CN109942616A - A kind of aryl amide analog derivative and its preparation method and application containing alkynyl - Google Patents
A kind of aryl amide analog derivative and its preparation method and application containing alkynyl Download PDFInfo
- Publication number
- CN109942616A CN109942616A CN201910313878.3A CN201910313878A CN109942616A CN 109942616 A CN109942616 A CN 109942616A CN 201910313878 A CN201910313878 A CN 201910313878A CN 109942616 A CN109942616 A CN 109942616A
- Authority
- CN
- China
- Prior art keywords
- formula
- alkynyl
- aryl
- analog derivative
- preparation
- 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.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to technical field of organic synthesis more particularly to a kind of aryl amide analog derivatives and its preparation method and application containing alkynyl.The present invention provides a kind of aryl amide analog derivative containing alkynyl, shown in the structural formula such as formula (I) of the aryl amide analog derivative containing alkynyl；Wherein, Ar is aryl, including fragrant heterocyclic radical, phenyl or aromatic condensed ring base；R1Selected from hydrogen, halogen element, ether or containing the alkyl of functional group；R2For hydrogen or alkyl；R3For polysubstituted silicon substrate.Aryl amide analog derivative of the present invention is introduced with multi-functional alkynyl, and alkynyl is located at the ortho position of amide groups on aryl, in view of the chemical activity abundant of the triple carbon-carbon bonds of alkynyl, and extensive use of the aryl amide in drug, aryl amide analog derivative of the present invention containing alkynyl have a good application prospect in drug development.
Description
Technical field
The invention belongs to technical field of organic synthesis more particularly to a kind of aryl amide analog derivatives and its system containing alkynyl
Preparation Method and application.
Background technique
In organic chemistry and biochemistry, amide is deposited as a kind of nearly ubiquitous functional group and structure fragment
It is drug, pesticide, in material.The relatively easy bonding of amido bond, structural rigidity is good, hydrolysis.Common material such as nylon, virtue
Synthetic fibre, Te Walun and Kafra fiber etc. are all the very strong polyamide of elasticity；And in biochemistry, amido bond is referred to as peptide bond
And it is widely present in protein and isopeptide bond.However, there is also aryl amide analog derivatives in the exploitation of new drug molecule
Type is limited, also needs the problem of being widened.
Thus, the type of aryl amide analog derivative how is widened, is always the coke of researcher's extensive concern in field
One of point.
Summary of the invention
In view of this, the present invention provides a kind of aryl amide analog derivative and its preparation method and application containing alkynyl,
For providing a kind of new aryl amide analog derivative, the type of aryl amide analog derivative is widened.
The specific technical solution of the present invention is as follows:
A kind of aryl amide analog derivative containing alkynyl, the structural formula such as formula of the aryl amide analog derivative containing alkynyl
(I) shown in:
Wherein, Ar is aryl, including fragrant heterocyclic radical, phenyl or aromatic condensed ring base；R1Selected from hydrogen, halogen element, ether or
Alkyl containing functional group；R2For hydrogen or alkyl；R3For polysubstituted silicon substrate.
Aryl amide analog derivative of the present invention is introduced with multi-functional alkynyl, and alkynyl is located at acyl on aryl
The ortho position of amido, in view of the extensive use in drug of chemical activity abundant and aryl amide of the triple carbon-carbon bonds of alkynyl,
Aryl amide analog derivative of the present invention containing alkynyl has a good application prospect in drug development.In conjunction with acylamino- and alkynyl
A variety of conversion reactions, reduction including amido bond resets and electrophilic addition, nucleophilic addition, the Click of alkynyl are anti-
It should wait, aryl amine derivant of the present invention containing alkynyl can be convenient for subsequent transformation.
In the present invention, in the present invention, Ar is preferably phenyl.Fragrant heterocyclic radical is the heterocycle containing N, O and/or S, preferably
Indyl, furyl, thienyl；Aromatic condensed ring base is preferably naphthalene or anthryl.Alkyl containing functional group is saturation or unsaturation
Straight-chain alkyl, branched hydrocarbyl or cyclic hydrocarbon radical.
Preferably, in the alkyl containing functional group functional group be selected from halogen element, ester group, carbonyl, amino, nitro, cyano,
Sulfuryl or acyl group；
The alkyl containing functional group is substituted straight chain alkyl or substitution cyclic hydrocarbon radical.
In the present invention, R1Selected from hydrogen, halogen element, ether or containing the alkyl of functional group；R1Can the ortho position of amido, meta position or
Contraposition.
Preferably, the Ar is phenyl, naphthalene, thienyl or indyl；
The R3For triisopropylsilyl (- TIPS), trimethyl silicon substrate (- TMS) or dimethyl tertiary butyl silicon substrate (- TBS).
In the present invention ,-NHTf is fluoroform sulfoamido.
Preferably, the aryl amide analog derivative containing alkynyl shown in formula (I) is selected from
The preparation method of the present invention also provides a kind of aryl amide analog derivative containing alkynyl, comprising the following steps:
Compound shown in compound shown in formula (II) and formula (III) is reacted, is obtained shown in formula (I) containing alkynyl
Aryl amine derivant；
Wherein,Ar is aryl, including fragrant heterocyclic radical, phenyl or aromatic condensed ring
Base, R1Selected from hydrogen, halogen element, ether or containing the alkyl of functional group, R2For hydrogen or alkyl；R3It is more
Replace silicon substrate, X is hydrogen, bromine, iodine or heterocyclic group containing iodine, and the iodine of the heterocyclic group containing iodine is connect with triple carbon-carbon bonds；
It is preferably, described to react compound shown in compound shown in formula (II) and formula (III) specifically:
Compound shown in compound shown in formula (II) and formula (III) is dissolved in atent solvent, in oxidant and [Cp*
IrCl2]2/AgNTf2Under the action of catalyst system, reacted under alkaline condition.
In the prior art, the high-efficiency synthesis method of aryl amide analog derivative is less, often refers to multistep reaction, is badly in need of seeking
The method for seeking rapid build aryl amides functional molecular.Although the triple carbon-carbon bonds of alkynyl have multifunctionality, aryl amide association
Exploitation is not yet received in the method that the ortho position helped introduces alkynyl moieties, is replaced at present by the aromatic ring ortho position of aryl amide with halogen
Substrate, carry out Sonogashira coupling reaction, obtain the aryl amide derivatives of ortho position alkynyl.However, aromatic ring ortho position has
The type of the aryl amide derivatives of halogen is few, and existing method is difficult to synthesize.Also, carbon-hydrogen bond activation reacts mainly with life
The selectivity of reaction is realized at metal ring intermediate, in the reaction of C-H bond function dough, to realize carbon-hydrogen bond activation
The reactivity of reaction and the balance of regioselectivity are often required to previously-introduced homing device, common amides guiding in molecule
Base has the amide derivatives for having additional substituents such as pyridine, quinoline etc. substituted on nitrogen-atoms, this results in whole process practical
Property on need to leave away after additional previously-introduced and reaction the homing device of no practical application.
In preparation method of the present invention, the aryl C-H bond alkynyl of the regioselectivity for arylamides is reacted
Reaction, in [Cp*IrCl2]2/AgNTf2Under the action of catalyst system, under the promotion of oxidant, using simple and easy to get and deposit extensively
Arylamides regioselectivity is directly carried out to the C-H bond of aryl function dough react, and into molecule
Introducing has multi-functional alkynyl, obtains having the active aryl amide derivatives containing alkynyl of potential source biomolecule.The preparation side
The substrate of method is simple and easy to get, and reaction step is few, easy to operate, can one pot process, can be realized a variety of polysubstituted containing alkynyl
Aryl amide analog derivative efficiently synthesizes；The ortho position of the aryl of reaction compound shown in formula (II) occurs, regional choice
Property is good；C-H bond is better than carbon-halogen bond in reaction, and chemo-selective is good, meets the demand for development of sustainable chemistry.
Preparation method of the present invention is very wide to the scope of application of substrate, and the obtained aryl amide analog derivative containing alkynyl is easy
In subsequent transformation, which also has good Atom economy.Also, the preparation method can be directly to potential life
The active amide derivatives of object carry out later period modification.
Preparation method of the present invention has good regioselectivity, wide substrate spectrum, Atom economy, containing alkynyl
Aryl amide analog derivative has good application value in biology, Material Field.The present invention is also brufen and amino acid etc.
Conversion with good biological, the compound of pharmaceutical activity provides new strategy.
In preparation method of the present invention, uses primary amide simple and easy to get as guiding base, avoid reaction later period needs
Homing device is eliminated, directly can be oriented to form hexa-atomic becket intermediate by aryl amide, amide is converted；The present invention
Reaction has splendid regioselectivity, that is, reacts and occur on the aryl ortho position C-H bond of aryl amide in specific manner；Reaction
Also there is good chemo-selective, i.e. reaction keeps primary amide N-H key constant, and electrophilic alkynyl reagent is not on amide
It reacts, and only carries out alkynylation reaction on aromatic ring C-H bond.
In the present invention, trivalent iridium catalyst [Cp*IrCl2]2Iridium (III) dimerization is closed for dichloro (pentamethylcyclopentadiene base)
Body.
In the present invention, Ar is preferably phenyl.Fragrant heterocyclic radical is the heterocycle containing N, O and/or S, preferably indyl, furan
It mutters base or thienyl；Aromatic condensed ring base is preferably naphthalene or anthryl.Alkyl containing functional group is saturations or undersaturated straight chain hydrocarbon
Base, branched hydrocarbyl or cyclic hydrocarbon radical.
Functional group is selected from halogen element, ester group, carbonyl, amino, nitro, cyano, sulfuryl or acyl group in alkyl containing functional group；
Alkyl containing functional group is substituted straight chain alkyl or substitution cyclic hydrocarbon radical.
In the present invention, R1Selected from hydrogen, halogen element, ether or containing the alkyl of functional group；R1Can the ortho position of amido, meta position or
Contraposition.
Ar is phenyl, naphthalene, thienyl or indyl；
R3For triisopropylsilyl (- TIPS), trimethyl silicon substrate (- TMS) or dimethyl tertiary butyl silicon substrate (- TBS).
In the present invention, the aryl amide analog derivative containing alkynyl shown in formula (I) is selected from
Compound shown in formula (III) is preferably(1-
((triisopropylsilyl) -1 λ 3- phenyl [d] [1,2] iodoso -3 (1H) -one), compound shown in formula (III) can pre-synthesis or
It is commercially available.
Compound shown in formula (II) is preferably Shown compound by Arylacetic acids pre-synthesis or can be commercially available.
Preferably, the temperature of the reaction is 80 DEG C~120 DEG C, more preferably 100 DEG C；
The time of the reaction is 12h~for 24 hours.
Preferably, the oxidant is selected from silver acetate, silver carbonate, silver trifluoromethanesulfonate, silver nitrate, copper acetate, halogenation Asia
Copper, copper halide, three iron halides or ferric nitrate, more preferably silver acetate；
The alkali for adjusting the alkaline condition is selected from sodium acetate, cesium acetate, potassium acetate, sodium carbonate, sodium carbonate or potassium phosphate, more
Preferably sodium acetate.
In the present invention, atent solvent be selected from toluene, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, N, N '-dimethyl formamide, N,
N '-dimethyl acetamide, N-Methyl pyrrolidone, dimethyl sulfoxide, acetonitrile, 1,2- dichloroethanes, ethyl alcohol or water, more preferably 1,
2- dichloroethanes.
Preferably, the molar ratio of compound shown in compound shown in the formula (II) and formula (III) is 1:1~1:5, more excellent
It is selected as 1:1.5；
[the Cp*IrCl2]2/AgNTf2Dosage be the formula (II) shown in compound amount 0.1mol%~
30mol%, more preferably 1mol%.
In the present invention, [Cp*IrCl2]2Dosage be the formula (II) shown in compound amount 0.2mol%~
10mol%, more preferably 1mol%；
AgNTf2Dosage be the formula (II) shown in compound amount 1mol%~30mol%, more preferably
5mol%.
The dosage of alkali is the 3mol%~100mol%, more preferably 15mol% of compound amount shown in formula (II)；
The dosage of oxidant is the 5mol%~200mol%, more preferably 30mol% of compound amount shown in formula (II).
Concentration of the compound in atent solvent shown in formula (II) is 0.05M~0.30M, preferably 0.1M.
In the present invention, preparation method preferably includes following steps: under air atmosphere, sequentially adding in the reactor
Compound shown in 0.2mmol formula (II), 0.002mmol [Cp*IrCl2]2、0.01mmolAgNTf2, 0.03mmol sodium acetate and
0.06mmol silver acetate contains the solution of 1, the 2- dichloroethanes of the triisopropylsilyl acetylene bromine of 20 μ L with syringe injection to instead
It answers in device, reactor is placed on reaction unit temperature regulating simultaneously and carries out 12h reaction to 120 DEG C, then uses column chromatography for separation
Reaction product obtains the aryl amide analog derivative containing alkynyl.
The present invention also provides described in above-mentioned technical proposal containing alkynyl aryl amide analog derivative and/or above-mentioned technical side
Application of the aryl amide analog derivative in medicine preparation containing alkynyl made from preparation method described in case.
In conjunction with a variety of conversion reactions of acylamino- and alkynyl, reduction, rearrangement and the electrophilic of alkynyl including amido bond add
At, nucleophilic addition, Click reaction etc., aryl amine derivant of the present invention containing alkynyl can be convenient for subsequent transformation,
It has a good application prospect in medicine preparation.
In conclusion the present invention provides a kind of aryl amide analog derivative containing alkynyl, the aryl acyl containing alkynyl
Shown in the structural formula of amide derivatives such as formula (I)；Wherein, Ar is aryl, including fragrant heterocyclic radical, phenyl or aromatic condensed ring
Base；R1Selected from hydrogen, halogen element, ether or containing the alkyl of functional group；R2For hydrogen or alkyl；R3For polysubstituted silicon substrate.Aryl of the present invention
Amide derivatives are introduced with multi-functional alkynyl, and alkynyl is located at the ortho position of amide groups on aryl, in view of alkynes
Extensive use of the chemical activity abundant and aryl amide of the triple carbon-carbon bonds of base in drug, virtue of the present invention containing alkynyl
Base amide derivatives have a good application prospect in drug development.In conjunction with a variety of conversion reactions of acylamino- and alkynyl,
Electrophilic addition, nucleophilic addition, Click reaction of reduction, rearrangement and alkynyl including amido bond etc., the present invention contains alkynes
The aryl amine derivant of base can be convenient for subsequent transformation.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described.
Fig. 1 is the nuclear magnetic resonance of 2- (2- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 1 provides1H spectrogram；
Fig. 2 is the nuclear magnetic resonance of 2- (2- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 1 provides13C spectrogram；
Fig. 3 is the nuclear-magnetism of 2- (the chloro- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 2 provides
Resonance1H spectrogram；
Fig. 4 is the nuclear-magnetism of 2- (the chloro- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 2 provides
Resonance13C spectrogram；
Fig. 5 is the nuclear-magnetism of 2- (the bromo- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 3 provides
Resonance1H spectrogram；
Fig. 6 is the nuclear-magnetism of 2- (the bromo- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 3 provides
Resonance13C spectrogram；
Fig. 7 is 2- (3- ((tri isopropyl silane base) acetenyl) naphthalene -2- base) acetamide that the embodiment of the present invention 4 provides
Nuclear magnetic resonance1H spectrogram；
Fig. 8 is 2- (3- ((tri isopropyl silane base) acetenyl) naphthalene -2- base) acetamide that the embodiment of the present invention 4 provides
Nuclear magnetic resonance13C spectrogram；
Fig. 9 is the core of 2- (4- nitro -2- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 5 provides
Magnetic resonance1H spectrogram；
Figure 10 is 2- (4- nitro -2- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 5 provides
Nuclear magnetic resonance13C spectrogram；
Figure 11 is the core of 2- (the fluoro- 6- of 2- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 6 provides
Magnetic resonance1H spectrogram；
Figure 12 is the core of 2- (the fluoro- 6- of 2- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 6 provides
Magnetic resonance13C spectrogram；
Figure 13 is the core of 2- (the fluoro- 6- of 2- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 6 provides
Magnetic resonance19F spectrogram；
Figure 14 is the core of 2- (the bromo- 2- of 5- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 7 provides
Magnetic resonance1H spectrogram；
Figure 15 is the core of 2- (the bromo- 2- of 5- ((triisopropyl) acetenyl) phenyl) acetamide that the embodiment of the present invention 7 provides
Magnetic resonance13C spectrogram；
Figure 16 is the 2- (4- (trifluoromethoxy) -2- (tri isopropyl silane base) acetenyl) that the embodiment of the present invention 8 provides
Phenyl) acetamide nuclear magnetic resonance1H spectrogram；
Figure 17 is the 2- (4- (trifluoromethoxy) -2- (tri isopropyl silane base) acetenyl) that the embodiment of the present invention 8 provides
Phenyl) acetamide nuclear magnetic resonance13C spectrogram；
Figure 18 is the 2- (4- (trifluoromethoxy) -2- (tri isopropyl silane base) acetenyl) that the embodiment of the present invention 8 provides
Phenyl) acetamide nuclear magnetic resonance19F spectrogram；
Figure 19 is the core of 2- (2- ((tri isopropyl silane base) acetenyl) phenyl) propionamide that the embodiment of the present invention 9 provides
Magnetic resonance1H spectrogram；
Figure 20 is the core of 2- (2- ((tri isopropyl silane base) acetenyl) phenyl) propionamide that the embodiment of the present invention 9 provides
Magnetic resonance13C spectrogram.
Specific embodiment
The present invention provides a kind of aryl amide analog derivative and its preparation method and application containing alkynyl, for providing one
The new aryl amide analog derivative of kind, widens the type of aryl amide analog derivative.
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment 1
The present embodiment carries out the preparation of 2- (2- ((triisopropyl) acetenyl) phenyl) acetamide (3a), and reaction equation is as follows
It is shown:
Under an atmospheric air atmosphere, phenyl acetamide compound 1a is sequentially added into 15mL Schlenk reaction tube
(27.0mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt AgNTf2(3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), finally
1,2- dichloroethanes (DCE, the 1mL) solution that alkynyl bromine compounds 2a (20 μ L, 0.30mmol) will be contained squeezes into reaction with syringe
It is to react 12h in 120 DEG C in temperature in device.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get thick production
Object.The silica gel plate of crude product preparation carries out thin layer chromatography separation, the petroleum that selected solvent or eluant, eluent are volume ratio 10:1
Ether and ethyl acetate, obtain product 2- (2- ((triisopropyl) acetenyl) phenyl) acetamide (3a), 47.9mg, and yield is
76%, purity 95%.
Magnetic resonance detection is carried out to 2- (2- ((triisopropyl) acetenyl) phenyl) acetamide (3a), please refers to Fig. 1 extremely
Fig. 2, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.53 (d, J=7.2Hz, 1H), 7.35-7.29 (m, 2H), 7.24-7.22
(m, 1H), 5.70 (d, J=16.8Hz, 2H), 3.79 (s, 2H), 1.13-1.12 (m, 21H)；13C NMR(100MHz,CDCl3):
δ172.9,137.1,133.2,129.8,129.1,127.3,123.3,105.0,96.0,42.2,18.6(6C),11.3(3C)。
Embodiment 2
The present embodiment carries out the preparation of 2- (the chloro- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide (3b), reaction
Formula is as follows:
Under an atmospheric air atmosphere, phenyl acetamide compound 1b is sequentially added into 15mL Schlenk reaction tube
(34.0mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt (3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), will finally contain alkynes
1,2- dichloroethanes (DCE, 1mL) solution of based compound 2a (20 μ L, 0.30mmol) is squeezed into reactor with syringe, in temperature
Degree is to react for 24 hours in 120 DEG C.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.Crude product
Thin layer chromatography separation, the petroleum ether and acetic acid second that selected solvent or eluant, eluent are volume ratio 10:1 are carried out with the silica gel plate of preparation
Ester obtains product 2- (the chloro- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide (3b), 52.3mg, yield 75%, purity
It is 95%.
Magnetic resonance detection is carried out to 2- (the chloro- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide (3b), is please referred to
Fig. 3 to Fig. 4, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.50 (s, 1H), 7.28 (d, J=1.2Hz, 2H), 5.73 (s,
1H),5.61(s,1H),3.75(s,2H),1.13-1.12(m,21)；13C NMR(100MHz,CDCl3): δ 172.3,135.5,
133.1,132.7,131.1,129.3,124.9,103.6,97.7,41.4,18.6(6C),11.2(3C)。
Embodiment 3
The present embodiment carries out the preparation of 2- (the bromo- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide (3c), reaction
Formula is as follows:
Under an atmospheric air atmosphere, phenyl acetamide compound 1c is sequentially added into 15mL Schlenk reaction tube
(42.4mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt (3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), will finally contain alkynes
1,2- dichloroethanes (DCE, 1mL) solution of based compound 2a (26 μ L, 0.40mmol) is squeezed into reactor with syringe, in temperature
Degree is to react 12h in 120 DEG C.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.Crude product
Thin layer chromatography separation, the petroleum ether and acetic acid second that selected solvent or eluant, eluent are volume ratio 10:1 are carried out with the silica gel plate of preparation
Ester obtains product 2- (the bromo- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide (3c), 48.7mg, yield 62%, purity
It is 95%.
Magnetic resonance detection is carried out to 2- (the bromo- 2- of 4- ((triisopropyl) acetenyl) phenyl) acetamide (3c), is please referred to
Fig. 5 to Fig. 6, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.65 (d, J=2.0Hz, 1H), 7.44 (dd, J=2.4Hz,
8.4Hz, 1H), 7.22 (d, J=8.4Hz, 1H), 5.66 (d, J=37.6Hz, 2H), 3.74 (s, 2H), 1.13-1.12 (m,
21H)；13C NMR(100MHz,CDCl3): δ 172.1,135.9,135.5,132.1,131.2,125.2,120.8,103.4,
97.8,41.5,18.6(6C),11.2(3C)。
This example demonstrates that influence of the steric hindrance of substrate to the reaction is unobvious in preparation method of the present invention, simultaneous reactions can
To be compatible with halogen, so as to realize the ethanamide chemical combination containing alkynyl of multifunctional dough by reactions such as coupling and nucleophilic displacement of fluorine
The synthesis of object.
Embodiment 4
The present embodiment carries out the preparation of 2- (3- ((tri isopropyl silane base) acetenyl) naphthalene -2- base) acetamide (3d),
Reaction equation is as follows:
Under an atmospheric air atmosphere, naphthaleneacetamide compound 1d is sequentially added into 15mL Schlenk reaction tube
(37.0mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt (3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), will finally contain alkynes
1,2- dichloroethanes (DCE, 1mL) solution of based compound 2a (20 μ L, 0.30mmol) is squeezed into reactor with syringe, in temperature
Degree is to react 12h in 120 DEG C.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.Crude product
Thin layer chromatography separation, the petroleum ether and acetic acid second that selected solvent or eluant, eluent are volume ratio 10:1 are carried out with the silica gel plate of preparation
Ester, obtains product 2- (3- ((tri isopropyl silane base) acetenyl) naphthalene -2- base) acetamide (3d), 55.5mg, yield 76%,
Purity is 95%.
Magnetic resonance detection is carried out to 2- (3- ((tri isopropyl silane base) acetenyl) naphthalene -2- base) acetamide (3d), is asked
Refering to Fig. 7 to Fig. 8, as a result are as follows:1H NMR(400MHz,CDCl3): δ 8.07 (s, 1H), 7.81 (s, 1H), 7.79-7.77 (m,
2H), 7.50-7.48 (m, 2H), 5.68 (d, J=31.2Hz, 2H), 3.95 (s, 2H), 1.17-1.16 (m, 21H)；13C NMR
(100MHz,CDCl3): δ 173.2,133.5,133.1,133.0,132.2,128.9,127.6,127.4,127.3,12 6.7,
121.0,105.2,96.0,42.2,18.7(6C),11.3(3C)。
This example demonstrates that the reaction of preparation method of the present invention can be compatible with the widely applied annelation in Material Field
Close object.
Embodiment 5
The present embodiment carries out the preparation of 2- (4- nitro -2- ((triisopropyl) acetenyl) phenyl) acetamide (3e), anti-
Answer formula as follows:
Under an atmospheric air atmosphere, phenyl acetamide compound 1e is sequentially added into 15mL Schlenk reaction tube
(36.0mg, 0.20mmol), alkynyl iodine compound 2c (278mg, 0.50mmol), trivalent iridium catalyst [Cp*IrCl2]2
(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver salt (3.9mg, 0.01mmol), sodium acetate (2.5mg,
0.03mmol), silver acetate (10.0mg, 0.06mmol), 1,2- dichloroethanes (DCE, 1mL) are to react 8h in 80 DEG C in temperature.
It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.The silica gel plate of crude product preparation carries out layer
Chromatographic isolation is analysed, the petroleum ether and ethyl acetate that selected solvent or eluant, eluent are volume ratio 10:1 obtain product 2- (4- nitre
Base -2- ((triisopropyl) acetenyl) phenyl) acetamide (3e), 43.9mg, yield 61%, purity 95%.
Magnetic resonance detection is carried out to 2- (4- nitro -2- ((triisopropyl) acetenyl) phenyl) acetamide (3e), please be join
Fig. 9 to Figure 10 is read, as a result are as follows:1H NMR(400MHz,CDCl3): δ 8.34 (d, J=2.4Hz, 1H), 8.15 (dd, J=2.4Hz,
8.8Hz, 1H), 7.56 (d, J=8.4Hz, 1H), 5.64 (s, 1H), 5.50 (s, 1H), 3.88 (s, 2H), 1.15-1.14 (m,
21H)；13C NMR(100MHz,CDCl3): δ 170.7,147.0,143.7,130.9,127.7,124.8,123.5,102.6,
99.4,41.7,18.6(6C),11.2(3C)。
This example demonstrates that the reaction of preparation method of the present invention can be compatible with nitro functions, and nitro is that one kind can be fast
Speed is converted into amino and related important functional group, the prominent practicability for showing preparation method of the present invention.
Embodiment 6
The present embodiment carries out the preparation of 2- (the fluoro- 6- of 2- ((triisopropyl) acetenyl) phenyl) acetamide (3f), reaction
Formula is as follows:
Under an atmospheric air atmosphere, phenyl acetamide compound 1f is sequentially added into 15mL Schlenk reaction tube
(30.6mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt (3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), will finally contain alkynes
1,2- dichloroethanes (DCE, 1mL) solution of based compound 2a (20 μ L, 0.30mmol) is squeezed into reactor with syringe, in temperature
Degree is to react 12h in 120 DEG C.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.Crude product
Thin layer chromatography separation, the petroleum ether and acetic acid second that selected solvent or eluant, eluent are volume ratio 10:1 are carried out with the silica gel plate of preparation
Ester obtains product 2- (the fluoro- 6- of 2- ((triisopropyl) acetenyl) phenyl) acetamide (3f), 47.9mg, yield 72%, purity
It is 95%.
Magnetic resonance detection is carried out to 2- (the fluoro- 6- of 2- ((triisopropyl) acetenyl) phenyl) acetamide (3f), is please referred to
Figure 11 to Figure 13, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.34 (d, J=7.6Hz, 1H), 7.24-7.20 (m, 1H),
7.08 (t, J=8.8Hz, 1H), 5.52 (s, 1H), 5.45 (s, 1H), 3.85 (d, J=2.0Hz, 2H), 1.13-1.12 (m,
21H)；13C NMR(100MHz,CDCl3): δ 171.2,162.3,159.8,128.8 (t, J=4.0Hz, 1C), 125.7 (d, J=
5.0Hz, 1C), 124.4 (d, J=18.0Hz, 1C), 116.1 (d, J=22.0Hz, 1C), 103.4 (d, J=4.0Hz, 1C),
97.3,34.9 (d, J=2.0Hz, 1C), 18.6 (6C), 11.2 (3C)；19F NMR(400MHz,CDCl3): δ -116.3.
It is answered extensively in biology, medicine, Material Field this example demonstrates that the reaction of preparation method of the present invention can be compatible with
Fluorine compounds, and react unobvious to the chemical effect of steric hindrance.
Embodiment 7
The present embodiment carries out the preparation of 2- (the bromo- 2- of 5- ((triisopropyl) acetenyl) phenyl) acetamide (3g), reaction
Formula is as follows:
Under an atmospheric air atmosphere, phenyl acetamide compound 1g is sequentially added into 15mL Schlenk reaction tube
(42.4mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt (3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), will finally contain alkynes
1,2- dichloroethanes (DCE, 1mL) solution of based compound 2a (20 μ L, 0.30mmol) is squeezed into reactor with syringe, in temperature
Degree is to react 12h in 120 DEG C.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.Crude product
Thin layer chromatography separation, the petroleum ether and acetic acid second that selected solvent or eluant, eluent are volume ratio 10:1 are carried out with the silica gel plate of preparation
Ester obtains product 2- (the bromo- 2- of 5- ((triisopropyl) acetenyl) phenyl) acetamide (3g), 51.1mg, yield 65%, purity
It is 95%.
Magnetic resonance detection is carried out to 2- (the bromo- 2- of 5- ((triisopropyl) acetenyl) phenyl) acetamide (3g), is please referred to
Figure 14 to Figure 15, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.52 (s, 1H), 7.38 (d, J=1.2Hz, 2H), 5.65 (s,
1H),5.55(s,1H),3.75(s,2H),1.13-1.12(m,21H)；13CNMR(100MHz,CDCl3): δ 171.8,138.9,
134.3,132.8,130.6,123.1,122.2,104.0,97.5,41.8,18.6(6C),11.2(3C)。
This example demonstrates that the reaction of preparation method of the present invention can be compatible with the group bromine easily converted, to be such chemical combination
The subsequent transformation of object, which is realized, provides basis.Simultaneously this example demonstrates that the reaction is for there are two types of show when reactive C-H bond
More sensitive to steric hindrance out, reaction only occurs on the lesser C-H bond of steric hindrance.
Embodiment 8
The present embodiment carries out 2- (4- (trifluoromethoxy) -2- (tri isopropyl silane base) acetenyl) phenyl) acetamide
The preparation of (3h), reaction equation are as follows:
Under an atmospheric air atmosphere, phenyl acetamide compound 1h is sequentially added into 15mL Schlenk reaction tube
(44.0mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt (3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), will finally contain alkynes
1,2- dichloroethanes (DCE, 1mL) solution of based compound 2a (20 μ L, 0.30mmol) is squeezed into reactor with syringe, in temperature
Degree is to react 16h in 120 DEG C.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.Crude product
Thin layer chromatography separation, the petroleum ether and acetic acid second that selected solvent or eluant, eluent are volume ratio 10:1 are carried out with the silica gel plate of preparation
Ester obtains product 2- (4- (trifluoromethoxy) -2- (tri isopropyl silane base) acetenyl) phenyl) acetamide (3h), 55.1mg,
Yield is 69%, purity 95%.
To 2- (4- (trifluoromethoxy) -2- (tri isopropyl silane base) acetenyl) phenyl) acetamide (3h) progress nuclear-magnetism
Resonance detection, please refers to Figure 16 to Figure 18, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.46-7.42 (m, 2H), 7.34-
7.33(m,1H),5.68(s,1H),5.49(s,1H),3.86(s,2H),1.33-1.21(m,21H)；13C NMR(100MHz,
CDCl3): δ 171.8,148.1,135.8,131.3,125.2,125.0,121.7,103.5,100.0,97 .9,41.4,18.6
(6C),11.2(3C)；19F NMR(100MHz,CDCl3): δ -57.9 (3F).
This example demonstrates that the reaction of preparation method of the present invention can be compatible with it is easily widely applied in fields such as biological medicines
Trifluoromethoxy functional group.
Embodiment 9
The present embodiment carries out the preparation of 2- (2- ((tri isopropyl silane base) acetenyl) phenyl) propionamide (3i), reaction
Formula is as follows:
Under an atmospheric air atmosphere, phenyl acetamide compound 1i is sequentially added into 15mL Schlenk reaction tube
(30.0mg, 0.20mmol), trivalent iridium catalyst [Cp*IrCl2]2(1.60mg, 0.002mmol), bis-trifluoromethylsulfoandimide silver
Salt (3.9mg, 0.01mmol), sodium acetate (2.5mg, 0.03mmol), silver acetate (10.0mg, 0.06mmol), will finally contain alkynes
1,2- dichloroethanes (DCE, 1mL) solution of based compound 2a (20 μ L, 0.30mmol) is squeezed into reactor with syringe, in temperature
Degree is to react 12h in 120 DEG C.It is cooled to room temperature after reaction, after suction filtered through kieselguhr, is concentrated to get crude product.Crude product
Thin layer chromatography separation, the petroleum ether and acetic acid second that selected solvent or eluant, eluent are volume ratio 10:1 are carried out with the silica gel plate of preparation
Ester, obtains product 2- (2- ((tri isopropyl silane base) acetenyl) phenyl) propionamide (3i), 44.1mg, and yield 67% is pure
Degree is 95%.
Magnetic resonance detection is carried out to 2- (2- ((tri isopropyl silane base) acetenyl) phenyl) propionamide (3i), is please referred to
Figure 19 to Figure 20, as a result are as follows:1H NMR(400MHz,CDCl3): δ 7.51 (d, J=7.6Hz, 1H), 7.39 (d, J=8.0Hz,
1H), 7.35-7.31 (m, 1H), 7.21 (t, J=7.6Hz, 1H), 5.64 (s, 1H), 5.35 (s, 1H), 4.31 (q, J=
7.2Hz, 1H), 1.50 (d, J=7.2Hz, 3H), 1.14-1.14 (m, 21H)；13C NMR(100MHz,CDCl3): δ 175.8,
143.3,133.1,129.3,126.9,126.5,122.6,105.3,96.0,43.3,18.7(6C),17.0,11.3(3C)。
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of aryl amide analog derivative containing alkynyl, which is characterized in that the aryl amide analog derivative containing alkynyl
Shown in structural formula such as formula (I):
Wherein, Ar is aryl, including fragrant heterocyclic radical, phenyl or aromatic condensed ring base；R1Selected from hydrogen, halogen element, ether or contain function
The alkyl of group；R2For hydrogen or alkyl；R3For polysubstituted silicon substrate.
2. the aryl amide analog derivative according to claim 1 containing alkynyl, which is characterized in that the hydrocarbon containing functional group
Ji Zhong functional group is selected from halogen element, ester group, carbonyl, amino, nitro, cyano, sulfuryl or acyl group；
The alkyl containing functional group is substituted straight chain alkyl or substitution cyclic hydrocarbon radical.
3. the aryl amide analog derivative according to claim 1 containing alkynyl, which is characterized in that the Ar is phenyl, naphthalene
Base, thienyl or indyl；
The R3For triisopropylsilyl, trimethyl silicon substrate or dimethyl tertiary butyl silicon substrate.
4. the aryl amide analog derivative according to claim 1 containing alkynyl, which is characterized in that contain alkynyl shown in formula (I)
Aryl amide analog derivative be selected from
5. a kind of preparation method of the aryl amide analog derivative containing alkynyl, which comprises the following steps:
Compound shown in compound shown in formula (II) and formula (III) is reacted, the aryl containing alkynyl shown in formula (I) is obtained
Amine derivant；
Wherein,Ar is aryl, including fragrant heterocyclic radical, phenyl or aromatic condensed ring base, R1
Selected from hydrogen, halogen element, ether or containing the alkyl of functional group, R2For hydrogen or alkyl；R3It is polysubstituted
Silicon substrate, X are hydrogen, bromine, iodine or heterocyclic group containing iodine, and the iodine of the heterocyclic group containing iodine is connect with triple carbon-carbon bonds；
6. preparation method according to claim 5, which is characterized in that described by compound shown in formula (II) and formula (III) institute
Show that compound is reacted specifically:
Compound shown in compound shown in formula (II) and formula (III) is dissolved in atent solvent, in oxidant and [Cp*IrCl2]2/
AgNTf2Under the action of catalyst system, reacted under alkaline condition.
7. preparation method according to claim 6, which is characterized in that the temperature of the reaction is 80 DEG C~120 DEG C；
The time of the reaction is 12h~for 24 hours.
8. preparation method according to claim 6, which is characterized in that the oxidant is selected from silver acetate, silver carbonate, trifluoro
Methanesulfonic acid silver, silver nitrate, copper acetate, cuprous halide, copper halide, three iron halides or ferric nitrate；
The alkali for adjusting the alkaline condition is selected from sodium acetate, cesium acetate, potassium acetate, sodium carbonate, sodium carbonate or potassium phosphate.
9. preparation method according to claim 6, which is characterized in that shown in compound shown in the formula (II) and formula (III)
The molar ratio of compound is 1:1~1:5；
[the Cp*IrCl2]2/AgNTf2Dosage be the formula (II) shown in compound amount 0.1mol%~30mol%.
10. the aryl amide analog derivative and/or claim 5 to 9 described in Claims 1-4 any one containing alkynyl are any
Application of the aryl amide analog derivative in medicine preparation containing alkynyl made from one preparation method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910313878.3A CN109942616A (en) | 2019-04-18 | 2019-04-18 | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910313878.3A CN109942616A (en) | 2019-04-18 | 2019-04-18 | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109942616A true CN109942616A (en) | 2019-06-28 |
Family
ID=67015449
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910313878.3A Pending CN109942616A (en) | 2019-04-18 | 2019-04-18 | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109942616A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110256480A (en) * | 2019-07-23 | 2019-09-20 | 广东工业大学 | A kind of nitogen-contained heterocycle derivant and its preparation method and application containing alkynyl |
| CN110305155A (en) * | 2019-07-23 | 2019-10-08 | 广东工业大学 | A kind of imine derivative and its preparation method and application containing alkynyl |
| CN110305156A (en) * | 2019-07-23 | 2019-10-08 | 广东工业大学 | A kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104736533A (en) * | 2012-08-17 | 2015-06-24 | 癌症治疗合作研究中心有限公司 | VEGFR3 inhibitors |
| CN104837835A (en) * | 2012-08-17 | 2015-08-12 | 癌症治疗合作研究中心有限公司 | VEGFR3 inhibitors |
| CN108640945A (en) * | 2018-06-11 | 2018-10-12 | 广东工业大学 | A kind of amides compound and the preparation method and application thereof |
| EP3395345A1 (en) * | 2015-12-22 | 2018-10-31 | Taiho Pharmaceutical Co., Ltd. | Antitumor effect potentiator comprising pyrrolopyrimidine compound |
| CN108822145A (en) * | 2018-06-11 | 2018-11-16 | 广东工业大学 | A kind of sulfamide compound and its preparation method and application |
-
2019
- 2019-04-18 CN CN201910313878.3A patent/CN109942616A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104736533A (en) * | 2012-08-17 | 2015-06-24 | 癌症治疗合作研究中心有限公司 | VEGFR3 inhibitors |
| CN104837835A (en) * | 2012-08-17 | 2015-08-12 | 癌症治疗合作研究中心有限公司 | VEGFR3 inhibitors |
| EP3395345A1 (en) * | 2015-12-22 | 2018-10-31 | Taiho Pharmaceutical Co., Ltd. | Antitumor effect potentiator comprising pyrrolopyrimidine compound |
| CN108640945A (en) * | 2018-06-11 | 2018-10-12 | 广东工业大学 | A kind of amides compound and the preparation method and application thereof |
| CN108822145A (en) * | 2018-06-11 | 2018-11-16 | 广东工业大学 | A kind of sulfamide compound and its preparation method and application |
Non-Patent Citations (2)
| Title |
|---|
| GUOCAI WU 等: "Cross-dehydrogenative alkynylation of sulfonamides and amides with terminal alkynes via Ir(III) catalysis", 《ORG. CHEM. FRONT》 * |
| XIANWEI LI 等: "Regioselective C-H Bond Alkynylation of Carbonyl Compounds through Ir(III) Catalysis", 《J.ORG.CHEM.》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110256480A (en) * | 2019-07-23 | 2019-09-20 | 广东工业大学 | A kind of nitogen-contained heterocycle derivant and its preparation method and application containing alkynyl |
| CN110305155A (en) * | 2019-07-23 | 2019-10-08 | 广东工业大学 | A kind of imine derivative and its preparation method and application containing alkynyl |
| CN110305156A (en) * | 2019-07-23 | 2019-10-08 | 广东工业大学 | A kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond |
| CN110256480B (en) * | 2019-07-23 | 2022-01-11 | 广东工业大学 | Alkynyl-containing nitrogen-containing heterocyclic derivative and preparation method and application thereof |
| CN110305155B (en) * | 2019-07-23 | 2022-04-19 | 广东工业大学 | Alkynyl-containing imine derivative and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109942616A (en) | A kind of aryl amide analog derivative and its preparation method and application containing alkynyl | |
| KR100283066B1 (en) | How to prepare biphenyl derivative | |
| CN110467579A (en) | A kind of preparation method for the 1,2,4- 3-triazole compounds that 5- trifluoromethyl replaces | |
| Katritzky et al. | Alkyl, unsaturated,(hetero) aryl, and N-protected α-amino ketones by acylation of organometallic reagents | |
| Dong et al. | Palladium-catalyzed anti-markovnikov oxidation of allylic amides to protected β-amino aldehydes | |
| CN108822145A (en) | A kind of sulfamide compound and its preparation method and application | |
| CN108610225A (en) | A kind of method that transition metal-catalyzed nitro-aromatic prepares fragrant alkynes with terminal aryl group alkynes cross-coupling | |
| CN109438205B (en) | Synthesis method of 2-methyl-2, 3-diaryl propionaldehyde derivative | |
| CN113943252A (en) | Pyrazolidinesulfonyl fluoride compounds and preparation method thereof | |
| CN105130872A (en) | Preparation method of 3-trifluoromethyl substituted indole | |
| CN105131044B (en) | Three core N-heterocyclic carbine palladium compounds and synthetic method and application | |
| CN110627703B (en) | Difluoromethylation synthesis method of aromatic amine compound | |
| CN106892826B (en) | A kind of preparation method and application of amine and imines N-methyl | |
| CN109867691A (en) | A kind of aryl amine derivant and its preparation method and application | |
| CN109942615B (en) | Aryl amine derivative containing alkynyl and preparation method and application thereof | |
| JP5859807B2 (en) | Copper-catalyzed process for preparing substituted or unsubstituted trifluoromethylated aryl and heteroaryl compounds | |
| CN108864173B (en) | Process for converting substituted sodium arylsulfinates into aryltri-n-butyltin | |
| Li et al. | Synthesis of new β-hydroxy amide ligands and their Ti (IV) complex-catalyzed enantioselective alkynylation of aliphatic and vinyl aldehydes | |
| CN104710376B (en) | Method for synthesis of oxazoline derivative based on electrophilic iodocyclization reaction of propargylamide | |
| CN106336378A (en) | Preparation method of quinoline-2-formic ether series | |
| CN110305156A (en) | A kind of alkynes derivative and its preparation method and application containing nitrogen-oxygen bond | |
| CN110256480A (en) | A kind of nitogen-contained heterocycle derivant and its preparation method and application containing alkynyl | |
| CN112961115A (en) | Method and compound for preparing (E) -alpha-aryl-alpha, beta-unsaturated oxazoline or carboxylic acid | |
| CN101891569B (en) | Preparation method of alpha-aromatic ketone compound | |
| Jiang et al. | Diastereoselective Room-Temperature Pd-Catalyzed α-Arylation and Vinylation of Arylmandelic Acid Derivatives |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190628 |
|
| RJ01 | Rejection of invention patent application after publication |