CN109438453A - The method of level-one amine guiding building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline - Google Patents
The method of level-one amine guiding building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline Download PDFInfo
- Publication number
- CN109438453A CN109438453A CN201811576562.5A CN201811576562A CN109438453A CN 109438453 A CN109438453 A CN 109438453A CN 201811576562 A CN201811576562 A CN 201811576562A CN 109438453 A CN109438453 A CN 109438453A
- Authority
- CN
- China
- Prior art keywords
- base
- indoles
- quinoxaline
- furans
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to a kind of level-one amine to be oriented to building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline method.In reaction tube, 2- (1 is addedHIndoles -1- base) aniline and 2- furoyl formic acid is raw material, 6- (furans -2- base) indoles simultaneously [1,2- is made in high yield through acylation/cyclizationa] quinoxaline.The present invention, for seamless guiding base, increases the step economy of reaction with level-one amine；And the raw materials required for the reaction is cheap and easy to get, mild condition and easy to operate, and selectivity is single, and separation yield is high, is conducive to industrialized production, meets the development need of green organic chemistry.
Description
Technical field
The present invention relates to medication chemistry synthesis technical fields, and in particular to a kind of level-one amine guiding building 6- (furans -2-
Base) indoles simultaneously [1,2-a] quinoxaline method.
Background technique
Organometallic Chemistry has obtained unprecedented development in recent years, becomes building carbon-carbon bond and the important hand of carbon-heterodesmic
Section.The C-H function dough reaction of homing device auxiliary has obtained the wide of scientists because of its good selectivity and reactivity
General concern.A series of nitrogenous guiding bases are reacted by Successful utilization in C-H function dough after decades of development, they include
Level-one amine, pyridine, amide, imines, oxime, enamine and various nitrogen-containing heterocycles.It is worth noting that, level-one amine is realized as guiding base
The report of C-H functionalization is considerably less, because level-one amine has very strong sequestering power, it is easy to catalyst poisoning be caused to be lost
It is living, it is achieved that the C-H functionalization of level-one amine guiding has very big challenge.Currently, utilizing transition metal-catalyzed level-one
Amine guiding strategy is successfully realized alkenyl, alkynyl, arylation and cyclization (Lazareva, A.；Daugulis
O.Org.Lett.,2006,8,5211-5213；Liang,D.；Hu,Z.；Peng,J.；et al.Chem.Commun.,2013,
49,173-175；Liang,Z.；Feng,R.；Yin,H.；et al.Org.Lett.,2013,15,4544-4547；Bai,P.；
Huang X.-F.；Xu,G.-D.；et al.Org.Lett.,2016,18,3058-3061；Suzuki,C.；Hirano,K.；
Satoh,T.；et al.Org.Lett.,2013,15,3990-3993；Liang,Z.；Ju,L.；Xie,Y.；et
al.Chem.Eur.J.,2012,18,15816-15821；Jiang,G.；Hu,W.；Zhu,C.；et al.Chem.Commun.,
2018,54,1746-1749.)；But level-one amine is used to realize that acylation/cyclization strategy never has for seamless guiding base
It is reported.Therefore, realize that acylation/cyclization of level-one amine guiding has very important researching value.
Quinoxaline derivant is important nitrogenous compound, the activity with antitumor, antimycotic and AntiHIV1 RT activity etc.,
It can also be used as angiotensin receptor inhibitor (Patel, M.；Mc Hugh,R.J.；Cordova,B.C.；Klabe,R.M.；
Erickson-Vitanen,S.；Trainor,G.L.；Rodger,J.D.Bioorg.Med.Chem.Lett.2000,10,
1729-1731；Guillon,J.；Dallemagne,P.；Pfeiffer,B.；Renard,P.；Manechez,D.；Kervran,
A.；Rault,S.Eur.J.Med.Chem.1998,33,293-308；Ramamohan,M.；Sridhar,R.；
Raghavendrarao,K.；Paradesi,N.；Chandrasekhar,K.B.；Jayaprakash,S.Synlett,2015,
26,1096-1100), at the same they be also some natural products important component.Because of the importance of this kind of compound,
Scientists have put into a large amount of energy and have carried out synthesizing quinoxaline derivant, after decades of development, achieve plentiful and substantial research
Achievement, but simultaneously its synthetic method is very limited as important quinoxaline derivant for [1,2-a] quinoxaline compounds for indoles.
(Xie,C.；Feng,L.；Li,W.；Ma,X.；Ma,X.；Liu,Y.；Ma,C.Org.Biomol.Chem.2016,14,8529-
8535；Rubio-Presa,R.；Pedrosa,M.；Fernández-Rodríguez,Arnáiz,F.；Sanz,
R.Org.Lett.2017,19,5470-5473；Ramamohan,M.；Sridhar,R.；Raghavendrarao,K.；
Paradesi,N.；Chandrasekhar,K.B.；Jayaprakash,S.Synlett,2015,26,1096-1100).And
There are reaction temperatures in reaction known to these, and high, substrate was difficult in place of the deficiencies of preparing.Here, we have invented a kind of palladiums
It is catalyzed the new method of level-one amine guiding synthesis 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline.This method reaction condition letter
Single, required raw material is cheap and easy to get, and preparation condition is mild, easy to operate, and selectivity is single, and separation yield is high, is conducive to industrialize
Production, has in the research and development of drug and the synthesis of natural products and has been widely used.
Summary of the invention
The object of the present invention is to provide a kind of level-one amine to be oriented to building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline
Method.
Thinking of the invention: using 2- (1H- indoles -1- base) aniline, 2- furoyl formic acid as raw material, persulfate is oxygen
Under the catalysis of palladium salt continuous acylation/cyclization occurs for agent, and step building has the chemical combination of pharmaceutical activity skeleton
Object 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline.This method avoid the uses of the additives such as acid, alkali, former needed for reacting
Expect cheap and easy to get, reaction condition is mild, and easy to operate, selectivity is single, and step economy is high, has potential practical value.
Specific steps are as follows:
2- (1H- indoles -1- base) aniline and 2- furoyl formic acid are sequentially added in reaction flask, using persulfate as oxygen
Agent, using organic solvent as solvent, stirs 10~24 hours using palladium salt as catalyst at 70~90 DEG C, cold after reaction
But to room temperature, filtering reacting liquid, after vacuum rotary steam crude product, obtain compound 6- (furans -2- base) Yin through column chromatographic purifying
Diindyl simultaneously [1,2-a] quinoxaline.
The molar ratio of 2- (1H- indoles -1- base) aniline and 2- furoyl formic acid is 1:1~2.
The oxidant is potassium peroxydisulfate, sodium peroxydisulfate or ammonium persulfate；Oxidant and 2- (1H- indoles -1- base) aniline
Molar ratio be 1~2:1.
The catalyst is palladium acetate, palladium trifluoroacetate, two (triphenylphosphine) palladium chlorides or palladium chloride；Catalyst and 2-
The molar ratio of (1H- indoles -1- base) aniline is 0.05:1.
The solvent is 1,4- dioxane or diethylene glycol dimethyl ether.
The column chromatography eluent is the mixed solvent of petroleum ether and ethyl acetate, the volume ratio of petroleum ether and ethyl acetate
For 100~10:1.
The present invention has the following advantages that compared with the prior art and effect:
The method that the present invention synthesizes 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline, it is raw materials used nontoxic and it is cheap easily
?；Reaction in air atmosphere carry out can and；The strategy has single selectivity；In addition, reaction also has step economy
Property high, easy to operate, safety, the advantages of reaction condition is mild, high income.The strategy is 6- (furans -2- base) indoles simultaneously [1,2-
A] preparation of quinoxaline provides effective synthetic method.
Detailed description of the invention
Fig. 1 is the synthesis equation of 6- in the present invention (furans -2- base) indoles simultaneously [1,2-a] quinoxaline.
Fig. 2 be 6- made from the embodiment of the present invention 14 (furans -2- base) indoles simultaneously [1,2-a] quinoxaline hydrogen spectrum.
Fig. 3 be 6- made from the embodiment of the present invention 14 (furans -2- base) indoles simultaneously [1,2-a] quinoxaline carbon spectrum.
Specific embodiment
The invention is further described below by specific embodiment.
Embodiment 1:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium chloride, 0.4 is sequentially added in reaction tube
MM potassium peroxydisulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, 78
Stop reaction after being stirred to react under the conditions of DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges
Organic phase is simultaneously dried, filtered using 0.5 gram of anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, institute
The petroleum ether for being volume ratio 75:1 with column chromatographic eluate: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base) Yin
Diindyl simultaneously [1,2-a] quinoxaline, yield 34%.
Embodiment 2:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM potassium peroxydisulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, 78
Stop reaction after being stirred to react under the conditions of DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges
Organic phase is simultaneously dried, filtered using 0.5 gram of anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, institute
The petroleum ether for being volume ratio 75:1 with column chromatographic eluate: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base) Yin
Diindyl simultaneously [1,2-a] quinoxaline, yield 47%.
Embodiment 3:
Sequentially added in reaction tube 0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium trifluoroacetate,
0.4 mM of potassium peroxydisulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, closes
And organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification,
Column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base)
Indoles simultaneously [1,2-a] quinoxaline, yield 19%.
Embodiment 4:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of four (triphenyl is sequentially added in reaction tube
Phosphine) palladium, 0.4 mM of potassium peroxydisulfate and 0.4 mM of 2- furoyl formic acid.2 milliliters of 1,4- dioxane, which are then added, is
Solvent stops reaction after being stirred to react under the conditions of 78 DEG C 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect
The generation of 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline.
Embodiment 5:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of two (triphen of dichloro are sequentially added in reaction tube
Base phosphine) palladium, 0.4 mM of potassium peroxydisulfate and 0.4 mM of 2- furoyl formic acid.2 milliliters of 1,4- dioxane are then added
For solvent, stops reaction after being stirred to react under the conditions of 78 DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate
It takes 3 times, merge organic phase and is dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most chromatographs afterwards through column
It isolates and purifies, column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6-
(furans -2- base) indoles simultaneously [1,2-a] quinoxaline, yield 38%.
Embodiment 6:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM copper acetate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, does not detect 6- (furans -2- base)
The generation of indoles simultaneously [1,2-a] quinoxaline.
Embodiment 7:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM silver acetate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, does not detect 6- (furans -2-
Base) indoles simultaneously [1,2-a] quinoxaline generation.
Embodiment 8:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM 1,4-benzoquinone and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, at 78 DEG C
Under the conditions of be stirred to react 12 hours after stop reaction.TLC (thin-layered chromatography) detection reaction, does not detect 6- (furans -2-
Base) indoles simultaneously [1,2-a] quinoxaline generation.
Embodiment 9:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, 78
Stop reaction after being stirred to react under the conditions of DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges
Organic phase is simultaneously dried, filtered using 0.5 gram of anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, institute
The petroleum ether for being volume ratio 75:1 with column chromatographic eluate: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base) Yin
Diindyl simultaneously [1,2-a] quinoxaline, yield 54%.
Embodiment 10:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM sodium peroxydisulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of Isosorbide-5-Nitrae-dioxane, which are then added, 78
Stop reaction after being stirred to react under the conditions of DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges
Organic phase is simultaneously dried, filtered using 0.5 gram of anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, institute
The petroleum ether for being volume ratio 75:1 with column chromatographic eluate: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base) Yin
Diindyl simultaneously [1,2-a] quinoxaline, yield 28%.
Embodiment 11:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of DMSO, which are then added, under the conditions of 78 DEG C
Stop reaction after being stirred to react 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect 6- (furans -2- base) indoles
And the generation of [1,2-a] quinoxaline.
Embodiment 12:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of DMF, which are then added, is stirred under the conditions of 78 DEG C
Stop reaction after mixing reaction 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect that indoles is simultaneously by 6- (furans -2- base)
The generation of [1,2-a] quinoxaline.
Embodiment 13:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of toluene, which are then added, under the conditions of 78 DEG C
Stop reaction after being stirred to react 12 hours.TLC (thin-layered chromatography) detection reaction, does not detect 6- (furans -2- base) indoles
And the generation of [1,2-a] quinoxaline.
Embodiment 14:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, closes
And organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification,
Column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base)
Simultaneously [1,2-a] quinoxaline, yield are up to 66% to indoles.
Simultaneously the hydrogen spectrum of [1,2-a] quinoxaline and carbon compose as shown in Figures 2 and 3, structure table respectively to 6- (furans -2- base) indoles
Needle data are as follows:
Yellow solid；mp 170-171℃；IR: ν=3028,2922,2854,2313,1742,1641,1641,
1521,1377,1126,875,795,729,592cm-1；1H NMR(400MHz,CDCl3) δ 8.47 (t, J=8.5Hz, 2H),
8.06 (d, J=7.9Hz, 1H), 7.99 (d, J=8.0Hz, 1H), 7.77 (s, 2H), 7.60-7.41 (m, 5H), 6.68 (dd, J
=3.4,1.7Hz, 1H)；13C NMR(100MHz,CDCl3)δ152.0,144.8,144.7,135.7,132.7,130.2,
130.0,129.4,128.2,126.7,124.4,124.2,122.9,122.7,114.6,114.5,113.4,112.1,
102.1；HRMS(ESI)m/z:calcd for C19H13N2O[M+H]+,285.1022；found 285.1020.
The structure of 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline is as follows:
Embodiment 15:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Stop reaction after being stirred to react under the conditions of 70 DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, closes
And organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification,
Column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base)
Indoles simultaneously [1,2-a] quinoxaline, yield 61%.
Embodiment 16:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Stop reaction after being stirred to react under the conditions of 85 DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, closes
And organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification,
Column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base)
Indoles simultaneously [1,2-a] quinoxaline, yield 64%.
Embodiment 17:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent, nitrogen that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Gas shielded stops reaction, is cooled to room temperature and filters, filtrate is extracted with ethyl acetate after being stirred to react under the conditions of 78 DEG C 12 hours
It takes 3 times, merge organic phase and is dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most chromatographs afterwards through column
It isolates and purifies, column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6-
(furans -2- base) indoles simultaneously [1,2-a] quinoxaline, yield 65%.
Embodiment 18:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.2 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, closes
And organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification,
Column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base)
Indoles simultaneously [1,2-a] quinoxaline, yield 47%.
Embodiment 19:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.2 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Stop reaction after being stirred to react under the conditions of 78 DEG C 12 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, closes
And organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification,
Column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base)
Indoles simultaneously [1,2-a] quinoxaline, yield 32%.
Embodiment 20:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Stop reaction after being stirred to react under the conditions of 78 DEG C 6 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, merges
Organic phase is simultaneously dried, filtered using 0.5 gram of anhydrous magnesium sulfate, and vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification, institute
The petroleum ether for being volume ratio 75:1 with column chromatographic eluate: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base) Yin
Diindyl simultaneously [1,2-a] quinoxaline, yield 46%.
Embodiment 21:
0.2 mM of 2- (1H- indoles -1- base) aniline, 0.01 mM of palladium acetate, 0.4 is sequentially added in reaction tube
MM ammonium persulfate and 0.4 mM of 2- furoyl formic acid.It is solvent that 2 milliliters of diethylene glycol dimethyl ethers, which are then added,
Stop reaction after being stirred to react under the conditions of 78 DEG C 24 hours, be cooled to room temperature and filter, filtrate is extracted with ethyl acetate 3 times, closes
And organic phase and dried, filtered using 0.5 gram of anhydrous magnesium sulfate, vacuum rotary steam obtains crude product, most afterwards through column chromatographic isolation and purification,
Column chromatographic eluate used is the petroleum ether of volume ratio 75:1: ethyl acetate mixed solvent.Obtain pure 6- (furans -2- base)
Indoles simultaneously [1,2-a] quinoxaline, yield 63%.
Test result in above-described embodiment is shown in Table 1.
Table 1: the conditional FP tree of reactiona
aReaction condition: 0.2 mM of aniline of 2- (1H- indoles -1- base), 0.4 mM of 2- furoyl formic acid, catalysis
0.01 mM of agent, 0.4 mM and 2.0 milliliters of solvent of oxidant sequentially adds in test tube, reacts 12 hours and (is not necessarily in 78 DEG C
Inert gas shielding)；bSeparation yield, n.d. representative do not detect product；cReaction temperature is 70 DEG C；dReaction temperature is 85 DEG C；e
Nitrogen protection；f2- furoyl formic acid dosage is 0.2 mM；gThe dosage of ammonium persulfate is 0.2 mM；hReaction time is
6 hours；iReaction time is 24 hours.
The present invention realizes 6- (furans -2- base) indoles, and simultaneously [1,2-a] quinoxaline efficiently synthesizes.The reaction condition is simple
It can complete in air；It is raw materials used nontoxic and cheap and easy to get；The reaction has stronger selectivity (mistake to oxidant and solvent
Sulfate is best oxidant, and diethylene glycol dimethyl ether is best reaction dissolvent)；Step economy is high, selectivity is single,
Safety easy to operate, mild condition, high income are the major advantages of reaction, which is 6- (furans -2- base) indoles simultaneously [1,2-
A] synthesis of quinoxaline provides new approaches.
Claims (1)
1. a kind of level-one amine guiding constructs 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline method, it is characterised in that it is specific
Step are as follows: in reaction tube, 2- (1 is addedHIndoles -1- base) aniline and 2- furoyl formic acid is raw material, with persulfate
For oxidant, using organic solvent as solvent, 70 ~ 90oIt stirs 10 ~ 24 hours under C, is cooled to room temperature after reaction, filter
Reaction solution, after vacuum rotary steam crude product, obtain 6- (furans -2- base) indoles simultaneously [1,2- through column chromatographic purifyinga] quinoxaline；
The 2- (1HIndoles -1- base) molar ratio of aniline and 2- furoyl formic acid is 1:1 ~ 2；
The oxidant is potassium peroxydisulfate, sodium peroxydisulfate and ammonium persulfate；Oxidant and 2- (1HIndoles -1- base) aniline rubs
You are than being 1 ~ 2:1；
The catalyst is palladium acetate, palladium trifluoroacetate, two (triphenylphosphine) palladium chlorides or palladium chloride；Catalyst and 2- (1H-
Indoles -1- base) aniline molar ratio be 0.05:1；
The solvent is 1,4- dioxane or diethylene glycol dimethyl ether；
The column chromatographs eluent as the mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is
100~10:1。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811576562.5A CN109438453A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811576562.5A CN109438453A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109438453A true CN109438453A (en) | 2019-03-08 |
Family
ID=65534877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811576562.5A Withdrawn CN109438453A (en) | 2018-12-22 | 2018-12-22 | The method of level-one amine guiding building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109438453A (en) |
-
2018
- 2018-12-22 CN CN201811576562.5A patent/CN109438453A/en not_active Withdrawn
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Regioselective and stereoselective sulfonylation of alkynylcarbonyl compounds in water | |
| CN107235923B (en) | Preparation method of 3-aryl quinoxalinone derivatives | |
| CN111233852B (en) | NON type chiral bisoxazoline ligand and synthetic method and application thereof | |
| CN102977017B (en) | Method for catalytically preparing 6(5H)-phenanthridine ketone by copper component | |
| CN109438451A (en) | The method of level-one amine guiding building 6- (2- bromophenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN109503603A (en) | The method of level-one amine guiding building 6- (4- n-butylphenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN105732648B (en) | The nitrogen-containing heterocycle compound and synthetic method of a kind of pyrrolo- furans | |
| CN109438453A (en) | The method of level-one amine guiding building 6- (furans -2- base) indoles simultaneously [1,2-a] quinoxaline | |
| CN109575032A (en) | The method of level-one amine guiding building 6- (3- fluorophenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN109438452A (en) | The method of level-one amine guiding building 6- (2- fluorophenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN109575033A (en) | The method of level-one amine guiding building 6- (2- aminomethyl phenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN109627249A (en) | The method of level-one amine guiding building 6- (naphthalene -1- base) indoles simultaneously [1,2-a] quinoxaline | |
| CN109503598A (en) | The method of level-one amine guiding building 6- (4- chlorphenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN109503601A (en) | The method of level-one amine guiding building 6- (4- bromophenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN109503596A (en) | The method of level-one amine guiding building 2- chloro-6-phenyl indoles simultaneously [1,2-a] quinoxaline | |
| CN109503600A (en) | The method of the level-one amine guiding building fluoro- 6- Phenylindole of 2- simultaneously [1,2-a] quinoxaline | |
| CN109627247A (en) | The method of level-one amine guiding building 8- benzyloxy -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
| CN109608466A (en) | The method of the level-one amine guiding building fluoro- 6- Phenylindole of 9- simultaneously [1,2-a] quinoxaline | |
| CN109503597A (en) | The method of level-one amine guiding building 6- (4- methoxyphenyl) indoles simultaneously [1,2-a] quinoxaline | |
| CN109575034A (en) | The method of level-one amine guiding building 6- Phenylindole simultaneously [1,2-a] quinoxaline | |
| CN109627245A (en) | The method of level-one amine guiding building 8- methoxyl group -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
| CN109503602A (en) | The method of the level-one amine guiding building fluoro- 6- Phenylindole of 8- simultaneously [1,2-a] quinoxaline | |
| CN109627246A (en) | The method of level-one amine guiding building 7- methyl -6- Phenylindole simultaneously [1,2-a] quinoxaline | |
| CN109485649A (en) | The method of the level-one amine guiding building fluoro- 6- Phenylindole of the chloro- 4- of 2- simultaneously [1,2-a] quinoxaline | |
| CN109438450A (en) | The method of level-one amine guiding building 9- methoxyl group -6- Phenylindole simultaneously [1,2-a] quinoxaline |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20190308 |
|
| WW01 | Invention patent application withdrawn after publication |