CN104311474B - Synthesis method of 3-alkynyl pyridine compound - Google Patents
Synthesis method of 3-alkynyl pyridine compound Download PDFInfo
- Publication number
- CN104311474B CN104311474B CN201410515647.8A CN201410515647A CN104311474B CN 104311474 B CN104311474 B CN 104311474B CN 201410515647 A CN201410515647 A CN 201410515647A CN 104311474 B CN104311474 B CN 104311474B
- Authority
- CN
- China
- Prior art keywords
- mmol
- reaction
- phenyl
- cdcl
- nmr
- 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
Links
Classifications
-
- 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
- C07D213/08—Preparation by ring-closure
- C07D213/09—Preparation by ring-closure involving the use of ammonia, amines, amine salts, or nitriles
- C07D213/12—Preparation by ring-closure involving the use of ammonia, amines, amine salts, or nitriles from unsaturated compounds
-
- 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
-
- 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
- C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
-
- 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
- C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- 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
- C07D213/24—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 with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a synthesis method of a 3-alkynyl pyridine compound and belongs to the technical field of organic synthesis. According to the synthesis method of the 3-alkynyl pyridine compound, the 3-alkynyl pyridine compound can be prepared by performing a stirring reaction on raw materials in a solvent at a temperature in the atmosphere of nitrogen under the promoting action of metal zinc, wherein the raw materials are nitrile and propargyl bromide, the solvent is selected from tetrahydrofuran, dichloromethane, N,N-dimethyl formamide or ethanol, and the temperature is within the range of a room temperature to 80 DEG C. The invention provides a new method which is economic, practical, green and environment-friendly for the synthesis of the 3-alkynyl pyridine compound.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to the synthetic method of a kind of 3-alkynyl pyridine compounds and their.
Background technology
Pyridine and its derivatives is the nitrogen-containing heterocycle compound that a class is important, not only has biological activity widely, and
Can serve as ligand transition metal and the highest analytical reagent of sensitivity.Therefore, the synthesis of pyridine compounds and their receives people
Attention, have been developed in multiple method at present, such as: classical Hantzsch reaction, 1-or 2-aza-diene and dienophile
Aza-Diels-Alder reaction and [2+2+2] cycloaddition reaction etc. of nitrile and alkynes.Although these are all the effective sides of synthesis
Method, but yet suffer from a lot of problem, and such as: severe reaction conditions, the response time is longer, and productivity is relatively low, and some reaction also needs
Use valuable metallic catalyst etc..
Alkynyl pyridine is important pyridine derivate.Owing to alkynyl has various reactivity worth, so alkynyl pyridine is
Synthetic drug and the conventional intermediate of agricultural insecticide, be also the important source material of the functional high molecule material such as optics, electricity.Such
The sonogashira coupling reaction that the synthesis of compound occurs generally by haloperidid, is incorporated into alkynyl on pyridine ring.
Such as, the synthesis of ethynyl pyridine is on the basis of first synthesizing pyridine ring, and pyridine ring is carried out halogenation, obtains halo pyrrole
Pyridine, this haloperidid is carried out with trimethyl silicane ethyl-acetylene or methyl butynol under catalysis at palladium reagent and combining of cupferron
Sonogashira coupling reaction, obtains ethynyl pyridine or the acetenyl of 2-hydroxyisopropyl protection of the silica-based protection of trimethyl
Pyridine, finally by sloughing trimethyl silicon-based protecting group or acetone obtains ethynyl pyridine.The reaction step that this synthetic method relates to
Rapid the most, operation complexity, post processing bothers, and particularly after coupling reaction terminates, process to metallic catalyst requires height, trace
Metallic catalyst residual the autoxidation coupling of product all can be caused to obtain diine by-product.Additionally, this reaction use certain
A little raw materials and reagent such as trimethyl silicane ethyl-acetylene and palladium reagent are expensive.These all make the method application in actual production
It is restricted.
In view of importance and the limitation of existing synthetic method of alkynyl pyridine compounds and their, in the urgent need to the green ring of development
Guarantor, new synthetic method economical and practical, applied widely.
Summary of the invention
Present invention solves the technical problem that the synthetic method that there is provided a kind of 3-alkynyl pyridine compounds and their, this synthesis side
Method is from raw material simple, inexpensive, that be easy to get, and by one pot of four component reaction, a step directly obtains 3-alkynyl pyridines chemical combination
Thing, i.e. while constructing pyridine ring, also introduces 3-position alkynyl, it is achieved that the One-step Synthesis of alkynyl pyridine, easy to operate, bar
Part is gentle, and response speed is fast, wide application range of substrates.
The technical scheme is that the synthetic method of a kind of 3-alkynyl pyridine compounds and their, it is characterised in that: with nitrile and
Propargyl bromide is raw material, with oxolane, dichloromethane, DMF or ethanol as solvent, in the rush of metallic zinc
Enter under effect, in nitrogen atmosphere, stir reaction in room temperature-80 DEG C, can be prepared by 3-alkynyl pyridine compounds and their, this synthesis side
Reaction equation main in method is:
,
Wherein R1For aryl, alkyl or alkenyl, described aryl is 1-naphthyl, 2-thienyl, phenyl or substituted-phenyl, should
Substituent group on substituted-phenyl phenyl ring be the one in methyl, methoxyl group, allyloxy, propargyl epoxide, fluorine, chlorine, bromine, thiazolinyl or
Multiple, the position of substituent group is the ortho position on phenyl ring, meta or para position, R2For hydrogen, alkyl, phenyl or substituted-phenyl, this replacement
Substituent group on phenyl phenyl ring is methyl, methoxyl group, allyloxy, propargyl epoxide, fluorine, chlorine, bromine, and the position of substituent group is phenyl ring
On ortho position, meta or para position.
The ratio of the amount of the material that feeds intake of nitrile of the present invention, propargyl bromide and metallic zinc is 1:1-4:1-6.
Metallic zinc of the present invention is the zinc powder after zinc powder or dilute hydrochloric acid activation.
The present invention compared with prior art has the advantage that (1) building-up process is single step reaction, easy and simple to handle, it is to avoid
Due to the use of plurality of reagents and the wasting of resources that the purification process etc. of each step intermediate is caused and ring in multistep reaction
Environment pollution；(2) raw material nitrile and propargyl bromide is simple, inexpensive, be easy to get；(3) reaction is entered under conditions of normal pressure, room temperature to 80 DEG C
OK, mild condition；(4) by zinc powder and propargyl bromide generated in-situ propargyl zinc bromide, there is active reactivity worth so that
The response speed of this reaction is fast, and reaction can complete in 10-30 minute；(5) substrate is applied widely.Therefore, the present invention
Synthesis for 3-alkynyl pyridine compounds and their provides a kind of economical and practical, new method of environmental protection.
Detailed description of the invention
By the following examples the foregoing of the present invention is described in further details, but this should be interpreted as this
The scope inventing above-mentioned theme is only limitted to below example, and all technology realized based on foregoing of the present invention belong to this
Bright scope.
Embodiment 1
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
The activation of zinc powder: 10 grams of zinc powders are joined in the dilute hydrochloric acid that 100 mL mass concentrations are 2%, is stirred at room temperature 30 points
Clock, sucking filtration, successively with water (25 mL × 3), acetone (15 mL × 3), ether (10 mL × 2) washing, it is dried, after being activated
Zinc powder, stand-by.
Equipped with benzonitrile (103 mg, 1 mmol), oxolane (2 mL) and 3-bromo-1-propine (238 mg, 2
Mmol) reaction bulb adds the zinc powder (130 mg, 2 mmol) after activation, reactant mixture is placed in nitrogen atmosphere, in
Reaction is stirred at room temperature.After 10 minutes, reaction terminates, and adds 10 mL saturated ammonium chlorides, filters out the zinc powder of excess.Concentrated filtrate,
10 mL water are joined in concentrated solution, is extracted with ethyl acetate (10 mL × 3).Merge organic facies, be dried with anhydrous sodium sulfate,
Filter, concentrate, cross silicagel column and separate (ethyl acetate/petroleum ether=2.5%), obtain compound 3a(100 mg, 74%).Compound
Structural formula and the sign data of 3a are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.60 (s, 3H), 3.50 (s, 1H), 7.42-7.50 (m,
6H), 7.61 (s, 1H), 8.05 (d, J = 6.0 Hz, 2H), 8.12 (d, J = 7.2 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ: 21.4, 80.3, 87.4, 115.4, 119.2, 127.2, 127.8, 128.7,
128.8, 129.3, 129.6, 138.8, 139.8, 151.9, 155.3, 160.3. HRMS calcd for
C20H16N: 270.1283 [M+H], found: 270.1287.
Embodiment 2
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
Equipped with benzonitrile (103 mg, 1 mmol), oxolane (2 mL) and 3-bromo-1-propine (476 mg, 4
Mmol) reaction bulb adds zinc powder (390 mg, 6 mmol), reactant mixture is placed in nitrogen atmosphere, is stirred at room temperature
Reaction.After 10 minutes, reaction terminates, and adds 10 mL saturated ammonium chlorides, filters out the zinc powder of excess.Concentrated filtrate, by 10 mL water
Join in concentrated solution, be extracted with ethyl acetate (10 mL × 3).Merge organic facies, be dried with anhydrous sodium sulfate, filter, dense
Contracting, crosses silicagel column and separates (ethyl acetate/petroleum ether=2.5%), obtain compound 3a(85 mg, and 63%).
Embodiment 3
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
According to the method described in embodiment 1, equipped with benzonitrile (103 mg, 1 mmol), oxolane (2 mL) and 3-
The reaction bulb of bromo-1-propine (119 mg, 1 mmol) adds the zinc powder (65 mg, 1 mmol) after activation, reaction is mixed
Thing is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3a(78 mg, 58%).
Embodiment 4
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
According to the method described in embodiment 1, equipped with benzonitrile (103 mg, 1 mmol), oxolane (2 mL) and 3-
The reaction bulb of bromo-1-propine (238 mg, 2 mmol) adds the zinc powder (195 mg, 3 mmol) after activation, reaction is mixed
Compound is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3a(93 mg, 69%).
Embodiment 5
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
According to the method described in embodiment 1, equipped with benzonitrile (103 mg, 1 mmol), oxolane (2 mL) and 3-
The reaction bulb of bromo-1-propine (238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, reaction is mixed
Compound is placed in nitrogen atmosphere, in 60 DEG C of stirring reactions.After reacting 10 minutes, obtain compound 3a(91 mg, 68%).
Embodiment 6
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
According to the method described in embodiment 1, equipped with benzonitrile (103 mg, 1 mmol), DMF (2
The reaction bulb of 3-bromo-1-propine (238 mg, 2 mmol) mL) and adds the zinc powder (130 mg, 2 mmol) after activation, will
Reactant mixture is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 30 minutes, obtain compound 3a(40 mg,
30%).
Embodiment 7
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
According to the method described in embodiment 1, equipped with benzonitrile (103 mg, 1 mmol), dichloromethane (2 mL) and 3-
The reaction bulb of bromo-1-propine (238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, reaction is mixed
Compound is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 30 minutes, obtain compound 3a(27 mg, 20%).
Embodiment 8
The preparation of 3-acetenyl-4-methyl-2,6-diphenyl pyridine (3a)
According to the method described in embodiment 1, bromo-equipped with benzonitrile (103 mg, 1 mmol), ethanol (2 mL) and 3-
The reaction bulb of 1-propine (238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, by reactant mixture
It is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 30 minutes, obtain compound 3a(34 mg, 25%).
Embodiment 9
The preparation of 3-acetenyl-4-methyl-2,6-two (4-aminomethyl phenyl) pyridine (3b)
According to the method described in embodiment 1, equipped with 4-methyl benzonitrile (117 mg, 1 mmol), oxolane (2
The reaction bulb of 3-bromo-1-propine (238 mg, 2 mmol) mL) and adds the zinc powder (130 mg, 2 mmol) after activation, will
Reactant mixture is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3b(92 mg,
62%).Structural formula and the sign data of compound 3b are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.42 (s, 3H), 2.44 (s, 3H), 2.58 (s, 3H),
3.50 (s, 1H), 7.28-7.31 (m, 4H), 7.57 (s, 1H), 7.98 (d, J = 7.6 Hz, 2H), 8.03
(d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 21.35, 21.45, 80.6, 87.1,
114.8, 118.6, 127.0, 128.5, 129.4, 129.6, 136.0, 137.1, 138.6, 139.3, 151.8,
155.3, 160.2. HRMS calcd for C22H20N: 298.1596 [M+H], found: 298.1602.
Embodiment 10
The preparation of 3-acetenyl-4-methyl-2,6-two (2-methoxyphenyl) pyridine (3c)
According to the method described in embodiment 1, equipped with 2-methoxy benzonitrile (133 mg, 1 mmol), oxolane (2
The reaction bulb of 3-bromo-1-propine (238 mg, 2 mmol) mL) and adds the zinc powder (130 mg, 2 mmol) after activation, will
Reactant mixture is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3c(123 mg,
75%).Structural formula and the sign data of compound 3c are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.54 (s, 3H), 3.26 (s, 1H), 3.81 (s, 3H),
3.88 (s, 3H), 6.95-7.04 (m, 5H), 7.50-7.56 (m, 3H), 7.71 (s, 1H). 13C NMR (100
MHz, CDCl3) δ: 21.0, 55.5, 55.6, 85.2, 101.7, 111.1, 111.3, 120.4, 120.7,
121.0, 124.0, 129.7, 130.0, 130.9, 131.6, 133.7, 134.4, 154.2, 157.0, 157.2,
161.2. HRMS calcd for C22H20NO2: 330.1494 [M+H], found: 330.1499.
Embodiment 11
The preparation of 3-acetenyl-4-methyl-2,6-two (2-allyloxy phenyl) pyridine (3d)
According to the method described in embodiment 1, equipped with 2-allyloxy benzonitrile (159 mg, 1 mmol), oxolane
In the reaction bulb of (2 mL) and 3-bromo-1-propine (238 mg, 2 mmol) add activation after zinc powder (130 mg, 2
Mmol), reactant mixture is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3d(114
Mg, 60%).Structural formula and the sign data of compound 3d are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.55 (s, 3H), 3.27 (s, 1H), 4.58-4.63 (m,
4H), 5.17 (dd, J 1 = 14.4 Hz, J 2 = 1.6 Hz, 1H), 5.27-5.32 (m, 2H), 5.42 (dd, J 1
= 14.8 Hz, J 2 = 1.6 Hz, 1H), 5.97-6.10 (m, 2H), 6.98 (d, J = 8.0 Hz, 2H),
7.03-7.07 (m, 2H), 7.30-7.38 (m, 2H), 7.47 (dd, J 1 = 7.6 Hz, J 2 = 1.6 Hz, 1H),
7.80 (s, 1H), 7.90 (dd, J 1 = 7.6 Hz, J 2 = 2.0 Hz, 1H). 13C NMR (100 MHz, CDCl3)
δ: 21.0, 69.31, 69.33, 80.3, 85.4, 112.6, 112.9, 116.6, 117.1, 117.4, 120.7,
121.4, 124.1, 129.1, 129.6, 129.9, 131.0, 131.8, 133.2, 133.7, 149.3, 154.1,
156.1, 156.4, 159.4. HRMS calcd for C26H24NO2: 382.1807 [M+H], found: 382.1815.
Embodiment 12
The preparation of 3-acetenyl-4-methyl-2,6-two (the propargyl phenyl of 2-) pyridine (3e)
According to the method described in embodiment 1, equipped with 2-propargyl epoxide benzonitrile (157 mg, 1 mmol), oxolane
In the reaction bulb of (2 mL) and 3-bromo-1-propine (238 mg, 2 mmol) add activation after zinc powder (130 mg, 2
Mmol), reactant mixture is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3e(100
Mg, 53%).Structural formula and the sign data of compound 3e are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.53-2.57 (m, 5H), 3.28 (s, 1H), 4.70 (d, J
= 2.4 Hz, 2H), 4.75 (d, J = 2.4 Hz, 2H), 7.06-7.17 (m, 3H), 7.33-7.56 (m,
4H), 7.74 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 24.4,
56.5, 56.6, 75.3, 75.7, 78.7, 79.0, 80.0, 85.8, 112.9, 113.0, 117.6, 121.5,
121.7, 122.2, 124.2, 129.6, 129.9, 131.2, 131.3, 131.9, 134.0, 134.2, 149.6,
153.9, 155.1. HRMS calcd for C26H20NO2: 378.1494 [M+H], found: 378.1501.
Embodiment 13
The preparation of 3-acetenyl-4-methyl-2,6-two (3-fluorophenyl) pyridine (3f)
According to the method described in embodiment 1, equipped with 3-fluorobenzonitrile (121 mg, 1 mmol), oxolane (2 mL)
The reaction bulb of 1-propine bromo-with 3-(238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, will be anti-
Answer mixture to be placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3f(104 mg, 68%).
Structural formula and the sign data of compound 3f are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.60 (s, 3H), 3.56 (s, 1H), 7.13 (d, J =
8.4 Hz, 2H), 7.41-7.45 (m, 2H), 7.60 (s, 1H), 7.76-7.85 (m, 4H). 13C NMR (100
MHz, CDCl3) δ: 21.3, 79.7, 88.3, 113.9, 114.2, 115.6, 115.8, 116.0, 116.1,
116.3, 116.5, 116.7, 119.6, 122.56, 122.59, 125.3, 129.26, 129.34, 130.2,
130.3, 140.9, 152.4, 153.9, 158.8, 162.1, 163.7. HRMS calcd for C20H14F2N:
306.1094 [M+H], found: 306.1097.
Embodiment 14
The preparation of 3-acetenyl-4-methyl-2,6-two (4-chlorphenyl) pyridine (3g)
According to the method described in embodiment 1, equipped with 4-chlorobenzonitrile (138 mg, 1 mmol), oxolane (2 mL)
The reaction bulb of 1-propine bromo-with 3-(238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, will be anti-
Answer mixture to be placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3g(108 mg, 64%).
Structural formula and the sign data of compound 3g are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.57 (s, 3H), 3.54 (s, 1H), 7.43 (d, J =
6.4 Hz, 2H), 7.45 (d, J = 6.8 Hz, 2H), 7.55 (s, 1H), 7.99 (d, J = 8.0 Hz,
2H), 8.02 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 21.3, 79.9, 88.1,
115.6, 119.1, 128.1, 128.3, 128.9, 131.0, 135.0, 135.5, 136.9, 138.0, 152.3,
154.1, 159.0. HRMS calcd for C20H14Cl2N: 338.0503 [M+H], found: 338.0508.
Embodiment 15
The preparation of 3-acetenyl-4-methyl-2,6-two (2-bromo-5-methoxyphenyl) pyridine (3h)
According to the method described in embodiment 1, equipped with 2-bromo-5-methoxy benzonitrile (212 mg, 1 mmol), tetrahydrochysene
In the reaction bulb of furan (2 mL) and 3-bromo-1-propine (238 mg, 2 mmol) add activation after zinc powder (130 mg, 2
Mmol), reactant mixture is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3h(141
Mg, 58%).Structural formula and the sign data of compound 3h are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.59 (s, 3H), 3.17 (s, 1H), 3.80 (s, 3H),
3.81 (s, 3H), 6.81-6.84 (m, 2H), 7.03 (d, J = 2.8 Hz, 1H), 7.16 (d, J = 2.8
Hz, 1H), 7.51-7.54 (m, 3H). 13C NMR (100 MHz, CDCl3) δ: 20.9, 55.6, 78.7,
87.6, 112.1, 113.1, 116.2, 116.5, 116.7, 117.7, 124.3, 133.4, 134.0, 141.3,
141.4, 150.6, 156.2, 158.5, 159.0, 160.7. HRMS calcd for C22H18Br2NO2: 485.9704
[M+H], found: 485.9708.
Embodiment 16
The preparation of 3-acetenyl-4-methyl-2,6-two (1-naphthyl) pyridine (3i)
According to the method described in embodiment 1, equipped with 1-naphthonitrile (153 mg, 1 mmol), oxolane (2 mL) and
The reaction bulb of 3-bromo-1-propine (238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, will reaction
Mixture is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3i(140 mg, 76%).Change
Structural formula and the sign data of compound 3i are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.68 (s, 3H), 3.20 (s, 1H), 7.49-7.60 (m,
7H), 7.71 (d, J = 7.2 Hz, 2H), 7.83-7.94 (m, 5H), 8.26 (d, J = 2.8 Hz, 1H).13C NMR (100 MHz, CDCl3) δ: 21.1, 79.4, 87.4, 118.1, 124.4, 125.1, 125.3,
125.6, 125.7, 125.9, 126.0, 126.1, 126.6, 127.5, 127.8, 128.3, 128.4, 128.8,
129.1, 131.2, 131.7, 133.7, 134.0, 137.9, 138.0, 151.0, 157.6, 161.4. HRMS
calcd for C28H20N: 370.1596 [M+H], found: 370.1608.
Embodiment 17
The preparation of 3-acetenyl-4-methyl-2,6-two (2-thienyl) pyridine (3j)
According to the method described in embodiment 1, equipped with 2-thiophene formonitrile HCN (109 mg, 1 mmol), oxolane (2 mL)
The reaction bulb of 1-propine bromo-with 3-(238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, will be anti-
Answer mixture to be placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3j(70 mg, 50%).
Structural formula and the sign data of compound 3j are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.54 (s, 3H), 3.82 (s, 1H), 7.11-7.14 (m,
2H), 7.38-7.46 (m, 3H), 7.63 (d, J = 3.2 Hz, 1H), 8.42 (d, J = 3.6 Hz, 1H).13C NMR (100 MHz, CDCl3) δ: 21.2, 80.4, 89.5, 111.8, 116.8, 125.3, 127.6,
128.0, 128.4, 128.5, 128.8, 144.3, 144.4, 150.4, 152.35, 152.38. HRMS calcd
for C16H12NS2: 282.0411 [M+H], found: 282.0414.
Embodiment 18
The preparation of 3-acetenyl-4-methyl-2,6-two (styryl) pyridine (3k)
According to the method described in embodiment 1, equipped with cinnamonitrile (129 mg, 1 mmol), oxolane (2 mL) and 3-
The reaction bulb of bromo-1-propine (238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, reaction is mixed
Compound is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3k(88 mg, 55%).Chemical combination
Structural formula and the sign data of thing 3k are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.48 (s, 3H), 3.75 (s, 1H), 7.16 (s, 1H),
7.17-7.43 (m, 7H), 7.62-7.82 (m, 6H), 8.04 (d, J = 16.4 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ: 20.7, 79.4, 88.5, 116.1, 120.9, 125.3, 127.3, 127.6, 127.9,
128.4, 128.46, 128.50, 128.7, 128.8, 133.9, 135.0, 136.7, 137.0, 153.8,
156.1. HRMS calcd for C24H20N: 322.1596 [M+H], found: 322.1599.
Embodiment 19
The preparation of 3-alkynyl-2,4,6-trimethylpyridine (3l)
According to the method described in embodiment 1, bromo-equipped with acetonitrile (41 mg, 1 mmol), oxolane (2 mL) and 3-
The reaction bulb of 1-propine (238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, by reactant mixture
It is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3l(44 mg, 60%).Compound 3l
Structural formula and characterize data as follows:
1H NMR (400 MHz, CDCl3) δ: 2.34 (s, 3H), 2.44 (s, 3H), 2.61 (s, 3H),
3.52 (s, 1H), 6.82 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 20.3, 23.5, 24.2,
79.5, 86.5, 115.3, 121.4, 150.1, 156.5, 160.1. HRMS calcd for C10H12N:
146.0970 [M+H], found: 146.0977.
Embodiment 20
The preparation of 3-acetenyl-4-methyl-2,6-dibenzyl pyridine (3m)
According to the method described in embodiment 1, equipped with benzene acetonitrile (117 mg, 1 mmol), oxolane (2 mL) and 3-
The reaction bulb of bromo-1-propine (238 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, reaction is mixed
Compound is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3m(99 mg, 67%).Chemical combination
Structural formula and the sign data of thing 3m are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.39 (s, 3H), 3.62 (s, 1H), 4.19 (s, 2H),
4.47 (s, 2H), 6.86 (s, 1H), 7.28-7.37 (m, 8H), 7.48 (d, J = 7.2 Hz, 2H). 13C
NMR (100 MHz, CDCl3) δ: 20.7, 42.9, 44.6, 79.8, 87.1, 116.0, 121.6, 126.2,
126.5, 128.3, 128.7, 129.2, 129.3, 139.4, 139.6, 151.0, 159.7, 162.2. HRMS
calcd for C22H20N: 298.1596 [M+H], found: 298.1601.
Embodiment 21
The preparation of compound 3n
According to the method described in embodiment 1, equipped withE-3-(4-cyanophenyl) acrylic acid methyl ester. (187 mg, 1
The reaction bulb of oxolane (2 mL) and 3-bromo-1-propine (238 mg, 2 mmol) mmol), adds the zinc powder after activation
(130 mg, 2 mmol), are placed in reactant mixture in nitrogen atmosphere, reaction are stirred at room temperature.After reacting 10 minutes, obtain
Compound 3n(131 mg, 60%).Structural formula and the sign data of compound 3n are as follows:
1H NMR (400 MHz, CDCl3) δ: 2.61 (s, 3H), 3.57 (s, 1H), 3.82 (s, 3H),
3.84 (s, 3H), 6.52 (d, J = 16.0 Hz, 1H), 6.53 (d, J = 16.0 Hz, 1H), 7.63-7.65
(m, 5H), 7.75 (d, J = 16.0 Hz, 1H), 7.78 (d, J = 16.4 Hz, 1H), 8.09 (d, J =
8.0 Hz, 2H), 8.14 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 21.4, 51.8,
79.9, 88.3, 115.9, 118.3, 118.4, 119.5, 127.5, 127.6, 128.5, 130.1, 134.8,
135.3, 140.2, 141.4, 144.2, 144.5, 152.3, 154.3, 159.3, 167.4, 167.5. HRMS
calcd for C28H24NO4: 438.1705 [M+H], found: 438.1709.
Embodiment 22
The preparation of 3-propinyl-4-ethyl-2,6-diphenyl pyridine (3o)
According to the method described in embodiment 1, equipped with benzonitrile (103 mg, 1 mmol), oxolane (2 mL) and 1-
The reaction bulb of bromo-2-butyne (266 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, reaction is mixed
Compound is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3o(97 mg, 65%).Chemical combination
Structural formula and the sign data of thing 3o are as follows:
1H NMR (400 MHz, CDCl3) δ: 1.34-1.38 (m, 3H), 2.06 (s, 3H), 2.93-2.94
(m, 2H), 7.40-7.49 (m, 6H), 7.59 (s, 1H), 8.06 (d, J = 7.6 H, 2H), 8.12 (d, J
= 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 4.7, 13.8, 27.9, 76.2, 95.8, 117.5,
127.0, 127.5, 127.6, 128.4, 128.6, 128.8, 128.9, 139.2, 140.5, 154.6, 156.5,
159.6. HRMS calcd for C22H20N: 298.1596 [M+H], found: 298.1599.
Embodiment 23
The preparation of 3-propinyl-4-ethyl-2,6-lutidines (3p)
According to the method described in embodiment 1, bromo-equipped with acetonitrile (41 mg, 1 mmol), oxolane (2 mL) and 1-
The reaction bulb of 2-butyne (266 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, by reactant mixture
It is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3p(52 mg, 60%).Compound 3p
Structural formula and characterize data as follows:
1H NMR (400 MHz, CDCl3) δ: 1.15 (t, J = 8.0 Hz, 3H), 2.07 (s, 3H),
2.42 (s, 3H), 2.57 (s, 3H), 2.66 (q, J = 8.0 Hz, 2H), 6.77 (s, 1H). 13C NMR
(100 MHz, CDCl3) δ: 4.5, 13.6, 23.5, 24.2, 27.2, 75.2, 94.9, 116.4, 119.6,
154.9, 155.3, 159.3. HRMS calcd for C12H16N: 174.1283 [M+H], found: 174.1288.
Embodiment 24
3-(1-butynyl) preparation of-4-propyl group-2,6-diphenyl pyridine (3q)
According to the method described in embodiment 1, equipped with benzonitrile (103 mg, 1 mmol), oxolane (2 mL) and 1-
The reaction bulb of bromo-valerylene (294 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, reaction is mixed
Compound is placed in nitrogen atmosphere, and reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3q(102 mg, 63%).Chemical combination
Structural formula and the sign data of thing 3q are as follows:
1H NMR (400 MHz, CDCl3) δ: 1.06 (t, J = 7.2 Hz, 3H), 1.21 (t, J = 7.2
Hz, 3H), 1.79 (q, J = 7.2 Hz, 2H), 2.43 (q, J = 7.2 Hz, 2H), 2.88 (t, J = 7.2
Hz, 2H), 7.41-7.50 (m, 6H), 7.57 (s, 1H), 8.07-8.12 (m, 4H). 13C NMR (100 MHz,
CDCl3) δ: 13.49, 13.53, 14.1, 22.9, 36.9, 101.3, 116.7, 118.4, 127.0, 127.5,
128.3, 128.6, 128.9, 129.7, 139.2, 140.4, 154.3, 155.0, 159.5. HRMS calcd for
C24H24N: 326.1909 [M+H], found: 326.1916.
Embodiment 25
3-(1-butynyl) preparation of-4-propyl group-2,6-lutidines (3r)
According to the method described in embodiment 1, bromo-equipped with acetonitrile (41 mg, 1 mmol), oxolane (2 mL) and 1-
The reaction bulb of valerylene (294 mg, 2 mmol) adds the zinc powder (130 mg, 2 mmol) after activation, by reactant mixture
It is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3r(57 mg, 57%).Compound 3r
Structural formula and characterize data as follows:
1H NMR (400 MHz, CDCl3) δ: 0.86 (t, J = 7.2 Hz, 3H), 1.16 (t, J = 7.6
Hz, 3H), 1.54 (q, J = 7.6 Hz, 2H), 2.36-2.42 (m, 5H), 2.50-2.57 (m, 5H), 6.69
(s, 1H). 13C NMR (100 MHz, CDCl3) δ: 13.3, 13.9, 14.0, 22.7, 23.6, 24.2, 36.1,
75.6, 100.6, 116.5, 120.3, 153.2, 155.1, 159.3. HRMS calcd for C14H20N:
202.1596 [M+H], found: 202.1599.
Embodiment 26
3-(phenylacetylene base) preparation of-4-benzyl-2,6-two (4-methoxyphenyl) pyridine (3s)
According to the method described in embodiment 1, equipped with 4-methoxy benzonitrile (133 mg, 1 mmol), oxolane (2
ML) add and in the reaction bulb of 3-bromo-1-propinyl benzene (390 mg, 2 mmol) zinc powder after activation (130 mg, 2
Mmol), reactant mixture is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3s
(132 mg, 55%).Structural formula and the sign data of compound 3s are as follows:
1H NMR (400 MHz, CDCl3) δ: 3.85 (s, 3H), 3.90 (s, 3H), 4.36 (s, 2H),
6.97 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 7.33-7.42 (m, 11H), 8.03
(d, J = 8.8 Hz, 2H), 8.15 (d, J = 8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ:
40.5, 55.3, 55.4, 87.1, 98.8, 113.1, 114.0, 114.8, 117.6, 123.3, 126.5,
128.2, 128.4, 128.7, 129.1, 131.15, 131.20, 131.5, 132.8, 139.0, 153.2,
154.7, 159.2, 160.1, 160.6. HRMS calcd for C34H28NO2: 482.2120 [M+H], found:
482.2129.
Embodiment 27
3-((4-fluorophenyl) acetenyl)-4-(4-luorobenzyl) preparation of-2,6-two (2-bromophenyl) pyridine (3t)
According to the method described in embodiment 1, equipped with 2-bromobenzylcyanide (182 mg, 1 mmol), oxolane (2 mL)
1-propinyl bromo-with 1-(3-)-4-fluorobenzene (426 mg, 2 mmol) reaction bulb in add activation after zinc powder (130 mg,
2 mmol), reactant mixture is placed in nitrogen atmosphere, reaction is stirred at room temperature.After reacting 10 minutes, obtain compound 3t
(123 mg, 40%).Structural formula and the sign data of compound 3t are as follows:
1H NMR (400 MHz, CDCl3) δ: 4.31 (s, 2H), 6.97 (t, J = 8.4 Hz, 2H),
7.03 (d, J = 8.4 Hz, 2H), 7.12-7.15 (m, 2H), 7.22-7.31 (m, 4H), 7.36-7.44 (m,
3H), 7.55 (d, J = 7.6 Hz, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 7.6 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ: 39.7, 83.8, 100.0, 115.71, 115.75, 115.9,
116.0, 118.4, 121.9, 123.0, 125.0, 127.2, 127.8, 130.6, 130.8, 130.9, 131.5,
132.1, 132.3, 132.7, 133.3, 133.41, 133.45, 133.49, 154.8, 160.7, 163.1,
164.2, 165.1. HRMS calcd for C32H20Br2F2N: 613.9931 [M+H], found: 613.9939.
Embodiment above describes the ultimate principle of the present invention, principal character and advantage, the technical staff of the industry should
Understanding, the present invention is not restricted to the described embodiments, and the simply explanation present invention's described in above-described embodiment and description is former
Reason, under the scope without departing from the principle of the invention, the present invention also has various changes and modifications, and these changes and improvements each fall within
In the scope of protection of the invention.
Claims (4)
1. the synthetic method of a 3-alkynyl pyridine compounds and their, it is characterised in that: with nitrile and propargyl bromide as raw material, with tetrahydrochysene
Furan, dichloromethane, DMF or ethanol are solvent, under the facilitation of metallic zinc, exist in room temperature-80 DEG C
In nitrogen atmosphere, stirring reaction, can be prepared by 3-alkynyl pyridine compounds and their, and the reaction equation in this synthetic method is:
,
Wherein R1For aryl, alkyl or alkenyl, described aryl is 1-naphthyl, 2-thienyl, phenyl or substituted-phenyl, this replacement
Substituent group on phenyl phenyl ring is the one or many in methyl, methoxyl group, allyloxy, propargyl epoxide, fluorine, chlorine, bromine or thiazolinyl
Kind, the position of substituent group is the ortho position on phenyl ring, meta or para position, R2For hydrogen, alkyl, phenyl or substituted-phenyl, this substituted benzene
Substituent group on base phenyl ring is methyl, methoxyl group, allyloxy, propargyl epoxide, fluorine, chlorine or bromine, and the position of substituent group is phenyl ring
On ortho position, meta or para position.
The synthetic method of 3-alkynyl pyridine compounds and their the most according to claim 1, it is characterised in that: described nitrile, alkynes
The ratio of the amount of the material that feeds intake of propyl bromide and metallic zinc is 1:1-4:1-6.
The synthetic method of 3-alkynyl pyridine compounds and their the most according to claim 1 and 2, it is characterised in that: described gold
Genus zinc is zinc powder.
The synthetic method of 3-alkynyl pyridine compounds and their the most according to claim 1 and 2, it is characterised in that: described gold
Belonging to zinc is the zinc powder after dilute hydrochloric acid activates.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410515647.8A CN104311474B (en) | 2014-09-30 | 2014-09-30 | Synthesis method of 3-alkynyl pyridine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410515647.8A CN104311474B (en) | 2014-09-30 | 2014-09-30 | Synthesis method of 3-alkynyl pyridine compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104311474A CN104311474A (en) | 2015-01-28 |
| CN104311474B true CN104311474B (en) | 2017-01-11 |
Family
ID=52366822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410515647.8A Active CN104311474B (en) | 2014-09-30 | 2014-09-30 | Synthesis method of 3-alkynyl pyridine compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104311474B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115572254A (en) * | 2021-06-21 | 2023-01-06 | 复旦大学 | 2, 6-diaryl pyridine HDAC/Tubulin bifunctional inhibitor, preparation method and application |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101798282A (en) * | 2010-03-30 | 2010-08-11 | 中国科学院上海有机化学研究所 | Multi-substituted fluorine-containing pyridine |
| CN103396357A (en) * | 2013-07-29 | 2013-11-20 | 江苏恒安化工有限公司 | Preparation method of 2,3-difluoro-5-chloropyridine |
-
2014
- 2014-09-30 CN CN201410515647.8A patent/CN104311474B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN104311474A (en) | 2015-01-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2049487B1 (en) | Process for the preparation of 2-substituted-5-(1-alkylthio)alkylpyridines | |
| Edwin Raja et al. | Nickel-catalyzed Hiyama-type decarboxylative coupling of propiolic acids and organosilanes | |
| CN107880079B (en) | Cyclic N-heterocyclic bis-carbene-palladium complex and preparation method and application thereof | |
| CN105001028A (en) | Synthesis method for asymmetric conjugate diyne compound | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN104311474B (en) | Synthesis method of 3-alkynyl pyridine compound | |
| CN110878035B (en) | Method for preparing symmetrical urea compound | |
| Saha et al. | Practical application of PhI (OAc) 2/I2 combination to synthesize benzimidazoles from 2-aminobenzylamine through ring distortion strategy | |
| CN106699632A (en) | Preparation method of 3-methylene isoindole-1-one derivatives | |
| CN105061348A (en) | Method for preparing 2-substituted benzoxazole compound | |
| CN103130810B (en) | Synthesis method of pyrrolo[1,5-c] quinazoline compounds | |
| CN104356110B (en) | A kind of the sulphur induction tetrazine compound of 3,6 aromatic heterocycle Asymmetrical substitute 1,2,4,5 and its synthetic method | |
| CN104086456B (en) | A kind of synthetic method of sartanbiphenyl | |
| CN106674105B (en) | A kind of position C5 selective halogenation method of amide quinoline | |
| CN104447391A (en) | Methylenebisamide derivative and preparation method thereof | |
| CN102060798A (en) | Method for synthesizing 2-(1-hydro-4-tetrazole)-4'-methylbiphenyl and derivatives thereof | |
| CN105237466B (en) | A kind of method for synthesizing three substituted pyridine derivatives | |
| CN112441981B (en) | 1,2, 5-polysubstituted imidazole derivative and synthesis method and application thereof | |
| CN104327025B (en) | A kind of preparation method of 4-arylnaphthalene lactone derivative | |
| CN104003895B (en) | A kind of method of cascade reaction synthesis Terphenyls compound of palladium chtalyst | |
| CN112939829A (en) | Synthetic method of aryl trifluoromethyl thioether | |
| CN109232282B (en) | Synthetic method of 2-aminobenzophenone compound | |
| CN105153048A (en) | Preparation method of benzoyleneurea compounds | |
| CN102718694B (en) | 3-cyan substituted indole compound and synthetic method thereof | |
| CN103936662B (en) | 1-R1-3, 3-difluoro-4-R2-piperidine and its derivatives and its prepn |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |