone:preparation method, with embodiment 26, adds hydrochloric acid fourth amidine 1 mmol, obtains colorless solid, productive rate 89%.
embodiment 36:2-butyl-4(3H) quinazolone:preparation method, with embodiment 26, adds hydrochloric acid the third amidine 1 mmol, obtains yellow solid, productive rate 83%.
embodiment 37:2-amyl group-4(3H) quinazolone:preparation method, with embodiment 26, adds hydrochloric acid fourth amidine 1 mmol, obtains yellow solid, productive rate 77%.
embodiment 38:2-hexyl-4(3H) quinazolone:preparation method, with embodiment 26, adds hydrochloric acid penta amidine 1 mmol, obtains yellow solid, productive rate 67%.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, all any amendments of doing within the spirit and principles in the present invention, are equal to replacement and improvement etc., within all should being included in protection scope of the present invention.
Claims (10)
1.
a kind of in water microwave catalysis prepare the method for Quinazolinone compoundsas chemical equation (B), its concrete steps are as follows: in reaction vessel, add catalytic amount water-soluble catalyst (B) and 2-halogenated benzoic acid substrate, amidine salt, mineral alkali and water, being placed in microwave reactor reacts, after certain hour, be cooled to room temperature, be extracted with ethyl acetate out product, concentrating under reduced pressure, product is through column chromatography purification;
Wherein catalyzer (B) is:
（B）;
Wherein R
1be selected from halogen atom, hydroxyl, C
1-7low alkyl group, phenyl, aralkyl, C
1-4lower alkoxy, nothing replace or have the phenoxy group of replacement, aralkoxy, pyridyl, Phenoxymethyl, ethanoyl, nitro or the cyano group that nothing replaces or have replacement; R
1substituting group is preferably placed at the ortho position of halogen X, and a position and contraposition, more preferably in contraposition; R
2for F, Cl, Br, I.
2. method according to claim 1, is characterized in that catalyzer in concrete steps (B) is a kind of hydroxyquinoline metal title complex, is preferably oxine copper complex.
3. method according to claim 1, the consumption that it is characterized in that concrete steps amidine salt is 1-30 times of 2-halogenated benzoic acid substrate.
4. method according to claim 1, is characterized in that in concrete steps, mineral alkali is sodium hydroxide, cesium carbonate, sodium carbonate, potassium hydroxide, potassiumphosphate or sodium hydroxide.
5. method according to claim 1 and 2, the usage quantity that it is characterized in that catalyzer in concrete steps is the 0.01-0.5 mol of 2-halogenated benzoic acid substrate, preferably 0.02-0.4 mol, more preferably 0.05-0.3 mol.
6. according to the method described in claim 1 or 4, it is characterized in that the consumption of mineral alkali in concrete steps is standard based on 1 mol 2-halogenated benzoic acid, the consumption of described alkali is 0.5-8 mol, is preferably 0.5-6 mol, more preferably 0.5-5 mol.
7. method according to claim 1, the concentration that it is characterized in that 2-halogenated benzoic acid substrate in concrete steps is 0.1-0.9 mol/L, more preferably 0.3-0.4 mol/L.
8. method according to claim 1, is characterized in that in concrete steps that temperature of reaction is 20-160 DEG C in microwave reactor, preferably 20-150 DEG C, and more preferably under the condition of 20-130 DEG C, implement.
9. method according to claim 1, is characterized in that in concrete steps that the reaction times is 1-300 minute in microwave reactor, preferably 5-160 minute.
10. method according to claim 1, is characterized in that in concrete steps that microwave irradiation power is 20-500 W in microwave reactor, preferably 30-300W.
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| CN107490630B (en) * | 2016-06-10 | 2021-08-03 | 山东新时代药业有限公司 | Analytical detection method of 7-fluoro-4-hydroxyquinazoline |
| CN106631915A (en) * | 2016-12-22 | 2017-05-10 | 福建医科大学 | Synthesis process of sulfonamide compounds in microwave system |
| WO2019170543A1 (en) | 2018-03-07 | 2019-09-12 | Bayer Aktiengesellschaft | Identification and use of erk5 inhibitors |
| CN112778218A (en) * | 2021-01-08 | 2021-05-11 | 湖北工程学院 | Method for preparing quinazolinone and derivative thereof by using chitosan loaded copper catalyst |
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