CN104692986B - The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate - Google Patents

The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate Download PDF

Info

Publication number
CN104692986B
CN104692986B CN201510100568.5A CN201510100568A CN104692986B CN 104692986 B CN104692986 B CN 104692986B CN 201510100568 A CN201510100568 A CN 201510100568A CN 104692986 B CN104692986 B CN 104692986B
Authority
CN
China
Prior art keywords
compound
synthetic method
formula
catalyst
alkali
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.)
Active
Application number
CN201510100568.5A
Other languages
Chinese (zh)
Other versions
CN104692986A (en
Inventor
翟学研
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nantong excellent art design Co., Ltd.
Original Assignee
Tan Yongshan
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Tan Yongshan filed Critical Tan Yongshan
Priority to CN201610217177.6A priority Critical patent/CN105753620B/en
Priority to CN201610216414.7A priority patent/CN105801338B/en
Priority to CN201610216546.XA priority patent/CN105801342B/en
Priority to CN201610216344.5A priority patent/CN105732246B/en
Priority to CN201610216389.2A priority patent/CN105801337B/en
Priority to CN201610217169.1A priority patent/CN105732247B/en
Priority to CN201610216500.8A priority patent/CN105753619B/en
Priority to CN201610216366.1A priority patent/CN105801336A/en
Priority to CN201610216498.4A priority patent/CN105777461B/en
Priority to CN201510100568.5A priority patent/CN104692986B/en
Publication of CN104692986A publication Critical patent/CN104692986A/en
Priority to PCT/CN2016/075413 priority patent/WO2016141828A1/en
Priority to PCT/CN2016/075439 priority patent/WO2016141839A1/en
Priority to PCT/CN2016/075402 priority patent/WO2016141825A1/en
Priority to PCT/CN2016/075414 priority patent/WO2016141829A1/en
Priority to PCT/CN2016/075417 priority patent/WO2016141832A1/en
Priority to PCT/CN2016/075400 priority patent/WO2016141823A1/en
Priority to PCT/CN2016/075416 priority patent/WO2016141831A1/en
Priority to PCT/CN2016/075437 priority patent/WO2016141837A1/en
Priority to PCT/CN2016/075454 priority patent/WO2016141844A1/en
Priority to PCT/CN2016/075446 priority patent/WO2016141840A1/en
Priority to PCT/CN2016/075453 priority patent/WO2016141843A1/en
Priority to PCT/CN2016/075452 priority patent/WO2016141842A1/en
Priority to PCT/CN2016/075438 priority patent/WO2016141838A1/en
Priority to PCT/CN2016/075434 priority patent/WO2016141834A1/en
Priority to PCT/CN2016/075435 priority patent/WO2016141835A1/en
Priority to PCT/CN2016/075401 priority patent/WO2016141824A1/en
Priority to PCT/CN2016/075404 priority patent/WO2016141827A1/en
Priority to PCT/CN2016/075415 priority patent/WO2016141830A1/en
Priority to PCT/CN2016/075436 priority patent/WO2016141836A1/en
Priority to PCT/CN2016/075449 priority patent/WO2016141841A1/en
Priority to PCT/CN2016/075403 priority patent/WO2016141826A1/en
Priority to PCT/CN2016/075418 priority patent/WO2016141833A1/en
Application granted granted Critical
Publication of CN104692986B publication Critical patent/CN104692986B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/10—Cyclisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/272—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions
    • C07C17/275—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions of hydrocarbons and halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2/00—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms
    • C07C2/02—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by addition between unsaturated hydrocarbons
    • C07C2/42—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by addition between unsaturated hydrocarbons homo- or co-oligomerisation with ring formation, not being a Diels-Alder conversion
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C15/00—Cyclic hydrocarbons containing only six-membered aromatic rings as cyclic parts
    • C07C15/20—Polycyclic condensed hydrocarbons
    • C07C15/27—Polycyclic condensed hydrocarbons containing three rings
    • C07C15/30—Phenanthrenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
    • C07C25/18—Polycyclic aromatic halogenated hydrocarbons
    • C07C25/22—Polycyclic aromatic halogenated hydrocarbons with condensed rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/127—Preparation from compounds containing pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The present invention relates to the synthetic method of phenanthrene compound shown in a kind of following formula (I),Described method comprises: under inert atmosphere, under catalyst, organic ligand and alkali exist, in solvent, following formula (II) compound and formula (III) compound react, thus the formula of obtaining (I) compound;Wherein, R1、R2Be H, C independently of one another1-C6Alkyl, C1-C6Alkoxy or halogen; R3For C6-C10Aryl or C5-C8Heteroaryl, described C6-C10Aryl or C4-C8Heteroaryl is optionally replaced by 1-3 substituting group, and described substituting group is C1-C6Alkyl or halogen. Described method has obtained good effect by the selection of suitable catalyst, organic ligand, alkali and solvent, possesses prospects for commercial application widely.

Description

The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate
Technical field
The present invention relates to a kind of synthetic method of fused ring compound, relate more specifically to a kind of medicine intermediateThe synthetic method of luxuriant and rich with fragrance compounds, belongs to the synthetic field of organic synthesis and medicine intermediate.
Background technology
Fused ring compound is if the compounds such as naphthalene, anthracene, phenanthrene are because its ubiquitous biologically active is curedMedicine research staff's attention and concern. Wherein, phenanthrene and derivative thereof are the important phenolic compounds of a class,Drug design and synthetic, material development field are widely used in.
Just because of excellent in performance like this and the potentiality of luxuriant and rich with fragrance compounds, thereby research phenanthrene and derivative thereofNovel method for synthesizing be also always organic chemical synthesis worker hot issue very deeply concerned.
Up to the present, had the preparation technology of multiple luxuriant and rich with fragrance compounds in prior art, it is from manyIndividual angle has been studied the applicable synthetic method of luxuriant and rich with fragrance compounds. For example:
(" PhenanthreneSynthesisbyEosinY-Catalyzed, the Visible such as XiaoTieboLight-Induced[4+2]BenzannulationofBiaryldiazoniumSaltswithAlkynes”,Adv.Synth.Catal., 2012,354,3195-3199) reported a kind of without metal catalytic, visible[4+2] benzo cyclization of photoinduced diaryl diazo salt. Its equation is as follows:
(" the ExpeditiousSynthesisofPhenanthrenesviaCuBr such as YeFei2-CatalyzedCouplingofTerminalAlkynesandN-TosylhydrazonesDerivedfromO-FoRmylBiphenyls ", OrganicLetters, 2011,13,5020-5023) a kind of benzyl CuBr disclosed2Coupling/the cyclization of catalysis, its N-Tosylhydrazone that is derived from adjacent formyl biphenyl is raw material,Reaction equation is as follows:
(" ExpedientSynthesisofPhenanthrenesviaIn (the III)-C such as KwonYongseokatalyzed6-Exo-DigCycloisomerization”,OrganicLetters,2013,15,920-923)Reported the reaction of the luxuriant and rich with fragrance compounds of preparation of a kind of In (III) catalysis, it has, and reaction is efficient, substrate is suitableBy the wide advantage of scope, its reaction equation is as follows:
As mentioned above, although disclose the preparation side of various types of luxuriant and rich with fragrance compounds in prior artMethod, but these methods still can not meet the Production requirement in medicine, the synthetic field of chemical industry, and this is due to itThe problems such as intrinsic production efficiency is low, raw material can not make full use of.
In view of this, the inventor has aimed to provide a kind of luxuriant and rich with fragrance compounds by a large amount of experimental studiesNew catalytic synthetic method, reached high, the willing object of yield, there is work very widelyIndustry application prospect.
Summary of the invention
For many defects of above-mentioned existence, the inventor is paying after a large amount of creative works, warpCross further investigation, and developed a kind of synthetic method of the phenanthrene compound that can be used as pharmaceutical intermediate, and thenComplete the present invention.
Particularly, the invention provides the synthetic method of phenanthrene compound shown in a kind of following formula (I),
Described method comprises: under inert atmosphere, under catalyst, organic ligand and alkali exist, in solventIn, following formula (II) compound and formula (III) compound react, thus the formula of obtaining (I) compound;
Wherein, R1、R2Be H, C independently of one another1-C6Alkyl, C1-C6Alkoxy or halogen;
R3For C6-C10Aryl or C5-C8Heteroaryl, described C6-C10Aryl or C4-C8Heteroaryl is optionalReplaced by 1-3 substituting group, for example, can be replaced by 1,2 or 3 substituting groups described replacementBase is C1-C6Alkyl or halogen.
In described synthetic method of the present invention, C1-C6Alkyl refers to the alkyl with 1-6 carbon atom,For example can be methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl, isobutyl group, the tert-butyl group,N-pentyl, isopentyl, n-hexyl etc.
In described synthetic method of the present invention, C1-C6Alkoxyl refers to " C defined above1-C6Alkyl "Group after being connected with O atom.
In described synthetic method of the present invention, described halogen for example can be fluorine, chlorine, bromine or iodine.
In described synthetic method of the present invention, described C6-C10Aryl refers to have 6-10 carbon atomAryl, for example can be phenyl or naphthyl.
In described synthetic method of the present invention, described C4-C8Heteroaryl refers to have 4-8 carbon atomHeteroaryl, for example can be pyridine radicals, furan thiophene base or thienyl etc.
In described synthetic method of the present invention, described catalyst is organic palladium compound and organic copper chemical combinationThe mixture of thing, both mol ratios are 1:2-4, for example, can be 1:2,1:3 or 1:4.
Wherein, described organic palladium compound example is acid chloride (Pd (OAc)2), palladium bichloride (PdCl2), acetylAcetone palladium (Pd (acac)2), (1,5-cyclo-octadiene) palladium bichloride (PdCl2(cod)), palladium trifluoroacetate (Pd (TFA)2), [1,1 '-bis-(diphenylphosphino) ferrocene] palladium chloride (PdCl2(dppf)), two (triphenylphosphine) palladium bichloride(PdCl2(PPh3)2) in any or any multiple mixture, most preferably be PdCl2(dppf)。
Wherein, described organocopper compound is hexafluorophosphoric acid tetrem nitrile copper ([(CH3CN)4Cu]PF6), trifluoroCopper methane sulfonate (Cu (OTf)2), acetylacetone copper (Cu (acac)2), in copper acetate any one or multiple,Most preferably be hexafluorophosphoric acid tetrem nitrile copper ([(CH3CN)4Cu]PF6)。
In described synthetic method of the present invention, described organic ligand is nitrogenous bidentate ligand, for example, can beReplace or unsubstituted bipyridyl, replacement or unsubstituted Phen etc., for example, can be following L1-L4：
Most preferably be L1.
In described synthetic method of the present invention, described alkali is Na2CO3、K2CO3、NaOH、KOH、K3PO4、Na3PO4、NaHCO3、KHCO3, sodium acetate, caustic alcohol, potassium tert-butoxide, diisopropylAny or any multiple mixture in amine, diisopropyl ethanolamine etc.; Most preferably be diisopropylEthylethanolamine.
In described synthetic method of the present invention, described solvent is PEG-400 and 1-pi-allyl-3-methylThe mixture of tetrafluoroborate, both volume ratios are 1:0.1-0.3, for example, can be 1:0.1,1:0.2Or 1:0.3.
In described synthetic method of the present invention, described inert atmosphere for example can be nitrogen atmosphere or argon atmospherEnclose.
In described synthetic method of the present invention, the mol ratio of described formula (II) compound and formula (III) compoundFor 1:2-4, for example, can be 1:2,1:3 or 1:4.
In described synthetic method of the present invention, the mol ratio of described formula (II) compound and catalyst is 1:0.08-0.15, i.e. rubbing of two kinds of components of the mole dosage of described formula (II) compound and the described catalyst of formationYour ratio of consumption sum is 1:0.08-0.15, for example, can be 1:0.08,1:0.1,1:0.12,1:0.14 or 1:0.15。
In described synthetic method of the present invention, the mol ratio of described formula (II) compound and organic ligand is 1:0.1-0.2, for example, can be 1:0.1,1:0.15 or 1:0.2.
In described synthetic method of the present invention, the mol ratio of described formula (II) compound and alkali is 1:2-3,For example can be 1:2,1:2.5 or 1:3.
In described synthetic method of the present invention, the consumption of described solvent does not have strict restriction, abilityField technique personnel can carry out suitable selection to its consumption, for example can according to make post processing be easy to carry out,Be enough to reaction smoothly.
In described synthetic method of the present invention, reaction temperature is 60-80 DEG C, for example, can be 60 DEG C, 70DEG C or 80 DEG C.
In described synthetic method of the present invention, the reaction time is 8-12 hour, for example can be 8 hours,10 hours or 12 hours.
In described synthetic method of the present invention, the post processing after reaction finishes is specific as follows: reaction finishesAfter, in reaction system, adding deionized water, fully vibration, washing, separate organic layer, again spendsIonized water washing, separates organic layer; By organic layer reduced pressure concentration, remove silicagel column on gained residueChromatogram, the n-hexyl alcohol using volume ratio as 1:2-4 and the mixed solvent of chloroform carry out wash-out as eluting solvent,Detect through TLC, merge same composition, remove eluting solvent, obtain target compound.
As mentioned above, the invention provides a kind of synthetic method of the phenanthrene compound as medicine intermediate,Selection/the combination of described method by suitable catalyst, You Jipei, alkali and solvent/work in coordination with, thereby with heightProductive rate has obtained object product, of great advantage to the actual production of the intermediates such as medicine, chemical industry, has wideGeneral prospects for commercial application.
Detailed description of the invention
Below by specific embodiment, the present invention is described in detail, but these exemplary embodimentsPurposes and object be only used for exemplifying the present invention, not real protection scope of the present invention is formed to any shapeAny restriction of formula, is more non-ly confined to this by protection scope of the present invention.
Wherein, in all embodiments, unless otherwise prescribed, the ligand L 1 using is above formula L1The part referring to.
Embodiment 1
In reactor, add in right amount by PEG-400 and 1-pi-allyl-3-methyl imidazolium tetrafluoroborate groupThe mixed solvent (both volume ratios are 1:0.1) becoming, then uses nitrogen replacement twice, makes in reactor to beNitrogen atmosphere; Then add the bromo-4 '-chlordiphenyl of 100mmol above formula (II) compound 2-, 200mmolAbove formula (III) compound styrene, by 3mmolPdCl2And 6mmol hexafluorophosphoric acid tetrem nitrile (dppf)Composite catalyst, 10mmol ligand L 1 and the 200mmol diisopropyl ethanolamine of copper composition, stirMix down and be warming up to 60 DEG C, and react 12 hours at this temperature.
After reaction finishes, in reaction system, add deionized water, fully vibration, washing, separate organicLayer, with deionized water washing, separates organic layer again; By organic layer reduced pressure concentration, to remove, gained is residualStay silica gel column chromatography on thing, the n-hexyl alcohol using volume ratio as 1:2 and the mixed solvent of chloroform are molten as wash-outWash-out is carried out in agent, detects through TLC, merges same composition, removes eluting solvent, obtains target chemical combinationThe chloro-10-phenyl of thing 2-phenanthrene, productive rate is 95.3%.
1H-NMR(300MHz,CDCl3)δ:8.63(d,J＝8.9Hz,1H),8.49-8.44(m,2H),7.84(d,J＝2.2Hz,1H),7.71(d,J＝8.1Hz,1H),7.63(s,1H),7.52(dd,J＝8.9,2.3Hz,1H),7.51-7.41(m,6H)。
Embodiment 2
In reactor, add in right amount by PEG-400 and 1-pi-allyl-3-methyl imidazolium tetrafluoroborate groupThe mixed solvent (both volume ratios are 1:0.2) becoming, then uses nitrogen replacement twice, makes in reactor to beNitrogen atmosphere; Then add 100mmol above formula (II) compound 2-bromo biphenyl, 300mmol above formula (III) compound 1-methyl-3-vinyl benzene, by 3mmolPdCl2And 9mmol hexafluorophosphoric acid four (dppf)Composite catalyst, 15mmol ligand L 1 and the 250mmol diisopropyl ethanolamine of acetonitrile copper composition,Under stirring, be warming up to 70 DEG C, and at this temperature, react 10 hours.
After reaction finishes, in reaction system, add deionized water, fully vibration, washing, separate organicLayer, with deionized water washing, separates organic layer again; By organic layer reduced pressure concentration, to remove, gained is residualStay silica gel column chromatography on thing, the n-hexyl alcohol using volume ratio as 1:3 and the mixed solvent of chloroform are molten as wash-outWash-out is carried out in agent, detects through TLC, merges same composition, removes eluting solvent, obtains target chemical combinationTolyl phenanthrene between thing 9-, productive rate is 94.7%.
1H-NMR(300MHz,CDCl3,)δ:8.72(dd,J＝8.3,1.2Hz,1H),8.51(d,J＝1.6Hz,1H),7.96(dd,J＝8.3,1.4Hz,1H),7.83(d,J＝8.0Hz,1H),7.68-7.61(m,2H),7.52(ddd,J＝8.2,6.9,1.3Hz,1H),7.45-7.31(m,4H),7.27-7.22(m,2H),2.63(s,3H)。
Embodiment 3
In reactor, add in right amount by PEG-400 and 1-pi-allyl-3-methyl imidazolium tetrafluoroborate groupThe mixed solvent (both volume ratios are 1:0.3) becoming, then uses nitrogen replacement twice, makes in reactor to beNitrogen atmosphere; Then add 100mmol above formula (II) compound 2-bromo biphenyl, 400mmol above formula (III) compound 1-vinyl naphthalene, by 3mmolPdCl2And 12mmol hexafluorophosphoric acid tetrem nitrile copper (dppf)Composite catalyst, 20mmol ligand L 1 and the 300mmol diisopropyl ethanolamine of composition, stirUnder be warming up to 80 DEG C, and at this temperature, react 8 hours.
After reaction finishes, in reaction system, add deionized water, fully vibration, washing, separate organicLayer, with deionized water washing, separates organic layer again; By organic layer reduced pressure concentration, to remove, gained is residualStay silica gel column chromatography on thing, the n-hexyl alcohol using volume ratio as 1:4 and the mixed solvent of chloroform are molten as wash-outWash-out is carried out in agent, detects through TLC, merges same composition, removes eluting solvent, obtains target chemical combinationThing 9-(naphthalene-1-yl) phenanthrene, productive rate is 95.7%.
1H-NMR(300MHz,CDCl3)δ:8.82(d,J＝8.2Hz,2H),8.61(s,1H),8.02-7.95(m,2H),7.83(d,J＝8.0Hz,1H),7.74(s,1H),7.65-7.31(m,9H)。
Embodiment 4
In reactor, add in right amount by PEG-400 and 1-pi-allyl-3-methyl imidazolium tetrafluoroborate groupThe mixed solvent (both volume ratios are 1:0.2) becoming, then uses nitrogen replacement twice, makes in reactor to beNitrogen atmosphere; Then add 100mmol above formula (II) compound 2-bromo biphenyl, 300mmol above formula (III) compound 2-vinylpyridine, by 2mmolPdCl2And 6mmol hexafluorophosphoric acid tetrem nitrile (dppf)Composite catalyst, 20mmol ligand L 1 and the 200mmol diisopropyl ethanolamine of copper composition, stirMix down and be warming up to 70 DEG C, and react 12 hours at this temperature.
After reaction finishes, in reaction system, add deionized water, fully vibration, washing, separate organicLayer, with deionized water washing, separates organic layer again; By organic layer reduced pressure concentration, to remove, gained is residualStay silica gel column chromatography on thing, the n-hexyl alcohol using volume ratio as 1:3 and the mixed solvent of chloroform are molten as wash-outWash-out is carried out in agent, detects through TLC, merges same composition, removes eluting solvent, obtains target chemical combinationThing 9-(pyridine-2-yl) phenanthrene, productive rate is 94.9%.
1H-NMR(300MHz,CDCl3)δ:8.83(d,J＝4.9Hz,1H),8.76(dd,J＝8.3,1.3Hz,1H),8.57-8.51(m,1H),8.07(dd,J＝8.2,1.4Hz,1H),7.89-7.83(m,3H),7.71-7.62(m,2H),7.58-7.52(m,1H),7.45(dd,J＝8.1 Hz,1.6Hz,1H),7.41-7.35(m,2H)。
Embodiment 5-28: the investigation of palladium catalyst compound component
Embodiment 5-8: remove respectively by PdCl wherein2(dppf) replace with acid chloride (Pd (OAc)2) outside, itsIts operation is all constant, to have implemented embodiment 5-8 with the same way of embodiment 1-4.
Embodiment 9-12: remove respectively by PdCl wherein2(dppf) replace with palladium bichloride (PdCl2) outside, otherOperate all constant, to have implemented embodiment 9-12 with the same way of embodiment 1-4.
Embodiment 13-16: remove respectively by PdCl wherein2(dppf) replace with palladium acetylacetonate (Pd (acac)2)Outward, other operation is all constant, to have implemented embodiment 13-16 with the same way of embodiment 1-4.
Embodiment 17-20: remove respectively by PdCl wherein2(dppf) replace with (1,5-cyclo-octadiene) palladium bichloride(PdCl2(cod)), other operation is all constant, to have implemented embodiment with the same way of embodiment 1-417-20。
Embodiment 21-24: remove respectively by PdCl wherein2(dppf) replace with palladium trifluoroacetate (Pd (TFA)2)Outward, other operation is all constant, to have implemented embodiment 21-24 with the same way of embodiment 1-4.
Embodiment 25-28: remove respectively by PdCl wherein2(dppf) replace with two (triphenylphosphine) palladium bichloride (PdCl2(PPh3)2) outside, other operation is all constant, to have implemented embodiment with the same way of embodiment 1-425-28。
The productive rate of products therefrom is as shown in table 1 below:
Table 1: the investigation of palladium compound component
As can be seen here, when by the PdCl in composite catalyst2(dppf) while replacing with other palladium compound, allCause productive rate to have significantly and reduce, this has proved PdCl2(dppf) can be together with hexafluorophosphoric acid tetrem nitrile copper toolThere is best catalytic effect.
Embodiment 29-40: the investigation of catalyst copper compound component
Embodiment 29-32: except respectively hexafluorophosphoric acid tetrem nitrile copper wherein being replaced with to copper trifluoromethanesulfcomposite(Cu(OTf)2) outside, other operation is all constant, to have implemented embodiment 2 with the same way of embodiment 1-49-32。
Embodiment 33-36: except respectively hexafluorophosphoric acid tetrem nitrile copper wherein being replaced with to acetylacetone copper (Cu(acac)2) outside, other operation is all constant, to have implemented embodiment 33-3 with the same way of embodiment 1-46。
Embodiment 37-40: except respectively hexafluorophosphoric acid tetrem nitrile copper wherein being replaced with copper acetate, itsIts operation is all constant, to have implemented embodiment 37-40 with the same way of embodiment 1-4.
The productive rate of products therefrom is as shown in table 2 below:
Table 2: the investigation of copper compound component
As can be seen here, when the hexafluorophosphoric acid tetrem nitrile copper in composite catalyst is replaced with to other copper compoundTime, all cause productive rate to have significantly and reduce, this proved hexafluorophosphoric acid tetrem nitrile copper can with PdCl2(dppf)Bring into play together best catalytic effect.
Embodiment 41-52: the investigation of organic ligand
Embodiment 41-44: except respectively organic ligand wherein being replaced with L2 by L1, other operationAll constant, to have implemented embodiment 41-44 with the same way of embodiment 1-4.
Embodiment 45-48: except respectively organic ligand wherein being replaced with L3 by L1, other operationAll constant, to have implemented embodiment 45-48 with the same way of embodiment 1-4.
Embodiment 49-52: except respectively organic ligand wherein being replaced with L4 by L1, other operationAll constant, to have implemented embodiment 49-52 with the same way of embodiment 1-4.
The productive rate of products therefrom is as shown in table 3 below:
Table 3: the investigation of organic ligand
As can be seen here, in all parts, L1 has best reaction effect, even if tie with L1Structure is L2 very similarly, and its productive rate also has suitable reduction.
Embodiment 53-64: the investigation of alkali
Except alkali is wherein replaced with other alkali by diisopropyl ethanolamine, other all constant and with enforcementThe same way of example 1-4 has been implemented embodiment 53-64, and the alkali that uses, corresponding relation and products collection efficiency are shown inFollowing table 4:
Table 4: the investigation of alkali
As can be seen here, when using when other alkali, all cause productive rate to have significantly and reduce, even if with enforcementThe very similar diisopropylamine of institute's diisopropyl ethanolamine that uses in example 1-4, its productive rate also has significantly and fallsLow.
Embodiment 65-72: the investigation of solvent
Embodiment 65-68: respectively the mixed solvent in embodiment 1-4 is replaced with to PEG-400, otherAll constant, and obtained embodiment 65-68.
Embodiment 69-72: respectively the mixed solvent in embodiment 1-4 is replaced with to 1-pi-allyl-3-methylTetrafluoroborate, other is all constant, and has obtained embodiment 69-72.
The productive rate of products therefrom is as shown in table 5 below:
Table 5: the investigation of solvent
As can be seen here, in the time using the solvent of one-component, productive rate has suitable reduction, only has and uses twoWhen person's composition, just can obtain excellent effect of the present invention.
Embodiment 73-80: the investigation of single catalyst component
Embodiment 73-76: the Pd that respectively composite catalyst in embodiment 1-4 is replaced with to same amount Cl2(dppf), i.e. PdCl2(dppf) consumption is total consumption of original two kinds of components, and has obtained embodiment73-76。
Embodiment 77-80: respectively the composite catalyst in embodiment 1-4 is replaced with to six of same amountFluorophosphoric acid tetrem nitrile copper, the consumption of hexafluorophosphoric acid tetrem nitrile copper is total consumption of original two kinds of components, andObtain embodiment 77-80.
The productive rate of products therefrom is as shown in table 6 below:
Table 6: the investigation of single catalyst component
As can be seen here, in the time using one-component catalyst, productive rate has suitable reduction, only has and uses twoWhen person's mixture, bring into play each other unique synergy, urged thereby obtained excellence of the present inventionChange effect, this is non-obvious.
In sum, the invention provides the synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate, at thisIn method, the comprehensive selection by catalyst, organic ligand, alkali and solvent and/or collaborative, thereby with heightProductive rate has obtained object product, and in the time changing any component or omitted, all causes productProductive rate has remarkable reduction. As can be seen here, method of the present invention have good, commercial Application is dived widelyPower, can be applicable to the synthetic field of medicine intermediate.
The purposes that should be appreciated that these embodiment is only for the present invention is described but not be intended to limit of the present inventionProtection domain. In addition, also should be understood that after having read technology contents of the present invention art technologyPersonnel can make various changes, amendment and/or modification to the present invention, and these all equivalent form of values fall equallyWithin the protection domain limiting in the application's appended claims.

Claims (8)

1. a synthetic method for phenanthrene compound shown in following formula (I),
Described method comprises: under inert atmosphere, and under catalyst, organic ligand and alkali exist,In solvent, following formula (II) compound and formula (III) compound react, thereby the formula of obtaining (I) is changedCompound;
Wherein, R1、R2Be H, C independently of one another1-C6Alkyl, C1-C6Alkoxy or halogen;
R3For C6-C10Aryl or C5-C8Heteroaryl, described C6-C10Aryl or C4-C8HeteroarylOptionally replaced by 1-3 substituting group, described substituting group is C1-C6Alkyl or halogen;
Described catalyst is the mixture of organic palladium compound and organocopper compound, and both rubYou are than being 1:2-4, and wherein, described organic palladium compound is PdCl2(dppf), described organic copperCompound is hexafluorophosphoric acid tetrem nitrile copper;
Described organic ligand is following L1-L4:
Described alkali is diisopropyl ethanolamine;
Described solvent is PEG-400 and the mixing of 1-pi-allyl-3-methyl imidazolium tetrafluoroborateThing, both volume ratios are 1:0.1-0.3.
2. synthetic method according to claim 1, is characterized in that: described organic ligandFor L1.
3. synthetic method according to claim 1 and 2, is characterized in that: described solventFor the mixture of PEG-400 and 1-pi-allyl-3-methyl imidazolium tetrafluoroborate, both volume ratiosFor 1:0.1-0.3.
4. synthetic method according to claim 1 and 2, is characterized in that: described formula (II)The mol ratio of compound and formula (III) compound is 1:2-4.
5. synthetic method according to claim 1 and 2, is characterized in that: described formula (II)The mol ratio of compound and catalyst is 1:0.08-0.15.
6. synthetic method according to claim 1 and 2, is characterized in that: described formula (II)The mol ratio of compound and organic ligand is 1:0.1-0.2.
7. synthetic method according to claim 1 and 2, is characterized in that: described formula (II)The mol ratio of compound and alkali is 1:2-3.
8. synthetic method according to claim 7, is characterized in that: reaction temperature is60-80 DEG C; Reaction time is 8-12 hour.
CN201510100568.5A 2015-03-06 2015-03-06 The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate Active CN104692986B (en)

Priority Applications (32)

Application Number Priority Date Filing Date Title
CN201610217177.6A CN105753620B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene compound using copper trifluoromethanesulfcomposite
CN201610216414.7A CN105801338B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene class compound using palladium acetylacetonate
CN201610216546.XA CN105801342B (en) 2015-03-06 2015-03-06 A kind of method that medicine intermediate phenanthrene compound is synthesized under diisopropylamine environment
CN201610216344.5A CN105732246B (en) 2015-03-06 2015-03-06 It is a kind of to apply PdCl2(PPh3)2The method for synthesizing medicine intermediate phenanthrene compound
CN201610216389.2A CN105801337B (en) 2015-03-06 2015-03-06 It is a kind of to apply PdCl2(cod) method for synthesizing medicine intermediate phenanthrene compound
CN201610217169.1A CN105732247B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene compound using acetylacetone copper
CN201610216500.8A CN105753619B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene compound using copper acetate
CN201610216366.1A CN105801336A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound from palladium trifluoroacetate
CN201610216498.4A CN105777461B (en) 2015-03-06 2015-03-06 A kind of method that medicine intermediate phenanthrene compound is synthesized under sodium carbonate environment
CN201510100568.5A CN104692986B (en) 2015-03-06 2015-03-06 The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate
PCT/CN2016/075416 WO2016141831A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds using palladium acetylacetonate
PCT/CN2016/075434 WO2016141834A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound using pdcl2(pph3)2
PCT/CN2016/075402 WO2016141825A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds in sodium acetate environment
PCT/CN2016/075414 WO2016141829A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds using palladium acetate
PCT/CN2016/075417 WO2016141832A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds using pdcl2(cod)
PCT/CN2016/075400 WO2016141823A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds in potassium bicarbonate environment
PCT/CN2016/075413 WO2016141828A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds
PCT/CN2016/075437 WO2016141837A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound using copper acetate
PCT/CN2016/075454 WO2016141844A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound in sodium bicarbonate environment
PCT/CN2016/075446 WO2016141840A1 (en) 2015-03-06 2016-03-03 Method synthesizing pharmaceutical intermediate phenanthrene compound in sodium hydroxide environment
PCT/CN2016/075453 WO2016141843A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound in sodium phosphate environment
PCT/CN2016/075452 WO2016141842A1 (en) 2015-03-06 2016-03-03 Method for synthesising pharmaceutical intermediate phenanthrene compound in potassium phosphate environment
PCT/CN2016/075438 WO2016141838A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound in sodium carbonate environment
PCT/CN2016/075439 WO2016141839A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium carbonate environment
PCT/CN2016/075435 WO2016141835A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound using copper trifluomethanesulfonate
PCT/CN2016/075401 WO2016141824A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds in sodium acetate environment
PCT/CN2016/075404 WO2016141827A1 (en) 2015-03-06 2016-03-03 Method of synthesizing pharmaceutical intermediate phenanthrene compound in the presence of diisopropylamine
PCT/CN2016/075415 WO2016141830A1 (en) 2015-03-06 2016-03-03 Method for applying palladium chloride to synthesise pharmaceutical intermediate phenanthrene compound
PCT/CN2016/075436 WO2016141836A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound using copper acetylacetonate
PCT/CN2016/075449 WO2016141841A1 (en) 2015-03-06 2016-03-03 Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium hydroxide environment
PCT/CN2016/075403 WO2016141826A1 (en) 2015-03-06 2016-03-03 Method for synthesising pharmaceutical intermediate phenanthrene compound in potassium tert-butoxide environment
PCT/CN2016/075418 WO2016141833A1 (en) 2015-03-06 2016-03-03 Method for synthesizing medical intermediate phenanthrene compounds using palladium trifluoroacetate

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510100568.5A CN104692986B (en) 2015-03-06 2015-03-06 The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate

Related Child Applications (21)

Application Number Title Priority Date Filing Date
CN201610216344.5A Division CN105732246B (en) 2015-03-06 2015-03-06 It is a kind of to apply PdCl2(PPh3)2The method for synthesizing medicine intermediate phenanthrene compound
CN201610217177.6A Division CN105753620B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene compound using copper trifluoromethanesulfcomposite
CN201610217151.1A Division CN105801343A (en) 2015-03-06 2015-03-06 Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium phosphate environment
CN201610217169.1A Division CN105732247B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene compound using acetylacetone copper
CN201610216435.9A Division CN105801340A (en) 2015-03-06 2015-03-06 Method for synthesizing pharmaceutical intermediate phenanthrene compound in sodium phosphate environment
CN201610216498.4A Division CN105777461B (en) 2015-03-06 2015-03-06 A kind of method that medicine intermediate phenanthrene compound is synthesized under sodium carbonate environment
CN201610216463.0A Division CN105801341A (en) 2015-03-06 2015-03-06 Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium hydroxide environment
CN201610216420.2A Division CN105801339A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate, namely, phenanthrene compound, in sodium bicarbonate environment
CN201610216561.4A Division CN105777481A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound in potassium tert-butoxide environment
CN201610216564.8A Division CN105777462A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound in potassium bicarbonate environment
CN201610216546.XA Division CN105801342B (en) 2015-03-06 2015-03-06 A kind of method that medicine intermediate phenanthrene compound is synthesized under diisopropylamine environment
CN201610217155.XA Division CN105801344A (en) 2015-03-06 2015-03-06 Method for synthesizing pharmaceutical intermediate phenanthrene compound in sodium hydroxide environment
CN201610216500.8A Division CN105753619B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene compound using copper acetate
CN201610217180.8A Division CN105669336A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound in sodium ethoxide environment
CN201610217136.7A Division CN105646118A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound from palladium acetate
CN201610216416.6A Division CN105646116A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound from palladium chloride
CN201610216465.XA Division CN105753618A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound in potassium carbonate environment
CN201610216366.1A Division CN105801336A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound from palladium trifluoroacetate
CN201610216389.2A Division CN105801337B (en) 2015-03-06 2015-03-06 It is a kind of to apply PdCl2(cod) method for synthesizing medicine intermediate phenanthrene compound
CN201610216580.7A Division CN105646117A (en) 2015-03-06 2015-03-06 Method for synthesizing medicinal midbody phenanthrene compound in sodium acetate environment
CN201610216414.7A Division CN105801338B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene class compound using palladium acetylacetonate

Publications (2)

Publication Number Publication Date
CN104692986A CN104692986A (en) 2015-06-10
CN104692986B true CN104692986B (en) 2016-05-25

Family

ID=53340585

Family Applications (3)

Application Number Title Priority Date Filing Date
CN201610216366.1A Withdrawn CN105801336A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound from palladium trifluoroacetate
CN201610216414.7A Active CN105801338B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene class compound using palladium acetylacetonate
CN201510100568.5A Active CN104692986B (en) 2015-03-06 2015-03-06 The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate

Family Applications Before (2)

Application Number Title Priority Date Filing Date
CN201610216366.1A Withdrawn CN105801336A (en) 2015-03-06 2015-03-06 Method for synthesizing medical intermediate phenanthrene compound from palladium trifluoroacetate
CN201610216414.7A Active CN105801338B (en) 2015-03-06 2015-03-06 A method of synthesizing medicine intermediate phenanthrene class compound using palladium acetylacetonate

Country Status (2)

Country Link
CN (3) CN105801336A (en)
WO (22) WO2016141826A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9996386B2 (en) 2014-07-23 2018-06-12 Intel Corporation Mid-thread pre-emption with software assisted context switch
CN105801336A (en) * 2015-03-06 2016-07-27 胡淑婷 Method for synthesizing medical intermediate phenanthrene compound from palladium trifluoroacetate
CN105153152B (en) * 2015-08-28 2017-06-13 泉州奔众空气过滤网有限公司 A kind of synthetic method of imidazoles fused ring compound

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102827077A (en) * 2012-09-07 2012-12-19 浙江大学 Preparation method for phenanthridine derivative

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105801336A (en) * 2015-03-06 2016-07-27 胡淑婷 Method for synthesizing medical intermediate phenanthrene compound from palladium trifluoroacetate

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102827077A (en) * 2012-09-07 2012-12-19 浙江大学 Preparation method for phenanthridine derivative

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Anna Iuliano et al.Ring-Closing Olefin Metathesis of 2,2&cent *
-Divinylbiphenyls: A Novel and General Approach to Phenanthrenes.《ORGANIC LETTERS》.2004,第6卷(第21期), *
Proton Abstraction Mechanism for the Palladium-Catalyzed Intramolecular Arylation;Domingo Garcia-Cuadrado et al;《J. AM. CHEM. SOC.》;20051231;第128卷(第4期);1066-1067 *
Synthesis of Fused Polycycles by 1,4-Palladium Migration Chemistry;Qinhua Huang et al;《J. Org. Chem.》;20041026;第69卷(第24期);8251-8257 *
Synthesis of Polycyclic Aromatics and Heteroaromatics via Electrophilic Cyclization;Tuanli Yao et al;《J. Org. Chem.》;20050323;第70卷(第9期);3511-3517 *
Total Syntheses of the Tylophora Alkaloids Cryptopleurine, (-)-Antofine,(-)-Tylophorine, and(-)-Ficuseptine C;Alois Fürstner;《Chem. Eur. J.》;20060731;第12卷;7398-7410 *

Also Published As

Publication number Publication date
WO2016141844A1 (en) 2016-09-15
WO2016141831A1 (en) 2016-09-15
WO2016141841A1 (en) 2016-09-15
CN105801336A (en) 2016-07-27
WO2016141833A1 (en) 2016-09-15
CN105801338A (en) 2016-07-27
CN105801338B (en) 2018-08-14
WO2016141832A1 (en) 2016-09-15
CN104692986A (en) 2015-06-10
WO2016141842A1 (en) 2016-09-15
WO2016141840A1 (en) 2016-09-15
WO2016141823A1 (en) 2016-09-15
WO2016141824A1 (en) 2016-09-15
WO2016141837A1 (en) 2016-09-15
WO2016141839A1 (en) 2016-09-15
WO2016141826A1 (en) 2016-09-15
WO2016141825A1 (en) 2016-09-15
WO2016141828A1 (en) 2016-09-15
WO2016141829A1 (en) 2016-09-15
WO2016141827A1 (en) 2016-09-15
WO2016141843A1 (en) 2016-09-15
WO2016141836A1 (en) 2016-09-15
WO2016141835A1 (en) 2016-09-15
WO2016141834A1 (en) 2016-09-15
WO2016141830A1 (en) 2016-09-15
WO2016141838A1 (en) 2016-09-15

Similar Documents

Publication Publication Date Title
CN104692986B (en) The synthetic method of the luxuriant and rich with fragrance compounds of a kind of medicine intermediate
CN105646118A (en) Method for synthesizing medical intermediate phenanthrene compound from palladium acetate
CN105646116A (en) Method for synthesizing medical intermediate phenanthrene compound from palladium chloride
CN105732247B (en) A method of synthesizing medicine intermediate phenanthrene compound using acetylacetone copper
CN105753620B (en) A method of synthesizing medicine intermediate phenanthrene compound using copper trifluoromethanesulfcomposite
CN105753619B (en) A method of synthesizing medicine intermediate phenanthrene compound using copper acetate
CN105777461B (en) A kind of method that medicine intermediate phenanthrene compound is synthesized under sodium carbonate environment
CN105646117A (en) Method for synthesizing medicinal midbody phenanthrene compound in sodium acetate environment
CN105801342B (en) A kind of method that medicine intermediate phenanthrene compound is synthesized under diisopropylamine environment
CN105801337B (en) It is a kind of to apply PdCl2(cod) method for synthesizing medicine intermediate phenanthrene compound
CN105732246B (en) It is a kind of to apply PdCl2(PPh3)2The method for synthesizing medicine intermediate phenanthrene compound
CN105669336A (en) Method for synthesizing medical intermediate phenanthrene compound in sodium ethoxide environment
CN105801340A (en) Method for synthesizing pharmaceutical intermediate phenanthrene compound in sodium phosphate environment
CN105753618A (en) Method for synthesizing medical intermediate phenanthrene compound in potassium carbonate environment
CN105801339A (en) Method for synthesizing medical intermediate, namely, phenanthrene compound, in sodium bicarbonate environment
CN105801341A (en) Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium hydroxide environment
CN105801344A (en) Method for synthesizing pharmaceutical intermediate phenanthrene compound in sodium hydroxide environment
CN105777481A (en) Method for synthesizing medical intermediate phenanthrene compound in potassium tert-butoxide environment
CN105801343A (en) Method for synthesizing pharmaceutical intermediate phenanthrene compound in potassium phosphate environment
CN105777462A (en) Method for synthesizing medical intermediate phenanthrene compound in potassium bicarbonate environment

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C41 Transfer of patent application or patent right or utility model
TA01 Transfer of patent application right

Effective date of registration: 20160331

Address after: 810008 Qinghai province Xining City West District Saline Lake No. 6 Lane

Applicant after: Tan Yongshan

Address before: 255399 No. 10, Xinjian West Road, Zhoucun District, Shandong, Zibo

Applicant before: Di Xueyan

C14 Grant of patent or utility model
GR01 Patent grant
CB03 Change of inventor or designer information

Inventor after: Fang Fang

Inventor before: Di Xueyan

CB03 Change of inventor or designer information
TR01 Transfer of patent right

Effective date of registration: 20170815

Address after: Qinhuangdao City, Hebei province 066000 Harbor District Qin District 22 Building 1 unit 5

Patentee after: Fang Fang

Address before: 810008 Qinghai province Xining City West District Saline Lake No. 6 Lane

Patentee before: Tan Yongshan

TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20180410

Address after: 226100 Fuxing Road, yuimen Town, Haimen City, Nantong, Jiangsu Province, No. 20

Patentee after: Nantong excellent art design Co., Ltd.

Address before: Qinhuangdao City, Hebei province 066000 Harbor District Qin District 22 Building 1 unit 5

Patentee before: Fang Fang

TR01 Transfer of patent right