CN106938985A - A kind of 5 amide groups quinolines of alkenyl 8 and its one-pot preparation thereof - Google Patents
A kind of 5 amide groups quinolines of alkenyl 8 and its one-pot preparation thereof Download PDFInfo
- Publication number
- CN106938985A CN106938985A CN201710164258.9A CN201710164258A CN106938985A CN 106938985 A CN106938985 A CN 106938985A CN 201710164258 A CN201710164258 A CN 201710164258A CN 106938985 A CN106938985 A CN 106938985A
- Authority
- CN
- China
- Prior art keywords
- reaction
- double
- phenyl
- preparation
- phosphine dichloride
- 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.)
- Granted
Links
- 0 *C=CC=C1C(C=C*)=CC=C([*-]C(*)=O)C1 Chemical compound *C=CC=C1C(C=C*)=CC=C([*-]C(*)=O)C1 0.000 description 3
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The present invention provides a kind of 5 amide groups quinolines of alkenyl 8 and preparation method thereof, using 8 amide groups quinolines, halide, alkenes compounds as raw material, and reaction dissolvent is made with conventional organic solvent；The first step is that without metal catalytic, second step common metal catalyst is as catalyst, the first halogenation of experience, without separation directly with alkenes compounds one pot reaction, obtain 5 amide groups quinolines of alkenyl 8 through column chromatography.Reaction yield is high, preparation method is simple, and cost is relatively low, with preferable prospects for commercial application.
Description
【Technical field】
The invention belongs to be catalyzed organic synthesis field, a kind of 5- alkenyl 8- amide groups quinolines are related in particular to
Compound and preparation method thereof.
【Background technology】
Quinolines are due to its important function in natural products, pharmacy industry, in recent years by vast chemical section
Grind the extensive concern of worker.Group is introduced on quinoline ring and may be such that the compound has special activity, with great
Medical value prospect.Since eighties of last century, many classical synthetic methods are reported in succession.Method relatively common at present
It is that carrying out cycloaddition reaction cyclization using presoma aniline and carbonyls or alkynes prepares corresponding quinolines.
But such method needs previously prepared expensive polysubstituted presoma aniline, step is more, complex operation, and sometimes selects
Property is also difficult to control to.Selective modification is carried out using existing quinoline mother nucleus structure and synthesizes corresponding quinoline derivatives, particularly
The report of 5- alkenyl 8- amide groups quinoline is then more rare.Introduce olefin functionalities on 5, quinoline, can be lifted its
Application prospect in terms of material, medicine.By first halogenation, not separate direct one kettle way coupling reaction be a kind of easy way.So
And in the method reported at present, the halogenation of quinoline is required for metallic catalyst or metal salt as halogen source
(J.Am.Chem.Soc.,2013,135,9797；Tetrahedron,2015,71,70；Org.Biomol.Chem.2016,14,
3016).And the presence of metal has negative effect for follow-up coupling reaction.The present invention is anti-without metal halide by the first step
The reaction for directly carrying out the follow-up coupling with alkene, should not be separated, to prepare the product of 5 alkenyls；Due to the first step without
Metal is participated in, and on subsequent reactions without influence, efficiently can easily obtain target product.The present invention is with aminoquinolines chemical combination
Thing, halide, alkenes compounds are raw material, and common metal makees reaction dissolvent as catalyst with conventional organic solvent；Through
Go through after first halogenation after alkenyl one kettle way Heck reactions, 5- alkenyl 8- amide groups quinolines are obtained through column chromatography.
【The content of the invention】
It is an object of the invention to provide a kind of easy side for preparing 5- alkenyl 8- amide groups quinolines
Method, to improve the yield and selectivity of target product.
To achieve the above object of the invention, the present invention proposes following technical scheme：
1) a kind of 5- alkenyl 8- acylamino-s quinolines (I) and preparation method thereof, the method is with 8- acylamino- quinolines
Quinoline class compound (II), terminal olefin class compound (III) are that raw material, halide are halide reagent, one pot in organic solvent
Two-step method effecting reaction：That is the first step：Without under metal function, 8- acylamino-s quinolines (II) are obtained with halide reaction
5- halogenated quinoline class compounds (IV)；Second step：Without separation in the presence of metallic catalyst directly with olefines chemical combination
Thing (III) occurs that 5- alkenyl 8- acylamino- quinoline are made under one kettle way He Ke (Heck) cross-coupling reaction, alkalescence condition
Class compound (I)；Wherein described compound I, II, III and IV structural formula are as follows：
Wherein described R1The alkyl group of aryl or C1-C6 for C6-C10, R2Aryl or C3-C6 for C6-C10 it is miscellaneous
Ring class group, halogen X is Cl, Br, I.
2) according to above-mentioned preparation method, wherein the R1Group be t-Bu, Me, Et, n-octyl, cyclohexyl,
cyclopentyl、Ph、p-MePh、p-OMePh、p-FPh、o-FPh、m-FPh、p-CF3One in Ph, 2-thienyl group
Kind.
3) according to above-mentioned preparation method, wherein the R2Group is Ph, p-MePh, o-MePh, m-MePh, p-MeOPh, m-
MeOPh、p-EtPh、p-t-BuPh、p-FPh、p-ClPh、p-BrPh、p-CNPh、p-NO2Ph、p-CF3Ph、3,5-di-FPh、p-
acetyl-Ph、2-Naphth、2-thienyl、3-thienyl。
4) according to above-mentioned preparation method, the halide is NCS, NBS, NIS, Br2、I2In one kind.
5) according to above-mentioned preparation method, the metallic catalyst described in it is double (triphenyl) phosphine dichloride palladiums, double (three (2-
Methyl) phenyl) phosphine dichloride palladium, double (three (4- methyl) phenyl) phosphine dichloride palladiums, double (three (the 4- tert-butyl groups) phenyl) phosphine dichlorides
Change palladium, double (three (4- chlorine) phenyl) phosphine dichloride palladiums, double (three (4- fluorine) phenyl) phosphine dichloride palladiums, double (three (4- trifluoromethyls)
Phenyl) phosphine dichloride palladium, palladium, palladium bichloride, double (triphenyl) phosphine dichloride nickel, double (three (2- methyl) phenyl) phosphine dichlorides
Nickel, double (three (4- methyl) phenyl) phosphine dichloride nickel, double (three (the 4- tert-butyl groups) phenyl) phosphine dichloride nickel, double (three (4- chlorine) benzene
Base) phosphine dichloride nickel, double (three (4- fluorine) phenyl) phosphine dichloride nickel, double (three (4- trifluoromethyls) phenyl) phosphine dichloride nickel, vinegar
One kind in sour nickel, nickel chloride.
6) according to above-mentioned preparation method, its described solvent is tetrahydrofuran, toluene, Isosorbide-5-Nitrae-dioxane, dimethyl sulfoxide
(DMSO), the one or two in DMF (DMF), the wherein first step and second step react can with identical or
It is different.
7) according to above-mentioned preparation method, its described alkalescence condition be sodium carbonate, saleratus, triethylamine, potassium tert-butoxide or
One kind of potassium hydroxide.
8) preparation method according to claim 1, mole addition of the metallic catalyst is 1%-20% (phases
For substrate II).
9) according to above-mentioned preparation method, the condition of the catalytic reaction is：First step reaction halogenation is in 50-160
Reacted 6-18 hours at DEG C；Second step coupling reaction is reaction 4-12 hours at 50-160 DEG C.
In terms of existing technologies, main advantage has the present invention：First step halogenation process is urged without metallic catalyst
Change or halogen metal salt is as halogen source, interference is not present to follow-up coupling reaction.Second step reaction, can without being pre-separated
Directly reacted.The present invention is more quick and efficient with respect to the method that first separation, second step are coupled again.
【Brief description of the drawings】
It is the synthesis path figure for the 5- positions alkenyl 8- amide groups quinolines that the present invention is provided shown in Fig. 1.
【Embodiment】
The synthesis path provided by the present invention for catalyzing and synthesizing 5- alkenyl quinolines methods, refers to accompanying drawing
1：Raw material quinoline and halide reagent are inserted in reaction vessel, solvent is added, reacted 6-18 hours in the environment of 50-160 DEG C,
Question response is cooled to room temperature after the completion of reaction, then adds olefin(e) compound and catalyst is inserted in reaction vessel, adds organic
Solvent, continues to react 4-12 hours, reaction obtains target product after completing through pillar layer separation in the environment of 50-160 DEG C.
With reference to specific preparation example, the present invention will be further described：
Preparation example 1
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NCS and 1mL tetrahydrofurans, nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to room temperature after the completion of reaction, so
Add 0.3mmol styrene, 0.4mmol sodium carbonate and double (triphenyl) phosphine dichlorides of 0.02mmol catalyst under nitrogen atmosphere afterwards
Change palladium to insert in reaction vessel, add 1mL DMF, reacted 12 hours in the environment of 50 DEG C, after reaction terminates, filtered, concentration,
5- styryls -8- (pivaloyl amino) quinoline is obtained through pillar layer separation, yield is 90%.
Preparation example 2
0.2mmol 8- (acetylamino) quinoline (R is added in 10mL reaction tubes1=Me), 0.22mmol NBS and 1mL
Under toluene, nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to room temperature after the completion of reaction, then in nitrogen atmosphere
Lower addition 0.3mmol styrene, 0.4mmol sodium carbonate and double (three (2- methyl) phenyl) the phosphine dichloride palladiums of 0.02mmol catalyst
Insert in reaction vessel, add solvent 1mL DMSO, reacted 12 hours in the environment of 50 DEG C, after reaction terminates, filtering is dense
Contracting, obtains 5- styryls -8- (acetylamino) quinoline, yield is 85% through pillar layer separation.
Preparation example 3
0.2mmol 8- (positive propionamido) quinoline (R is added in 10mL reaction tubes1=Et), 0.22mmolNIS and 1mL
Under DMF, nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to room temperature after the completion of reaction, then in nitrogen atmosphere
Lower addition 0.3mmol styrene, 0.4mmol sodium carbonate and double (three (4- methyl) phenyl) the phosphine dichloride palladiums of 0.02mmol catalyst
Insert in reaction vessel, add solvent 1mL toluene, reacted 12 hours in the environment of 50 DEG C, after reaction terminates, filtered, concentration,
5- styryls -8- (positive propionamido) quinoline is obtained through pillar layer separation, yield is 88%.
Preparation example 4
0.2mmol 8- (positive certain herbaceous plants with big flowers acylamino-) quinoline (R is added in 10mL reaction tubes1=n-octyl), 0.22mmol Br2
With 1mL DMSO, under nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to room temperature after the completion of reaction, then in nitrogen
Atmosphere encloses lower addition 0.3mmol styrene, 0.4mmol sodium carbonate and double (three (the 4- tert-butyl groups) phenyl) phosphines of 0.02mmol catalyst
Palladium chloride is inserted in reaction vessel, adds solvent 1mL Isosorbide-5-Nitraes-dioxane, is reacted 12 hours in the environment of 50 DEG C, reaction
After end, filter, concentration obtains 5- styryls -8- (positive certain herbaceous plants with big flowers acylamino-) quinoline, yield is 80% through pillar layer separation.
Preparation example 5
0.2mmol 8- (cyclohexyl acylamino-) quinoline (R is added in 10mL reaction tubes1=cyclohexyl),
0.22mmol I2With 1mL Isosorbide-5-Nitrae dioxane, under nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response after the completion of reaction
Room temperature is cooled to, 0.3mmol styrene, 0.4mmol sodium carbonate and 0.02mmol catalyst are then added under nitrogen atmosphere double
(three (4- fluorine) phenyl) phosphine dichloride palladium is inserted in reaction vessel, adds solvent 1mL tetrahydrofurans, is reacted in the environment of 50 DEG C
12 hours, after reaction terminates, filter, concentration obtains 5- styryls -8- (Cyclohexylamino) quinoline, yield through pillar layer separation
For 75%.
Preparation example 6
0.2mmol 8- (cyclopenta acylamino-) quinoline (R is added in 10mL reaction tubes1=cyclopentyl),
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol sodium carbonate and the double (three (4- of 0.02mmol catalyst under nitrogen atmosphere
Trifluoromethyl) phenyl) phosphine dichloride palladium inserted in reaction vessel, solvent 1mL Isosorbide-5-Nitraes-dioxane is added, in 50 DEG C of environment
Lower reaction 12 hours, after reaction terminates, is filtered, and concentration obtains 5- styryls -8- (cyclopenta acylamino-) quinoline through pillar layer separation
Quinoline, yield is 78%.
Preparation example 7
0.2mmol 8- (benzamido) quinoline (R is added in 10mL reaction tubes1=Ph), 0.22mmol Br2And 1mL
Under DMSO, nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to room temperature after the completion of reaction, then in nitrogen atmosphere
Lower addition 0.3mmol styrene, 0.4mmol saleratus and 0.02mmol catalyst acetic acid palladiums are inserted in reaction vessel, are added
Solvent 1mL Isosorbide-5-Nitraes-dioxane, react 12 hours in the environment of 50 DEG C, after reaction terminates, and filter, concentration, through column chromatography point
From 5- styryls -8- (benzamido) quinoline is obtained, yield is 88%.
Preparation example 8
0.2mmol 8- ((4- methyl) benzamido) quinoline (R is added in 10mL reaction tubes1=p-MePh),
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol potassium hydroxide and 0.02mmol catalyst palladium bichlorides under nitrogen atmosphere
Insert in reaction vessel, add solvent 1mL Isosorbide-5-Nitraes-dioxane, reacted 12 hours in the environment of 50 DEG C, after reaction terminates,
Filtering, concentration, obtains 5- styryls -8- ((4- methylbenzenes first) acylamino-) quinoline, yield is 90% through pillar layer separation.
Preparation example 9
0.2mmol 8- ((4- fluorine) benzamido) quinoline (R is added in 10mL reaction tubes1=p-FPh),
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol triethylamines and the double (triphens of 0.02mmol catalyst under nitrogen atmosphere
Base) phosphine dichloride nickel inserted in reaction vessel, adds solvent 1mL Isosorbide-5-Nitraes-dioxane, 12 is reacted in the environment of 50 DEG C small
When, after reaction terminates, filter, concentration obtains 5- styryls -8- ((4- fluorine) benzamido) quinoline through pillar layer separation, produces
Rate is 84%.
Preparation example 10
0.2mmol 8- ((2- fluorine) benzamido) quinoline (R is added in 10mL reaction tubes1=o-FPh),
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 18h at 50 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol potassium tert-butoxides and 0.02mmol catalyst double (three under nitrogen atmosphere
(2- methyl) phenyl) phosphine dichloride nickel inserted in reaction vessel, solvent 1mL Isosorbide-5-Nitraes-dioxane is added, in the environment of 50 DEG C
Reaction 12 hours, after reaction terminates, is filtered, and concentration obtains 5- styryls -8- ((2- fluorine) benzamido) through pillar layer separation
Quinoline, yield is 81%.
Preparation example 11
0.2mmol 8- ((3- fluorine) benzamido) quinoline (R is added in 10mL reaction tubes1=m-FPh),
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 18h at 80 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol triethylamines and the double (three (4- of 0.02mmol catalyst under nitrogen atmosphere
Methyl) phenyl) phosphine dichloride nickel inserted in reaction vessel, adds solvent 1mL Isosorbide-5-Nitraes-dioxane, anti-in the environment of 70 DEG C
Answer 12 hours, after reaction terminates, filter, concentration obtains 5- styryls -8- ((3- fluorine) benzamido) quinoline through pillar layer separation
Quinoline, yield is 78%.
Preparation example 12
0.2mmol 8- ((4- trifluoromethyls) benzamido) quinoline (R is added in 10mL reaction tubes1=p-CF3Ph)、
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 12h at 100 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol triethylamines and the double (three (4- of 0.02mmol catalyst under nitrogen atmosphere
The tert-butyl group) phenyl) phosphine dichloride nickel inserted in reaction vessel, solvent 1mL Isosorbide-5-Nitraes-dioxane is added, in the environment of 120 DEG C
Reaction 8 hours, after reaction terminates, is filtered, and concentration obtains 5- styryls -8- ((4- trifluoromethyls) benzoyls through pillar layer separation
Amino) quinoline, yield is 75%.
Preparation example 13
0.2mmol 8- ((2- thiophene) formamido group) quinoline (R is added in 10mL reaction tubes1=2-thienyl),
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 8h at 120 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol triethylamines and the double (three (4- of 0.02mmol catalyst under nitrogen atmosphere
Chlorine) phenyl) phosphine dichloride nickel inserted in reaction vessel, adds solvent 1mL Isosorbide-5-Nitraes-dioxane, reacted in the environment of 140 DEG C
6 hours, after reaction terminates, filter, concentration obtains 5- styryls -8- ((2- thiophene) formamido group) quinoline through pillar layer separation,
Yield is 86%.
Preparation example 14
0.2mmol 8- ((4- methoxyl groups) benzamido) quinoline (R is added in 10mL reaction tubes1=p-OMePh),
0.22mmol Br2With 1mL DMSO, under nitrogen atmosphere, reaction carries out 6h at 160 DEG C.Question response is cooled to after the completion of reaction
Room temperature, then adds 0.3mmol styrene, 0.4mmol triethylamines and the double (three (4- of 0.02mmol catalyst under nitrogen atmosphere
Fluorine) phenyl) phosphine dichloride nickel inserted in reaction vessel, adds solvent 1mL Isosorbide-5-Nitraes-dioxane, reacted in the environment of 160 DEG C
4 hours, after reaction terminates, filter, concentration obtains 5- styryls -8- ((4- methoxyl groups) benzamido) through pillar layer separation
Quinoline, yield is 89%.
Preparation example 15
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- methyl styrenes, 0.4mmol sodium carbonate and double (three (the 4- trifluoros of 0.02mmol catalyst are added under nitrogen atmosphere
Methyl) phenyl) phosphine dichloride nickel inserted in reaction vessel, adds 1mL DMF, reacted 12 hours in the environment of 100 DEG C, reaction
After end, filter, concentration obtains 5- (4- methyl styrenes base) -8- (pivaloyl amino) quinoline, yield is through pillar layer separation
94%.
Preparation example 16
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 2-methyl styrenes, 0.4mmol sodium carbonate and 0.02mmol catalyst acetic acid nickel is added under nitrogen atmosphere to insert instead
Answer in container, add 1mL DMF, reacted 12 hours in the environment of 100 DEG C, after reaction terminates, filtered, concentration, through column chromatography
5- (2-methyl styrene base) -8- (pivaloyl amino) quinoline is separated to obtain, yield is 92%.
Preparation example 17
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 3- methyl styrenes, 0.4mmol sodium carbonate and 0.02mmol catalyst nickel chloride is added under nitrogen atmosphere (to insert anti-
Answer in container, add 1mL DMF, reacted 12 hours in the environment of 100 DEG C, after reaction terminates, filtered, concentration, through column chromatography
5- (3- methyl styrenes base) -8- (pivaloyl amino) quinoline is separated to obtain, yield is 90%.
Preparation example 18
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- methoxy styrenes, 0.4mmol sodium carbonate and double (three (the 4- chlorine) of 0.02mmol catalyst are added under nitrogen atmosphere
Phenyl) and phosphine dichloride nickel (insert in reaction vessel, add 1mL DMF, reaction 12 hours in the environment of 100 DEG C, reaction terminates
Afterwards, filter, concentration obtains 5- (4- methoxyl-styrenes) -8- (pivaloyl amino) quinoline, yield is through pillar layer separation
93%.
Preparation example 19
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 3- methoxy styrenes, 0.4mmol sodium carbonate and double (three (the 4- chlorine) of 0.02mmol catalyst are added under nitrogen atmosphere
Phenyl) and phosphine dichloride nickel (insert in reaction vessel, add 1mL DMF, reaction 12 hours in the environment of 100 DEG C, reaction terminates
Afterwards, filter, concentration obtains 5- (3- methoxyl-styrenes) -8- (pivaloyl amino) quinoline, yield is through pillar layer separation
91%.
Preparation example 20
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- ethyl styrenes, 0.4mmol sodium carbonate and double (three (the 4- trifluoros of 0.002mmol catalyst are added under nitrogen atmosphere
Methyl) phenyl) phosphine dichloride nickel (insert in reaction vessel, add 1mL DMF, reaction 12 hours in the environment of 100 DEG C, instead
After should terminating, filter, concentration obtains 5- (4- ethyl styrenes base) -8- (pivaloyl amino) quinoline, yield is through pillar layer separation
90%.
Preparation example 21
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- t-butyl styrenes, 0.4mmol sodium carbonate and the double (three (4- tri- of 0.01mmol catalyst are added under nitrogen atmosphere
Methyl fluoride) phenyl) phosphine dichloride nickel (insert in reaction vessel, add 1mL DMF, reacted 12 hours in the environment of 100 DEG C,
After reaction terminates, filter, concentration obtains 5- (4- t-butyl styrenes base) -8- (pivaloyl amino) quinoline through pillar layer separation, produces
Rate is 83%.
Preparation example 22
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- fluorobenzene ethenes, 0.4mmol sodium carbonate and double (triphenyl) phosphines two of catalyst 0.02mmol are added under nitrogen atmosphere
Nickel chloride (insert in reaction vessel, add 1mL DMF, reacted 12 hours in the environment of 100 DEG C, after reaction terminates, filtering,
Concentration, obtains 5- (4- fluorostyryls) -8- (pivaloyl amino) quinoline, yield is 81% through pillar layer separation.
Preparation example 23
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- chlorostyrenes, 0.4mmol sodium carbonate and double (triphenyl) phosphines two of 0.03mmol catalyst are added under nitrogen atmosphere
Nickel chloride (insert in reaction vessel, add 1mL DMF, reacted 12 hours in the environment of 100 DEG C, after reaction terminates, filtering,
Concentration, obtains 5- (4- chlorostyrenes base) -8- (pivaloyl amino) quinoline, yield is 83% through pillar layer separation.
Preparation example 24
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- bromstyrols, 0.4mmol sodium carbonate and double (triphenyl) phosphines two of 0.04mmol catalyst are added under nitrogen atmosphere
Nickel chloride (insert in reaction vessel, add 1mL DMF, reacted 12 hours in the environment of 100 DEG C, after reaction terminates, filtering,
Concentration, obtains 5- (4- bromstyrols base) -8- (pivaloyl amino) quinoline, yield is 80% through pillar layer separation.
Preparation example 25
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
I2With 1mL DMF, under nitrogen atmosphere, reaction carries out 18h at 100 DEG C.Question response is cooled to room temperature, Ran Hou after the completion of reaction
0.3mmol 4- cyano styrenes, 0.4mmol sodium carbonate and double (triphenyl) phosphines of 0.02mmol catalyst are added under nitrogen atmosphere
Nickel Chloride (insert in reaction vessel, add 1mL DMF, reacted 12 hours in the environment of 100 DEG C, after reaction terminates, mistake
Filter, concentration, obtains 5- (4- cyano styrenes base) -8- (pivaloyl amino) quinoline, yield is 76% through pillar layer separation.
Preparation example 26
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NBS and 1mL DMSO, nitrogen atmosphere, reaction carries out 18h at 140 DEG C.Question response is cooled to room temperature after the completion of reaction, then
It is double (triphenyl) that 0.3mmol 4- nitrostyrolenes, 0.4mmol sodium carbonate and 0.02mmol catalyst are added under nitrogen atmosphere
Phosphine dichloride nickel (insert in reaction vessel, add 1mL DMSO, reacted 8 hours in the environment of 100 DEG C, after reaction terminates, mistake
Filter, concentration, obtains 5- (4- nitrostyrolenes base) -8- (pivaloyl amino) quinoline, yield is 70% through pillar layer separation.
Preparation example 27
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NBS and 1mL DMSO, nitrogen atmosphere, reaction carries out 18h at 140 DEG C.Question response is cooled to room temperature after the completion of reaction, then
0.3mmol 4- trifluoromethyl styrenes, 0.4mmol sodium carbonate and the double (triphens of 0.02mmol catalyst are added under nitrogen atmosphere
Base) and phosphine dichloride nickel (insert in reaction vessel, add 1mL DMSO, reaction 8 hours in the environment of 100 DEG C, reaction terminates
Afterwards, filter, concentration obtains 5- (4- trifluoromethyl styrenes base) -8- (pivaloyl amino) quinoline, yield is through pillar layer separation
77%.
Preparation example 28
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NBS and 1mL DMSO, nitrogen atmosphere, reaction carries out 18h at 140 DEG C.Question response is cooled to room temperature after the completion of reaction, then
0.3mmol 3,5- difluoros styrene, 0.4mmol sodium carbonate and the double (triphens of 0.02mmol catalyst are added under nitrogen atmosphere
Base) and phosphine dichloride nickel (insert in reaction vessel, add 1mL DMSO, reaction 8 hours in the environment of 100 DEG C, reaction terminates
Afterwards, filter, concentration obtains 5- (3,5- difluoro styryl) -8- (pivaloyl amino) quinoline, yield is through pillar layer separation
70%.
Preparation example 29
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NIS and 1mL DMSO, nitrogen atmosphere, reaction carries out 18h at 140 DEG C.Question response is cooled to room temperature after the completion of reaction, then
0.3mmol 4- acetyl styrene, 0.4mmol saleratus and 0.02mmol catalyst acetic acid palladiums is added under nitrogen atmosphere (to put
Enter in reaction vessel, add 1mL DMSO, reacted 8 hours in the environment of 100 DEG C, after reaction terminates, filtered, concentration, through post
Chromatographic isolation obtains 5- (4- acetyl styryl) -8- (pivaloyl amino) quinoline, and yield is 76%.
Preparation example 30
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NIS and 1mL DMSO, nitrogen atmosphere, reaction carries out 18h at 140 DEG C.Question response is cooled to room temperature after the completion of reaction, then
0.3mmol 2- vinyl naphthalenes, 0.4mmol saleratus and 0.02mmol catalyst acetic acid palladiums is added under nitrogen atmosphere (to insert
In reaction vessel, 1mL DMSO are added, are reacted 8 hours in the environment of 100 DEG C, after reaction terminates, are filtered, concentration, through post color
Spectrum separates to obtain 5- (2- vinyl naphthalenes) -8- (pivaloyl amino) quinoline, and yield is 83%.
Preparation example 31
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NIS and 1mL DMSO, nitrogen atmosphere, reaction carries out 18h at 140 DEG C.Question response is cooled to room temperature after the completion of reaction, then
0.3mmol 2- vinyl thiophenes, 0.4mmol saleratus and 0.02mmol catalyst acetic acid palladiums are added under nitrogen atmosphere
(1%) insert in reaction vessel, add 1mL DMSO, reacted 8 hours in the environment of 100 DEG C, after reaction terminates, filtering is dense
Contracting, obtains 5- (2- vinyl thiophenes) -8- (pivaloyl amino) quinoline, yield is 81% through pillar layer separation.
Preparation example 32
0.2mmol 8- (pivaloyl amino) quinoline (R is added in 10mL reaction tubes1=tert-butyl), 0.22mmol
Under NIS and 1mL DMSO, nitrogen atmosphere, reaction carries out 18h at 140 DEG C.Question response is cooled to room temperature after the completion of reaction, then
0.3mmol 3- vinyl thiophenes, 0.4mmol saleratus and 0.02mmol catalyst acetic acid palladiums is added under nitrogen atmosphere (to put
Enter in reaction vessel, add 1mL DMSO, reacted 8 hours in the environment of 100 DEG C, after reaction terminates, filtered, concentration, through post
Chromatographic isolation obtains 5- (3- vinyl thiophenes) -8- (pivaloyl amino) quinoline, and yield is 79%.
Embodiment described above only expresses the several embodiments of the present invention, and it describes more specific and detailed, but simultaneously
Therefore the limitation to the scope of the claims of the present invention can not be interpreted as.It should be pointed out that for one of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (9)
1. a kind of 5- alkenyl 8- acylamino-s quinolines (I) and preparation method thereof, the method is with 8- acylamino- quinolines
Compound (II), terminal olefin class compound (III) are that raw material, halide are halide reagent, in organic solvent one pot of two step
Method effecting reaction：That is the first step：Without under metal function, 8- acylamino-s quinolines (II) obtain 5- with halide reaction
Halogenated quinoline class compound (IV)；Second step：Without separation in the presence of metallic catalyst directly and alkenes compounds
(III) occur that 5- alkenyl 8- acylamino- quinolines are made under one kettle way He Ke (Heck) cross-coupling reaction, alkalescence condition
Compound (I)；Wherein described compound I, II, III and IV structural formula are as follows：
Wherein described R1 is C6-C10 aryl or C1-C6 alkyl group, and R2 is C6-C10 aryl or C3-C6 heterocyclic
Group, halogen X is Cl, Br, I.
2. preparation method according to claim 1, wherein the R1Group be t-Bu, Me, Et, n-octyl,
cyclohexyl、cyclopentyl、Ph、p-MePh、p-OMePh、p-FPh、o-FPh、m-FPh、p-CF3Ph、2-thienyl
One kind in group.
3. preparation method according to claim 1, wherein the R2Group is Ph, p-MePh, o-MePh, m-MePh, p-
MeOPh、m-MeOPh、p-EtPh、p-t-BuPh、p-FPh、p-ClPh、p-BrPh、p-CNPh、p-NO2Ph、p-CF3Ph、3,5-
di-FPh、p-acetyl-Ph、2-Naphth、2-thienyl、3-thienyl。
4. preparation method according to claim 1, the halide is NCS, NBS, NIS, Br2、I2In one kind.
5. preparation method according to claim 1, the metallic catalyst described in it is double (triphenyl) phosphine dichloride palladiums, double
(three (2- methyl) phenyl) phosphine dichloride palladium, double (three (4- methyl) phenyl) phosphine dichloride palladiums, double (three (the 4- tert-butyl groups) phenyl)
Phosphine dichloride palladium, double (three (4- chlorine) phenyl) phosphine dichloride palladiums, double (three (4- fluorine) phenyl) phosphine dichloride palladiums, double (three (4- trifluoros
Methyl) phenyl) phosphine dichloride palladium, palladium, palladium bichloride, double (triphenyl) phosphine dichloride nickel, double (three (2- methyl) phenyl) phosphines
Nickel Chloride, double (three (4- methyl) phenyl) phosphine dichloride nickel, double (three (the 4- tert-butyl groups) phenyl) phosphine dichloride nickel, double (three (4-
Chlorine) phenyl) phosphine dichloride nickel, double (three (4- fluorine) phenyl) phosphine dichloride nickel, double (three (4- trifluoromethyls) phenyl) phosphine dichlorides
One kind in nickel, nickel acetate, nickel chloride.
6. preparation method according to claim 1, its described solvent is tetrahydrofuran, toluene, Isosorbide-5-Nitrae-dioxane, diformazan
What the one or two in sulfoxide (DMSO), DMF (DMF), the wherein first step and second step reacted can phase
It is same or different.
7. preparation method according to claim 1, its described alkalescence condition is sodium carbonate, saleratus, triethylamine, tertiary fourth
One kind of potassium alcoholate or potassium hydroxide.
8. preparation method according to claim 1, mole addition of the metallic catalyst for 1%-20% (relative to
Substrate II).
9. preparation method according to claim 1, the condition of the catalytic reaction is：The first step reaction halogenation be
Reacted 6-18 hours at 50-160 DEG C；Second step coupling reaction is reaction 4-12 hours at 50-160 DEG C.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610785567 | 2016-08-31 | ||
| CN2016107855673 | 2016-08-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106938985A true CN106938985A (en) | 2017-07-11 |
| CN106938985B CN106938985B (en) | 2020-05-05 |
Family
ID=59463941
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710164258.9A Active CN106938985B (en) | 2016-08-31 | 2017-03-20 | 5-site alkenylated 8-acylaminoquinoline compound and one-pot preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106938985B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107790186A (en) * | 2017-11-07 | 2018-03-13 | 山西医科大学 | A kind of new decamethyl Zirconocenes and its preparation method and application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2168959A1 (en) * | 2007-06-19 | 2010-03-31 | Kyorin Pharmaceutical Co., Ltd. | Pyridazinone derivative and pde inhibitor containing the same as active ingredient |
-
2017
- 2017-03-20 CN CN201710164258.9A patent/CN106938985B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2168959A1 (en) * | 2007-06-19 | 2010-03-31 | Kyorin Pharmaceutical Co., Ltd. | Pyridazinone derivative and pde inhibitor containing the same as active ingredient |
Non-Patent Citations (2)
| Title |
|---|
| CHUNSHENG HE等: "A ratiometric fluorescent probe for oxalate based on alkyne-conjugated carboxamidoquinolines in aqueous solution and imaging in living cells", 《DALTON TRANS.》 * |
| HAREKRISHNA SAHOO等: "Functionalization of Quinolines through Copper-Catalyzed Regioselective Halogenation Reaction", 《CHEMISTRYSELECT》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107790186A (en) * | 2017-11-07 | 2018-03-13 | 山西医科大学 | A kind of new decamethyl Zirconocenes and its preparation method and application |
| CN107790186B (en) * | 2017-11-07 | 2020-10-30 | 山西医科大学 | Novel decamethyl cyclopentadienyl zirconium complex and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106938985B (en) | 2020-05-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109516998B (en) | Synthesis method of Barosavir intermediate | |
| CN106458943A (en) | Synthesis of vortioxetine via (2,4-dimethylphenyl)(2-iodophenyl)sulfane intermediate | |
| CN106938985A (en) | A kind of 5 amide groups quinolines of alkenyl 8 and its one-pot preparation thereof | |
| Gogoi et al. | An Efficient Protocol for the Carbon–Sulfur Cross-Coupling of Sulfenyl Chlorides with Arylboronic Acids using a Palladium Catalyst | |
| WO2016141840A1 (en) | Method synthesizing pharmaceutical intermediate phenanthrene compound in sodium hydroxide environment | |
| CN106008316A (en) | New method for synthesizing Ledipasvir chiral intermediate | |
| Tang et al. | POxAP Precatalysts and the Negishi Cross-Coupling Reaction | |
| CN105949119B (en) | A method of polysubstituted 2 (the 1H)-quinolinones compound of synthesis | |
| CN105693778B (en) | The method of N- methoxymethylamide guiding synthesis ferrocene and Pyridione derivatives | |
| CN105017211A (en) | 2-phenyl propionic ester derivative and preparation method and application thereof | |
| CN105837633B (en) | A kind of preparation method of antimicrobial compound | |
| CN106938984A (en) | A kind of 5 amide groups quinolines of substituted (hetero) aryl/jeterocyclic chemistry 8 and its one-pot preparation thereof | |
| CN102936219B (en) | Chiral 6, 6'-2 carbazole base binaphthol | |
| CN105272793B (en) | Method for synthesizing aryl hydrazone | |
| CN104945298B (en) | Trifluoromethyl thioperoxide and preparation method thereof | |
| CN108912001A (en) | A kind of process for catalytic synthesis of 1,3- dicarbapentaborane class compound | |
| CN103483267A (en) | Diverse arylimidazole quaternary ammonium salt, preparation method and application thereof | |
| CN102295497B (en) | Synthesis method of halogenated aromatic hydrocarbon compound with water as solvent | |
| CN105130898B (en) | One kind is together with difluoro polycyclic compound and preparation method thereof | |
| CN106905233A (en) | A kind of 5 amide groups quinolines of alkynyl 8 and its one-pot preparation thereof | |
| CN102977033B (en) | Synthesis method of alpha-halogenated alkenyl amide | |
| CN101885653B (en) | Synthesis method of N-heteroaryl amino acid | |
| CN109369618A (en) | Cook different foods in one pot and prepare the chloro- 5-((2-(Nitromethylene of 2-) imidazoline -1- base) methyl) and pyridine method | |
| CN112521419A (en) | Method for preparing chiral nitrogen-phosphorus ligand L-8 containing pyridocyclopentane | |
| CN117800981A (en) | Preparation method of chiral dihydroquinolone compound |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |