CN111718301B - Synthetic method of quinazolinone derivative - Google Patents
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- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 238000010189 synthetic method Methods 0.000 title claims description 6
- 238000000034 method Methods 0.000 claims abstract description 22
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 11
- -1 aldehyde compounds Chemical class 0.000 claims abstract description 10
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 78
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 30
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 30
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
- 239000003208 petroleum Substances 0.000 claims description 26
- 238000004440 column chromatography Methods 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 21
- ATHHXGZTWNVVOU-UHFFFAOYSA-N monomethyl-formamide Natural products CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 238000001308 synthesis method Methods 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical group OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
- 230000005526 G1 to G0 transition Effects 0.000 claims description 12
- 239000003480 eluent Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 239000012046 mixed solvent Substances 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 12
- 229910002027 silica gel Inorganic materials 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 8
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 229920000767 polyaniline Polymers 0.000 claims description 3
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000005909 Kieselgur Substances 0.000 claims 1
- ATHHXGZTWNVVOU-VQEHIDDOSA-N n-methylformamide Chemical group CN[13CH]=O ATHHXGZTWNVVOU-VQEHIDDOSA-N 0.000 claims 1
- 150000003246 quinazolines Chemical class 0.000 claims 1
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 abstract description 12
- 230000002194 synthesizing effect Effects 0.000 abstract description 11
- 239000002994 raw material Substances 0.000 abstract description 8
- 150000001408 amides Chemical class 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 4
- 231100000252 nontoxic Toxicity 0.000 abstract description 4
- 230000003000 nontoxic effect Effects 0.000 abstract description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 238000001228 spectrum Methods 0.000 description 32
- 229910052799 carbon Inorganic materials 0.000 description 20
- 238000003756 stirring Methods 0.000 description 16
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000012512 characterization method Methods 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 5
- 238000002390 rotary evaporation Methods 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 3
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- XGPOMXSYOKFBHS-UHFFFAOYSA-M sodium;trifluoromethanesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C(F)(F)F XGPOMXSYOKFBHS-UHFFFAOYSA-M 0.000 description 3
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- UBKGOWGNYKVYEF-UHFFFAOYSA-N 6-fluoro-1h-3,1-benzoxazine-2,4-dione Chemical compound N1C(=O)OC(=O)C2=CC(F)=CC=C21 UBKGOWGNYKVYEF-UHFFFAOYSA-N 0.000 description 1
- FTOHSJGKIFDLQU-UHFFFAOYSA-N 7-methyl-1h-3,1-benzoxazine-2,4-dione Chemical compound N1C(=O)OC(=O)C=2C1=CC(C)=CC=2 FTOHSJGKIFDLQU-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- KJMRWDHBVCNLTQ-UHFFFAOYSA-N N-methylisatoic anhydride Chemical compound C1=CC=C2C(=O)OC(=O)N(C)C2=C1 KJMRWDHBVCNLTQ-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000007243 oxidative cyclization reaction Methods 0.000 description 1
- 238000011909 oxidative ring-opening Methods 0.000 description 1
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for synthesizing quinazolinone derivatives, belonging to the technical field of organic synthesis. The method takes isatoic anhydride or derivatives thereof, aldehyde compounds and inert amide as raw materials, and the quinazolinone derivatives are obtained through one-step synthesis treatment, so that the method has the advantages of simple synthesis steps, non-toxic raw materials, low price and easy obtainment, good functional group compatibility and high atom economy, and has the potential to prepare the quinazolinone derivatives in a large scale by one step.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a quinazolinone derivative.
Background
Quinazolinone derivatives are core structures constituting many natural alkaloids and synthetic compounds, exhibiting interesting biological and pharmacological activities, such as antidepressant activity, antithrombotic activity, anti-inflammatory activity, anticancer activity and use as free radical scavengers. In addition, quinazolinone has high affinity and multi-site characteristics, which is helpful for the development of drug-related products. (org.Lett.2016,18, 5280-5283; Bioorg.Med.chem.2017,25, 4533-4552; ACS Med.chem.Lett.2014,5, 884-888; chem.Rev.2003,103, 893-930).
Quinazolinones are traditionally prepared by ring-closing condensation of anthranilamide with an aldehyde or an aldehyde substitute. In recent years, a series of new methods have been developed to construct quinazolinone backbone molecules, representative examples being mainly carbonylation cyclization reactions, formation of the corresponding carbon-nitrogen bond by 2-halobenzoic acid first followed by intramolecular cyclocondensation reactions, oxidative cyclization reactions of anthranilamide derivatives, oxidative ring-opening reactions of indoles and free radical-induced cascade reactions (org. Lett.2017,19, 6432-. In addition, the use of three components, benzyl chloride, arylamine and isatoic anhydride, in K has been reported2CO3With the catalyst of (1), the DSMO is used as a solvent to react to generate the quinazolinone derivative. Although these methods have been developed with significant utility, most of them suffer from one or more disadvantages, such as the use of environmentally unfriendlyThe oxidizing agent and the coupling agent of (a), require a multi-step preparation process to prepare reactants and catalysts that are difficult to reuse.
Disclosure of Invention
In order to solve the defects and shortcomings in the prior art, the invention aims to provide a method for obtaining a target quinazolinone derivative by using isatoic anhydride or a derivative thereof, an aldehyde compound and inert amide as raw materials and only performing one-step synthesis treatment, wherein the synthesis method has the advantages of simple synthesis steps, non-toxic and cheap and easily available raw materials, good functional group compatibility and high atom economy.
In order to achieve the purpose, the invention adopts the technical scheme that: a synthetic method of quinazolinone derivatives comprises the following steps: reacting a compound with a structure shown in a formula (1), a compound with a structure shown in a formula (2) and a compound with a structure shown in a formula (3) in a solvent in the presence of a catalyst to obtain the quinazolinone derivative;
wherein each R is1Independently represents alkyl, alkoxy, halogen or hydrogen, R2Represents an alkyl group, an aromatic group or hydrogen, R3Represents an aliphatic hydrocarbon group, an aromatic group, a heteroaromatic group or an aromatic group having a substituent, R4Represents alkyl or hydrogen, R5Represents alkyl or hydrogen, n represents 1, 2, 3 or 4;
when R is2When the quinazoline ketone derivative represents hydrogen, the quinazoline ketone derivative is a compound with a structure shown as a formula (4); when R is2When the derivative represents alkyl or benzyl, the quinazolinone derivative is a compound with a structure shown as a formula (5).
In the method, isatoic anhydride or derivatives thereof, aldehyde compounds and inert amide are used as raw materials to synthesize the quinazolinone derivatives in one step, and as shown in figure 1, amide bonds are broken in the reaction process. The method has the advantages of simple synthesis steps, non-toxic and cheap and easily-obtained raw materials, good functional group compatibility and high atom economy, and has the potential to prepare the quinazolinone derivative in a large scale in one step.
Wherein R is1Alkyl groups represented include straight chain alkyl, branched chain alkyl, and cycloalkyl groups such as methyl, ethyl, isopropyl, cyclopropyl, and the like;
R1examples of the alkoxy group include methoxy, ethoxy, isopropoxy and the like;
R1examples of the halogen include fluorine, chlorine, bromine, iodine, etc.;
R2alkyl groups represented include straight chain alkyl, branched chain alkyl, and cycloalkyl groups such as methyl, ethyl, isopropyl, cyclopropyl, and the like;
R2examples of the aromatic group include phenyl and benzyl;
R3examples of the aliphatic hydrocarbon group include hexyl group;
R3examples of the aromatic group include phenyl and benzyl;
R3examples of the heteroaryl group include a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group and the like;
R3examples of the substituted aromatic group include 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group and the like;
R4alkyl groups represented include straight chain alkyl, branched chain alkyl, and cycloalkyl groups such as methyl, ethyl, isopropyl, cyclopropyl, and the like;
R5alkyl groups represented include straight chain alkyl, branched chain alkyl, and cycloalkyl groups such as methyl, ethyl, isopropyl, cyclopropyl, and the like.
Preferably, said R is1Represents methyl, methoxy, fluorine or hydrogen, said R2Represents methyl, benzyl or hydrogen, said R3Represents hexyl, phenyl, benzyl, 4-chlorophenyl or 4-pyridyl, said R4Represents methyl or hydrogen, said R5Represents methyl, ethyl, cyclopropyl or hydrogen.
Preferably, the molar ratio of the compound with the structure shown in the formula (1) to the compound with the structure shown in the formula (2) is the compound with the structure shown in the formula (1): the structure of the compound is shown as a formula (2), wherein the compound is 1-10.
Preferably, the molar ratio of the compound with the structure shown in the formula (1) to the compound with the structure shown in the formula (3) is the compound with the structure shown in the formula (1): the structure of the compound is shown as a formula (3), wherein the compound is 1 (10-20).
Preferably, the molar ratio of the compound with the structure shown in the formula (1) to the catalyst is the compound with the structure shown in the formula (1): and (0.02-0.08) as a catalyst.
Preferably, the volume ratio of the compound with the structure shown in the formula (1) to the solvent is the compound with the structure shown in the formula (1): the solvent is 1 (1-2).
Preferably, the reaction temperature is 25-130 ℃, and the reaction time is 1-24 h.
Preferably, the catalyst is an acidic catalyst.
Preferably, the acidic catalyst comprises at least one of p-toluenesulfonic acid, trifluoroacetic acid, sodium triflate, ytterbium triflate, hydrochloric acid, phosphoric acid, pivalic acid, carrier-supported p-toluenesulfonic acid, carrier-supported trifluoroacetic acid, carrier-supported sodium triflate, carrier-supported ytterbium triflate, carrier-supported hydrochloric acid, carrier-supported phosphoric acid, carrier-supported pivalic acid. Preferably, a catalyst loaded by a carrier is adopted, so that the catalyst is easy to recover, the catalyst can be recycled, and the obtained quinazolinone derivative has no metal residue, such as p-toluenesulfonic acid loaded by activated carbon, p-toluenesulfonic acid loaded by diatomite, and p-toluenesulfonic acid loaded by polyaniline.
Preferably, the carrier adopted by the carrier-loaded p-toluenesulfonic acid, the carrier-loaded trifluoroacetic acid, the carrier-loaded sodium trifluoromethanesulfonate, the carrier-loaded ytterbium trifluoromethanesulfonate, the carrier-loaded hydrochloric acid, the carrier-loaded phosphoric acid and the carrier-loaded pivalic acid is at least one of activated carbon, diatomite and polyaniline.
Preferably, the solvent is at least one of acetonitrile, tetrahydrofuran, N-methylformamide, formamide, N-ethylformamide, tert-amyl alcohol, isopropanol, isobutanol, N-dimethylformamide, toluene, p-xylene, methanol, water.
Preferably, the synthesis method further comprises the steps of: and after the reaction is finished, removing the solvent of the reaction system or removing the solvent of the reaction system after cooling, and purifying by column chromatography to obtain the quinazolinone derivative.
Preferably, the stationary phase adopted by the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is petroleum ether: and (0.5-50) 1 for ethyl acetate.
Compared with the prior art, the invention has the following advantages: the method takes isatoic anhydride or derivatives thereof, aldehyde compounds and inert amide as raw materials, and the quinazolinone derivatives are obtained through one-step synthesis treatment, so that the method has the advantages of simple synthesis steps, non-toxic raw materials, low price and easy obtainment, good functional group compatibility and high atom economy, and has the potential to prepare the quinazolinone derivatives in a large scale by one step.
Drawings
FIG. 1 is a chemical reaction equation involved in the synthesis method of quinazolinone derivatives according to the present invention;
FIGS. 2 and 3 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 1;
FIGS. 4 and 5 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 2;
FIGS. 6 and 7 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 3;
FIGS. 8 and 9 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 4;
FIGS. 10 and 11 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 5;
FIGS. 12 and 13 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 6;
FIGS. 14 and 15 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 7;
FIGS. 16 and 17 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 8;
FIGS. 18 and 19 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 9;
FIGS. 20 and 21 are a hydrogen spectrum and a carbon spectrum, respectively, of the product obtained in example 10;
Detailed Description
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to specific examples.
Example 1
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: adding 0.25 mmol of isatoic anhydride, 0.375 mmol of benzaldehyde, 60 mg of activated carbon-supported p-toluenesulfonic acid catalyst and 1 ml of N-methylformamide into a schlenk tube (a schlenk tube), stirring and reacting for 12 hours at 120 ℃ under the condition of air, stopping heating and stirring, cooling to room temperature, performing reduced pressure rotary evaporation to remove the solvent, and performing column chromatography separation and purification to obtain the target product, wherein a stationary phase of the column chromatography is silica gel, an eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate is 6:1, v/v), and the yield of the target product is 89%.
The hydrogen spectrogram and the carbon spectrogram of the obtained product are respectively shown in fig. 2 and fig. 3, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ8.37-8.30(m,1H),7.78–7.72(m,2H),7.60–7.56(m,2H),7.51(m,4H),3.50(s,3H)；
13C NMR(126MHz,CDCl3):δ162.7,156.1,147.3,135.4,134.3,130.1,128.9,128.0,127.5,127.0,126.7,120.5,34.3；
IR(KBr):3053,1674,1556,1471,1345,763,695cm-1；
MS(EI,m/z):236.10[M]+。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 2
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: 0.25 mmol of isatoic anhydride, 0.375 mmol of p-tolualdehyde, 60 mg of polyaniline-supported p-toluenesulfonic acid catalyst and 1 ml of N-methylformamide are added into a schlenk tube, the mixture is stirred and reacted for 16 hours at 100 ℃ under the condition of air, heating and stirring are stopped, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation under reduced pressure, and the mixture is separated and purified by column chromatography, wherein the stationary phase of the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate ═ 5:1, v/v), and the yield of the target product is 84%.
The hydrogen spectrogram and the carbon spectrogram of the obtained product are respectively shown in fig. 4 and fig. 5, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ8.35–8.29(m,1H),7.77–7.71(m,2H),7.53–7.45(m,3H),7.33(d,J＝8.0Hz,2H),3.51(s,3H),2.44(s,3H)；
13C NMR(126MHz,CDCl3)：δ162.8,156.3,147.4,140.3,134.2,132.6,129.5,128.0,127.5,126.8,126.6,120.5,34.3,21.4；
IR(KBr):3741，3030，2317，1671，1465，1340，776cm-1；
MS(EI,m/z):250.10[M]+。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 3
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: adding 0.25 mmol of isatoic anhydride, 0.375 mmol of p-chlorobenzaldehyde, 60 mg of trifluoroacetic acid and 1 ml of N-methylformamide into a schlenk tube, stirring and reacting at 110 ℃ under the condition of air for 10 hours, stopping heating and stirring, cooling to room temperature, decompressing and rotary evaporating to remove the solvent, and then separating and purifying by column chromatography to obtain the target product, wherein the stationary phase of the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate: 7:1, v/v), and the yield of the target product is 83%.
The hydrogen spectrogram and the carbon spectrogram of the obtained product are respectively shown in fig. 6 and 7, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ8.32(dd,J＝8.0,1.0Hz,1H),7.79–7.70(m,2H),7.56–7.49(m,5H),3.50(s,3H)；
13C NMR(126MHz,CDCl3):δ162.6,155.0,147.2,136.4,134.4,133.8,129.6,129.2,127.5,127.2,126.7,120.5,34.3；
IR(KBr):3064，2317，1674，1553，1345，1095，833cm-1；
HRMS(ESI):270.0[M]+。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 4
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: adding 0.25 mmol of isatoic anhydride, 0.375 mmol of 3-pyridine benzaldehyde, 60 mg of trifluoroacetic acid and 1 ml of N-methylformamide into a schlenk tube, stirring at 120 ℃ under the air condition for 10 hours, stopping heating and stirring, cooling to room temperature, decompressing and rotary evaporating to remove the solvent, and then separating and purifying by column chromatography to obtain the target product, wherein the stationary phase of the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate: 3:1, v/v), and the yield of the target product is 87%.
The hydrogen spectrogram and the carbon spectrogram of the obtained product are respectively shown in fig. 8 and fig. 9, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ8.87(d,J＝1.5Hz,1H),8.75(dd,J 5.0,1.5Hz,1H),8.28(d,J＝8.0Hz,1H),7.99–7.88(m,1H),7.77–7.65(m,2H),7.55–7.39(m,2H),3.49(s,3H)；
13C NMR(126MHz,CDCl3):δ162.4,153.3,151.0,148.9,147.1,135.7,134.5,131.5,127.5,127.4,126.7,123.4,120.6,34.2；
IR(KBr):3740,2361,1673,1550,1463,1018,700cm-1；
MS(EI,m/z):237.10[M]+。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 5
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: adding 0.25 mmol of isatoic anhydride, 0.375 mmol of N-heptanal, 60 mg of activated carbon-supported p-toluenesulfonic acid and 1 ml of N-methylformamide into a schlenk tube, stirring and reacting for 10 hours at 130 ℃ under the condition of air, stopping heating and stirring, cooling to room temperature, decompressing and rotary evaporating to remove the solvent, and then separating and purifying by column chromatography to obtain the target product, wherein a stationary phase of the column chromatography is silica gel, an eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate ═ 8:1, v/v), and the yield of the target product is 65%.
The hydrogen spectrum and the carbon spectrum of the obtained product are respectively shown in fig. 10 and fig. 11, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ8.25(dd,J＝8.0,1.0Hz,1H),7.73–7.67(m,1H),7.66–7.60(m,1H),7.46–7.39(m,1H),3.63(s,3H),2.86–2.79(m,2H),1.87–1.78(m,2H),1.51-1.48(m,2H),1.40–1.32(m,4H),0.91(t,J＝7.0Hz,3H)；
13C NMR(126MHz,CDCl3):δ162.6,157.3,147.3,134.0,126.8,126.7,126.3,120.2,35.8,31.6,30.5,29.1,26.9,22.5,14.0；
IR(KBr):3458，2917，2320，1668，1415，1139，770cm-1；
HRMS(ESI):Calcd.for C15H21N2O[M+1]+245.1648; found 245.1641 (i.e., C)15H21N2O[M+1]+Calculated 245.1648, found 245.1641).
The structure of the resulting product is deduced from the above data as shown in the following formula:
example 6
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: adding 0.25 mmol of 4-methylisatoic anhydride, 0.375 mmol of benzaldehyde, 60 mg of pivalic acid and 1 ml of N-methylformamide into a schlenk tube, stirring at 130 ℃ under the air condition for 12 hours, stopping heating and stirring, cooling to room temperature, decompressing and rotary evaporating to remove the solvent, and then separating and purifying by column chromatography to obtain the target product, wherein the stationary phase of the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate: 6:1, v/v), and the yield of the target product is 85%.
The hydrogen spectrum and the carbon spectrum of the obtained product are respectively shown in fig. 12 and 13, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3)：δ8.21(d,J＝8.5Hz,1H),7.59–7.51(m,6H),7.32(dd,J＝8.5,1.5Hz,1H),3.49(s,3H),2.50(s,3H)；
13C NMR(126MHz,CDCl3):δ162.6,156.2,147.4,145.2,135.5,130.0,128.9,128.6,128.0,127.2,126.5,118.2,34.2,21.9；
IR(KBr):3063，2360，1673，1576，1348，1033，781cm-1；
MS(EI,m/z):250.10[M]+。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 7
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: 0.25 mmol of 5-fluoroisatoic anhydride, 0.375 mmol of benzaldehyde, 60 mg of activated carbon-supported p-toluenesulfonic acid and 1 ml of N-methylformamide are added into a schlenk tube, the mixture is stirred and reacted for 12 hours at 120 ℃ under the condition of air, heating and stirring are stopped, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation under reduced pressure, and the mixture is separated and purified by column chromatography to obtain the target product, wherein the stationary phase of the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate ═ 6:1, v/v), and the yield of the target product is 68%.
The hydrogen spectrum and the carbon spectrum of the obtained product are respectively shown in fig. 14 and fig. 15, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ7.95(dd,J＝8.5,3.0Hz,1H),7.75(q,J＝5.0Hz,1H),7.56-7.53(m,5H),7.50–7.44(m,1H),3.50(s,3H)；
13C NMR(126MHz,CDCl3):δ162.0(d,J＝3.5Hz),161.0(d,J＝248.9Hz),155.47(d,J＝2.0Hz),144.0(d,J＝1.6Hz),135.1,130.2,130.0(d,J＝7.6Hz),128.9,128.0,123.0(d,J＝24.4Hz),121.8(d,J＝8.8Hz),111.5(d,J＝23.8Hz),34.37；
IR(KBr):2315,1680,1554,1484,1346,832,696cm-1；
HRMS(ESI):Calcd.for C15H12FN2O[M+1]+:255.0928；found:255.0920。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 8
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: 0.25 mmol of N-methylisatoic anhydride, 0.375 mmol of benzaldehyde, 60 mg of activated carbon-supported p-toluenesulfonic acid and 1.2 ml of N-methylformamide are added into a schlenk tube, the mixture is stirred and reacted for 12 hours at 120 ℃ under the condition of air, heating and stirring are stopped, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation under reduced pressure, and the mixture is separated and purified by column chromatography to obtain the target product, wherein the stationary phase of the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate is 4:1, v/v), and the yield of the target product is 72%.
The hydrogen spectrum and the carbon spectrum of the obtained product are respectively shown in fig. 16 and 17, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ8.03(dd,J＝7.5,1.5Hz,1H),7.38–7.28(m,4H),7.23(dd,J＝8.0,1.5Hz,2H),6.89–6.83(m,1H),6.50(d,J＝8.0Hz,1H),5.43(s,1H),3.01(s,3H),2.81(s,3H)。
13C NMR(126MHz,CDCl3):δ162.5,146.2,136.9,133.8,129.3,128.9,128.5,126.3,118.0,116.0,111.4,81.0,35.4,32.4。
IR(KBr):2924,1647,1495,1449,1388,752,699cm-1。
MS(EI,m/z):252.10[M]+。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 9
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: 0.25 mmol of isatoic anhydride, 0.375 mmol of benzaldehyde, 60 mg of diatomite-supported p-toluenesulfonic acid and 1.2 ml of formamide are added into a schlenk tube, the mixture is stirred and reacted for 12 hours at 120 ℃ under the condition of air, heating and stirring are stopped, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation under reduced pressure, and the mixture is separated and purified by column chromatography, wherein the stationary phase of the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate: 4:1, v/v), and the yield of the target product is 67%.
The hydrogen spectrum and the carbon spectrum of the obtained product are respectively shown in fig. 18 and fig. 19, and the structural characterization data are as follows:
1H NMR(500MHz,DMSO):δ12.56(s,1H),8.29–8.10(m,3H),7.87–7.80(m,1H),7.75(d,J＝8.0Hz,1H),7.64–7.47(m,4H)；
13C NMR(126MHz,DMSO):δ162.7,152.8,149.2,135.1,133.2,131.9,129.1,128.2,128.0,127.1,126.3,121.5；
IR(KBr):2979，2317，1675，1570，1379，1067，771cm-1；
MS(EI,m/z):222.10[M]+。
the structure of the resulting product is deduced from the above data as shown in the following formula:
example 10
This example is an embodiment of the method for synthesizing quinazolinone derivatives according to the present invention. The synthesis method of the quinazolinone derivative in the embodiment comprises the following steps: adding 0.25 mmol of isatoic anhydride, 0.375 mmol of benzaldehyde, 60 mg of diatomite-supported p-toluenesulfonic acid and 1 ml of N-ethylformamide into a schlenk tube, stirring and reacting at 120 ℃ under the air condition for 12 hours, stopping heating and stirring, cooling to room temperature, decompressing and rotary evaporating to remove the solvent, and then carrying out column chromatography separation and purification to obtain the target product, wherein a stationary phase of the column chromatography is silica gel, an eluent is a mixed solvent of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate ═ 6:1, v/v), and the yield of the target product is 62%.
The hydrogen spectrum and the carbon spectrum of the obtained product are respectively shown in fig. 20 and 21, and the structural characterization data are as follows:
1H NMR(500MHz,CDCl3):δ8.36(d,J＝7.5Hz,1H),7.79–7.74(m,2H),7.61–7.47(m,6H),4.06(q,J＝7.0Hz,2H),1.23(t,J＝7.0Hz,3H)；
13C NMR(126MHz,CDCl3):δ162.0,156.2,147.2,135.6,134.3,129.8,128.8,127.7,127.5,127.0,126.7,121.0,41.2,14.1。
IR(KBr):3354，2317，1664，1605，1288，765，686cm-1；
MS(EI,m/z):250.10[M]+.
the structure of the resulting product is deduced from the above data as shown in the following formula:
finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (7)
1. A synthetic method of a quinazolinone derivative is characterized by comprising the following steps: reacting a compound with a structure shown in a formula (1), a compound with a structure shown in a formula (2) and a compound with a structure shown in a formula (3) in a solvent in the presence of a catalyst to obtain the quinazolinone derivative;
wherein each R is1Independently represents alkyl, alkoxy, halogen or hydrogen, R2Represents alkyl, aryl, benzyl or hydrogen, R3Represents an aliphatic hydrocarbon group, an aromatic group, a heteroaromatic group, a benzyl group or an aromatic group having a substituent, R4Represents alkyl or hydrogen, R5Represents alkyl or hydrogen, n represents 1, 2, 3 or 4;
when R is2When the quinazoline ketone derivative represents hydrogen, the quinazoline ketone derivative is a compound with a structure shown as a formula (4); when R is2When the quinazoline derivative represents alkyl, aryl or benzyl, the quinazoline ketone derivative is a compound with a structure shown as a formula (5);
wherein the solvent is N-methylformamide, formamide or N-ethylformamide; the catalyst is trifluoroacetic acid, pivalic acid, p-toluenesulfonic acid, carrier-supported trifluoroacetic acid, carrier-supported pivalic acid or carrier-supported p-toluenesulfonic acid.
2. The method of synthesis of claim 1, wherein R is1Represents methyl, methoxy, fluorine or hydrogen, said R2Represents methyl, benzyl or hydrogen, said R3Represents hexyl, phenyl, benzyl, 4-chlorophenyl or 4-pyridyl, said R4Represents methyl or hydrogen, said R5Represents methyl, ethyl, cyclopropyl or hydrogen.
3. The synthesis method according to claim 1 or 2, wherein the molar ratio of the compound having the structure shown in formula (1) to the compound having the structure shown in formula (2) is the compound having the structure shown in formula (1): the structure of the compound is shown as a formula (2), wherein the compound is 1-10.
4. The synthesis method according to claim 1 or 2, wherein the reaction temperature is 25-130 ℃, and the reaction time is 1-24 h.
5. The method of synthesis according to claim 1, wherein the support is activated carbon, diatomaceous earth or polyaniline.
6. The synthesis method according to claim 1 or 2, characterized in that it further comprises the following steps: and after the reaction is finished, removing the solvent of the reaction system or removing the solvent of the reaction system after cooling, and purifying by column chromatography to obtain the quinazolinone derivative.
7. The synthetic method according to claim 6, wherein the stationary phase adopted by the column chromatography is silica gel, the eluent is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is petroleum ether: and (0.5-50) 1 for ethyl acetate.
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Effective date of registration: 20240703 Address after: 256600 99 Wutong nine road, Binbei office, Bincheng District, Binzhou, Shandong Patentee after: SHANDONG HOLLY PHARMACEUTICAL CO.,LTD. Country or region after: China Address before: 1003, Building A, Zhiyun Industrial Park, No. 13 Huaxing Road, Tongsheng Community, Dalang Street, Longhua District, Shenzhen City, Guangdong Province, 518110 Patentee before: Shenzhen Wanzhida Enterprise Management Co.,Ltd. Country or region before: China |