CN106967077A - A kind of chromene simultaneously [2,3 b] quinoline and its preparation method and application - Google Patents
A kind of chromene simultaneously [2,3 b] quinoline and its preparation method and application Download PDFInfo
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- CN106967077A CN106967077A CN201710352936.4A CN201710352936A CN106967077A CN 106967077 A CN106967077 A CN 106967077A CN 201710352936 A CN201710352936 A CN 201710352936A CN 106967077 A CN106967077 A CN 106967077A
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- Prior art keywords
- quinoline
- chromene
- formaldehyde
- hydroresorcinol
- derivatives
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- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 74
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title description 3
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims abstract description 32
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 230000000118 anti-neoplastic effect Effects 0.000 claims abstract description 4
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 30
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 230000005855 radiation Effects 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 11
- SDKQWXCBSNMYBN-UHFFFAOYSA-N 2-chloroquinoline-3-carbaldehyde Chemical compound C1=CC=C2C=C(C=O)C(Cl)=NC2=C1 SDKQWXCBSNMYBN-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000010189 synthetic method Methods 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 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 3
- WZUNMOMEOMPYKZ-UHFFFAOYSA-N 2,6-dichloroquinoline-3-carbaldehyde Chemical compound N1=C(Cl)C(C=O)=CC2=CC(Cl)=CC=C21 WZUNMOMEOMPYKZ-UHFFFAOYSA-N 0.000 claims description 2
- ZFEJTYQUWRVCFW-UHFFFAOYSA-N 2-chloro-6-methoxyquinoline Chemical class N1=C(Cl)C=CC2=CC(OC)=CC=C21 ZFEJTYQUWRVCFW-UHFFFAOYSA-N 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- RBSGIVJDQUQHEJ-UHFFFAOYSA-N C(CCC)C1=NC2=CC=CC=C2C=C1C=O Chemical compound C(CCC)C1=NC2=CC=CC=C2C=C1C=O RBSGIVJDQUQHEJ-UHFFFAOYSA-N 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 5
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 abstract description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 238000011156 evaluation Methods 0.000 abstract description 2
- 238000011084 recovery Methods 0.000 abstract description 2
- 210000004881 tumor cell Anatomy 0.000 abstract description 2
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical class O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000012046 mixed solvent Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 239000002253 acid Substances 0.000 description 5
- 235000015177 dried meat Nutrition 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- -1 nitrogen-containing heterocycle compound Chemical class 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 0 CC(C)(C1)CC(Oc2c(C3C(C#N)C#N)cc(cc(*)cc4)c4n2)=C3C1=* Chemical compound CC(C)(C1)CC(Oc2c(C3C(C#N)C#N)cc(cc(*)cc4)c4n2)=C3C1=* 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- LPDFGLZUUCLXGM-UHFFFAOYSA-N 2,6-dichloroquinoline Chemical class N1=C(Cl)C=CC2=CC(Cl)=CC=C21 LPDFGLZUUCLXGM-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WZPLXMFLUHMOSK-UHFFFAOYSA-N CC(C)(C1)CC(Oc2c(C3C(C#N)C#N)cc(cc(cc4)Cl)c4n2)=C3C1=O Chemical compound CC(C)(C1)CC(Oc2c(C3C(C#N)C#N)cc(cc(cc4)Cl)c4n2)=C3C1=O WZPLXMFLUHMOSK-UHFFFAOYSA-N 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- UYIQKPVSAKFTOA-UHFFFAOYSA-N N#CC(C1C(C(CC(C2)c3ccccc3)=O)=C2Oc2nc3ccccc3cc12)C#N Chemical compound N#CC(C1C(C(CC(C2)c3ccccc3)=O)=C2Oc2nc3ccccc3cc12)C#N UYIQKPVSAKFTOA-UHFFFAOYSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000008371 chromenes Chemical class 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical compound CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 150000002515 isoflavone derivatives Chemical class 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- RYGIHSLRMNXWCN-UHFFFAOYSA-N quinoline-3-carbaldehyde Chemical class C1=CC=CC2=CC(C=O)=CN=C21 RYGIHSLRMNXWCN-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
A kind of chromene simultaneously [2,3 b] quinoline, structure shown in its structural formula as I：Wherein, R1For H, CH3O, Cl or (CH3)3Any one in C；R2For H or CH3；R3For H, CH3Or Ph.The derivative is with formaldehyde of 2 chloroquinoline 3 or derivatives thereof, malononitrile and 1, and 3 cyclohexanediones or derivatives thereof are raw material, one-step synthesis.Synthesis route is simple and direct, mild condition, and total recovery is up to more than 61%.The compound that the present invention is provided confirms that there is preferably external Inhibit proliferaton to act on to human body hepatoma cell line HepG2 through pharmacological evaluation, with the effect for suppressing growth of tumour cell, can be applied in antineoplastic is prepared.
Description
Technical field
The invention belongs to technical field of organic synthesis, it is related to the preparation method of chromene simultaneously [2,3-b] quinoline, and
Application in antineoplastic
Background technology
Chromene, also known as chromene, its skeleton are widely present in natural products, for example：Vitamin E, flavones, isoflavones
Deng all contain chromene skeleton.Chromene derivative has extensive biological and pharmacological activity.Existing antiallergy and anticancer isoreactivity side
The report in face.
Quinoline, is also benzo pyridine or azanaphthalene, is the very important nitrogen-containing heterocycle compound of a class, especially in pharmacy work
Had a wide range of applications in industry.Moreover, they are also the parent nucleus of many natural products and biologically active drug structure, such as：Chlorine
The peaceful alkali of quinoline, camel, camptothecine.By the continuous research of medicine scholar, substantial amounts of quinoline derivatives are synthesized, and it
Have extensive bioactivity, for example：Anti-malarial, antibacterial, anti-inflammatory, antitumor, anti-diabetic, anti-asthma, anti-hypertension,
Anti- alzheimer that disease, platelet aggregation-against, AntiHIV1 RT activity isoreactivity.
Simultaneously quinoline is the important fused heterocyclic compound of a class to chromene, with extensive bioactivity, in medicine
Thing chemical field has important application value.For example：Simultaneously [4,3-b] quinoline can be female as beta-selective for 6H- chromenes
Androgen receptor ligand.Further, since it has a very strong photoluminescent property, chromene and quinoline can also be applied to it is biological into
Picture.There is document report that there is the derivatives such as the chromene and quinoline of spirane structure to have good antitumor activity recently, as a result table
Such bright compound has cytotoxic activity to breast cancer, cervical carcinoma.So, design and synthesize some structures novelty has color
Simultaneously quinoline has certain meaning to alkene.
The content of the invention
It is an object of the invention to provide a kind of synthesis of new chromene simultaneously [2,3-b] quinoline, through extracorporeal anti-tumor
Active testing, such compound has preferable antitumor activity.
A kind of chromene simultaneously [2,3-b] quinoline, structure shown in its structural formula as I：
Wherein, R1For H, CH3O, Cl or (CH3)3Any one in C；R2For H or CH3；R3For H, CH3Or Ph.
It is a kind of such as the synthetic method of chromene simultaneously [2,3-b] quinoline, with 2- chloroquinoline -3- formaldehyde or derivatives thereof,
Malononitrile and 1, hydroresorcinol or derivatives thereof be raw material, the compound shown in one-step synthesis Formulas I, its reaction equation is such as
Under：
Described 2- chloroquinoline -3- formaldehyde derivatives are the chloro- 6- methoxy quinolines -3- formaldehyde of 2-, 2,6- dichloroquinolines -3-
Any one in formaldehyde and the chloro- 6- tert-butyl groups quinoline-3-formaldehydes of 2-；Described hydroresorcinol derivative is 5,5- diformazans
Any of base-hydroresorcinol, 5- phenyl-hydroresorcinol.
The solvent of reaction is acetonitrile, tetrahydrofuran, toluene, ethylene glycol, N,N-dimethylformamide (DMF), water and ethanol
Any of, wherein preferred alcohol.The catalyst of reaction can be alkali, for example sodium hydroxide, sodium carbonate, cesium carbonate, hexahydro
Pyridine or acid, such as p-methyl benzenesulfonic acid, acetic acid either organic micromolecule catalyst such as L-PROLINE.Preferably L-
Proline.
Mole of 2- chloroquinoline -3- formaldehyde or derivatives thereof, malononitrile, hydroresorcinol or derivatives thereof and catalyst
Than for 1:1:1：0.1~0.6.It is preferred that 1:1:1:0.5.Reaction is carried out in microwave reactor, and the temperature of reaction is 80~110
DEG C, preferably 100 DEG C, the effect of microwave can accelerate reaction.
It is preferred that, 2- chloroquinoline -3- formaldehyde, malononitrile and 1, hydroresorcinol is catalyst in microwave using L-PROLINE
Under radiation, 100 DEG C are reacted 20 minutes, and the mol ratio of raw material is 2- chloroquinoline -3- formaldehyde：Malononitrile：Hydroresorcinol：L- dried meat
Propylhomoserin=1:1:1:0.5.
The chromene that the present invention is synthesized simultaneously [2,3-b] quinoline, is a kind of compound of quite stable, these compounds
There is preferably external Inhibit proliferaton effect to human body hepatoma cell line HepG2, show by anti tumor activity in vitro test,
Most compounds have obvious antitumor activity, and wherein compound Ic, Id, Ig, Ii has good antitumor activity, it
IC50Value is as follows：
Beneficial effect：The synthesis route of the present invention is simple and direct, mild condition, and total recovery is up to more than 61%, and the present invention is carried
For chromene, simultaneously [2,3-b] quinoline confirms have to human body hepatoma cell line HepG2 preferably in vitro through pharmacological evaluation
Inhibit proliferaton is acted on, and with the effect for suppressing growth of tumour cell, can be applied in antineoplastic is prepared.
Embodiment
Embodiment 1
By 2- chloroquinoline -3- formaldehyde (0.2mmol), malononitrile (0.2mmol) and 5,5- dimethyl-hydroresorcinol
(0.2mmol) is added in 5mL microwave reaction pipes, is added L-PROLINE (0.1mmol) and ethanol 2mL, will be reacted the seal of tube,
Stir 10 seconds in advance, mixture is reacted 30 minutes under microwave radiation in 100 DEG C, and after reaction terminates, reaction system is cooled to
Room temperature, suction filtration is carried out after solid is separated out, then is carried out with the mixed solvent of DMF and water being recrystallized to give 2- (3,3- dimethyl -1-
Oxo -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile (Ia)：Yield 71%；m.p.:248-
250℃；IR(KBr,ν,cm-1):3047,2920,2254,1622,1598,1448,1399,1215,1091,1055,1027,
999,752,689；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.71 (s, 1H, ArH), 8.07 (d, J=7.6Hz, 1H,
), ArH 7.94 (d, J=8.4Hz, 1H, ArH), 7.88-7.84 (m, 1H, ArH), 7.67-7.63 (m, 1H, ArH), 5.23 (d, J
=4.0Hz, 1H, CH), 5.00 (d, J=4.0Hz, 1H, CH), 2.81 (d, J=18.0Hz, 1H, CH), 2.68 (d, J=
18.0Hz, 1H, CH), 2.48 (d, J=16.0Hz, 1H, CH), 2.35 (d, J=16.0Hz, 1H, CH), 1.16 (s, 3H, CH3),
1.14(s,3H,CH3)。
Embodiment 2
According to the method for embodiment 1,2- chloroquinoline -3- formaldehyde is changed into 6- methoxyl group -2- chloroquinoline -3- formaldehyde, with L-
Proline is catalyst, is reacted 30 minutes under microwave radiation, target product 2- is recrystallized to give with DMF and water mixed solvent
(9- methoxyl group -3,3- dimethyl -1- oxo -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile
(Ib)：Yield 74%；m.p.:268-270℃；IR(KBr,ν,cm-1):2896,2254,1635,1613,1466,1356,
1238,1216,1142,1112,1029,834；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.57(s,1H,ArH),7.84
(d, J=9.2Hz, 1H, ArH), 7.51-7.48 (m, 1H, ArH), 7.45 (d, J=2.4Hz, 1H, ArH), 5.20 (d, J=
4.0Hz, 1H, CH), 4.97 (d, J=3.6Hz, 1H, CH), 3.93 (s, 3H, CH3), O 2.79 (d, J=17.6Hz, 1H, CH),
2.65 (d, J=17.2Hz, 1H, CH), 2.45 (d, J=16.4Hz, 1H, CH), 2.33 (d, J=16.4Hz, 1H, CH), 1.15
(s,3H,CH3),1.13(s,3H,CH3)。
Embodiment 3
According to the method for embodiment 1,2- chloroquinoline -3- formaldehyde is changed into the 6- tert-butyl group -2- chloroquinoline -3- formaldehyde, with L-
Proline is catalyst, is reacted 30 minutes under microwave radiation, target product 2- is recrystallized to give with DMF and water mixed solvent
(the 9- tert-butyl group -3,3- dimethyl -1- oxo -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile
(Ic)：Yield 75%；m.p.:228-230℃；IR(KBr,ν,cm-1):2960,2937,2254,1642,1611,1439,
1394,1346,1265,1236,1212,1174,1145,1118,1024,997,831；1HNMR(400MHz,DMSO-d6)(δ,
ppm):8.68 (s, 1H, ArH), 8.01-7.89 (m, 3H, ArH), 5.25 (d, J=3.6Hz, 1H, CH), 4.99 (d, J=
3.6Hz, 1H, CH), 2.81 (d, J=18.0Hz, 1H, CH), 2.52 (d, J=18.8Hz, 2H, CH2), 2.36 (d, J=
16.0Hz,1H,CH),1.41(s,9H,(CH3)3C)。
Embodiment 4
According to the method for embodiment 1,2- chloroquinoline -3- formaldehyde is changed into 2,6- dichloroquinoline -3- formaldehyde, with L-PROLINE
For catalyst, reacted 30 minutes under microwave radiation, being recrystallized to give target product 2- with DMF and water mixed solvent, (9- is chloro-
3,3- dimethyl -1- oxo -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile (Id)：Yield
70%；m.p.:264-266℃；IR(KBr,ν,cm-1):2901,2257,1637,1345,1232,1212,1024,993,827,
763；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.69 (s, 1H, ArH), 8.25 (d, J=2.4Hz, 1H, ArH), 7.96
(d, J=9.2Hz, 1H, ArH), 7.89-7.86 (m, 1H, ArH), 5.23 (d, J=4.4Hz, 1H, CH), 5.00 (d, J=
4.0Hz, 1H, CH), 2.80 (d, J=18.0Hz, 1H, CH), 2.67 (d, J=18.0Hz, 1H, CH), 2.47 (d, J=
16.4Hz, 1H, CH), 2.34 (d, J=16.4Hz, 1H, CH), 1.15 (s, 3H, CH3),1.13(s,3H,CH3)。
Embodiment 5
According to the method for embodiment 1, by 5,5- dimethyl -1, hydroresorcinol changes 1, hydroresorcinol, with L- dried meat ammonia into
Acid is catalyst, is reacted 30 minutes under microwave radiation, target product 2- (1- are recrystallized to give with DMF and water mixed solvent
Oxo -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile (Ie)：Yield 75%；m.p.:272-
274℃；IR(KBr,ν,cm-1):2930,2253,1656,1634,1498,1240,1214,1184,1048,1024,789,
764；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.71 (s, 1H, ArH), 8.07 (d, J=8.0Hz, 1H, ArH), 7.94
(d, J=8.4Hz, 1H, ArH), 7.88-7.84 (m, 1H, ArH), 7.67-7.63 (m, 1H, ArH), 5.14 (d, J=4.0Hz,
1H, CH), 5.00 (d, J=3.6Hz, 1H, CH), 2.85-2.82 (m, 2H, CH2),2.49-2.43(m,2H,CH2),2.15-
1.97(m,2H,CH2)。
Embodiment 6
According to the method for embodiment 2, by 5,5- dimethyl -1, hydroresorcinol changes 1, hydroresorcinol, with L- dried meat ammonia into
Acid is catalyst, is reacted 30 minutes under microwave radiation, target product 2- (9- are recrystallized to give with DMF and water mixed solvent
Methoxyl group -1- oxo -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile (If)：Yield 73%；
m.p.:278-280℃；IR(KBr,ν,cm-1):2912,2254,1629,1614,1504,1457,1398,1358,1218,
1142,1025,1002,829,785；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.57 (s, 1H, ArH), 7.84 (d, J=
9.2Hz, 1H, ArH), 7.51-7.48 (m, 1H, ArH), 7.45 (d, J=2.8Hz, 1H, ArH), 5.11 (d, J=4.0Hz, 1H,
), CH 4.97 (d, J=3.6Hz, 1H, CH), 3.92 (s, 3H, CH3O),2.84-2.82(m,2H,CH2),2.49-2.47(m,2H,
CH2),2.15-1.96(m,2H,CH2)。
Embodiment 7
According to the method for embodiment 3, by 5,5- dimethyl -1, hydroresorcinol changes 1, hydroresorcinol, with L- dried meat ammonia into
Acid is catalyst, is reacted 30 minutes under microwave radiation, target product 2- (9- are recrystallized to give with DMF and water mixed solvent
The tert-butyl group -1- oxo -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile (Ig)：Yield 73%；
m.p.:246-248℃；IR(KBr,ν,cm-1):2956,2931,2257,1639,1504,1393,1236,1211,1185,
1047,1023,995,831,763；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.66(s,1H,ArH),8.00-7.97
(m, 1H, ArH), 7.93 (d, J=2.0Hz, 1H, ArH), 7.87 (d, J=8.8Hz, 1H, ArH), 5.12 (d, J=3.6Hz,
1H, CH), 4.97 (d, J=3.6Hz, 1H, CH), 2.84-2.81 (m, 2H, CH2),2.48-2.46(m,2H,CH2),2.14-
1.99(m,2H,CH2),1.40(s,9H,(CH3)3C)。
Embodiment 8
According to the method for embodiment 4, by 5,5- dimethyl -1, hydroresorcinol changes 1, hydroresorcinol, with L- dried meat ammonia into
Acid is catalyst, is reacted 30 minutes under microwave radiation, target product 2- (9- are recrystallized to give with DMF and water mixed solvent
Chloro- 1- oxos -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile (Ih)：Yield 68%；
m.p.:292-294℃；IR(KBr,ν,cm-1):2895,2256,1630,1486,1391,1341,1234,1185,1024,
995,921,827；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.68(s,1H,ArH),8.24(s,1H,ArH),7.96-
7.93(m,1H,ArH),7.88-7.84(m,1H,ArH),5.14-5.12(m,1H,CH),5.01-4.96(m,1H,CH),
2.89-2.92(m,4H,2×CH2),2.15-1.96(m,2H,CH2)。
Embodiment 9
According to the method for embodiment 1, by 5,5- dimethyl -1, hydroresorcinol changes 5- phenyl -1 into, hydroresorcinol, with
L-PROLINE is catalyst, is reacted 30 minutes under microwave radiation, target product is recrystallized to give with the mixed solvent of DMF and water
2- (1- oxo -3- phenyl -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile (Ii)：Yield
64%；m.p.:226-228℃；IR(KBr,ν,cm-1):2936,2257,1636,1497,1397,1240,1203,1024,
993,761；1H NMR(400MHz,CDCl3)(δ,ppm):8.75-8.73 (m, 1H, ArH), 8.09 (d, J=8.4Hz, 1H,
), ArH 7.95 (d, J=8.0Hz, 1H, ArH), 7.89-7.85 (m, 1H, ArH), 7.68-7.64 (m, 1H, ArH), 7.47-
7.34(m,4H,ArH),7.31-7.25(m,1H,ArH),5.18-5.13(m,1H,CH),5.08-5.05(m,1H,CH),
3.67-3.50(m,1H,CH),3.26-3.13(m,1H,CH),3.06-2.99(m,1H,CH),2.88-2.74(m,1H,CH),
2.68-2.63(m,1H,CH)。
Embodiment 10
According to the method for embodiment 3, by 5,5- dimethyl -1, hydroresorcinol changes 5- phenyl -1 into, hydroresorcinol, with
Hexahydropyridine is catalyst, is reacted 30 minutes under microwave radiation, target product is recrystallized to give with the mixed solvent of DMF and water
2- (the 9- tert-butyl group -1- oxo -3- phenyl -2,3,4,12- tetrahydro -1H- chromenes simultaneously [2,3-b] quinoline -12- bases) malononitrile
(Ij)：Yield 67%；m.p.:248-250℃；IR(KBr,ν,cm-1):2963,2933,2255,1638,1502,1418,
1366,1239,1205,1123,1098,1025,999,947,833；1H NMR(400MHz,DMSO-d6)(δ,ppm):8.73-
8.72(m,1H,ArH),8.04-7.91(m,3H,ArH),7.50-7.30(m,5H,ArH),5.20-5.15(m,1H,CH),
5.09-5.05(m,1H,CH),3.70-3.53(m,1H,CH),3.26-3.16(m,1H,CH),3.08-3.02(m,1H,CH),
2.95-2.88(m,1H,CH),2.71-2.66(m,1H,CH),1.44(s,9H,(CH3)3C)。
Embodiment 11
According to the method for embodiment 4, by 5,5- dimethyl -1, hydroresorcinol changes 5- phenyl -1 into, hydroresorcinol, with
P-methyl benzenesulfonic acid is catalyst, is reacted 30 minutes under microwave radiation, and target production is recrystallized to give with DMF and water mixed solvent
Thing 2- (the chloro- 1- oxos -3- phenyl -2,3,4,12- tetrahydros -1H- chromenes of 9- simultaneously [2,3-b] quinoline -12- bases) malononitrile
(Ik)：Yield 69%；m.p.:270-272℃；IR(KBr,ν,cm-1):2902,2256,1639,1492,1454,1444,
1234,1200,1024,997,839,762；1H NMR(400MHz,CDCl3)(δ,ppm):8.73-8.71(m,1H,ArH),
8.27-7.86(m,1H,ArH),7.98-7.96(m,1H,ArH),7.89-7.86(m,1H,ArH),7.47-7.34(m,4H,
ArH),7.31-7.25(m,1H,ArH),5.19-5.14(m,1H,CH),5.08-5.05(m,1H,CH),3.67-3.50(m,
1H,CH),3.26-3.11(m,1H,CH),3.06-2.98(m,1H,CH),2.87-2.77(m,1H,CH),2.68-2.63(m,
1H,CH)。
Claims (9)
1. a kind of chromene simultaneously [2,3-b] quinoline, structure shown in its structural formula as I：
Wherein, R1For H, CH3O, Cl or (CH3)3Any one in C；R2For H or CH3；R3For H, CH3Or Ph.
2. the synthetic method of a kind of chromene as claimed in claim 1 simultaneously [2,3-b] quinoline, it is characterised in that with 2-
Chloroquinoline -3- formaldehyde or derivatives thereof, malononitrile and 1, hydroresorcinol or derivatives thereof are raw material, shown in one-step synthesis Formulas I
Compound, its reaction equation is as follows：
3. the synthetic method of chromene as claimed in claim 2 simultaneously [2,3-b] quinoline, it is characterised in that described 2-
Chloroquinoline -3- formaldehyde derivatives are the chloro- 6- methoxy quinolines -3- formaldehyde of 2-, 2,6- dichloroquinoline -3- formaldehyde and chloro- uncles 6- of 2-
Any one in butyl quinoline-3-formaldehyde；Described hydroresorcinol derivative is 5,5- dimethyl -1,3- hexamethylenes two
Any of ketone, 5- phenyl-hydroresorcinol.
4. the synthetic method of chromene as claimed in claim 2 simultaneously [2,3-b] quinoline, it is characterised in that reaction it is molten
Agent is any of acetonitrile, tetrahydrofuran, toluene, ethylene glycol, N,N-dimethylformamide, water and ethanol.
5. the synthetic method of chromene as claimed in claim 2 simultaneously [2,3-b] quinoline, it is characterised in that reaction is urged
Agent is any one in sodium hydroxide, sodium carbonate, cesium carbonate, hexahydropyridine, p-methyl benzenesulfonic acid, acetic acid and L-PROLINE or several
Kind.
6. the synthetic method of chromene as claimed in claim 5 simultaneously [2,3-b] quinoline, it is characterised in that 2- chloroquinolines-
The mol ratio of 3- formaldehyde or derivatives thereof, malononitrile, hydroresorcinol or derivatives thereof and catalyst is 1:1:1：0.1~
0.6。
7. the synthetic method of chromene as claimed in claim 2 simultaneously [2,3-b] quinoline, it is characterised in that reaction is micro-
Carried out in ripple reactor, the temperature of reaction is 80~110 DEG C.
8. the synthetic method of chromene as claimed in claim 2 simultaneously [2,3-b] quinoline, it is characterised in that 2- chloroquinolines-
3- formaldehyde, malononitrile and 1, hydroresorcinol, by catalyst of L-PROLINE under microwave radiation, 100 DEG C are reacted 20 minutes, former
The mol ratio of material is 2- chloroquinoline -3- formaldehyde：Malononitrile：Hydroresorcinol：L-PROLINE=1:1:1:0.5.
9. a kind of simultaneously application of [2,3-b] quinoline in antineoplastic is prepared of chromene as claimed in claim 1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109824685A (en) * | 2019-04-03 | 2019-05-31 | 辽宁中医药大学 | Compound oleracone G and its extraction separation method and application in purslane |
| CN113234083A (en) * | 2021-04-16 | 2021-08-10 | 华南理工大学 | Tetrahydroquinoline pyran compound and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1950375A (en) * | 2004-02-25 | 2007-04-18 | 配体药物公司 | Glucocorticoid receptor modulator compounds and methods- utility |
| CN102584841A (en) * | 2011-12-16 | 2012-07-18 | 浙江工业大学 | Quinoline coumarin derivate and preparation method and application thereof |
-
2017
- 2017-05-18 CN CN201710352936.4A patent/CN106967077B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1950375A (en) * | 2004-02-25 | 2007-04-18 | 配体药物公司 | Glucocorticoid receptor modulator compounds and methods- utility |
| CN102584841A (en) * | 2011-12-16 | 2012-07-18 | 浙江工业大学 | Quinoline coumarin derivate and preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| CA: "445390-75-0", 《STN-REGISTRY》 * |
| MORTEZA SHIRI，等: "Highly selective organocatalytic three-component reaction of 2-chloroquinoline-3-carbaldehydes, 6-aminouracils, and cyclic methylene active compounds", 《TETRAHEDRON LETTERS》 * |
| RYABUKHIN, SERGEY V.，等: "A one-pot fusion of nitrogen-containing heterocycles", 《SYNTHESIS》 * |
| ZEBA N. SIDDIQUI，KULSUM KHAN: "[Et3NH][HSO4]-Catalyzed Efficient, Eco-Friendly, and Sustainable Synthesis of Quinoline Derivatives via Knoevenagel Condensation", 《ACS SUSTAINABLE CHEMISTRY & ENGINEERING》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109824685A (en) * | 2019-04-03 | 2019-05-31 | 辽宁中医药大学 | Compound oleracone G and its extraction separation method and application in purslane |
| CN109824685B (en) * | 2019-04-03 | 2021-03-23 | 辽宁中医药大学 | Compound oleracene G in purslane, extraction and separation method and application thereof |
| CN113234083A (en) * | 2021-04-16 | 2021-08-10 | 华南理工大学 | Tetrahydroquinoline pyran compound and preparation method and application thereof |
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Application publication date: 20170721 Assignee: NANTONG WANNIANCHANG PHARMACEUTICAL Co.,Ltd. Assignor: JIANGSU University OF TECHNOLOGY Contract record no.: X2023980054244 Denomination of invention: A chromogenic [2,3-b] quinoline derivative and its preparation method and application Granted publication date: 20190219 License type: Common License Record date: 20231227 |