CN106938984B - 5-substituted arylation/heterocycle 8-acylamino quinoline compound and one-pot preparation method thereof - Google Patents
5-substituted arylation/heterocycle 8-acylamino quinoline compound and one-pot preparation method thereof Download PDFInfo
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- CN106938984B CN106938984B CN201710164173.0A CN201710164173A CN106938984B CN 106938984 B CN106938984 B CN 106938984B CN 201710164173 A CN201710164173 A CN 201710164173A CN 106938984 B CN106938984 B CN 106938984B
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
Abstract
The invention selectively obtains the 5-substituted arylation/heterocycle 8-acylamino quinoline compound through the metal-free halogenation reaction of the first step and the coupling reaction directly with the boric acid compound without separation. Because the first step does not involve metal, the subsequent reaction is not influenced. The preparation method comprises the following steps of (1) taking aminoquinoline compounds, halides and boric acid compounds as raw materials, taking common metals as catalysts and taking common organic solvents as reaction solvents; the 5-substituted arylation/heterocycle 8-amido quinoline compound is obtained by column chromatography after halogenation and arylation one-pot reaction.
Description
[ technical field ] A method for producing a semiconductor device
The invention belongs to the field of catalytic organic synthesis, and particularly relates to a 5-substituted arylation/heterocycle 8-acylamino quinoline compound and a preparation method thereof.
[ background of the invention ]
Due to the important role of the quinoline compounds in natural products and pharmaceutical industry, the quinoline compounds are widely concerned by the majority of chemical researchers in recent years. The introduction of an aryl structure (-AR) or a heterocyclic structure (-hetero) enables the compound to have special activity and great medicinal value prospect. Since the last century, many classical synthetic methods have been reported in succession. At present, the common method is to prepare the corresponding quinoline compound by performing cycloaddition reaction on precursor aniline and carbonyl compound or alkyne to close the ring. However, such a method requires the preparation of an expensive polysubstituted precursor aniline in advance, and has many steps, complicated operation, and sometimes difficulty in controlling the selectivity. The prior quinoline parent nucleus structure is selectively modified to synthesize the corresponding quinoline derivatives, and particularly, reports of 5-site arylation are rare. The direct one-pot coupling reaction through halogenation and no separation is a convenient way. However, the methods reported so far require a metal catalyst or a metal salt as a halogen source for the halogenation of quinoline (J.Am.chem.Soc.,2013,135,9797; Tetrahedron,2015,71, 70; org.Biomol.chem.2016,14,3016). The presence of metal salts has a negative effect on the subsequent coupling reaction. The invention prepares the products of 5-site arylation and heteroaromatization by the first step of metal-free halogenation reaction and the subsequent coupling reaction with arylboronic acid directly without separation; because the first step does not involve metal, the subsequent reaction is not influenced, and the target product can be efficiently and conveniently obtained. The invention takes aminoquinoline compounds, halides and boric acid compounds as raw materials, takes a metal catalyst as a catalyst and takes an organic solvent as a reaction solvent; the 5-substituted arylation/heterocycle 8-acylamino quinoline compound is prepared by a one-pot reaction of halogenation and arylation.
[ summary of the invention ]
The invention aims to provide a simple method for preparing a 5-substituted arylation/heterocycle 8-acylaminoquinoline compound so as to improve the yield and the selectivity of a target product.
In order to achieve the above purpose, the invention provides the following technical scheme:
1) a5-substituted arylation/heterocycle 8-acylamino quinoline compound I and its preparation method, regard amino quinoline compound II, halide, boric acid compound III as raw materials, the metal catalyst is regarded as the catalyst, regard organic solvent as the reaction solvent; carrying out halogenation and arylation one-pot reaction to prepare a 5-substituted arylation/heterocycle 8-amido quinoline compound I; the structural formulas of the compounds I, II and III are as follows:
wherein R1 is C6-C10 aryl or C1-C6 alkyl group, and R2 is C6-C10 aryl or C3-C6 heterocyclic group.
2) In the above synthesis method, R is1The groups are t-Bu, Me, n-octyl, cyclohexyl, cyclopentyl, Ph, o-FPh, o-CF3One of Ph, 2-thienyl and 2-oxole groups.
3) In the above synthesis method, R is2The group is Ph, p-MePh, o-MePh, m-MePh, p-MeOPh, o-MeOPh, p-EtPh, p-t-BuPh, p-ClPh, p-BrPh, p-FPh, p-CNPh, 3,5-di-FPh, p-acetyl-Ph, p-CF3Ph, 4-Pyridyl, Naphth, 2-thienyl, 3-thienyl and 3-oxole group.
4) In the above synthesis method, the halide is NCS, NBS, NIS, Br2、I2One kind of (1).
5) The process according to claim 1, wherein the zero-valent metal catalyst is tetrakis (triphenyl) phosphine palladium, tetrakis (tris (2-methyl) phenyl) phosphine palladium, tetrakis (tris (4-tert-butyl) phenyl) phosphine palladium, tetrakis (tris (4-chloro) phenyl) phosphine palladium, tetrakis (tris (4-fluoro) phenyl) phosphine palladium, tetrakis (tris (4-trifluoromethyl) phenyl) phosphine palladium, one of tetrakis (triphenyl) phosphine nickel, tetrakis (tris (2-methyl) phenyl) phosphine nickel, tetrakis (tris (4-tert-butyl) phenyl) phosphine nickel, tetrakis (tris (4-chloro) phenyl) phosphine nickel, tetrakis (tris (4-fluoro) phenyl) phosphine nickel, and tetrakis (tris (4-trifluoromethyl) phenyl) phosphine nickel.
6) In the above synthesis method, the solvent is one of toluene, 1, 4-dioxane, dimethyl sulfoxide (DMSO), Tetrahydrofuran (THF), and N, N-Dimethylformamide (DMF), wherein the first step and the second step may be the same or different.
7) In the above synthesis method, the molar addition amount of the metal catalyst is 1% to 20% (relative to the substrate II).
8) In the above synthesis method, the catalytic reaction conditions are as follows: the first step of reaction halogenation is reaction at 50-160 ℃ for 10-24 hours; the second coupling reaction is carried out for 4 to 16 hours at a temperature of between 50 and 160 ℃.
[ description of the drawings ]
FIG. 1 is a synthetic pathway diagram of a 5-substituted arylation/heterocycle 8-acylaminoquinoline compound provided by the invention.
[ detailed description ] embodiments
The synthesis route of the method for catalytically synthesizing the 5-substituted arylation/heterocycle 8-acylaminoquinoline compound provided by the invention is shown in the attached figure 1: adding a solvent into a quinoline and halogenating reagent reaction container which is taken as a raw material, reacting for 10-24 hours at 50-160 ℃, cooling to room temperature after the reaction is finished, then adding an organic solvent into aryl boric acid or heterocyclic boric acid alkali and a catalyst, reacting for 4-16 hours at 50-160 ℃, and separating by column chromatography after the reaction is finished to obtain a target product
The invention is further illustrated below with reference to specific preparation examples:
preparation example 1
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1Tert-butyl), 0.22mmol nbs and 1mL DMF, the reaction was carried out at 160 ℃ for 24h under nitrogen atmosphere. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (2-methyl) phenyl) phosphine palladium under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL) (1mL), reacting for 6 hours under the environment of 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5-phenyl-8- (pivaloyl) aminoquinoline with the yield of 83%.
Preparation example 2
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1Me), 0.22mmol NIS and 1mLDMF, under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, and then adding the mixture in a nitrogen atmosphere0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tri (4-methyl) phenyl) phosphine palladium are added, solvent Dimethylsulfoxide (DMSO) (1mL) is added, the reaction is carried out for 6 hours at 140 ℃, after the reaction is finished, filtration and concentration are carried out, and the 5-phenyl-8- (methylacetamido) quinoline is obtained by column chromatography separation, wherein the yield is 78%.
Preparation example 3
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1N-octly), 0.22 mmolencs and 1mL DMF, the reaction was carried out at 160 ℃ for 24h under a nitrogen atmosphere. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-tert-butyl) phenyl) phosphine palladium under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5-phenyl-8- (n-octyl acetamido) quinoline with the yield of 73%.
Preparation example 4
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1＝cyclohexyl)、0.22mmolBr2And 1mL of DMF under a nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-chloro) phenyl) phosphine palladium under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5-phenyl-8- (cyclohexyl acetamido) quinoline with the yield of 70%.
Preparation example 5
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1＝cyclopentyl)、0.22mmol I2And 1mL of DMF under a nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tri (4-fluoro) phenyl) phosphine palladium under the atmosphere of nitrogen, adding solvent dimethyl sulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5-benzene8- (Cyclopentylacetylamino) quinoline in 67% yield.
Preparation example 6
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1Ph), 0.22mmol NBS and 1mL toluene, under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-trifluoromethyl) phenyl) phosphine palladium under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5-phenyl-8- (phenylacetamido) quinoline with the yield of 63%.
Preparation example 7
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)12-oxole), 0.22mmol nbs and 1mL 1, 4-dioxane, under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (triphenyl) phosphine nickel in a nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain the 5-phenyl-8- (p-F phenyl acetamido) quinoline with the yield of 43%.
Preparation example 8
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1o-FPh), 0.22mmol NBS and 1mL Dimethylsulfoxide (DMSO), under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (2-methyl) phenyl) phosphine nickel under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5-phenyl-8- (2-fluorophenyl acetamido) quinoline with the yield of 53%.
Preparation example 9
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)1＝o-CF3Ph), 0.22mmol NBS and 1mL THF, under nitrogen, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tri (4-methyl) phenyl) phosphine nickel under the atmosphere of nitrogen, adding solvent dimethyl sulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5-phenyl-8- (ortho-trifluoromethylphenyl acetamido) quinoline with the yield of 70%.
Preparation example 10
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)12-thienyl), 0.22mmol nbs and 1mL toluene, under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-tert-butyl) phenyl) phosphine nickel under the atmosphere of nitrogen, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5-phenyl-8- (2-thiophene acetamido) quinoline with the yield of 57%.
Preparation example 11
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2Ph), 0.22mmol NBS and 1mL DMF, the reaction was carried out at 50 ℃ for 24h under a nitrogen atmosphere. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-trifluoromethyl) phenyl) phosphine nickel under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5-phenyl-8- (pivaloyl) aminoquinoline with the yield of 32%.
Preparation example 12
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-MePh), 0.22mmol NBS and 1mL DMF, the reaction was carried out at 80 ℃ for 24h under nitrogen atmosphere. After the reaction is finished, the reaction is cooled to room temperature, and then 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tri (4-fluoro) phenyl) phosphine are added under the nitrogen atmosphereNickel was added to dimethyl sulfoxide (DMSO) (1mL) as a solvent, and the mixture was reacted at 140 ℃ for 6 hours, and after the reaction was completed, the reaction mixture was filtered, concentrated, and separated by column chromatography to obtain 5- (4-methylphenyl) -8- (pivaloyl) aminoquinoline with a yield of 53%.
Preparation example 13
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2o-MePh), 0.22mmol NBS and 1mL DMF, the reaction was carried out at 120 ℃ for 24h under a nitrogen atmosphere. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-methyl) phenyl) phosphine palladium under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (2-methylphenyl) -8- (pivaloyl) aminoquinoline with the yield of 67%.
Preparation example 14
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2m-MePh), 0.22mmol NBS and 1mL DMF, the reaction was carried out at 140 ℃ for 24h under nitrogen atmosphere. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-chloro) phenyl) phosphine palladium under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5- (3-methylphenyl) -8- (pivaloyl) aminoquinoline with the yield of 73%.
Preparation example 15
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-MeOPh), 0.22mmol nbs and 1mL 1, 4-dioxane, under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst palladium tetrakis (triphenyl) phosphine under the atmosphere of nitrogen, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (4-methoxyphenyl) -8- (pivaloyl) aminoquinoline with the yield of 70%.
Preparation example 16
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2o-MeOPh), 0.22mmol nbs and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 10 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-fluoro) phenyl) phosphine nickel under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (2-methoxyphenyl) -8- (pivaloyl) aminoquinoline with the yield of 45%.
Preparation example 17
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-EtPh), 0.22mmol NBS and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 14 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (4-chloro) phenyl) phosphine nickel under nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (4-ethylphenyl) -8- (pivaloyl) aminoquinoline with the yield of 53%.
Preparation example 18
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-t-BuPh), 0.22mmol nbs and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 16 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (tris (2-methyl) phenyl) phosphine palladium under nitrogen atmosphere, adding solvent dimethyl sulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (4-tert-butylphenyl) -8- (pivaloyl) aminoquinoline with the yield of 43%.
Preparation example 19
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-ClPh), 0.22mmol NBS and 1mL DMF, the reaction was carried out at 160 ℃ for 18h under a nitrogen atmosphere. After the reaction is finishedThe reaction was cooled to room temperature, then 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.002mmol of tetrakis (triphenyl) phosphine palladium as a catalyst were added under nitrogen atmosphere, Dimethylsulfoxide (DMSO) (1mL) as a solvent was added, the reaction was carried out at 50 ℃ for 6 hours, after the reaction was completed, filtration and concentration were carried out, and 5- (p-chlorophenyl) -8- (pivaloyl) aminoquinoline was obtained by column chromatography with a yield of 8%.
Preparation example 20
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-BrPh), 0.22mmol NBS and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.01mmol of catalyst tetrakis (triphenyl) phosphine palladium under the nitrogen atmosphere, adding solvent dimethyl sulfoxide (DMSO) (1mL), reacting for 6 hours at 80 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (p-bromophenyl) -8- (pivaloyl) aminoquinoline with the yield of 13%.
Preparation example 21
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-FPh), 0.22mmol NBS and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst palladium tetrakis (triphenyl) phosphine under the nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 100 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (p-fluorophenyl) -8- (pivaloyl) aminoquinoline with the yield of 65%.
Preparation example 22
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2p-CNPh), 0.22mmol NBS and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.03mmol of catalyst tetrakis (triphenyl) phosphine palladium under the atmosphere of nitrogen, adding solvent dimethyl sulfoxide (DMSO) (1mL), reacting for 6 hours at 120 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (p-cyano group)Phenyl) -8- (pivaloyl) aminoquinoline in 35% yield.
Preparation example 23
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)23,5-di-FPh), 0.22mmol nbs and 1mL DMF, the reaction was carried out at 160 ℃ for 24h under nitrogen atmosphere. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.04mmol of catalyst palladium tetrakis (triphenyl) phosphine under the nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (3, 5-fluorophenyl) -8- (pivaloyl) aminoquinoline with the yield of 45%.
Preparation example 24
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2P-acetyl-ph), 0.22mmol NBS and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst palladium tetrakis (triphenyl) phosphine under the nitrogen atmosphere, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 6 hours at 160 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (4-acetylphenyl) -8- (pivaloyl) aminoquinoline with the yield of 77%.
Preparation example 25
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2＝p-CF3ph), 0.22mmol NBS and 1mL DMF under nitrogen, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst palladium tetrakis (triphenyl) phosphine under the nitrogen atmosphere, adding a solvent toluene (1mL), reacting for 4 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (4-trifluoromethylphenyl) -8- (pivaloyl) aminoquinoline with the yield of 43%.
Preparation example 26
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)2Naphthh), 0.22mmol NBS and 1mLDMF, under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst tetrakis (triphenyl) phosphine palladium under nitrogen atmosphere, adding a solvent 1, 4-dioxane (1mL), reacting for 8 hours at 140 ℃, filtering after the reaction is finished, concentrating, and separating by column chromatography to obtain 5-naphthyl-8- (pivaloyl) aminoquinoline with the yield of 62%.
Preparation example 27
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)22-thienyl), 0.22mmol nbs and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst palladium tetrakis (triphenyl) phosphine under the atmosphere of nitrogen, adding solvent Dimethylsulfoxide (DMSO) (1mL), reacting for 10 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (2-thiophene) -8- (pivaloyl) aminoquinoline with the yield of 58%.
Preparation example 28
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)23-thienyl), 0.22mmol nbs and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst palladium tetrakis (triphenyl) phosphine under the nitrogen atmosphere, adding a solvent THF (1mL), reacting for 12 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain 5- (3-thiophene) -8- (pivaloyl) aminoquinoline with the yield of 86%.
Preparation example 29
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)23-oxole), 0.22mmol nbs and 1mL DMF, the reaction was carried out under nitrogen atmosphere at 160 ℃ for 24 h. After the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst palladium tetrakis (triphenyl) phosphine under the nitrogen atmosphere, adding a solvent THF (1mL), reacting for 14 hours at 140 ℃, filtering and concentrating after the reaction is finished,the 5- (3-furan) -8- (pivaloyl) aminoquinoline was obtained in 87% yield by column chromatography.
Preparation example 30
To a 10mL reaction tube was added 0.2mmol of 8- (pivaloyl) aminoquinoline (R)24-Pyridyl), 0.22 mmols nbs and 1mL DMF, under nitrogen atmosphere, the reaction was carried out at 160 ℃ for 24 h. After the reaction was completed and the reaction was cooled to room temperature, 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of catalyst pd (pph) were added under nitrogen atmosphere3)4Adding solvent DMF (1mL), reacting at 140 deg.C for 16h, filtering, concentrating, and separating by column chromatography to obtain 5- (3-thiophene) -8- (pivaloyl) aminoquinoline with yield of 76%.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (1)
1. A preparation method of a 5-substituted arylation/heterocycle 8-acylaminoquinoline compound comprises the steps of adding 8- (pivaloyl) aminoquinoline 0.2mmol, N-monobromo succinimide (NBS) 0.22mmol and 1mLN, N-Dimethylformamide (DMF), and reacting at 160 ℃ for 24 hours under a nitrogen atmosphere; after the reaction is finished, cooling the reaction to room temperature, then adding 0.3mmol of phenylboronic acid, 0.4mmol of sodium carbonate and 0.02mmol of palladium tetrakis (triphenyl) phosphine catalyst under the nitrogen atmosphere, adding 1mL of Tetrahydrofuran (THF) serving as a solvent, reacting for 14 hours at 140 ℃, filtering and concentrating after the reaction is finished, and separating by column chromatography to obtain the 5- (3-furan) -8- (pivaloyl) aminoquinoline.
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| A ratiometric fluorescent probe for oxalate based on alkyne-conjugated carboxamidoquinolines in aqueous solution and imaging in living cells;Chunsheng He等;《Dalton Trans.》;20101223;第40卷;Supporting Information第1-3页 * |
| Functionalization of Quinolines through Copper-Catalyzed Regioselective Halogenation Reaction;Harekrishna Sahoo等;《ChemistrySelect》;20160621;第1卷(第9期);第1950-1952页、Supporting Information第S3-S12页 * |
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